WorldWideScience

Sample records for age related diseases

  1. Interventions for age-related diseases

    DEFF Research Database (Denmark)

    Figueira, Inês; Fernandes, Adelaide; Mladenovic Djordjevic, Aleksandra

    2016-01-01

    Over 60% of people aged over 65 are affected by multiple morbidities, which are more difficult to treat, generate increased healthcare costs and lead to poor quality of life compared to individual diseases. With the number of older people steadily increasing this presents a societal challenge. Age...... is the major risk factor for age-related diseases and recent research developments have led to the proposal that pharmacological interventions targeting common mechanisms of ageing may be able to delay the onset of multimorbidity. Here we review the state of the knowledge of multimorbidity, appraise...... the available evidence supporting the role of mechanisms of ageing in the development of the most common age-related diseases and assess potential molecules that may successfully target those key mechanisms....

  2. Splicing regulatory factors, ageing and age-related disease.

    Science.gov (United States)

    Latorre, Eva; Harries, Lorna W

    2017-07-01

    Alternative splicing is a co-transcriptional process, which allows for the production of multiple transcripts from a single gene and is emerging as an important control point for gene expression. Alternatively expressed isoforms often have antagonistic function and differential temporal or spatial expression patterns, yielding enormous plasticity and adaptability to cells and increasing their ability to respond to environmental challenge. The regulation of alternative splicing is critical for numerous cellular functions in both pathological and physiological conditions, and deregulated alternative splicing is a key feature of common chronic diseases. Isoform choice is controlled by a battery of splicing regulatory proteins, which include the serine arginine rich (SRSF) proteins and the heterogeneous ribonucleoprotein (hnRNP) classes of genes. These important splicing regulators have been implicated in age-related disease, and in the ageing process itself. This review will outline the important contribution of splicing regulator proteins to ageing and age-related disease. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Association of age-related macular degeneration and reticular macular disease with cardiovascular disease.

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    Rastogi, Neelesh; Smith, R Theodore

    2016-01-01

    Age-related macular degeneration is the leading cause of adult blindness in the developed world. Thus, major endeavors to understand the risk factors and pathogenesis of this disease have been undertaken. Reticular macular disease is a proposed subtype of age-related macular degeneration correlating histologically with subretinal drusenoid deposits located between the retinal pigment epithelium and the inner segment ellipsoid zone. Reticular lesions are more prevalent in females and in older age groups and are associated with a higher mortality rate. Risk factors for developing age-related macular degeneration include hypertension, smoking, and angina. Several genes related to increased risk for age-related macular degeneration and reticular macular disease are also associated with cardiovascular disease. Better understanding of the clinical and genetic risk factors for age-related macular degeneration and reticular macular disease has led to the hypothesis that these eye diseases are systemic. A systemic origin may help to explain why reticular disease is diagnosed more frequently in females as males suffer cardiovascular mortality at an earlier age, before the age of diagnosis of reticular macular disease and age-related macular degeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. The Rationale for Delaying Aging and the Prevention of Age-Related Diseases

    Directory of Open Access Journals (Sweden)

    Nir Barzilai

    2012-10-01

    Full Text Available [Excerpt] We offer a different approach to delaying or preventing age-related diseases. To understand the necessity for a new approach we have plotted the mortality rates in Israelis in relation to specific age groups and diseases. With the common phenomenon of aging of Western populations it is of utmost importance to follow time-dependent and age-dependent mortality patterns to predict future needs of Western health systems. Age-specific, gender-specific, and cause-of-death-specific mortality rates were extracted from the statistical abstract of Israel1 and include data for the period of 1975–2010; these are presented in Figure 1, separately for men (A and women (B. Detailed age-specific causes of death data were available for the year 2009. Data presented were restricted to 5-year age groups starting at age 50, and for cause-specific mortality to the following age groups: 45–54, 55–64, 65–74, 75–84, and 85+. Causes of mortality were separated into malignant diseases, acute myocardial infarction, other ischemic heart diseases, other forms of heart diseases, cerebrovascular disease, diabetes mellitus, respiratory diseases, diseases of kidney, infectious diseases, all external causes, signs/symptoms and ill-defined conditions, and all other diseases. Figure 1 is similar to the one posted on the National Institute of Aging website and similar to data across the industrial world. The striking feature of this graph is that aging is a major log scale risk for most diseases, including the major killers: heart disease, cancer, diabetes, and Alzheimer’s. For example, while aging is a 100-fold risk for cardiovascular disease (CVD according to Figure 1, hypercholesterolemia is known to carry only a three-fold risk for CVD. For each of the mentioned diseases, aging is a log risk greater than the most important known risk factor for that disease.

  5. The application of information theory for the research of aging and aging-related diseases.

    Science.gov (United States)

    Blokh, David; Stambler, Ilia

    2017-10-01

    This article reviews the application of information-theoretical analysis, employing measures of entropy and mutual information, for the study of aging and aging-related diseases. The research of aging and aging-related diseases is particularly suitable for the application of information theory methods, as aging processes and related diseases are multi-parametric, with continuous parameters coexisting alongside discrete parameters, and with the relations between the parameters being as a rule non-linear. Information theory provides unique analytical capabilities for the solution of such problems, with unique advantages over common linear biostatistics. Among the age-related diseases, information theory has been used in the study of neurodegenerative diseases (particularly using EEG time series for diagnosis and prediction), cancer (particularly for establishing individual and combined cancer biomarkers), diabetes (mainly utilizing mutual information to characterize the diseased and aging states), and heart disease (mainly for the analysis of heart rate variability). Few works have employed information theory for the analysis of general aging processes and frailty, as underlying determinants and possible early preclinical diagnostic measures for aging-related diseases. Generally, the use of information-theoretical analysis permits not only establishing the (non-linear) correlations between diagnostic or therapeutic parameters of interest, but may also provide a theoretical insight into the nature of aging and related diseases by establishing the measures of variability, adaptation, regulation or homeostasis, within a system of interest. It may be hoped that the increased use of such measures in research may considerably increase diagnostic and therapeutic capabilities and the fundamental theoretical mathematical understanding of aging and disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. The epigenetic landscape of age-related diseases: the geroscience perspective.

    Science.gov (United States)

    Gensous, Noémie; Bacalini, Maria Giulia; Pirazzini, Chiara; Marasco, Elena; Giuliani, Cristina; Ravaioli, Francesco; Mengozzi, Giacomo; Bertarelli, Claudia; Palmas, Maria Giustina; Franceschi, Claudio; Garagnani, Paolo

    2017-08-01

    In this review, we summarize current knowledge regarding the epigenetics of age-related diseases, focusing on those studies that have described DNA methylation landscape in cardio-vascular diseases, musculoskeletal function and frailty. We stress the importance of adopting the conceptual framework of "geroscience", which starts from the observation that advanced age is the major risk factor for several of these pathologies and aims at identifying the mechanistic links between aging and age-related diseases. DNA methylation undergoes a profound remodeling during aging, which includes global hypomethylation of the genome, hypermethylation at specific loci and an increase in inter-individual variation and in stochastic changes of DNA methylation values. These epigenetic modifications can be an important contributor to the development of age-related diseases, but our understanding on the complex relationship between the epigenetic signatures of aging and age-related disease is still poor. The most relevant results in this field come from the use of the so called "epigenetics clocks" in cohorts of subjects affected by age-related diseases. We report these studies in final section of this review.

  7. NAD+ Deficits in Age-Related Diseases and Cancer.

    Science.gov (United States)

    Garrido, Amanda; Djouder, Nabil

    2017-08-01

    The phenomenon of aging has gained widespread attention in recent times. Although significant advances have been made to better understand aging and its related pathologies including cancer, there is not yet a clear mechanism explaining why diseases and cancer are inherent parts of the aging process. Finding a unifying equation that could bridge aging and its related diseases would allow therapeutic development and solve an immense human health problem to live longer and better. In this review, we discuss NAD + reduction as the central mechanism that may connect aging to its related pathologies and cancer. NAD + boosters would ensure and ameliorate health quality during aging. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Telomere in Aging and Age-Related Diseases

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    Anna Meiliana

    2017-12-01

    Full Text Available BACKGROUND: The number of elderly population in the world keep increasing. In their advanced ages, many elderly face years of disability because of multiple chronic diseases, frailty, making them lost their independence. Consequently, this could have impacts on social and economic stability. A huge challenge has been sent for biomedical researchers to compress or at least eliminate this period of disability and increase the health span. CONTENT: Over the past decades, many studies of telomere biology have demonstrated that telomeres and telomere-associated proteins are implicated in human diseases. Accelerated telomere erosion was clearly correlated with a pack of metabolic and inflammatory diseases. Critically short telomeres or the unprotected end, are likely to form telomeric fusion, generating genomic instability, the cornerstone for carcinogenesis. Enlightening how telomeres involved in the mechanisms underlying the diseases’ pathogenesis was expected to uncover new molecular targets for any important diagnosis or therapeutic implications. SUMMARY: Telomere shortening was foreseen as an imporant mechanism to supress tumor by limiting cellular proliferative capacity by regulating senescence check point activation. Many human diseases and carcinogenesis are causally related to defective telomeres, asserting the importance of telomeres sustainment. Thus, telomere length assessment might serve as an important tool for clinical prognostic, diagnostic, monitoring and management. KEYWORDS: telomerase, cellular senescence, aging, cancer

  9. Nutritional Considerations for Healthy Aging and Reduction in Age-Related Chronic Disease.

    Science.gov (United States)

    Shlisky, Julie; Bloom, David E; Beaudreault, Amy R; Tucker, Katherine L; Keller, Heather H; Freund-Levi, Yvonne; Fielding, Roger A; Cheng, Feon W; Jensen, Gordon L; Wu, Dayong; Meydani, Simin N

    2017-01-01

    A projected doubling in the global population of people aged ≥60 y by the year 2050 has major health and economic implications, especially in developing regions. Burdens of unhealthy aging associated with chronic noncommunicable and other age-related diseases may be largely preventable with lifestyle modification, including diet. However, as adults age they become at risk of "nutritional frailty," which can compromise their ability to meet nutritional requirements at a time when specific nutrient needs may be high. This review highlights the role of nutrition science in promoting healthy aging and in improving the prognosis in cases of age-related diseases. It serves to identify key knowledge gaps and implementation challenges to support adequate nutrition for healthy aging, including applicability of metrics used in body-composition and diet adequacy for older adults and mechanisms to reduce nutritional frailty and to promote diet resilience. This review also discusses management recommendations for several leading chronic conditions common in aging populations, including cognitive decline and dementia, sarcopenia, and compromised immunity to infectious disease. The role of health systems in incorporating nutrition care routinely for those aged ≥60 y and living independently and current actions to address nutritional status before hospitalization and the development of disease are discussed. © 2017 American Society for Nutrition.

  10. ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases

    Directory of Open Access Journals (Sweden)

    Pierpaola Davalli

    2016-01-01

    Full Text Available The aging process worsens the human body functions at multiple levels, thus causing its gradual decrease to resist stress, damage, and disease. Besides changes in gene expression and metabolic control, the aging rate has been associated with the production of high levels of Reactive Oxygen Species (ROS and/or Reactive Nitrosative Species (RNS. Specific increases of ROS level have been demonstrated as potentially critical for induction and maintenance of cell senescence process. Causal connection between ROS, aging, age-related pathologies, and cell senescence is studied intensely. Senescent cells have been proposed as a target for interventions to delay the aging and its related diseases or to improve the diseases treatment. Therapeutic interventions towards senescent cells might allow restoring the health and curing the diseases that share basal processes, rather than curing each disease in separate and symptomatic way. Here, we review observations on ROS ability of inducing cell senescence through novel mechanisms that underpin aging processes. Particular emphasis is addressed to the novel mechanisms of ROS involvement in epigenetic regulation of cell senescence and aging, with the aim to individuate specific pathways, which might promote healthy lifespan and improve aging.

  11. Nutritional Considerations for Healthy Aging and Reduction in Age-Related Chronic Disease12

    Science.gov (United States)

    Shlisky, Julie; Bloom, David E; Beaudreault, Amy R; Tucker, Katherine L; Keller, Heather H; Freund-Levi, Yvonne; Fielding, Roger A; Cheng, Feon W; Jensen, Gordon L; Wu, Dayong; Meydani, Simin N

    2017-01-01

    A projected doubling in the global population of people aged ≥60 y by the year 2050 has major health and economic implications, especially in developing regions. Burdens of unhealthy aging associated with chronic noncommunicable and other age-related diseases may be largely preventable with lifestyle modification, including diet. However, as adults age they become at risk of “nutritional frailty,” which can compromise their ability to meet nutritional requirements at a time when specific nutrient needs may be high. This review highlights the role of nutrition science in promoting healthy aging and in improving the prognosis in cases of age-related diseases. It serves to identify key knowledge gaps and implementation challenges to support adequate nutrition for healthy aging, including applicability of metrics used in body-composition and diet adequacy for older adults and mechanisms to reduce nutritional frailty and to promote diet resilience. This review also discusses management recommendations for several leading chronic conditions common in aging populations, including cognitive decline and dementia, sarcopenia, and compromised immunity to infectious disease. The role of health systems in incorporating nutrition care routinely for those aged ≥60 y and living independently and current actions to address nutritional status before hospitalization and the development of disease are discussed. PMID:28096124

  12. Nutritional influences on epigenetics and age-related disease

    Science.gov (United States)

    Nutritional epigenetics has emerged as a novel mechanism underlying gene–diet interactions, further elucidating the modulatory role of nutrition in aging and age-related disease development. Epigenetics is defined as a heritable modification to the DNA that regulates chromosome architecture and modu...

  13. Genome and Epigenome Editing in Mechanistic Studies of Human Aging and Aging-Related Disease.

    Science.gov (United States)

    Lau, Cia-Hin; Suh, Yousin

    2017-01-01

    The recent advent of genome and epigenome editing technologies has provided a new paradigm in which the landscape of the human genome and epigenome can be precisely manipulated in their native context. Genome and epigenome editing technologies can be applied to many aspects of aging research and offer the potential to develop novel therapeutics against age-related diseases. Here, we discuss the latest technological advances in the CRISPR-based genome and epigenome editing toolbox, and provide insight into how these synthetic biology tools could facilitate aging research by establishing in vitro cell and in vivo animal models to dissect genetic and epigenetic mechanisms underlying aging and age-related diseases. We discuss recent developments in the field with the aims to precisely modulate gene expression and dynamic epigenetic landscapes in a spatial and temporal manner in cellular and animal models, by complementing the CRISPR-based editing capability with conditional genetic manipulation tools including chemically inducible expression systems, optogenetics, logic gate genetic circuits, tissue-specific promoters, and the serotype-specific adeno-associated virus. We also discuss how the combined use of genome and epigenome editing tools permits investigators to uncover novel molecular pathways involved in the pathophysiology and etiology conferred by risk variants associated with aging and aging-related disease. A better understanding of the genetic and epigenetic regulatory mechanisms underlying human aging and age-related disease will significantly contribute to the developments of new therapeutic interventions for extending health span and life span, ultimately improving the quality of life in the elderly populations. © 2016 S. Karger AG, Basel.

  14. Molecular Diagnostics of Ageing and Tackling Age-related Disease.

    Science.gov (United States)

    Timmons, James A

    2017-01-01

    As average life expectancy increases there is a greater focus on health-span and, in particular, how to treat or prevent chronic age-associated diseases. Therapies which were able to control 'biological age' with the aim of postponing chronic and costly diseases of old age require an entirely new approach to drug development. Molecular technologies and machine-learning methods have already yielded diagnostics that help guide cancer treatment and cardiovascular procedures. Discovery of valid and clinically informative diagnostics of human biological age (combined with disease-specific biomarkers) has the potential to alter current drug-discovery strategies, aid clinical trial recruitment and maximize healthy ageing. I will review some basic principles that govern the development of 'ageing' diagnostics, how such assays could be used during the drug-discovery or development process. Important logistical and statistical considerations are illustrated by reviewing recent biomarker activity in the field of Alzheimer's disease, as dementia represents the most pressing of priorities for the pharmaceutical industry, as well as the chronic disease in humans most associated with age. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Aging Is Not a Disease: Distinguishing Age-Related Macular Degeneration from Aging

    Science.gov (United States)

    Ardeljan, Daniel; Chan, Chi-Chao

    2013-01-01

    Age-related macular degeneration (AMD) is a disease of the outer retina, characterized most significantly by atrophy of photoreceptors and retinal pigment epithelium accompanied with or without choroidal neovascularization. Development of AMD has been recognized as contingent on environmental and genetic risk factors, the strongest being advanced age. In this review, we highlight pathogenic changes that destabilize ocular homeostasis and promote AMD development. With normal aging, photoreceptors are steadily lost, Bruch's membrane thickens, the choroid thins, and hard drusen may form in the periphery. In AMD, many of these changes are exacerbated in addition to the development of disease-specific factors such as soft macular drusen. Para-inflammation, which can be thought of as an intermediate between basal and robust levels of inflammation, develops within the retina in an attempt to maintain ocular homeostasis, reflected by increased expression of the anti-inflammatory cytokine IL-10 coupled with shifts in macrophage plasticity from the pro-inflammatory M1 to the anti-inflammatory M2 polarization. In AMD, imbalances in the M1 and M2 populations together with activation of retinal microglia are observed and potentially contribute to tissue degeneration. Nonetheless, the retina persists in a state of chronic inflammation and increased expression of certain cytokines and inflammasomes is observed. Since not everyone develops AMD, the vital question to ask is how the body establishes a balance between normal age-related changes and the pathological phenotypes in AMD. PMID:23933169

  16. Physical Activity and Telomere Biology: Exploring the Link with Aging-Related Disease Prevention

    Directory of Open Access Journals (Sweden)

    Andrew T. Ludlow

    2011-01-01

    Full Text Available Physical activity is associated with reduced risk of several age-related diseases as well as with increased longevity in both rodents and humans. Though these associations are well established, evidence of the molecular and cellular factors associated with reduced disease risk and increased longevity resulting from physical activity is sparse. A long-standing hypothesis of aging is the telomere hypothesis: as a cell divides, telomeres shorten resulting eventually in replicative senescence and an aged phenotype. Several reports have recently associated telomeres and telomere-related proteins to diseases associated with physical inactivity and aging including cardiovascular disease, insulin resistance, and hypertension. Interestingly several reports have also shown that longer telomeres are associated with higher physical activity levels, indicating a potential mechanistic link between physical activity, reduced age-related disease risk, and longevity. The primary purpose of this review is to discuss the potential importance of physical activity in telomere biology in the context of inactivity- and age-related diseases. A secondary purpose is to explore potential mechanisms and important avenues for future research in the field of telomeres and diseases associated with physical inactivity and aging.

  17. Bioactive Nutrients and Nutrigenomics in Age-Related Diseases

    Directory of Open Access Journals (Sweden)

    Tania Rescigno

    2017-01-01

    Full Text Available The increased life expectancy and the expansion of the elderly population are stimulating research into aging. Aging may be viewed as a multifactorial process that results from the interaction of genetic and environmental factors, which include lifestyle. Human molecular processes are influenced by physiological pathways as well as exogenous factors, which include the diet. Dietary components have substantive effects on metabolic health; for instance, bioactive molecules capable of selectively modulating specific metabolic pathways affect the development/progression of cardiovascular and neoplastic disease. As bioactive nutrients are increasingly identified, their clinical and molecular chemopreventive effects are being characterized and systematic analyses encompassing the “omics” technologies (transcriptomics, proteomics and metabolomics are being conducted to explore their action. The evolving field of molecular pathological epidemiology has unique strength to investigate the effects of dietary and lifestyle exposure on clinical outcomes. The mounting body of knowledge regarding diet-related health status and disease risk is expected to lead in the near future to the development of improved diagnostic procedures and therapeutic strategies targeting processes relevant to nutrition. The state of the art of aging and nutrigenomics research and the molecular mechanisms underlying the beneficial effects of bioactive nutrients on the main aging-related disorders are reviewed herein.

  18. Chlorinative stress in age-related diseases: a literature review.

    Science.gov (United States)

    Casciaro, Marco; Di Salvo, Eleonora; Pace, Elisabetta; Ventura-Spagnolo, Elvira; Navarra, Michele; Gangemi, Sebastiano

    2017-01-01

    Aging is an agglomerate of biological long-lasting processes that result being inevitable. Main actors in this scenario are both long-term inflammation and oxidative stress. It has been proved that oxidative stress induce alteration in proteins and this fact itself is critically important in the pathophysiological mechanisms leading to diseases typical of aging. Among reactive species, chlorine ones such as hypochlorous acid (HOCl) are cytotoxic oxidants produced by activated neutrophils during chronic inflammation processes. HOCl can also cause damages by reacting with biological molecules. HOCl is generated by myeloperoxidase (MPO) and augmented serum levels of MPO have been described in acute and chronic inflammatory conditions in cardiovascular patients and has been implicated in many inflammatory diseases such as atherosclerosis, neurodegenerative conditions, and some cancers. Due to these data, we decided to conduct an up-to-date review evaluating chlorinative stress effects on every age-related disease linked; potential anti-oxidant countermeasures were also assessed. Results obtained associated HOCl generation to the aging processes and confirmed its connection with diseases like neurodegenerative and cardiovascular pathologies, atherosclerosis and cancer; chlorination was mainly linked to diseases where molecular (protein) alteration constitute the major suspected cause: i.e. inflammation, tissue lesions, DNA damages, apoptosis and oxidative stress itself. According data collected, a healthy lifestyle together with some dietary suggestion and/or the administration of nutracetical antioxidant integrators could balance the effects of chlorinative stress and, in some cases, slow down or prevent the onset of age-releated diseases.

  19. Nutritional Considerations for Healthy Aging and Reduction in Age-Related Chronic Disease12

    OpenAIRE

    Shlisky, Julie; Bloom, David E; Beaudreault, Amy R; Tucker, Katherine L; Keller, Heather H; Freund-Levi, Yvonne; Fielding, Roger A; Cheng, Feon W; Jensen, Gordon L; Wu, Dayong; Meydani, Simin N

    2017-01-01

    A projected doubling in the global population of people aged ≥60 y by the year 2050 has major health and economic implications, especially in developing regions. Burdens of unhealthy aging associated with chronic noncommunicable and other age-related diseases may be largely preventable with lifestyle modification, including diet. However, as adults age they become at risk of “nutritional frailty,” which can compromise their ability to meet nutritional requirements at a time when specific nutr...

  20. Kidney disease and aging: A reciprocal relation.

    Science.gov (United States)

    Kooman, Jeroen P; van der Sande, Frank M; Leunissen, Karel M L

    2017-01-01

    Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are overrepresented in elderly patients. This provides specific challenges for the treatment, as the start of dialysis in vulnerable elderly patients may be associated with a rapid decline in functional performance. However, prognosis in elderly patients with ESRD is quite variable and related to the presence of comorbidity and geriatric impairments. The decision to start dialysis in elderly patients should always be based on shared decision making, which may be aided by the use of prediction models which should however not be used to withhold dialysis treatment. The treatment of ESRD in elderly patients should be based on a multidimensional treatment plan with a role for active rehabilitation. Moreover, there also appears to be a reciprocal relationship between aging and CKD, as the presence of geriatric complications is also high in younger patients with ESRD. This has led to the hypothesis of a premature aging process associated with CKD, resulting in different phenotypes such as premature vascular aging, muscle wasting, bone disease, cognitive dysfunction and frailty. Prevention and treatment of this phenotype is based on optimal treatment of CKD, associated comorbidities, and lifestyle factors by established treatments. For the future, interventions, which are developed to combat the aging process in general, might also have relevance for the treatment of patients with CKD, but their role should always be investigated in adequately powered clinical trials, as results obtained in experimental trials may not be directly translatable to the clinical situation of elderly patients. In the meantime, physical exercise is a very important intervention, by improving both physical capacity and functional performance, as well as by a direct effect on the aging process. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Does eating particular diets alter risk of age-related macular degeneration in users of the Age-Related Eye Disease Study supplements?

    Science.gov (United States)

    Background: Recent information suggests that the Age-Related Eye Disease Study (AREDS) supplement, enhanced intake of omega-3 fatty acids, and diminishing dietary glycemic index (dGI) are protective against advanced age-related macular degeneration (AMD). Methods: Dietary information was collected a...

  2. Emerging therapies for idiopathic pulmonary fibrosis, a progressive age-related disease

    Science.gov (United States)

    Mora, Ana L.; Rojas, Mauricio; Pardo, Annie; Selman, Moises

    2018-01-01

    Idiopathic pulmonary fibrosis (IPF) is a fatal age-associated disease that is characterized by progressive and irreversible scarring of the lung. The pathogenesis of IPF is not completely understood and current therapies are limited to those that reduce the rate of functional decline in patients with mild-to-moderate disease. In this context, new therapeutic approaches that substantially improve the survival time and quality of life of these patients are urgently needed. Our incomplete understanding of the pathogenic mechanisms of IPF and the lack of appropriate experimental models that reproduce the key characteristics of the human disease are major challenges. As ageing is a major risk factor for IPF, age-related cell perturbations such as telomere attrition, senescence, epigenetic drift, stem cell exhaustion, loss of proteostasis and mitochondrial dysfunction are becoming targets of interest for IPF therapy. In this Review, we discuss current and emerging therapies for IPF, particularly those targeting age-related mechanisms, and discuss future therapeutic approaches. PMID:29081515

  3. The lysosomal storage disease continuum with ageing-related neurodegenerative disease.

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    Lloyd-Evans, Emyr; Haslett, Luke J

    2016-12-01

    Lysosomal storage diseases and diseases of ageing share many features both at the physiological level and with respect to the mechanisms that underlie disease pathogenesis. Although the exact pathophysiology is not exactly the same, it is astounding how many similar pathways are altered in all of these diseases. The aim of this review is to provide a summary of the shared disease mechanisms, outlining the similarities and differences and how genetics, insight into rare diseases and functional research has changed our perspective on the causes underlying common diseases of ageing. The lysosome should no longer be considered as just the stomach of the cell or as a suicide bag, it has an emerging role in cellular signalling, nutrient sensing and recycling. The lysosome is of fundamental importance in the pathophysiology of diseases of ageing and by comparing against the LSDs we not only identify common pathways but also therapeutic targets so that ultimately more effective treatments can be developed for all neurodegenerative diseases. Copyright © 2016. Published by Elsevier B.V.

  4. Glycomics and glycoproteomics focused on aging and age-related diseases--Glycans as a potential biomarker for physiological alterations.

    Science.gov (United States)

    Miura, Yuri; Endo, Tamao

    2016-08-01

    Since glycosylation depends on glycosyltransferases, glycosidases, and sugar nucleotide donors, it is susceptible to the changes associated with physiological and pathological conditions. Therefore, alterations in glycan structures may be good targets and biomarkers for monitoring health conditions. Since human aging and longevity are affected by genetic and environmental factors such as diseases, lifestyle, and social factors, a scale that reflects various environmental factors is required in the study of human aging and longevity. We herein focus on glycosylation changes elucidated by glycomic and glycoproteomic studies on aging, longevity, and age-related diseases including cognitive impairment, diabetes mellitus, and frailty. We also consider the potential of glycan structures as biomarkers and/or targets for monitoring physiological and pathophysiological changes. Glycan structures are altered in age-related diseases. These glycans and glycoproteins may be involved in the pathophysiology of these diseases and, thus, be useful diagnostic markers. Age-dependent changes in N-glycans have been reported previously in cohort studies, and characteristic N-glycans in extreme longevity have been proposed. These findings may lead to a deeper understanding of the mechanisms underlying aging as well as the factors influencing longevity. Alterations in glycosylation may be good targets and biomarkers for monitoring health conditions, and be applicable to studies on age-related diseases and healthy aging. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Dietary compound score and risk of age-related macular degeneration in the Age-Related Eye Disease Study

    Science.gov (United States)

    Purpose: Because foods provide many nutrients, which may interact with each other to modify risk for multifactorial diseases such as age-related macular degeneration (AMD), we sought to develop a composite scoring system to summarize the combined effect of multiple dietary nutrients on AMD risk. Th...

  6. The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates

    Directory of Open Access Journals (Sweden)

    Claudio Franceschi

    2018-03-01

    Full Text Available Geroscience, the new interdisciplinary field that aims to understand the relationship between aging and chronic age-related diseases (ARDs and geriatric syndromes (GSs, is based on epidemiological evidence and experimental data that aging is the major risk factor for such pathologies and assumes that aging and ARDs/GSs share a common set of basic biological mechanisms. A consequence is that the primary target of medicine is to combat aging instead of any single ARD/GSs one by one, as favored by the fragmentation into hundreds of specialties and sub-specialties. If the same molecular and cellular mechanisms underpin both aging and ARDs/GSs, a major question emerges: which is the difference, if any, between aging and ARDs/GSs? The hypothesis that ARDs and GSs such as frailty can be conceptualized as accelerated aging will be discussed by analyzing in particular frailty, sarcopenia, chronic obstructive pulmonary disease, cancer, neurodegenerative diseases such as Alzheimer and Parkinson as well as Down syndrome as an example of progeroid syndrome. According to this integrated view, aging and ARDs/GSs become part of a continuum where precise boundaries do not exist and the two extremes are represented by centenarians, who largely avoided or postponed most ARDs/GSs and are characterized by decelerated aging, and patients who suffered one or more severe ARDs in their 60s, 70s, and 80s and show signs of accelerated aging, respectively. In between these two extremes, there is a continuum of intermediate trajectories representing a sort of gray area. Thus, clinically different, classical ARDs/GSs are, indeed, the result of peculiar combinations of alterations regarding the same, limited set of basic mechanisms shared with the aging process. Whether an individual will follow a trajectory of accelerated or decelerated aging will depend on his/her genetic background interacting lifelong with environmental and lifestyle factors. If ARDs and GSs are

  7. Hypoxia-Inducible Histone Lysine Demethylases: Impact on the Aging Process and Age-Related Diseases

    Science.gov (United States)

    Salminen, Antero; Kaarniranta, Kai; Kauppinen, Anu

    2016-01-01

    Hypoxia is an environmental stress at high altitude and underground conditions but it is also present in many chronic age-related diseases, where blood flow into tissues is impaired. The oxygen-sensing system stimulates gene expression protecting tissues against hypoxic insults. Hypoxia stabilizes the expression of hypoxia-inducible transcription factor-1α (HIF-1α), which controls the expression of hundreds of survival genes related to e.g. enhanced energy metabolism and autophagy. Moreover, many stress-related signaling mechanisms, such as oxidative stress and energy metabolic disturbances, as well as the signaling cascades via ceramide, mTOR, NF-κB, and TGF-β pathways, can also induce the expression of HIF-1α protein to facilitate cell survival in normoxia. Hypoxia is linked to prominent epigenetic changes in chromatin landscape. Screening studies have indicated that the stabilization of HIF-1α increases the expression of distinct histone lysine demethylases (KDM). HIF-1α stimulates the expression of KDM3A, KDM4B, KDM4C, and KDM6B, which enhance gene transcription by demethylating H3K9 and H3K27 sites (repressive epigenetic marks). In addition, HIF-1α induces the expression of KDM2B and KDM5B, which repress transcription by demethylating H3K4me2,3 sites (activating marks). Hypoxia-inducible KDMs support locally the gene transcription induced by HIF-1α, although they can also control genome-wide chromatin landscape, especially KDMs which demethylate H3K9 and H3K27 sites. These epigenetic marks have important role in the control of heterochromatin segments and 3D folding of chromosomes, as well as the genetic loci regulating cell type commitment, proliferation, and cellular senescence, e.g. the INK4 box. A chronic stimulation of HIF-1α can provoke tissue fibrosis and cellular senescence, which both are increasingly present with aging and age-related diseases. We will review the regulation of HIF-1α-dependent induction of KDMs and clarify their role in

  8. A Systematic Investigation into Aging Related Genes in Brain and Their Relationship with Alzheimer's Disease.

    Science.gov (United States)

    Meng, Guofeng; Zhong, Xiaoyan; Mei, Hongkang

    2016-01-01

    Aging, as a complex biological process, is accompanied by the accumulation of functional loses at different levels, which makes age to be the biggest risk factor to many neurological diseases. Even following decades of investigation, the process of aging is still far from being fully understood, especially at a systematic level. In this study, we identified aging related genes in brain by collecting the ones with sustained and consistent gene expression or DNA methylation changes in the aging process. Functional analysis with Gene Ontology to these genes suggested transcriptional regulators to be the most affected genes in the aging process. Transcription regulation analysis found some transcription factors, especially Specificity Protein 1 (SP1), to play important roles in regulating aging related gene expression. Module-based functional analysis indicated these genes to be associated with many well-known aging related pathways, supporting the validity of our approach to select aging related genes. Finally, we investigated the roles of aging related genes on Alzheimer's Disease (AD). We found that aging and AD related genes both involved some common pathways, which provided a possible explanation why aging made the brain more vulnerable to Alzheimer's Disease.

  9. OMEGA-3 FATTY ACIDS AND AGE-RELATED DISEASES: REALITIES AND PROSPECTS

    Directory of Open Access Journals (Sweden)

    O. M. Drapkina

    2015-01-01

    Full Text Available Efficacy of omega-3 fatty acids in cardiology is so high that in many countries omega-3 fatty acids are included into the treatment protocols for patients with cardiovascular diseases. This therapeutic class slows down oxidative stress and chronic inflammation processes, thereby providing a significant contribution to the complex treatment of hypertension. Besides, omega-3 fatty acids slow down the aging process and prevent the development of age-related diseases affecting the rate of telomere shortening.

  10. Age-related macular disease : studies on incidence, risk factors, and prognosis

    NARCIS (Netherlands)

    R. van Leeuwen (Redmer)

    2003-01-01

    textabstractAge-related macular disease (AMD) is a new name, recently coined by Bird,25 for a progressive and degenerative disease in elderly persons affecting the macula lutea. Dysfunction of this part of the retina, and especially its centre, the fovea, results in the inability to read,

  11. Novel gene function revealed by mouse mutagenesis screens for models of age-related disease.

    Science.gov (United States)

    Potter, Paul K; Bowl, Michael R; Jeyarajan, Prashanthini; Wisby, Laura; Blease, Andrew; Goldsworthy, Michelle E; Simon, Michelle M; Greenaway, Simon; Michel, Vincent; Barnard, Alun; Aguilar, Carlos; Agnew, Thomas; Banks, Gareth; Blake, Andrew; Chessum, Lauren; Dorning, Joanne; Falcone, Sara; Goosey, Laurence; Harris, Shelley; Haynes, Andy; Heise, Ines; Hillier, Rosie; Hough, Tertius; Hoslin, Angela; Hutchison, Marie; King, Ruairidh; Kumar, Saumya; Lad, Heena V; Law, Gemma; MacLaren, Robert E; Morse, Susan; Nicol, Thomas; Parker, Andrew; Pickford, Karen; Sethi, Siddharth; Starbuck, Becky; Stelma, Femke; Cheeseman, Michael; Cross, Sally H; Foster, Russell G; Jackson, Ian J; Peirson, Stuart N; Thakker, Rajesh V; Vincent, Tonia; Scudamore, Cheryl; Wells, Sara; El-Amraoui, Aziz; Petit, Christine; Acevedo-Arozena, Abraham; Nolan, Patrick M; Cox, Roger; Mallon, Anne-Marie; Brown, Steve D M

    2016-08-18

    Determining the genetic bases of age-related disease remains a major challenge requiring a spectrum of approaches from human and clinical genetics to the utilization of model organism studies. Here we report a large-scale genetic screen in mice employing a phenotype-driven discovery platform to identify mutations resulting in age-related disease, both late-onset and progressive. We have utilized N-ethyl-N-nitrosourea mutagenesis to generate pedigrees of mutagenized mice that were subject to recurrent screens for mutant phenotypes as the mice aged. In total, we identify 105 distinct mutant lines from 157 pedigrees analysed, out of which 27 are late-onset phenotypes across a range of physiological systems. Using whole-genome sequencing we uncover the underlying genes for 44 of these mutant phenotypes, including 12 late-onset phenotypes. These genes reveal a number of novel pathways involved with age-related disease. We illustrate our findings by the recovery and characterization of a novel mouse model of age-related hearing loss.

  12. Glaucoma and Alzheimer Disease: A Single Age-Related Neurodegenerative Disease of the Brain.

    Science.gov (United States)

    Mancino, Raffaele; Martucci, Alessio; Cesareo, Massimo; Giannini, Clarissa; Corasaniti, Maria Tiziana; Bagetta, Giacinto; Nucci, Carlo

    2017-12-06

    Open Angle Glaucoma is one of the leading causes of irreversible blindness worldwide. Elevated intraocular pressure is considered an important risk factor for glaucoma, however a subset of patients experience disease progression even in presence of normal intraocular pressure values. This implies that risk factors other than intraocular pressure are involved in the pathogenesis of glaucoma. A possible relationship between glaucoma and neurodegenerative diseases such as Alzheimer Disease has been suggested. In this regard, we have recently described a high prevalence of alterations typical of glaucoma, using Heidelberg Retinal Tomograph-3 (HRT-3), in a group of patients with Alzheimer Disease. Interestingly, these alterations were not associated with elevated intraocular pressure or abnormal Central Corneal Thickness values. Alzheimer Disease is the most common form of dementia associated with progressive deterioration of memory and cognition. Complaints related to vision are common among Alzheimer Disease patients. Features common to both diseases, including risk factors and pathophysiological mechanisms, gleaned from the recent literature do suggest that Alzheimer Disease and glaucoma can be considered age-related neurodegenerative diseases that may co-exist in the elderly. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Glycated Lysine Residues: A Marker for Non-Enzymatic Protein Glycation in Age-Related Diseases

    Directory of Open Access Journals (Sweden)

    Nadeem A. Ansari

    2011-01-01

    Full Text Available Nonenzymatic glycosylation or glycation of macromolecules, especially proteins leading to their oxidation, play an important role in diseases. Glycation of proteins primarily results in the formation of an early stage and stable Amadori-lysine product which undergo further irreversible chemical reactions to form advanced glycation endproducts (AGEs. This review focuses these products in lysine rich proteins such as collagen and human serum albumin for their role in aging and age-related diseases. Antigenic characteristics of glycated lysine residues in proteins together with the presence of serum autoantibodies to the glycated lysine products and lysine-rich proteins in diabetes and arthritis patients indicates that these modified lysine residues may be a novel biomarker for protein glycation in aging and age-related diseases.

  14. Stem cells: Potential therapy for age-related diseases

    DEFF Research Database (Denmark)

    Kassem, Moustapha

    2006-01-01

    Aging is associated with a progressive failing of tissues and organs of the human body leading to a large number of age-related diseases. Regenerative medicine is an emerging clinical discipline that aims to employ cellular medicines (normal cells, ex vivo expanded cells, or tissue......-engineered organs) to restore the functions of damaged or defective tissues and organs and thus to "rejuvenate" the failing aging body. One of the most important sources for cellular medicine is embryonic and adult (somatic) stem cells (SSCs). One example of SCCs with enormous clinical potential is the mesenchymal...... and organs in tissue-engineering protocols. However, several challenges confront the use of these cells in the clinic, ranging from biological challenges (e.g., how to isolate a homogenous populations of the cells with specific criteria from the bone marrow and how to expand them ex vivo without affecting...

  15. Perspectives of Stem Cell-Based Therapy for Age-Related Retinal Degenerative Diseases.

    Science.gov (United States)

    Holan, Vladimir; Hermankova, Barbora; Kossl, Jan

    2017-09-01

    Retinal degenerative diseases, which include age-related macular degeneration, retinitis pigmentosa, diabetic retinopathy, and glaucoma, mostly affect the elderly population and are the most common cause of decreased quality of vision or even blindness. So far, there is no satisfactory treatment protocol to prevent, stop, or cure these disorders. A great hope and promise for patients suffering from retinal diseases is represented by stem cell-based therapy that could replace diseased or missing retinal cells and support regeneration. In this respect, mesenchymal stem cells (MSCs) that can be obtained from the particular patient and used as autologous cells have turned out to be a promising stem cell type for treatment. Here we show that MSCs can differentiate into cells expressing markers of retinal cells, inhibit production of pro-inflammatory cytokines by retinal tissue, and produce a number of growth and neuroprotective factors for retinal regeneration. All of these properties make MSCs a prospective cell type for cell-based therapy of age-related retinal degenerative diseases.

  16. The Potential of Chitosan and Its Derivatives in Prevention and Treatment of Age-Related Diseases

    Science.gov (United States)

    Kerch, Garry

    2015-01-01

    Age-related, diet-related and protein conformational diseases, such as atherosclerosis, diabetes mellitus, cancer, hypercholesterolemia, cardiovascular and neurodegenerative diseases are common in the elderly population. The potential of chitosan, chitooligosaccharides and their derivatives in prevention and treatment of age-related dysfunctions is reviewed and discussed in this paper. The influence of oxidative stress, low density lipoprotein oxidation, increase of tissue stiffness, protein conformational changes, aging-associated chronic inflammation and their pathobiological significance have been considered. The chitosan-based functional food also has been reviewed. PMID:25871293

  17. Pleiotropic Meta-Analyses of Longitudinal Studies Discover Novel Genetic Variants Associated with Age-Related Diseases

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    Liang He

    2016-10-01

    Full Text Available Age-related diseases may result from shared biological mechanisms in intrinsic processes of aging. Genetic effects on age-related diseases are often modulated by environmental factors due to their little contribution to fitness or are mediated through certain endophenotypes. Identification of genetic variants with pleiotropic effects on both common complex diseases and endophenotypes may reveal potential conflicting evolutionary pressures and deliver new insights into shared genetic contribution to healthspan and lifespan. Here, we performed pleiotropic meta-analyses of genetic variants using five NIH-funded datasets by integrating univariate summary statistics for age-related diseases and endophenotypes. We investigated three groups of traits: (1 endophenotypes such as blood glucose, blood pressure, lipids, hematocrit, and body mass index, (2 time-to-event outcomes such as the age-at-onset of diabetes mellitus (DM, cancer, cardiovascular diseases (CVDs and neurodegenerative diseases (NDs, and (3 both combined. In addition to replicating previous findings, we identify seven novel genome-wide significant loci (< 5e-08, out of which five are low-frequency variants. Specifically, from Group 2, we find rs7632505 on 3q21.1 in SEMA5B, rs460976 on 21q22.3 (1 kb from TMPRSS2 and rs12420422 on 11q24.1 predominantly associated with a variety of CVDs, rs4905014 in ITPK1 associated with stroke and heart failure, rs7081476 on 10p12.1 in ANKRD26 associated with multiple diseases including DM, CVDs, and NDs. From Group 3, we find rs8082812 on 18p11.22 and rs1869717 on 4q31.3 associated with both endophenotypes and CVDs. Our follow-up analyses show that rs7632505, rs4905014, and rs8082812 have age-dependent effects on coronary heart disease or stroke. Functional annotation suggests that most of these SNPs are within regulatory regions or DNase clusters and in linkage disequilibrium with expression quantitative trait loci, implying their potential regulatory

  18. The Association of Statin Use with Age-Related Macular Degeneration Progression: The Age-Related Eye Disease Study 2 Report Number 9.

    Science.gov (United States)

    Al-Holou, Shaza N; Tucker, William R; Agrón, Elvira; Clemons, Traci E; Cukras, Catherine; Ferris, Frederick L; Chew, Emily Y

    2015-12-01

    To evaluate the association of statin use with progression of age-related macular degeneration (AMD). Preplanned, prospective cohort study within a controlled clinical trial of oral supplementation for age-related eye diseases. Age-Related Eye Disease Study 2 (AREDS2) participants, aged 50 to 85 years. Factors, including age, gender, smoking status, aspirin use, and history of diabetes, hypertension, heart disease, angina, and stroke-all known to be associated with statin use-were included in a logistic regression model to estimate propensity scores for each participant. Age-adjusted proportional hazards regression models, with and without propensity score matching, were performed to evaluate the association of statin use with progression to late AMD. Analyses adjusting for the competing risk of death were also performed. Baseline and annual stereoscopic fundus photographs were assessed centrally by masked graders for the development of late AMD, either neovascular AMD or geographic atrophy (GA). Of the 3791 participants (2462 with bilateral large drusen and 1329 with unilateral late AMD at baseline), 1659 (43.8%) were statin users. The overall analysis, with no matching of propensity scores and no adjustment for death as a competing risk, showed that statin use was not associated with progression to late AMD (hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.83-1.41; P = 0.56). When matched for propensity scores and adjusted for death as a competing risk, the result was not statistically significant (HR, 0.81; 95% CI, 0.55-1.20; P = 0.29). Furthermore, subgroup analyses of persons with or without late AMD at baseline and the various components of late AMD (neovascular AMD, central GA, or any GA) also showed no statistically significant association of statin use with progression to AMD. Statin use was not statistically significantly associated with progression to late AMD in the AREDS2 participants, and these findings are consistent with findings in the

  19. The Association of Statin Use with Age-Related Macular Degeneration Progression The Age-Related Eye Disease Study 2 Report Number 9

    Science.gov (United States)

    Al-Holou, Shaza N.; Tucker, William R.; Agrón, Elvira; Clemons, Traci E.; Cukras, Catherine; Ferris, Frederick L.; Chew, Emily Y.

    2015-01-01

    Objective/purpose To evaluate the association of statin use with progression of age-related macular degeneration (AMD). Design Preplanned, prospective cohort study within a controlled clinical trial of oral supplementation for age-related eye diseases. Subjects Age-Related Eye Disease Study 2 participants, aged 50 to 85 years. Methods Factors, including age, gender, smoking status, aspirin use, and history of diabetes, hypertension, heart disease, angina, and stroke, all known to be associated with statin use, were included in a logistic regression model to estimate propensity scores for each participant. Age-adjusted proportional hazards regression models, with and without propensity score matching, were performed to evaluate the association of statin use with progression to late AMD. Analyses were also performed adjusting for the competing risk of death. Main Outcome Measures Baseline and annual stereoscopic fundus photographs were assessed centrally by masked graders for the development of late AMD, either neovascular AMD or geographic atrophy (GA). Results Of the 3791 participants (2462 with bilateral large drusen and 1329 with unilateral late AMD at baseline), 1659 (43.8%) were statin users. The overall analysis, with no matching of propensity scores and no adjustment for death as a competing risk, showed that statin use was not associated with progression to late AMD (hazard ratios [HR] of 1.08, 95% confidence intervals [CI] of 0.83–1.41, P=0.56). When matched for propensity scores and adjusted for death as a competing risk, the result was not statistically significant with HR: 0.81, 95% CI: 0.55–1.20, P=0.29. Further subgroup analyses of persons with or without late AMD at baseline to the various components of late AMD (neovascular, central geographic atrophy, or any geographic atrophy) also showed no statistically significant association of statin use with progression to AMD. Conclusions Statin use was not statistically significantly associated with the

  20. Physical Activity and Telomere Biology: Exploring the Link with Aging-Related Disease Prevention

    OpenAIRE

    Andrew T. Ludlow; Stephen M. Roth

    2011-01-01

    Physical activity is associated with reduced risk of several age-related diseases as well as with increased longevity in both rodents and humans. Though these associations are well established, evidence of the molecular and cellular factors associated with reduced disease risk and increased longevity resulting from physical activity is sparse. A long-standing hypothesis of aging is the telomere hypothesis: as a cell divides, telomeres shorten resulting eventually in replicative senescence and...

  1. Diminished stress resistance and defective adaptive homeostasis in age-related diseases.

    Science.gov (United States)

    Lomeli, Naomi; Bota, Daniela A; Davies, Kelvin J A

    2017-11-01

    Adaptive homeostasis is defined as the transient expansion or contraction of the homeostatic range following exposure to subtoxic, non-damaging, signaling molecules or events, or the removal or cessation of such molecules or events ( Mol. Aspects Med. (2016) 49, 1-7 ). Adaptive homeostasis allows us to transiently adapt (and then de-adapt) to fluctuating levels of internal and external stressors. The ability to cope with transient changes in internal and external environmental stress, however, diminishes with age. Declining adaptive homeostasis may make older people more susceptible to many diseases. Chronic oxidative stress and defective protein homeostasis (proteostasis) are two major factors associated with the etiology of age-related disorders. In the present paper, we review the contribution of impaired responses to oxidative stress and defective adaptive homeostasis in the development of age-associated diseases. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  2. The Interleukin-6 inflammation pathway from cholesterol to aging – Role of statins, bisphosphonates and plant polyphenols in aging and age-related diseases

    Directory of Open Access Journals (Sweden)

    Omoigui Sota

    2007-03-01

    Full Text Available Abstract We describe the inflammation pathway from Cholesterol to Aging. Interleukin 6 mediated inflammation is implicated in age-related disorders including Atherosclerosis, Peripheral Vascular Disease, Coronary Artery Disease, Osteoporosis, Type 2 Diabetes, Dementia and Alzheimer's disease and some forms of Arthritis and Cancer. Statins and Bisphosphonates inhibit Interleukin 6 mediated inflammation indirectly through regulation of endogenous cholesterol synthesis and isoprenoid depletion. Polyphenolic compounds found in plants, fruits and vegetables inhibit Interleukin 6 mediated inflammation by direct inhibition of the signal transduction pathway. Therapeutic targets for the control of all the above diseases should include inhibition of Interleukin-6 mediated inflammation.

  3. Interest of active posturography to detect age-related and early Parkinson's disease-related impairments in mediolateral postural control.

    Science.gov (United States)

    Bonnet, Cédrick T; Delval, Arnaud; Defebvre, Luc

    2014-11-15

    Patients with Parkinson's disease display impairments of postural control most particularly in active, challenging conditions. The objective of the present study was to analyze early signs of disease-related and also age-related impairments in mediolateral body extension and postural control. Fifty-five participants (18 Hoehn and Yahr stage 2 patients in the off-drug condition, 18 healthy elderly control subjects, and 19 young adults) were included in the study. The participants performed a quiet stance task and two active tasks that analyzed the performance in mediolateral body motion: a limit of stability and a rhythmic weight shift task. As expected, the patients displayed significantly lower and slower body displacement (head, neck, lower back, center of pressure) than elderly control subjects when performing the two body excursion tasks. However, the behavioral variability in both tasks was similar between the groups. Under these active conditions, the patients showed significantly lower contribution of the hip postural control mechanisms compared with the elderly control subjects. Overall, the patients seemed to lower their performance in order to prevent a mediolateral postural instability. However, these patients, at an early stage of their disease, were not unstable in quiet stance. Complementarily, elderly control subjects displayed slower body performance than young adults, which therefore showed an additional age-related impairment in mediolateral postural control. Overall, the study illustrated markers of age-related and Parkinson's disease impairments in mediolateral postural control that may constrain everyday activities in elderly adults and even more in patients with Parkinson's disease. Copyright © 2014 the American Physiological Society.

  4. Telomeres and telomerase as therapeutic targets to prevent and treat age-related diseases [version 1; referees: 4 approved

    Directory of Open Access Journals (Sweden)

    Christian Bär

    2016-01-01

    Full Text Available Telomeres, the protective ends of linear chromosomes, shorten throughout an individual’s lifetime. Telomere shortening is a hallmark of molecular aging and is associated with premature appearance of diseases associated with aging. Here, we discuss the role of telomere shortening as a direct cause for aging and age-related diseases. In particular, we draw attention to the fact that telomere length influences longevity. Furthermore, we discuss intrinsic and environmental factors that can impact on human telomere erosion. Finally, we highlight recent advances in telomerase-based therapeutic strategies for the treatment of diseases associated with extremely short telomeres owing to mutations in telomerase, as well as age-related diseases, and ultimately aging itself.

  5. [Non-pharmacologic therapy of age-related macular degeneration, based on the etiopathogenesis of the disease].

    Science.gov (United States)

    Fischer, Tamás

    2015-07-12

    It has a great therapeutic significance that the disorder of the vascular endothelium, which supplies the affected ocular structures, plays a major role in the development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfuncition and age-related macular degeneration is accompanied by a general inflammatory response. The vascular wall including those in chorioids may be activated by several repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic and genetic factors causing a protracted host defence response with a consequent vascular damage, which leads to age-related macular degeneration. Based on this concept, age-related macular degeneration is a local manifestation of the systemic vascular disease. This recognition should have therapeutic implications because restoration of endothelial dysfunction can stabilize the condition of chronic vascular disease including age-related macular degeneration, as well. Restoration of endothelial dysfunction by non-pharmacological or pharmacological interventions may prevent the development or improve endothelial dysfunction resulting in prevention or improvement of age-related macular degeneration. Non-pharmacological interventions which may have beneficial effect in endothelial dysfunction include (1) smoking cessation; (2) reduction of increased body weight; (3) adequate physical activity; (4) appropriate diet (a) proper dose of flavonoids, polyphenols and kurcumin; (b) omega-3 long-chain polyunsaturated fatty acids: docosahexaenoic acid and eicosapentaenoic acid; (c) carotenoids, lutein and zeaxanthins), (d) management of dietary glycemic index, (e) caloric restriction, and (5) elimination of stressful lifestyle. Non-pharmacological interventions should be preferable even if medicaments are also used for the treatment of endothelial dysfunction.

  6. Anti-Inflamm-Ageing and/or Anti-Age-Related Disease Emerging Treatments: A Historical Alchemy or Revolutionary Effective Procedures?

    Directory of Open Access Journals (Sweden)

    Carmela Rita Balistreri

    2018-01-01

    Full Text Available The “long-life elixir” has long represented for humans a dream, a vanity’s sin for remaining young and to long survive. Today, because of ageing population phenomenon, the research of antiageing interventions appears to be more important than ever, for preserving health in old age and retarding/or delaying the onset of age-related diseases. A hope is given by experimental data, which evidence the possibility of retarding ageing in animal models. In addition, it has been also demonstrated in animal life-extending studies not only the possibility of increasing longevity but also the ability to retard the onset of age-related diseases. Interestingly, this recent evidence is leading to promise of obtaining the same effects in humans and resulting in benefits for their health in old ages. In order to achieve this goal, different approaches have been used ranging from pharmacological targeting of ageing, basic biological assays, and big data analysis to the recent use of young blood, stem cells, cellular, genetic, and epigenetic reprogramming, or other techniques of regenerative medicine. However, only a little fraction of these approaches has the features for being tested in clinical applications. Here, new emerging molecules, drugs, and procedures will be described, by evidencing potential benefits and limitations.

  7. Protective role of the apolipoprotein E2 allele in age-related disease traits and survival

    DEFF Research Database (Denmark)

    Kulminski, Alexander M; Raghavachari, Nalini; Arbeev, Konstantin G

    2016-01-01

    , which can link this allele with age-related phenotypes. We focused on age-related macular degeneration, bronchitis, asthma, pneumonia, stroke, creatinine, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, diseases of heart (HD), cancer, and survival. Our analysis......-related mechanism is also sensitive to gender. The LDL-C-related mechanism appears to be independent of these factors. Insights into mechanisms linking ε2 allele with age-related phenotypes given biodemographic structure of the population studied may benefit translation of genetic discoveries to health care...

  8. [The age-related macular degeneration as a vascular disease/part of systemic vasculopathy: contributions to its pathogenesis].

    Science.gov (United States)

    Fischer, Tamás

    2015-03-01

    The wall of blood vessels including those in choroids may be harmed by several repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic, and genetic impacts (risk factors), which may trigger a protracted response, the so-called host defense response. As a consequence, pathological changes resulting in vascular injury (e. g. atherosclerosis, age-related macular degeneration) may be evolved. Risk factors can also act directly on the endothelium through an increased production of reactive oxygen species promoting an endothelial activation, which leads to endothelial dysfunction, the onset of vascular disease. Thus, endothelial dysfunction is a link between the harmful stimulus and vascular injury; any kind of harmful stimuli may trigger the defensive chain that results in inflammation that may lead to vascular injury. It has been shown that even early age-related macular degeneration is associated with the presence of diffuse arterial disease and patients with early age-related macular degeneration demonstrate signs of systemic and retinal vascular alterations. Chronic inflammation, a feature of AMD, is tightly linked to diseases associated with ED: AMD is accompanied by a general inflammatory response, in the form of complement system activation, similar to that observed in degenerative vascular diseases such as atherosclerosis. All these facts indicate that age-related macular degeneration may be a vascular disease (or part of a systemic vasculopathy). This recognition could have therapeutic implications because restoration of endothelial dysfunction may prevent the development or improve vascular disease resulting in prevention or improvement of age-related macular degeneration as well.

  9. Gender Differences in Age-Related Striatal Dopamine Depletion in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Jae Jung Lee

    2015-09-01

    Full Text Available Objective Gender differences are a well-known clinical characteristic of Parkinson’s disease (PD. In-vivo imaging studies demonstrated that women have greater striatal dopamine transporter (DAT activity than do men, both in the normal population and in PD patients. We hypothesize that women exhibit more rapid aging-related striatal DAT reduction than do men, as the potential neuroprotective effect of estrogen wanes with age. Methods This study included 307 de novo PD patients (152 men and 155 women who underwent DAT scans for an initial diagnostic work-up. Gender differences in age-related DAT decline were assessed in striatal sub-regions using linear regression analysis. Results Female patients exhibited greater DAT activity compared with male patients in all striatal sub-regions. The linear regression analysis revealed that age-related DAT decline was greater in the anterior and posterior caudate, and the anterior putamen in women compared with men; we did not observe this difference in other sub-regions. Conclusions This study demonstrated the presence of gender differences in age-related DAT decline in striatal sub-regions, particularly in the antero-dorsal striatum, in patients with PD, presumably due to aging-related decrease in estrogen. Because this difference was not observed in the sensorimotor striatum, this finding also suggests that women may not have a greater capacity to tolerate PD pathogenesis than do men.

  10. Selected biomarkers of age-related diseases in older subjects with different nutrition.

    Science.gov (United States)

    Krajcovicova-Kudlackova, M; Babinska, K; Blazicek, P; Valachovicova, M; Spustova, V; Mislanova, C; Paukova, V

    2011-01-01

    The nutritionists introduce on the base of epidemiological and clinical studies that appropriately planned vegetarian diets are healthful, and may provide health benefits in the prevention and treatment of certain diseases. Aging belongs to the main risks of cardiovascular disease. Markers of age-related diseases (cardiovascular, metabolic syndrome, diabetes) were assessed in two nutritional groups of older apparently healthy non-obese non-smoking women aged 60-70 years, 45 vegetarians (lacto-ovo-vegetarians and semi-vegetarians) and 38 non-vegetarians (control group on a traditional mixed diet, general population). Vegetarian values of total cholesterol, LDL-cholesterol, triacylglycerols, C-reactive protein, glucose, insulin and insulin resistance are significantly reduced. Non-vegetarian average values of total cholesterol, LDL-cholesterol and C-reactive protein are risk. Vegetarians have a better antioxidative status (significantly increased vitamin C, lipid-standardized vitamine E and beta-carotene plasma concentrations). Favourable values of cardiovascular risk markers in older vegetarian women document a beneficial effect of vegetarian nutrition in prevention of this disease as well as the vegetarian diet can be an additional factor in therapy. Vegetarians suffer from mild hyperhomocysteinemia; it is due to the lower vitamin B12 concentration. Vitamin B12 supplements are inevitable for the hyperhomocysteinemia prevention (Tab. 2, Ref. 26).

  11. Age-Related Eye Diseases and Visual Impairment Among U.S. Adults

    Science.gov (United States)

    Chou, Chiu-Fang; Cotch, Mary Frances; Vitale, Susan; Zhang, Xinzhi; Klein, Ronald; Friedman, David S.; Klein, Barbara E.K.; Saaddine, Jinan B.

    2014-01-01

    Background Visual impairment is a common health-related disability in the U.S. The association between clinical measurements of age-related eye diseases and visual impairment in data from a national survey has not been reported. Purpose To examine common eye conditions and other correlates associated with visual impairment in the U.S. Methods Data from the 2005–2008 National Health and Nutrition Examination Survey of 5222 Americans aged ≥40 years were analyzed in 2012 for visual impairment (presenting distance visual acuity worse than 20/40 in the better-seeing eye), and visual impairment not due to refractive error (distance visual acuity worse than 20/40 after refraction). Diabetic retinopathy (DR) and age-related macular degeneration (AMD) were assessed from retinal fundus images; glaucoma was assessed from two successive frequency-doubling tests and a cup-to-disc ratio measurement. Results Prevalence of visual impairment and of visual impairment not due to refractive error was 7.5% (95% CI=6.9%, 8.1%) and 2.0% (1.7%, 2.3%), respectively. The prevalence of visual impairment not due to refractive error was significantly higher among people with AMD (2.2%) compared to those without AMD (0.8%), or with DR (3.5%) compared to those without DR (1.2%). Independent predictive factors of visual impairment not due to refractive error were AMD (OR=4.52, 95% CI=2.50, 8.17); increasing age (OR=1.09 per year, 95% CI=1.06, 1.13); and less than a high school education (OR=2.99, 95% CI=1.18, 7.55). Conclusions Visual impairment is a public health problem in the U.S. Visual impairment in two thirds of adults could be eliminated with refractive correction. Screening of the older population may identify adults at increased risk of visual impairment due to eye diseases. PMID:23790986

  12. Peripheral Retinal Changes Associated with Age-Related Macular Degeneration in the Age-Related Eye Disease Study 2: Age-Related Eye Disease Study 2 Report Number 12 by the Age-Related Eye Disease Study 2 Optos PEripheral RetinA (OPERA) Study Research Group.

    Science.gov (United States)

    Domalpally, Amitha; Clemons, Traci E; Danis, Ronald P; Sadda, SriniVas R; Cukras, Catherine A; Toth, Cynthia A; Friberg, Thomas R; Chew, Emily Y

    2017-04-01

    To compare rates of peripheral retinal changes in Age-Related Eye Disease Study 2 (AREDS2) participants with at least intermediate age-related macular degeneration (AMD) with control subjects without intermediate age-related changes (large drusen). Cross-sectional evaluation of clinic-based patients enrolled in AREDS2 and a prospective study. Participants from prospective studies. The 200° pseudocolor and fundus autofluorescence (FAF) images were captured on the Optos 200 Tx Ultrawide-field device (Optos, Dunfermline, Scotland) by centering on the fovea and then steering superiorly and inferiorly. The montaged images were graded at a reading center with the images divided into 3 zones (zone 1 [posterior pole], zone 2 [midperiphery], and zone 3 [far periphery]) to document the presence of peripheral lesions. Peripheral retinal lesions: drusen, hypopigmentary/hyperpigmentary changes, reticular pseudodrusen, senile reticular pigmentary changes, cobblestone degeneration, and FAF abnormalities. A total of 484 (951 eyes) AREDS2 participants with AMD (cases) and 89 (163 eyes) controls without AMD had gradable color and FAF images. In zones 2 and 3, neovascularization and geographic atrophy (GA) were present, ranging from 0.4% to 6% in eyes of cases, respectively, and GA was present in 1% of eyes of controls. Drusen were detected in 97%, 78%, and 64% of eyes of cases and 48%, 21%, and 9% of eyes of controls in zones 2 and 3 superior and 3 inferior, respectively (P < 0.001 for all). Peripheral reticular pseudodrusen were seen in 15%. Senile reticular pigmentary change was the predominant peripheral change seen in 48% of cases and 16% of controls in zone 2 (P < 0.001). Nonreticular pigment changes were less frequent in the periphery than in the posterior pole (46% vs. 76%) and negligible in controls. Peripheral retinal changes are more prevalent in eyes with AMD than in control eyes. Drusen are seen in a majority of eyes with AMD in both the mid and far periphery, whereas

  13. A review of creatine supplementation in age-related diseases: more than a supplement for athletes

    Science.gov (United States)

    Smith, Rachel N.; Agharkar, Amruta S.; Gonzales, Eric B.

    2014-01-01

    Creatine is an endogenous compound synthesized from arginine, glycine and methionine. This dietary supplement can be acquired from food sources such as meat and fish, along with athlete supplement powders. Since the majority of creatine is stored in skeletal muscle, dietary creatine supplementation has traditionally been important for athletes and bodybuilders to increase the power, strength, and mass of the skeletal muscle. However, new uses for creatine have emerged suggesting that it may be important in preventing or delaying the onset of neurodegenerative diseases associated with aging. On average, 30% of muscle mass is lost by age 80, while muscular weakness remains a vital cause for loss of independence in the elderly population. In light of these new roles of creatine, the dietary supplement’s usage has been studied to determine its efficacy in treating congestive heart failure, gyrate atrophy, insulin insensitivity, cancer, and high cholesterol. In relation to the brain, creatine has been shown to have antioxidant properties, reduce mental fatigue, protect the brain from neurotoxicity, and improve facets/components of neurological disorders like depression and bipolar disorder. The combination of these benefits has made creatine a leading candidate in the fight against age-related diseases, such as Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, long-term memory impairments associated with the progression of Alzheimer’s disease, and stroke. In this review, we explore the normal mechanisms by which creatine is produced and its necessary physiology, while paying special attention to the importance of creatine supplementation in improving diseases and disorders associated with brain aging and outlining the clinical trials involving creatine to treat these diseases. PMID:25664170

  14. Advanced glycation end-products (AGEs accumulation in skin: relations with chronic kidney disease-mineral and bone disorder

    Directory of Open Access Journals (Sweden)

    Renata de Almeida França

    2017-08-01

    Full Text Available Abstract Introduction: Chronic kidney disease (CKD is associated with high morbidity and mortality rates, main causes related with cardiovascular disease (CVD and bone mineral disorder (CKD-BMD. Uremic toxins, as advanced glycation end products (AGEs, are non-traditional cardiovascular risk factor and play a role on development of CKD-BMD in CKD. The measurement of skin autofluorescence (sAF is a noninvasive method to assess the level of AGEs in tissue, validated in CKD patients. Objective: The aim of this study is analyze AGEs measured by sAF levels (AGEs-sAF and its relations with CVD and BMD parameters in HD patients. Methods: Twenty prevalent HD patients (HD group and healthy subjects (Control group, n = 24, performed biochemical tests and measurements of anthropometric parameters and AGEs-sAF. In addition, HD group performed measurement of intact parathormone (iPTH, transthoracic echocardiogram and radiographies of pelvis and hands for vascular calcification score. Results: AGEs-sAF levels are elevated both in HD and control subjects ranged according to the age, although higher at HD than control group. Single high-flux HD session does not affect AGEs-sAF levels. AGEs-sAF levels were not related to ventricular mass, interventricular septum or vascular calcification in HD group. AGEs-sAF levels were negatively associated with serum iPTH levels. Conclusion: Our study detected a negative correlation of AGEs-sAF with serum iPTH, suggesting a role of AGEs on the pathophysiology of bone disease in HD prevalent patients. The nature of this relation and the clinical application of this non-invasive methodology for evaluation AGEs deposition must be confirmed and clarified in future studies.

  15. Glycated Lysine Residues: A Marker for Non-Enzymatic Protein Glycation in Age-Related Diseases

    OpenAIRE

    Ansari, Nadeem A.; Moinuddin,; Ali, Rashid

    2011-01-01

    Nonenzymatic glycosylation or glycation of macromolecules, especially proteins leading to their oxidation, play an important role in diseases. Glycation of proteins primarily results in the formation of an early stage and stable Amadori-lysine product which undergo further irreversible chemical reactions to form advanced glycation endproducts (AGEs). This review focuses these products in lysine rich proteins such as collagen and human serum albumin for their role in aging and age-related dise...

  16. A Deep Learning Algorithm for Prediction of Age-Related Eye Disease Study Severity Scale for Age-Related Macular Degeneration from Color Fundus Photography.

    Science.gov (United States)

    Grassmann, Felix; Mengelkamp, Judith; Brandl, Caroline; Harsch, Sebastian; Zimmermann, Martina E; Linkohr, Birgit; Peters, Annette; Heid, Iris M; Palm, Christoph; Weber, Bernhard H F

    2018-04-10

    Age-related macular degeneration (AMD) is a common threat to vision. While classification of disease stages is critical to understanding disease risk and progression, several systems based on color fundus photographs are known. Most of these require in-depth and time-consuming analysis of fundus images. Herein, we present an automated computer-based classification algorithm. Algorithm development for AMD classification based on a large collection of color fundus images. Validation is performed on a cross-sectional, population-based study. We included 120 656 manually graded color fundus images from 3654 Age-Related Eye Disease Study (AREDS) participants. AREDS participants were >55 years of age, and non-AMD sight-threatening diseases were excluded at recruitment. In addition, performance of our algorithm was evaluated in 5555 fundus images from the population-based Kooperative Gesundheitsforschung in der Region Augsburg (KORA; Cooperative Health Research in the Region of Augsburg) study. We defined 13 classes (9 AREDS steps, 3 late AMD stages, and 1 for ungradable images) and trained several convolution deep learning architectures. An ensemble of network architectures improved prediction accuracy. An independent dataset was used to evaluate the performance of our algorithm in a population-based study. κ Statistics and accuracy to evaluate the concordance between predicted and expert human grader classification. A network ensemble of 6 different neural net architectures predicted the 13 classes in the AREDS test set with a quadratic weighted κ of 92% (95% confidence interval, 89%-92%) and an overall accuracy of 63.3%. In the independent KORA dataset, images wrongly classified as AMD were mainly the result of a macular reflex observed in young individuals. By restricting the KORA analysis to individuals >55 years of age and prior exclusion of other retinopathies, the weighted and unweighted κ increased to 50% and 63%, respectively. Importantly, the algorithm

  17. Activation analysis in a multitechnique study of trace element imbalances in age-related neurological diseases

    International Nuclear Information System (INIS)

    Ehmann, W.D.; Ding, X.X.; Khare, S.S.; Lovell, M.A.; Ni, B.F.; Tandon, L.; Vance, D.E.; Wenstrup, D.E.

    1993-01-01

    It has been suggested that several age-related neurological diseases such as Alzheimer's disease and amyotrophic lateral sclerosis may be related to environmental toxins. Bulk sample multielemental analyses by INAA alone are not adequate to define the role of trace elements in these diseases. A multitechnique approach has been developed that incorporates 14 MeV, instrumental reactor, radiochemical, and pre-irradiation chemical neutron activation analysis, together with laser microprobe mass spectrometry. The analytical scheme is able to provide bulk or protein normalized elemental concentrations, as well as microstructural, cellular, and subcellular localization information. (author) 21 refs.; 3 figs.; 3 tabs

  18. Visible Age-Related Signs and Risk of Ischemic Heart Disease in the General Population

    DEFF Research Database (Denmark)

    Christoffersen, Mette; Frikke-Schmidt, Ruth; Schnohr, Peter

    2014-01-01

    developed MI. Presence of frontoparietal baldness, crown top baldness, earlobe crease, and xanthelasmata was associated with increased risk of IHD or MI after multifactorial adjustment for chronological age and well-known cardiovascular risk factors. The risk of IHD and MI increased stepwise with increasing...... risk of IHD and MI increased with increasing number of visible age-related signs. CONCLUSIONS: Male pattern baldness, earlobe crease, and xanthelasmata-alone or in combination-associate with increased risk of ischemic heart disease and myocardial infarction independent of chronological age and other...

  19. Perspectives of Stem Cell-Based Therapy for Age-Related Retinal Degenerative Diseases

    Czech Academy of Sciences Publication Activity Database

    Holáň, Vladimír; Heřmánková, Barbora; Kössl, Jan

    2017-01-01

    Roč. 26, č. 9 (2017), s. 1538-1541 ISSN 0963-6897 R&D Projects: GA ČR(CZ) GA17-04800S; GA MŠk(CZ) ED1.1.00/02.0109; GA MŠk(CZ) LO1309 Institutional support: RVO:68378041 Keywords : age-related retinal degenerative diseases * mesenchymal stem cells * stem cell therapy Subject RIV: FF - HEENT, Dentistry OBOR OECD: Ophthalmology Impact factor: 3.006, year: 2016

  20. Genome-wide analysis of disease progression in age-related macular degeneration.

    Science.gov (United States)

    Yan, Qi; Ding, Ying; Liu, Yi; Sun, Tao; Fritsche, Lars G; Clemons, Traci; Ratnapriya, Rinki; Klein, Michael L; Cook, Richard J; Liu, Yu; Fan, Ruzong; Wei, Lai; Abecasis, Gonçalo R; Swaroop, Anand; Chew, Emily Y; Weeks, Daniel E; Chen, Wei

    2018-03-01

    Family- and population-based genetic studies have successfully identified multiple disease-susceptibility loci for Age-related macular degeneration (AMD), one of the first batch and most successful examples of genome-wide association study. However, most genetic studies to date have focused on case-control studies of late AMD (choroidal neovascularization or geographic atrophy). The genetic influences on disease progression are largely unexplored. We assembled unique resources to perform a genome-wide bivariate time-to-event analysis to test for association of time-to-late-AMD with ∼9 million variants on 2721 Caucasians from a large multi-center randomized clinical trial, the Age-Related Eye Disease Study. To our knowledge, this is the first genome-wide association study of disease progression (bivariate survival outcome) in AMD genetic studies, thus providing novel insights to AMD genetics. We used a robust Cox proportional hazards model to appropriately account for between-eye correlation when analyzing the progression time in the two eyes of each participant. We identified four previously reported susceptibility loci showing genome-wide significant association with AMD progression: ARMS2-HTRA1 (P = 8.1 × 10-43), CFH (P = 3.5 × 10-37), C2-CFB-SKIV2L (P = 8.1 × 10-10) and C3 (P = 1.2 × 10-9). Furthermore, we detected association of rs58978565 near TNR (P = 2.3 × 10-8), rs28368872 near ATF7IP2 (P = 2.9 × 10-8) and rs142450006 near MMP9 (P = 0.0006) with progression to choroidal neovascularization but not geographic atrophy. Secondary analysis limited to 34 reported risk variants revealed that LIPC and CTRB2-CTRB1 were also associated with AMD progression (P < 0.0015). Our genome-wide analysis thus expands the genetics in both development and progression of AMD and should assist in early identification of high risk individuals.

  1. Age-related declines and disease-associated variation in immune cell telomere length in a wild mammal.

    Directory of Open Access Journals (Sweden)

    Christopher Beirne

    Full Text Available Immunosenescence, the deterioration of immune system capability with age, may play a key role in mediating age-related declines in whole-organism performance, but the mechanisms that underpin immunosenescence are poorly understood. Biomedical research on humans and laboratory models has documented age and disease related declines in the telomere lengths of leukocytes ('immune cells', stimulating interest their having a potentially general role in the emergence of immunosenescent phenotypes. However, it is unknown whether such observations generalise to the immune cell populations of wild vertebrates living under ecologically realistic conditions. Here we examine longitudinal changes in the mean telomere lengths of immune cells in wild European badgers (Meles meles. Our findings provide the first evidence of within-individual age-related declines in immune cell telomere lengths in a wild vertebrate. That the rate of age-related decline in telomere length appears to be steeper within individuals than at the overall population level raises the possibility that individuals with short immune cell telomeres and/or higher rates of immune cell telomere attrition may be selectively lost from this population. We also report evidence suggestive of associations between immune cell telomere length and bovine tuberculosis infection status, with individuals detected at the most advanced stage of infection tending to have shorter immune cell telomeres than disease positive individuals. While male European badgers are larger and show higher rates of annual mortality than females, we found no evidence of a sex difference in either mean telomere length or the average rate of within-individual telomere attrition with age. Our findings lend support to the view that age-related declines in the telomere lengths of immune cells may provide one potentially general mechanism underpinning age-related declines in immunocompetence in natural populations.

  2. Time trends for risk of severe age-related diseases in individuals with and without HIV infection in Denmark

    DEFF Research Database (Denmark)

    Rasmussen, Line D; May, Margaret T; Kronborg, Gitte

    2015-01-01

    BACKGROUND: Whether the reported high risk of age-related diseases in HIV-infected people is caused by biological ageing or HIV-associated risk factors such as chronic immune activation and low-grade inflammation is unknown. We assessed time trends in age-standardised and relative risks of nine...... serious age-related diseases in a nationwide cohort study of HIV-infected individuals and population controls. METHODS: We identified all HIV-infected individuals in the Danish HIV Cohort Study who had received HIV care in Denmark between Jan 1, 1995, and June 1, 2014. Population controls were identified...... from the Danish Civil Registration System and individually matched in a ratio of nine to one to the HIV-infected individuals for year of birth, sex, and date of study inclusion. Individuals were included in the study if they had a Danish personal identification number, were aged 16 years or older...

  3. A genome-wide scan reveals important roles of DNA methylation in human longevity by regulating age-related disease genes.

    Directory of Open Access Journals (Sweden)

    Fu-Hui Xiao

    Full Text Available It is recognized that genetic factors contribute to human longevity. Besides the hypothesis of existence of longevity genes, another suggests that a lower frequency of risk alleles decreases the incidence of age-related diseases in the long-lived people. However, the latter finds no support from recent genetic studies. Considering the crucial role of epigenetic modification in gene regulation, we then hypothesize that suppressing disease-related genes in longevity individuals is likely achieved by epigenetic modification, e.g. DNA methylation. To test this hypothesis, we investigated the genome-wide methylation profile in 4 Chinese female centenarians and 4 middle-aged controls using methyl-DNA immunoprecipitation sequencing. 626 differentially methylated regions (DMRs were observed between both groups. Interestingly, genes with these DMRs were enriched in age-related diseases, including type-2 diabetes, cardiovascular disease, stroke and Alzheimer's disease. This pattern remains rather stable after including methylomes of two white individuals. Further analyses suggest that the observed DMRs likely have functional roles in regulating disease-associated gene expressions, with some genes [e.g. caspase 3 (CASP3] being down-regulated whereas the others [i.e. interleukin 1 receptor, type 2 (IL1R2] up-regulated. Therefore, our study suggests that suppressing the disease-related genes via epigenetic modification is an important contributor to human longevity.

  4. Age-related disease association of endogenous γ-H2AX foci in mononuclear cells derived from leukapheresis.

    Directory of Open Access Journals (Sweden)

    Shepherd H Schurman

    Full Text Available The phosphorylated form of histone H2AX (γ-H2AX forms immunohistochemically detectable foci at DNA double strand breaks. In peripheral blood mononuclear cells (PBMCs derived from leukapheresis from patients enrolled in the Baltimore Longitudinal Study of Aging, γ-H2AX foci increased in a linear fashion with regards to age, peaking at ~57 years. The relationship between the frequency of γ-H2AX foci and age-related pathologies was assessed. We found a statistically significant (p = 0.023 50% increase in foci in PBMCs derived from patients with a known history of vitamin D deficiency. In addition, there were trends toward increased γ-H2AX foci in patients with cataracts (34% increase, p<0.10 and in sleep apnea patients (44%, p<0.10. Among patients ≥57 y/o, we found a significant (p = 0.037 36% increase in the number of γ-H2AX foci/cell for patients with hypertension compared to non-hypertensive patients. Our results support a role for increased DNA damage in the morbidity of age-related diseases. γ -H2AX may be a biomarker for human morbidity in age-related diseases.

  5. Age-related macular degeneration.

    Science.gov (United States)

    Cheung, Lily K; Eaton, Angie

    2013-08-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly, and the prevalence of the disease increases exponentially with every decade after age 50 years. It is a multifactorial disease involving a complex interplay of genetic, environmental, metabolic, and functional factors. Besides smoking, hypertension, obesity, and certain dietary habits, a growing body of evidence indicates that inflammation and the immune system may play a key role in the development of the disease. AMD may progress from the early form to the intermediate form and then to the advanced form, where two subtypes exist: the nonneovascular (dry) type and the neovascular (wet) type. The results from the Age-Related Eye Disease Study have shown that for the nonneovascular type of AMD, supplementation with high-dose antioxidants (vitamin C, vitamin E, and β-carotene) and zinc is recommended for those with the intermediate form of AMD in one or both eyes or with advanced AMD or vision loss due to AMD in one eye. As for the neovascular type of the advanced AMD, the current standard of therapy is intravitreal injections of vascular endothelial growth factor inhibitors. In addition, lifestyle and dietary modifications including improved physical activity, reduced daily sodium intake, and reduced intake of solid fats, added sugars, cholesterol, and refined grain foods are recommended. To date, no study has demonstrated that AMD can be cured or effectively prevented. Clearly, more research is needed to fully understand the pathophysiology as well as to develop prevention and treatment strategies for this devastating disease. © 2013 Pharmacotherapy Publications, Inc.

  6. Increased brain-predicted aging in treated HIV disease

    NARCIS (Netherlands)

    Cole, James H; Underwood, Jonathan; Caan, Matthan W A; De Francesco, Davide; van Zoest, Rosan A; Leech, Robert; Wit, Ferdinand W N M; Portegies, Peter; Geurtsen, Gert J; Schmand, Ben A; Schim van der Loeff, Maarten F; Franceschi, Claudio; Sabin, Caroline A; Majoie, Charles B L M; Winston, Alan; Reiss, Peter; Sharp, David J; Kalsbeek, A.

    OBJECTIVE: To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. METHODS: A

  7. Increased brain-predicted aging in treated HIV disease

    NARCIS (Netherlands)

    Cole, James H.; Underwood, Jonathan; Caan, Matthan W. A.; de Francesco, Davide; van Zoest, Rosan A.; Leech, Robert; Wit, Ferdinand W. N. M.; Portegies, Peter; Geurtsen, Gert J.; Schmand, Ben A.; Schim van der Loeff, Maarten F.; Franceschi, Claudio; Sabin, Caroline A.; Majoie, Charles B. L. M.; Winston, Alan; Reiss, Peter; Sharp, David J.; Schouten, J.; Kooij, K. W.; Elsenga, B. C.; Janssen, F. R.; Heidenrijk, M.; Schrijver, J. H. N.; Zikkenheiner, W.; van der Valk, M.; Henderiks, A.; Kootstra, N. A.; Harskamp-Holwerda, A. M.; Maurer, I.; Ruiz, M. M. Mangas; Booiman, T.; Girigorie, A. F.; Villaudy, J.; Frankin, E.; Pasternak, A.; Berkhout, B.; van der Kuyl, T.; Stege, J. A. ter; Twennaar, M. Klein; Su, T.; Siteur-van Rijnstra, E.; Weijer, K.; Bisschop, P. H. L. T.; Kalsbeek, A.; Wezel, M.; Visser, I.; Ruhé , H. G.; Tembo, L.; Stott, M.; Prins, M. [= Maria

    2017-01-01

    To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. A large sample of

  8. Serum Levels of Toxic AGEs (TAGE May Be a Promising Novel Biomarker for the Onset/Progression of Lifestyle-Related Diseases

    Directory of Open Access Journals (Sweden)

    Masayoshi Takeuchi

    2016-06-01

    Full Text Available Advanced glycation end-products (AGEs generated with aging or in the presence of diabetes mellitus, particularly AGEs derived from the glucose/fructose metabolism intermediate glyceraldehyde (Glycer-AGEs; termed toxic AGEs (TAGE, were recently shown to be closely involved in the onset/progression of diabetic vascular complications via the receptor for AGEs (RAGE. TAGE also contribute to various diseases, such as cardiovascular disease; nonalcoholic steatohepatitis; cancer; Alzheimer’s disease, and; infertility. This suggests the necessity of minimizing the influence of the TAGE-RAGE axis in order to prevent the onset/progression of lifestyle-related diseases (LSRD and establish therapeutic strategies. Changes in serum TAGE levels are closely associated with LSRD related to overeating, a lack of exercise, or excessive ingestion of sugars/dietary AGEs. We also showed that serum TAGE levels, but not those of hemoglobin A1c, glucose-derived AGEs, or Nε-(carboxymethyllysine, have potential as a biomarker for predicting the progression of atherosclerosis and future cardiovascular events. We herein introduce the usefulness of serum TAGE levels as a biomarker for the prevention/early diagnosis of LSRD and the evaluation of the efficacy of treatments; we discuss whether dietary AGE/sugar intake restrictions reduce the generation/accumulation of TAGE, thereby preventing the onset/progression of LSRD.

  9. Differential Disease Progression in Atrophic Age-Related Macular Degeneration and Late-Onset Stargardt Disease.

    Science.gov (United States)

    Lindner, Moritz; Lambertus, Stanley; Mauschitz, Matthias M; Bax, Nathalie M; Kersten, Eveline; Lüning, Anna; Nadal, Jennifer; Schmitz-Valckenberg, Steffen; Schmid, Matthias; Holz, Frank G; Hoyng, Carel B; Fleckenstein, Monika

    2017-02-01

    To compare the disease course of retinal pigment epithelium (RPE) atrophy secondary to age-related macula degeneratio (AMD) and late-onset Stargardt disease (STGD1). Patients were examined longitudinally by fundus autofluorescence, near-infrared reflectance imaging, and best-corrected visual acuity (BCVA). Areas of RPE atrophy were quantified using semi-automated software, and the status of the fovea was evaluated based on autofluorescence and near-infrared reflectance images. Mixed-effects models were used to compare atrophy progression rates. BCVA loss and loss of foveal integrity were analyzed using Turnbull's estimator. A total of 151 patients (226 eyes) with RPE atrophy secondary to AMD and 38 patients (66 eyes) with RPE atrophy secondary to late-onset STGD1 were examined for a median time of 2.3 years (interquartile range, 2.7). Mean baseline age was 74.2 years (SD, 7.6) in AMD and 63.4 (SD, 9.9) in late-onset STGD1 (P = 1.1 × 10-7). Square root atrophy progression was significantly faster in AMD when compared with late-onset STGD1 (0.28 mm/year [SE, 0.01] vs. 0.23 [SE, 0.03]; P = 0.030). In late-onset STGD1, the median survival of the fovea was significantly longer when compared with eyes with AMD (8.60 vs. 3.35 years; P = 0.005) with a trend to a later BCVA loss of ≥3 lines (5.97 vs. 4.37 years; P = 0.382). These natural history data indicate differential disease progression in AMD versus late-onset STGD1. The results underline the relevance of refined phenotyping in elderly patients presenting with RPE atrophy in regard to prognosis and design of interventional trials.

  10. The microbiota and microbiome in aging: potential implications in health and age-related diseases.

    Science.gov (United States)

    Zapata, Heidi J; Quagliarello, Vincent J

    2015-04-01

    Advances in bacterial deoxyribonucleic acid sequencing allow for characterization of the human commensal bacterial community (microbiota) and its corresponding genome (microbiome). Surveys of healthy adults reveal that a signature composite of bacteria characterizes each unique body habitat (e.g., gut, skin, oral cavity, vagina). A myriad of clinical changes, including a basal proinflammatory state (inflamm-aging), that directly interface with the microbiota of older adults and enhance susceptibility to disease accompany aging. Studies in older adults demonstrate that the gut microbiota correlates with diet, location of residence (e.g., community dwelling, long-term care settings), and basal level of inflammation. Links exist between the microbiota and a variety of clinical problems plaguing older adults, including physical frailty, Clostridium difficile colitis, vulvovaginal atrophy, colorectal carcinoma, and atherosclerotic disease. Manipulation of the microbiota and microbiome of older adults holds promise as an innovative strategy to influence the development of comorbidities associated with aging. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

  11. Biological age as a health index for mortality and major age-related disease incidence in Koreans: National Health Insurance Service – Health screening 11-year follow-up study

    Directory of Open Access Journals (Sweden)

    Kang YG

    2018-03-01

    Full Text Available Young Gon Kang,1 Eunkyung Suh,2 Jae-woo Lee,3 Dong Wook Kim,4 Kyung Hee Cho,5 Chul-Young Bae1 1Department of R&D, MediAge Research Center, Seongnam, Republic of South Korea; 2Department of Family Medicine, College of Medicine, CHA University, Chaum, Seoul, Republic of South Korea; 3Department of Family Medicine, College of Medicine, Chungbuk National University, Cheongju, Republic of South Korea; 4Department of Policy Research Affairs, National Health Insurance Service Ilsan Hospital, Goyang, Republic of South Korea; 5Department of Family Medicine, National Health Insurance Service Ilsan Hospital, Goyang, Republic of South KoreaPurpose: A comprehensive health index is needed to measure an individual’s overall health and aging status and predict the risk of death and age-related disease incidence, and evaluate the effect of a health management program. The purpose of this study is to demonstrate the validity of estimated biological age (BA in relation to all-cause mortality and age-related disease incidence based on National Sample Cohort database.Patients and methods: This study was based on National Sample Cohort database of the National Health Insurance Service – Eligibility database and the National Health Insurance Service – Medical and Health Examination database of the year 2002 through 2013. BA model was developed based on the National Health Insurance Service – National Sample Cohort (NHIS – NSC database and Cox proportional hazard analysis was done for mortality and major age-related disease incidence.Results: For every 1 year increase of the calculated BA and chronological age difference, the hazard ratio for mortality significantly increased by 1.6% (1.5% in men and 2.0% in women and also for hypertension, diabetes mellitus, heart disease, stroke, and cancer incidence by 2.5%, 4.2%, 1.3%, 1.6%, and 0.4%, respectively (p<0.001.Conclusion: Estimated BA by the developed BA model based on NHIS – NSC database is expected to be

  12. Age-Related White Matter Changes

    Directory of Open Access Journals (Sweden)

    Yun Yun Xiong

    2011-01-01

    Full Text Available Age-related white matter changes (WMC are considered manifestation of arteriolosclerotic small vessel disease and are related to age and vascular risk factors. Most recent studies have shown that WMC are associated with a host of poor outcomes, including cognitive impairment, dementia, urinary incontinence, gait disturbances, depression, and increased risk of stroke and death. Although the clinical relevance of WMC has been extensively studied, to date, only very few clinical trials have evaluated potential symptomatic or preventive treatments for WMC. In this paper, we reviewed the current understanding in the pathophysiology, epidemiology, clinical importance, chemical biomarkers, and treatments of age-related WMC.

  13. Nutrition and Age-Related Eye Diseases: The ALIENOR (Antioxydants, Lipides Essentiels, Nutrition et Maladies Oculaires) Study.

    OpenAIRE

    Delcourt , Cécile; Korobelnik , Jean-François; Barberger-Gateau , Pascale; Delyfer , Marie-Noëlle; Marie-Bénédicte , Rougier; Le Goff , Mélanie; Malet , Florence; Joseph , Colin; Dartigues , Jean-François

    2010-01-01

    International audience; Background: Worldwide, degenerative eye diseases (age-related maculopathy (ARM), cataract, glaucoma) are the main causes of visual impairment and blindness, which contribute to disability in the elderly. Mainly three types of nutritional factors are investigated for their potential protection against eye ageing: antioxidants; lutein and zeaxanthin (carotenoids which accumulate specifically in the eye); omega 3 polyunsaturated fatty acids. Few epidemiological studies ha...

  14. Geroprotectors.org: a new, structured and curated database of current therapeutic interventions in aging and age-related disease

    Science.gov (United States)

    Moskalev, Alexey; Chernyagina, Elizaveta; de Magalhães, João Pedro; Barardo, Diogo; Thoppil, Harikrishnan; Shaposhnikov, Mikhail; Budovsky, Arie; Fraifeld, Vadim E.; Garazha, Andrew; Tsvetkov, Vasily; Bronovitsky, Evgeny; Bogomolov, Vladislav; Scerbacov, Alexei; Kuryan, Oleg; Gurinovich, Roman; Jellen, Leslie C.; Kennedy, Brian; Mamoshina, Polina; Dobrovolskaya, Evgeniya; Aliper, Alex; Kaminsky, Dmitry; Zhavoronkov, Alex

    2015-01-01

    As the level of interest in aging research increases, there is a growing number of geroprotectors, or therapeutic interventions that aim to extend the healthy lifespan and repair or reduce aging-related damage in model organisms and, eventually, in humans. There is a clear need for a manually-curated database of geroprotectors to compile and index their effects on aging and age-related diseases and link these effects to relevant studies and multiple biochemical and drug databases. Here, we introduce the first such resource, Geroprotectors (http://geroprotectors.org). Geroprotectors is a public, rapidly explorable database that catalogs over 250 experiments involving over 200 known or candidate geroprotectors that extend lifespan in model organisms. Each compound has a comprehensive profile complete with biochemistry, mechanisms, and lifespan effects in various model organisms, along with information ranging from chemical structure, side effects, and toxicity to FDA drug status. These are presented in a visually intuitive, efficient framework fit for casual browsing or in-depth research alike. Data are linked to the source studies or databases, providing quick and convenient access to original data. The Geroprotectors database facilitates cross-study, cross-organism, and cross-discipline analysis and saves countless hours of inefficient literature and web searching. Geroprotectors is a one-stop, knowledge-sharing, time-saving resource for researchers seeking healthy aging solutions. PMID:26342919

  15. The Oxygen Paradox, the French Paradox, and age-related diseases.

    Science.gov (United States)

    Davies, Joanna M S; Cillard, Josiane; Friguet, Bertrand; Cadenas, Enrique; Cadet, Jean; Cayce, Rachael; Fishmann, Andrew; Liao, David; Bulteau, Anne-Laure; Derbré, Frédéric; Rébillard, Amélie; Burstein, Steven; Hirsch, Etienne; Kloner, Robert A; Jakowec, Michael; Petzinger, Giselle; Sauce, Delphine; Sennlaub, Florian; Limon, Isabelle; Ursini, Fulvio; Maiorino, Matilde; Economides, Christina; Pike, Christian J; Cohen, Pinchas; Salvayre, Anne Negre; Halliday, Matthew R; Lundquist, Adam J; Jakowec, Nicolaus A; Mechta-Grigoriou, Fatima; Mericskay, Mathias; Mariani, Jean; Li, Zhenlin; Huang, David; Grant, Ellsworth; Forman, Henry J; Finch, Caleb E; Sun, Patrick Y; Pomatto, Laura C D; Agbulut, Onnik; Warburton, David; Neri, Christian; Rouis, Mustapha; Cillard, Pierre; Capeau, Jacqueline; Rosenbaum, Jean; Davies, Kelvin J A

    2017-12-01

    transduction pathways to increase expression of protective genes, by mechanisms that are completely different from those by which the same agent induces toxicity at high concentrations. In this review, we explore the influences and effects of paradoxes such as the Oxygen Paradox and the French Paradox on the etiology, progression, and outcomes of many of the major human age-related diseases, as well as the basic biological phenomenon of ageing itself.

  16. Specialist report : Dry eye disease and aging

    NARCIS (Netherlands)

    van Tilborg, M.M.A.; Kort, H.S.M.; Murphy, P.J.

    2017-01-01

    The common ocular pathologies relating to the aging eye, such as cataract, diabetic retinopathy, glaucoma, or macular degeneration, are all known to reduce visual functioning. Less wellknown is the effect of common, age-related dry eye disease (DED). The impact of DED on daily activities can be

  17. Ill or just old? Towards a conceptual framework of the relation between ageing and disease

    Directory of Open Access Journals (Sweden)

    Westendorp Rudi GJ

    2003-12-01

    Full Text Available Abstract Background Is this person ill or just old? This question reflects the pondering mind of a doctor while interpreting the complaints of an elderly person who seeks his help. Many doctors think that ageing is a non-disease. Accordingly, various attempts have been undertaken to separate pathological ageing from normal ageing. However, the existence of a normal ageing process distinct from the pathological processes causing disease later in life can be questioned. Discussion Ageing is the accumulation of damage to somatic cells, leading to cellular dysfunction, and culminates in organ dysfunction and an increased vulnerability to death. Analogously, chronic diseases initiate early in life and their development is slow before they become clinically apparent and culminate in disability or death. The definition of disease is also subject to current opinions and scientific understanding and usually, it is an act of individual creativity when physical changes are recognised as symptoms of a new disease. New diseases, however, are only rarely really new. Most new diseases have gone undiagnosed because their signs and symptoms escaped recognition or were interpreted otherwise. Many physical changes in the elderly that are not yet recognised as a disease are thus ascribed to normal ageing. Therefore, the distinction between normal ageing and disease late in life seems in large part arbitrary. Summary We think that normal ageing cannot be separated from pathological processes causing disease later in life, and we propose that the distinction is avoided.

  18. The Prevalence of Age-Related Eye Diseases and Visual Impairment in Aging: Current Estimates

    Science.gov (United States)

    Klein, Ronald; Klein, Barbara E. K.

    2013-01-01

    Purpose. To examine prevalence of five age-related eye conditions (age-related cataract, AMD, open-angle glaucoma, diabetic retinopathy [DR], and visual impairment) in the United States. Methods. Review of published scientific articles and unpublished research findings. Results. Cataract, AMD, open-angle glaucoma, DR, and visual impairment prevalences are high in four different studies of these conditions, especially in people over 75 years of age. There are disparities among racial/ethnic groups with higher age-specific prevalence of DR, open-angle glaucoma, and visual impairment in Hispanics and blacks compared with whites, higher prevalence of age-related cataract in whites compared with blacks, and higher prevalence of late AMD in whites compared with Hispanics and blacks. The estimates are based on old data and do not reflect recent changes in the distribution of age and race/ethnicity in the United States population. There are no epidemiologic estimates of prevalence for many visually-impairing conditions. Conclusions. Ongoing prevalence surveys designed to provide reliable estimates of visual impairment, AMD, age-related cataract, open-angle glaucoma, and DR are needed. It is important to collect objective data on these and other conditions that affect vision and quality of life in order to plan for health care needs and identify areas for further research. PMID:24335069

  19. Age-related changes in mastication.

    Science.gov (United States)

    Peyron, M A; Woda, A; Bourdiol, P; Hennequin, M

    2017-04-01

    The paper reviews human mastication, focusing on its age-related changes. The first part describes mastication adaptation in young healthy individuals. Adaptation to obtain a food bolus ready to be swallowed relies on variations in number of cycles, muscle strength and volume of emitted saliva. As a result, the food bolus displays granulometric and rheological properties, the values of which are maintained within the adaptive range of deglutition. The second part concerns healthy ageing. Some mastication parameters are slightly modified by age, but ageing itself does not impair mastication, as the adaptation possibilities remain operant. The third part reports on very aged subjects, who display frequent systemic or local diseases. Local and/or general diseases such as tooth loss, salivary defect, or motor impairment are then indistinguishably superimposed on the effects of very old age. The resulting impaired function increases the risk of aspiration and choking. Lastly, the consequences for eating behaviour and nutrition are evoked. © 2016 John Wiley & Sons Ltd.

  20. Ageing and the border between health and disease.

    Science.gov (United States)

    MacNee, William; Rabinovich, Roberto A; Choudhury, Gourab

    2014-11-01

    Ageing is associated with a progressive degeneration of the tissues, which has a negative impact on the structure and function of vital organs and is among the most important known risk factors for most chronic diseases. Since the proportion of the world's population aged >60 years will double in the next four decades, this will be accompanied by an increased incidence of chronic age-related diseases that will place a huge burden on healthcare resources. There is increasing evidence that many chronic inflammatory diseases represent an acceleration of the ageing process. Chronic pulmonary diseases represents an important component of the increasingly prevalent multiple chronic debilitating diseases, which are a major cause of morbidity and mortality, particularly in the elderly. The lungs age and it has been suggested that chronic obstructive pulmonary disease (COPD) is a condition of accelerated lung ageing and that ageing may provide a mechanistic link between COPD and many of its extrapulmonary effects and comorbidities. In this article we will describe the physiological changes and mechanisms of ageing, with particular focus on the pulmonary effects of ageing and how these may be relevant to the development of COPD and its major extrapulmonary manifestations. ©ERS 2014.

  1. Nature Versus Nurture: Does Proteostasis Imbalance Underlie the Genetic, Environmental, and Age-Related Risk Factors for Alzheimer's Disease?

    Science.gov (United States)

    Kikis, Elise A

    2017-08-22

    Aging is a risk factor for a number of "age-related diseases", including Alzheimer's disease (AD). AD affects more than a third of all people over the age of 85, and is the leading cause of dementia worldwide. Symptoms include forgetfulness, memory loss, and cognitive decline, ultimately resulting in the need for full-time care. While there is no cure for AD, pharmacological approaches to alleviate symptoms and target underlying causes of the disease have been developed, albeit with limited success. This review presents the age-related, genetic, and environmental risk factors for AD and proposes a hypothesis for the mechanistic link between genetics and the environment. In short, much is known about the genetics of early-onset familial AD (EO-FAD) and the central role played by the Aβ peptide and protein misfolding, but late-onset AD (LOAD) is not thought to have direct genetic causes. Nonetheless, genetic risk factors such as isoforms of the protein ApoE have been identified. Additional findings suggest that air pollution caused by the combustion of fossil fuels may be an important environmental risk factor for AD. A hypothesis suggesting that poor air quality might act by disrupting protein folding homeostasis (proteostasis) is presented.

  2. Age-related macular degeneration

    DEFF Research Database (Denmark)

    la Cour, Morten; Kiilgaard, Jens Folke; Nissen, Mogens Holst

    2002-01-01

    Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterised by the appearance of drusen in the macula, accompanied by choroidal neovascularisation (CNV) or geographic atrophy. The disease is more common in Caucasian....... Smoking is probably also a risk factor. Preventive strategies using macular laser photocoagulation are under investigation, but their efficacy in preventing visual loss is as yet unproven. There is no treatment with proven efficacy for geographic atrophy. Optimal treatment for exudative AMD requires...

  3. Discursive constructions of falls prevention : Discourses of active aging versus old age as disease

    DEFF Research Database (Denmark)

    Evron, Lotte; Ulrich, Anita; Tanggaard, Lene

    2012-01-01

    information and investment in falls prevention programs, many still drop out or decline to participate in such programs. The study explores how discourses cross swords in the domain of falls prevention. We identify two main discourses in the field: Discourses of active aging opposed to discourses of old age...... as disease. In discourses of active aging falls are constructed as preventable and not necessarily related to old age; in discourses of old age as disease falls are constructed as a disease of old age. Specific agent positions are created within discourses. Discourses of active aging construct self......-responsible citizens who are physically active and motivated to participate in falls prevention programmes; discourses of old age as disease on the other hand construct “fall patients” who accept being passive in the health care system. Older citizens who are not in need of treatment or less physically active...

  4. A methodological approach to studying resilience mechanisms: demonstration of utility in age and Alzheimer's disease-related brain pathology.

    Science.gov (United States)

    Wolf, Dominik; Fischer, Florian Udo; Fellgiebel, Andreas

    2018-05-01

    The present work aims at providing a methodological approach for the investigation of resilience factors and mechanisms in normal aging, Alzheimer's disease (AD) and other neurodegenerative disorders. By expanding and re-conceptualizing traditional regression approaches, we propose an approach that not only aims at identifying potential resilience factors but also allows for a differentiation between general and dynamic resilience factors in terms of their association with pathology. Dynamic resilience factors are characterized by an increasing relevance with increasing levels of pathology, while the relevance of general resilience factors is independent of the amount of pathology. Utility of the approach is demonstrated in age and AD-related brain pathology by investigating widely accepted resilience factors, including education and brain volume. Moreover, the approach is used to test hippocampal volume as potential resilience factor. Education and brain volume could be identified as general resilience factors against age and AD-related pathology. Beyond that, analyses highlighted that hippocampal volume may not only be disease target but also serve as a potential resilience factor in age and AD-related pathology, particularly at higher levels of tau-pathology (i.e. dynamic resilience factor). Given its unspecific and superordinate nature the approach is suitable for the investigation of a wide range of potential resilience factors in normal aging, AD and other neurodegenerative disorders. Consequently, it may find a wide application and thereby promote the comparability between studies.

  5. Aging is not a disease: implications for intervention

    DEFF Research Database (Denmark)

    Rattan, Suresh

    2014-01-01

    Aging of biological systems occurs in spite of numerous complex pathways of maintenance, repair and defense. There are no gerontogenes which have the specific evolutionary function to cause aging. Although aging is the common cause of all age-related diseases, aging in itself cannot be considered...... a disease. This understanding of aging as a process should transform our approach towards interventions from developing illusory anti-aging treatments to developing realistic and practical methods for maintaining health throughout the lifespan. The concept of homeodynamic space can be a useful one in order...... to identify a set of measurable, evidence-based and demonstratable parameters of health, robustness and resilience. Age-induced health problems, for which there are no other clear-cut causative agents, may be better tackled by focusing on health mechanisms and their maintenance, rather than only disease...

  6. Redefining meaningful age groups in the context of disease.

    Science.gov (United States)

    Geifman, Nophar; Cohen, Raphael; Rubin, Eitan

    2013-12-01

    Age is an important factor when considering phenotypic changes in health and disease. Currently, the use of age information in medicine is somewhat simplistic, with ages commonly being grouped into a small number of crude ranges reflecting the major stages of development and aging, such as childhood or adolescence. Here, we investigate the possibility of redefining age groups using the recently developed Age-Phenome Knowledge-base (APK) that holds over 35,000 literature-derived entries describing relationships between age and phenotype. Clustering of APK data suggests 13 new, partially overlapping, age groups. The diseases that define these groups suggest that the proposed divisions are biologically meaningful. We further show that the number of different age ranges that should be considered depends on the type of disease being evaluated. This finding was further strengthened by similar results obtained from clinical blood measurement data. The grouping of diseases that share a similar pattern of disease-related reports directly mirrors, in some cases, medical knowledge of disease-age relationships. In other cases, our results may be used to generate new and reasonable hypotheses regarding links between diseases.

  7. Classifying Aging as a Disease in the context of ICD-11

    Directory of Open Access Journals (Sweden)

    Alex eZhavoronkov

    2015-11-01

    Full Text Available Aging is a complex continuous multifactorial process leading to loss of function and crystalizing into the many age-related diseases. Here, we explore the arguments for classifying aging as a disease in the context of the upcoming World Health Organization’s 11th International Statistical Classification of Diseases and Related Health Problems (ICD-11, expected to be finalized in 2018. We hypothesize that classifying aging as a disease will result in new approaches and business models for addressing aging as a treatable condition, which will lead to both economic and healthcare benefits for all stakeholders. Classification of aging as a disease may lead to more efficient allocation of resources by enabling funding bodies and other stakeholders to use quality-adjusted life years (QALYs and healthy-years equivalent (HYE as metrics when evaluating both research and clinical programs. We propose forming a Task Force to interface the WHO in order to develop a multidisciplinary framework for classifying aging as a disease.

  8. [Pharmacological therapy of age-related macular degeneration based on etiopathogenesis].

    Science.gov (United States)

    Fischer, Tamás

    2015-11-15

    It is of great therapeutic significance that disordered function of the vascular endothelium which supply the affected ocular structures plays a major role in the pathogenesis and development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfunction, and age-related macular degeneration is accompanied by a general inflammatory response. According to current concept, age-related macular degeneration is a local manifestation of systemic vascular disease. This recognition could have therapeutic implications because restoration of endothelial dysfunction can restabilize the condition of chronic vascular disease including age-related macular degeneration as well. Restoration of endothelial dysfunction by pharmaacological or non pharmacological interventions may prevent the development or improve endothelial dysfunction, which result in prevention or improvement of age related macular degeneration as well. Medicines including inhibitors of the renin-angiotensin system (converting enzyme inhibitors, angiotensin-receptor blockers and renin inhibitors), statins, acetylsalicylic acid, trimetazidin, third generation beta-blockers, peroxisome proliferator-activated receptor gamma agonists, folate, vitamin D, melatonin, advanced glycation end-product crosslink breaker alagebrium, endothelin-receptor antagonist bosentan, coenzyme Q10; "causal" antioxidant vitamins, N-acetyl-cysteine, resveratrol, L-arginine, serotonin receptor agonists, tumor necrosis factor-alpha blockers, specific inhibitor of the complement alternative pathway, curcumin and doxycyclin all have beneficial effects on endothelial dysfunction. Restoration of endothelial dysfunction can restabilize chronic vascular disease including age-related macular degeneration as well. Considering that the human vascular system is consubstantial, medicines listed above should be given to patients (1) who have no macular degeneration but have risk factors

  9. Age by Disease Biological Interactions: Implications for Late-Life Depression

    Directory of Open Access Journals (Sweden)

    Brandon eMcKinney

    2012-11-01

    Full Text Available Onset of depressive symptoms after the age of 65, or late-life depression (LLD, is common and poses a significant burden on affected individuals, caretakers and society. Evidence suggests a unique biological basis for LLD, but current hypotheses do not account for its pathophysiological complexity. Here we propose a novel etiological framework for LLD, the age-by-disease biological interaction hypothesis, based on the observations that the subset of genes that undergoes lifelong progressive changes in expression is restricted to a specific set of biological processes, and that a disproportionate number of these age-dependent genes have been previously and similarly implicated in neurodegenerative and neuropsychiatric disorders, including depression. The age-by-disease biological interaction hypothesis posits that age-dependent biological processes (i are pushed in LLD-promoting directions by changes in gene expression naturally occurring during brain aging, which (ii directly contribute to pathophysiological mechanisms of LLD, and (iii that individual variability in rates of age-dependent changes determines risk or resiliency to develop age-related disorders, including LLD. We review observations supporting this hypothesis, including consistent and specific age-dependent changes in brain gene expression, and their overlap with neuropsychiatric and neurodegenerative disease pathways. We then review preliminary reports supporting the genetic component of this hypothesis. Other potential biological mediators of age-dependent gene changes are proposed. We speculate that studies examining the relative contribution of these mechanisms to age-dependent changes and related disease mechanisms will not only provide critical information on the biology of normal aging of the human brain, but will inform our understanding our age-dependent diseases, in time fostering the development of new interventions for prevention and treatment of age-dependent diseases

  10. Classifying aging as a disease in the context of ICD-11.

    Science.gov (United States)

    Zhavoronkov, Alex; Bhullar, Bhupinder

    2015-01-01

    Aging is a complex continuous multifactorial process leading to loss of function and crystalizing into the many age-related diseases. Here, we explore the arguments for classifying aging as a disease in the context of the upcoming World Health Organization's 11th International Statistical Classification of Diseases and Related Health Problems (ICD-11), expected to be finalized in 2018. We hypothesize that classifying aging as a disease with a "non-garbage" set of codes will result in new approaches and business models for addressing aging as a treatable condition, which will lead to both economic and healthcare benefits for all stakeholders. Actionable classification of aging as a disease may lead to more efficient allocation of resources by enabling funding bodies and other stakeholders to use quality-adjusted life years (QALYs) and healthy-years equivalent (HYE) as metrics when evaluating both research and clinical programs. We propose forming a Task Force to interface the WHO in order to develop a multidisciplinary framework for classifying aging as a disease with multiple disease codes facilitating for therapeutic interventions and preventative strategies.

  11. The role of hydrogen sulfide in aging and age-related pathologies.

    Science.gov (United States)

    Perridon, Bernard W; Leuvenink, Henri G D; Hillebrands, Jan-Luuk; van Goor, Harry; Bos, Eelke M

    2016-09-27

    When humans grow older, they experience inevitable and progressive loss of physiological function, ultimately leading to death. Research on aging largely focuses on the identification of mechanisms involved in the aging process. Several proposed aging theories were recently combined as the 'hallmarks of aging'. These hallmarks describe (patho-)physiological processes that together, when disrupted, determine the aging phenotype. Sustaining evidence shows a potential role for hydrogen sulfide (H 2 S) in the regulation of aging. Nowadays, H 2 S is acknowledged as an endogenously produced signaling molecule with various (patho-) physiological effects. H 2 S is involved in several diseases including pathologies related to aging. In this review, the known, assumed and hypothetical effects of hydrogen sulfide on the aging process will be discussed by reviewing its actions on the hallmarks of aging and on several age-related pathologies.

  12. Alzheimer's disease and age-related memory decline (preclinical).

    Science.gov (United States)

    Terry, Alvin V; Callahan, Patrick M; Hall, Brandon; Webster, Scott J

    2011-08-01

    An unfortunate result of the rapid rise in geriatric populations worldwide is the increasing prevalence of age-related cognitive disorders such as Alzheimer's disease (AD). AD is a devastating neurodegenerative illness that is characterized by a profound impairment of cognitive function, marked physical disability, and an enormous economic burden on the afflicted individual, caregivers, and society in general. The rise in elderly populations is also resulting in an increase in individuals with related (potentially treatable) conditions such as "Mild Cognitive Impairment" (MCI) which is characterized by a less severe (but abnormal) level of cognitive impairment and a high-risk for developing dementia. Even in the absence of a diagnosable disorder of cognition (e.g., AD and MCI), the perception of increased forgetfulness and declining mental function is a clear source of apprehension in the elderly. This is a valid concern given that even a modest impairment of cognitive function is likely to be associated with significant disability in a rapidly evolving, technology-based society. Unfortunately, the currently available therapies designed to improve cognition (i.e., for AD and other forms of dementia) are limited by modest efficacy and adverse side effects, and their effects on cognitive function are not sustained over time. Accordingly, it is incumbent on the scientific community to develop safer and more effective therapies that improve and/or sustain cognitive function in the elderly allowing them to remain mentally active and productive for as long as possible. As diagnostic criteria for memory disorders evolve, the demand for pro-cognitive therapeutic agents is likely to surpass AD and dementia to include MCI and potentially even less severe forms of memory decline. The purpose of this review is to provide an overview of the contemporary therapeutic targets and preclinical pharmacologic approaches (with representative drug examples) designed to enhance memory

  13. Increased brain-predicted aging in treated HIV disease.

    Science.gov (United States)

    Cole, James H; Underwood, Jonathan; Caan, Matthan W A; De Francesco, Davide; van Zoest, Rosan A; Leech, Robert; Wit, Ferdinand W N M; Portegies, Peter; Geurtsen, Gert J; Schmand, Ben A; Schim van der Loeff, Maarten F; Franceschi, Claudio; Sabin, Caroline A; Majoie, Charles B L M; Winston, Alan; Reiss, Peter; Sharp, David J

    2017-04-04

    To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. A large sample of virologically suppressed HIV-positive adults (n = 162, age 45-82 years) and highly comparable HIV-negative controls (n = 105) were recruited as part of the Comorbidity in Relation to AIDS (COBRA) collaboration. Using T1-weighted MRI scans, a machine-learning model of healthy brain aging was defined in an independent cohort (n = 2,001, aged 18-90 years). Neuroimaging data from HIV-positive and HIV-negative individuals were then used to estimate brain-predicted age; then brain-predicted age difference (brain-PAD = brain-predicted brain age - chronological age) scores were calculated. Neuropsychological and clinical assessments were also carried out. HIV-positive individuals had greater brain-PAD score (mean ± SD 2.15 ± 7.79 years) compared to HIV-negative individuals (-0.87 ± 8.40 years; b = 3.48, p brain-PAD score was associated with decreased performance in multiple cognitive domains (information processing speed, executive function, memory) and general cognitive performance across all participants. Brain-PAD score was not associated with age, duration of HIV infection, or other HIV-related measures. Increased apparent brain aging, predicted using neuroimaging, was observed in HIV-positive adults, despite effective viral suppression. Furthermore, the magnitude of increased apparent brain aging related to cognitive deficits. However, predicted brain age difference did not correlate with chronological age or duration of HIV infection, suggesting that HIV disease may accentuate rather than accelerate brain aging. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  14. Perceptions of competence: age moderates views of healthy aging and Alzheimer's disease.

    Science.gov (United States)

    Berry, Jane M; Williams, Helen L; Thomas, Kevin D; Blair, Jamie

    2015-01-01

    BACKGROUND/STUDY CONTEXT: Older adults have more complex and differentiated views of aging than do younger adults, but less is known about age-related perceptions of Alzheimer's disease. This study investigated age-related perceptions of competence of an older adult labeled as "in good health" (healthy) or "has Alzheimer's disease" (AD), using a person-perception paradigm. It was predicted that older adults would provide more differentiated assessments of the two targets than would younger adults. Younger (n=86; 18-36 years) and older (n=66; 61-95 years) adults rated activities of daily living (ADL), instrumental activities of daily living (IADL), and memory abilities of a female target aged 75 years, described as healthy or with AD. Data on anxiety about aging, knowledge of and experience with aging and AD, knowledge of memory aging, and positive and negative biases toward aging and AD were also collected. Older adults perceived the healthy target as more capable of cognitively effortful activities (e.g., managing finances) and as possessing better memory abilities than the AD target. As predicted, these differences were greater than differences between targets perceived by younger adults. The interaction effect remained significant after statistically controlling for relevant variables, including education and gender. Additionally, exploratory analyses revealed that older adults held less positively biased views of AD than younger adults, but negatively biased views were equivalent between age groups. The results demonstrate that mere labels of "healthy" and "Alzheimer's disease" produce significant and subtle age differences in perceived competencies of older adults, and that biases towards AD vary by age group and valence. Our findings extend the person-perception paradigm to an integrative analysis of aging and AD, are consistent with models of adult development, and complement current research and theory on stereotypes of aging. Future directions for research

  15. Age at menarche and pregnancy-related pelvic pain

    DEFF Research Database (Denmark)

    Kirkeby, Mette J; Biering, Karin; Olsen, Jørn

    2013-01-01

    AIM: Menarcheal age is a predictor of several complications related to pregnancy and diseases later in life. We aimed to study if menarcheal age is a risk factor for pregnancy-related pelvic pain. MATERIAL AND METHODS: A nested case-control study was conducted within the Danish National Birth...

  16. [Sense of smell, physiological ageing and neurodegenerative diseases: II. Ageing and neurodegenerative diseases].

    Science.gov (United States)

    Fusari, A; Molina, J A

    The sense of smell, which was once studied because of its biological and evolutionary significance, is today one of the centres of interest in research on normal and pathological ageing. The latest scientific developments point to an inversely proportional relationship between age and olfactory sensitivity. In certain neurodegenerative diseases this sensory decline is one of the first symptoms of the disorder and is correlated with the progression of the disease. In this work we are going to review the scientific knowledge on loss of sense of smell in ageing and in neurodegenerative diseases, with special attention given to Alzheimer's and Parkinson's diseases. A survey of studies that have examined the olfactory deficits in ageing and in some neurodegenerative diseases offers conclusive results about the presence of these impairments in the early stages of these disorders and even among healthy elderly persons. Although a number of causes contribute to these sensory losses in physiological ageing, a common neurological foundation has been proposed for Alzheimer's and Parkinson's diseases. Nevertheless, despite certain initial similarities, the olfactory deficits shown in these disorders seem to be qualitatively different.

  17. Recent advances in treatment of wet age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Ming Li

    2015-02-01

    Full Text Available Age-related macular degeneration(AMDis one of the important eye diseases of the WHO present three big blindness, is one of the main blinding eye disease in people over the age of 50, people over the age of 65, about 2% of the disease caused by monocular blindness, as the population ages, AMD prevalence is increasing in our country. AMD with respect to its clinical manifestations can be divided into dry AMD and wet AMD, wet AMD is the most harmful for the vision of patients, at present there are many treatments for AMD(mainly for wet age-related macular degeneration, mainly including laser treatment, drug therapy, surgical treatment, gene therapy,etc. The treatments of AMD would be illuminated in this article.

  18. Celiac disease and new diseases related to gluten

    Science.gov (United States)

    Jiménez Ortega, Ana Isabel; Martínez García, Rosa María; Quiles Blanco, María José; Majid Abu Naji, Jamil Abdel; González Iglesias, María José

    2016-07-12

    Celiac disease is the most common chronic intestinal disease. Nowadays it´s known that this is a multisistemic pathology of immune mechanism, triggered by gluten, which occurs in genetically susceptible individuals. It affects approximately 1% of the world population, which is a very high prevalence, affects all age groups and has symptoms both digestive and extra-digestive. Since it is a disease that requires maintaining a gluten-free diet and medical monitoring for life, it is important to know it and establish its diagnosis properly. Along with celiac disease a number of new diseases related to gluten are diagnosed increasingly, including the non celiac gluten sensitivity or wheat allergy. The suffering of celiac disease, or other related diseases, by conditioning diet changes of the affected individual, it may be associated with nutritional imbalances that need to monitor and try to solve. Therefore patients with this problem need special nutritional advice.

  19. Relative importance of redox buffers GSH and NAD(P)H in age-related neurodegeneration and Alzheimer disease-like mouse neurons.

    Science.gov (United States)

    Ghosh, Debolina; Levault, Kelsey R; Brewer, Gregory J

    2014-08-01

    Aging, a major risk factor in Alzheimer's disease (AD), is associated with an oxidative redox shift, decreased redox buffer protection, and increased free radical reactive oxygen species (ROS) generation, probably linked to mitochondrial dysfunction. While NADH is the ultimate electron donor for many redox reactions, including oxidative phosphorylation, glutathione (GSH) is the major ROS detoxifying redox buffer in the cell. Here, we explored the relative importance of NADH and GSH to neurodegeneration in aging and AD neurons from nontransgenic and 3xTg-AD mice by inhibiting their synthesis to determine whether NADH can compensate for the GSH loss to maintain redox balance. Neurons stressed by either depleting NAD(P)H or GSH indicated that NADH redox control is upstream of GSH levels. Further, although depletion of NAD(P)H or GSH correlated linearly with neuron death, compared with GSH depletion, higher neurodegeneration was observed when NAD(P)H was extrapolated to zero, especially in old age, and in the 3xTg-AD neurons. We also observed an age-dependent loss of gene expression of key redox-dependent biosynthetic enzymes, NAMPT (nicotinamide phosphoribosyltransferase), and NNT (nicotinamide nucleotide transhydrogenase). Moreover, age-related correlations between brain NNT or NAMPT gene expression and NADPH levels suggest that these genes contribute to the age-related declines in NAD(P)H. Our data indicate that in aging and more so in AD-like neurons, NAD(P)H redox control is upstream of GSH and an oxidative redox shift that promotes neurodegeneration. Thus, NAD(P)H generation may be a more efficacious therapeutic target upstream of GSH and ROS. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  20. [Decline in renal function in old age : Part of physiological aging versus age-related disease].

    Science.gov (United States)

    Braun, F; Brinkkötter, P T

    2016-08-01

    The incidence and prevalence of chronic renal disease (CKD) in elderly patients are continuously increasing worldwide. Loss of renal function is not only considered to be part of the aging process itself but also reflects the multimorbidity of many geriatric patients. Calculating the glomerular filtration rate using specific algorithms validated for the elderly population and measuring the amount of proteinuria allow an estimation of renal function in elderly patients with high accuracy. Chronic renal failure has many clinical consequences and not only results in a delayed excretion of toxins cleared by the kidneys but also affects hematogenesis, water and electrolyte balance as well as mineral bone metabolism. Furthermore, CKD directly leads to and aggravates geriatric syndromes and in particular the onset of frailty. Therapeutic strategies to halt progression of CKD not only comprise treatment of the underlying disease but also efficient blood pressure and diabetic control and the avoidance of nephrotoxic medications.

  1. Age-related Defects in Ocular and Nasal Mucosal Immune System and the Immunopathology of Dry Eye Disease

    Science.gov (United States)

    Farid, Marjan; Agrawal, Anshu; Fremgen, Daniel; Tao, Jeremiah; Chuyi, He; Nesburn, Anthony B.; BenMohamed, Lbachir

    2014-01-01

    Dry eye disease (DED) is a prevalent public health concern that affects up to 30% of adults and is particularly chronic and severe in the elderly. Two interconnected mechanisms cause DED: (1) an age-related dysfunction of lacrimal and meibomian glands, which leads to decreased tear production and/or an increase in tear evaporation; and (2) an age-related uncontrolled inflammation of the surface of the eye triggered by yet-to-be-determined internal immunopathological mechanisms, independent of tear deficiency and evaporation. In this review we summarize current knowledge on animal models that mimic both the severity and chronicity of inflammatory DED and that have been reliably used to provide insights into the immunopathological mechanisms of DED, and we provide an overview of the opportunities and limitations of the rabbit model in investigating the role of both ocular and nasal mucosal immune systems in the immunopathology of inflammatory DED and in testing novel immunotherapies aimed at delaying or reversing the uncontrolled age-related inflammatory DED. PMID:25535823

  2. Study of relation between the onset age of type 1 diabetes and celiac disease in children andadole scents

    Directory of Open Access Journals (Sweden)

    robabe Ghergherehchi

    2010-02-01

    Full Text Available Celiac disease (CD is a chronic enteropathy caused by hypersensitivity to gluten. Most studies have showed more prevalence of CD in the patients with diabetes mellitus type 1. Both diseases are autoimmune and their incidence is related to inheritance and environmental factors. The aim of this research is the study of relation between CD prevalence and diabetic age onset. Materials and Methods: In this descriptive cross-sectional study, 135 children with diabetes mellitus type 1 referring to Tabriz children hospital endocrine department and clinic between 2006-2008 were selected. After filling individual identity of the patients and the measurement of weight and height, the serumic level of anti-tissue Trans glutaminase IgA antibody (A-tTG-A-IgA, anti endomisial IgA antibody (AEA-IgA and anti-gliadin IgG antibody (AGA-IgG were measured. In the case that A-tTG-A either AEA alone or with AGA was high, small intestinal biopsy was preformed. The data was analysed using SPSS ver 16 software. Results: 28 of 135 patients with diabetes mellitus type 1, were serologically positive for celiac. Confirmed celiac prevalence based on biopsy was 6. 8%. From diabetic age onset and celiac incidence point of view there was not any significant relation (P=0. 996. Conclusion: Celiac disease in type1 diabetic patients dose not have correlation with the onset age of type 1 diabetes and diabetic patients should be followed up from celiac point of view during treatment and prevention.

  3. Assessing Age-Related Etiologic Heterogeneity in the Onset of Islet Autoimmunity

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    Brittni N. Frederiksen

    2015-01-01

    Full Text Available Type 1 diabetes (T1D, a chronic autoimmune disease, is often preceded by a preclinical phase of islet autoimmunity (IA where the insulin-producing beta cells of the pancreas are destroyed and circulating autoantibodies can be detected. The goal of this study was to demonstrate methods for identifying exposures that differentially influence the disease process at certain ages by assessing age-related heterogeneity. The Diabetes Autoimmunity Study in the Young (DAISY has followed 2,547 children at increased genetic risk for T1D from birth since 1993 in Denver, Colorado, 188 of whom developed IA. Using the DAISY population, we evaluated putative determinants of IA, including non-Hispanic white (NHW ethnicity, maternal age at birth, and erythrocyte membrane n-3 fatty acid (FA levels, for age-related heterogeneity. A supremum test, weighted Schoenfeld residuals, and restricted cubic splines were used to assess nonproportional hazards, that is, an age-related association of the exposure with IA risk. NHW ethnicity, maternal age, and erythrocyte membrane n-3 FA levels demonstrated a significant age-related association with IA risk. Assessing heterogeneity in disease etiology enables researchers to identify associations that may lead to better understanding of complex chronic diseases.

  4. The Age-Related Eye Disease 2 Study: Micronutrients in the Treatment of Macular Degeneration.

    Science.gov (United States)

    Gorusupudi, Aruna; Nelson, Kelly; Bernstein, Paul S

    2017-01-01

    Age-related macular degeneration (AMD) is one of the leading causes of vision loss in the elderly. With an increasingly aged population worldwide, the need for the prevention of AMD is rising. Multiple studies investigating AMD with the use of animal models and cell culture have identified oxidative stress-related retinal damage as an important contributing factor. In general, diet is an excellent source of the antioxidants, vitamins, and minerals necessary for healthy living; moreover, the general public is often receptive to recommendations made by physicians and health care workers regarding diet and supplements as a means of empowering themselves to avoid common and worrisome ailments such as AMD, which has made epidemiologists and clinicians enthusiastic about dietary intervention studies. A wide variety of nutrients, such as minerals, vitamins, ω-3 (n-3) fatty acids, and various carotenoids, have been associated with reducing the risk of AMD. Initial results from the Age-Related Eye Disease Study (AREDS) indicated that supplementation with antioxidants (β-carotene and vitamins C and E) and zinc was associated with a reduced risk of AMD progression. The AREDS2 follow-up study, designed to improve upon the earlier formulation, tested the addition of lutein, zeaxanthin, and ω-3 fatty acids. In this review, we examine the science behind the nutritional factors included in these interventional studies and the reasons for considering their inclusion to lower the rate of AMD progression. © 2017 American Society for Nutrition.

  5. Oxidative stress, aging, and diseases

    Directory of Open Access Journals (Sweden)

    Liguori I

    2018-04-01

    Full Text Available Ilaria Liguori,1 Gennaro Russo,1 Francesco Curcio,1 Giulia Bulli,1 Luisa Aran,1 David Della-Morte,2,3 Gaetano Gargiulo,4 Gianluca Testa,1,5 Francesco Cacciatore,1,6 Domenico Bonaduce,1 Pasquale Abete1 1Department of Translational Medical Sciences, University of Naples “Federico II”, Naples, Italy; 2Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy; 3San Raffaele Roma Open University, Rome, Italy; 4Division of Internal Medicine, AOU San Giovanni di Dio e Ruggi di Aragona, Salerno, Italy; 5Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy; 6Azienda Ospedaliera dei Colli, Monaldi Hospital, Heart Transplantation Unit, Naples, Italy Abstract: Reactive oxygen and nitrogen species (RONS are produced by several endogenous and exogenous processes, and their negative effects are neutralized by antioxidant defenses. Oxidative stress occurs from the imbalance between RONS production and these antioxidant defenses. Aging is a process characterized by the progressive loss of tissue and organ function. The oxidative stress theory of aging is based on the hypothesis that age-associated functional losses are due to the accumulation of RONS-induced damages. At the same time, oxidative stress is involved in several age-related conditions (ie, cardiovascular diseases [CVDs], chronic obstructive pulmonary disease, chronic kidney disease, neurodegenerative diseases, and cancer, including sarcopenia and frailty. Different types of oxidative stress biomarkers have been identified and may provide important information about the efficacy of the treatment, guiding the selection of the most effective drugs/dose regimens for patients and, if particularly relevant from a pathophysiological point of view, acting on a specific therapeutic target. Given the important role of oxidative stress in the pathogenesis of many clinical conditions and aging, antioxidant therapy could positively affect the natural history of

  6. Identification of age- and disease-related alterations in circulating miRNAs in a mouse model of Alzheimer's disease

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    Sylvia eGarza-Manero

    2015-02-01

    Full Text Available Alzheimer's disease (AD is a neurodegenerative disorder characterized clinically by the progressive decline of memory and cognition. Histopathologically, two main hallmarks have been identified in AD: amyloid-β peptide extracellular neuritic plaques and neurofibrillary tangles formed by posttranslational modified tau protein. A definitive diagnosis can only be achieved after the post mortem verification of the histological mentioned alterations. Therefore the development of biomarkers that allow an early diagnosis and/or predict disease progression is imperative. The prospect of a blood-based biomarker is possible with the finding of circulating microRNAs (miRNAs, a class of small non-coding RNAs of 22-25 nucleotides length that regulate mRNA translation rate. miRNAs travel through blood and recent studies performed in potential AD cases suggest the possibility of finding pathology-associated differences in circulating miRNA levels that may serve to assist in early diagnosis of the disease. However, these studies analyzed samples at a single time-point, limiting the use of miRNAs as biomarkers in AD progression. In this study we evaluated miRNA levels in plasma samples at different time-points of the evolution of an AD-like pathology in a transgenic mouse model of the disease (3xTg-AD. We performed multiplex qRT-PCR and compared the plasmatic levels of 84 miRNAs previously associated to central nervous system development and disease. No significant differences were detected between WT and transgenic young mice. However, age-related significant changes in miRNA abundance were observed for both WT and transgenic mice, and some of these were specific for the 3xTg-AD. In agreement, variations in the levels of particular miRNAs were identified between WT and transgenic old mice thus suggesting that the age-dependent evolution of the AD-like pathology, rather than the presence and expression of the transgenes, modifies the circulating miRNA levels in

  7. Development of age-related maculopathy: a histochemical and molecular approach

    NARCIS (Netherlands)

    A.C. Lambooij (Antoinette)

    2002-01-01

    textabstractAge-related maculopathy (ARM) is a severe threat to the visual ability of people over 65 years of age. In the late stages of ARM, called age-related macular degeneration (AMD), photoreceptor cells gradually disappear. New vessels growing beneath the retina may complicateb the disease;

  8. Age-Related Diseases and Clinical and Public Health Implications for the 85 Years Old and Over Population

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    Efraim Jaul

    2017-12-01

    Full Text Available By 2050, the American 85 years old and over population will triple. Clinicians and the public health community need to develop a culture of sensitivity to the needs of this population and its subgroups. Sensory changes, cognitive changes, and weakness may be subtle or may be severe in the heterogeneous population of people over age 85. Falls, cardiovascular disease, and difficulty with activities of daily living are common but not universal. This paper reviews relevant changes of normal aging, diseases, and syndromes common in people over age 85, cognitive and psychological changes, social and environmental changes, and then reviews common discussions which clinicians routinely have with these patients and their families. Some hearing and vision loss are a part of normal aging as is decline in immune function. Cardiovascular disease and osteoporosis and dementia are common chronic conditions at age 85. Osteoarthritis, diabetes, and related mobility disability will increase in prevalence as the population ages and becomes more overweight. These population changes have considerable public health importance. Caregiver support, services in the home, assistive technologies, and promotion of home exercise programs as well as consideration of transportation and housing policies are recommended. For clinicians, judicious prescribing and ordering of tests includes a consideration of life expectancy, lag time to benefit, and patient goals. Furthermore, healthy behaviors starting in early childhood can optimize quality of life among the oldest-old.

  9. Hodgkin's disease and age

    DEFF Research Database (Denmark)

    Specht, L; Nissen, N I

    1989-01-01

    506 unselected, previously untreated patients with Hodgkin's disease were treated at the Finsen Institute between 1969 and 1983. The prognostic significance of age, sex, stage, systemic symptoms, histologic subtype, number of involved nodal regions, total tumour burden (peripheral + intrathoracic...... nodal tumour burden, intraabdominal nodal tumour burden, and number of involved extranodal sites), pretreatment ESR, lymphocytopenia, and treatment modality were examined in multivariate analyses. The only factors of independent prognostic significance for disease-free survival proved to be treatment...... modality, stage, and total tumour burden, whereas age had no prognostic significance. With regard to death from Hodgkin's disease only age and total tumour burden had independent significance. The significance of age would seem to stem from the fact that some older patients could not be given adequate...

  10. Hodgkin's disease and age

    DEFF Research Database (Denmark)

    Specht, L.; Nissen, N.I.

    1989-01-01

    506 unselected, previously untreated patients with Hodgkin's disease were treated at the Finsen Institute between 1969 and 1983. The prognostic significance of age, sex, stage, systemic symptoms, histologic subtype, number of involved nodal regions, total tumour burden (peripheral + intrathoracic...... modality, stage, and total tumour burden, whereas age had no prognostic significance. With regard to death from Hodgkin's disease only age and total tumour burden had independent significance. The significance of age would seem to stem from the fact that some older patients could not be given adequate...

  11. Pathophysiology of Age-Related Hearing Loss (Peripheral and Central)

    OpenAIRE

    Lee, Kyu-Yup

    2013-01-01

    Age-related hearing loss (presbycusis) refers to bilaterally symmetrical hearing loss resulting from aging process. Presbycusis is a complex phenomenon characterized by audiometric threshold shift, deterioration in speech-understanding and speech-perception difficulties in noisy environments. Factors contributing to presbycusis include mitochondria DNA mutation, genetic disorders including Ahl, hypertension, diabetes, metabolic disease and other systemic diseases in the intrinsic aspects. Ext...

  12. Identification of Age-Related Macular Degeneration Using OCT Images

    Science.gov (United States)

    Arabi, Punal M., Dr; Krishna, Nanditha; Ashwini, V.; Prathibha, H. M.

    2018-02-01

    Age-related Macular Degeneration is the most leading retinal disease in the recent years. Macular degeneration occurs when the central portion of the retina, called macula deteriorates. As the deterioration occurs with the age, it is commonly referred as Age-related Macular Degeneration. This disease can be visualized by several imaging modalities such as Fundus imaging technique, Optical Coherence Tomography (OCT) technique and many other. Optical Coherence Tomography is the widely used technique for screening the Age-related Macular Degeneration disease, because it has an ability to detect the very minute changes in the retina. The Healthy and AMD affected OCT images are classified by extracting the Retinal Pigmented Epithelium (RPE) layer of the images using the image processing technique. The extracted layer is sampled, the no. of white pixels in each of the sample is counted and the mean value of the no. of pixels is calculated. The average mean value is calculated for both the Healthy and the AMD affected images and a threshold value is fixed and a decision rule is framed to classify the images of interest. The proposed method showed an accuracy of 75%.

  13. Mitochondria, Cybrids, Aging, and Alzheimer’s Disease

    Science.gov (United States)

    Swerdlow, Russell H.; Koppel, Scott; Weidling, Ian; Hayley, Clay; Ji, Yan; Wilkins, Heather M.

    2018-01-01

    Mitochondrial and bioenergetic function change with advancing age and may drive aging phenotypes. Mitochondrial and bioenergetic changes are also documented in various age-related neurodegenerative diseases, including Alzheimer’s disease (AD). In some instances AD mitochondrial and bioenergetic changes are reminiscent of those observed with advancing age, but are greater in magnitude. Mitochondrial and bioenergetic dysfunction could, therefore, link neurodegeneration to brain aging. Interestingly, mitochondrial defects in AD patients are not brain-limited, and mitochondrial function can be linked to classic AD histologic changes including amyloid precursor protein processing to beta amyloid. Also, transferring mitochondria from AD subjects to cell lines depleted of endogenous mitochondrial DNA (mtDNA) creates cytoplasmic hybrid (cybrid) cell lines that recapitulate specific biochemical, molecular, and histologic AD features. Such findings have led to the formulation of a “mitochondrial cascade hypothesis” that places mitochondrial dysfunction at the apex of the AD pathology pyramid. Data pertinent to this premise are reviewed. PMID:28253988

  14. [Current concepts in pathogenesis of age-related macular degeneration].

    Science.gov (United States)

    Kubicka-Trząska, Agnieszka; Karska-Basta, Izabella; Romanowska-Dixon, Bożena

    2014-01-01

    Age-related macular degeneration is the leading cause of central blindness in elderly population of the western world. The pathogenesis of this disease, likely multifactorial, is not well known, although a number of theories have been put forward, including oxidative stress, genetic interactions, hemodynamic imbalance, immune and inflammatory processes. The understanding of age-related macular degeneration pathogenesis will give rise to new approaches in prevention and treatment of the early and late stages of both atrophic and neovascular age-related macular degeneration.

  15. The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients

    DEFF Research Database (Denmark)

    Metzger, Silke; Walter, Carolin; Riess, Olaf

    2013-01-01

    The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently......, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second...... independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the "REGISTRY" cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing...

  16. Use of Curcumin, a Natural Polyphenol for Targeting Molecular Pathways in Treating Age-Related Neurodegenerative Diseases

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    Panchanan Maiti

    2018-05-01

    Full Text Available Progressive accumulation of misfolded amyloid proteins in intracellular and extracellular spaces is one of the principal reasons for synaptic damage and impairment of neuronal communication in several neurodegenerative diseases. Effective treatments for these diseases are still lacking but remain the focus of much active investigation. Despite testing several synthesized compounds, small molecules, and drugs over the past few decades, very few of them can inhibit aggregation of amyloid proteins and lessen their neurotoxic effects. Recently, the natural polyphenol curcumin (Cur has been shown to be a promising anti-amyloid, anti-inflammatory and neuroprotective agent for several neurodegenerative diseases. Because of its pleotropic actions on the central nervous system, including preferential binding to amyloid proteins, Cur is being touted as a promising treatment for age-related brain diseases. Here, we focus on molecular targeting of Cur to reduce amyloid burden, rescue neuronal damage, and restore normal cognitive and sensory motor functions in different animal models of neurodegenerative diseases. We specifically highlight Cur as a potential treatment for Alzheimer’s, Parkinson’s, Huntington’s, and prion diseases. In addition, we discuss the major issues and limitations of using Cur for treating these diseases, along with ways of circumventing those shortcomings. Finally, we provide specific recommendations for optimal dosing with Cur for treating neurological diseases.

  17. How are self-rated health and diagnosed disease related to early or deferred retirement? A cross-sectional study of employees aged 55-64

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    Kerstin Nilsson

    2016-08-01

    Full Text Available Abstract Background More people will probably continue working into old age in the future due to the increased size of aging populations in many countries. We therefore need to know more about older workers’ health in relation to their work situation and retirement. This study is a part of a theoretical development of older workers’ situations. Older workers’ situations are theoretically themed in nine areas by the authors of this study. The aims of the study were to investigate the relationship between: i diagnosed disease and factors in older workers’ situations, theoretically themed in nine areas; ii self-rated health and factors in older workers’ situations, theoretically themed in nine areas; iii diagnosed disease and self-rated health; and iv the relationships between these health measures and retirement. Methods A questionnaire-based cross-sectional study, using logistic regression, with 1,756 health care personnel aged 55–64 years. The questionnaire used gave an overview of most different areas in the older workers’ situations. Result There was a difference in the participants’ frequency of objectively specified diagnosed disease and their subjectively experienced self-rated health. A bad self-rated health was related higher to early retirement than diagnosed diseases. In the multivariate model, having ‘Diagnosed disease’ was not significantly related to whether older workers thought they could not work beyond 65 years of age. A bad ‘Self-rated health’ was also more highly related to whether older workers thought they could not work beyond 65 years, than if the respondents stated that a ‘Diagnosed disease is a hindrance in my daily work’ in the multivariate model. Conclusion This study showed an important difference between older workers’ own experiences and the effect of their self-rated health and their diagnosed diseases. Subjective self-rated health seems to be more important to people’s retirement

  18. A method for age-matched OCT angiography deviation mapping in the assessment of disease- related changes to the radial peripapillary capillaries.

    Science.gov (United States)

    Pinhas, Alexander; Linderman, Rachel; Mo, Shelley; Krawitz, Brian D; Geyman, Lawrence S; Carroll, Joseph; Rosen, Richard B; Chui, Toco Y

    2018-01-01

    To present a method for age-matched deviation mapping in the assessment of disease-related changes to the radial peripapillary capillaries (RPCs). We reviewed 4.5x4.5mm en face peripapillary OCT-A scans of 133 healthy control eyes (133 subjects, mean 41.5 yrs, range 11-82 yrs) and 4 eyes with distinct retinal pathologies, obtained using spectral-domain optical coherence tomography angiography. Statistical analysis was performed to evaluate the impact of age on RPC perfusion densities. RPC density group mean and standard deviation maps were generated for each decade of life. Deviation maps were created for the diseased eyes based on these maps. Large peripapillary vessel (LPV; noncapillary vessel) perfusion density was also studied for impact of age. Average healthy RPC density was 42.5±1.47%. ANOVA and pairwise Tukey-Kramer tests showed that RPC density in the ≥60yr group was significantly lower compared to RPC density in all younger decades of life (pDeviation mapping enabled us to quantitatively and visually elucidate the significance of RPC density changes in disease. It is important to consider changes that occur with aging when analyzing RPC and LPV density changes in disease. RPC density, coupled with age-matched deviation mapping techniques, represents a potentially clinically useful method in detecting changes to peripapillary perfusion in disease.

  19. The Age-Related Eye Disease 2 Study: Micronutrients in the Treatment of Macular Degeneration123

    Science.gov (United States)

    Gorusupudi, Aruna; Nelson, Kelly; Bernstein, Paul S

    2017-01-01

    Age-related macular degeneration (AMD) is one of the leading causes of vision loss in the elderly. With an increasingly aged population worldwide, the need for the prevention of AMD is rising. Multiple studies investigating AMD with the use of animal models and cell culture have identified oxidative stress–related retinal damage as an important contributing factor. In general, diet is an excellent source of the antioxidants, vitamins, and minerals necessary for healthy living; moreover, the general public is often receptive to recommendations made by physicians and health care workers regarding diet and supplements as a means of empowering themselves to avoid common and worrisome ailments such as AMD, which has made epidemiologists and clinicians enthusiastic about dietary intervention studies. A wide variety of nutrients, such as minerals, vitamins, ω-3 (n–3) fatty acids, and various carotenoids, have been associated with reducing the risk of AMD. Initial results from the Age-Related Eye Disease Study (AREDS) indicated that supplementation with antioxidants (β-carotene and vitamins C and E) and zinc was associated with a reduced risk of AMD progression. The AREDS2 follow-up study, designed to improve upon the earlier formulation, tested the addition of lutein, zeaxanthin, and ω-3 fatty acids. In this review, we examine the science behind the nutritional factors included in these interventional studies and the reasons for considering their inclusion to lower the rate of AMD progression. PMID:28096126

  20. Mechanism of Inflammation in Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Francesco Parmeggiani

    2012-01-01

    Full Text Available Age-related macular degeneration (AMD is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease.

  1. Mechanism of Inflammation in Age-Related Macular Degeneration

    Science.gov (United States)

    Parmeggiani, Francesco; Romano, Mario R.; Costagliola, Ciro; Semeraro, Francesco; Incorvaia, Carlo; D'Angelo, Sergio; Perri, Paolo; De Palma, Paolo; De Nadai, Katia; Sebastiani, Adolfo

    2012-01-01

    Age-related macular degeneration (AMD) is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease. PMID:23209345

  2. The changes of cerebral morphology related to aging in Taiwanese population.

    Directory of Open Access Journals (Sweden)

    Hsiao-Lan Sharon Wang

    Full Text Available A cross-sectional study with the 3-dimensional (3D MRI reconstruction technique was conducted to investigate cerebral complexity changes related to age differences in native Taiwanese population. In our sample of 85 participants aged between 25 and 81, age was associated with gradual ventricular expansion. A nonlinear quadratic relationship between white matter volume and age was found overall in the brain. Widespread age-related reduction in white matter was detected from late adulthood onwards. However, no significant age-related changes in the cortex and whole brain volume were determined throughout adulthood. These findings provided information in describing brain structural complexity, which might in the future serve as an objective diagnostic index or as a predictive parameter for neurological diseases. Our method then may be used for cross-cultural longitudinal studies to evaluate the effect of disease, environment and aging on the brain.

  3. Negative aspects of close social relations and 10-year incident ischaemic heart disease hospitalization among middle-aged Danes

    DEFF Research Database (Denmark)

    Lund, Rikke; Rod, Naja Hulvej; Thielen, Karsten

    2014-01-01

    BACKGROUND: Little is known about the association between negative aspects of close social relations and development of ischaemic heart disease (IHD). We aim to address if the experience of worries/demands and conflicts with close social relations are related to risk of first-time hospitalization...... National Patient Registry. Cox regression analysis was used to analyse data and all analyses were adjusted for age, gender, social class, cohabitation, and depressive symptoms. RESULTS: Worries/demands from and conflicts with children were associated with IHD hospitalization in an exposure-dependent manner...

  4. A dual agonist of farnesoid X receptor (FXR) and the G protein-coupled receptor TGR5, INT-767, reverses age-related kidney disease in mice.

    Science.gov (United States)

    Wang, Xiaoxin X; Luo, Yuhuan; Wang, Dong; Adorini, Luciano; Pruzanski, Mark; Dobrinskikh, Evgenia; Levi, Moshe

    2017-07-21

    Even in healthy individuals, renal function gradually declines during aging. However, an observed variation in the rate of this decline has raised the possibility of slowing or delaying age-related kidney disease. One of the most successful interventional measures that slows down and delays age-related kidney disease is caloric restriction. We undertook the present studies to search for potential factors that are regulated by caloric restriction and act as caloric restriction mimetics. Based on our prior studies with the bile acid-activated nuclear hormone receptor farnesoid X receptor (FXR) and G protein-coupled membrane receptor TGR5 that demonstrated beneficial effects of FXR and TGR5 activation in the kidney, we reasoned that FXR and TGR5 could be excellent candidates. We therefore determined the effects of aging and caloric restriction on the expression of FXR and TGR5 in the kidney. We found that FXR and TGR5 expression levels are decreased in the aging kidney and that caloric restriction prevents these age-related decreases. Interestingly, in long-lived Ames dwarf mice, renal FXR and TGR5 expression levels were also increased. A 2-month treatment of 22-month-old C57BL/6J mice with the FXR-TGR5 dual agonist INT-767 induced caloric restriction-like effects and reversed age-related increases in proteinuria, podocyte injury, fibronectin accumulation, TGF-β expression, and, most notably, age-related impairments in mitochondrial biogenesis and mitochondrial function. Furthermore, in podocytes cultured in serum obtained from old mice, INT-767 prevented the increases in the proinflammatory markers TNF-α, toll-like receptor 2 (TLR2), and TLR4. In summary, our results indicate that FXR and TGR5 may play an important role in modulation of age-related kidney disease. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. European survey on the opinion and use of micronutrition in age-related macular degeneration: 10 years on from the Age-Related Eye Disease Study

    Directory of Open Access Journals (Sweden)

    Aslam T

    2014-10-01

    Full Text Available Tariq Aslam,1 Cécile Delcourt,2 Frank Holz,3 Alfredo García-Layana,4 Anita Leys,5 Rufino M Silva,6 Eric Souied7 1Manchester Royal Eye Hospital, Manchester, UK; 2University of Bordeaux, Bordeaux, France; 3University of Bonn, Bonn, Germany; 4Clínica Universidad de Navarra, Pamplona, Spain; 5University Hospitals, Leuven, Belgium; 6University of Coimbra, Coimbra, Portugal; 7Université Paris Est Créteil, Créteil, FrancePurpose: To evaluate ophthalmologists’ opinion of, and use of, micronutritional dietary supplements 10 years after publication of the first Age-Related Eye Disease Study (AREDS study.Methods: Participation was solicited from 4,000 European ophthalmologists. Responding physicians were screened, and those treating at least 40 patients with age-related macular degeneration (AMD per month and prescribing nutrition supplements at least 4 times per month were admitted and completed a 40-item questionnaire.Results: The surveyed sample included 112 general ophthalmologists and 104 retinal specialists. Most nutritional supplements (46% were initiated when early/intermediate AMD was confirmed, although 18% were initiated on confirmation of neovascular AMD. Clinical studies were well known: 90% were aware of AREDS, with 88% aware of AREDS1 and 36% aware of the, as-yet-unpublished, AREDS2 studies. Respondents considered lutein, zeaxanthin, zinc, omega-3, and vitamins to be the most important components of nutritional supplements, with the results of AREDS2 already having been taken into consideration by many. Ophthalmologists anticipate more scientific studies as well as improved product quality but identify cost as a barrier to wider uptake.Conclusion: Micronutrition is now part of the routine management of AMD for many ophthalmologists. Ophthalmologists choosing to use nutritional supplements are well-informed regarding current scientific studies. Keywords: age-related macular degeneration, micronutrition, nutritional

  6. The involvement of BDNF, NGF and GDNF in aging and Alzheimer’s disease

    OpenAIRE

    Budni, Josiane; Bellettini-Santos, Tatiani; Mina, Francielle; Garcez, Michelle Lima; Zugno, Alexandra Ioppi

    2015-01-01

    Aging is a normal physiological process accompanied by cognitive decline. This aging process has been the primary risk factor for development of aging-related diseases such as Alzheimer’s disease (AD). Cognitive deficit is related to alterations of neurotrophic factors level such as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and glial cell-derived neurotrophic factor (GDNF). These strong relationship between aging and AD is important to investigate the time which they...

  7. Shared molecular and cellular mechanisms of premature ageing and ageing-associated diseases.

    Science.gov (United States)

    Kubben, Nard; Misteli, Tom

    2017-10-01

    Ageing is the predominant risk factor for many common diseases. Human premature ageing diseases are powerful model systems to identify and characterize cellular mechanisms that underpin physiological ageing. Their study also leads to a better understanding of the causes, drivers and potential therapeutic strategies of common diseases associated with ageing, including neurological disorders, diabetes, cardiovascular diseases and cancer. Using the rare premature ageing disorder Hutchinson-Gilford progeria syndrome as a paradigm, we discuss here the shared mechanisms between premature ageing and ageing-associated diseases, including defects in genetic, epigenetic and metabolic pathways; mitochondrial and protein homeostasis; cell cycle; and stem cell-regenerative capacity.

  8. Peculiarities of roentgenosemiotics of ulcerous disease in different age groups

    International Nuclear Information System (INIS)

    Kinoshenko, Yu.T.; Reztsova, N.S.

    1984-01-01

    Roentgenomorphological and functional signs of stomach and duodenum ulcer disease was studied in different age groups in 382 patients that were subjected to a complex of clinico-laboratory and roentgenological examinations. It is concluded that in different age groups ulcerous disease of stomach and duodenum is characterized by a considerable peculiarities of roengenomorphologic characters. In some age groups disclosed are characteristic symptomocomplexes of roentgenofunctional shifts typical of ulcers of different localisations. It is shown that there is a regular relation between the type of functional shifts, age of a patient and location of ulcers

  9. Aging-associated renal disease in mice is fructokinase dependent.

    Science.gov (United States)

    Roncal-Jimenez, Carlos A; Ishimoto, Takuji; Lanaspa, Miguel A; Milagres, Tamara; Hernando, Ana Andres; Jensen, Thomas; Miyazaki, Makoto; Doke, Tomohito; Hayasaki, Takahiro; Nakagawa, Takahiko; Marumaya, Shoichi; Long, David A; Garcia, Gabriela E; Kuwabara, Masanari; Sánchez-Lozada, Laura G; Kang, Duk-Hee; Johnson, Richard J

    2016-10-01

    Aging-associated kidney disease is usually considered a degenerative process associated with aging. Recently, it has been shown that animals can produce fructose endogenously, and that this can be a mechanism for causing kidney damage in diabetic nephropathy and in association with recurrent dehydration. We therefore hypothesized that low-level metabolism of endogenous fructose might play a role in aging-associated kidney disease. Wild-type and fructokinase knockout mice were fed a normal diet for 2 yr that had minimal (renal injury was amplified by provision of high-salt diet for 3 wk, as noted by the presence of glomerular hypertrophy, mesangial matrix expansion, and alpha smooth muscle actin expression, and with segmental thrombi. Fructokinase knockout mice were protected from renal injury both at baseline and after high salt intake (3 wk) compared with wild-type mice. This was associated with higher levels of active (phosphorylated serine 1177) endothelial nitric oxide synthase in their kidneys. These studies suggest that aging-associated renal disease might be due to activation of specific metabolic pathways that could theoretically be targeted therapeutically, and raise the hypothesis that aging-associated renal injury may represent a disease process as opposed to normal age-related degeneration.

  10. Early childhood environment related to microbial exposure and the occurrence of atopic disease at school age.

    Science.gov (United States)

    de Meer, G; Janssen, N A H; Brunekreef, B

    2005-05-01

    There is a growing body of evidence that the early childhood environment with respect to day care attendance, older siblings, pet ownership, and early life airway infections may protect from developing atopic disease. Few studies have distinguished between atopic sensitization and symptoms, and none have evaluated independent contributions for all of these different environmental conditions. Examine independent effects on atopic sensitization and symptoms of day care attendance, older siblings, pet ownership, and early infancy's airway disease. A cross-sectional survey among 8-13-year-old school children with complete data for 1555 children. After adjustment for confounders, atopic sensitization occurred less frequently in children that had attended a day care centre (OR: 0.73, 95% CI: 0.55-0.98) or had a cat or dog before 2 years of age (OR: 0.78, 95% CI: 0.61-0.99). Having older siblings yielded a nonsignificant trend towards protection (OR: 0.88, 95% CI: 0.70-1.11). For symptoms, there was no relation with having older sibs, day care attendance and pet ownership, although there was a trend towards protection for the combination of atopy and symptoms. In contrast, children with doctors' treated airway disease before age 2, more frequently reported recent symptoms of wheeze, asthma, rhinitis, or dermatitis (all P atopic sensitization. Protection against symptoms only occurred if atopic sensitization was present as well.

  11. Role of 4-hydroxy-2-nonenal (HNE) in the pathogenesis of alzheimer disease and other selected age-related neurodegenerative disorders.

    Science.gov (United States)

    Di Domenico, Fabio; Tramutola, Antonella; Butterfield, D Allan

    2017-10-01

    Oxidative stress is involved in various and numerous pathological states including several age-related neurodegenerative diseases. Peroxidation of the membrane lipid bilayer is one of the major sources of free radical-mediated injury that directly damages neurons causing increased membrane rigidity, decreased activity of membrane-bound enzymes, impairment of membrane receptors and altered membrane permeability and eventual cell death. Moreover, the peroxidation of polyunsaturated fatty acids leads to the formation of aldehydes, which can act as toxic by-products. One of the most abundant and cytotoxic lipid -derived aldehydes is 4-hydroxy 2-nonenal (HNE). HNE toxicity is mainly due to the alterations of cell functions by the formation of covalent adducts of HNE with proteins. A key marker of lipid peroxidation, HNE-protein adducts, were found to be elevated in brain tissues and body fluids of Alzheimer disease, Parkinson disease, Huntington disease and amyotrophic lateral sclerosis subjects and/or models of the respective age-related neurodegenerative diseases. Although only a few proteins were identified as common targets of HNE modification across all these listed disorders, a high overlap of these proteins occurs concerning the alteration of common pathways, such as glucose metabolism or mitochondrial function that are known to contribute to cognitive decline. Within this context, despite the different etiological and pathological mechanisms that lead to the onset of different neurodegenerative diseases, the formation of HNE-protein adducts might represent the shared leit-motif, which aggravates brain damage contributing to disease specific clinical presentation and decline in cognitive performance observed in each case. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Endocrine Disease in Aged Horses.

    Science.gov (United States)

    Durham, Andy E

    2016-08-01

    Aging horses may be at particular risk of endocrine disease. Two major equine endocrinopathies, pituitary pars intermedia dysfunction and equine metabolic syndrome, are commonly encountered in an aging population and may present with several recognizable signs, including laminitis. Investigation, treatment, and management of these diseases are discussed. Additionally, aging may be associated with development of rarer endocrinopathic problems, often associated with neoplasia, including diabetes mellitus and other confounders of glucose homeostasis, as well as thyroid, parathyroid, and adrenal diseases. Brief details of the recognition and management of these conditions are presented. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Risk of therapy-related leukaemia and preleukaemia after Hodgkin's disease. Relation to age, cumulative dose of alkylating agents, and time from chemotherapy

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, J.; Specht, L.; Larsen, S.O.

    1987-01-01

    391 patients treated intensively for Hodgkin's disease were followed for up to 15 years to evaluate the risk of therapy-related acute non-lymphocytic leukaemia (t-ANLL) and preleukaemia. Only two independent factors, patient age and cumulative dose of alkylating agents, were related to the risk...... of t-ANLL. The hazard rate of t-ANLL was roughly proportional to the square of patient age and to the total cumulative dose of alkylating agents. In 320 patients treated with alkylating agents the cumulative risk of t-ANLL increased steadily from 1 year after the start of treatment and reached 13.......0% (SE 3.0) at 10 years after which time there were no further cases. Calculated from cessation of therapy with alkylating agents, however, the cumulative risk curve increased steeply during the first 1-2 years then gradually levelled out and no new cases were observed beyond 7 years. With a 15-year...

  14. AVE0991, a nonpeptide analogue of Ang-(1-7), attenuates aging-related neuroinflammation.

    Science.gov (United States)

    Jiang, Teng; Xue, Liu-Jun; Yang, Yang; Wang, Qing-Guang; Xue, Xiao; Ou, Zhou; Gao, Qing; Shi, Jian-Quan; Wu, Liang; Zhang, Ying-Dong

    2018-04-17

    During the aging process, chronic neuroinflammation induced by microglia is detrimental for the brain and contributes to the etiology of several aging-related neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. As a newly identified axis of renin-angiotensin system, ACE2/Ang-(1-7)/MAS1 axis plays a crucial role in modulating inflammatory responses under various pathological conditions. However, its relationship with aging-related neuroinflammation is less studied so far. In this study, by using SAMP8 mice, an animal model of accelerated aging, we revealed that the neuroinflammation in the aged brain might be attributed to a decreased level of Ang-(1-7). More importantly, we provided evidence that AVE0991, a nonpeptide analogue of Ang-(1-7), attenuated the aging-related neuroinflammation via suppression of microglial-mediated inflammatory response through a MAS1 receptor-dependent manner. Meanwhile, this protective effect might be ascribed to the M2 activation of microglia induced by AVE0991. Taken together, these findings reveal the association of Ang-(1-7) with the inflammatory response in the aged brain and uncover the potential of its nonpeptide analogue AVE0991 in attenuation of aging-related neuroinflammation.

  15. Factors influencing the relation between alcohol and cardiovascular disease

    DEFF Research Database (Denmark)

    Grønbaek, Morten

    2006-01-01

    PURPOSE OF REVIEW: Light-to-moderate alcohol intake is known to have cardioprotective properties in some subsets of the population. This review focuses on factors that modify the relation between alcohol and cardiovascular disease. RECENT FINDINGS: Several large American studies have shown...... to a binge - intake of alcohol have benefits with regard to cardiovascular disease. Prospective studies from the UK, Sweden and Denmark have further suggested that wine drinkers have a lower mortality than beer and spirits drinkers. SUMMARY: The J-shaped relation between alcohol intake and cardiovascular...... that the J-shaped relation is influenced by age and coronary heart disease risk-factor status since only middle-aged and elderly and those already at risk of developing coronary heart disease seem protected by drinking alcohol. It has also been suggested that only those who have a steady - in contrast...

  16. Why AMD is a disease of ageing and not of development: mechanisms and insights

    Directory of Open Access Journals (Sweden)

    Kaushal eSharma

    2014-07-01

    Full Text Available Age related macular degeneration (AMD is retinal degenerative disorder which starts with the progression of age. Metabolism plays important role in initiation of ageing related diseases. The cholesterol metabolism components and their oxidized products like 7-ketocholesterol have been shown impact on RPE cells degeneration. These molecules can initiate the mitochondrial apoptotic process and also influenced the complements factors and expression of angiogenic proteins like VEGF etc. In this review we have suggested that AMD is ageing disorder not developmental which has been substantiated with disrupted cholesterol metabolism as described in several age related degenerative diseases.

  17. Life styles related to coronary artery disease in Saudi males older than 12 years of age life styles related to coronary artery disease in Saudi males older than 12 years of age

    International Nuclear Information System (INIS)

    AlTurki, Yousef Abdullah

    2007-01-01

    The present study highlighted life styles related to coronary artery disease risk factors among patients attending a primary care clinic at King Khalid University Hospital, in Riyadh, Saudi Arabia Methods: We conducted a cross-sectional study at a primary care clinic at King Khalid University Hospital, Riyadh, Saudi Arabia, during the period from 18/4/2006 to 13/6/2006. All adult male patients older than 12 years of age who attended one consultant primary care clinic were included in the study. All patients were interviewed by one consultant in family medicine during the study period. The patients were asked about dietary habits, physical activity and type of exercise, and smoking habits. Weight and height was taken for all patients by the nurse in the clinic and body mass index (BMI) was calculated for all patients. The total numbers of participants were 246 patients. The data were analyzed using the Statistical Package of Social Science (SPSS) version 11.5. A p value of less than 0.05 was considered statistically significant. Results: Of the 246 male adult patients, 45.4% always consumed vegetables and fruits in their diet, 21.5% exercised on a daily bases, 51.2% exercised sometimes, and 26% did not exercise at all. The type of exercise practiced by active participants was walking (76.5%) and sports (22.9%). Sports included football, basketball, swimming, and other sport club activity. Only 20.7% of the participants had an ideal body weight (BMI<25), 37.4% were overweight (BMI 25 to <30), while 37.7% of the participants were obese (BMI ? 30). 8.9% of the participants were current smokers. Conclusion and recommendation: Overweight and obesity is a common health problem among male adult patients attending a primary care setting. Improved dietary habits (consumption of vegetables and fruits, and minimization of fat and sweets), encouraging exercise and walking, and helping current smokers to quit smoking are essential steps towards improving life styles in the

  18. Age-Related Macular Degeneration: Insights into Inflammatory Genes

    Directory of Open Access Journals (Sweden)

    Raffaella Cascella

    2014-01-01

    Full Text Available Age-related macular degeneration (AMD is a progressive neurodegenerative disease that affects approximately 8.7% of elderly people worldwide (>55 years old. AMD is characterized by a multifactorial aetiology that involves several genetic and environmental risk factors (genes, ageing, smoking, family history, dietary habits, oxidative stress, and hypertension. In particular, ageing and cigarette smoking (including oxidative compounds and reactive oxygen species have been shown to significantly increase susceptibility to the disease. Furthermore, different genes (CFH, CFI, C2, C3, IL-6, IL-8, and ARMS2 that play a crucial role in the inflammatory pathway have been associated with AMD risk. Several genetic and molecular studies have indicated the participation of inflammatory molecules (cytokines and chemokines, immune cells (macrophages, and complement proteins in the development and progression of the disease. Taking into consideration the genetic and molecular background, this review highlights the genetic role of inflammatory genes involved in AMD pathogenesis and progression.

  19. [Anti-ageing therapies in Alzheimer's disease].

    Science.gov (United States)

    Alonso Abreu, Gara S; Brito Armas, José M; Castro Fuentes, Rafael

    Alzheimer's disease is the most common cause of dementia in the elderly population. Currently, there are no effective treatments to prevent or delay the natural course of the disease. Numerous studies have provided information about the molecular processes underlying biological ageing and, perhaps more importantly, potential interventions to slow ageing and promote healthy longevity in laboratory model systems. The main issue addressed in this review is whether an intervention that has anti-ageing properties can alter the appearance and/or progression of Alzheimer's disease, a disease in which age is the biggest risk factor. Different anti-ageing interventions have been shown to prevent (and in some cases possibly restore) several parameters recognised as central symptoms to the development of Alzheimer's disease. In addition, they are taking the first steps towards translating these laboratory discoveries into clinical applications. Copyright © 2017 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. A common brain network links development, aging, and vulnerability to disease.

    Science.gov (United States)

    Douaud, Gwenaëlle; Groves, Adrian R; Tamnes, Christian K; Westlye, Lars Tjelta; Duff, Eugene P; Engvig, Andreas; Walhovd, Kristine B; James, Anthony; Gass, Achim; Monsch, Andreas U; Matthews, Paul M; Fjell, Anders M; Smith, Stephen M; Johansen-Berg, Heidi

    2014-12-09

    Several theories link processes of development and aging in humans. In neuroscience, one model posits for instance that healthy age-related brain degeneration mirrors development, with the areas of the brain thought to develop later also degenerating earlier. However, intrinsic evidence for such a link between healthy aging and development in brain structure remains elusive. Here, we show that a data-driven analysis of brain structural variation across 484 healthy participants (8-85 y) reveals a largely--but not only--transmodal network whose lifespan pattern of age-related change intrinsically supports this model of mirroring development and aging. We further demonstrate that this network of brain regions, which develops relatively late during adolescence and shows accelerated degeneration in old age compared with the rest of the brain, characterizes areas of heightened vulnerability to unhealthy developmental and aging processes, as exemplified by schizophrenia and Alzheimer's disease, respectively. Specifically, this network, while derived solely from healthy subjects, spatially recapitulates the pattern of brain abnormalities observed in both schizophrenia and Alzheimer's disease. This network is further associated in our large-scale healthy population with intellectual ability and episodic memory, whose impairment contributes to key symptoms of schizophrenia and Alzheimer's disease. Taken together, our results suggest that the common spatial pattern of abnormalities observed in these two disorders, which emerge at opposite ends of the life spectrum, might be influenced by the timing of their separate and distinct pathological processes in disrupting healthy cerebral development and aging, respectively.

  1. Natural history of drusenoid pigment epithelial detachment in age-related macular degeneration: Age-Related Eye Disease Study Report No. 28.

    Science.gov (United States)

    Cukras, Catherine; Agrón, Elvira; Klein, Michael L; Ferris, Frederick L; Chew, Emily Y; Gensler, Gary; Wong, Wai T

    2010-03-01

    To describe the natural history of eyes with drusenoid pigment epithelial detachments (DPEDs) associated with age-related macular degeneration (AMD). Multicenter, clinic-based, prospective cohort study. Among 4757 participants enrolled in the Age-Related Eye Disease Study (AREDS), 255 were identified as having DPED in at least 1 eye and having 5 or more years of follow-up after the initial detection of the DPED. Baseline and annual fundus photographs were evaluated for the evolution of the fundus features and the development of advanced AMD in the forms of central geographic atrophy (CGA) or neovascular (NV) AMD. Kaplan-Meier analyses of progression to advanced AMD and of moderate vision loss (> or =15 letters compared with baseline) were performed. Rate of progression to advanced AMD and change in visual acuity from baseline (in terms of mean letters lost and proportion losing > or =15 letters). A total of 311 eyes (from 255 participants) with DPED were followed for a median follow-up time of 8 years subsequent to the initial detection of a DPED. Of the 282 eyes that did not have advanced AMD at baseline, advanced AMD developed within 5 years in 119 eyes (42%) (19% progressing to CGA and 23% progressing to NV-AMD). In the remaining eyes that did not develop advanced AMD (n=163), progressive fundus changes, typified by the development of calcified drusen and pigmentary changes, were detected. Visual decline was prominent among study eyes, with approximately 40% of all eyes decreasing in visual acuity by > or =15 letters at 5 years follow-up. Mean visual acuity decreased from 76 letters ( approximately 20/30) at baseline to 61 letters ( approximately 20/60) at 5 years. Five-year decreases in mean visual acuity averaged 26 letters for eyes progressing to advanced AMD and 8 letters for non-progressing eyes. The natural history of eyes containing DPED is characterized by a high rate of progression to both CGA and NV-AMD. Among eyes not progressing to advanced AMD

  2. Therapeutic Targeting of Redox Signaling in Myofibroblast Differentiation and Age-Related Fibrotic Disease

    Directory of Open Access Journals (Sweden)

    Natalie Sampson

    2012-01-01

    Full Text Available Myofibroblast activation plays a central role during normal wound healing. Whereas insufficient myofibroblast activation impairs wound healing, excessive myofibroblast activation promotes fibrosis in diverse tissues (including benign prostatic hyperplasia, BPH leading to organ dysfunction and also promotes a stromal response that supports tumor progression. The incidence of impaired wound healing, tissue fibrosis, BPH, and certain cancers strongly increases with age. This paper summarizes findings from in vitro fibroblast-to-myofibroblast differentiation systems that serve as cellular models to study fibrogenesis of diverse tissues. Supported by substantial in vivo data, a large body of evidence indicates that myofibroblast differentiation induced by the profibrotic cytokine transforming growth factor beta is driven by a prooxidant shift in redox homeostasis due to elevated production of NADPH oxidase 4 (NOX4-derived hydrogen peroxide and supported by concomitant decreases in nitric oxide/cGMP signaling and reactive oxygen species (ROS scavenging enzymes. Fibroblast-to-myofibroblast differentiation can be inhibited and reversed by restoring redox homeostasis using antioxidants or NOX4 inactivation as well as enhancing nitric oxide/cGMP signaling via activation of soluble guanylyl cyclases or inhibition of phosphodiesterases. Current evidence indicates the therapeutic potential of targeting the prooxidant shift in redox homeostasis for the treatment of age-related diseases associated with myofibroblast dysregulation.

  3. Sirtuins and renal diseases: relationship with aging and diabetic nephropathy.

    Science.gov (United States)

    Kitada, Munehiro; Kume, Shinji; Takeda-Watanabe, Ai; Kanasaki, Keizo; Koya, Daisuke

    2013-02-01

    Sirtuins are members of the Sir2 (silent information regulator 2) family, a group of class III deacetylases. Mammals have seven different sirtuins, SIRT1-SIRT7. Among them, SIRT1, SIRT3 and SIRT6 are induced by calorie restriction conditions and are considered anti-aging molecules. SIRT1 has been the most extensively studied. SIRT1 deacetylates target proteins using the coenzyme NAD+ and is therefore linked to cellular energy metabolism and the redox state through multiple signalling and survival pathways. SIRT1 deficiency under various stress conditions, such as metabolic or oxidative stress or hypoxia, is implicated in the pathophysiologies of age-related diseases including diabetes, cardiovascular diseases, neurodegenerative disorders and renal diseases. In the kidneys, SIRT1 may inhibit renal cell apoptosis, inflammation and fibrosis, and may regulate lipid metabolism, autophagy, blood pressure and sodium balance. Therefore the activation of SIRT1 in the kidney may be a new therapeutic target to increase resistance to many causal factors in the development of renal diseases, including diabetic nephropathy. In addition, SIRT3 and SIRT6 are implicated in age-related disorders or longevity. In the present review, we discuss the protective functions of sirtuins and the association of sirtuins with the pathophysiology of renal diseases, including diabetic nephropathy.

  4. Prevention of age-related macular degeneration.

    Science.gov (United States)

    Wong, Ian Yat Hin; Koo, Simon Chi Yan; Chan, Clement Wai Nang

    2011-02-01

    Age-related macular degeneration (AMD) is one of the leading causes of blindness in the developed world. Although effective treatment modalities such as anti-VEGF treatment have been developed for neovascular AMD, there is still no effective treatment for geographical atrophy, and therefore the most cost-effective management of AMD is to start with prevention. This review looks at current evidence on preventive measures targeted at AMD. Modalities reviewed include (1) nutritional supplements such as the Age-Related Eye Disease Study (AREDS) formula, lutein and zeaxanthin, omega-3 fatty acid, and berry extracts, (2) lifestyle modifications, including smoking and body-mass-index, and (3) filtering sunlight, i.e. sunglasses and blue-blocking intraocular lenses. In summary, the only proven effective preventive measures are stopping smoking and the AREDS formula.

  5. Speech disorders did not correlate with age at onset of Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    Alice Estevo Dias

    2016-02-01

    Full Text Available ABSTRACT Speech disorders are common manifestations of Parkinson´s disease. Objective To compare speech articulation in patients according to age at onset of the disease. Methods Fifty patients was divided into two groups: Group I consisted of 30 patients with age at onset between 40 and 55 years; Group II consisted of 20 patients with age at onset after 65 years. All patients were evaluated based on the Unified Parkinson’s Disease Rating Scale scores, Hoehn and Yahr scale and speech evaluation by perceptual and acoustical analysis. Results There was no statistically significant difference between the two groups regarding neurological involvement and speech characteristics. Correlation analysis indicated differences in speech articulation in relation to staging and axial scores of rigidity and bradykinesia for middle and late-onset. Conclusions Impairment of speech articulation did not correlate with age at onset of disease, but was positively related with disease duration and higher scores in both groups.

  6. Cell ageing: a flourishing field for neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Dora Brites

    2015-06-01

    Full Text Available Cellular senescence is viewed as an irreversible cell-cycle arrest mechanism involving a complexity of biological progressive processes and the acquisition of diverse cellular phenotypes. Several cell-intrinsic and extrinsic causes (stresses may lead to diverse cellular signaling cascades that include oxidative stress, mitochondrial dysfunction, DNA damage, excessive accumulation of misfolded proteins, impaired microRNA processing and inflammation. Here we review recent advances in the causes and consequences of brain cell ageing, including the senescence of endothelial cells at the central nervous system barriers, as well as of neurons and glial cells. We address what makes ageing an important risk factor for neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and cerebrovascular disease. In particular, we highlight the importance of defects in mitochondrial dynamics, in the cathepsin activity imbalance, in cell-cell communication, in the accumulation of misfolded and unfolded proteins and in the microRNA profiling as having potential impact on cellular ageing processes. Another important aspect is that the absence of specific senescence biomarkers has hampered the characterization of senescent cells in ageing and age-associated diseases. In accordance, the senescence-associated secretory phenotype (SASP or secretome was shown to vary in distinct cell types and upon different stressors, and SASP heterogeneity is believed to create subsets of senenescent cells. In addition to secreted proteins, we then place extracellular vesicles (exosomes and ectosomes as important mediators of intercellular communication with pathophysiological roles in disease spreading, and as emerging targets for therapeutic intervention. We also discuss the application of engineered extracellular vesicles as vehicles for drug delivery. Finally, we summarize current knowledge on methods to rejuvenate senescent cells

  7. Visible aging signs as risk markers for ischemic heart disease

    DEFF Research Database (Denmark)

    Christoffersen, Mette; Tybjærg-Hansen, Anne

    2016-01-01

    Association of common aging signs (i.e., male pattern baldness, hair graying, and facial wrinkles) as well as other age-related appearance factors (i.e., arcus corneae, xanthelasmata, and earlobe crease) with increased risk of ischemic heart disease was initially described in anecdotal reports from...

  8. A randomised controlled trial investigating the effect of nutritional supplementation on visual function in normal, and age-related macular disease affected eyes: design and methodology [ISRCTN78467674

    Directory of Open Access Journals (Sweden)

    Eperjesi Frank

    2003-10-01

    Full Text Available Abstract Background Age-related macular disease is the leading cause of blind registration in the developed world. One aetiological hypothesis involves oxidation, and the intrinsic vulnerability of the retina to damage via this process. This has prompted interest in the role of antioxidants, particularly the carotenoids lutein and zeaxanthin, in the prevention and treatment of this eye disease. Methods The aim of this randomised controlled trial is to determine the effect of a nutritional supplement containing lutein, vitamins A, C and E, zinc, and copper on measures of visual function in people with and without age-related macular disease. Outcome measures are distance and near visual acuity, contrast sensitivity, colour vision, macular visual field, glare recovery, and fundus photography. Randomisation is achieved via a random number generator, and masking achieved by third party coding of the active and placebo containers. Data collection will take place at nine and 18 months, and statistical analysis will employ Student's t test. Discussion A paucity of treatment modalities for age-related macular disease has prompted research into the development of prevention strategies. A positive effect on normals may be indicative of a role of nutritional supplementation in preventing or delaying onset of the condition. An observed benefit in the age-related macular disease group may indicate a potential role of supplementation in prevention of progression, or even a degree reversal of the visual effects caused by this condition.

  9. Age-related changes in normal adult pancreas: MR imaging evaluation

    International Nuclear Information System (INIS)

    Sato, Tomohiro; Ito, Katsuyoshi; Tamada, Tsutomu; Sone, Teruki; Noda, Yasufumi; Higaki, Atsushi; Kanki, Akihiko; Tanimoto, Daigo; Higashi, Hiroki

    2012-01-01

    Objective: To investigate age-related changes in normal adult pancreas as identified by magnetic resonance imaging (MRI). Materials and methods: We examined 115 patients without pancreatic diseases (21–90 years) who underwent upper abdominal MRI to evaluate the normal pancreatic MRI findings related to aging. The parameters examined were the pancreatic anteroposterior (AP) diameter, pancreatic lobulation, pancreatic signal intensity (SI), depiction of the main pancreatic duct (MPD), grade of the visual SI decrease on the opposed-phase T1-weighted images compared with in-phase images, and enhancement effect of the pancreas in the arterial phase of dynamic imaging. Results: The pancreatic AP diameter significantly reduced (head, p = 0.0172; body, p = 0.0007; tail, p < 0.0001), and lobulation (p < 0.0001) and parenchymal fatty change (p < 0.0001) became more evident with aging. No significant correlation was observed between aging and pancreatic SI, however the SI on the in-phase T1-weighted images tended to decrease with aging. No significant correlation was observed between aging and the depiction of the MPD as well as aging and contrast enhancement. Conclusion: MRI findings of pancreatic atrophy, lobulation, and fatty degeneration are characteristic changes related to aging, and it is necessary to recognize these changes in the interpretation of abdominal MRI in patients with and without pancreatic disease

  10. Impact of age-related neuroglial cell responses on hippocampal deterioration

    Directory of Open Access Journals (Sweden)

    Joseph O Ojo

    2015-04-01

    Full Text Available Aging is one of the greatest risk factors for the development of sporadic age-related neurodegenerative diseases and neuroinflammation is a common feature of this disease phenotype. In the immunoprivileged brain, neuroglial cells, which mediate neuroinflammatory responses, are influenced by the physiological factors in the microenvironment of the central nervous system (CNS. These physiological factors include but are not limited to cell-to-cell communication involving cell adhesion molecules, neuronal electrical activity and neurotransmitter and neuromodulator action. However, despite this dynamic control of neuroglial activity, in the healthy aged brain there is an alteration in the underlying neuroinflammatory response notably seen in the hippocampus, typified by astrocyte/microglia activation and increased pro-inflammatory cytokine production and signalling. Normally, these changes occur without any concurrent pathology, however, they can correlate with deteriorations in hippocampal or cognitive function. In this review we examine two important phenomenons, firstly the relationship between age-related brain deterioration (focusing on hippocampal function and underlying neuroglial response(s, and secondly how the latter affects molecular and cellular processes within the hippocampus that makes it vulnerable to age-related cognitive decline.

  11. Gene-diet interactions in age-related macular degeneration

    Science.gov (United States)

    Age-related macular degeneration (AMD) is a prevalent blinding disease, accounting for roughly 50% of blindness in developed nations. Very significant advances have been made in terms of discovering genetic susceptibilities to AMD as well as dietary risk factors. To date, nutritional supplementation...

  12. Are religiosity and prayer use related with multiple behavioural risk factors for chronic diseases in European adults aged 50+ years?

    Science.gov (United States)

    Linardakis, M; Papadaki, A; Smpokos, E; Sarri, K; Vozikaki, M; Philalithis, A

    2015-05-01

    Behavioural risk factors for chronic diseases involve factors relating to lifestyle habits. This study examined the relationship of religious and spiritual beliefs with the adoption and presence of multiple behavioural risk factors (MBRFs) in European adults. Cross-sectional study. Data were used from 16,557 individuals, aged 50+ years, participating in the Survey of Health, Ageing and Retirement in Europe (2004/05). MBRFs clustering was defined by high body weight, smoking, physical inactivity and risky alcohol consumption, and regression estimations with religiosity and prayer use were assessed based on sampling weights. In total, 79.4% of participants had received religious education, 33.4% had used prayer '≥1 time/day' and 53.3% had clustering of 2+ MBRFs. Lower prevalence of smoking was found in males (20.6% vs. 29.4%, P prayer use (standardized beta = 0.056, P prayer use were related to the presence of fewer MBRFs in European adults aged 50+ years. These lifestyle factors should be assessed as potential determinants of MBRFs adoption when examining chronic disease development in multicultural populations. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  13. Prevalence of Age-Related Macular Degeneration in Europe

    NARCIS (Netherlands)

    Colijn, Johanna M.; Buitendijk, Gabriëlle H. S.; Prokofyeva, Elena; Alves, Dalila; Cachulo, Maria L.; Khawaja, Anthony P.; Cougnard-Gregoire, Audrey; Merle, Bénédicte M. J.; Korb, Christina; Erke, Maja G.; Bron, Alain; Anastasopoulos, Eleftherios; Meester-Smoor, Magda A.; Segato, Tatiana; Piermarocchi, Stefano; de Jong, Paulus T. V. M.; Vingerling, Johannes R.; Topouzis, Fotis; Creuzot-Garcher, Catherine; Bertelsen, Geir; Pfeiffer, Norbert; Fletcher, Astrid E.; Foster, Paul J.; Silva, Rufino; Korobelnik, Jean-François; Delcourt, Cécile; Klaver, Caroline C. W.; Ajana, Soufiane; Arango-Gonzalez, Blanca; Arndt, Verena; Bhatia, Vaibhav; Bhattacharya, Shomi S.; Biarnés, Marc; Borrell, Anna; Bühren, Sebastian; Calado, Sofia M.; Cougnard-Grégoire, Audrey; Dammeier, Sascha; de Jong, Eiko K.; de la Cerda, Berta; den Hollander, Anneke I.; Diaz-Corrales, Francisco J.; Diether, Sigrid; Emri, Eszter; Endermann, Tanja; Ferraro, Lucia L.; Garcia, Míriam; Heesterbeek, Thomas J.; Honisch, Sabina; Bergen, Arthur

    2017-01-01

    Purpose: Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in

  14. Prevalence of Age-Related Macular Degeneration in Europe

    DEFF Research Database (Denmark)

    Colijn, Johanna M; Buitendijk, Gabriëlle H S; Prokofyeva, Elena

    2017-01-01

    PURPOSE: Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD...

  15. Awareness, Knowledge, and Concern about Age-Related Macular Degeneration

    Science.gov (United States)

    Cimarolli, Verena R.; Laban-Baker, Allie; Hamilton, Wanda S.; Stuen, Cynthia

    2012-01-01

    Age-related macular degeneration (AMD)--a common eye disease causing vision loss--can be detected early through regular eye-health examinations, and measures can be taken to prevent visual decline. Getting eye examinations requires certain levels of awareness, knowledge, and concern related to AMD. However, little is known about AMD-related…

  16. [Age-related macular degeneration as a local manifestation of atherosclerosis - a novel insight into pathogenesis].

    Science.gov (United States)

    Machalińska, Anna

    2013-01-01

    Age-related macular degeneration is the leading cause of irreversible visual impairment and disability among the elderly in developed countries. There is compelling evidence that atherosclerosis and age-related macular degeneration share a similar pathogenic process. The association between atherosclerosis and age-related macular degeneration has been inferred from histological, biochemical and epidemiological studies. Many published data indicate that drusen are similar in molecular composition to plaques in atherosclerosis. Furthermore, a great body of evidence has emerged over the past decade that implicates the chronic inflammatory processes in the pathogenesis and progression of both disorders. We speculate that vascular atherosclerosis and age-related macular degeneration may represent different manifestations of the same disease induced by a pathologic tissue response to the damage caused by oxidative stress and local ischemia. In this review, we characterise in detail a strong association between age-related macular degeneration and atherosclerosis development, and we postulate the hypothesis that age-related macular degeneration is a local manifestation of a systemic disease. This provides a new approach for understanding the aspects of pathogenesis and might improve the prevention and treatment of both diseases which both result from ageing of the human body.

  17. Transcriptome changes in age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Whitmore S Scott

    2012-02-01

    Full Text Available Abstract Age-related macular degeneration (AMD is a debilitating, common cause of visual impairment. While the last decade has seen great progress in understanding the pathophysiology of AMD, the molecular changes that occur in eyes with AMD are still poorly understood. In the current issue of Genome Medicine, Newman and colleagues present the first systematic transcriptional profile analysis of AMD-affected tissues, providing a comprehensive set of expression data for different regions (macula versus periphery, tissues (retina versus retinal pigment epithelium (RPE/choroid, and disease state (control versus early or advanced AMD. Their findings will serve as a foundation for additional systems-level research into the pathogenesis of this blinding disease. Please see related article: http://genomemedicine.com/content/4/2/16

  18. Connective tissue diseases, multimorbidity and the ageing lung.

    Science.gov (United States)

    Spagnolo, Paolo; Cordier, Jean-François; Cottin, Vincent

    2016-05-01

    Connective tissue diseases encompass a wide range of heterogeneous disorders characterised by immune-mediated chronic inflammation often leading to tissue damage, collagen deposition and possible loss of function of the target organ. Lung involvement is a common complication of connective tissue diseases. Depending on the underlying disease, various thoracic compartments can be involved but interstitial lung disease is a major contributor to morbidity and mortality. Interstitial lung disease, pulmonary hypertension or both are found most commonly in systemic sclerosis. In the elderly, the prevalence of connective tissue diseases continues to rise due to both longer life expectancy and more effective and better-tolerated treatments. In the geriatric population, connective tissue diseases are almost invariably accompanied by age-related comorbidities, and disease- and treatment-related complications, which contribute to the significant morbidity and mortality associated with these conditions, and complicate treatment decision-making. Connective tissue diseases in the elderly represent a growing concern for healthcare providers and an increasing burden of global health resources worldwide. A better understanding of the mechanisms involved in the regulation of the immune functions in the elderly and evidence-based guidelines specifically designed for this patient population are instrumental to improving the management of connective tissue diseases in elderly patients. Copyright ©ERS 2016.

  19. Risk of Cardiovascular Disease in an Aging HIV Population

    DEFF Research Database (Denmark)

    Martin-Iguacel, R; Llibre, J M; Friis-Moller, N

    2015-01-01

    With more effective and widespread antiretroviral treatment, the overall incidence of AIDS- or HIV-related death has decreased dramatically. Consequently, as patients are aging, cardiovascular disease (CVD) has emerged as an important cause of morbidity and mortality in the HIV population....... The incidence of CVD overall in HIV is relatively low, but it is approximately 1.5-2-fold higher than that seen in age-matched HIV-uninfected individuals. Multiple factors are believed to explain this excess in risk such as overrepresentation of traditional cardiovascular risk factors (particularly smoking...

  20. The relationship of major American dietary patterns to age-related macular degeneration

    Science.gov (United States)

    We hypothesized that major American dietary patterns are associated with age-related macular degeneration (AMD) risk. This was a cross-sectional study with 8,103 eyes from 4,088 eligible participants in the baseline Age-Related Eye Disease Study (AREDS) were classified into control (n=2,739), early ...

  1. The Existence of Primary Age-Related Tauopathy Suggests that not all the Cases with Early Braak Stages of Neurofibrillary Pathology are Alzheimer's Disease.

    Science.gov (United States)

    Giaccone, Giorgio

    2015-01-01

    The distinction between Alzheimer's disease (AD) and Primary Age-Related Tauopathy (PART) is a hotly debated issue. As most lines of evidence support the tenet that tau pathology occurs downstream of amyloid-β deposition, it seems reasonable to consider PART as a separate disease process not necessarily related to Aβ and hence AD. Following this view, the early stages of neurofibrillary pathology may not always be the forerunner of diffuse neurofibrillary changes and AD. The ongoing debate further enhances the need for greater caution against any future predictions using tau cerebrospinal fluid and imaging biomarkers.

  2. Hot Topics in Pharmacogenetics of Age-Related Macular Degeneration.

    Science.gov (United States)

    Schwartz, Stephen G; Brantley, Milam A; Kovach, Jaclyn L; Grzybowski, Andrzej

    2017-01-01

    Age-related macular degeneration (AMD) is a leading cause of irreversible visual loss and is primarily treated with nutritional supplementation as well as with anti-vascular endothelial growth factor (VEGF) agents for certain patients with neovascular disease. AMD is a complex disease with both genetic and environmental risk factors. In addition, treatment outcomes from nutritional supplementation and anti-VEGF agents vary considerably. Therefore, it is reasonable to suspect that there may be pharmacogenetic influences on these treatments. Many series have reported individual associations with variants in complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2), and other loci. However, at this time there are no validated associations. With respect to AMD, pharmacogenetics remains an intriguing area of research but is not helpful for routine clinical management. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Ancestry, Socioeconomic Status, and Age-Related Cataract in Asians: The Singapore Epidemiology of Eye Diseases Study.

    Science.gov (United States)

    Chua, Jacqueline; Koh, Jia Yu; Tan, Ava Grace; Zhao, Wanting; Lamoureux, Ecosse; Mitchell, Paul; Wang, Jie Jin; Wong, Tien Yin; Cheng, Ching-Yu

    2015-11-01

    To determine the prevalence of age-related cataract and its ancestral and socioeconomic risk factors in a multi-ethnic Asian population. Population-based, cross-sectional study. A total of 10 033 adults (3353 Chinese, 3280 Malays, and 3400 Indians) aged >40 years in the Singapore Epidemiology of Eye Diseases Study. Study participants were invited for a structured interview and received a standardized comprehensive eye examination. Digital lens photographs were taken from eyes of each participant and graded for nuclear, cortical, and posterior subcapsular (PSC) cataract, following the Wisconsin Cataract Grading System. Prevalence data were compared with the Blue Mountains Eye Study (BMES) in Australia. Information on medical and lifestyle factors was collected using questionnaires and blood samples. To increase the precision of racial definition, genetic ancestry was derived from genome-wide single nucleotide polymorphism markers using principal component analysis. Regression models were used to investigate the association of cataract with socioeconomic factors (education and income) and genetic ancestry. Age-related cataract. A total of 8750 participants (94.0%) had gradable lens photographs. The age-standardized prevalence of cataract surgery in Chinese (16.0%), Malays (10.6%), and Indians (20.2%) was higher than in white subjects (4.1%). We found the age-standardized cataract prevalence in Chinese (30.4%), Malays (37.8%), and Indians (33.1%) was higher than in whites (18.5%). Cataract was 1.5 to 2 times more common in Asians and began 10 years earlier than in white subjects. Malays had significantly higher age-standardized prevalence of nuclear, cortical, and PSC cataract than Chinese (PChinese and Indians but not Malays. The presence of visual impairment associated with cataract was higher in people aged ≥60 years and Malays. We showed that people of different Asian ethnicities had a higher prevalence and earlier age of onset of cataract than Europeans. People

  4. Polarization sensitive changes in the human macula associated with normal aging and age-related macular degeneration

    Science.gov (United States)

    VanNasdale, Dean Allan, Jr.

    2011-12-01

    The human macula occupies a relatively small, but crucial retinal area, as it is the location responsible for our most acute spatial vision and best color discrimination. Localizing important landmarks in the retina is difficult even in normal eyes where morphological inter-individual variability is high. This becomes even more challenging in the presence of sight-threatening pathology. With respect to the human macula, there remains a significant gap in the understanding of normal structure and function. Even less is known about the pathological mechanisms that occur in sight-threatening diseases including age-related macular degeneration. Because relatively little is known about normal aging changes, it is also difficult to differentiate those changes from changes associated with retinal disease. To better understand normal and pathological changes in the macula, imaging techniques using specific optical signatures are required. Structural features in the macula can be distinguished based on their intrinsic properties using specific light/tissue interactions. Because of the high degree of structural regularity in the macula, polarization sensitive imaging is potentially a useful tool for evaluating the morphology and integrity of the cellular architecture for both normal individuals and those affected by disease. In our investigations, we used polarization sensitive imaging to determining normal landmarks that are important clinically and for research investigations. We found that precision and accuracy in localizing the central macula was greatly improved through the use of polarization sensitive imaging. We also found that specific polarization alterations can be used to demonstrate systematic changes as a function of age, disproportionately affecting the central macular region. When evaluating patients with age-related macular degeneration, we found that precision and accuracy of localizing the central macula was also improved, even when significant pathology

  5. Genetics of Unilateral and Bilateral Age-Related Macular Degeneration Severity Stages

    NARCIS (Netherlands)

    Schick, T.; Altay, L.; Viehweger, E.; Hoyng, C.B.; Hollander, A.I. den; Felsch, M.; Fauser, S.

    2016-01-01

    BACKGROUND: Age-related macular degeneration (AMD) is a common disease causing visual impairment and blindness. Various gene variants are strongly associated with late stage AMD, but little is known about the genetics of early forms of the disease. This study evaluated associations of genetic

  6. Cardiovascular disease and cognitive performance in middle-aged and elderly men

    NARCIS (Netherlands)

    Muller, M.; Grobbee, D. E.; Aleman, A.; Bots, M.; van der Schouw, Y. T.

    Background: Decline of cognitive function with age may be due, in part, to atherosclerotic changes. The aim of the present study was to determine the relative contribution of cardiovascular disease (CVD) to cognitive functioning in middle-aged and elderly men. Methods: In a cross-sectional study,

  7. A culture-brain link: Negative age stereotypes predict Alzheimer's disease biomarkers.

    Science.gov (United States)

    Levy, Becca R; Ferrucci, Luigi; Zonderman, Alan B; Slade, Martin D; Troncoso, Juan; Resnick, Susan M

    2016-02-01

    Although negative age stereotypes have been found to predict adverse outcomes among older individuals, it was unknown whether the influence of stereotypes extends to brain changes associated with Alzheimer's disease. To consider this possibility, we drew on dementia-free participants, in the Baltimore Longitudinal Study of Aging, whose age stereotypes were assessed decades before yearly magnetic resonance images and brain autopsies were performed. Those holding more-negative age stereotypes earlier in life had significantly steeper hippocampal-volume loss and significantly greater accumulation of neurofibrillary tangles and amyloid plaques, adjusting for relevant covariates. These findings suggest a new pathway to identifying mechanisms and potential interventions related to the pathology of Alzheimer's disease. (c) 2016 APA, all rights reserved).

  8. [Exercise for prevention of osteoporosis and other lifestyle-related diseases].

    Science.gov (United States)

    Suzuki, Takao

    2011-05-01

    The prevalence of lifestyle-related diseases including hypertension, dyslipidemia (hyperlipidemia) and diabetes increases with aging, and all these conditions are risk factors of arteriosclerotic diseases such as cerebrovascular event (stroke) and myocardial infarction. The term "metabolic domino" has been used to describe the collective concept of the development and progression of these lifestyle-related diseases, the sequence of events, and the progression process of complications. Like the first tile of a domino toppling game, undesirable lifestyle such as overeating and underexercising first triggers obesity, and is followed in succession by onset of an insulin resistance state (underlied by a genetic background indigenous to Japanese) , hypertension, hyperlipidemia, and further postprandial hyperglycemia (the pre-diabetic state) , the so-called metabolic syndrome, at around the same time. On the other hand, apart from the other lifestyle-related diseases, the prevalence of osteoporosis also increases rapidly accompanying aging. Osteoporosis is known to be strongly related to disorders due to the metabolic domino such as arteriosclerosis and vascular calcification, and a new disease category called "osteo-vascular interaction" has attracted attention recently. Regarding "osteo-vascular interaction" , a close relation between bone density loss or osteoporotic changes and vascular lesion-associated lifestyle-related diseases such as hypertension, dyslipidemia and diabetes has been reported. Therefore, as a common preventive factor for bone mass loss or osteoporosis and lifestyle-related diseases including hypertension, dyslipidemia and diabetes (osteo-vascular interaction) , exercise has been recognized anew as an important non-pharmaceutical therapy that should take top priority. This article overviews the evidence of exercise therapy for the prevention of osteoporosis and other lifestyle-related diseases, from the viewpoint of health promotion, especially of

  9. Overview of clinical trials for dry age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Wen-Sheng Cheng

    2017-01-01

    Full Text Available The overall goal of treating age-related macular degeneration (AMD is to target the underlying cause of the disease and prevent, or at least slow down, the loss of vision, which requires the preservation of the choroid, retinal pigment epithelium (RPE, and photoreceptors. At present, there is no proven drug treatment for dry AMD; however, the cessation of smoking and treatments based on the age-related eye diseases study vitamin formula combined with a healthy diet are considered the only options for slowing disease progression. A number of pharmaceutical agents are currently under evaluation for the treatment of dry AMD using strategies such as reduction RPE and photoreceptor loss, neuroprotection, visual cycle modulators, suppression of inflammation, prevention of oxidative damage, and choroidal perfusion enhancers. The hope is that some of these therapies will achieve significant improvement to current management and prevent future loss of vision in this devastating eye condition.

  10. Slower Dynamics and Aged Mitochondria in Sporadic Alzheimer's Disease

    Science.gov (United States)

    Gargini, Ricardo; García, Esther; Perry, George

    2017-01-01

    Sporadic Alzheimer's disease corresponds to 95% of cases whose origin is multifactorial and elusive. Mitochondrial dysfunction is a major feature of Alzheimer's pathology, which might be one of the early events that trigger downstream principal events. Here, we show that multiple genes that control mitochondrial homeostasis, including fission and fusion, are downregulated in Alzheimer's patients. Additionally, we demonstrate that some of these dysregulations, such as diminished DLP1 levels and its mitochondrial localization, as well as reduced STOML2 and MFN2 fusion protein levels, take place in fibroblasts from sporadic Alzheimer's disease patients. The analysis of mitochondrial network disruption using CCCP indicates that the patients' fibroblasts exhibit slower dynamics and mitochondrial membrane potential recovery. These defects lead to strong accumulation of aged mitochondria in Alzheimer's fibroblasts. Accordingly, the analysis of autophagy and mitophagy involved genes in the patients demonstrates a downregulation indicating that the recycling mechanism of these aged mitochondria might be impaired. Our data reinforce the idea that mitochondrial dysfunction is one of the key early events of the disease intimately related with aging. PMID:29201274

  11. Targeting Mitochondria to Counteract Age-Related Cellular Dysfunction

    Directory of Open Access Journals (Sweden)

    Corina T. Madreiter-Sokolowski

    2018-03-01

    Full Text Available Senescence is related to the loss of cellular homeostasis and functions, which leads to a progressive decline in physiological ability and to aging-associated diseases. Since mitochondria are essential to energy supply, cell differentiation, cell cycle control, intracellular signaling and Ca2+ sequestration, fine-tuning mitochondrial activity appropriately, is a tightrope walk during aging. For instance, the mitochondrial oxidative phosphorylation (OXPHOS ensures a supply of adenosine triphosphate (ATP, but is also the main source of potentially harmful levels of reactive oxygen species (ROS. Moreover, mitochondrial function is strongly linked to mitochondrial Ca2+ homeostasis and mitochondrial shape, which undergo various alterations during aging. Since mitochondria play such a critical role in an organism’s process of aging, they also offer promising targets for manipulation of senescent cellular functions. Accordingly, interventions delaying the onset of age-associated disorders involve the manipulation of mitochondrial function, including caloric restriction (CR or exercise, as well as drugs, such as metformin, aspirin, and polyphenols. In this review, we discuss mitochondria’s role in and impact on cellular aging and their potential to serve as a target for therapeutic interventions against age-related cellular dysfunction.

  12. Age-related macular degeneration: epidemiology and optimal treatment

    DEFF Research Database (Denmark)

    la Cour, Morten; Kiilgaard, Jens Folke; Nissen, Mogens Holst

    2002-01-01

    Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterised by the appearance of drusen in the macula, accompanied by choroidal neovascularisation (CNV) or geographic atrophy. The disease is more common in Caucasian....... Smoking is probably also a risk factor. Preventive strategies using macular laser photocoagulation are under investigation, but their efficacy in preventing visual loss is as yet unproven. There is no treatment with proven efficacy for geographic atrophy. Optimal treatment for exudative AMD requires...

  13. Imaging geographic atrophy in age-related macular degeneration.

    Science.gov (United States)

    Göbel, Arno P; Fleckenstein, Monika; Schmitz-Valckenberg, Steffen; Brinkmann, Christian K; Holz, Frank G

    2011-01-01

    Advances in retinal imaging technology have largely contributed to the understanding of the natural history, prognostic markers and disease mechanisms of geographic atrophy (GA) due to age-related macular degeneration. There is still no therapy available to halt or slow the disease process. In order to evaluate potential therapeutic effects in interventional trials, there is a need for precise quantification of the GA progression rate. Fundus autofluorescence imaging allows for accurate identification and segmentation of atrophic areas and currently represents the gold standard for evaluating progressive GA enlargement. By means of high-resolution spectral-domain optical coherence tomography, distinct microstructural alterations related to GA can be visualized. Copyright © 2011 S. Karger AG, Basel.

  14. Parkinson's disease as a result of aging

    OpenAIRE

    Rodriguez, Manuel; Rodriguez-Sabate, Clara; Morales, Ingrid; Sanchez, Alberto; Sabate, Magdalena

    2015-01-01

    It is generally considered that Parkinson's disease is induced by specific agents that degenerate a clearly defined population of dopaminergic neurons. Data commented in this review suggest that this assumption is not as clear as is often thought and that aging may be critical for Parkinson's disease. Neurons degenerating in Parkinson's disease also degenerate in normal aging, and the different agents involved in the etiology of this illness are also involved in aging. Senescence is a wider p...

  15. Protein stress and stress proteins: implications in aging and disease

    Indian Academy of Sciences (India)

    Madhu Sudhan

    2007-04-02

    Apr 2, 2007 ... age-related disease by DAF-16 and heat-shock factor; Science. 300 1142–1145. Macario A J and Conway de Macario E 2005 Sick chaperones, cellular stress, and disease; N. Engl. J. Med. 353 1489–1501. Massey A C, Kaushik S, Sovak G, Kiffin R and Cuervo A M 2006. Consequences of the selective ...

  16. Life styles related to coronary artery disease in Saudi Males older than 12 years of age

    International Nuclear Information System (INIS)

    Al-Turki, Yousef Abdullah

    2007-01-01

    The present study highlighted life styles related to coronary artery disease risk factors among patients attending a primary care clinic at King Khalid University Hospital, in Riyadh, Saudi Arabia. We conducted a cross-sectional study at a primary care clinic at King Khalid University Hospital, Riyadh, Saudi Arabia, during the period from 18/4/2006 to 13/6/2006. All adult male patients older than 12 years of age who attended one consultant primary care clinic were included in the study. All patients were interviewed by one consultant in family medicine during the study period. The patients were asked about dietary habits, physical activity and type of exercise, and smoking habits. Weight and height was taken for all patients by the nurse in the clinic and body mass index (BMI) were calculated for all patients. The total number of participants was 246 patients. The data were analyzed using the Statistical Package of Social Science (SPSS) version 11.5. A p value of less than 0.05 was considered statistically significant. Of the 246 male adult patients, 45.4% always consumed vegetables and fruits in their diet, 21.5% exercised on a daily basis, 51.2% exercised sometimes and 26% did not exercise at all. The type of exercise practiced by active participants was walking (76.5%) and sports (22.9%). Sports included football, basketball, swimming and other sports club activity. Only 20.7% of the participants had an ideal body weight (BMI =30). 8.9% of the participants were current smokers. Overweight and obesity is a common health problem among male adult patients attending a primary care setting. Improved dietary habits (consumption of vegetables and fruits and minimization of fat and suits) encouraging exercise and walking and helping current smokers to quit smoking are essential steps towards improving life styles in the community. It is an important health plan priority to concentrate on improving life styles in the Saudi community, to prevent cardiovascular risk

  17. Gene Ontology and KEGG Enrichment Analyses of Genes Related to Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Jian Zhang

    2014-01-01

    Full Text Available Identifying disease genes is one of the most important topics in biomedicine and may facilitate studies on the mechanisms underlying disease. Age-related macular degeneration (AMD is a serious eye disease; it typically affects older adults and results in a loss of vision due to retina damage. In this study, we attempt to develop an effective method for distinguishing AMD-related genes. Gene ontology and KEGG enrichment analyses of known AMD-related genes were performed, and a classification system was established. In detail, each gene was encoded into a vector by extracting enrichment scores of the gene set, including it and its direct neighbors in STRING, and gene ontology terms or KEGG pathways. Then certain feature-selection methods, including minimum redundancy maximum relevance and incremental feature selection, were adopted to extract key features for the classification system. As a result, 720 GO terms and 11 KEGG pathways were deemed the most important factors for predicting AMD-related genes.

  18. Mitochondrial and Ubiquitin Proteasome System Dysfunction in Ageing and Disease: Two Sides of the Same Coin?

    Directory of Open Access Journals (Sweden)

    Jaime M. Ross

    2015-08-01

    Full Text Available Mitochondrial dysfunction and impairment of the ubiquitin proteasome system have been described as two hallmarks of the ageing process. Additionally, both systems have been implicated in the etiopathogenesis of many age-related diseases, particularly neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease. Interestingly, these two systems are closely interconnected, with the ubiquitin proteasome system maintaining mitochondrial homeostasis by regulating organelle dynamics, the proteome, and mitophagy, and mitochondrial dysfunction impairing cellular protein homeostasis by oxidative damage. Here, we review the current literature and argue that the interplay of the two systems should be considered in order to better understand the cellular dysfunction observed in ageing and age-related diseases. Such an approach may provide valuable insights into molecular mechanisms underlying the ageing process, and further discovery of treatments to counteract ageing and its associated diseases. Furthermore, we provide a hypothetical model for the heterogeneity described among individuals during ageing.

  19. Potential importance of B cells in aging and aging-associated neurodegenerative diseases.

    Science.gov (United States)

    Biragyn, Arya; Aliseychik, Maria; Rogaev, Evgeny

    2017-04-01

    Our understanding of B cells as merely antibody producers is slowly changing. Alone or in concert with antibody, they control outcomes of seemingly different diseases such as cancer, rheumatoid arthritis, diabetes, and multiple sclerosis. While their role in activation of effector immune cells is beneficial in cancer but bad in autoimmune diseases, their immunosuppressive and regulatory subsets (Bregs) inhibit autoimmune and anticancer responses. These pathogenic and suppressive functions are not static and appear to be regulated by the nature and strength of inflammation. Although aging increases inflammation and changes the composition and function of B cells, surprisingly, little is known whether the change affects aging-associated neurodegenerative disease, such as Alzheimer's disease (AD). Here, by analyzing B cells in cancer and autoimmune and neuroinflammatory diseases, we elucidate their potential importance in AD and other aging-associated neuroinflammatory diseases.

  20. From lymphopoiesis to plasma cells differentiation, the age-related modifications of B cell compartment are influenced by "inflamm-ageing".

    Science.gov (United States)

    Bulati, Matteo; Caruso, Calogero; Colonna-Romano, Giuseppina

    2017-07-01

    Ageing is a complex process characterized by a general decline in physiological functions with increasing morbidity and mortality. The most important aspect of ageing is the chronic inflammatory status, named "inflamm-ageing", strictly associated with the deterioration of the immune function, termed "immunosenescence". Both are causes of increased susceptibility of elderly to infectious diseases, cancer, dementia, cardiovascular diseases and autoimmunity, and of a decreased response to vaccination. It has been widely demonstrated that ageing has a strong impact on the remodelling of the B cell branch of immune system. The first evident effect is the significant decrease in circulating B cells, primarily due to the reduction of new B cell coming from bone marrow (BM) progenitors, as inflammation directly impacts on B lymphopoiesis. Besides, in aged individuals, there is a shift from naïve to memory immunoglobulins production, accompanied by the impaired ability to produce high affinity protective antibodies against newly encountered antigens. This is accompanied by the increase of expanded clones of B cells, which correlates with poor health status. Age-related modifications also occur in naïve/memory B cells subsets. Indeed, in the elderly, there is a reduction of naïve B cells, accompanied by the expansion of memory B cells that show a senescence-associated phenotype. Finally, elderly show the impaired ability of memory B cells to differentiate into plasma cells. It can be concluded that inflammation is the leading cause of the age-related impairment of B cell compartment, which play certainly a key role in the development of age-related diseases. This makes study of B cells in the aged an important tool for monitoring immunosenescence, chronic inflammatory disorders and the effectiveness of vaccines or pharmacological therapies. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Age-Related Decline of Precision and Binding in Visual Working Memory

    Science.gov (United States)

    2013-01-01

    Working memory declines with normal aging, but the nature of this impairment is debated. Studies based on detecting changes to arrays of visual objects have identified two possible components to age-related decline: a reduction in the number of items that can be stored, or a deficit in maintaining the associations (bindings) between individual object features. However, some investigations have reported intact binding with aging, and specific deficits arising only in Alzheimer’s disease. Here, using a recently developed continuous measure of recall fidelity, we tested the precision with which adults of different ages could reproduce from memory the orientation and color of a probed array item. The results reveal a further component of cognitive decline: an age-related decrease in the resolution with which visual information can be maintained in working memory. This increase in recall variability with age was strongest under conditions of greater memory load. Moreover, analysis of the distribution of errors revealed that older participants were more likely to incorrectly report one of the unprobed items in memory, consistent with an age-related increase in misbinding. These results indicate a systematic decline with age in working memory resources that can be recruited to store visual information. The paradigm presented here provides a sensitive index of both memory resolution and feature binding, with the potential for assessing their modulation by interventions. The findings have implications for understanding the mechanisms underpinning working memory deficits in both health and disease. PMID:23978008

  2. Age Features Of Peptic And Duodenal Ulcer Disease

    Directory of Open Access Journals (Sweden)

    Е.А. Islamova

    2009-12-01

    Full Text Available Peptic ulcer disease is one of the most widespread diseases. 6-10 % of adult population in Russia suffer from it. Demographic processes in the Russian Federation determine the increase of patients' number aged over 60 with peptic ulcer disease. It counts 10-35 % of all patients with this disease. The modern views on pathogenesis of peptic ulcer disease, including factor of Helicobacter pylori, in patients of different age groups have been highlighted in the article. Pathogenetic features and clinical morphological manifestations of peptic ulcer disease in young and aged patients have been considered

  3. CDDUX: A disease-specific health-related quality-of-life questionnaire for children with celiac disease

    NARCIS (Netherlands)

    van Doorn, Roesja K.; Winkler, Lex M. F.; Zwinderman, Koos H.; Mearin, M. Luisa; Koopman, Hendrik M.

    2008-01-01

    Objective: The development of a disease-specific, health-related, quality-of-life questionnaire for children ages 8 to 18 with celiac disease (CD), together with a parent-as-proxy version. Materials and Methods: We used a focus-group method (bottom-up approach) to investigate the impact of CD on

  4. New approaches and potential treatments for dry age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Francisco Max Damico

    2012-02-01

    Full Text Available Emerging treatments for dry age-related macular degeneration (AMD and geographi c atrophy focus on two strategies that target components involved in physiopathological pathways: prevention of photoreceptors and retinal pigment epithelium loss (neuroprotection induction, oxidative damage prevention, and visual cycle modification and suppression of inflammation. Neuroprotective drugs, such as ciliary neurotrophic factor, brimonidine tartrate, tandospirone, and anti-amyloid β antibodies, aim to prevent apoptosis of retinal cells. Oxidative stress and depletion of essential micronutrients are targeted by the Age-Related Eye Disease Study (AREDS formulation. Visual cycle modulators reduce the activity of the photoreceptors and retinal accumulation of toxic fluorophores and lipofuscin. Eyes with dry age-related macular degeneration present chronic inflammation and potential treatments include corticosteroid and complement inhibition. We review the current concepts and rationale of dry age-related macular degeneration treatment that will most likely include a combination of drugs targeting different pathways involved in the development and progression of age-related macular degeneration.

  5. The African Turquoise Killifish: A Model for Exploring Vertebrate Aging and Diseases in the Fast Lane.

    Science.gov (United States)

    Harel, Itamar; Brunet, Anne

    2015-01-01

    Why and how organisms age remains a mystery, and it defines one of the biggest challenges in biology. Aging is also the primary risk factor for many human pathologies, such as cancer, diabetes, cardiovascular diseases, and neurodegenerative diseases. Thus, manipulating the aging rate and potentially postponing the onset of these devastating diseases could have a tremendous impact on human health. Recent studies, relying primarily on nonvertebrate short-lived model systems, have shown the importance of both genetic and environmental factors in modulating the aging rate. However, relatively little is known about aging in vertebrates or what processes may be unique and specific to these complex organisms. Here we discuss how advances in genomics and genome editing have significantly expanded our ability to probe the aging process in a vertebrate system. We highlight recent findings from a naturally short-lived vertebrate, the African turquoise killifish, which provides an attractive platform for exploring mechanisms underlying vertebrate aging and age-related diseases. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.

  6. A review of creatine supplementation in age-related diseases: more than a supplement for athletes [v1; ref status: indexed, http://f1000r.es/4ak

    Directory of Open Access Journals (Sweden)

    Rachel N. Smith

    2014-09-01

    Full Text Available Creatine is an endogenous compound synthesized from arginine, glycine and methionine. This dietary supplement can be acquired from food sources such as meat and fish, along with athlete supplement powders. Since the majority of creatine is stored in skeletal muscle, dietary creatine supplementation has traditionally been important for athletes and bodybuilders to increase the power, strength, and mass of the skeletal muscle. However, new uses for creatine have emerged suggesting that it may be important in preventing or delaying the onset of neurodegenerative diseases associated with aging. On average, 30% of muscle mass is lost by age 80, while muscular weakness remains a vital cause for loss of independence in the elderly population. In light of these new roles of creatine, the dietary supplement’s usage has been studied to determine its efficacy in treating congestive heart failure, gyrate atrophy, insulin insensitivity, cancer, and high cholesterol. In relation to the brain, creatine has been shown to have antioxidant properties, reduce mental fatigue, protect the brain from neurotoxicity, and improve facets/components of neurological disorders like depression and bipolar disorder. The combination of these benefits has made creatine a leading candidate in the fight against age-related diseases, such as Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis, long-term memory impairments associated with the progression of Alzheimer’s disease, and stroke. In this review, we explore the normal mechanisms by which creatine is produced and its necessary physiology, while paying special attention to the importance of creatine supplementation in improving diseases and disorders associated with brain aging and outlining the clinical trials involving creatine to treat these diseases.

  7. Aging of marrow stromal (skeletal) stem cells and their contribution to age-related bone loss

    DEFF Research Database (Denmark)

    Bellantuono, Ilaria; Aldahmash, Abdullah; Kassem, Moustapha

    2009-01-01

    Marrow stromal cells (MSC) are thought to be stem cells with osteogenic potential and therefore responsible for the repair and maintenance of the skeleton. Age related bone loss is one of the most prevalent diseases in the elder population. It is controversial whether MSC undergo a process of agi...

  8. Accelerated Age-Dependent Hippocampal Volume Loss in Parkinson Disease With Mild Cognitive Impairment.

    Science.gov (United States)

    Schneider, Christine B; Donix, Markus; Linse, Katharina; Werner, Annett; Fauser, Mareike; Klingelhoefer, Lisa; Löhle, Matthias; von Kummer, Rüdiger; Reichmann, Heinz; Storch, Alexander

    2017-09-01

    Patients with Parkinson disease are at high risk of developing dementia. During the course of the disease, a substantial number of patients will experience a cognitive decline, indicating the dynamics of the underlying neuropathology. Magnetic resonance imaging (MRI) has become increasingly useful for identifying structural characteristics in radiological brain anatomy existing prior to clinical symptoms. Whether these changes reflect pathology, whether they are aging related, or both often remains unclear. We hypothesized that aging-associated brain structural changes would be more pronounced in the hippocampal region among patients with Parkinson disease having mild cognitive deficits relative to cognitively unimpaired patients. Using MRI, we investigated 30 cognitively healthy patients with Parkinson disease and 33 patients with nondemented Parkinson disease having mild cognitive impairment. All participants underwent structural MRI scanning and extensive clinical and neuropsychological assessments. Irrespective of the study participants' cognitive status, older age was associated with reduced cortical thickness in various neocortical regions. Having mild cognitive impairment was not associated with an increased rate of cortical thinning or volume loss in these regions, except in the hippocampus bilaterally. Patients with Parkinson disease having mild cognitive impairment show an accelerated age-dependent hippocampal volume loss when compared with cognitively healthy patients with Parkinson disease. This may indicate pathological processes in a key region for memory functioning in patients with Parkinson disease at risk of developing dementia. Structural MRI of the hippocampal region could potentially contribute to identifying patients who should receive early treatment aimed at delaying the clinical onset of dementia.

  9. Can Vitamin A be Improved to Prevent Blindness due to Age-Related Macular Degeneration, Stargardt Disease and Other Retinal Dystrophies?

    Science.gov (United States)

    Saad, Leonide; Washington, Ilyas

    2016-01-01

    We discuss how an imperfect visual cycle results in the formation of vitamin A dimers, thought to be involved in the pathogenesis of various retinal diseases, and summarize how slowing vitamin A dimerization has been a therapeutic target of interest to prevent blindness. To elucidate the molecular mechanism of vitamin A dimerization, an alternative form of vitamin A, one that forms dimers more slowly yet maneuvers effortlessly through the visual cycle, was developed. Such a vitamin A, reinforced with deuterium (C20-D3-vitamin A), can be used as a non-disruptive tool to understand the contribution of vitamin A dimers to vision loss. Eventually, C20-D3-vitamin A could become a disease-modifying therapy to slow or stop vision loss associated with dry age-related macular degeneration (AMD), Stargardt disease and retinal diseases marked by such vitamin A dimers. Human clinical trials of C20-D3-vitamin A (ALK-001) are underway.

  10. Patient Awareness of Cataract and Age-related Macular Degeneration among the Korean Elderly: A Population-based Study.

    Science.gov (United States)

    Lee, Hankil; Jang, Yong Jung; Lee, Hyung Keun; Kang, Hye Young

    2017-12-01

    Age-related eye disease is often considered part of natural aging. Lack of awareness of eye conditions can result in missed treatment. We investigated the rates of awareness of cataract and age-related macular degeneration, the most common age-related eye-diseases, and the associated factors among elderly Koreans. We identified 7,403 study subjects (≥40 years old) with cataract or age-related macular degeneration based on ophthalmic examination results during the 5th Korean National Health and Nutrition Examination Survey conducted between 2010 and 2012. We assessed whether patients were aware of their eye condition based on a previous diagnosis by a physician. The average awareness rate over the 3-year study period was 23.69% in subjects with cataract and 1.45% in subjects with age-related macular degeneration. Logistic regression analysis showed that patients with cataract were more likely to recognize their condition if they had myopia (odds ratio, 2.08), hyperopia (odds ratio, 1.33), family history of eye disease (odds ratio, 1.44), or a past eye examination (odds ratio, 4.07-29.10). The presence of diabetes mellitus was also a significant predictor of patient awareness of cataract (odds ratio, 1.88). Poor patient recognition of eye disease among the Korean elderly highlights the seriousness of this potential public health problem in our aging society. Pre-existing eye-related conditions and diabetes were significant predictors of awareness; therefore, patients in frequent contact with their doctors have a greater chance of detecting eye disease. © 2017 The Korean Ophthalmological Society

  11. Potential public health impact of Age-Related Eye Disease Study results: AREDS report no. 11.

    Science.gov (United States)

    Bressler, Neil M; Bressler, Susan B; Congdon, Nathan G; Ferris, Frederick L; Friedman, David S; Klein, Ronald; Lindblad, Anne S; Milton, Roy C; Seddon, Johanna M

    2003-11-01

    To estimate the potential public health impact of the findings of the Age-Related Eye Disease Study (AREDS) on reducing the number of persons developing advanced age-related macular degeneration (AMD) during the next 5 years in the United States. The AREDS clinical trial provides estimates of AMD progression rates and of reduction in risk of developing advanced AMD when a high-dose nutritional supplement of antioxidants and zinc is used. These results are applied to estimates of the US population at risk, to estimate the number of people who would potentially avoid advanced AMD during 5 years if those at risk were to take a supplement such as that used in AREDS. An estimated 8 million persons at least 55 years old in the United States have monocular or binocular intermediate AMD or monocular advanced AMD. They are considered to be at high risk for advanced AMD and are those for whom the AREDS formulation should be considered. Of these people, 1.3 million would develop advanced AMD if no treatment were given to reduce their risk. If all of these people at risk received supplements such as those used in AREDS, more than 300,000 (95% confidence interval, 158,000-487,000) of them would avoid advanced AMD and any associated vision loss during the next 5 years. If people at high risk for advanced AMD received supplements such as those suggested by AREDS results, the potential impact on public health in the United States would be considerable during the next 5 years.

  12. Age-Related Neurodegeneration and Memory Loss in Down Syndrome

    Directory of Open Access Journals (Sweden)

    Jason P. Lockrow

    2012-01-01

    Full Text Available Down syndrome (DS is a condition where a complete or segmental chromosome 21 trisomy causes variable intellectual disability, and progressive memory loss and neurodegeneration with age. Many research groups have examined development of the brain in DS individuals, but studies on age-related changes should also be considered, with the increased lifespan observed in DS. DS leads to pathological hallmarks of Alzheimer's disease (AD by 40 or 50 years of age. Progressive age-related memory deficits occurring in both AD and in DS have been connected to degeneration of several neuronal populations, but mechanisms are not fully elucidated. Inflammation and oxidative stress are early events in DS pathology, and focusing on these pathways may lead to development of successful intervention strategies for AD associated with DS. Here we discuss recent findings and potential treatment avenues regarding development of AD neuropathology and memory loss in DS.

  13. The lumbar spine age-related degenerative disease influences the BMD not the TBS: the Osteolaus cohort.

    Science.gov (United States)

    Padlina, I; Gonzalez-Rodriguez, E; Hans, D; Metzger, M; Stoll, D; Aubry-Rozier, B; Lamy, O

    2017-03-01

    We evaluated the influence of degenerative disease and fractured vertebra on lumbar spine bone mineral density (BMD) and trabecular bone score (TBS) in 1500 women aged 50-80 years. TBS was not affected by a degenerative disease. While BMD increases after 62.5 years, TBS continues to decline. TBS should play a leading role in lumbar spine evaluation. After menopause, lumbar spine (LS) BMD and TBS values decrease. Degenerative disease (DD) increases with age and affect LS BMD. The aim of this study was to measure changes in LS BMD and TBS in women 50 to 80 years old, taking into account the impact of fractured vertebrae and DD. LS BMD, TBS, and vertebral fracture assessment were evaluated in the OsteoLaus cohort (1500 women, 50-80 years old). The exams were analyzed following ISCD guidelines to identify vertebrae with fractures or DD (Vex). 1443 women were enrolled: mean age 66.7 ± 11.7 years, BMI 25.7 ± 4.4. LS BMD and TBS were weakly correlated (r2 = 0.16). The correlation (Vex excluded) between age and BMD was +0.03, between age and TBS -0.34. According to age group, LS BMD was 1.2 to 3.2% higher before excluding Vex (p < 0.001). TBS had an insignificant change of <1% after excluding Vex. LS BMD (Vex) decreased by 4.6% between 52.5 and 62.5 years, and increased by 2.6% between 62.5 and 77.5 years. TBS (Vex excluded) values decreased steadily with age with an overall loss of 8.99% between 52.5 and 77.5 years. Spine TBS, femoral neck, and total hip BMD gradually decreased with age, reaching one SD between the oldest and youngest group. TBS is not affected by DD. While BMD increases after 62.5 years, TBS continues to decline. For lumbar spine evaluation, in view of its independence from DD, TBS should play a leading role in the diagnosis in complement to BMD.

  14. Inflammatory bowel disease in relation to contact allergy

    DEFF Research Database (Denmark)

    Engkilde, Kåre; Menné, Torkil; Johansen, Jeanne Duus

    2007-01-01

    for ulcerative colitis (UC) diagnosis. Using logistic regression, with the result of the patch test as the dependent variable, we calculated the odds ratios for IBD, CD and UC, adjusted for gender and age. RESULTS: An inverse association between CA and IBD was found, odds ratio adjusted for age and gender 0.......71 (CI 95% 0.53-0.94), which is mainly the result of an inverse association between CA and CD, odds ratio adjusted for age and gender 0.42 (CI 95% 0.23-0.76). CONCLUSIONS: The association found between CA and IBD might be related to shared genetic factors or common environmental determinates. It may also...... be that having either disease result in skewness of the immune system might lead to an inverse disease association....

  15. Healthy aging and disease : role for telomere biology?

    NARCIS (Netherlands)

    Zhu, Haidong; Belcher, Matthew; van der Harst, Pim

    Aging is a biological process that affects most cells, organisms and species. Human aging is associated with increased susceptibility to a variety of chronic diseases, including cardiovascular disease, Type 2 diabetes, neurological diseases and cancer. Despite the remarkable progress made during the

  16. A Culture-Brain Link: Negative Age Stereotypes Predict Alzheimer’s-disease Biomarkers

    Science.gov (United States)

    Levy, Becca R.; Ferrucci, Luigi; Zonderman, Alan B.; Slade, Martin D.; Troncoso, Juan; Resnick, Susan M.

    2016-01-01

    Although negative age stereotypes have been found to predict adverse outcomes among older individuals, it was unknown whether the influence of stereotypes extends to brain changes associated with Alzheimer’s disease. To consider this possibility, we drew on the age stereotypes of dementia-free participants in the Baltimore Longitudinal Study of Aging that had been measured decades before yearly MRIs and brain autopsies were performed. Those with more negative age stereotypes earlier in life had significantly steeper hippocampal-volume loss, and significantly greater accumulation of neurofibrillary tangles and amyloid plaques at autopsy, adjusting for relevant covariates. These findings suggest a new pathway to identifying mechanisms and potential interventions related to the neuropathology of Alzheimer’s disease. PMID:26641877

  17. Risk assessment model for development of advanced age-related macular degeneration.

    Science.gov (United States)

    Klein, Michael L; Francis, Peter J; Ferris, Frederick L; Hamon, Sara C; Clemons, Traci E

    2011-12-01

    To design a risk assessment model for development of advanced age-related macular degeneration (AMD) incorporating phenotypic, demographic, environmental, and genetic risk factors. We evaluated longitudinal data from 2846 participants in the Age-Related Eye Disease Study. At baseline, these individuals had all levels of AMD, ranging from none to unilateral advanced AMD (neovascular or geographic atrophy). Follow-up averaged 9.3 years. We performed a Cox proportional hazards analysis with demographic, environmental, phenotypic, and genetic covariates and constructed a risk assessment model for development of advanced AMD. Performance of the model was evaluated using the C statistic and the Brier score and externally validated in participants in the Complications of Age-Related Macular Degeneration Prevention Trial. The final model included the following independent variables: age, smoking history, family history of AMD (first-degree member), phenotype based on a modified Age-Related Eye Disease Study simple scale score, and genetic variants CFH Y402H and ARMS2 A69S. The model did well on performance measures, with very good discrimination (C statistic = 0.872) and excellent calibration and overall performance (Brier score at 5 years = 0.08). Successful external validation was performed, and a risk assessment tool was designed for use with or without the genetic component. We constructed a risk assessment model for development of advanced AMD. The model performed well on measures of discrimination, calibration, and overall performance and was successfully externally validated. This risk assessment tool is available for online use.

  18. Mechanisms and consequences of oxidative stress in lung disease: therapeutic implications for an aging populace.

    Science.gov (United States)

    Hecker, Louise

    2018-04-01

    The rapid expansion of the elderly population has led to the recent epidemic of age-related diseases, including increased incidence and mortality of chronic and acute lung diseases. Numerous studies have implicated aging and oxidative stress in the pathogenesis of various pulmonary diseases; however, despite recent advances in these fields, the specific contributions of aging and oxidative stress remain elusive. This review will discuss the consequences of aging on lung morphology and physiology, and how redox imbalance with aging contributes to lung disease susceptibility. Here, we focus on three lung diseases for which aging is a significant risk factor: acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). Preclinical and clinical development for redox- and senescence-altering therapeutic strategies are discussed, as well as scientific advancements that may direct current and future therapeutic development. A deeper understanding of how aging impacts normal lung function, redox balance, and injury-repair processes will inspire the development of new therapies to prevent and/or reverse age-associated pulmonary diseases, and ultimately increase health span and longevity. This review is intended to encourage basic, clinical, and translational research that will bridge knowledge gaps at the intersection of aging, oxidative stress, and lung disease to fuel the development of more effective therapeutic strategies for lung diseases that disproportionately afflict the elderly.

  19. Prevention of age-related macular degeneration-like retinopathy by rapamycin in rats.

    Science.gov (United States)

    Kolosova, Nataliya G; Muraleva, Natalia A; Zhdankina, Anna A; Stefanova, Natalia A; Fursova, Anzhela Z; Blagosklonny, Mikhail V

    2012-08-01

    Age-related macular degeneration, a neurodegenerative and vascular retinal disease, is the most common cause of blindness in the Western countries. Evidence accumulates that target of rapamycin is involved in aging and age-related diseases, including neurodegeneration. The target of rapamycin inhibitor, rapamycin, suppresses the senescent cell phenotype and extends life span in diverse species, including mice. Rapamycin decreases senescence-associated phenotypes in retinal pigment epithelial cells in culture. Herein, we investigated the effect of rapamycin on spontaneous retinopathy in senescence-accelerated OXYS rats, an animal model of age-related macular degeneration. Rats were treated with either 0.1 or 0.5 mg/kg rapamycin, which was given orally as a food mixture. In a dose-dependent manner, rapamycin decreased the incidence and severity of retinopathy. Rapamycin improved some (but not all) histological abnormalities associated with retinopathy. Thus, in retinal pigment epithelial cell layers, rapamycin decreased nuclei heterogeneity and normalized intervals between nuclei. In photoreceptor cells, associated neurons, and radial glial cells, rapamycin prevented nuclear and cellular pyknosis. More important, rapamycin prevented destruction of ganglionar neurons in the retina. Rapamycin did not exert any adverse effects on the retina in control disease-free Wistar rats. Taken together, our data suggest the therapeutic potential of rapamycin for treatment and prevention of retinopathy. Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  20. Age and disease at an arms length

    DEFF Research Database (Denmark)

    Lassen, Aske Juul

    How are the boundaries of disease and health, age, life and death negotiated through technology and active aging? The paper focuses on how disease and age are dealt with by active elderly at activity centres in the Copenhagen area. New health technologies lead to new expectations to the longevity...... of life. A new ethics is emerging, focused on longevity and spreading through healthcare policies and technologies . At activity centres active elderly talk about health in old age, share experiences with health technologies and reflect on longevity, while working out. Chronic diseases are common in old...... age, but this does not mean that you give up or accept decreased quality of life. Ends change as new means emerge . The technological and medical abilities change the reflexive longevity. One expects to live a long and healthy life. Thus, technology can be conceived as a world-changing mediation. What...

  1. Oxidative stress participates in age-related changes in rat lumbar intervertebral discs.

    Science.gov (United States)

    Hou, Gang; Lu, Huading; Chen, Mingjuan; Yao, Hui; Zhao, Huiqing

    2014-01-01

    Aging is a major factor associated with lumber intervertebral disc degeneration, and oxidative stress is known to play an essential role in the pathogenesis of many age-related diseases. In this study, we investigated oxidative stress in intervertebral discs of Wistar rats in three different age groups: youth, adult, and geriatric. Age-related intervertebral disc changes were examined by histological analysis. In addition, oxidative stress was evaluated by assessing nitric oxide (NO), superoxide dismutase (SOD), malondialdehyde (MDA), and advanced oxidation protein products (AOPPs). Intervertebral disc, but not serum, NO concentrations significantly differed between the three groups. Serum and intervertebral disc SOD activity gradually decreased with age. Furthermore, both serum and intervertebral disc MDA and AOPP levels gradually increased with age. Our studies suggest that oxidative stress is associated with age-related intervertebral disc changes. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. Animal models of age related macular degeneration

    Science.gov (United States)

    Pennesi, Mark E.; Neuringer, Martha; Courtney, Robert J.

    2013-01-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations. PMID:22705444

  3. Accelerated Vascular Aging as a Paradigm for Hypertensive Vascular Disease: Prevention and Therapy.

    Science.gov (United States)

    Barton, Matthias; Husmann, Marc; Meyer, Matthias R

    2016-05-01

    Aging is considered the most important nonmodifiable risk factor for cardiovascular disease and death after age 28 years. Because of demographic changes the world population is expected to increase to 9 billion by the year 2050 and up to 12 billion by 2100, with several-fold increases among those 65 years of age and older. Healthy aging and prevention of aging-related diseases and associated health costs have become part of political agendas of governments around the world. Atherosclerotic vascular burden increases with age; accordingly, patients with progeria (premature aging) syndromes die from myocardial infarctions or stroke as teenagers or young adults. The incidence and prevalence of arterial hypertension also increases with age. Arterial hypertension-like diabetes and chronic renal failure-shares numerous pathologies and underlying mechanisms with the vascular aging process. In this article, we review how arterial hypertension resembles premature vascular aging, including the mechanisms by which arterial hypertension (as well as other risk factors such as diabetes mellitus, dyslipidemia, or chronic renal failure) accelerates the vascular aging process. We will also address the importance of cardiovascular risk factor control-including antihypertensive therapy-as a powerful intervention to interfere with premature vascular aging to reduce the age-associated prevalence of diseases such as myocardial infarction, heart failure, hypertensive nephropathy, and vascular dementia due to cerebrovascular disease. Finally, we will discuss the implementation of endothelial therapy, which aims at active patient participation to improve primary and secondary prevention of cardiovascular disease. Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

  4. Health-related quality of life is related to COPD disease severity

    Directory of Open Access Journals (Sweden)

    Rönmark Eva

    2005-09-01

    Full Text Available Abstract Background The aim of this study was to evaluate the association between health-related quality of life (HRQL and disease severity using lung function measures. Methods A survey was performed in subjects with COPD in Sweden. 168 subjects (70 women, mean age 64.3 years completed the generic HRQL questionnaire, the Short Form 36 (SF-36, the disease-specific HRQL questionnaire; the St George's Respiratory Questionnaire (SGRQ, and the utility measure, the EQ-5D. The subjects were divided into four severity groups according to FEV1 per cent of predicted normal using two clinical guidelines: GOLD and BTS. Age, gender, smoking status and socio-economic group were regarded as confounders. Results The COPD severity grades affected the SGRQ Total scores, varying from 25 to 53 (GOLD p = 0.0005 and from 25 to 45 (BTS p = 0.0023. The scores for SF-36 Physical were significantly associated with COPD severity (GOLD p = 0.0059, BTS p = 0.032. No significant association were noticed for the SF-36, Mental Component Summary scores and COPD severity. Scores for EQ-5D VAS varied from 73 to 37 (GOLD I-IV p = 0.0001 and from 73 to 50 (BTS 0-III p = 0.0007. The SGRQ Total score was significant between age groups (p = 0.0047. No significant differences in HRQL with regard to gender, smoking status or socio-economic group were noticed. Conclusion The results show that HRQL in COPD deteriorates with disease severity and with age. These data show a relationship between HRQL and disease severity obtained by lung function.

  5. [Is aging a disease?

    Science.gov (United States)

    Novoselov, V M

    2017-01-01

    Recently, among gerontologists and the community, adjoining them for scientific interests, an acute discussion has arisen about the need to recognize the aging as a disease. The author discusses the philosophical, deontological, nosological, pathophysiological, clinical and biological aspects of this issue.

  6. Periodontal disease level-butyric acid putatively contributes to the ageing blood: A proposed link between periodontal diseases and the ageing process.

    Science.gov (United States)

    Cueno, Marni E; Seki, Keisuke; Ochiai, Kuniyasu; Imai, Kenichi

    2017-03-01

    Periodontal diseases are partly attributable to periodontopathic bacteria found in the host, whereas, butyric acid (BA) is a common secondary metabolite produced by periodontopathic bacterial pathogens. BA has been linked to oxidative stress induction while oxidative stress has long been associated with the ageing process. However, the possible link between BA-induced oxidative stress and the ageing process has never been elucidated. Here, we attempted to show the possible role of periodontal diseaselevel-BA (PDL-BA) in influencing the rat blood ageing process. We injected PDL-BA into the young rat gingiva and, after 24h, heart blood extraction was performed. Blood obtained from PDL-BA-treated young rats was compared to untreated young and middle-aged rats. We found that cytosolic, but not mitochondrial, heme was affected 24h post-injection. In addition, we observed that PDL-BA treatment altered blood NOX activation, NADPH-related oxidative stress components (H 2 O 2 and GR), calcium homeostasis, cell death signals (CASP3 and CASP1), and age-related markers (SIRT1 and mTOR) in young rats, with some components more closely mimicking levels found in middle-aged rats. In this regard, we propose that PDL-BA may play a role in contributing to the rat blood ageing process. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. The Influence of Age-Related Cues on Health and Longevity.

    Science.gov (United States)

    Hsu, Laura M; Chung, Jaewoo; Langer, Ellen J

    2010-11-01

    Environmental cues that signal aging may directly and indirectly prime diminished capacity. Similarly, the absence of these cues may prime improved health. The authors investigated the effects of age cues on health and longevity in five very different settings. The findings include the following: First, women who think they look younger after having their hair colored/cut show a decrease in blood pressure and appear younger in photographs (in which their hair is cropped out) to independent raters. Second, clothing is an age-related cue. Uniforms eliminate these age-related cues: Those who wear work uniforms have lower morbidity than do those who earn the same amount of money and do not wear work uniforms. Third, baldness cues old age. Men who bald prematurely see an older self and therefore age faster: Prematurely bald men have an excess risk of getting prostate cancer and coronary heart disease than do men who do not prematurely bald. Fourth, women who bear children later in life are surrounded by younger age-related cues: Older mothers have a longer life expectancy than do women who bear children earlier in life. Last, large spousal age differences result in age-incongruent cues: Younger spouses live shorter lives and older spouses live longer lives than do controls. © The Author(s) 2010.

  8. A critical review of vitamin C for the prevention of age-related cognitive decline and Alzheimer's disease.

    Science.gov (United States)

    Harrison, Fiona E

    2012-01-01

    Antioxidants in the diet have long been thought to confer some level of protection against the oxidative damage that is involved in the pathology of Alzheimer's disease as well as general cognitive decline in normal aging. Nevertheless, support for this hypothesis in the literature is equivocal. In the case of vitamin C (ascorbic acid) in particular, lack of consideration of some of the specific features of vitamin C metabolism has led to studies in which classification of participants according to vitamin C status is inaccurate, and the absence of critical information precludes the drawing of appropriate conclusions. Vitamin C levels in plasma are not always reported, and estimated daily intake from food diaries may not be accurate or reflect actual plasma values. The ability to transport ingested vitamin C from the intestines into blood is limited by the saturable sodium-dependent vitamin C transporter (SVCT1) and thus very high intakes and the use of supplements are often erroneously considered to be of greater benefit that they really are. The current review documents differences among the studies in terms of vitamin C status of participants. Overall, there is a large body of evidence that maintaining healthy vitamin C levels can have a protective function against age-related cognitive decline and Alzheimer's disease, but avoiding vitamin C deficiency is likely to be more beneficial than taking supplements on top of a normal, healthy diet.

  9. Age-Dependent Fecal Bacterial Correlation to Inflammatory Bowel Disease for Newly Diagnosed Untreated Children

    Directory of Open Access Journals (Sweden)

    Felix Chinweije Nwosu

    2013-01-01

    Full Text Available The knowledge about correlation patterns between the fecal microbiota and inflammatory bowel diseases (IBD—comprising the two subforms Crohn's disease (CD and ulcerative colitis (UC—for newly diagnosed untreated children is limited. To address this knowledge gap, a selection of faecal specimens (CD, n=27 and UC, n=16 and non-IBD controls (n=30 children (age < 18 years was analysed utilising bacterial small subunit (SSU rRNA. We found, surprising age dependence for the fecal microbiota correlating to IBD. The most pronounced patterns were that E. coli was positively (R2=0.16, P=0.05 and Bacteroidetes, negatively (R2=0.15, P=0.05 correlated to age for CD patients. For UC, we found an apparent opposite age-related disease correlation for both Bacteroides and Escherichia. In addition, there was an overrepresentation of Haemophilus for the UC children. From our, results we propose a model where the aetiology of IBD is related to an on-going immunological development in children requiring different age-dependent bacterial stimuli. The impact of our findings could be a better age stratification for understanding and treating IBD in children.

  10. Effects of sensorimotor exercise on swallowing outcomes relative to age and age-related disease.

    Science.gov (United States)

    Kays, Stephanie; Robbins, JoAnne

    2006-11-01

    Parallel to the growing number of adults over age 65 years and the increasing use of exercise in geriatric medicine to improve function and decrease fall risk, recent advances in the treatment of geriatric dysphagia have focused on rehabilitating swallowing function with active exercise. Specific changes in central neural pathways as well as peripheral end organs (muscles) that occur with natural aging may predispose older adults to an increased risk for dysphagia when faced with chronic medical conditions. Research to date primarily has focused on the utility of nonswallow motor exercises to increase muscle strength and range of motion in oropharyngeal structures. Future directions in the field of dysphagia rehabilitation demand evidence-based investigations into the ability of exercise to affect neural plasticity, representing long-lasting alterations in neural organization.

  11. Age-related hearing loss

    Science.gov (United States)

    ... grow older. Your genes and loud noise (from rock concerts or music headphones) may play a large role. The following factors contribute to age-related hearing loss: Family history (age-related hearing loss tends to run in ...

  12. Prevalence and nature of cardiovascular disease in methamphetamine-related death: A national study.

    Science.gov (United States)

    Darke, Shane; Duflou, Johan; Kaye, Sharlene

    2017-10-01

    Methamphetamine dependence is a major public health problem. This study examined the nature, and extent, of cardiovascular disease amongst cases of methamphetamine-related death in Australia, 2009-2015. Analysis of 894 cases of methamphetamine-related death with full autopsy reports retrieved from the National Coronial Information System. The mean age was 37.9yrs (range 15-69yrs) and 78.5% were male. A quarter (26.3%) of cases had enlarged hearts and left ventricular hypertrophy was diagnosed in 18.9%. Severe coronary artery disease was present in 19.0%, the left coronary artery being the vessel most frequently stenosed (16.6%). Replacement fibrosis (evidence of earlier ischaemic events) in the heart muscle was observed in 19.8% of cases, and cardiomyopathy was diagnosed in 5.5%. Histological evidence of hypertension was observed in 32.7% of cases. With the exception of cardiomyopathy, equally common amongst both sexes, cardiovascular disease was more common amongst males, and those aged >35yrs. Clinically significant levels of cardiovascular disease were also observed amongst cases where the cause of death was not attributed to cardiovascular disease: cardiomegaly (19.3%), left ventricular hypertrophy (14.6%), severe coronary artery disease (9.4%), replacement fibrosis (14.4%), cardiomyopathy (3.3%). Cardiovascular disease was highly prevalent, despite the relatively young age of cases. With methamphetamine use increasing rapidly in major regions, cardiovascular disease and cardiovascular-related death will likely increase amongst methamphetamine users. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Insufficient DNA methylation affects healthy aging and promotes age-related health problems.

    Science.gov (United States)

    Liu, Liang; van Groen, Thomas; Kadish, Inga; Li, Yuanyuan; Wang, Deli; James, Smitha R; Karpf, Adam R; Tollefsbol, Trygve O

    2011-08-01

    DNA methylation plays an integral role in development and aging through epigenetic regulation of genome function. DNA methyltransferase 1 (Dnmt1) is the most prevalent DNA methyltransferase that maintains genomic methylation stability. To further elucidate the function of Dnmt1 in aging and age-related diseases, we exploited the Dnmt1+/- mouse model to investigate how Dnmt1 haploinsufficiency impacts the aging process by assessing the changes of several major aging phenotypes. We confirmed that Dnmt1 haploinsufficiency indeed decreases DNA methylation as a result of reduced Dnmt1 expression. To assess the effect of Dnmt1 haploinsufficiency on general body composition, we performed dual-energy X-ray absorptiometry analysis and showed that reduced Dnmt1 activity decreased bone mineral density and body weight, but with no significant impact on mortality or body fat content. Using behavioral tests, we demonstrated that Dnmt1 haploinsufficiency impairs learning and memory functions in an age-dependent manner. Taken together, our findings point to the interesting likelihood that reduced genomic methylation activity adversely affects the healthy aging process without altering survival and mortality. Our studies demonstrated that cognitive functions of the central nervous system are modulated by Dnmt1 activity and genomic methylation, highlighting the significance of the original epigenetic hypothesis underlying memory coding and function.

  14. Age-related changes in aortic 3D blood flow velocities and wall shear stress: Implications for the identification of altered hemodynamics in patients with aortic valve disease

    NARCIS (Netherlands)

    van Ooij, Pim; Garcia, Julio; Potters, Wouter V.; Malaisrie, S. Chris; Collins, Jeremy D.; Carr, James C.; Markl, Michael; Barker, Alex J.

    2016-01-01

    To investigate age-related changes in peak systolic aortic 3D velocity and wall shear stress (WSS) in healthy controls and to investigate the importance of age-matching for 3D mapping of abnormal aortic hemodynamics in bicuspid aortic valve disease (BAV). 4D flow MRI (fields strengths = 1.5-3T;

  15. Prevalence of peripheral arterial disease and related risk factors in Turkish elders

    Directory of Open Access Journals (Sweden)

    Yesilkayali Teoman

    2011-09-01

    Full Text Available Abstract Background It is known that prevalence of peripheral arterial disease being a widespread atherosclerotic vascular disease increases by age. On the other hand, no comprehensive study showing the prevalence of peripheral arterial disease in Turkish elders is seen. In this study, it is aimed to assess prevalence of peripheral arterial disease and related risk factors in Turkish elders in primary health center. Methods 507 elderly staying at Narlidere Geriatric Care Center and Residential Home and accepting to participate in the study were included in the study. Epidemiological data for diagnosis of peripheral arterial disease, risk factors, findings of physical examination and ankle brachial index measurements were assessed in the study. Data were analyzed in terms of prevalence of peripheral arterial disease, age and gender relation and other cardiovascular risk factors. Results Of the participants, 317 (62.5% were female. The mean age was 77.61 ± 6.93 years (62-102. The most wide-spread chronic diseases in elderly included hypertension, coronary artery disease, hyperlipidemia and Type 2 DM, respectively. On the other hand, only 7 (1.4% elderly were diagnosed with peripheral arterial disease. The number of elderly ABI of whom was measured as Conclusions Peripheral arterial disease is expected to be seen prevailing in elderly. However, it was determined at very low rate before the study due to the fact that the disease cannot be diagnosed clinically especially in early-period. Peripheral arterial disease determined in the study is lower than expected as per the age group. This can be associated with practices of geriatrics nursing and family practice including continuous care to reduce cardiovascular risk factors of patients staying at the unit.

  16. Complement pathway biomarkers and age-related macular degeneration

    Science.gov (United States)

    Gemenetzi, M; Lotery, A J

    2016-01-01

    In the age-related macular degeneration (AMD) ‘inflammation model', local inflammation plus complement activation contributes to the pathogenesis and progression of the disease. Multiple genetic associations have now been established correlating the risk of development or progression of AMD. Stratifying patients by their AMD genetic profile may facilitate future AMD therapeutic trials resulting in meaningful clinical trial end points with smaller sample sizes and study duration. PMID:26493033

  17. Intake of key chronic disease-related nutrients among baby boomers.

    Science.gov (United States)

    King, Dana E; Xiang, Jun; Brown, Alexander

    2014-06-01

    The dietary habits of baby boomers (people born between 1946 and 1964) undoubtedly will have a substantial impact on their future health; however, dietary information regarding the intake of key chronic disease-related nutrients is lacking for this generation. The objective of this study was to compare the dietary intake of key chronic disease-related nutrients of the baby boomer generation with the previous generation of middle-aged adults. National cross-sectional study comparison analyzing data from the National Health and Nutrition Examination Survey (NHANES) including NHANES III (1988-1994) and the NHANES for 2007-2010, focused on adult respondents ages 46 to 64 years who were not institutionalized at the time of each survey. The two cohorts were compared with regard to dietary intake of key nutritional components. The main outcome measures were intake of total calories, sodium, cholesterol, fat, fruits, vegetables, vitamin C, water, and fiber. The baby boomers' average daily intake of nutrients exceeded that of the previous generation of middle-aged adults for total calories (2118/1999), total fat (82/76 g), sodium (3513/3291 mg), and cholesterol (294/262 g; all P generation (P baby boomers compared with the previous generation of middle-aged adults. These findings are indicative of a diet that may contribute to increased rates of chronic disease among individuals in this age group.

  18. Alterations in neuropeptides in aging and disease. Pathophysiology and potential for clinical intervention.

    Science.gov (United States)

    Leake, A; Ferrier, I N

    1993-01-01

    Marked specific and selective changes in the levels of some neuropeptides in age-related diseases, such as senile dementia of the Alzheimer (SDAT) or Lewy body (SDLT) types, Parkinson's disease, Huntington's disease and major depressive disorder, versus normal aging have been noted. However, the levels of most neuropeptides are normal. The only 2 peptides consistently altered in SDAT are somatostatin and corticotrophin-releasing hormone both of which are reduced. In Huntington's disease, the level of substance P in the basal ganglia is reduced suggesting a preferential vulnerability of spiny neurones in this disease. In Parkinson's disease, substance P is attenuated in the basal ganglia while somatostatin is reduced in the neocortex. These and other results suggest that substance P deficits are related to movement disorders while somatostatin deficits are related to cognitive impairment. SDLT is a type of dementia with features common to both SDAT and Parkinson's disease, although the changes in neuropeptides suggest that neurochemically the disease is more closely related to SDAT. In major depressive disorder, the level of corticotrophin-releasing hormone is reduced while there is a reciprocal increase in corticotrophin-releasing hormone receptors suggesting that the neurones remain functional. Potential clinical intervention has been limited by problems such as poor penetration of agents into the brain and the short half-lives of neuropeptide agonists and antagonists. However, some currently available agents may act, at least in part, through modulation of neuropeptide pathways, e.g. carbamazepine and alprazolam both modulate the corticotrophin-releasing hormone system in animals, and both have clinically proven antidepressant activity.

  19. GRM7 variants confer susceptibility to age-related hearing impairment

    DEFF Research Database (Denmark)

    Friedman, Rick A; Van Laer, Lut; Huentelman, Matthew J

    2009-01-01

    Age-related hearing impairment (ARHI), or presbycusis, is the most prevalent sensory impairment in the elderly. ARHI is a complex disease caused by an interaction between environmental and genetic factors. Here we describe the results of the first whole genome association study for ARHI. The stud...

  20. DNA-Related Pathways Defective in Human Premature Aging

    OpenAIRE

    Bohr, Vilhelm A.

    2002-01-01

    One of the major issues in studies on aging is the choice of biological model system. The human premature aging disorders represent excellent model systems for the study of the normal aging process, which occurs at a much earlier stage in life in these individuals than in normals. The patients with premature aging also get the age associated diseases at an early stage in life, and thus age associated disease can be studied as well. It is thus of great interest to understand the molecular path...

  1. Gender- and age-related differences in clinical presentation and management of outpatients with stable coronary artery disease.

    Science.gov (United States)

    Ferrari, Roberto; Abergel, Hélène; Ford, Ian; Fox, Kim M; Greenlaw, Nicola; Steg, Ph Gabriel; Hu, Dayi; Tendera, Michal; Tardif, Jean-Claude

    2013-09-10

    Contemporary generalizable data on the demographics and management of outpatients with stable coronary artery disease (CAD) in routine clinical practice are sparse. Using the data from the CLARIFY registry we describe gender- and age-related differences in baseline characteristics and management of these patients across broad geographic regions. This international, prospective, observational, longitudinal registry enrolled stable CAD outpatients from 45 countries in Africa, Asia, Australia, Europe, the Middle East, and North, Central, and South America. Baseline data were available for 33280 patients. Mean (SD) age was 64 (10.5) years and 22.5% of patients were female. The prevalence of CAD risk factors was generally higher in women than in men. Women were older (66.6 vs 63.4 years), more frequently diagnosed with diabetes (33% vs 28%), hypertension (79% vs 69%), and higher resting heart rate (69 vs 67 bpm), and were less physically active. Smoking and a history of myocardial infarction were more common in men. Women were more likely to have angina (28% vs 20%), but less likely to have undergone revascularization procedures. CAD was more likely to be asymptomatic in older patients perhaps because of reduced levels of physical activity. Prescription of evidence-based medication for secondary prevention varied with age, with patients ≥ 75 years treated less often with beta blockers, aspirin and angiotensin-converting enzyme inhibitors than patients age groups of outpatients with stable CAD. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  2. Inflammation and premature aging in advanced chronic kidney disease.

    Science.gov (United States)

    Kooman, Jeroen P; Dekker, Marijke J; Usvyat, Len A; Kotanko, Peter; van der Sande, Frank M; Schalkwijk, Casper G; Shiels, Paul G; Stenvinkel, Peter

    2017-10-01

    Systemic inflammation in end-stage renal disease is an established risk factor for mortality and a catalyst for other complications, which are related to a premature aging phenotype, including muscle wasting, vascular calcification, and other forms of premature vascular disease, depression, osteoporosis, and frailty. Uremic inflammation is also mechanistically related to mechanisms involved in the aging process, such as telomere shortening, mitochondrial dysfunction, and altered nutrient sensing, which can have a direct effect on cellular and tissue function. In addition to uremia-specific causes, such as abnormalities in the phosphate-Klotho axis, there are remarkable similarities between the pathophysiology of uremic inflammation and so-called "inflammaging" in the general population. Potentially relevant, but still somewhat unexplored in this respect, are abnormal or misplaced protein structures, as well as abnormalities in tissue homeostasis, which evoke danger signals through damage-associated molecular patterns, as well as the senescence-associated secretory phenotype. Systemic inflammation, in combination with the loss of kidney function, can impair the resilience of the body to external and internal stressors by reduced functional and structural tissue reserves, and by impairing normal organ crosstalk, thus providing an explanation for the greatly increased risk of homeostatic breakdown in this population. In this review, the relationship between uremic inflammation and a premature aging phenotype, as well as potential causes and consequences, are discussed. Copyright © 2017 the American Physiological Society.

  3. Aging-related episodic memory decline: are emotions the key?

    Science.gov (United States)

    Kinugawa, Kiyoka; Schumm, Sophie; Pollina, Monica; Depre, Marion; Jungbluth, Carolin; Doulazmi, Mohamed; Sebban, Claude; Zlomuzica, Armin; Pietrowsky, Reinhard; Pause, Bettina; Mariani, Jean; Dere, Ekrem

    2013-01-01

    Episodic memory refers to the recollection of personal experiences that contain information on what has happened and also where and when these events took place. Episodic memory function is extremely sensitive to cerebral aging and neurodegerative diseases. We examined episodic memory performance with a novel test in young (N = 17, age: 21–45), middle-aged (N = 16, age: 48–62) and aged but otherwise healthy participants (N = 8, age: 71–83) along with measurements of trait and state anxiety. As expected we found significantly impaired episodic memory performance in the aged group as compared to the young group. The aged group also showed impaired working memory performance as well as significantly decreased levels of trait anxiety. No significant correlation between the total episodic memory and trait or state anxiety scores was found. The present results show an age-dependent episodic memory decline along with lower trait anxiety in the aged group. Yet, it still remains to be determined whether this difference in anxiety is related to the impaired episodic memory performance in the aged group. PMID:23378831

  4. Molecular insights into the pathogenesis of Alzheimer's disease and its relationship to normal aging.

    Directory of Open Access Journals (Sweden)

    Alexei A Podtelezhnikov

    Full Text Available Alzheimer's disease (AD is a complex neurodegenerative disorder that diverges from the process of normal brain aging by unknown mechanisms. We analyzed the global structure of age- and disease-dependent gene expression patterns in three regions from more than 600 brains. Gene expression variation could be almost completely explained by four transcriptional biomarkers that we named BioAge (biological age, Alz (Alzheimer, Inflame (inflammation, and NdStress (neurodegenerative stress. BioAge captures the first principal component of variation and includes genes statistically associated with neuronal loss, glial activation, and lipid metabolism. Normally BioAge increases with chronological age, but in AD it is prematurely expressed as if some of the subjects were 140 years old. A component of BioAge, Lipa, contains the AD risk factor APOE and reflects an apparent early disturbance in lipid metabolism. The rate of biological aging in AD patients, which cannot be explained by BioAge, is associated instead with NdStress, which includes genes related to protein folding and metabolism. Inflame, comprised of inflammatory cytokines and microglial genes, is broadly activated and appears early in the disease process. In contrast, the disease-specific biomarker Alz was selectively present only in the affected areas of the AD brain, appears later in pathogenesis, and is enriched in genes associated with the signaling and cell adhesion changes during the epithelial to mesenchymal (EMT transition. Together these biomarkers provide detailed description of the aging process and its contribution to Alzheimer's disease progression.

  5. Modelling the genetic risk in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Felix Grassmann

    Full Text Available Late-stage age-related macular degeneration (AMD is a common sight-threatening disease of the central retina affecting approximately 1 in 30 Caucasians. Besides age and smoking, genetic variants from several gene loci have reproducibly been associated with this condition and likely explain a large proportion of disease. Here, we developed a genetic risk score (GRS for AMD based on 13 risk variants from eight gene loci. The model exhibited good discriminative accuracy, area-under-curve (AUC of the receiver-operating characteristic of 0.820, which was confirmed in a cross-validation approach. Noteworthy, younger AMD patients aged below 75 had a significantly higher mean GRS (1.87, 95% CI: 1.69-2.05 than patients aged 75 and above (1.45, 95% CI: 1.36-1.54. Based on five equally sized GRS intervals, we present a risk classification with a relative AMD risk of 64.0 (95% CI: 14.11-1131.96 for individuals in the highest category (GRS 3.44-5.18, 0.5% of the general population compared to subjects with the most common genetic background (GRS -0.05-1.70, 40.2% of general population. The highest GRS category identifies AMD patients with a sensitivity of 7.9% and a specificity of 99.9% when compared to the four lower categories. Modeling a general population around 85 years of age, 87.4% of individuals in the highest GRS category would be expected to develop AMD by that age. In contrast, only 2.2% of individuals in the two lowest GRS categories which represent almost 50% of the general population are expected to manifest AMD. Our findings underscore the large proportion of AMD cases explained by genetics particularly for younger AMD patients. The five-category risk classification could be useful for therapeutic stratification or for diagnostic testing purposes once preventive treatment is available.

  6. Vitamin D and Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Alfredo Garcia Layana

    2017-10-01

    Full Text Available In recent years, the relationship between vitamin D and health has received growing attention from the scientific and medical communities. Vitamin D deficiencies have been repeatedly associated with various acute and chronic diseases, including age-related macular degeneration (AMD. Its active metabolite, 1α,25-dihydoxy vitamin D, acts as a modulator of cell proliferation, differentiation and apoptosis, and cumulative data from experimental and observational studies suggest that relatively a lower vitamin D status could be a potential risk factor for the development of early and/or late AMD. Herein, we made a narrative review of the mechanisms linking a potential role of vitamin D with the current concepts of AMD pathophysiology.

  7. Vitamin D and Age-Related Macular Degeneration.

    Science.gov (United States)

    Layana, Alfredo Garcia; Minnella, Angelo Maria; Garhöfer, Gerhard; Aslam, Tariq; Holz, Frank G; Leys, Anita; Silva, Rufino; Delcourt, Cécile; Souied, Eric; Seddon, Johanna M

    2017-10-13

    In recent years, the relationship between vitamin D and health has received growing attention from the scientific and medical communities. Vitamin D deficiencies have been repeatedly associated with various acute and chronic diseases, including age-related macular degeneration (AMD). Its active metabolite, 1α,25-dihydoxy vitamin D, acts as a modulator of cell proliferation, differentiation and apoptosis, and cumulative data from experimental and observational studies suggest that relatively a lower vitamin D status could be a potential risk factor for the development of early and/or late AMD. Herein, we made a narrative review of the mechanisms linking a potential role of vitamin D with the current concepts of AMD pathophysiology.

  8. Dizziness and Imbalance in the Elderly: Age-related Decline in the Vestibular System

    Science.gov (United States)

    Iwasaki, Shinichi; Yamasoba, Tatsuya

    2015-01-01

    Dizziness and imbalance are amongst the most common complaints in older people, and are a growing public health concern since they put older people at a significantly higher risk of falling. Although the causes of dizziness in older people are multifactorial, peripheral vestibular dysfunction is one of the most frequent causes. Benign paroxysmal positional vertigo is the most frequent form of vestibular dysfunction in the elderly, followed by Meniere’s disease. Every factor associated with the maintenance of postural stability deteriorates during aging. Age-related deterioration of peripheral vestibular function has been demonstrated through quantitative measurements of the vestibulo-ocular reflex with rotational testing and of the vestibulo-collic reflex with testing of vestibular evoked myogenic potentials. Age-related decline of vestibular function has been shown to correlate with the age-related decrease in the number of vestibular hair cells and neurons. The mechanism of age-related cellular loss in the vestibular endorgan is unclear, but it is thought that genetic predisposition and cumulative effect of oxidative stress may both play an important role. Since the causes of dizziness in older people are multi-factorial, management of this disease should be customized according to the etiologies of each individual. Vestibular rehabilitation is found to be effective in treating both unilateral and bilateral vestibular dysfunction. Various prosthetic devices have also been developed to improve postural balance in older people. Although there have been no medical treatments improving age-related vestibular dysfunction, new medical treatments such as mitochondrial antioxidants or caloric restriction, which have been effective in preventing age-related hearing loss, should be ienvestigated in the future. PMID:25657851

  9. Estrogen signalling in the pathogenesis of age-related macular degeneration.

    Science.gov (United States)

    Kaarniranta, Kai; Machalińska, Anna; Veréb, Zoltán; Salminen, Antero; Petrovski, Goran; Kauppinen, Anu

    2015-02-01

    Age-related macular degeneration (AMD) is a multifactorial eye disease that is associated with aging, family history, smoking, obesity, cataract surgery, arteriosclerosis, hypertension, hypercholesterolemia and unhealthy diet. Gender has commonly been classified as a weak or inconsistent risk factor for AMD. This disease is characterized by degeneration of retinal pigment epithelial (RPE) cells, Bruch's membrane, and choriocapillaris, which secondarily lead to damage and death of photoreceptor cells and central visual loss. Pathogenesis of AMD involves constant oxidative stress, chronic inflammation, and increased accumulation of lipofuscin and drusen. Estrogen has both anti-oxidative and anti-inflammatory capacity and it regulates signaling pathways that are involved in the pathogenesis of AMD. In this review, we discuss potential cellular signaling targets of estrogen in retinal cells and AMD pathology.

  10. [The Utilization of Health-Related Applications in Chronic Disease Self-Management].

    Science.gov (United States)

    Kao, Chi-Wen; Chuang, Hui-Wan; Chen, Ting-Yu

    2017-08-01

    The dramatic increase in smartphone usage has spurred the development of many health-related mobile applications (apps). On the other hand, population aging and the associated rise in the incidence of chronic disease is increasing the demand for long-term care. Effective chronic disease self-management has been shown to help patients improve their health condition. Numerous smartphone applications currently support patient self-management of chronic disease, facilitating health management and health promotion. The purpose of the present article was to introduce the definition, contents, and types of health-related apps; to discuss the effectiveness of self-management health-related apps in promoting chronic disease management; and to assess and evaluate these apps. We hope that the present article helps give to healthcare professionals and patients who are willing to manage their diseases a general understanding of health-related apps and their potential to facilitate the self-management of chronic diseases.

  11. Psychophysical function in age-related maculopathy.

    LENUS (Irish Health Repository)

    Neelam, Kumari

    2012-02-01

    Age-related macular degeneration (AMD), the late stage of age-related maculopathy (ARM), is the leading cause of blind registration in developed countries. The visual loss in AMD occurs due to dysfunction and death of photoreceptors (rods and cones) secondary to an atrophic or a neovascular event. The psychophysical tests of vision, which depend on the functional status of the photoreceptors, may detect subtle alterations in the macula before morphological fundus changes are apparent ophthalmoscopically, and before traditional measures of visual acuity exhibit deterioration, and may be a useful tool for assessing and monitoring patients with ARM. Furthermore, worsening of these visual functions over time may reflect disease progression, and some of these, alone or in combination with other parameters, may act as a prognostic indicator for identifying eyes at risk for developing neovascular AMD. Lastly, psychophysical tests often correlate with subjective and relatively undefined symptoms in patients with early ARM, and may reflect limitation of daily activities for ARM patients. However, clinical studies investigating psychophysical function have largely been cross-sectional in nature, with small sample sizes, and lack consistency in terms of the grading and classification of ARM. This article aims to comprehensively review the literature germane to psychophysical tests in ARM, and to furnish the reader with an insight into this complex area of research.

  12. Asbestos-related diseases in automobile mechanics.

    Science.gov (United States)

    Ameille, Jacques; Rosenberg, Nicole; Matrat, Mireille; Descatha, Alexis; Mompoint, Dominique; Hamzi, Lounis; Atassi, Catherine; Vasile, Manuela; Garnier, Robert; Pairon, Jean-Claude

    2012-01-01

    Automobile mechanics have been exposed to asbestos in the past, mainly due to the presence of chrysotile asbestos in brakes and clutches. Despite the large number of automobile mechanics, little is known about the non-malignant respiratory diseases observed in this population. The aim of this retrospective multicenter study was to analyse the frequency of pleural and parenchymal abnormalities on high-resolution computed tomography (HRCT) in a population of automobile mechanics. The study population consisted of 103 automobile mechanics with no other source of occupational exposure to asbestos, referred to three occupational health departments in the Paris area for systematic screening of asbestos-related diseases. All subjects were examined by HRCT and all images were reviewed separately by two independent readers; who in the case of disagreement discussed until they reached agreement. Multiple logistic regression models were constructed to investigate factors associated with pleural plaques. Pleural plaques were observed in five cases (4.9%) and interstitial abnormalities consistent with asbestosis were observed in one case. After adjustment for age, smoking status, and a history of non-asbestos-related respiratory diseases, multiple logistic regression models showed a significant association between the duration of exposure to asbestos and pleural plaques. The asbestos exposure experienced by automobile mechanics may lead to pleural plaques. The low prevalence of non-malignant asbestos-related diseases, using a very sensitive diagnostic tool, is in favor of a low cumulative exposure to asbestos in this population of workers.

  13. Asbestos-related diseases in automobile mechanics

    Science.gov (United States)

    Ameille, Jacques; Rosenberg, Nicole; Matrat, Mireille; Descatha, Alexis; Mompoint, Dominique; Hamzi, Lounis; Atassi, Catherine; Vasile, Manuela; Garnier, Robert; Pairon, Jean-Claude

    2012-01-01

    Purpose Automobile mechanics have been exposed to asbestos in the past, mainly due to the presence of chrysotile asbestos in brakes and clutches. Despite the large number of automobile mechanics, little is known about the non-malignant respiratory diseases observed in this population. The aim of this retrospective multicenter study was to analyze the frequency of pleural and parenchymal abnormalities on HRCT in a population of automobile mechanics. Methods The study population consisted of 103 automobile mechanics with no other source of occupational exposure to asbestos, referred to three occupational health departments in the Paris area for systematic screening of asbestos–related diseases. All subjects were examined by HRCT and all images were reviewed separately by two independent readers, with further consensus in the case of disagreement. Multiple logistic regression models were constructed to investigate factors associated with pleural plaques. Results Pleural plaques were observed in 5 cases (4.9%) and interstitial abnormalities consistent with asbestosis were observed in 1 case. After adjustment for age, smoking status, and a history of non-asbestos-related respiratory diseases, multiple logistic regression models showed a significant association between the duration of exposure to asbestos and pleural plaques. Conclusions The asbestos exposure experienced by automobile mechanics may lead to pleural plaques. The low prevalence of non-malignant asbestos-related diseases, using a very sensitive diagnostic tool, is in favor of a low cumulative exposure to asbestos in this population of workers. PMID:21965465

  14. Voluntary exercise confers protection against age-related deficits in brain oxygenation in awake mice model of Alzheimer's disease

    Science.gov (United States)

    Lu, Xuecong; Moeini, Mohammad; Li, Baoqiang; Sakadžić, Sava; Lesage, Frédéric

    2018-02-01

    Alzheimer's disease (AD) is a neurodegenerative disease characterized by short-term memory loss and cognitive inabilities. This work seeks to study the effects of voluntary exercise on the change in oxygen delivery in awake mice models of Alzheimer's disease by monitoring brain tissue oxygenation. Experiments were performed on Young (AD_Y, 3-4 months, n=8), Old (AD_O, 6-7 months, n=8), and Old with exercise (AD_OEX, 6-7 months, n=8) transgenic APPPS1 mice and their controls. Brain tissue oxygenation was measured by two photon phosphorescence lifetime microscopy on the left sensory motor cortex. We found that the average tissue PO2 decreased with age but were regulated by exercise. The results suggest a potential for exercise to improve brain function with age and AD.

  15. Diets based on virgin olive oil or fish oil but not on sunflower oil prevent age-related alveolar bone resorption by mitochondrial-related mechanisms.

    Directory of Open Access Journals (Sweden)

    Pedro Bullon

    Full Text Available Aging enhances frequency of chronic diseases like cardiovascular diseases or periodontitis. Here we reproduced an age-dependent model of the periodontium, a fully physiological approach to periodontal conditions, to evaluate the impact of dietary fat type on gingival tissue of young (6 months old and old (24 months old rats.Animals were fed life-long on diets based on monounsaturated fatty acids (MUFA as virgin olive oil, n-6 polyunsaturated fatty acids (n-6PUFA, as sunflower oil, or n-3PUFA, as fish oil. Age-related alveolar bone loss was higher in n-6PUFA fed rats, probably as a consequence of the ablation of the cell capacity to adapt to aging. Gene expression analysis suggests that MUFA or n-3PUFA allowed mitochondria to maintain an adequate turnover through induction of biogenesis, autophagy and the antioxidant systems, and avoiding mitochondrial electron transport system alterations.The main finding is that the enhanced alveolar bone loss associated to age may be targeted by an appropriate dietary treatment. The mechanisms involved in this phenomenon are related with an ablation of the cell capacity to adapt to aging. Thus, MUFA or n-3PUFA might allow mitochondrial maintaining turnover through biogenesis or autophagy. They might also be able to induce the corresponding antioxidant systems to counteract age-related oxidative stress, and do not inhibit mitochondrial electron transport chain. From the nutritional and clinical point of view, it is noteworthy that the potential treatments to attenuate alveolar bone loss (a feature of periodontal disease associated to age could be similar to some of the proposed for the prevention and treatment of cardiovascular diseases, a group of pathologies recently associated with age-related periodontitis.

  16. Serum levels of lipid metabolites in age-related macular degeneration

    OpenAIRE

    Orban, Tivadar; Johnson, William M.; Dong, Zhiqian; Maeda, Tadao; Maeda, Akiko; Sakai, Tsutomu; Tsuneoka, Hiroshi; Mieyal, John J.; Palczewski, Krzysztof

    2015-01-01

    Age-related macular degeneration (AMD) is a neurodegenerative disease that causes adult-onset blindness. There are 2 forms of this progressive disease: wet and dry. Currently there is no cure for AMD, but several treatment options have started to emerge making early detection critical for therapeutic success. Analysis of the eyes of Abca4−/−Rdh8−/− mice that display light-induced retinal degeneration indicates that 11-cis-retinal and docosahexaenoic acid (DHA) levels were significantly decrea...

  17. Fracture, aging and disease in bone

    Energy Technology Data Exchange (ETDEWEB)

    Ager, J.W.; Balooch, G.; Ritchie, R.O.

    2006-02-01

    From a public health perspective, developing a detailed mechanistic understanding of the well-known increase in fracture risk of human bone with age is essential. This also represents a challenge from materials science and fracture mechanics viewpoints. Bone has a complex, hierarchical structure with characteristic features ranging from nanometer to macroscopic dimensions; it is therefore significantly more complex than most engineering materials. Nevertheless, by examining the micro-/nano-structural changes accompanying the process of aging using appropriate multiscale experimental methods and relating them to fracture mechanics data, it is possible to obtain a quantitative picture of how bone resists fracture. As human cortical bone exhibits rising ex vivo crack-growth resistance with crack extension, its fracture toughness must be evaluated in terms of resistance-curve (R-curve) behavior. While the crack initiation toughness declines with age, the more striking finding is that the crack-growth toughness declines even more significantly and is essentially absent in bone from donors exceeding 85 years in age. To explain such an age-induced deterioration in the toughness of bone, we evaluate its fracture properties at multiple length scales, specifically at the molecular and nanodimensions using pico-force atomic-force microscopy, nanoindentation and vibrational spectroscopies, at the microscale using electron microscopy and hard/soft x-ray computed tomography, and at the macroscale using R-curve measurements. We show that the reduction in crack-growth toughness is associated primarily with a degradation in the degree of extrinsic toughening, in particular involving crack bridging, and that this occurs at relatively coarse size-scales in the range of tens to hundreds of micrometers. Finally, we briefly describe how specific clinical treatments, e.g., with steroid hormones to treat various inflammatory conditions, can prematurely damage bone, thereby reducing its

  18. Age-period-cohort analysis of infectious disease mortality in urban-rural China, 1990-2010.

    Science.gov (United States)

    Li, Zhi; Wang, Peigang; Gao, Ge; Xu, Chunling; Chen, Xinguang

    2016-03-31

    Although a number of studies on infectious disease trends in China exist, these studies have not distinguished the age, period, and cohort effects simultaneously. Here, we analyze infectious disease mortality trends among urban and rural residents in China and distinguish the age, period, and cohort effects simultaneously. Infectious disease mortality rates (1990-2010) of urban and rural residents (5-84 years old) were obtained from the China Health Statistical Yearbook and analyzed with an age-period-cohort (APC) model based on Intrinsic Estimator (IE). Infectious disease mortality is relatively high at age group 5-9, reaches a minimum in adolescence (age group 10-19), then rises with age, with the growth rate gradually slowing down from approximately age 75. From 1990 to 2010, except for a slight rise among urban residents from 2000 to 2005, the mortality of Chinese residents experienced a substantial decline, though at a slower pace from 2005 to 2010. In contrast to the urban residents, rural residents experienced a rapid decline in mortality during 2000 to 2005. The mortality gap between urban and rural residents substantially narrowed during this period. Overall, later birth cohorts experienced lower infectious disease mortality risk. From the 1906-1910 to the 1941-1945 birth cohorts, the decrease of mortality among urban residents was significantly faster than that of subsequent birth cohorts and rural counterparts. With the rapid aging of the Chinese population, the prevention and control of infectious disease in elderly people will present greater challenges. From 1990 to 2010, the infectious disease mortality of Chinese residents and the urban-rural disparity have experienced substantial declines. However, the re-emergence of previously prevalent diseases and the emergence of new infectious diseases created new challenges. It is necessary to further strengthen screening, immunization, and treatment for the elderly and for older cohorts at high risk.

  19. The effect of aging on brain barriers and the consequences for Alzheimer's disease development.

    Science.gov (United States)

    Gorlé, Nina; Van Cauwenberghe, Caroline; Libert, Claude; Vandenbroucke, Roosmarijn E

    2016-08-01

    Life expectancy has increased in most developed countries, which has led to an increase in the proportion of elderly people in the world's population. However, this increase in life expectancy is not accompanied by a lengthening of the health span since aging is characterized with progressive deterioration in cellular and organ functions. The brain is particularly vulnerable to disease, and this is reflected in the onset of age-related neurodegenerative diseases such as Alzheimer's disease. Research shows that dysfunction of two barriers in the central nervous system (CNS), the blood-brain barrier (BBB) and the blood-cerebrospinal fluid (CSF) barrier (BCSFB), plays an important role in the progression of these neurodegenerative diseases. The BBB is formed by the endothelial cells of the blood capillaries, whereas the BCSFB is formed by the epithelial cells of the choroid plexus (CP), both of which are affected during aging. Here, we give an overview of how these barriers undergo changes during aging and in Alzheimer's disease, thereby disturbing brain homeostasis. Studying these changes is needed in order to gain a better understanding of the mechanisms of aging at the brain barriers, which might lead to the development of new therapies to lengthen the health span (including mental health) and reduce the chances of developing Alzheimer's disease.

  20. Changes in the etiology of valvular heart disease in the rapidly aging Korean population.

    Science.gov (United States)

    Jang, Shin Yi; Ju, Eun-Young; Seo, Su Ra; Choi, Ji Yeon; Park, Sung-Ji; Kim, Duk-Kyung; Park, Seung Woo

    2014-06-15

    The aim of this study is to assess the changes in the causes of valvular heart disease between 2006 and 2011 in Korea. Data were collected from the Korean National Health Insurance Service from 2006 through 2011. These data consisted of primary diagnoses related to valvular heart disease regardless of other conditions. Valvular heart disease included non-rheumatic mitral valve disorders, non-rheumatic aortic valve disorders, rheumatic mitral valve disorders, and rheumatic aortic valve disorders. Overall, the age-standardized cumulative prevalence of non-rheumatic valvular heart disease was 70.6 per 100,000 persons in 2006 and 110.3 in 2011. This represented an increase from 42.2 to 65.2 in women and from 28.4 to 45.1 in men. In particular, there was a greater increase in prevalence in patients aged 65 years or older compared with groups aged 20-44 years or 45-64 years for both genders. The age-standardized cumulative prevalence of rheumatic valve disease did not change dramatically between 2006 and 2011. The overall age-standardized cumulative prevalence of non-rheumatic valvular heart diseases increased between 2006 and 2011, especially in individuals older than 65 years. These changes should be considered in future designs of cardiovascular healthcare services in countries with a rapidly aging population. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Self-reported optometric practise patterns in age-related macular degeneration.

    Science.gov (United States)

    Ly, Angelica; Nivison-Smith, Lisa; Zangerl, Barbara; Assaad, Nagi; Kalloniatis, Michael

    2017-11-01

    The use of advanced imaging in clinical practice is emerging and the use of this technology by optometrists in assessing patients with age-related macular degeneration is of interest. Therefore, this study explored contemporary, self-reported patterns of practice regarding age-related macular degeneration diagnosis and management using a cross-sectional survey of optometrists in Australia and New Zealand. Practising optometrists were surveyed on four key areas, namely, demographics, clinical skills and experience, assessment and management of age-related macular degeneration. Questions pertaining to self-rated competency, knowledge and attitudes used a five-point Likert scale. Completed responses were received from 127 and 87 practising optometrists in Australia and New Zealand, respectively. Advanced imaging showed greater variation in service delivery than traditional techniques (such as slitlamp funduscopy) and trended toward optical coherence tomography, which was routinely performed in age-related macular degeneration by 49 per cent of respondents. Optical coherence tomography was also associated with higher self-rated competency, knowledge and perceived relevance to practice than other modalities. Most respondents (93 per cent) indicated that they regularly applied patient symptoms, case history, visual function results and signs from traditional testing, when queried about their management of patients with age-related macular degeneration. Over half (63 per cent) also considered advanced imaging, while 31 per cent additionally considered all of these as well as the disease stage and clinical guidelines. Contrary to the evidence base, 68 and 34 per cent rated nutritional supplements as highly relevant or relevant in early age-related macular degeneration and normal aging changes, respectively. These results highlight the emergence of multimodal and advanced imaging (especially optical coherence tomography) in the assessment of age-related macular degeneration

  2. Conflict and diarrheal and related diseases: a global analysis.

    Science.gov (United States)

    Kerridge, Bradley T; Khan, Maria R; Rehm, Jürgen; Sapkota, Amir

    2013-12-01

    The purpose of this study was to determine the association between deaths owing to terrorism, civil war and one-sided violence from 1994-2000 and disability-adjusted life years (DALYs) attributable to diarrheal and related diseases, schistosomiasis, trachoma and the nematode infections (DSTN diseases) in 2002 among World Health Organization Member States. Deaths resulting from terrorism, civil war and one-sided violence were significantly related to DSTN DALYs across the majority of sex-age subgroups of the populace, after controlling for baseline levels of improved water/sanitation and a variety of economic measures: overall, a 1.0% increase in deaths owing to terrorism and related violence was associated with an increase of 0.16% in DALYs lost to DSTN diseases. Associations were greatest among 0-to-4-year olds. The results of the present study suggest that DSTN disease control efforts should target conflict-affected populations with particular attention to young children who suffer disproportionately from DSTN diseases in these settings. In view of the evidence that terrorism and related violence may influence DSTN DALYs in the longer term, control strategies should move beyond immediate responses to decrease the incidence and severity of DSTN diseases to seek solutions through bolstering health systems infrastructure development among conflict-affected populations. Copyright © 2013. Published by Elsevier Ltd.

  3. Imaging movement-related activity in medicated Parkin-associated and sporadic Parkinson's disease

    DEFF Research Database (Denmark)

    van Eimeren, Thilo; Binkofski, Ferdinand; Buhmann, Carsten

    2010-01-01

    Treatment-related motor complications such as dyskinesias are a major problem in the long-term management of Parkinson's disease (PD). In sporadic PD, a relatively early onset of the disease is known to be associated with an early development of dyskinesias. Although linked with early onset...... selected movements. Patients with Parkin-associated and sporadic PD showed no difference in movement-related activation patterns. Moreover, the covariates 'age' and 'disease duration' similarly influenced brain activation in both patient groups. The present finding suggests that a stable long-term motor...

  4. Nutritional supplements in age-related macular degeneration.

    Science.gov (United States)

    Schmidl, Doreen; Garhöfer, Gerhard; Schmetterer, Leopold

    2015-03-01

    Age-related macular degeneration (AMD) is the most frequent cause of blindness in the Western World. While with new therapies that are directed towards vascular endothelial growth factor (VEGF), a potentially efficient treatment option for the wet form of the disease has been introduced, a therapeutic regimen for dry AMD is still lacking. There is evidence from several studies that oral intake of supplements is beneficial in preventing progression of the disease. Several formulations of micronutrients are currently available. The present review focuses on the role of supplements in the treatment and prevention of AMD and sums up the current knowledge about the most frequently used micronutrients. In addition, regulatory issues are discussed, and future directions for the role of supplementation in AMD are highlighted. © 2015 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  5. SIRT2 as a therapeutic target for age-related disorders

    Directory of Open Access Journals (Sweden)

    RIta eMachado de Oliveira

    2012-05-01

    Full Text Available Sirtuin proteins are conserved regulators of aging that have recently emerged as important modifiers of several diseases which commonly occur later in life, such as cancer, diabetes, cardiovascular and neurodegenerative diseases. In mammals, there are seven sirtuins (SIRT1-7, which display diversity in subcellular localization and function. SIRT1 has received much of attention due to its possible impact on longevity, while important biological and therapeutic roles of other sirtuins have been underestimated and just recently recognized. Here we focus on SIRT2, a member of the sirtuin family, and discuss its role in cellular and tissue-specific functions. This review summarizes the main scientific advances on SIRT2 protein biology and explores its potential as a therapeutic target for treatment of age-related disorders.

  6. Age related macular degeneration - modern diagnostic and therapeutic preventive approach

    OpenAIRE

    Gogelová, Blanka

    2009-01-01

    Age-related macular degeneration (AMD) is a disease associated with aging that gradually destroys sharp, central vision. Central vision is needed for seeing objects clearly and for common daily tasks such as reading and driving. AMD affects the macula, the part of the eye that alows seeing of fine details. AMD occurs in two form: dry and wet. In dry AMD, the light sensitive cells in the macula slowly break down. As fewer cells in the macula are able to function, people will see details less c...

  7. Quality of life and relation to disease in patients with bone sarcoma.

    Directory of Open Access Journals (Sweden)

    Shchelkova O.Yu.

    2015-03-01

    Full Text Available The study aimed to investigate the basic aspects of quality of life and relation to disease in patients with malignant or premalignant bone tumors. Study participants (N=82 were aged 18 to 67 years (average age 34 ± 2 years. They were separated into three groups depending on diagnosis: patients with osteosarcoma, patients with giant cell tumor and patients with chondrosarcoma. The SF-36 Health Status Survey and the Quality of Life Questionnaire - Core 30 with Bone Metastasis (BM22 Module were used to assess patient quality of life. The type of relation to disease method (TOBOL was used to determine the relation to disease of the patients. According to the results of the quality of life study, patients with giant cell tumor exhibited the highest degree of limiting physical activity and reduced social functioning, the greatest financial difficulties and more pain sites than either patients with osteosarcoma or patients with chondrosarcoma. The study of relation to disease revealed that all studied groups of patients were susceptible to ergopathic and sensitive types of relation to disease. Moreover, patients with giant cell tumor experienced increased levels of tension and irritability with respect to relation to disease and treatment, while patients with chondrosarcoma were more susceptible to anxiety and hypochondria with respect to relation to disease. Patients with different types of bone tumors have different experiences with respect to their physical and mental health, their social functioning and their general health. The results of the study may be useful in developing individualized psychological aid programs for patients with malignant and premalignant bone tumors.

  8. Diet, ageing and genetic factors in the pathogenesis of diverticular disease

    Science.gov (United States)

    Commane, Daniel Martin; Arasaradnam, Ramesh Pulendran; Mills, Sarah; Mathers, John Cummings; Bradburn, Mike

    2009-01-01

    Diverticular disease (DD) is an age-related disorder of the large bowel which may affect half of the population over the age of 65 in the UK. This high prevalence ranks it as one of the most common bowel disorders in western nations. The majority of patients remain asymptomatic but there are associated life-threatening co-morbidities, which, given the large numbers of people with DD, translates into a considerable number of deaths per annum. Despite this public health burden, relatively little seems to be known about either the mechanisms of development or causality. In the 1970s, a model of DD formulated the concept that diverticula occur as a consequence of pressure-induced damage to the colon wall amongst those with a low intake of dietary fiber. In this review, we have examined the evidence regarding the influence of ageing, diet, inflammation and genetics on DD development. We argue that the evidence supporting the barotrauma hypothesis is largely anecdotal. We have also identified several gaps in the knowledge base which need to be filled before we can complete a model for the etiology of diverticular disease. PMID:19468998

  9. Age-related changes in the retinal pigment epithelium (RPE.

    Directory of Open Access Journals (Sweden)

    Xiaorong Gu

    Full Text Available Age-related changes in the retina are often accompanied by visual impairment but their mechanistic details remain poorly understood.Proteomic studies were pursued toward a better molecular understanding of retinal pigment epithelium (RPE aging mechanisms. RPE cells were isolated from young adults (3-4 month-old and old (24-25 month-old F344BN rats, and separated into subcellular fractions containing apical microvilli (MV and RPE cell bodies (CB lacking their apical microvilli. Proteins were extracted in detergent, separated by SDS-PAGE, digested in situ with trypsin and analyzed by LC MS/MS. Select proteins detected in young and old rat RPE were further studied using immunofluorescence and Western blot analysis.A total of 356 proteins were identified in RPE MV from young and 378 in RPE MV from old rats, 48% of which were common to each age group. A total of 897 proteins were identified in RPE CB from young rats and 675 in old CB, 56% of which were common to each age group. Several of the identified proteins, including proteins involved in response to oxidative stress, displayed both quantitative and qualitative changes in overall abundance during RPE aging. Numerous proteins were identified for the first time in the RPE. One such protein, collectrin, was localized to the apical membrane of apical brush border of proximal tubules where it likely regulates several amino acid transporters. Elsewhere, collectrin is involved in pancreatic β cell proliferation and insulin secretion. In the RPE, collectrin expression was significantly modulated during RPE aging. Another age-regulated, newly described protein was DJ-1, a protein extensively studied in brain where oxidative stress-related functions have been described.The data presented here reveals specific changes in the RPE during aging, providing the first protein database of RPE aging, which will facilitate future studies of age-related retinal diseases.

  10. Mechanisms and Implications of Age-Related Changes in the Liver: Nonalcoholic Fatty Liver Disease in the Elderly

    Directory of Open Access Journals (Sweden)

    Lay Gan

    2011-01-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD is hepatic steatosis associated with metabolic abnormalities such as overweight/central obesity, insulin resistance, type 2 diabetes (T2D, and dyslipidemia. NAFLD is becoming the most common liver disease in contemporary society, with the highest prevalence in those over 60 years. NAFLD pathology ranges from simple steatosis to a necroinflammatory fibrosing disorder called steatohepatitis (SH, the latter associated with high risk of developing cirrhosis, often occuring in the seventh to ninth decades of life. While the main health implications of NAFLD are increased risk of developing T2D, cardiovascular diseases, and common cancers, there is substantantially increased standardized mortality, and deaths from decompensated cirrhosis and hepatocellular carcinoma (HCC. Little is known about the interactive effects of ageing and NAFLD, with most studies focusing on the younger population. This paper summarises the epidemiology, pathogenesis, and clinical course of NAFLD, with particular attention to persons over age 60 years. An approach to the management of NASH and its complications in the elderly, will also be presented here.

  11. A data mining approach for classifying DNA repair genes into ageing-related or non-ageing-related

    Directory of Open Access Journals (Sweden)

    Vasieva Olga

    2011-01-01

    Full Text Available Abstract Background The ageing of the worldwide population means there is a growing need for research on the biology of ageing. DNA damage is likely a key contributor to the ageing process and elucidating the role of different DNA repair systems in ageing is of great interest. In this paper we propose a data mining approach, based on classification methods (decision trees and Naive Bayes, for analysing data about human DNA repair genes. The goal is to build classification models that allow us to discriminate between ageing-related and non-ageing-related DNA repair genes, in order to better understand their different properties. Results The main patterns discovered by the classification methods are as follows: (a the number of protein-protein interactions was a predictor of DNA repair proteins being ageing-related; (b the use of predictor attributes based on protein-protein interactions considerably increased predictive accuracy of attributes based on Gene Ontology (GO annotations; (c GO terms related to "response to stimulus" seem reasonably good predictors of ageing-relatedness for DNA repair genes; (d interaction with the XRCC5 (Ku80 protein is a strong predictor of ageing-relatedness for DNA repair genes; and (e DNA repair genes with a high expression in T lymphocytes are more likely to be ageing-related. Conclusions The above patterns are broadly integrated in an analysis discussing relations between Ku, the non-homologous end joining DNA repair pathway, ageing and lymphocyte development. These patterns and their analysis support non-homologous end joining double strand break repair as central to the ageing-relatedness of DNA repair genes. Our work also showcases the use of protein interaction partners to improve accuracy in data mining methods and our approach could be applied to other ageing-related pathways.

  12. IgG4-related disease with sinonasal involvement: A case series

    International Nuclear Information System (INIS)

    Prabhu, Shailesh M; Yadav, Vikas; Irodi, Aparna; Mani, Sunithi; Varghese, Ajoy Mathew

    2014-01-01

    We present the imaging findings in two cases of IgG4-related disease involving the sinonasal region in the pediatric age group. Imaging findings in IgG4-related disease affecting the nasal cavity and paranasal sinuses have been rarely reported in literature. The diagnosis is made by a combination of clinical, imaging, and histopathologic findings. Radiologists should be aware of the imaging findings of this condition to ensure early diagnosis and treatment

  13. Epigenetic Control of Stem Cell Potential During Homeostasis, Aging, and Disease

    Science.gov (United States)

    Beerman, Isabel; Rossi, Derrick J.

    2015-01-01

    Stem cell decline is an important cellular driver of aging-associated pathophysiology in multiple tissues. Epigenetic regulation is central to establishing and maintaining stem cell function, and emerging evidence indicates that epigenetic dysregulation contributes to the altered potential of stem cells during aging. Unlike terminally differentiated cells, the impact of epigenetic dysregulation in stem cells is propagated beyond self; alterations can be heritably transmitted to differentiated progeny, in addition to being perpetuated and amplified within the stem cell pool through self-renewal divisions. This review focuses on recent studies examining epigenetic regulation of tissue-specific stem cells in homeostasis, aging, and aging-related disease. PMID:26046761

  14. Modifiable risk factors in periodontitis: at the intersection of aging and disease.

    Science.gov (United States)

    Reynolds, Mark A

    2014-02-01

    Chronic inflammation is a prominent feature of aging and of common age-related diseases, including atherosclerosis, cancer and periodontitis. This volume examines modifiable risk factors for periodontitis and other chronic inflammatory diseases. Oral bacterial communities and viral infections, particularly with cytomegalovirus and other herpesviruses, elicit distinct immune responses and are central in the initiation of periodontal diseases. Risk of disease is dynamic and changes in response to complex interactions of genetic, environmental and stochastic factors over the lifespan. Many modifiable risk factors, such as smoking and excess caloric intake, contribute to increases in systemic markers of inflammation and can modify gene regulation through a variety of biologic mechanisms (e.g. epigenetic modifications). Periodontitis and other common chronic inflammatory diseases share multiple modifiable risk factors, such as tobacco smoking, psychological stress and depression, alcohol consumption, obesity, diabetes, metabolic syndrome and osteoporosis. Interventions that target modifiable risk factors have the potential to improve risk profiles for periodontitis as well as for other common chronic diseases. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Fluency in Parkinson?s disease: disease duration, cognitive status and age

    Directory of Open Access Journals (Sweden)

    Natalia Casagrande Brabo

    2014-05-01

    Full Text Available The objective of this study was to determine the frequency of occurrence and to characterize the typology of dysfluencies in individuals with Parkinson’s disease (PD, including the variables age, gender, schooling, disease duration, score on the Hoehn and Yahr scale and cognitive status (score on Mini-Mental State Examination. A cross-sectional study of a sample comprising 60 adults matched for gender, age and schooling was conducted. Group I comprised 30 adults with idiopathic PD, and Group II comprised 30 healthy adults. For assessment of fluency of speech, subjects were asked to utter a narrative based on a sequence of drawings and a transcription of 200 fluent syllables was performed to identify speech dysfluencies. PD patients exhibited a higher overall number of dysfluencies in speech with a large number of atypical dysfluencies. Additionally, results showed an influence of the variables cognitive status, disease duration and age on occurrence of dysfluencies.

  16. Stressors of School-age Children With Allergic Diseases: A Qualitative Study.

    Science.gov (United States)

    Iio, Misa; Hamaguchi, Mana; Nagata, Mayumi; Yoshida, Koichi

    2018-05-08

    Most studies of stress in children with chronic diseases have been geared toward parents and caregivers have not considered allergic diseases together. This study aimed to identify the stressors associated with allergic diseases in Japanese school-age children. Stressors associated with allergic diseases of 11 school-age children (seven boys and four girls; age range: 9-12 years) were investigated using semi-structured interviews. In the qualitative thematic analysis of stressors about allergic diseases, two themes: allergic disease-specific stressors and common stressors in chronic diseases, and 12 categories were identified. A thematic map was applied to four domains of stressor: physiological factors, psychological factors, social factors, and environmental factors. The results showed that school-age children with allergic diseases have a variety of stressors. Future studies should aim to develop an allergic disease-specific stress management program with school-age children. In children with allergic diseases, not only is stress management in daily life important, but also stress management for disease-specific matters to control the symptoms and maintain mental health. Stress management should be supported for school-age children with allergic diseases. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. TIA, stroke and orthostatic hypotension: a disease spectrum related to ageing vasculature?

    Science.gov (United States)

    Kwok, C S; Ong, A C L; Potter, J F; Metcalf, A K; Myint, P K

    2014-06-01

    We sought to identify the determinants of orthostatic hypotension (OH) among patients referred to the transient ischaemic attack (TIA) clinic. We conducted a retrospective analysis of prospectively collected data on patients who attended the TIA clinic in a UK hospital between January 2006 and September 2009. Each patient had their supine and standing or sitting blood pressure measured. Logistic regression was used to estimate the univariate and multivariate odds of OH for the subgroups of patients based on their diagnosis. A 10% significance level for the univariate analysis was used to identify variables in the multivariate model. A total of 3222 patients were studied of whom 1131 had a TIA, 665 a stroke and 1426 had other diagnoses. The prevalence of either systolic or diastolic OH in the TIA, stroke and patients with other diagnoses was similar being 22% (n = 251), 24% (n = 162) and 20% (n = 292), respectively. Multivariate analyses showed age, prior history of TIA, and diabetes were independently significantly associated with systolic OH alone or diastolic OH alone or either systolic or diastolic OH [ORs 1.03 (1.02-1.05); 1.56 (1.05-2.31); 1.65 (1.10-2.47), respectively]. Among the patients with the diagnosis of stroke, peripheral vascular disease (PVD) was significantly associated with increased odds of OH (3.56, 1.53-8.31), whereas male gender had a significantly lower odds of OH (0.61, 0.42-0.88). In patients with other diagnoses, age (1.04, 1.02-1.05) and diabetes (1.47, 1.04-2.09) were associated with OH, whereas male gender was (0.76, 0.58-1.00) not associated with OH. Orthostatic hypotension is prevalent among patients presenting to TIA clinic. Previous history of vascular disease (prior TIA/stroke/PVD) appears to be a significant associate of OH in this patient population. © 2014 John Wiley & Sons Ltd.

  18. Gene expression changes for antioxidants pathways in the mouse cochlea: relations to age-related hearing deficits.

    Directory of Open Access Journals (Sweden)

    Sherif F Tadros

    Full Text Available Age-related hearing loss - presbycusis - is the number one neurodegenerative disorder and top communication deficit of our aged population. Like many aging disorders of the nervous system, damage from free radicals linked to production of reactive oxygen and/or nitrogen species (ROS and RNS, respectively may play key roles in disease progression. The efficacy of the antioxidant systems, e.g., glutathione and thioredoxin, is an important factor in pathophysiology of the aging nervous system. In this investigation, relations between the expression of antioxidant-related genes in the auditory portion of the inner ear - cochlea, and age-related hearing loss was explored for CBA/CaJ mice. Forty mice were classified into four groups according to age and degree of hearing loss. Cochlear mRNA samples were collected and cDNA generated. Using Affymetrix® GeneChip, the expressions of 56 antioxidant-related gene probes were analyzed to estimate the differences in gene expression between the four subject groups. The expression of Glutathione peroxidase 6, Gpx6; Thioredoxin reductase 1, Txnrd1; Isocitrate dehydrogenase 1, Idh1; and Heat shock protein 1, Hspb1; were significantly different, or showed large fold-change differences between subject groups. The Gpx6, Txnrd1 and Hspb1 gene expression changes were validated using qPCR. The Gpx6 gene was upregulated while the Txnrd1 gene was downregulated with age/hearing loss. The Hspb1 gene was found to be downregulated in middle-aged animals as well as those with mild presbycusis, whereas it was upregulated in those with severe presbycusis. These results facilitate development of future interventions to predict, prevent or slow down the progression of presbycusis.

  19. Synchronizing an aging brain: can entraining circadian clocks by food slow Alzheimer's disease?

    Science.gov (United States)

    Kent, Brianne A

    2014-01-01

    Alzheimer's disease (AD) is a global epidemic. Unfortunately, we are still without effective treatments or a cure for this disease, which is having devastating consequences for patients, their families, and societies around the world. Until effective treatments are developed, promoting overall health may hold potential for delaying the onset or preventing neurodegenerative diseases such as AD. In particular, chronobiological concepts may provide a useful framework for identifying the earliest signs of age-related disease as well as inexpensive and noninvasive methods for promoting health. It is well reported that AD is associated with disrupted circadian functioning to a greater extent than normal aging. However, it is unclear if the central circadian clock (i.e., the suprachiasmatic nucleus) is dysfunctioning, or whether the synchrony between the central and peripheral clocks that control behavior and metabolic processes are becoming uncoupled. Desynchrony of rhythms can negatively affect health, increasing morbidity and mortality in both animal models and humans. If the uncoupling of rhythms is contributing to AD progression or exacerbating symptoms, then it may be possible to draw from the food-entrainment literature to identify mechanisms for re-synchronizing rhythms to improve overall health and reduce the severity of symptoms. The following review will briefly summarize the circadian system, its potential role in AD, and propose using a feeding-related neuropeptide, such as ghrelin, to synchronize uncoupled rhythms. Synchronizing rhythms may be an inexpensive way to promote healthy aging and delay the onset of neurodegenerative disease such as AD.

  20. Onset of mortality increase with age and age trajectories of mortality from all diseases in the four Nordic countries

    Directory of Open Access Journals (Sweden)

    Dolejs J

    2017-01-01

    Full Text Available Josef Dolejs,1 Petra Marešová2 1Department of Informatics and Quantitative Methods, 2Department of Economics, Faculty of Informatics and Management, University of Hradec Králové, Hradec Králové, Czech Republic Background: The answer to the question “At what age does aging begin?” is tightly related to the question “Where is the onset of mortality increase with age?” Age affects mortality rates from all diseases differently than it affects mortality rates from nonbiological causes. Mortality increase with age in adult populations has been modeled by many authors, and little attention has been given to mortality decrease with age after birth.Materials and methods: Nonbiological causes are excluded, and the category “all diseases” is studied. It is analyzed in Denmark, Finland, Norway, and Sweden during the period 1994–2011, and all possible models are screened. Age trajectories of mortality are analyzed separately: before the age category where mortality reaches its minimal value and after the age category.Results: Resulting age trajectories from all diseases showed a strong minimum, which was hidden in total mortality. The inverse proportion between mortality and age fitted in 54 of 58 cases before mortality minimum. The Gompertz model with two parameters fitted as mortality increased with age in 17 of 58 cases after mortality minimum, and the Gompertz model with a small positive quadratic term fitted data in the remaining 41 cases. The mean age where mortality reached minimal value was 8 (95% confidence interval 7.05–8.95 years. The figures depict an age where the human population has a minimal risk of death from biological causes.Conclusion: Inverse proportion and the Gompertz model fitted data on both sides of the mortality minimum, and three parameters determined the shape of the age–mortality trajectory. Life expectancy should be determined by the two standard Gompertz parameters and also by the single parameter in

  1. Sleep-related erections throughout the ages.

    Science.gov (United States)

    van Driel, Mels F

    2014-07-01

    The occurrence of sleep-related erections (SREs) has been known since antiquity. To highlight historical, theological, and sexual medicine-related aspects of SREs throughout the ages. Review of old medical books on male sexual functioning and review of scientific medical and theological articles on SREs from about 1900 on. The cyclic character of SREs was first noted by German researchers in the forties of the 20th century. However, already before the beginning of the Christian era, one knew that men had erections and ejaculations during sleep. In the Middle Ages, SREs were generally considered to be rebellious manifestations of the male body, while it seemed to disobey its owner and showed up its perverted and sinful side. From the fifteenth to the end of the 17th century, severe erectile dysfunction (ED) was ground for divorce. The ecclesiastical court records show that if necessary, the members of the jury sat at the defendant's bedside at night to be able to judge any SREs occurring. Since the 17th century, SREs were considered to be part of masturbation, which could cause many ailments and diseases. Psychoanalyst Stekel acknowledged in 1920 that a morning erection, the last SRE, is a naturally occurring phenomenon in healthy men from infancy to old age. Today, some scientists assume that SREs protect the integrity of the penile cavernous bodies. Throughout the ages, philosophers, theologians, physicians, members of ecclesial law courts, psychoanalysts, psychiatrists, sexologists, physiologists, and urologists have shown interest in SREs. Obviously, the observations and testing of SREs have a long history, from antiquity to modern sleep labs, in men and in women, in newborns and old adults, by penis rings with sharp spikes to fancy strain gauge devices. Despite all these efforts, the mechanisms leading to SREs and its function are however not yet completely understood. © 2014 International Society for Sexual Medicine.

  2. Heart Disease Affects Women of All Ages

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Heart Disease Affects Women of All Ages Past Issues / Winter ... weeks of a heart attack. For Women with Heart Disease: About 6 million American women have coronary heart ...

  3. IgG4-related disease simulating Hodgkin lymphoma in a child

    Directory of Open Access Journals (Sweden)

    D. Eric Ewing, MD

    2016-06-01

    Full Text Available Immunoglobulin (Ig G4-related disease is a recently described syndrome characterized by mass forming lymphoplasmacytic tissue infiltration and elevated serum IgG4 concentrations usually affecting middle-aged or older individuals. Lymphadenopathy is frequently observed and is sometimes the first or only manifestation of the disease. We report a case of IgG4-related disease mimicking Hodgkin lymphoma in a 13-year-old girl. The patient presented with progressive unilateral cervical lymphadenopathy of several months duration. Biopsy showed follicular hyperplasia with progressive transformation of germinal centers. Interfollicular areas were expanded by small lymphocytes, histiocytes, eosinophils and fibrosis with occasional CD30 positive cells initially concerning for interfollicular Hodgkin lymphoma. Immunohistochemical analysis revealed an intrafollicular plasmacytosis with an IgG4-positive/IgG-positive plasma cell ratio of 50% supporting a diagnosis of IgG4-related lymphadenopathy, progressively transformed germinal centers type. Laboratory studies were supportive with elevated serum IgG4 (178 mg/dL and IgE (30.40 kU/L levels along with an elevated serum IgG4/IgG ratio (0.16. Very few cases of IgG4-related disease have been described in children. Within this age group, there is considerable clinical overlap between IgG4-related disease associated lymphadenopathy and Hodgkin lymphoma. In addition, lymphadenopathy secondary to IgG4-related disease demonstrates substantial histologic diversity with the potential to simulate the inflammatory background and fibrosis of Hodgkin lymphoma. The importance of accurate diagnosis is underscored by the prognostic implications considering the marked response of the syndrome to steroid therapy. In addition, appropriate follow up is critical to monitor for relapse and additional organ involvement.

  4. [Physiological ageing is not a disease].

    Science.gov (United States)

    Delmas, Philippe

    2014-01-01

    Physiological ageing is a slow process which brings about natural changes in the functioning of the organism. These changes are to be distinguished from the effects of diseases. Nurses, who care for more and more elderly people due to the ageing of the population, must be able to distinguish between these changes to adjust their practice.

  5. Relations between Household Livestock Ownership, Livestock Disease, and Young Child Growth.

    Science.gov (United States)

    Mosites, Emily; Thumbi, Samuel M; Otiang, Elkanah; McElwain, Terry F; Njenga, M K; Rabinowitz, Peter M; Rowhani-Rahbar, Ali; Neuhouser, Marian L; May, Susanne; Palmer, Guy H; Walson, Judd L

    2016-05-01

    In resource-limited settings in which child malnutrition is prevalent, humans live in close proximity to household livestock. However, the relation between household livestock and child nutrition represents a considerable knowledge gap. We assessed whether household livestock ownership or livestock disease episodes were associated with growth in young children in western Kenya. We incorporated monthly anthropometric measurements for children livestock ownership was related to baseline child height for age or prospective growth rate. We also evaluated whether livestock disease episodes were associated with child growth rate over 11 mo of follow-up. We collected data on 925 children over the course of follow-up. Greater household livestock ownership at baseline was not related to baseline child height-for-age z score (adjusted β: 0.01 SD; 95% CI: -0.02, 0.04 SD) or child growth rate (adjusted β: 0.02 cm/y; 95% CI: -0.03, 0.07 cm/y). Livestock disease episodes were not significantly associated with child growth across the entire cohort (adjusted β: -0.007 cm/mo; 95% CI: -0.02, 0.006 cm/mo). However, children in households with livestock digestive disease between June and November gained less height than did children in households that did not report livestock disease (β: -0.063 cm/mo; 95% CI: -0.112, -0.016 cm/mo). Children livestock digestive disease gained less weight than did those who did not report disease (β: -0.033 kg/mo; 95% CI: -0.063, -0.003 kg/mo). In this cohort of young children in western Kenya, we did not find an association between ownership of livestock and child growth status. However, disease episodes in household livestock may be related to a lower child growth rate in some groups. © 2016 American Society for Nutrition.

  6. Calorie restriction: A new therapeutic intervention for age-related dry eye disease in rats

    International Nuclear Information System (INIS)

    Kawashima, Motoko; Kawakita, Tetsuya; Okada, Naoko; Ogawa, Yoko; Murat, Dogru; Nakamura, Shigeru; Nakashima, Hideo; Shimmura, Shigeto; Shinmura, Ken; Tsubota, Kazuo

    2010-01-01

    A decrease in lacrimal gland secretory function is closely related to aging and leads to an increased prevalence of dry eye syndrome. Since calorie restriction (CR) is considered to prevent functional decline of various organs due to aging, we hypothesized that CR could prevent age-related lacrimal dysfunction. Six-month-old male Fischer 344 rats were randomly divided into ad libitum (AL) and CR (-35%) groups. After 6 months of CR, tear function was examined under conscious state. After euthanasia, lacrimal glands were subjected to histological examination, tear protein secretion stimulation test with Carbachol, and assessment of oxidative stress with 8-hydroxy-2 deoxyguanosine (8-OHdG) and 4-hydroxynonenal (HNE) antibodies. CR significantly improved tear volume and tended to increase tear protein secretion volume after stimulation with Carbachol compared to AL. The acinar unit density was significantly higher in the CR rats compared to AL rats. Lacrimal glands in the CR rats showed a lesser degree of interstitial fibrosis. CR reduced the concentration of 8-OHdG and the extent of staining with HNE in the lacrimal gland, compared to AL. Furthermore, our electron microscopic observations showed that mitochondrial structure of the lacrimal gland obtained from the middle-aged CR rats was preserved in comparison to the AL rats. Collectively, these results demonstrate for the first time that CR may attenuate oxidative stress related damage in the lacrimal gland with preservation of lacrimal gland functions. Although molecular mechanism(s) by which CR maintains lacrimal gland function remains to be resolved, CR might provide a novel therapeutic strategy for treating dry eye syndrome.

  7. Calorie restriction: A new therapeutic intervention for age-related dry eye disease in rats

    Energy Technology Data Exchange (ETDEWEB)

    Kawashima, Motoko; Kawakita, Tetsuya; Okada, Naoko; Ogawa, Yoko [Department of Ophthalmology, Keio University School of Medicine, Tokyo (Japan); Murat, Dogru [Department of Ocular Surface and Visual Optics, Keio University School of Medicine, Tokyo (Japan); Nakamura, Shigeru; Nakashima, Hideo [Research Center, Ophtecs Corporation, Hyogo (Japan); Shimmura, Shigeto [Department of Ophthalmology, Keio University School of Medicine, Tokyo (Japan); Shinmura, Ken [Division of Geriatric Medicine, Department of Internal Medicine, Keio University School of Medicine, Tokyo (Japan); Tsubota, Kazuo, E-mail: tsubota@sc.itc.keio.ac.jp [Department of Ophthalmology, Keio University School of Medicine, Tokyo (Japan)

    2010-07-09

    A decrease in lacrimal gland secretory function is closely related to aging and leads to an increased prevalence of dry eye syndrome. Since calorie restriction (CR) is considered to prevent functional decline of various organs due to aging, we hypothesized that CR could prevent age-related lacrimal dysfunction. Six-month-old male Fischer 344 rats were randomly divided into ad libitum (AL) and CR (-35%) groups. After 6 months of CR, tear function was examined under conscious state. After euthanasia, lacrimal glands were subjected to histological examination, tear protein secretion stimulation test with Carbachol, and assessment of oxidative stress with 8-hydroxy-2 deoxyguanosine (8-OHdG) and 4-hydroxynonenal (HNE) antibodies. CR significantly improved tear volume and tended to increase tear protein secretion volume after stimulation with Carbachol compared to AL. The acinar unit density was significantly higher in the CR rats compared to AL rats. Lacrimal glands in the CR rats showed a lesser degree of interstitial fibrosis. CR reduced the concentration of 8-OHdG and the extent of staining with HNE in the lacrimal gland, compared to AL. Furthermore, our electron microscopic observations showed that mitochondrial structure of the lacrimal gland obtained from the middle-aged CR rats was preserved in comparison to the AL rats. Collectively, these results demonstrate for the first time that CR may attenuate oxidative stress related damage in the lacrimal gland with preservation of lacrimal gland functions. Although molecular mechanism(s) by which CR maintains lacrimal gland function remains to be resolved, CR might provide a novel therapeutic strategy for treating dry eye syndrome.

  8. Adaptation to Low Vision Caused by Age-Related Macular Degeneration: A Case Study

    Science.gov (United States)

    Smith, Theresa Marie

    2008-01-01

    One in eight Americans aged 65 and older has an eye disease resulting in low vision, and more women than men are visually impaired, mainly because women live longer. Age-related visual impairments are an indicator of a decline in activities of daily living and self-help skills. The top eye conditions that affect older adults are macular…

  9. Age-related oral changes.

    LENUS (Irish Health Repository)

    Mckenna, Gerald

    2010-10-01

    Age-related oral changes are seen in the oral hard and soft tissues as well as in bone, the temporomandibular joints and the oral mucosa. As older patients retain their natural teeth for longer, the clinical picture consists of normal physiological age changes in combination with pathological and iatrogenic effects. Clinical Relevance: With an ageing population retaining more of its natural teeth for longer, dental professionals should expect to observe oral age changes more frequently.

  10. Environmental stress, ageing and glial cell senescence: a novel mechanistic link to Parkinson's disease?

    Science.gov (United States)

    Chinta, S J; Lieu, C A; Demaria, M; Laberge, R-M; Campisi, J; Andersen, J K

    2013-05-01

    Exposure to environmental toxins is associated with a variety of age-related diseases including cancer and neurodegeneration. For example, in Parkinson's disease (PD), chronic environmental exposure to certain toxins has been linked to the age-related development of neuropathology. Neuronal damage is believed to involve the induction of neuroinflammatory events as a consequence of glial cell activation. Cellular senescence is a potent anti-cancer mechanism that occurs in a number of proliferative cell types and causes the arrest of proliferation of cells at risk of malignant transformation following exposure to potentially oncogenic stimuli. With age, senescent cells accumulate and express a senescence-associated secretory phenotype (SASP; that is the robust secretion of many inflammatory cytokines, growth factors and proteases). Whereas cell senescence in peripheral tissues has been causally linked to a number of age-related pathologies, little is known about the induction of cellular senescence and the SASP in the brain. On the basis of recently reported findings, we propose that environmental stressors associated with PD may act in part by eliciting senescence and the SASP within non neuronal glial cells in the ageing brain, thus contributing to the characteristic decline in neuronal integrity that occurs in this disorder. © 2013 The Association for the Publication of the Journal of Internal Medicine.

  11. Knowledge and Awareness of Age Related Eye Diseases: a Population-Based Survey

    Directory of Open Access Journals (Sweden)

    Marzieh Katibeh

    2014-01-01

    Full Text Available Purpose: To determine general awareness and knowledge about cataracts, glaucoma and diabetic retinopathy (DR, as common avoidable causes of blindness in an Iranian population. Methods: This cross-sectional population-based survey was performed on residents over 45 years of age in Tehran. The sampling frame was the list of all landline phone numbers registered by the Telecommunications Center of Iran, through which systematic random sampling was performed. Data was collected by phone-call interviews and completing a semi-structured questionnaire. Awareness was defined as whether the respondent had ever heard of the disease. Knowledge was assessed by realizing different aspects of each disease. Results: Of a total of 1,084 eligible people including 574 (52.9% women and 510 (47.1% men were included and 957 subjects (response rate, 88.3% completed the interview. Awareness regarding glaucoma, cataract and DR was 46.6% (95% confidence interval [CI]:43.4 -49.8%, 82.9% (95% CI: 80.5 -85.3% and 86.2% (95% CI: 84-88.4%. In addition, 19.2% (95% CI: 16.7 -21.7%, 57.3% (95% CI: 54.2-60.4% and 72% (95% CI: 69.2 -74.8% of respondents could give at least a basic definition of the mentioned diseases, respectively. Only 22.6% (95% CI: 20-25.2% and 41.6% (95% CI: 38.5-44.7% realized glaucoma and DR as a treatable condition; in contrast, 77.2% (95% CI: 74.5-79.9% categorized cataract as treatable. Only 19% and 7.1% knew that DR and glaucoma may commence without any apparent symptoms. Conclusion: Compared with cataract and DR, most participants had limited information about glaucoma. In addition, few of the respondents were familiar with the initial symptoms of DR and glaucoma.

  12. Pharmacologic MRI (phMRI) as a tool to differentiate Parkinson's disease-related from age-related changes in basal ganglia function.

    Science.gov (United States)

    Andersen, Anders H; Hardy, Peter A; Forman, Eric; Gerhardt, Greg A; Gash, Don M; Grondin, Richard C; Zhang, Zhiming

    2015-02-01

    The prevalence of both parkinsonian signs and Parkinson's disease (PD) per se increases with age. Although the pathophysiology of PD has been studied extensively, less is known about the functional changes taking place in the basal ganglia circuitry with age. To specifically address this issue, 3 groups of rhesus macaques were studied: normal middle-aged animals (used as controls), middle-aged animals with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism, and aged animals (>20 years old) with declines in motor function. All animals underwent the same behavioral and pharmacologic magnetic resonance imaging (phMRI) procedures to measure changes in basal ganglia function in response to dopaminergic drug challenges consisting of apomorphine administration followed by either a D1 (SCH23390) or a D2 (raclopride) receptor antagonist. Significant functional changes were predominantly seen in the external segment of the globus pallidus (GPe) in aged animals and in the striatum (caudate nucleus and putamen) in MPTP-lesioned animals. Despite significant differences seen in the putamen and GPe between MPTP-lesioned versus aged animals, a similar response profile to dopaminergic stimulations was found between these 2 groups in the internal segment of the GP. In contrast, the pharmacologic responses seen in the control animals were much milder compared with the other 2 groups in all the examined areas. Our phMRI findings in MPTP-lesioned parkinsonian and aged animals suggest that changes in basal ganglia function in the elderly may differ from those seen in parkinsonian patients and that phMRI could be used to distinguish PD from other age-associated functional alterations in the brain. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Age groups related glioblastoma study based on radiomics approach.

    Science.gov (United States)

    Li, Zeju; Wang, Yuanyuan; Yu, Jinhua; Guo, Yi; Zhang, Qi

    2017-12-01

    Glioblastoma is the most aggressive malignant brain tumor with poor prognosis. Radiomics is a newly emerging and promising technique to reveal the complex relationships between high-throughput medical image features and deep information of disease including pathology, biomarkers and genomics. An approach was developed to investigate the internal relationship between magnetic resonance imaging (MRI) features and the age-related origins of glioblastomas based on a quantitative radiomics method. A fully automatic image segmentation method was applied to segment the tumor regions from three dimensional MRI images. 555 features were then extracted from the image data. By analyzing large numbers of quantitative image features, some predictive and prognostic information could be obtained by the radiomics approach. 96 patients diagnosed with glioblastoma pathologically have been divided into two age groups (age groups (T test, p age difference (T test, p= .006). In conclusion, glioblastoma in different age groups present different radiomics-feature patterns with statistical significance, which indicates that glioblastoma in different age groups should have different pathologic, protein, or genic origins.

  14. Neurovascular and Neurometabolic Derailment in Aging and Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Cátia eLourenço

    2015-05-01

    Full Text Available The functional and structural integrity of the brain requires local adjustment of blood flow and regulated delivery of metabolic substrates to meet the metabolic demands imposed by neuronal activation. This process – neurovascular coupling – and ensued alterations of glucose and oxygen metabolism - neurometabolic coupling - are accomplished by concerted communication between neural and vascular cells. Evidence suggests that neuronal-derived nitric oxide (•NO is a key player in both phenomena. Alterations in the mechanisms underlying the intimate communication between neural cells and vessels ultimately lead to neuronal dysfunction. Both neurovascular and neurometabolic coupling are perturbed during brain aging and in age-related neuropathologies in close association with cognitive decline. However, despite decades of intense investigation, many aspects remain poorly understood, such as the impact of these alterations. In this review, we address neurovascular and neurometabolic derailment in aging and Alzheimer’s disease, discussing its significance in connection with •NO-related pathways.

  15. Nutrition and age-related macular degeneration: research evidence in practice.

    Science.gov (United States)

    Downie, Laura Elizabeth; Keller, Peter Richard

    2014-08-01

    Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment in developed countries. In the absence of effective treatments to slow AMD progression, it is predicted that the prevalence of AMD will double over the next 20 years. One area of significant interest is the potential role that nutrition may play in preventing and/or delaying the progression of AMD. Specifically, is there any benefit in oral antioxidant and/or mineral supplementation? This review critically evaluates the currently available evidence relating to nutrition and AMD, with particular reference to the key findings of two large National Eye Institute-sponsored clinical studies, namely, the Age-Related Eye Disease Study (AREDS) and AREDS2. Topical controversies relating to nutrition and AMD are considered and analyzed in the context of the published literature to guide practitioners through assessing the merit, or otherwise, of common claims. This article provides a foundation for clinicians to provide informed advice to AMD patients based on available research evidence.

  16. Age-Related Defects in Erythrocyte 2,3-Diphosphoglycerate Metabolism in Dementia

    OpenAIRE

    Kaminsky, Yury G.; Reddy, V. Prakash; Ashraf, Ghulam Md; Ahmad, Ausaf; Benberin, Valery V.; Kosenko, Elena A.; Aliev, Gjumrakch

    2013-01-01

    Alzheimer disease (AD) is the most common dementing illness. Metabolic defects in the brain with aging contribute to the pathogenesis of AD. These changes can be found systematically and thus can be used as potential biomarkers. Erythrocytes (RBCs) are passive “reporter cells” that are not well studied in AD. In the present study, we analyzed an array of glycolytic and related enzymes and intermediates in RBCs from patients with AD and non-Alzheimer dementia (NA), age-matched controls (AC) an...

  17. Deep Machine Learning Application to the Detection of Preclinical Neurodegenerative Diseases of Aging

    Directory of Open Access Journals (Sweden)

    Mathew J. Summers

    2017-12-01

    Full Text Available Artificial intelligence (AI deep learning protocols offer solutions to complex data processing and analysis. Increasingly these solutions are being applied in the healthcare field, most commonly in processing complex medical imaging data used for diagnosis. Current models apply AI to screening populations of patients for markers of disease and report detection accuracy rates exceeding those of human data screening. In this paper, we explore an alternate model for AI deployment, that of monitoring and analysing an individual’s level of function over time. In adopting this approach, we propose that AI may provide highly accurate and reliable detection of preclinical disease states associated with aging-related neurodegenerative diseases. One of the key challenges facing clinical detection of preclinical phases of diseases such as dementia is the high degree of inter-individual variability in aging-related changes to cognitive function. AI based monitoring of an individual over time offers the potential for the early detection of change in function for the individual, rather than relying on comparing the individual’s performance to population norms. We explore an approach to developing AI platforms for individual monitoring and preclinical disease detection and examine the potential benefits to the stakeholders in this technological development.

  18. Risk factors for age-related macular degeneration: Pooled findings from three continents

    NARCIS (Netherlands)

    Smith, W.; Assink, J.; Klein, R.; Mitchell, P.; Klaver, C. C.; Klein, B. E.; Hofman, A.; Jensen, S.; Wang, J. J.; de Jong, P. T.

    2001-01-01

    To assess the prevalence and potential risk factors for late age-related macular degeneration (AMD) in three racially similar populations from North America, Europe, and AUSTRALIA: Combined analysis of population-based eye disease prevalence data. There were 14,752 participants with gradable

  19. Brain aging, Alzheimer's disease, and mitochondria

    Science.gov (United States)

    Swerdlow, Russell H.

    2011-01-01

    The relationship between brain aging and Alzheimer’s disease (AD) is contentious. One view holds AD results when brain aging surpasses a threshold. The other view postulates AD is not a consequence of brain aging. This review discusses this conundrum from the perspective of different investigative lines that have tried to address it, as well as from the perspective of the mitochondrion, an organelle that appears to play a role in both AD and brain aging. Specific issues addressed include the question of whether AD and brain aging should be conceptually lumped or split, the extent to which AD and brain aging potentially share common molecular mechanisms, whether beta amyloid should be primarily considered a marker of AD or simply brain aging, and the definition of AD itself. PMID:21920438

  20. Renal microvascular disease in an aging population: a reversible process?

    Science.gov (United States)

    Futrakul, Narisa; Futrakul, Prasit

    2008-01-01

    Renal microvascular disease and tubulointerstitial fibrosis are usually demonstrated in aging in humans and animals. It has recently been proposed that renal microvascular disease is the crucial determinant of tubulointerstitial disease or fibrosis. Enhanced circulating endothelial cell loss is a biomarker that reflects glomerular endothelial injury or renal microvascular disease, and fractional excretion of magnesium (FE Mg) is a sensitive biomarker that reflects an early stage of tubulointerstitial fibrosis. In aging in humans, both of these biomarkers are abnormally elevated. In addition, a glomerular endothelial dysfunction determined by altered hemodynamics associated with peritubular capillary flow reduction is substantiated. A correction of such hemodynamic alteration with vasodilators can effectively improve renal perfusion and restore renal function. Thus, anti-aging therapy can reverse the renal microvascular disease and dysfunction associated with the aging process.

  1. Overlap between age-at-onset and disease-progression determinants in Huntington disease.

    Science.gov (United States)

    Aziz, N Ahmad; van der Burg, Jorien M M; Tabrizi, Sarah J; Landwehrmeyer, G Bernhard

    2018-05-09

    A fundamental but still unresolved issue regarding Huntington disease (HD) pathogenesis is whether the factors that determine age at onset are the same as those that govern disease progression. Because elucidation of this issue is crucial for the development as well as optimal timing of administration of novel disease-modifying therapies, we aimed to assess the extent of overlap between age-at-onset and disease-progression determinants in HD. Using observational data from Enroll-HD, the largest cohort of patients with HD worldwide, in this study we present, validate, and apply an intuitive method based on linear mixed-effect models to quantify the variability in the rate of disease progression in HD. A total of 3,411 patients with HD met inclusion criteria. We found that (1) about two-thirds of the rate of functional, motor, and cognitive progression in HD is determined by the same factors that also determine age at onset, with CAG repeat-dependent mechanisms having by far the largest effect; (2) although expanded HTT CAG repeat size had a large influence on average body weight, the rate of weight loss was largely independent of factors that determine age at onset in HD; and (3) about one-third of the factors that determine the rate of functional, motor, and cognitive progression are different from those that govern age at onset and need further elucidation. Our findings imply that targeting of CAG repeat-dependent mechanisms, for example through gene-silencing approaches, is likely to affect the rate of functional, motor, and cognitive impairment, but not weight loss, in manifest HD mutation carriers. Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  2. The role of vitamin K in chronic aging diseases: inflammation, cardiovascular disease and osteoarthritis

    Science.gov (United States)

    Vitamin K is an enzyme cofactor required for the carboxylation of vitamin K dependent proteins, several of which have been implicated in diseases of aging. Inflammation is recognized as a crucial component of many chronic aging diseases, and evidence suggests vitamin K has an anti-inflammatory actio...

  3. Calorie restriction: A new therapeutic intervention for age-related dry eye disease in rats.

    Science.gov (United States)

    Kawashima, Motoko; Kawakita, Tetsuya; Okada, Naoko; Ogawa, Yoko; Murat, Dogru; Nakamura, Shigeru; Nakashima, Hideo; Shimmura, Shigeto; Shinmura, Ken; Tsubota, Kazuo

    2010-07-09

    A decrease in lacrimal gland secretory function is closely related to aging and leads to an increased prevalence of dry eye syndrome. Since calorie restriction (CR) is considered to prevent functional decline of various organs due to aging, we hypothesized that CR could prevent age-related lacrimal dysfunction. Six-month-old male Fischer 344 rats were randomly divided into ad libitum (AL) and CR (-35%) groups. After 6months of CR, tear function was examined under conscious state. After euthanasia, lacrimal glands were subjected to histological examination, tear protein secretion stimulation test with Carbachol, and assessment of oxidative stress with 8-hydroxy-2 deoxyguanosine (8-OHdG) and 4-hydroxynonenal (HNE) antibodies. CR significantly improved tear volume and tended to increase tear protein secretion volume after stimulation with Carbachol compared to AL. The acinar unit density was significantly higher in the CR rats compared to AL rats. Lacrimal glands in the CR rats showed a lesser degree of interstitial fibrosis. CR reduced the concentration of 8-OHdG and the extent of staining with HNE in the lacrimal gland, compared to AL. Furthermore, our electron microscopic observations showed that mitochondrial structure of the lacrimal gland obtained from the middle-aged CR rats was preserved in comparison to the AL rats. Collectively, these results demonstrate for the first time that CR may attenuate oxidative stress related damage in the lacrimal gland with preservation of lacrimal gland functions. Although molecular mechanism(s) by which CR maintains lacrimal gland function remains to be resolved, CR might provide a novel therapeutic strategy for treating dry eye syndrome. Copyright 2010 Elsevier Inc. All rights reserved.

  4. Mortality forecast from gastroduodenal ulcer disease for different gender and age population groups in Ukraine

    Directory of Open Access Journals (Sweden)

    Duzhiy I.D.

    2016-03-01

    Full Text Available Until 2030 the ulcer mortality will have a growing trend as estimated by the World Health Organization. Detection of countries and population groups with high risks for the ulcer mortality is possible using forecast method. The authors made a forecast of mortality rate from complicated ulcer disease in males and females and their age groups (15-24, 25-34, 35-54, 55-74, over 75, 15 - over 75 in our country. The study included data of the World Health Organization Database from 1991 to 2012. The work analyzed absolute all-Ukrainian numbers of persons of both genders died from the ulcer causes (К25-К27 coded by the 10th International Diseases Classification. The relative mortality per 100 000 of alive persons of the same age was calculated de novo. The analysis of distribution laws and their estimation presents a trend of growth of the relative mortality. A remarkable increase of deaths from the ulcer disease is observed in males and females of the age after 55 years old. After the age of 75 years this trend is more expressed.

  5. Age-Dependence and Aging-Dependence: Neuronal Loss and Lifespan in a C. elegans Model of Parkinson's Disease.

    Science.gov (United States)

    Apfeld, Javier; Fontana, Walter

    2017-12-23

    It is often assumed, but not established, that the major neurodegenerative diseases, such as Parkinson's disease, are not just age-dependent (their incidence changes with time) but actually aging-dependent (their incidence is coupled to the process that determines lifespan). To determine a dependence on the aging process requires the joint probability distribution of disease onset and lifespan. For human Parkinson's disease, such a joint distribution is not available, because the disease cuts lifespan short. To acquire a joint distribution, we resorted to an established C. elegans model of Parkinson's disease in which the loss of dopaminergic neurons is not fatal. We find that lifespan is not correlated with the loss of individual neurons. Therefore, neuronal loss is age-dependent and aging-independent. We also find that a lifespan-extending intervention into insulin/IGF1 signaling accelerates the loss of specific dopaminergic neurons, while leaving death and neuronal loss times uncorrelated. This suggests that distinct and compartmentalized instances of the same genetically encoded insulin/IGF1 signaling machinery act independently to control neurodegeneration and lifespan in C. elegans . Although the human context might well be different, our study calls attention to the need to maintain a rigorous distinction between age-dependence and aging-dependence.

  6. Aging-related systemic manifestations in COPD patients and cigarette smokers.

    Directory of Open Access Journals (Sweden)

    Laurent Boyer

    Full Text Available Chronic obstructive pulmonary disease (COPD is often associated with age-related systemic abnormalities that adversely affect the prognosis. Whether these manifestations are linked to the lung alterations or are independent complications of smoking remains unclear.To look for aging-related systemic manifestations and telomere shortening in COPD patients and smokers with minor lung destruction responsible for a decline in the diffusing capacity for carbon monoxide (DLCO corrected for alveolar volume (KCO.Cross-sectional study in 301 individuals (100 with COPD, 100 smokers without COPD, and 101 nonsmokers without COPD.Compared to control smokers, patients with COPD had higher aortic pulse-wave velocity (PWV, lower bone mineral density (BMD and appendicular skeletal muscle mass index (ASMMI, and shorter telomere length (TL. Insulin resistance (HOMA-IR and glomerular filtration rate (GFR were similar between control smokers and COPD patients. Smokers did not differ from nonsmokers for any of these parameters. However, smokers with normal spirometry but low KCO had lower ASMMI values compared to those with normal KCO. Moreover, female smokers with low KCO, had lower BMD and shorter TL compared to those with normal KCO.Aging-related abnormalities in patients with COPD are also found in smokers with minor lung dysfunction manifesting as a KCO decrease. Decreased KCO might be useful, particularly among women, for identifying smokers at high risk for aging-related systemic manifestations and telomere shortening.

  7. Estrogen-related and other disease diagnoses preceding Parkinson's disease

    DEFF Research Database (Denmark)

    Latourelle, Jeanne C; Dybdal, Merete; Destefano, Anita L

    2010-01-01

    Estrogen exposure has been associated with the occurrence of Parkinson's disease (PD), as well as many other disorders, and yet the mechanisms underlying these relations are often unknown. While it is likely that estrogen exposure modifies the risk of various diseases through many different...... mechanisms, some estrogen-related disease processes might work in similar manners and result in association between the diseases. Indeed, the association between diseases need not be due only to estrogen-related factors, but due to similar disease processes from a variety of mechanisms....

  8. Capturing age-related changes in functional contrast sensitivity with decreasing light levels in monocular and binocular vision.

    Science.gov (United States)

    Gillespie-Gallery, Hanna; Konstantakopoulou, Evgenia; Harlow, Jonathan A; Barbur, John L

    2013-09-09

    It is challenging to separate the effects of normal aging of the retina and visual pathways independently from optical factors, decreased retinal illuminance, and early stage disease. This study determined limits to describe the effect of light level on normal, age-related changes in monocular and binocular functional contrast sensitivity. We recruited 95 participants aged 20 to 85 years. Contrast thresholds for correct orientation discrimination of the gap in a Landolt C optotype were measured using a 4-alternative, forced-choice (4AFC) procedure at screen luminances from 34 to 0.12 cd/m(2) at the fovea and parafovea (0° and ±4°). Pupil size was measured continuously. The Health of the Retina index (HRindex) was computed to capture the loss of contrast sensitivity with decreasing light level. Participants were excluded if they exhibited performance outside the normal limits of interocular differences or HRindex values, or signs of ocular disease. Parafoveal contrast thresholds showed a steeper decline and higher correlation with age at the parafovea than the fovea. Of participants with clinical signs of ocular disease, 83% had HRindex values outside the normal limits. Binocular summation of contrast signals declined with age, independent of interocular differences. The HRindex worsens more rapidly with age at the parafovea, consistent with histologic findings of rod loss and its link to age-related degenerative disease of the retina. The HRindex and interocular differences could be used to screen for and separate the earliest stages of subclinical disease from changes caused by normal aging.

  9. Myelin Breakdown Mediates Age-Related Slowing in Cognitive Processing Speed in Healthy Elderly Men

    Science.gov (United States)

    Lu, Po H.; Lee, Grace J.; Tishler, Todd A.; Meghpara, Michael; Thompson, Paul M.; Bartzokis, George

    2013-01-01

    Background: To assess the hypothesis that in a sample of very healthy elderly men selected to minimize risk for Alzheimer's disease (AD) and cerebrovascular disease, myelin breakdown in late-myelinating regions mediates age-related slowing in cognitive processing speed (CPS). Materials and methods: The prefrontal lobe white matter and the genu of…

  10. The period-age relation for cepheids

    International Nuclear Information System (INIS)

    Efremov, Yu.N.

    1978-01-01

    The list of 119 cepheid-members of 55 clusters and associations of the Magellanic Clouds, the Galaxy, and M31 is given. The period-age relation is found from the data on 64 cepheids in 29 clusters for which the age determinations are available, the ages of extragalactic clusters were determined mainly from their integral colours. The U-B colours are found to be of much better age parameters than the B-V ones. The composite period-age relation agrees well with the theoretical one. The observed dispersion of the period-age relation leads to an estimate of the age dispersion about 1x10 7 years in the associations. Some peculiarities of the cepheids with the shortest periods amongst others in the same clusters are probably explained if they are overtone pulsators. The period-age relation may be used for an investigation of the recent history of star formation in the galaxies. This relation allows to determine the age gradient across the spiral arm in M31 which is in agreement with the density wave theory predictions. The distribution of cepheids in our Galaxy and neighbouring galaxies is consistent with the conception of star formation lasting for some dozen million years in cells with a dimension of some hundreds of parsecs

  11. Age-related macular degeneration—emerging pathogenetic and therapeutic concepts

    Science.gov (United States)

    GEHRS, KAREN M.; ANDERSON, DON H.; JOHNSON, LINCOLN V.; HAGEMAN, GREGORY S.

    2014-01-01

    Today, the average life expectancy in developed nations is over 80 years and climbing. And yet, the quality of life during those additional years is often significantly diminished by the effects of age-related, degenerative diseases, including age-related macular degeneration (AMD), the leading cause of blindness in the elderly worldwide. AMD is characterized by a progressive loss of central vision attributable to degenerative and neovascular changes in the macula, a highly specialized region of the ocular retina responsible for fine visual acuity. Estimates gathered from the most recent World Health Organization (WHO) global eye disease survey conservatively indicate that 14 million persons are blind or severely visually impaired because of AMD. The disease has a tremendous impact on the physical and mental health of the geriatric population and their families and is becoming a major public health burden. Currently, there is neither a cure nor a means to prevent AMD. Palliative treatment options for the less prevalent, late-stage ‘wet’ form of the disease include anti-neovascular agents, photodynamic therapy and thermal laser. There are no current therapies for the more common ‘dry’ AMD, except for the use of antioxidants that delay progression in 20%–25% of eyes. New discoveries, however, are beginning to provide a much clearer picture of the relevant cellular events, genetic factors, and biochemical processes associated with early AMD. Recently, compelling evidence has emerged that the innate immune system and, more specifically, uncontrolled regulation of the complement alternative pathway plays a central role in the pathobiology of AMD. The complement Factor H gene—which encodes the major inhibitor of the complement alternative pathway—is the first gene identified in multiple independent studies that confers a significant genetic risk for the development of AMD. The emergence of this new paradigm of AMD pathogenesis should hasten the development

  12. A final size relation for epidemic models of vector-transmitted diseases

    OpenAIRE

    Fred Brauer

    2017-01-01

    We formulate and analyze an age of infection model for epidemics of diseases transmitted by a vector, including the possibility of direct transmission as well. We show how to determine a basic reproduction number. While there is no explicit final size relation as for diseases transmitted directly, we are able to obtain estimates for the final size of the epidemic.

  13. Differences in stroke and ischemic heart disease mortality by occupation and industry among Japanese working-aged men

    Directory of Open Access Journals (Sweden)

    Koji Wada

    2016-12-01

    Full Text Available Occupation- and industry-based risks for stroke and ischemic heart disease may vary among Japanese working-aged men. We examined the differences in mortality rates between stroke and ischemic heart disease by occupation and industry among employed Japanese men aged 25–59 years. In 2010, we obtained occupation- and industry-specific vital statistics data from the Japanese Ministry of Health, Labour, and Welfare dataset. We analyzed data for Japanese men who were aged 25–59 years in 2010, grouped in 5-year age intervals. We estimated the mortality rates of stroke and ischemic heart disease in each age group for occupation and industry categories as defined in the national census. We did not have detailed individual-level variables. We used the number of employees in 2010 as the denominator and the number of events as the numerator, assuming a Poisson distribution. We conducted separate regression models to estimate the incident relative risk for stroke and ischemic heart disease for each category compared with the reference categories “sales” (occupation and “wholesale and retail” (industry. When compared with the reference groups, we found that occupations and industries with a relatively higher risk of stroke and ischemic heart disease were: service, administrative and managerial, agriculture and fisheries, construction and mining, electricity and gas, transport, and professional and engineering. This suggests there are occupation- and industry-based mortality risk differences of stroke and ischemic heart disease for Japanese working-aged men. These differences in risk might be explained to factors associated with specific occupations or industries, such as lifestyles or work styles, which should be explored in further research. The mortality risk differences of stroke and ischemic heart disease shown in the present study may reflect an excessive risk of Karoshi (death from overwork. Keywords: Occupation, Industry, Mortality

  14. Age- and Parkinson's disease-related evaluation of gait by General Tau Theory.

    Science.gov (United States)

    Zhang, Shutao; Qian, Jinwu; Zhang, Zhen; Shen, Linyong; Wu, Xi; Hu, Xiaowu

    2016-10-01

    The degeneration of postural control in the elderly and patients with Parkinson's disease (PD) can be debilitating and may lead to increased fall risk. This study evaluated the changes in postural control during gait affected by PD and aging using a new method based on the General Tau Theory. Fifteen patients with PD, 11 healthy old adults (HOs), and 15 healthy young adults (HYs) were recruited. Foot trajectories of each participant were monitored during walking by a three-camera Optotrak Certus(®) motion capture system. The anteroposterior direction of foot movement during stepping was analyzed by tau-G and tau-J guidance strategies. Two linear regression analyses suggested that the tau of the step-gap was strongly coupled onto the tau-J guidance during walking. The regression slope K could estimate the coupling ratio in the tau-coupling equation which reflects the performance of postural control during gait. The mean K value for the PD group, which was highest among the three groups, was approximately 0.5. Therefore, participants in the PD group walked with the poorest postural control and exhibited a relatively hard contact with the endpoint during stepping when compared with those in the HO and HY groups. The HY and HO groups obtained mean K values significantly lower than 0.5, which indicated that the gait was well controlled and ended at low speed with low deceleration. However, the HO group showed a decreased tendency for postural control, in which the mean K value was significantly higher than that of the HY group. The K value was moderately positively correlated with the double support time and negatively correlated with the stride length and walking speed. The tau-J coupling ratio can provide additional insight into gait disturbances and may serve as a reliable, objective, and quantitative tool to evaluate dynamic postural control during walking.

  15. The natural history of prevalent ischaemic heart disease in middle-aged men.

    Science.gov (United States)

    Lampe, F C; Whincup, P H; Wannamethee, S G; Shaper, A G; Walker, M; Ebrahim, S

    2000-07-01

    To describe the long-term outcome of different forms of symptomatic and asymptomatic ischaemic heart disease in middle-aged men. 7735 men aged 40-59, randomly selected from 24 general practices in Britain were classified into one of seven ischaemic heart disease groups according to a questionnaire and electrocardiogram (ECG): I=diagnosed myocardial infarction; II=unrecognized myocardial infarction; III= diagnosed angina; IV=angina symptoms; V=possible myocardial infarction symptoms; VI=ECG ischaemia or possible myocardial infarction; VII=no evidence of ischaemic heart disease. The association of disease group with a range of fatal and non-fatal outcomes during 15 years of follow-up was assessed. At baseline 25% of men had evidence of ischaemic heart disease (groups I-VI). Risks of major ischaemic heart disease events, total and cardiovascular mortality, stroke, and major cardiovascular events tended to increase strongly from group VII to I. Diagnosed myocardial infarction was associated with a much poorer prognosis than all other groups (including unrecognized infarction) for all cardiovascular outcomes other than stroke. The relative risk associated with ischaemic heart disease at baseline declined dramatically over time. However, men with myocardial infarction who survived event-free for 10 years continued to experience a high excess risk in the subsequent 5 years, in contrast to event-free survivors of angina and other ischaemic heart disease. Adjusted to an average age of 50, the percentage of men surviving for 15 years free of a new major cardiovascular event was 44 for diagnosed myocardial infarction, 52 for unrecognized myocardial infarction, 66 for diagnosed angina, 68 for angina symptoms, 73 for possible myocardial infarction symptoms, 73 for ECG ischaemia, and 79 for no ischaemic heart disease. Comparison of outcome between prevalent and incident myocardial infarction illustrated the improved prognosis of men surviving the initial years after their event

  16. A mathematical model of aging-related and cortisol induced hippocampal dysfunction

    Directory of Open Access Journals (Sweden)

    Jones Janette JL

    2009-03-01

    Full Text Available Abstract Background The hippocampus is essential for declarative memory synthesis and is a core pathological substrate for Alzheimer's disease (AD, the most common aging-related dementing disease. Acute increases in plasma cortisol are associated with transient hippocampal inhibition and retrograde amnesia, while chronic cortisol elevation is associated with hippocampal atrophy. Thus, cortisol levels could be monitored and managed in older people, to decrease their risk of AD type hippocampal dysfunction. We generated an in silicomodel of the chronic effects of elevated plasma cortisol on hippocampal activity and atrophy, using the systems biology mark-up language (SBML. We further challenged the model with biologically based interventions to ascertain if cortisol associated hippocampal dysfunction could be abrogated. Results The in silicoSBML model reflected the in vivoaging of the hippocampus and increased plasma cortisol and negative feedback to the hypothalamic pituitary axis. Aging induced a 12% decrease in hippocampus activity (HA, increased to 30% by acute and 40% by chronic elevations in cortisol. The biological intervention attenuated the cortisol associated decrease in HA by 2% in the acute cortisol simulation and by 8% in the chronic simulation. Conclusion Both acute and chronic elevations in cortisol secretion increased aging-associated hippocampal atrophy and a loss of HA in the model. We suggest that this first SMBL model, in tandem with in vitroand in vivostudies, may provide a backbone to further frame computational cortisol and brain aging models, which may help predict aging-related brain changes in vulnerable older people.

  17. Recent Developments in Understanding Brain Aging: Implications for Alzheimer’s Disease and Vascular Cognitive Impairment

    Science.gov (United States)

    Deak, Ferenc; Freeman, Willard M.; Ungvari, Zoltan; Csiszar, Anna

    2016-01-01

    As the population of the Western world is aging, there is increasing awareness of age-related impairments in cognitive function and a rising interest in finding novel approaches to preserve cerebral health. A special collection of articles in The Journals of Gerontology: Biological Sciences and Medical Sciences brings together information of different aspects of brain aging, from latest developments in the field of neurodegenerative disorders to cerebral microvascular mechanisms of cognitive decline. It is emphasized that although the cellular changes that occur within aging neurons have been widely studied, more research is required as new signaling pathways are discovered that can potentially protect cells. New avenues for research targeting cellular senescence, epigenetics, and endocrine mechanisms of brain aging are also discussed. Based on the current literature it is clear that understanding brain aging and reducing risk for neurological disease with age requires searching for mechanisms and treatment options beyond the age-related changes in neuronal function. Thus, comprehensive approaches need to be developed that address the multiple, interrelated mechanisms of brain aging. Attention is brought to the importance of maintenance of cerebromicrovascular health, restoring neuroendocrine balance, and the pressing need for funding more innovative research into the interactions of neuronal, neuroendocrine, inflammatory and microvascular mechanisms of cognitive impairment, and Alzheimer’s disease. PMID:26590911

  18. Age-related aspects of addiction

    OpenAIRE

    Koechl, Birgit; Unger, Annemarie; Fischer, Gabriele

    2012-01-01

    Research has shown that substance use, abuse and addiction are not limited to a specific age group. Problems related to substance addiction are an important cause of morbidity in the population aged 65 and above, especially the abuse of prescription drugs and legal substances. A lack of evidence-based studies and tailored treatment options for the aging population is evident. Appropriate and effective health-care is an important goal to improve health-related quality of life of elderly people...

  19. Prevalence of chronic obstructive pulmonary disease according to BTS, ERS, GOLD and ATS criteria in relation to doctor's diagnosis, symptoms, age, gender, and smoking habits.

    Science.gov (United States)

    Lindberg, Anne; Jonsson, Ann-Christin; Rönmark, Eva; Lundgren, Rune; Larsson, Lars-Gunnar; Lundbäck, Bo

    2005-01-01

    Guidelines and standards for diagnosis and management of chronic obstructive pulmonary disease (COPD) have been presented by different national and international societies, but the spirometric criteria for COPD differ between guidelines. To estimate prevalence of COPD using the guidelines of the British Thoracic Society (BTS), the European Respiratory Society (ERS), the Global Initiative for Chronic Obstructive Lung Disease (GOLD), and the American Thoracic Society (ATS). Further, to evaluate reported airway symptoms, contacts with health care providers, and physician diagnosis of COPD in relation to the respective criteria, and gender differences. In 1992 a postal questionnaire was sent to a random sample of adults aged 20-69 years, 4,851 (85%) out of 5,681 subjects responded. In 1994-1995 a random sample of the responders, 970 subjects, were invited to a structured interview and a lung function test; 666 (69%) participated. The prevalence of COPD was 7.6, 14.0, 14.1, 12.2 and 34.1% according to BTS, ERS, GOLD, clinical ATS (with symptoms or physician diagnosis), and spirometric ATS criteria, respectively. Prevalent COPD was related to age, smoking habits and family history of obstructive airway disease but not to gender. Physician diagnosis of chronic bronchitis or emphysema was only reported by 16.3, 12.2, 11.0, 23.4 and 8.2% of subjects fulfilling the respective criteria, though a majority reported airway symptoms. The main determinants for prevalent COPD were age, smoking habits and spirometric criteria of COPD. Though a majority reported airway symptoms and contact with health care providers due to respiratory complaints, only a minority was diagnosed as having COPD, indicating a large underdiagnosis. Copyright (c) 2005 S. Karger AG, Basel.

  20. Aging and Vision.

    Science.gov (United States)

    Alavi, Marcel V

    2016-01-01

    Aging involves defined genetic, biochemical and cellular pathways that regulate lifespan. These pathways are called longevity pathways and they have relevance for many age-related diseases. In the eye, longevity pathways are involved in the major blinding diseases, cataract, glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy. Pharmaceutical targeting of longevity pathways can extend healthy lifespan in laboratory model systems. This offers the possibility of therapeutic interventions to also delay onset or slow the progression of age-related eye diseases. I suggest that retinal degeneration may be viewed as accelerated aging of photoreceptors and that interventions extending healthy lifespan may also slow the pace of photoreceptor loss.

  1. Αlpha-Synuclein as a Mediator in the Interplay between Aging and Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Wojciech Bobela

    2015-10-01

    Full Text Available Accumulation and misfolding of the alpha-synuclein protein are core mechanisms in the pathogenesis of Parkinson’s disease. While the normal function of alpha-synuclein is mainly related to the control of vesicular neurotransmission, its pathogenic effects are linked to various cellular functions, which include mitochondrial activity, as well as proteasome and autophagic degradation of proteins. Remarkably, these functions are also affected when the renewal of macromolecules and organelles becomes impaired during the normal aging process. As aging is considered a major risk factor for Parkinson’s disease, it is critical to explore its molecular and cellular implications in the context of the alpha-synuclein pathology. Here, we discuss similarities and differences between normal brain aging and Parkinson’s disease, with a particular emphasis on the nigral dopaminergic neurons, which appear to be selectively vulnerable to the combined effects of alpha-synuclein and aging.

  2. Can innate and autoimmune reactivity forecast early and advance stages of age-related macular degeneration?

    Science.gov (United States)

    Adamus, Grazyna

    2017-03-01

    Age-related macular degeneration (AMD) is a major cause of central vision loss in persons over 55years of age in developed countries. AMD is a complex disease in which genetic, environmental and inflammatory factors influence its onset and progression. Elevation in serum anti-retinal autoantibodies, plasma and local activation of complement proteins of the alternative pathway, and increase in secretion of proinflammatory cytokines have been seen over the course of disease. Genetic studies of AMD patients confirmed that genetic variants affecting the alternative complement pathway have a major influence on AMD risk. Because the heterogeneity of this disease, there is no sufficient strategy to identify the disease onset and progression sole based eye examination, thus identification of reliable serological biomarkers for diagnosis, prognosis and response to treatment by sampling patient's blood is necessary. This review provides an outline of the current knowledge on possible serological (autoantibodies, complement factors, cytokines, chemokines) and related genetic biomarkers relevant to the pathology of AMD, and discusses their application for prediction of disease activity and prognosis in AMD. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Identification of a sustainable two-plant diet that effectively prevents age-related metabolic syndrome and extends lifespan in aged mice.

    Science.gov (United States)

    Li, Xiang-Yong; Liu, Ying-Hua; Wang, Bin; Chen, Chih-Yu; Zhang, Hong-Man; Kang, Jing X

    2018-01-01

    The current system of food production is linked to both the increasing prevalence of chronic disease and the deterioration of the environment, and thereby calls for novel ways of producing nutritious foods in a sustainable manner. In the "longevity village" of Bama, China, we have identified two plant foods, hemp seed and bitter vegetable (Sonchus oleraceus), that are commonly consumed by its residents and grow abundantly in unfarmed land without fertilizers or pesticides. Here, we show that a diet composed of these two foods (the "HB diet") provides a sufficient variety of nutrients and confers significant health benefits. Aged mice allowed ad libitum access to the HB diet not only had longer life spans and improved cognitive function but were also protected against age-related metabolic syndrome, fatty liver, gut dysbiosis and chronic inflammation compared to aged mice fed a control Western diet. Furthermore, longevity-related genes (including 5'adenosine monophosphate-activated protein kinase, sirtuin 1, nuclear respiratory factor 1 and forkhead box O3) were significantly up-regulated, while aging-related genes (including mammalian target of rapamycin and nuclear factor kappa B) were down-regulated. These results demonstrate that the HB diet is capable of promoting health and longevity, and present a sustainable source of healthy foods that can help control the prevalence of chronic diseases and reduce agricultural impact on the environment. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Health-related quality of life in residents aged 18 years and older with and without disease: findings from the First Provincial Health Services Survey of Hunan, China.

    Science.gov (United States)

    Deng, Xin; Dong, Peng; Zhang, Lingling; Tian, Danping; Zhang, Lin; Zhang, Wei; Li, Li; Deng, Jing; Ning, Peishan; Hu, Guoqing

    2017-09-03

    Published research has not considered acute diseases and injuries in assessing the impact of varying disease counts on health-related quality of life (HRQoL). We used Chinese value sets of EQ-5D-3L to examine the relationship between the number of diseases individuals had (including chronic diseases, acute diseases and injuries) and their HRQoL. A total of 19 387 individuals aged 18 years and older were included in the study. Using data from the First Provincial Health Services Survey of Hunan, China, HRQoL was assessed with the EQ-5D-3L scale, a standardized instrument developed by the EuroQoL group. The EQ-5D-3L utility score was calculated using the Chinese EQ-5D-3L value set. This survey coded disease using the list of 133 conditions that was defined by the First Provincial Health Services Survey of Hunan, China, based on the 10th International Classification of Diseases. 126 conditions were disease-related and were therefore included in data analysis. Of 15 245 respondents, urban residents and male constituted 53.0% and 48.2%, respectively. 19.3% of respondents had one disease and 5.0% had at least two diseases. Of the five dimensions of the EQ-5D-3L, the pain/discomfort dimension had the highest proportion of moderate or serious problems among the respondents (14.4%, 95% CI 10.5% to 18.2%). The average Visual Analogue Scale (VAS) score and utility score were 78.0 (95% CI 76.9 to 79.1) and 0.958 (95% CI 0.946 to 0.970), respectively. Residents with 1 and ≥2 diseases had higher proportions of moderate or serious problems in five dimensions of the EQ-5D-3L scale during the previous 2 weeks than those without disease after controlling for location (urban/rural), sex, age, education level and household income, respectively (adjusted ORs: 3.1-3.7 and 4.4-6.6, respectively). The mean of the EQ VAS score was 8.4 and 13.6 points lower in respondents with 1 and ≥2 diseases than in respondents without disease; the corresponding mean score difference was 0

  5. Age-related differences in plasma proteins: how plasma proteins change from neonates to adults.

    Directory of Open Access Journals (Sweden)

    Vera Ignjatovic

    Full Text Available The incidence of major diseases such as cardiovascular disease, thrombosis and cancer increases with age and is the major cause of mortality world-wide, with neonates and children somehow protected from such diseases of ageing. We hypothesized that there are major developmental differences in plasma proteins and that these contribute to age-related changes in the incidence of major diseases. We evaluated the human plasma proteome in healthy neonates, children and adults using the 2D-DIGE approach. We demonstrate significant changes in number and abundance of up to 100 protein spots that have marked differences in during the transition of the plasma proteome from neonate and child through to adult. These proteins are known to be involved in numerous physiological processes such as iron transport and homeostasis, immune response, haemostasis and apoptosis, amongst others. Importantly, we determined that the proteins that are differentially expressed with age are not the same proteins that are differentially expressed with gender and that the degree of phosphorylation of plasma proteins also changes with age. Given the multi-functionality of these proteins in human physiology, understanding the differences in the plasma proteome in neonates and children compared to adults will make a major contribution to our understanding of developmental biology in humans.

  6. NNDSS - Table II. Invasive Pneumococcal Diseases, Age <5

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Invasive Pneumococcal Diseases, Age <5 - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during...

  7. Common diseases as determinants of menopausal age.

    Science.gov (United States)

    Li, Jingmei; Eriksson, Mikael; Czene, Kamila; Hall, Per; Rodriguez-Wallberg, Kenny A

    2016-12-01

    Can the diagnosis of common diseases before menopause influence age at natural menopause (ANM) onset? Polycystic ovary syndrome (PCOS) and depression were observed to delay menopause. It has been observed that women who undergo early menopause experience a higher burden of health problems related to metabolic syndromes, heart disease and depression, but whether ANM can be influenced by common adult diseases has not been studied extensively. All women attending mammography screening or clinical mammography at four hospitals in Sweden were invited to participate in the Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA) study. Between January 2011 and March 2013, 70 877 women were recruited. Information from the baseline questionnaire filled out upon enrollment was used in this cross-sectional analysis on predictors of ANM onset. We limited our analyses to 61 936 women with complete data on ANM and covariates and a follow-up time (from birth to menopause or censoring) of at least 35 years. Premenopausal diagnoses of depression, anorexia, bulimia, PCOS, ovarian cyst, heart failure, myocardial infarction, angina pectoris, stroke, preeclampsia, diabetes, hypertension and hyperlipidemia were examined as time-dependent variables in multivariable Cox regression analyses, adjusting for reproductive factors (age at menarche, menstrual cycle regularity in adult life, number of children and premenopausal oral contraceptive use) and risk factors of common diseases (education, physical activity at 18 years and information at the time of questionnaire including BMI, ever smoking and alcohol consumption). Women with PCOS and depression were independently associated with later menopause (hazard ratio (95% CI): 0.44 (0.28-0.71) and 0.95 (0.91-1.00), respectively), compared to women with no such histories. The associations remained significant in a subset of women who had never received gynecological surgery or hormone treatment (n = 32313, 0.21 (0

  8. Effects of aging and Parkinson's disease on motor unit remodeling: influence of resistance exercise training.

    Science.gov (United States)

    Kelly, Neil A; Hammond, Kelley G; Bickel, C Scott; Windham, Samuel T; Tuggle, S Craig; Bamman, Marcas M

    2018-04-01

    Aging muscle atrophy is in part a neurodegenerative process revealed by denervation/reinnervation events leading to motor unit remodeling (i.e., myofiber type grouping). However, this process and its physiological relevance are poorly understood, as is the wide-ranging heterogeneity among aging humans. Here, we attempted to address 1) the relation between myofiber type grouping and molecular regulators of neuromuscular junction (NMJ) stability; 2) the impact of motor unit remodeling on recruitment during submaximal contractions; 3) the prevalence and impact of motor unit remodeling in Parkinson's disease (PD), an age-related neurodegenerative disease; and 4) the influence of resistance exercise training (RT) on regulators of motor unit remodeling. We compared type I myofiber grouping, molecular regulators of NMJ stability, and the relative motor unit activation (MUA) requirement during a submaximal sit-to-stand task among untrained but otherwise healthy young (YA; 26 yr, n = 27) and older (OA; 66 yr, n = 91) adults and OA with PD (PD; 67 yr, n = 19). We tested the effects of RT on these outcomes in OA and PD. PD displayed more motor unit remodeling, alterations in NMJ stability regulation, and a higher relative MUA requirement than OA, suggesting PD-specific effects. The molecular and physiological outcomes tracked with the severity of type I myofiber grouping. Together these findings suggest that age-related motor unit remodeling, manifested by type I myofiber grouping, 1) reduces MUA efficiency to meet submaximal contraction demand, 2) is associated with disruptions in NMJ stability, 3) is further impacted by PD, and 4) may be improved by RT in severe cases. NEW & NOTEWORTHY Because the physiological consequences of varying amounts of myofiber type grouping are unknown, the current study aims to characterize the molecular and physiological correlates of motor unit remodeling. Furthermore, because exercise training has demonstrated neuromuscular benefits in aged

  9. Differences in stroke and ischemic heart disease mortality by occupation and industry among Japanese working-aged men.

    Science.gov (United States)

    Wada, Koji; Eguchi, Hisashi; Prieto-Merino, David

    2016-12-01

    Occupation- and industry-based risks for stroke and ischemic heart disease may vary among Japanese working-aged men. We examined the differences in mortality rates between stroke and ischemic heart disease by occupation and industry among employed Japanese men aged 25-59 years. In 2010, we obtained occupation- and industry-specific vital statistics data from the Japanese Ministry of Health, Labour, and Welfare dataset. We analyzed data for Japanese men who were aged 25-59 years in 2010, grouped in 5-year age intervals. We estimated the mortality rates of stroke and ischemic heart disease in each age group for occupation and industry categories as defined in the national census. We did not have detailed individual-level variables. We used the number of employees in 2010 as the denominator and the number of events as the numerator, assuming a Poisson distribution. We conducted separate regression models to estimate the incident relative risk for stroke and ischemic heart disease for each category compared with the reference categories "sales" (occupation) and "wholesale and retail" (industry). When compared with the reference groups, we found that occupations and industries with a relatively higher risk of stroke and ischemic heart disease were: service, administrative and managerial, agriculture and fisheries, construction and mining, electricity and gas, transport, and professional and engineering. This suggests there are occupation- and industry-based mortality risk differences of stroke and ischemic heart disease for Japanese working-aged men. These differences in risk might be explained to factors associated with specific occupations or industries, such as lifestyles or work styles, which should be explored in further research. The mortality risk differences of stroke and ischemic heart disease shown in the present study may reflect an excessive risk of Karoshi (death from overwork).

  10. Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels.

    Science.gov (United States)

    Horvath, Steve; Langfelder, Peter; Kwak, Seung; Aaronson, Jeff; Rosinski, Jim; Vogt, Thomas F; Eszes, Marika; Faull, Richard L M; Curtis, Maurice A; Waldvogel, Henry J; Choi, Oi-Wa; Tung, Spencer; Vinters, Harry V; Coppola, Giovanni; Yang, X William

    2016-07-01

    Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=-0.41, p=5.5×10-8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels.

  11. The Impact of Aging on Cardio and Cerebrovascular Diseases

    Directory of Open Access Journals (Sweden)

    Carmine Izzo

    2018-02-01

    Full Text Available A growing number of evidences report that aging represents the major risk factor for the development of cardio and cerebrovascular diseases. Understanding Aging from a genetic, biochemical and physiological point of view could be helpful to design a better medical approach and to elaborate the best therapeutic strategy to adopt, without neglecting all the risk factors associated with advanced age. Of course, the better way should always be understanding risk-to-benefit ratio, maintenance of independence and reduction of symptoms. Although improvements in treatment of cardiovascular diseases in the elderly population have increased the survival rate, several studies are needed to understand the best management option to improve therapeutic outcomes. The aim of this review is to give a 360° panorama on what goes on in the fragile ecosystem of elderly, why it happens and what we can do, right now, with the tools at our disposal to slow down aging, until new discoveries on aging, cardio and cerebrovascular diseases are at hand.

  12. NNDSS - Table II. Invasive Pneumococcal Diseases, All Ages

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Invasive Pneumococcal Diseases, All Ages - 2017. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...

  13. NNDSS - Table II. Invasive pneumococcal disease, all ages

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Invasive pneumococcal disease, all ages - 2018. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...

  14. NNDSS - Table II. Invasive pneumococcal disease, age <5

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Invasive pneumococcal disease, age <5 - 2018. In this Table, provisional cases of selected notifiable diseases (≥1,000 cases reported during the...

  15. Environmental stress, ageing and glial cell senescence: a novel mechanistic link to Parkinson’s disease?

    Science.gov (United States)

    Chinta, Shankar J; Lieu, Christopher A; DeMaria, Marco; Laberge, Remi-Martin; Campisi, Judith; Andersen, Julie K

    2013-01-01

    Exposure to environmental toxins is associated with a variety of age-related diseases including cancer and neurodegeneration. For example, in Parkinson’s disease (PD), chronic environmental exposure to certain toxins has been linked to the age-related development of neuropathology. Neuronal damage is believed to involve the induction of neuroinflammatory events as a consequence of glial cell activation. Cellular senescence is a potent anti-cancer mechanism that occurs in a number of proliferative cell types and causes the arrest of proliferation of cells at risk of malignant transformation following exposure to potentially oncogenic stimuli. With age, senescent cells accumulate and express a senescence-associated secretory phenotype (SASP; i.e. the robust secretion of many inflammatory cytokines, growth factors and proteases). Whereas cell senescence in peripheral tissues has been causally linked to a number of age-related pathologies, little is known about the induction of cellular senescence and the SASP in the brain. Based on recently reported findings, we propose that environmental stressors associated with PD may act in part by eliciting senescence and the SASP within non-neuronal glial cells in the ageing brain, thus contributing to the characteristic decline in neuronal integrity that occurs in this disorder. PMID:23600398

  16. Visualization of dietary patterns and their associations with age-related macular degeneration

    Science.gov (United States)

    PURPOSE: We aimed to visualize the relationship of predominant dietary patterns and their associations with AMD. METHODS: A total of 8103 eyes from 4088 participants in the baseline Age-Related Eye Disease Study (AREDS) were classified into three groups: control (n=2739), early AMD (n=4599), and adv...

  17. Relations between Household Livestock Ownership, Livestock Disease, and Young Child Growth123

    Science.gov (United States)

    Mosites, Emily; Thumbi, Samuel M; Otiang, Elkanah; McElwain, Terry F; Njenga, MK; Rabinowitz, Peter M; Rowhani-Rahbar, Ali; Neuhouser, Marian L; May, Susanne; Palmer, Guy H; Walson, Judd L

    2016-01-01

    Background: In resource-limited settings in which child malnutrition is prevalent, humans live in close proximity to household livestock. However, the relation between household livestock and child nutrition represents a considerable knowledge gap. Objective: We assessed whether household livestock ownership or livestock disease episodes were associated with growth in young children in western Kenya. Methods: We incorporated monthly anthropometric measurements for children livestock ownership was related to baseline child height for age or prospective growth rate. We also evaluated whether livestock disease episodes were associated with child growth rate over 11 mo of follow-up. Results: We collected data on 925 children over the course of follow-up. Greater household livestock ownership at baseline was not related to baseline child height-for-age z score (adjusted β: 0.01 SD; 95% CI: −0.02, 0.04 SD) or child growth rate (adjusted β: 0.02 cm/y; 95% CI: −0.03, 0.07 cm/y). Livestock disease episodes were not significantly associated with child growth across the entire cohort (adjusted β: −0.007 cm/mo; 95% CI: −0.02, 0.006 cm/mo). However, children in households with livestock digestive disease between June and November gained less height than did children in households that did not report livestock disease (β: −0.063 cm/mo; 95% CI: −0.112, −0.016 cm/mo). Children livestock digestive disease gained less weight than did those who did not report disease (β: −0.033 kg/mo; 95% CI: −0.063, −0.003 kg/mo). Conclusion: In this cohort of young children in western Kenya, we did not find an association between ownership of livestock and child growth status. However, disease episodes in household livestock may be related to a lower child growth rate in some groups. PMID:27075911

  18. Recent Developments in Understanding Brain Aging: Implications for Alzheimer's Disease and Vascular Cognitive Impairment.

    Science.gov (United States)

    Deak, Ferenc; Freeman, Willard M; Ungvari, Zoltan; Csiszar, Anna; Sonntag, William E

    2016-01-01

    As the population of the Western world is aging, there is increasing awareness of age-related impairments in cognitive function and a rising interest in finding novel approaches to preserve cerebral health. A special collection of articles in The Journals of Gerontology: Biological Sciences and Medical Sciences brings together information of different aspects of brain aging, from latest developments in the field of neurodegenerative disorders to cerebral microvascular mechanisms of cognitive decline. It is emphasized that although the cellular changes that occur within aging neurons have been widely studied, more research is required as new signaling pathways are discovered that can potentially protect cells. New avenues for research targeting cellular senescence, epigenetics, and endocrine mechanisms of brain aging are also discussed. Based on the current literature it is clear that understanding brain aging and reducing risk for neurological disease with age requires searching for mechanisms and treatment options beyond the age-related changes in neuronal function. Thus, comprehensive approaches need to be developed that address the multiple, interrelated mechanisms of brain aging. Attention is brought to the importance of maintenance of cerebromicrovascular health, restoring neuroendocrine balance, and the pressing need for funding more innovative research into the interactions of neuronal, neuroendocrine, inflammatory and microvascular mechanisms of cognitive impairment, and Alzheimer's disease. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Familial aggregation of age-related macular degeneration in the Utah population.

    Science.gov (United States)

    Luo, Ling; Harmon, Jennifer; Yang, Xian; Chen, Haoyu; Patel, Shrena; Mineau, Geraldine; Yang, Zhenglin; Constantine, Ryan; Buehler, Jeanette; Kaminoh, Yuuki; Ma, Xiang; Wong, Tien Y; Zhang, Maonian; Zhang, Kang

    2008-02-01

    We examined familial aggregation and risk of age-related macular degeneration in the Utah population using a population-based case-control study. Over one million unique patient records were searched within the University of Utah Health Sciences Center and the Utah Population Database (UPDB), identifying 4764 patients with AMD. Specialized kinship analysis software was used to test for familial aggregation of disease, estimate the magnitude of familial risks, and identify families at high risk for disease. The population-attributable risk (PAR) for AMD was calculated to be 0.34. Recurrence risks in relatives indicate increased relative risks in siblings (2.95), first cousins (1.29), second cousins (1.13), and parents (5.66) of affected cases. There were 16 extended large families with AMD identified for potential use in genetic studies. Each family had five or more living affected members. The familial aggregation of AMD shown in this study exemplifies the merit of the UPDB and supports recent research demonstrating significant genetic contribution to disease development and progression.

  20. Age-Related Effects of the Apolipoprotein E Gene on Brain Function.

    Science.gov (United States)

    Matura, Silke; Prvulovic, David; Hartmann, Daniel; Scheibe, Monika; Sepanski, Beate; Butz, Marius; Oertel-Knöchel, Viola; Knöchel, Christian; Karakaya, Tarik; Fußer, Fabian; Hattingen, Elke; Pantel, Johannes

    2016-03-16

    The apolipoprotein E (ApoE) ɛ4 allele is a well-established genetic risk factor for sporadic Alzheimer's disease. Some evidence suggests a negative role of the ApoE ɛ4 allele for cognitive performance in late life, while beneficial effects on cognition have been shown in young age. We investigated age-related effects of the ApoE gene on brain function by assessing cognitive performance, as well as functional activation patterns during retrieval of Face-Name pairs in a group of young (n = 50; age 26.4±4.6 years, 25 ɛ4 carriers) and old (n = 40; age 66.1±7.0 years, 20 ɛ4 carriers) participants. A cross-sectional factorial design was used to examine the effects of age, ApoE genotype, and their interaction on both cognitive performance and the blood oxygenation level dependent (BOLD) brain response during retrieval of Face-Name pairs. While there were no genotype-related differences in cognitive performance, we found a significant interaction of age and ApoE genotype on task-related activation bilaterally in anterior cingulate gyrus and superior frontal gyrus, as well as left and right insula. Old age was associated with increased activity in ɛ4 carriers. The increased BOLD response in old ɛ4 carriers during retrieval could indicate a neurocognitive disadvantage associated with the ɛ4 allele with increasing age. Furthermore, recruitment of neuronal resources resulted in enhanced memory performance in young ɛ4 carriers, pointing to a better neurofunctional capacity associated with the ApoE4 genotype in young age.

  1. Aging and Alzheimer's Disease: Lessons from the Nun Study.

    Science.gov (United States)

    Snowdon, David A.

    1997-01-01

    Describes a woman who maintained high cognitive test scores until her death at 101 years of age despite anatomical evidence of Alzheimer's disease. The woman was part of a larger "Nun Study" in which 678 sisters donated their brains to teach others about the etiology of aging and Alzheimer's disease. Findings are discussed. (RJM)

  2. Aging-Related Systemic Manifestations in COPD Patients and Cigarette Smokers

    Science.gov (United States)

    Boyer, Laurent; Marcos, Elisabeth; Margarit, Laurent; Le Corvoisier, Philippe; Vervoitte, Laetitia; Hamidou, Leila; Frih, Lamia; Audureau, Etienne; Covali-Noroc, Ala; Andujar, Pascal; Saakashvili, Zakaria; Lino, Anne; Ghaleh, Bijan; Hue, Sophie; Derumeaux, Geneviève; Housset, Bruno; Dubois-Randé, Jean-Luc; Boczkowski, Jorge; Maitre, Bernard; Adnot, Serge

    2015-01-01

    Rationale Chronic obstructive pulmonary disease (COPD) is often associated with age-related systemic abnormalities that adversely affect the prognosis. Whether these manifestations are linked to the lung alterations or are independent complications of smoking remains unclear. Objectives To look for aging-related systemic manifestations and telomere shortening in COPD patients and smokers with minor lung destruction responsible for a decline in the diffusing capacity for carbon monoxide (DLCO) corrected for alveolar volume (KCO). Methods Cross-sectional study in 301 individuals (100 with COPD, 100 smokers without COPD, and 101 nonsmokers without COPD). Measurements and Main Results Compared to control smokers, patients with COPD had higher aortic pulse-wave velocity (PWV), lower bone mineral density (BMD) and appendicular skeletal muscle mass index (ASMMI), and shorter telomere length (TL). Insulin resistance (HOMA-IR) and glomerular filtration rate (GFR) were similar between control smokers and COPD patients. Smokers did not differ from nonsmokers for any of these parameters. However, smokers with normal spirometry but low KCO had lower ASMMI values compared to those with normal KCO. Moreover, female smokers with low KCO, had lower BMD and shorter TL compared to those with normal KCO. Conclusions Aging-related abnormalities in patients with COPD are also found in smokers with minor lung dysfunction manifesting as a KCO decrease. Decreased KCO might be useful, particularly among women, for identifying smokers at high risk for aging-related systemic manifestations and telomere shortening. PMID:25785739

  3. The zebrafish as a gerontology model in nervous system aging, disease, and repair.

    Science.gov (United States)

    Van Houcke, Jessie; De Groef, Lies; Dekeyster, Eline; Moons, Lieve

    2015-11-01

    Considering the increasing number of elderly in the world's population today, developing effective treatments for age-related pathologies is one of the biggest challenges in modern medical research. Age-related neurodegeneration, in particular, significantly impacts important sensory, motor, and cognitive functions, seriously constraining life quality of many patients. Although our understanding of the causal mechanisms of aging has greatly improved in recent years, animal model systems still have much to tell us about this complex process. Zebrafish (Danio rerio) have gained enormous popularity for this research topic over the past decade, since their life span is relatively short but, like humans, they are still subject to gradual aging. In addition, the extensive characterization of its well-conserved molecular and cellular physiology makes the zebrafish an excellent model to unravel the underlying mechanisms of aging, disease, and repair. This review provides a comprehensive overview of the progress made in zebrafish gerontology, with special emphasis on nervous system aging. We review the evidence that classic hallmarks of aging can also be recognized within this small vertebrate, both at the molecular and cellular level. Moreover, we illustrate the high level of similarity with age-associated human pathologies through a survey of the functional deficits that arise as zebrafish age. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Ocular Surface Temperature in Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Andrea Sodi

    2014-01-01

    Full Text Available Background. The aim of this study is to investigate the ocular thermographic profiles in age-related macular degeneration (AMD eyes and age-matched controls to detect possible hemodynamic abnormalities, which could be involved in the pathogenesis of the disease. Methods. 32 eyes with early AMD, 37 eyes with atrophic AMD, 30 eyes affected by untreated neovascular AMD, and 43 eyes with fibrotic AMD were included. The control group consisted of 44 healthy eyes. Exclusion criteria were represented by any other ocular diseases other than AMD, tear film abnormalities, systemic cardiovascular abnormalities, diabetes mellitus, and a body temperature higher than 37.5°C. A total of 186 eyes without pupil dilation were investigated by infrared thermography (FLIR A320. The ocular surface temperature (OST of three ocular points was calculated by means of an image processing technique from the infrared images. Two-sample t-test and one-way analysis of variance (ANOVA test were used for statistical analyses. Results. ANOVA analyses showed no significant differences among AMD groups (P value >0.272. OST in AMD patients was significantly lower than in controls (P>0.05. Conclusions. Considering the possible relationship between ocular blood flow and OST, these findings might support the central role of ischemia in the pathogenesis of AMD.

  5. Current evidence for the use of coffee and caffeine to prevent age-related cognitive decline and Alzheimer's disease.

    Science.gov (United States)

    Carman, A J; Dacks, P A; Lane, R F; Shineman, D W; Fillit, H M

    2014-04-01

    Although nothing has been proven conclusively to protect against cognitive aging, Alzheimer's disease or related dementias, decades of research suggest that specific approaches including the consumption of coffee may be effective. While coffee and caffeine are known to enhance short-term memory and cognition, some limited research also suggests that long-term use may protect against cognitive decline or dementia. In vitro and pre-clinical animal models have identified plausible neuroprotective mechanisms of action of both caffeine and other bioactive components of coffee, though epidemiology has produced mixed results. Some studies suggest a protective association while others report no benefit. To our knowledge, no evidence has been gathered from randomized controlled trials. Although moderate consumption of caffeinated coffee is generally safe for healthy people, it may not be for everyone, since comorbidities and personal genetics influence potential benefits and risks. Future studies could include short-term clinical trials with biomarker outcomes to validate findings from pre-clinical models and improved epidemiological studies that incorporate more standardized methods of data collection and analysis. Given the enormous economic and emotional toll threatened by the current epidemic of Alzheimer's disease and other dementias, it is critically important to validate potential prevention strategies such as coffee and caffeine.

  6. Prevalence of age-related maculopathy and age-related macular degeneration among the inuit in Greenland. The Greenland Inuit Eye Study

    DEFF Research Database (Denmark)

    Andersen, Mads Varis Nis; Rosenberg, Thomas; la Cour, Morten

    2008-01-01

    To examine the age- and gender-specific prevalence and describe the common phenotype of early age-related maculopathy (ARM) and late-stage age-related macular degeneration (AMD) among the Inuit in Greenland.......To examine the age- and gender-specific prevalence and describe the common phenotype of early age-related maculopathy (ARM) and late-stage age-related macular degeneration (AMD) among the Inuit in Greenland....

  7. CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism.

    Science.gov (United States)

    Camacho-Pereira, Juliana; Tarragó, Mariana G; Chini, Claudia C S; Nin, Veronica; Escande, Carlos; Warner, Gina M; Puranik, Amrutesh S; Schoon, Renee A; Reid, Joel M; Galina, Antonio; Chini, Eduardo N

    2016-06-14

    Nicotinamide adenine dinucleotide (NAD) levels decrease during aging and are involved in age-related metabolic decline. To date, the mechanism responsible for the age-related reduction in NAD has not been elucidated. Here we demonstrate that expression and activity of the NADase CD38 increase with aging and that CD38 is required for the age-related NAD decline and mitochondrial dysfunction via a pathway mediated at least in part by regulation of SIRT3 activity. We also identified CD38 as the main enzyme involved in the degradation of the NAD precursor nicotinamide mononucleotide (NMN) in vivo, indicating that CD38 has a key role in the modulation of NAD-replacement therapy for aging and metabolic diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Dietary Curcumin Ameliorates Aging-Related Cerebrovascular Dysfunction through the AMPK/Uncoupling Protein 2 Pathway

    Directory of Open Access Journals (Sweden)

    Yunfei Pu

    2013-11-01

    Full Text Available Background/Aims: Age-related cerebrovascular dysfunction contributes to stroke, cerebral amyloid angiopathy, cognitive decline and neurodegenerative diseases. One pathogenic mechanism underlying this effect is increased oxidative stress. Up-regulation of mitochondrial uncoupling protein 2 (UCP2 plays a crucial role in regulating reactive oxygen species (ROS production. Dietary patterns are widely recognized as contributors to cardiovascular and cerebrovascular disease. In this study, we tested the hypothesis that dietary curcumin, which has an antioxidant effect, can improve aging-related cerebrovascular dysfunction via UCP2 up-regulation. Methods: The 24-month-old male rodents used in this study, including male Sprague Dawley (SD rats and UCP2 knockout (UCP2-/- and matched wild type mice, were given dietary curcumin (0.2%. The young control rodents were 6-month-old. Rodent cerebral artery vasorelaxation was detected by wire myograph. The AMPK/UCP2 pathway and p-eNOS in cerebrovascular and endothelial cells were observed by immunoblotting. Results: Dietary curcumin administration for one month remarkably restored the impaired cerebrovascular endothelium-dependent vasorelaxation in aging SD rats. In cerebral arteries from aging SD rats and cultured endothelial cells, curcumin promoted eNOS and AMPK phosphorylation, up-regulated UCP2 and reduced ROS production. These effects of curcumin were abolished by either AMPK or UCP2 inhibition. Chronic dietary curcumin significantly reduced ROS production and improved cerebrovascular endothelium-dependent relaxation in aging wild type mice but not in aging UCP2-/- mice. Conclusions: Curcumin improves aging-related cerebrovascular dysfunction via the AMPK/UCP2 pathway.

  9. Molecular Age-Related Changes in the Anterior Segment of the Eye

    Directory of Open Access Journals (Sweden)

    Luis Fernando Hernandez-Zimbron

    2017-01-01

    Full Text Available Purpose. To examine the current knowledge about the age-related processes in the anterior segment of the eye at a biological, clinical, and molecular level. Methods. We reviewed the available published literature that addresses the aging process of the anterior segment of the eye and its associated molecular and physiological events. We performed a search on PubMed, CINAHL, and Embase using the MeSH terms “eye,” “anterior segment,” and “age.” We generated searches to account for synonyms of these keywords and MESH headings as follows: (1 “Eye” AND “ageing process” OR “anterior segment ageing” and (2 “Anterior segment” AND “ageing process” OR “anterior segment” AND “molecular changes” AND “age.” Results. Among the principal causes of age-dependent alterations in the anterior segment of the eye, we found the mutation of the TGF-β gene and loss of autophagy in addition to oxidative stress, which contributes to the pathogenesis of degenerative diseases. Conclusions. In this review, we summarize the current knowledge regarding some of the molecular mechanisms related to aging in the anterior segment of the eye. We also introduce and propose potential roles of autophagy, an important mechanism responsible for maintaining homeostasis and proteostasis under stress conditions in the anterior segment during aging.

  10. Mouse models of ageing and their relevance to disease.

    Science.gov (United States)

    Kõks, Sulev; Dogan, Soner; Tuna, Bilge Guvenc; González-Navarro, Herminia; Potter, Paul; Vandenbroucke, Roosmarijn E

    2016-12-01

    Ageing is a process that gradually increases the organism's vulnerability to death. It affects different biological pathways, and the underlying cellular mechanisms are complex. In view of the growing disease burden of ageing populations, increasing efforts are being invested in understanding the pathways and mechanisms of ageing. We review some mouse models commonly used in studies on ageing, highlight the advantages and disadvantages of the different strategies, and discuss their relevance to disease susceptibility. In addition to addressing the genetics and phenotypic analysis of mice, we discuss examples of models of delayed or accelerated ageing and their modulation by caloric restriction. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  11. Variability of disease activity in patients treated with ranibizumab for neovascular age-related macular degeneration.

    Science.gov (United States)

    Enders, P; Scholz, P; Muether, P S; Fauser, S

    2016-08-01

    PurposeTo analyze choroidal neovasularization (CNV) activity and recurrence patterns in patients with neovascular age-related macular degeneration (nAMD) treated with ranibizumab, and the correlation with individual intraocular vascular endothelial growth factor (VEGF) suppression time (VST).MethodsPost-hoc analysis of data from a prospective, non-randomized clinical study. Patients with nAMD treated with ranibizumab on a pro re nata regimen. Disease activity was analyzed monthly by spectral-domain optical coherence tomography and correlated with VSTs.ResultsOverall, 73 eyes of 73 patients were included in the study with a mean follow-up of 717 days (range: 412-1239 days). Overall, the mean CNV-activity-free interval was 76.5 days (range: 0-829 days). The individual range of the length of dry intervals was high. A total of 42% of patients had a range of more than 90 days. Overall, 16% of patients showed persistent activity. And 12% stayed dry after the initial ranibizumab treatment. No significant correlation was found between the CNV-recurrence pattern and VST (P=0.12).ConclusionsCNV activity in nAMD is irregular, which is reflected in the range of the duration of dry intervals and late recurrences. The biomarker VST solely seems not to be sufficient to explain recurrence pattern of CNV in all AMD patients.

  12. Treatments for dry age-related macular degeneration and Stargardt disease: a systematic review.

    Science.gov (United States)

    Waugh, Norman; Loveman, Emma; Colquitt, Jill; Royle, Pamela; Yeong, Jian Lee; Hoad, Geraldine; Lois, Noemi

    2018-05-01

    Age-related macular degeneration (AMD) is the leading cause of visual loss in older people. Advanced AMD takes two forms, neovascular (wet) and atrophic (dry). Stargardt disease (STGD) is the commonest form of inherited macular dystrophy. To carry out a systematic review of treatments for dry AMD and STGD, and to identify emerging treatments where future NIHR research might be commissioned. Systematic review. We searched MEDLINE, EMBASE, Web of Science and The Cochrane Library from 2005 to 13 July 2017 for reviews, journal articles and meeting abstracts. We looked for studies of interventions that aim to preserve or restore vision in people with dry AMD or STGD. The most important outcomes are those that matter to patients: visual acuity (VA), contrast sensitivity, reading speed, ability to drive, adverse effects of treatment, quality of life, progression of disease and patient preference. However, visual loss is a late event and intermediate predictors of future decline were accepted if there was good evidence that they are strong predictors of subsequent visual outcomes. These include changes detectable by investigation, but not necessarily noticed by people with AMD or STGD. ClinicalTrials.gov, the World Health Organization search portal and the UK Clinical Trials gateway were searched for ongoing and recently completed clinical trials. The titles and abstracts of 7948 articles were screened for inclusion. The full text of 398 articles were obtained for further screening and checking of references and 112 articles were included in the final report. Overall, there were disappointingly few good-quality studies (including of sufficient size and duration) reporting useful outcomes, particularly in STGD. However we did identify a number of promising research topics, including drug treatments, stem cells, new forms of laser treatment, and implantable intraocular lens telescopes. In many cases, research is already under way, funded by industry or governments. In AMD

  13. A common copy number variation polymorphism in the CNTNAP2 gene: sexual dimorphism in association with healthy aging and disease.

    Science.gov (United States)

    Iakoubov, Leonid; Mossakowska, Malgorzata; Szwed, Malgorzata; Puzianowska-Kuznicka, Monika

    2015-01-01

    New therapeutic targets are needed to fight aging-related diseases and increase life span. A new female-specific association with diseases and limited survival past 80 years was recently reported for a copy number variation (CNV) in the CNTNAP4 gene from the neurexin superfamily. We asked whether there are CNVs that are associated with aging phenotypes within other genes from the neurexin superfamily and whether this association is sex specific. Select CNV polymorphisms were genotyped with proprietary TaqMan qPCR assays. A case/control study, in which a group of 81- to 90-year-old community-dwelling Caucasians with no chronic diseases (case) was compared to a similar control group of 65- to 75-year-olds, revealed a negative association with healthy aging for the ins allele of common esv11910 CNV in the CNTNAP2 gene (n = 388; OR = 0.29, 95% CI: 0.14-0.59, p = 0.0004 for males, and OR = 0.82, 95% CI: 0.42-1.57, p = 0.625 for females). This male-specific association was validated in a study of an independent group of 76- to 80-year-olds. To look for a corresponding positive association of the allele with aging-related diseases, two case subgroups of 81- to 90-year-olds, one composed of individuals with cognitive impairment and the other with various diseases not directly related to the nervous system, such as cardiovascular diseases, etc., were compared to a healthy control subgroup of the same age. A positive male-specific association was found for both cases (OR = 2.75, p = 0.008 for association with cognitive impairment, and OR = 3.18, p = 0.002 for other diseases combined). A new male-specific association with aging is reported for a CNV in the CNTNAP2 gene. The polymorphism might be useful for diagnosing individual genetic predispositions to healthy aging versus aging complicated by chronic diseases. © 2014 S. Karger AG, Basel.

  14. 8 Areas of Age-Related Change

    Science.gov (United States)

    ... please turn Javascript on. Photo: PhotoDisc 1. Brain: Memory and Alzheimer's Disease (AD) As adults age, many ... optic nerve. This leads to vision loss and blindness. Most people with glaucoma have no early symptoms ...

  15. A comprehensive survey of sequence variation in the ABCA4 (ABCR) gene in Stargardt disease and age-related macular degeneration.

    Science.gov (United States)

    Rivera, A; White, K; Stöhr, H; Steiner, K; Hemmrich, N; Grimm, T; Jurklies, B; Lorenz, B; Scholl, H P; Apfelstedt-Sylla, E; Weber, B H

    2000-10-01

    Stargardt disease (STGD) is a common autosomal recessive maculopathy of early and young-adult onset and is caused by alterations in the gene encoding the photoreceptor-specific ATP-binding cassette (ABC) transporter (ABCA4). We have studied 144 patients with STGD and 220 unaffected individuals ascertained from the German population, to complete a comprehensive, population-specific survey of the sequence variation in the ABCA4 gene. In addition, we have assessed the proposed role for ABCA4 in age-related macular degeneration (AMD), a common cause of late-onset blindness, by studying 200 affected individuals with late-stage disease. Using a screening strategy based primarily on denaturing gradient gel electrophoresis, we have identified in the three study groups a total of 127 unique alterations, of which 90 have not been previously reported, and have classified 72 as probable pathogenic mutations. Of the 288 STGD chromosomes studied, mutations were identified in 166, resulting in a detection rate of approximately 58%. Eight different alleles account for 61% of the identified disease alleles, and at least one of these, the L541P-A1038V complex allele, appears to be a founder mutation in the German population. When the group with AMD and the control group were analyzed with the same methodology, 18 patients with AMD and 12 controls were found to harbor possible disease-associated alterations. This represents no significant difference between the two groups; however, for detection of modest effects of rare alleles in complex diseases, the analysis of larger cohorts of patients may be required.

  16. Age-related fat deposition in multifidus muscle could be a marker for nonalcoholic fatty liver disease

    International Nuclear Information System (INIS)

    Kitajima, Yoichiro; Eguchi, Yuichiro; Ishibashi, Eriko

    2010-01-01

    Although nonalcoholic fatty liver disease (NAFLD) is associated with visceral obesity, the relationship between visceral fat accumulation and skeletal muscle steatosis in patients with NAFLD has not been established. We evaluated: the relationship between multifidus muscular tissue steatosis, visceral fat accumulation, and biochemical data in a cross-sectional study, and the influence of weight reduction on multifidus muscular tissue steatosis in a longitudinal study. Three hundred thirty-three NAFLD patients were enrolled. Hepatic steatosis, visceral fat area, and the multifidus muscle/subcutaneous fat attenuation ratio (MM/F ratio) were evaluated by computed tomography. To evaluate how weight reduction produced by diet and exercise affected the MM/F ratio, changes in the MM/F ratio were compared between weight reduction and non-weight reduction groups. There was a gender difference in MM/F ratios. The MM/F ratio was significantly correlated with age (male r=0.613, P<0.01; female r=0.440, P<0.01). The MM/F ratio was positively correlated with visceral fat area (male: r=0.262, P<0.01; female: r=0.214, P<0.01). A decrease in the MM/F ratio, concomitant with reduced visceral fat accumulation, led to alleviation of hepatic steatosis in 20 patients with weight reduction, but not in 22 patients without weight reduction. The MM/F ratio was closely related to aging and visceral fat accumulation. The MM/F ratio was improved by weight reduction, indicating that fat accumulation in the multifidus muscle evaluated by computed tomography might be a therapeutic indicator of NAFLD. (author)

  17. The Impacts of Cellular Senescence in Elderly Pneumonia and in Age-Related Lung Diseases That Increase the Risk of Respiratory Infections.

    Science.gov (United States)

    Yanagi, Shigehisa; Tsubouchi, Hironobu; Miura, Ayako; Matsuo, Ayako; Matsumoto, Nobuhiro; Nakazato, Masamitsu

    2017-02-25

    Pneumonia generates considerable negative impacts on the elderly. Despite the widespread uses of vaccines and appropriate antibiotics, the morbidity and mortality of elderly pneumonia are significantly higher compared to the counterparts of young populations. The definitive mechanisms of high vulnerability in the elderly against pathogen threats are unclear. Age-associated, chronic low-grade inflammation augments the susceptibility and severity of pneumonia in the elderly. Cellular senescence, one of the hallmarks of aging, has its own characteristics, cell growth arrest and senescence-associated secretory phenotype (SASP). These properties are beneficial if the sequence of senescence-clearance-regeneration is transient in manner. However, persisting senescent cell accumulation and excessive SASP might induce sustained low-grade inflammation and disruption of normal tissue microenvironments in aged tissue. Emerging evidence indicates that cellular senescence is a key component in the pathogenesis of chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), which are known to be age-related and increase the risk of pneumonia. In addition to their structural collapses, COPD and IPF might increase the vulnerability to pathogen insults through SASP. Here, we discuss the current advances in understanding of the impacts of cellular senescence in elderly pneumonia and in these chronic lung disorders that heighten the risk of respiratory infections.

  18. Associations between genetic polymorphisms of insulin-like growth factor axis genes and risk for age-related macular degeneration

    Science.gov (United States)

    Purpose: Our objective was to investigate if insulin-like growth factor (IGF) axis genes affect the risk for age-related macular degeneration (AMD). Methods: 864 Caucasian non-diabetic participants from the Age-Related Eye Disease Study (AREDS) Genetic Repository were used in this case control st...

  19. Recent developments in age-related macular degeneration: a review

    Science.gov (United States)

    Al-Zamil, Waseem M; Yassin, Sanaa A

    2017-01-01

    Background Visual impairment in elderly people is a considerable health problem that significantly affects quality of life of millions worldwide. The magnitude of this issue is becoming more evident with an aging population and an increasing number of older individuals. Objective The objective of this article was to review the clinical and pathological aspects of age-related macular degeneration (AMD), diagnostic tools, and therapeutic modalities presently available or underway for both atrophic and wet forms of the disease. Methods An online review of the PubMed database was performed, searching for the key words. The search was limited to articles published since 1980 to date. Results Several risk factors have been linked to AMD, such as age (>60 years), lifestyle (smoking and diet), and family history. Although the pathogenesis of AMD remains unclear, genetic factors have been implicated in the condition. Treatment for atrophic AMD is mainly close observation, coupled with nutritional supplements such as zinc and antioxidants, whereas treatment of wet AMD is based on targeting choroidal neovascular membranes. Conclusion Identification of modifiable risk factors would improve the possibilities of preventing the progression of AMD. The role of anti-vascular endothelial growth factor (anti-VEGF) agents has transformed the therapeutic approach of the potentially blinding disease “wet AMD” into a more favorable outcome. PMID:28860733

  20. Risk Factors and Biomarkers of Age-Related Macular Degeneration

    Science.gov (United States)

    Lambert, Nathan G.; Singh, Malkit K.; ElShelmani, Hanan; Mansergh, Fiona C.; Wride, Michael A.; Padilla, Maximilian; Keegan, David; Hogg, Ruth E.; Ambati, Balamurali K.

    2016-01-01

    A biomarker can be a substance or structure measured in body parts, fluids or products that can affect or predict disease incidence. As age-related macular degeneration (AMD) is the leading cause of blindness in the developed world, much research and effort has been invested in the identification of different biomarkers to predict disease incidence, identify at risk individuals, elucidate causative pathophysiological etiologies, guide screening, monitoring and treatment parameters, and predict disease outcomes. To date, a host of genetic, environmental, proteomic, and cellular targets have been identified as both risk factors and potential biomarkers for AMD. Despite this, their use has been confined to research settings and has not yet crossed into the clinical arena. A greater understanding of these factors and their use as potential biomarkers for AMD can guide future research and clinical practice. This article will discuss known risk factors and novel, potential biomarkers of AMD in addition to their application in both academic and clinical settings. PMID:27156982

  1. Age-related differences in metabolites in the posterior cingulate cortex and hippocampus of normal ageing brain: A 1H-MRS study

    International Nuclear Information System (INIS)

    Reyngoudt, Harmen; Claeys, Tom; Vlerick, Leslie; Verleden, Stijn; Acou, Marjan; Deblaere, Karel; De Deene, Yves; Audenaert, Kurt; Goethals, Ingeborg; Achten, Eric

    2012-01-01

    Objective: To study age-related metabolic changes in N-acetylaspartate (NAA), total creatine (tCr), choline (Cho) and myo-inositol (Ins). Materials and methods: Proton magnetic resonance spectroscopy ( 1 H-MRS) was performed in the posterior cingulate cortex (PCC) and the left hippocampus (HC) of 90 healthy subjects (42 women and 48 men aged 18–76 years, mean ± SD, 48.4 ± 16.8 years). Both metabolite ratios and absolute metabolite concentrations were evaluated. Analysis of covariance (ANCOVA) and linear regression were used for statistical analysis. Results: Metabolite ratios Ins/tCr and Ins/H 2 O were found significantly increased with age in the PCC (P 2 O was only observed in the PCC (P 1 H-MRS results in these specific brain regions can be important to differentiate normal ageing from age-related pathologies such as mild cognitive impairment (MCI) and Alzheimer's disease.

  2. Functional and Homeostatic Impact of Age-Related Changes in Lymph Node Stroma

    Directory of Open Access Journals (Sweden)

    Heather L. Thompson

    2017-06-01

    Full Text Available Adults over 65 years of age are more vulnerable to infectious disease and show poor responses to vaccination relative to those under 50. A complex set of age-related changes in the immune system is believed to be largely responsible for these defects. These changes, collectively termed immune senescence, encompass alterations in both the innate and adaptive immune systems, in the microenvironments where immune cells develop or reside, and in soluble factors that guide immune homeostasis and function. While age-related changes in primary lymphoid organs (bone marrow, and, in particular, the thymus, which involutes in the first third of life have been long appreciated, changes affecting aging secondary lymphoid organs, and, in particular, aging lymph nodes (LNs have been less well characterized. Over the last 20 years, LN stromal cells have emerged as key players in maintaining LN morphology and immune homeostasis, as well as in coordinating immune responses to pathogens. Here, we review recent progress in understanding the contributions of LN stromal cells to immune senescence. We discuss approaches to understand the mechanisms behind the decline in LN stromal cells and conclude by considering potential strategies to rejuvenate aging LN stroma to improve immune homeostasis, immune responses, and vaccine efficacy in the elderly.

  3. Genetics of Age-Related Macular Degeneration: Current Concepts, Future Directions

    Science.gov (United States)

    DeAngelis, Margaret M.; Silveira, Alexandra C.; Carr, Elizabeth A.; Kim, Ivana K.

    2014-01-01

    Age-related macular degeneration (AMD) is a progressive degenerative disease which leads to blindness, affecting the quality of life of millions of Americans. More than 1.75 million individuals in the United States are affected by the advanced form of AMD. The etiological pathway of AMD is not yet fully understood, but there is a clear genetic influence on disease risk. To date, the 1q32 (CFH) and 10q26 (PLEKHA1/ARMS2/HTRA1) loci are the most strongly associated with disease; however, the variation in these genomic regions alone is unable to predict disease development with high accuracy. Therefore, current genetic studies are aimed at identifying new genes associated with AMD and their modifiers, with the goal of discovering diagnostic or prognostic biomarkers. Moreover, these studies provide the foundation for further investigation into the pathophysiology of AMD by utilizing a systems-biology-based approach to elucidate underlying mechanistic pathways. PMID:21609220

  4. Dry age-related macular degeneration: mechanisms, therapeutic targets, and imaging.

    Science.gov (United States)

    Bowes Rickman, Catherine; Farsiu, Sina; Toth, Cynthia A; Klingeborn, Mikael

    2013-12-13

    Age-related macular degeneration is the leading cause of irreversible visual dysfunction in individuals over 65 in Western Society. Patients with AMD are classified as having early stage disease (early AMD), in which visual function is affected, or late AMD (generally characterized as either "wet" neovascular AMD, "dry" atrophic AMD or both), in which central vision is severely compromised or lost. Until recently, there have been no therapies available to treat the disorder(s). Now, the most common wet form of late-stage AMD, choroidal neovascularization, generally responds to treatment with anti-vascular endothelial growth factor therapies. Nevertheless, there are no current therapies to restore lost vision in eyes with advanced atrophic AMD. Oral supplementation with the Age-Related Eye Disease Study (AREDS) or AREDS2 formulation (antioxidant vitamins C and E, lutein, zeaxanthin, and zinc) has been shown to reduce the risk of progression to advanced AMD, although the impact was in neovascular rather than atrophic AMD. Recent findings, however, have demonstrated several features of early AMD that are likely to be druggable targets for treatment. Studies have established that much of the genetic risk for AMD is associated with complement genes. Consequently, several complement-based therapeutic treatment approaches are being pursued. Potential treatment strategies against AMD deposit formation and protein and/or lipid deposition will be discussed, including anti-amyloid therapies. In addition, the role of autophagy in AMD and prevention of oxidative stress through modulation of the antioxidant system will be explored. Finally, the success of these new therapies in clinical trials and beyond relies on early detection, disease typing, and predicting disease progression, areas that are currently being rapidly transformed by improving imaging modalities and functional assays.

  5. Dry Age-Related Macular Degeneration: Mechanisms, Therapeutic Targets, and Imaging

    Science.gov (United States)

    Bowes Rickman, Catherine; Farsiu, Sina; Toth, Cynthia A.; Klingeborn, Mikael

    2013-01-01

    Age-related macular degeneration is the leading cause of irreversible visual dysfunction in individuals over 65 in Western Society. Patients with AMD are classified as having early stage disease (early AMD), in which visual function is affected, or late AMD (generally characterized as either “wet” neovascular AMD, “dry” atrophic AMD or both), in which central vision is severely compromised or lost. Until recently, there have been no therapies available to treat the disorder(s). Now, the most common wet form of late-stage AMD, choroidal neovascularization, generally responds to treatment with anti–vascular endothelial growth factor therapies. Nevertheless, there are no current therapies to restore lost vision in eyes with advanced atrophic AMD. Oral supplementation with the Age-Related Eye Disease Study (AREDS) or AREDS2 formulation (antioxidant vitamins C and E, lutein, zeaxanthin, and zinc) has been shown to reduce the risk of progression to advanced AMD, although the impact was in neovascular rather than atrophic AMD. Recent findings, however, have demonstrated several features of early AMD that are likely to be druggable targets for treatment. Studies have established that much of the genetic risk for AMD is associated with complement genes. Consequently, several complement-based therapeutic treatment approaches are being pursued. Potential treatment strategies against AMD deposit formation and protein and/or lipid deposition will be discussed, including anti-amyloid therapies. In addition, the role of autophagy in AMD and prevention of oxidative stress through modulation of the antioxidant system will be explored. Finally, the success of these new therapies in clinical trials and beyond relies on early detection, disease typing, and predicting disease progression, areas that are currently being rapidly transformed by improving imaging modalities and functional assays. PMID:24335072

  6. Overexpression of Amyloid Precursor Protein Promotes the Onset of Seborrhoeic Keratosis and is Related to Skin Ageing.

    Science.gov (United States)

    Li, Yuanying; Wang, Yu; Zhang, Wei; Jiang, Leiwei; Zhou, Wenming; Liu, Zhi; Li, Shijun; Lu, Hongguang

    2018-02-28

    Seborrhoeic keratosis is an age-related skin disease. Amyloid precursor protein (APP) plays an important role in the pathogenesis of age-related Alzheimer's disease. The aim of this study was to elucidate the expression characteristics of APP in seborrhoeic keratosis tissues (n = 50), and explore whether the production of APP is related to the onset of seborrhoeic keratosis and skin ageing, including ultraviolet (UV)-induced ageing, as observed in normal skin (n = 79). The results of immunohistochemistry, Western blotting and quantitative real-time PCR showed that APP and its downstream products (i.e. amyloid-β42) were more highly expressed in seborrhoeic keratosis than in paired adjacent normal skin tissues. In contrast, the expression of its key secretase (i.e. β-secretase1) was generally low. Furthermore, APP expression was higher in UV-exposed than non-exposed skin sites, and expression in the older age group (61-85 years) was greater than that in the younger age group (41-60 years) in seborrhoeic keratosis tissues (pkeratosis and is a marker of skin ageing and UV damage. Further research will elucidate whether therapeutic mitigation of increased levels of APP in the skin might delay the onset of seborrhoeic keratosis and skin ageing.

  7. Integrated Evaluation of Age-Related Changes in Structural and Functional Vascular Parameters Used to Assess Arterial Aging, Subclinical Atherosclerosis, and Cardiovascular Risk in Uruguayan Adults: CUiiDARTE Project.

    Science.gov (United States)

    Bia, Daniel; Zócalo, Yanina; Farro, Ignacio; Torrado, Juan; Farro, Federico; Florio, Lucía; Olascoaga, Alicia; Brum, Javier; Alallón, Walter; Negreira, Carlos; Lluberas, Ricardo; Armentano, Ricardo L

    2011-01-01

    This work was carried out in a Uruguayan (South American) population to characterize aging-associated physiological arterial changes. Parameters markers of subclinical atherosclerosis and that associate age-related changes were evaluated in healthy people. A conservative approach was used and people with nonphysiological and pathological conditions were excluded. Then, we excluded subjects with (a) cardiovascular (CV) symptoms, (b) CV disease, (c) diabetes mellitus or renal failure, and (d) traditional CV risk factors (other than age and gender). Subjects (n = 388) were submitted to non-invasive vascular studies (gold-standard techniques), to evaluate (1) common (CCA), internal, and external carotid plaque prevalence, (2) CCA intima-media thickness and diameter, (3) CCA stiffness (percentual pulsatility, compliance, distensibility, and stiffness index), (4) aortic stiffness (carotid-femoral pulse wave velocity), and (5) peripheral and central pressure wave-derived parameters. Age groups: ≤20, 21-30, 31-40, 41-50, 51-60, 61-70, and 71-80 years old. Age-related structural and functional vascular parameters profiles were obtained and analyzed considering data from other populations. The work has the strength of being the first, in Latin America, that uses an integrative approach to characterize vascular aging-related changes. Data could be used to define vascular aging and abnormal or disease-related changes.

  8. The healthcare burden imposed by liver disease in aging Baby Boomers.

    Science.gov (United States)

    Davis, Gary L; Roberts, William L

    2010-02-01

    The Baby Boomer generation is composed of 78 million Americans who are just beginning to reach their retirement years. Most Boomers have at least one chronic health problem, and these significantly increase the expense of providing medical care. Liver disease is the 12th most common cause of death in the United States, representing a relatively small portion of overall healthcare costs compared with cardiovascular disease and malignancy. Nonetheless, hepatitis C and fatty liver disease are more common in the Boomers and may play a more dominant role as they age. As a consequence, primary liver cancer is likely to become more prevalent. As with most chronic illnesses, prevention rather than disease management is likely to have the greatest impact. For those already afflicted by chronic liver disease, recognition and treatment can reduce the incidence of late complications, as was clearly demonstrated with chronic hepatitis B and C. Perhaps obesity is the greatest threat to our future health, and fatty liver disease, although likely preventable, will probably become the disease that fills the waiting rooms of future hepatologists.

  9. Bone quality changes associated with aging and disease: a review.

    Science.gov (United States)

    Boskey, Adele L; Imbert, Laurianne

    2017-12-01

    Bone quality encompasses all the characteristics of bone that, in addition to density, contribute to its resistance to fracture. In this review, we consider changes in architecture, porosity, and composition, including collagen structure, mineral composition, and crystal size. These factors all are known to vary with tissue and animal ages, and health status. Bone morphology and presence of microcracks, which also contribute to bone quality, will not be discussed in this review. Correlations with mechanical performance for collagen cross-linking, crystallinity, and carbonate content are contrasted with mineral content. Age-dependent changes in humans and rodents are discussed in relation to rodent models of disease. Examples are osteoporosis, osteomalacia, osteogenesis imperfecta (OI), and osteopetrosis in both humans and animal models. Each of these conditions, along with aging, is associated with increased fracture risk for distinct reasons. © 2017 New York Academy of Sciences.

  10. On the relative role of different age groups in influenza epidemics.

    Science.gov (United States)

    Worby, Colin J; Chaves, Sandra S; Wallinga, Jacco; Lipsitch, Marc; Finelli, Lyn; Goldstein, Edward

    2015-12-01

    The identification of key "driver" groups in influenza epidemics is of much interest for the implementation of effective public health response strategies, including vaccination programs. However, the relative importance of different age groups in propagating epidemics is uncertain. During a communicable disease outbreak, some groups may be disproportionately represented during the outbreak's ascent due to increased susceptibility and/or contact rates. Such groups or subpopulations can be identified by considering the proportion of cases within the subpopulation occurring before (Bp) and after the epidemic peak (Ap) to calculate the subpopulation's relative risk, RR=Bp/Ap. We estimated RR for several subpopulations (age groups) using data on laboratory-confirmed US influenza hospitalizations during epidemics between 2009-2014. Additionally, we simulated various influenza outbreaks in an age-stratified population, relating the RR to the impact of vaccination in each subpopulation on the epidemic's initial effective reproductive number R_e(0). We found that children aged 5-17 had the highest estimates of RR during the five largest influenza A outbreaks, though the relative magnitude of RR in this age group compared to other age groups varied, being highest for the 2009 A/H1N1 pandemic. For the 2010-2011 and 2012-2013 influenza B epidemics, adults aged 18-49, and 0-4 year-olds had the highest estimates of RR respectively. For 83% of simulated epidemics, the group with the highest RR was also the group for which initial distribution of a given quantity of vaccine would result in the largest reduction of R_e(0). In the largest 40% of simulated outbreaks, the group with the highest RR and the largest vaccination impact was children 5-17. While the relative importance of different age groups in propagating influenza outbreaks varies, children aged 5-17 play the leading role during the largest influenza A epidemics. Extra vaccination efforts for this group may contribute

  11. Age-related decrease in the mitochondrial sirtuin deacetylase Sirt3 expression associated with ROS accumulation in the auditory cortex of the mimetic aging rat model.

    Science.gov (United States)

    Zeng, Lingling; Yang, Yang; Hu, Yujuan; Sun, Yu; Du, Zhengde; Xie, Zhen; Zhou, Tao; Kong, Weijia

    2014-01-01

    Age-related dysfunction of the central auditory system, also known as central presbycusis, can affect speech perception and sound localization. Understanding the pathogenesis of central presbycusis will help to develop novel approaches to prevent or treat this disease. In this study, the mechanisms of central presbycusis were investigated using a mimetic aging rat model induced by chronic injection of D-galactose (D-Gal). We showed that malondialdehyde (MDA) levels were increased and manganese superoxide dismutase (SOD2) activity was reduced in the auditory cortex in natural aging and D-Gal-induced mimetic aging rats. Furthermore, mitochondrial DNA (mtDNA) 4834 bp deletion, abnormal ultrastructure and cell apoptosis in the auditory cortex were also found in natural aging and D-Gal mimetic aging rats. Sirt3, a mitochondrial NAD+-dependent deacetylase, has been shown to play a crucial role in controlling cellular reactive oxygen species (ROS) homeostasis. However, the role of Sirt3 in the pathogenesis of age-related central auditory cortex deterioration is still unclear. Here, we showed that decreased Sirt3 expression might be associated with increased SOD2 acetylation, which negatively regulates SOD2 activity. Oxidative stress accumulation was likely the result of low SOD2 activity and a decline in ROS clearance. Our findings indicate that Sirt3 might play an essential role, via the mediation of SOD2, in central presbycusis and that manipulation of Sirt3 expression might provide a new approach to combat aging and oxidative stress-related diseases.

  12. Cerebral glucose metabolic patterns in Alzheimer's disease. Effect of gender and age at dementia onset

    International Nuclear Information System (INIS)

    Small, G.W.; Kuhl, D.E.; Riege, W.H.; Fujikawa, D.G.; Ashford, J.W.; Metter, E.J.; Mazziotta, J.C.

    1989-01-01

    No previous study of Alzheimer's disease has, to our knowledge, assessed the effect of both age at dementia onset and gender on cerebral glucose metabolic patterns. To this end, we used positron emission tomography (fludeoxyglucose F 18 method) to study 24 patients with clinical diagnoses of probable Alzheimer's disease. Comparisons of the 13 patients with early-onset dementia (less than 65 years of age) with the 11 patients with late-onset dementia (greater than 65 years of age) revealed significantly lower left parietal metabolic ratios (left posterior parietal region divided by the hemispheric average) in the early-onset group. The metabolic ratio of posterior parietal cortex divided by the relatively disease-stable average of caudate and thalamus also separated patients with early-onset dementia from those with late-onset dementia, but not men from women. Further comparisons between sexes showed that, in all brain regions studied, the 9 postmenopausal women had higher nonweighted mean metabolic rates than the 15 men from the same age group, with hemispheric sex differences of 9% on the right and 7% on the left. These results demonstrate decreased parietal ratios in early-onset dementia of Alzheimer's disease, independent of a gender effect

  13. Protein Oxidation in Aging: Does It Play a Role in Aging Progression?

    Science.gov (United States)

    Reeg, Sandra

    2015-01-01

    Abstract Significance: A constant accumulation of oxidized proteins takes place during aging. Oxidation of proteins leads to a partial unfolding and, therefore, to aggregation. Protein aggregates impair the activity of cellular proteolytic systems (proteasomes, lysosomes), resulting in further accumulation of oxidized proteins. In addition, the accumulation of highly crosslinked protein aggregates leads to further oxidant formation, damage to macromolecules, and, finally, to apoptotic cell death. Furthermore, protein oxidation seems to play a role in the development of various age-related diseases, for example, neurodegenerative diseases. Recent Advances: The highly oxidized lipofuscin accumulates during aging. Lipofuscin formation might cause impaired lysosomal and proteasomal degradation, metal ion accumulation, increased reactive oxygen species formation, and apoptosis. Critical Issues: It is still unclear to which extent protein oxidation is involved in the progression of aging and in the development of some age-related diseases. Future Directions: An extensive knowledge of the effects of protein oxidation on the aging process and its contribution to the development of age-related diseases could enable further strategies to reduce age-related impairments. Strategies aimed at lowering aggregate formation might be a straightforward intervention to reduce age-related malfunctions of organs. Antioxid. Redox Signal. 23, 239–255. PMID:25178482

  14. Age and osteoarthritis: are AGEs the link?

    NARCIS (Netherlands)

    Vos, P.A.J.M.

    2012-01-01

    Osteoarthritis is a common joint disease in the elderly. By far the most important risk factor for osteoarthritis is aging. Age-related changes in the articular cartilage may be responsible for age-related increase in the number of people with osteoarthritis. One of the most striking changes in

  15. Is parental age related to the risk of Alzheimer's disease

    NARCIS (Netherlands)

    C.M. van Duijn (Cornelia); W. Schulte (Wim); T.A. Tanja (Teun); R. Haaxma (Rob); A.J. Lameris; R.J. Saan; A. Hofman (Albert)

    1990-01-01

    textabstractAdvanced maternal and paternal age were investigated as putative risk factors for AD in 198 clinically diagnosed Alzheimer patients and in 198 randomly selected healthy controls. No significant differences in average age of fathers and of mothers at birth of the subject were observed.

  16. The Role of Free Radicals in the Aging Brain and Parkinson’s Disease: Convergence and Parallelism

    OpenAIRE

    Dong-Kug Choi; In Su Kim; Sushruta Koppula; Byung-Wook Kim; Sandeep Vasant More; Hyung-Woo Lim; Hemant Kumar

    2012-01-01

    Free radical production and their targeted action on biomolecules have roles in aging and age-related disorders such as Parkinson’s disease (PD). There is an age-associated increase in oxidative damage to the brain, and aging is considered a risk factor for PD. Dopaminergic neurons show linear fallout of 5–10% per decade with aging; however, the rate and intensity of neuronal loss in patients with PD is more marked than that of aging. Here, we enumerate the common link between aging and PD at...

  17. Aging on a different scale--chronological versus pathology-related aging.

    Science.gov (United States)

    Melis, Joost P M; Jonker, Martijs J; Vijg, Jan; Hoeijmakers, Jan H J; Breit, Timo M; van Steeg, Harry

    2013-10-01

    In the next decades the elderly population will increase dramatically, demanding appropriate solutions in health care and aging research focusing on healthy aging to prevent high burdens and costs in health care. For this, research targeting tissue-specific and individual aging is paramount to make the necessary progression in aging research. In a recently published study we have attempted to make a step interpreting aging data on chronological as well as pathological scale. For this, we sampled five major tissues at regular time intervals during the entire C57BL/6J murine lifespan from a controlled in vivo aging study, measured the whole transcriptome and incorporated temporal as well as physical health aspects into the analyses. In total, we used 18 different age-related pathological parameters and transcriptomic profiles of liver, kidney, spleen, lung and brain and created a database that can now be used for a broad systems biology approach. In our study, we focused on the dynamics of biological processes during chronological aging and the comparison between chronological and pathology-related aging.

  18. Modifiable Coronary Heart Disease Risk Factors in the Population Aged 20-49 Years

    Directory of Open Access Journals (Sweden)

    Francisco Carlos Valladares Mas

    2014-04-01

    Full Text Available Background: evidence provided by the Framingham Heart Study established the critical role of risk factors in the development of coronary heart disease. Over half a century later, current detection and control are still inadequate. Objective: to identify modifiable risk factors of coronary heart disease in individuals aged 20 to 49 years. Methods: a descriptive, cross-sectional study was conducted in 276 individuals from the doctor’s office No. 1 of the Fabio di Celmo Community Teaching Polyclinic in Cienfuegos. Patients were examined in the clinic visit and/or whole family visit. The studied variables included age, sex, skin color, risk factors (excess weight/obesity, physical inactivity, smoking, hypertension, diabetes, dyslipidemia and psychosocial factors, which were obtained from the medical interview, physical examination, laboratory tests (total cholesterol and triglycerides and review of individual medical records and family history. Results: risk factors most frequently identified were excess weight/obesity (42.4 %, physical inactivity (34.4 % and smoking (20.3 %. Presence of these risk factors increased with age, showing differences in the distribution by sex and was associated with psychosocial factors. Their coexistence and progress with age was significant. Conclusion: prevalence of modifiable risk factors for coronary heart disease in a young population was high, with frequent association, predominating factors related to unhealthy lifestyles.

  19. Dengvaxia sensitizes seronegatives to vaccine enhanced disease regardless of age.

    Science.gov (United States)

    Halstead, Scott B

    2017-11-07

    During a large scale clinical efficacy trial of the Sanofipasteur live-attenuated tetravalent dengue vaccine (Dengvaxia), features of hospitalized disease accompanying dengue infections in placebo recipients were closely similar to those in vaccinated children. However, the age specific hospitalization curves for these two populations differed. The curve for children vaccinated at ages 2-16 years closely resembled the 1981 age specific hospitalization rate curve for Cuban children infected with DENV 2 who were sensitized by a prior DENV 1 infection. The corresponding age specific hospitalization curve for placebos experiencing heterotypic secondary dengue infections peaked at age, 9-11 years. These differing epidemiological features support the conclusion that antibody dependent enhanced (ADE) dengue disease occurred in seronegatives who were sensitized by vaccine. As hospitalizations continue to occur in all age groups Dengvaxia consumers should be warned that sensitized vaccinated seronegatives will experience enhanced dengue disease into the forseeable future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. NAD+ biosynthesis, aging, and disease [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Sean Johnson

    2018-02-01

    Full Text Available Nicotinamide adenine dinucleotide (NAD+ biosynthesis and its regulation have recently been attracting markedly increasing interest. Aging is marked by a systemic decrease in NAD+ across multiple tissues. The dysfunction of NAD+ biosynthesis plays a critical role in the pathophysiologies of multiple diseases, including age-associated metabolic disorders, neurodegenerative diseases, and mental disorders. As downstream effectors, NAD+-dependent enzymes, such as sirtuins, are involved in the progression of such disorders. These recent studies implicate NAD+ biosynthesis as a potential target for preventing and treating age-associated diseases. Indeed, new studies have demonstrated the therapeutic potential of supplementing NAD+ intermediates, such as nicotinamide mononucleotide and nicotinamide riboside, providing a proof of concept for the development of an effective anti-aging intervention.

  1. Research status of conbercept treating age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Hai-Yan He

    2015-08-01

    Full Text Available Age-related macular degeneration(AMDis one of the major reasons of blindness among the elderly in the developed countries. As AMD patients are increasing year by year, AMD has become one of the important topics of ophthalmic research to prevent blindness. Its pathogenesis is not fully understood, but many studies have shown that vascular endothelial growth factor(VEGFplays an important role in the pathogenesis. With the development and application of anti-VEGF drugs, there are a variety of drugs applied to the disease. This article introduces conbercept for the treatment of AMD.

  2. Metabolic syndrome and dementia associated with Parkinson's disease: impact of age and hypertension

    Directory of Open Access Journals (Sweden)

    Arthur Oscar Schelp

    2012-02-01

    Full Text Available OBJECTIVE: To determine correlations between age and metabolic disorders in Parkinson's disease (PD patients. METHODS: This observational cross-sectional study included brief tests for dementia and the Mattis test. Signals of metabolic syndrome were evaluated. RESULTS: There was no significant effect from the presence of hypertension (OR=2.36 for patients under 65 years old and OR=0.64 for patients over 65, diabetes or hypercholesterolemia regarding occurrences of dementia associated with PD (24% of the patients. The study demonstrated that each year of age increased the estimated risk of dementia in PD patients by 9% (OR=1.09; 95%CI: 1.01-1.17. CONCLUSION: There was no evidence to correlate the presence of metabolic syndrome with the risk of dementia that was associated with PD. The study confirmed that dementia in PD is age dependent and not related to disease duration.

  3. Age impact on autoimmune thyroid disease in females

    Science.gov (United States)

    Stoian, Dana; Craciunescu, Mihalea; Timar, Romulus; Schiller, Adalbert; Pater, Liana; Craina, Marius

    2013-10-01

    Thyroid autoimmune disease, a widespread phenomenon in female population, impairs thyroid function during pregnancy. Identifying cases, which will develop hypothyroidism during pregnancy, is crucial in the follow-up process. The study group comprised 108 females, with ages between 20-40 years; with known inactive autoimmune thyroid disease, before pregnancy that became pregnant in the study follow-up period. They were monitored by means of clinical, hormonal and immunological assays. Supplemental therapy with thyroid hormones was used, where needed. Maternal age and level of anti-thyroid antibodies were used to predict thyroid functional impairment.

  4. Lipid and Alzheimer's disease genes associated with healthy aging and longevity in healthy oldest-old.

    Science.gov (United States)

    Tindale, Lauren C; Leach, Stephen; Spinelli, John J; Brooks-Wilson, Angela R

    2017-03-28

    Several studies have found that long-lived individuals do not appear to carry lower numbers of common disease-associated variants than ordinary people; it has been hypothesized that they may instead carry protective variants. An intriguing type of protective variant is buffering variants that protect against variants that have deleterious effects. We genotyped 18 variants in 15 genes related to longevity or healthy aging that had been previously reported as having a gene-gene interaction or buffering effect. We compared a group of 446 healthy oldest-old 'Super-Seniors' (individuals 85 or older who have never been diagnosed with cancer, cardiovascular disease, dementia, diabetes or major pulmonary disease) to 421 random population-based midlife controls. Cases and controls were of European ancestry. Association tests of individual SNPs showed that Super-Seniors were less likely than controls to carry an APOEε4 allele or a haptoglobin HP2 allele. Interactions between APOE/FOXO3, APOE/CRYL1, and LPA/CRYL1 did not remain significant after multiple testing correction. In a network analysis of the candidate genes, lipid and cholesterol metabolism was a common theme. APOE, HP, and CRYL1 have all been associated with Alzheimer's Disease, the pathology of which involves lipid and cholesterol pathways. Age-related changes in lipid and cholesterol maintenance, particularly in the brain, may be central to healthy aging and longevity.

  5. Neuroimaging Studies Illustrate the Commonalities Between Ageing and Brain Diseases.

    Science.gov (United States)

    Cole, James H

    2018-07-01

    The lack of specificity in neuroimaging studies of neurological and psychiatric diseases suggests that these different diseases have more in common than is generally considered. Potentially, features that are secondary effects of different pathological processes may share common neurobiological underpinnings. Intriguingly, many of these mechanisms are also observed in studies of normal (i.e., non-pathological) brain ageing. Different brain diseases may be causing premature or accelerated ageing to the brain, an idea that is supported by a line of "brain ageing" research that combines neuroimaging data with machine learning analysis. In reviewing this field, I conclude that such observations could have important implications, suggesting that we should shift experimental paradigm: away from characterizing the average case-control brain differences resulting from a disease toward methods that place individuals in their age-appropriate context. This will also lead naturally to clinical applications, whereby neuroimaging can contribute to a personalized-medicine approach to improve brain health. © 2018 WILEY Periodicals, Inc.

  6. Increased risk of cardiovascular disease (CVD) with age in HIV-positive men

    DEFF Research Database (Denmark)

    Petoumenos, K; Reiss, P; Ryom, L

    2014-01-01

    equations. METHODS: We analysed three endpoints: myocardial infarction (MI), coronary heart disease (CHD: MI or invasive coronary procedure) and CVD (CHD or stroke). We fitted a number of parametric age effects, adjusting for known risk factors and antiretroviral therapy (ART) use. The best-fitting age...... rates per 1000 person-years increased from 2.29, 3.11 and 3.65 in those aged 40-45 years to 6.53, 11.91 and 15.89 in those aged 60-65 years, respectively. The best-fitting models included inverse age for MI and age + age(2) for CHD and CVD. In D:A:D there was a slowly accelerating increased risk of CHD...... and CVD per year older, which appeared to be only modest yet was consistently raised compared with the risk in the general population. The relative risk of MI with age was not different between D:A:D and the general population. CONCLUSIONS: We found only limited evidence of accelerating increased risk...

  7. Protective role of the apolipoprotein E2 allele in age-related disease traits and survival: evidence from the Long Life Family Study.

    Science.gov (United States)

    Kulminski, Alexander M; Raghavachari, Nalini; Arbeev, Konstantin G; Culminskaya, Irina; Arbeeva, Liubov; Wu, Deqing; Ukraintseva, Svetlana V; Christensen, Kaare; Yashin, Anatoliy I

    2016-11-01

    The apolipoprotein E (apoE) is a classic example of a gene exhibiting pleiotropism. We examine potential pleiotropic associations of the apoE2 allele in three biodemographic cohorts of long-living individuals, offspring, and spouses from the Long Life Family Study, and intermediate mechanisms, which can link this allele with age-related phenotypes. We focused on age-related macular degeneration, bronchitis, asthma, pneumonia, stroke, creatinine, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, diseases of heart (HD), cancer, and survival. Our analysis detected favorable associations of the ε2 allele with lower LDL-C levels, lower risks of HD, and better survival. The ε2 allele was associated with LDL-C in each gender and biodemographic cohort, including long-living individuals, offspring, and spouses, resulting in highly significant association in the entire sample (β = -7.1, p = 6.6 × 10 -44 ). This allele was significantly associated with HD in long-living individuals and offspring (relative risk [RR] = 0.60, p = 3.1 × 10 -6 ) but this association was not mediated by LDL-C. The protective effect on survival was specific for long-living women but it was not explained by LDL-C and HD in the adjusted model (RR = 0.70, p = 2.1 × 10 -2 ). These results show that ε2 allele may favorably influence LDL-C, HD, and survival through three mechanisms. Two of them (HD- and survival-related) are pronounced in the long-living parents and their offspring; the survival-related mechanism is also sensitive to gender. The LDL-C-related mechanism appears to be independent of these factors. Insights into mechanisms linking ε2 allele with age-related phenotypes given biodemographic structure of the population studied may benefit translation of genetic discoveries to health care and personalized medicine.

  8. Age-related changes in factor VII proteolysis in vivo.

    Science.gov (United States)

    Ofosu, F A; Craven, S; Dewar, L; Anvari, N; Andrew, M; Blajchman, M A

    1996-08-01

    Previous studies have reported that pre-operative plasmas of patients over the age of 40 years who developed post-operative deep vein thrombosis (DVT) had approximately twice the amount of proteolysed factor VII found in plasmas of patients in whom prophylaxis with heparin or low M(r) heparin was successful. These and other studies also reported higher concentrations of thrombin-antithrombin III in pre- and post-operative plasmas of patients who developed post-operative thrombosis than in plasmas of patients in whom prophylaxis was successful. Whether the extent of factor VII proteolysis seen in the patients who developed post-operative DVT is related to the severity of their disease or age is not known. This report investigated age-related changes in the concentrations of total factor VII protein, factor VII zymogen, factor VIIa, tissue factor pathway inhibitor, thrombin-antithrombin III, and prothrombin fragment 1 + 2 in normal plasmas and the relationships between these parameters. With the exception of thrombin-antithrombin III, statistically significant increases in the concentrations of these parameters with age were found. Additionally, the differences between the concentrations of total factor VII protein and factor VII zymogen, an index factor VII proteolysis in vivo, were statistically significant only for individuals over age 40. Using linear regression analysis, a significant correlation was found to exist between the concentrations of plasma factor VIIa and prothrombin fragment 1 + 2. Since factor VIIa-tissue factor probably initiates coagulation in vivo, we hypothesize that the elevated plasma factor VIIa (reflecting a less tightly regulated tissue factor activity and therefore increased thrombin production in vivo) accounts for the high risk for post-operative thrombosis seen in individuals over the age of 40.

  9. Glucose and age-related changes in memory.

    Science.gov (United States)

    Gold, Paul E

    2005-12-01

    Epinephrine, released from the adrenal medulla, enhances memory in young rats and mice and apparently does so, at least in part, by increasing blood glucose levels. Like epinephrine, administration of glucose enhances cognitive functions in humans and rodents, including reversing age-related impairments in learning and memory. Epinephrine responses to training are increased in aged rats but the subsequent increase in blood glucose levels is severely blunted. The absence of increases in blood glucose levels during training might contribute to age-related deficits in learning and memory. Also, extracellular glucose levels in the hippocampus are depleted during spontaneous alternation testing to a far greater extent in aged than in young rats. Importantly, systemic injections of glucose block the depletion in the hippocampus and also enhance performance on the alternation task. Thus, the extensive depletion of extracellular glucose during training in aged rats may be associated with age-related memory impairments, an effect that might be related to - or may exacerbate - the effects on learning and memory of an absence of the increases in blood glucose levels to training as seen in young rats. Together, these findings suggest that age-related changes in both peripheral and central glucose physiology contribute to age-related impairments in memory.

  10. DNA damage and repair in age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Szaflik, Jacek P. [Department of Ophthalmology, Medical University of Warsaw and Samodzielny Publiczny Szpital Okulistyczny, Sierakowskiego 13, 03-710 Warsaw (Poland); Janik-Papis, Katarzyna; Synowiec, Ewelina; Ksiazek, Dominika [Department of Molecular Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland); Zaras, Magdalena [Department of Ophthalmology, Medical University of Warsaw and Samodzielny Publiczny Szpital Okulistyczny, Sierakowskiego 13, 03-710 Warsaw (Poland); Wozniak, Katarzyna [Department of Molecular Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland); Szaflik, Jerzy [Department of Ophthalmology, Medical University of Warsaw and Samodzielny Publiczny Szpital Okulistyczny, Sierakowskiego 13, 03-710 Warsaw (Poland); Blasiak, Janusz, E-mail: januszb@biol.uni.lodz.pl [Department of Molecular Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland)

    2009-10-02

    Age-related macular degeneration (AMD) is a retinal degenerative disease that is the main cause of vision loss in individuals over the age of 55 in the Western world. Clinically relevant AMD results from damage to the retinal pigment epithelial (RPE) cells thought to be mainly caused by oxidative stress. The stress also affects the DNA of RPE cells, which promotes genome instability in these cells. These effects may coincide with the decrease in the efficacy of DNA repair with age. Therefore individuals with DNA repair impaired more than average for a given age may be more susceptible to AMD if oxidative stress affects their RPE cells. This may be helpful in AMD risk assessment. In the present work we determined the level of basal (measured in the alkaline comet assay) endogenous and endogenous oxidative DNA damage, the susceptibility to exogenous mutagens and the efficacy of DNA repair in lymphocytes of 100 AMD patients and 110 age-matched individuals without visual disturbances. The cells taken from AMD patients displayed a higher extent of basal endogenous DNA damage without differences between patients of dry and wet forms of the disease. DNA double-strand breaks did not contribute to the observed DNA damage as checked by the neutral comet assay and pulsed field gel electrophoresis. The extent of oxidative modification to DNA bases was grater in AMD patients than in the controls, as probed by DNA repair enzymes NTH1 and Fpg. Lymphocytes from AMD patients displayed a higher sensitivity to hydrogen peroxide and UV radiation and repaired lesions induced by these factors less effectively than the cells from the control individuals. We postulate that the impaired efficacy of DNA repair may combine with enhanced sensitivity of RPE cells to blue and UV lights, contributing to the pathogenesis of AMD.

  11. DNA damage and repair in age-related macular degeneration

    International Nuclear Information System (INIS)

    Szaflik, Jacek P.; Janik-Papis, Katarzyna; Synowiec, Ewelina; Ksiazek, Dominika; Zaras, Magdalena; Wozniak, Katarzyna; Szaflik, Jerzy; Blasiak, Janusz

    2009-01-01

    Age-related macular degeneration (AMD) is a retinal degenerative disease that is the main cause of vision loss in individuals over the age of 55 in the Western world. Clinically relevant AMD results from damage to the retinal pigment epithelial (RPE) cells thought to be mainly caused by oxidative stress. The stress also affects the DNA of RPE cells, which promotes genome instability in these cells. These effects may coincide with the decrease in the efficacy of DNA repair with age. Therefore individuals with DNA repair impaired more than average for a given age may be more susceptible to AMD if oxidative stress affects their RPE cells. This may be helpful in AMD risk assessment. In the present work we determined the level of basal (measured in the alkaline comet assay) endogenous and endogenous oxidative DNA damage, the susceptibility to exogenous mutagens and the efficacy of DNA repair in lymphocytes of 100 AMD patients and 110 age-matched individuals without visual disturbances. The cells taken from AMD patients displayed a higher extent of basal endogenous DNA damage without differences between patients of dry and wet forms of the disease. DNA double-strand breaks did not contribute to the observed DNA damage as checked by the neutral comet assay and pulsed field gel electrophoresis. The extent of oxidative modification to DNA bases was grater in AMD patients than in the controls, as probed by DNA repair enzymes NTH1 and Fpg. Lymphocytes from AMD patients displayed a higher sensitivity to hydrogen peroxide and UV radiation and repaired lesions induced by these factors less effectively than the cells from the control individuals. We postulate that the impaired efficacy of DNA repair may combine with enhanced sensitivity of RPE cells to blue and UV lights, contributing to the pathogenesis of AMD.

  12. Age and muscle strength mediate the age-related biomechanical plasticity of gait

    NARCIS (Netherlands)

    Hortobagyi, Tibor; Rider, Patrick; Gruber, Allison H.; DeVita, Paul

    Old compared with young adults walk with reduced ankle and increased hip mechanical output. We examined the idea that age, leg strength, or both are related to the age-related changes in mechanical output during gait. Healthy young (n = 32, age 21.5 years) and old adults (n = 32, age 76.8 years)

  13. Association of HTRA1 rs11200638 with age-related macular degeneration (AMD) in Brazilian patients.

    Science.gov (United States)

    Lana, Tamires Prates; da Silva Costa, Sueli Matilde; Ananina, Galina; Hirata, Fábio Endo; Rim, Priscila Hae Hyun; Medina, Flávio MacCord; de Vasconcellos, José Paulo Cabral; de Melo, Mônica Barbosa

    2018-01-01

    Age-related macular degeneration is a multifactorial disease that can lead to vision impairment in older individuals. Although the etiology of age-related macular degeneration remains unknown, risk factors include age, ethnicity, smoking, hypertension, obesity, and genetic factors. Two main loci have been identified through genome-wide association studies, on chromosomes 1 and 10. Among the variants located at the 10q26 region, rs11200638, located at the HTRA1 gene promoter, has been associated with age-related macular degeneration in several populations and is considered the main polymorphism. We conducted a replication case-control study to analyze the frequency and participation of rs11200638 in the etiology of age-related macular degeneration in a sample of patients and controls from the State of São Paulo, Brazil, through polymerase chain reaction and enzymatic digestion. The frequency of the A allele was 57.60% in patients with age-related macular degeneration and 36.45% in controls (p value age-related macular degeneration group compared to the control group (p = 1.21 e-07 and 0.0357, respectively). No statistically significant results were observed after stratification in dry versus wet types or advanced versus non-advanced forms. To our knowledge, this is the first time the association between rs11200638 and overall age-related macular degeneration has been reported in South America.

  14. Oxidative stress, innate immunity, and age-related macular degeneration

    Science.gov (United States)

    Shaw, Peter X.; Stiles, Travis; Douglas, Christopher; Ho, Daisy; Fan, Wei; Du, Hongjun; Xiao, Xu

    2016-01-01

    Age-related macular degeneration (AMD) is a leading cause of vision loss affecting tens of millions of elderly worldwide. Early AMD is characterized by the appearance of soft drusen, as well as pigmentary changes in the retinal pigment epithelium (RPE). These soft, confluent drusen can progress into two forms of advanced AMD: geographic atrophy (GA, or dry AMD) or choroidal neovascularization (CNV, or wet AMD). Both forms of AMD result in a similar clinical progression in terms of loss of central vision. The exact mechanism for developing early AMD, as well as triggers responsible for progressing to advanced stage of disease, is still largely unknown. However, significant evidence exists demonstrating a complex interplay of genetic and environmental factors as causes of AMD progression. Multiple genes and/or single nucleotide polymorphisms (SNPs) have been found associated with AMD, including various genes involved in the complement pathway, lipid metabolism and extracellular matrix (ECM) remodeling. Of the known genetic contributors to disease risk, the CFH Y402H and HTRA1/ARMS polymorphisms contribute to more than 50% of the genetic risk for AMD. Environmentally, oxidative stress plays a critical role in many aging diseases including cardiovascular disease, cancer, Alzheimer’s disease and AMD. Due to the exposure to sunlight and high oxygen concentration, the oxidative stress burden is higher in the eye than other tissues, which can be further complicated by additional oxidative stressors such as smoking. Increasingly, evidence is accumulating suggesting that functional abnormalities of the innate immune system incurred via high risk genotypes may be contributing to the pathogenesis of AMD by altering the inflammatory homeostasis in the eye, specifically in the handling of oxidation products. As the eye in non-pathological instances maintains a low level of inflammation despite the presence of a relative abundance of potentially inflammatory molecules, we have

  15. Exercise-related changes of networks in aging and mild cognitive impairment brain

    Directory of Open Access Journals (Sweden)

    Pei eHuang

    2016-03-01

    Full Text Available Aging and mild cognitive impairment are accompanied by decline of cognitive functions. Meanwhile, the most common form of dementia is Alzheimer’s disease, which is characterized by loss of memory and other intellectual abilities serious to make difficulties for patients in their daily life. Mild cognitive impairment is a transition period between normal aging and dementia, which has been used for early detection of emerging dementia. It converts to dementia with an annual rate of 5-15% as compared to normal aging with 1% rate. Small decreases in the conversion rate of mild cognitive impairment to Alzheimer’s disease might significantly reduce the prevalence of dementia. Thus, it is important to intervene at the preclinical stage. Since there are still no effective drugs to treat Alzheimer’s disease, non-drug intervention is crucial for the prevention and treatment of cognitive decline in aging and mild cognitive impairment populations. Previous studies have found some cognitive brain networks disrupted in aging and mild cognitive impairment population, and physical exercise could effectively remediate the function of these brain networks. Understanding the exercise-related mechanisms is crucial to design efficient and effective physical exercise programs for treatment/intervention of cognitive decline. In this review, we provide an overview of the neuroimaging studies on physical training in normal aging and mild cognitive impairment to identify the potential mechanisms underlying current physical training procedures. Studies of functional magnetic resonance imaging, electroencephalography, magnetoencephalography and positron emission tomography on brain networks were all included. Based on our review, the default mode network, fronto-parietal network and fronto-executive network are probably the three most valuable targets for efficiency evaluation of interventions.

  16. Advanced age, cardiovascular risk burden, and timed up and go test performance in Parkinson disease.

    Science.gov (United States)

    Kotagal, Vikas; Albin, Roger L; Müller, Martijn L T M; Koeppe, Robert A; Studenski, Stephanie; Frey, Kirk A; Bohnen, Nicolaas I

    2014-12-01

    . Modifiable cardiovascular risk factors and older age may independently exacerbate balance-related disability in Parkinson disease and may exert additive or synergistic pathological effects. The pathophysiology of these impairments cannot be explained completely by nigrostriatal dopaminergic denervation or leukoaraiosis burden and may relate to systemic factors seen with accelerated aging. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Age and neurodegeneration imaging biomarkers in persons with Alzheimer disease dementia.

    Science.gov (United States)

    Knopman, David S; Jack, Clifford R; Wiste, Heather J; Weigand, Stephen D; Vemuri, Prashanthi; Lowe, Val J; Kantarci, Kejal; Gunter, Jeffrey L; Senjem, Matthew L; Mielke, Michelle M; Machulda, Mary M; Roberts, Rosebud O; Boeve, Bradley F; Jones, David T; Petersen, Ronald C

    2016-08-16

    To examine neurodegenerative imaging biomarkers in Alzheimer disease (AD) dementia from middle to old age. Persons with AD dementia and elevated brain β-amyloid with Pittsburgh compound B (PiB)-PET imaging underwent [(18)F]-fluorodeoxyglucose (FDG)-PET and structural MRI. We evaluated 3 AD-related neurodegeneration biomarkers: hippocampal volume adjusted for total intracranial volume (HVa), FDG standardized uptake value ratio (SUVR) in regions of interest linked to AD, and cortical thickness in AD-related regions of interest. We examined associations of each biomarker with age and evaluated age effects on cutpoints defined by the 90th percentile in AD dementia. We assembled an age-, sex-, and intracranial volume-matched group of 194 similarly imaged clinically normal (CN) persons. The 97 participants with AD dementia (aged 49-93 years) had PiB SUVR ≥1.8. A nonlinear (inverted-U) relationship between FDG SUVR and age was seen in the AD group but an inverse linear relationship with age was seen in the CN group. Cortical thickness had an inverse linear relationship with age in AD but a nonlinear (flat, then inverse linear) relationship in the CN group. HVa showed an inverse linear relationship with age in both AD and CN groups. Age effects on 90th percentile cutpoints were small for FDG SUVR and cortical thickness, but larger for HVa. In persons with AD dementia with elevated PiB SUVR, values of each neurodegeneration biomarker were associated with age. Cortical thickness had the smallest differences in 90th percentile cutpoints from middle to old age, and HVa the largest differences. © 2016 American Academy of Neurology.

  18. Macular xanthophylls, lipoprotein-related genes, and age-related macular degeneration.

    Science.gov (United States)

    Koo, Euna; Neuringer, Martha; SanGiovanni, John Paul

    2014-07-01

    Plant-based macular xanthophylls (MXs; lutein and zeaxanthin) and the lutein metabolite meso-zeaxanthin are the major constituents of macular pigment, a compound concentrated in retinal areas that are responsible for fine-feature visual sensation. There is an unmet need to examine the genetics of factors influencing regulatory mechanisms and metabolic fates of these 3 MXs because they are linked to processes implicated in the pathogenesis of age-related macular degeneration (AMD). In this work we provide an overview of evidence supporting a molecular basis for AMD-MX associations as they may relate to DNA sequence variation in AMD- and lipoprotein-related genes. We recognize a number of emerging research opportunities, barriers, knowledge gaps, and tools offering promise for meaningful investigation and inference in the field. Overviews on AMD- and high-density lipoprotein (HDL)-related genes encoding receptors, transporters, and enzymes affecting or affected by MXs are followed with information on localization of products from these genes to retinal cell types manifesting AMD-related pathophysiology. Evidence on the relation of each gene or gene product with retinal MX response to nutrient intake is discussed. This information is followed by a review of results from mechanistic studies testing gene-disease relations. We then present findings on relations of AMD with DNA sequence variants in MX-associated genes. Our conclusion is that AMD-associated DNA variants that influence the actions and metabolic fates of HDL system constituents should be examined further for concomitant influence on MX absorption, retinal tissue responses to MX intake, and the capacity to modify MX-associated factors and processes implicated in AMD pathogenesis. © 2014 American Society for Nutrition.

  19. Age-related hearing loss: prevention of threshold declines, cell loss and apoptosis in spiral ganglion neurons

    Science.gov (United States)

    Zhu, Xiaoxia; Walton, Joseph P.

    2016-01-01

    Age-related hearing loss (ARHL) -presbycusis - is the most prevalent neurodegenerative disease and number one communication disorder of our aged population; and affects hundreds of millions of people worldwide. Its prevalence is close to that of cardiovascular disease and arthritis, and can be a precursor to dementia. The auditory perceptual dysfunction is well understood, but knowledge of the biological bases of ARHL is still somewhat lacking. Surprisingly, there are no FDA-approved drugs for treatment. Based on our previous studies of human subjects, where we discovered relations between serum aldosterone levels and the severity of ARHL, we treated middle age mice with aldosterone, which normally declines with age in all mammals. We found that hearing thresholds and suprathreshold responses significantly improved in the aldosterone-treated mice compared to the non-treatment group. In terms of cellular and molecular mechanisms underlying this therapeutic effect, additional experiments revealed that spiral ganglion cell survival was significantly improved, mineralocorticoid receptors were upregulated via post-translational protein modifications, and age-related intrinsic and extrinsic apoptotic pathways were blocked by the aldosterone therapy. Taken together, these novel findings pave the way for translational drug development towards the first medication to prevent the progression of ARHL. PMID:27667674

  20. Gastroesophageal reflux disease vs. Panayiotopoulos syndrome: an underestimated misdiagnosis in pediatric age?

    Science.gov (United States)

    Parisi, Pasquale; Pacchiarotti, Claudia; Ferretti, Alessandro; Bianchi, Simona; Paolino, Maria Chiara; Barreto, Mario; Principessa, Luigi; Villa, Maria Pia

    2014-12-01

    Autonomic signs and symptoms could be of epileptic or nonepileptic origin, and the differential diagnosis depends on a number of factors which include the nature of the autonomic manifestations themselves, the occurrence of other nonictal autonomic signs/symptoms, and the age of the patient. Here, we describe twelve children (aged from ten months to six years at the onset of the symptoms) with Panayiotopoulos syndrome misdiagnosed as gastroesophageal reflux disease. Gastroesophageal reflux disease and Panayiotopoulos syndrome may represent an underestimated diagnostic challenge. When the signs/symptoms occur mainly during sleep, a sleep EEG or, if available, a polysomnographic evaluation may be the most useful investigation to make a differential diagnosis between autonomic epileptic and nonepileptic disorders. An early detection can reduce both the high morbidity related to mismanagement and the high costs to the national health service related to the incorrect diagnostic and therapeutic approaches. To decide if antiseizure therapy is required, one should take into account both the frequency and severity of epileptic seizures and the tendency to have potentially lethal autonomic cardiorespiratory involvement. In conclusion, we would emphasize the need to make a differential diagnosis between gastroesophageal reflux disease and Panayiotopoulos syndrome in patients with "an unusual" late-onset picture of GERD and acid therapy-resistant gastroesophageal reflux, especially if associated with other autonomic symptoms and signs. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status.

    Science.gov (United States)

    Sood, Sanjana; Gallagher, Iain J; Lunnon, Katie; Rullman, Eric; Keohane, Aoife; Crossland, Hannah; Phillips, Bethan E; Cederholm, Tommy; Jensen, Thomas; van Loon, Luc J C; Lannfelt, Lars; Kraus, William E; Atherton, Philip J; Howard, Robert; Gustafsson, Thomas; Hodges, Angela; Timmons, James A

    2015-09-07

    Diagnostics of the human ageing process may help predict future healthcare needs or guide preventative measures for tackling diseases of older age. We take a transcriptomics approach to build the first reproducible multi-tissue RNA expression signature by gene-chip profiling tissue from sedentary normal subjects who reached 65 years of age in good health. One hundred and fifty probe-sets form an accurate classifier of young versus older muscle tissue and this healthy ageing RNA classifier performed consistently in independent cohorts of human muscle, skin and brain tissue (n = 594, AUC = 0.83-0.96) and thus represents a biomarker for biological age. Using the Uppsala Longitudinal Study of Adult Men birth-cohort (n = 108) we demonstrate that the RNA classifier is insensitive to confounding lifestyle biomarkers, while greater gene score at age 70 years is independently associated with better renal function at age 82 years and longevity. The gene score is 'up-regulated' in healthy human hippocampus with age, and when applied to blood RNA profiles from two large independent age-matched dementia case-control data sets (n = 717) the healthy controls have significantly greater gene scores than those with cognitive impairment. Alone, or when combined with our previously described prototype Alzheimer disease (AD) RNA 'disease signature', the healthy ageing RNA classifier is diagnostic for AD. We identify a novel and statistically robust multi-tissue RNA signature of human healthy ageing that can act as a diagnostic of future health, using only a peripheral blood sample. This RNA signature has great potential to assist research aimed at finding treatments for and/or management of AD and other ageing-related conditions.

  2. [Major depressive disorder in relation with coronary heart disease and stroke in Chinese adults aged 30-79 years].

    Science.gov (United States)

    Yu, C Q; Chen, Y P; Lv, J; Guo, Y; Sherliker, P; Bian, Z; Zhou, H Y; Tan, Y L; Chen, J S; Chen, Z M; Li, L M

    2016-06-18

    To investigate the associations of major depressive disorder with coronary heart disease (CHD) and stroke in Chinese adults aged 30-79 years. In 2004-2008, China Kadoorie Biobank was conducted in 10 geographically defined regions (5 urban and 5 rural) of China. A total number of 512 891 participants aged 30-79 years were recruited in the baseline survey. A laptop-based electronic questionnaire was administrated face-to-face by trained health workers, collecting the general demographic and socio-economic status, dietary and other lifestyle behaviours (e.g. smoking, alcohol drinking, physical activity), medical history and family history of common chronic diseases. Major depressive episodes (MDE) in the past 12 months were assessed with the World Health Organization composite international diagnostic interview-short form (CIDI-SF). The physical measurements included the heights and weights, which were used to calculate the body mass indexes (BMI).Chi squared and t test were used to compare the differences in participants characteristics according to their major depressive disorder. Logistic models were employed to estimate the odds ratios (OR) and 95% CI of their major depressive disorder with prevalent coronary heart disease and stroke. Among the 512 891 participants, 3 281 (0.6%) showed an MDE in the preceding 12 months, 15 472 (3.0%) reported prevalent CHD, and 8 884 (1.7%) reported prevalent stroke. Major depressive disorder was significantly associated with an increased risk of CHD and risk of stroke. Age- and gender-adjusted ORs (95% CI) were 1.80 (1.53-2.12) for CHD and 2.53 (2.09-3.05) for stroke. The associations were significant after further adjustment for potential confounders, such as other socio-demographic status, smoking, alcohol drinking, physical activity, and BMI, prevalent hypertension, diabetes as well as family history of cardiovascular diseases (OR=1.83, 95% CI=1.54-2.18 for CHD; OR=2.19, 95% CI=1.79-2.69 for stroke). Moreover, gender

  3. Men and mice: Relating their ages.

    Science.gov (United States)

    Dutta, Sulagna; Sengupta, Pallav

    2016-05-01

    Since the late 18th century, the murine model has been widely used in biomedical research (about 59% of total animals used) as it is compact, cost-effective, and easily available, conserving almost 99% of human genes and physiologically resembling humans. Despite the similarities, mice have a diminutive lifespan compared to humans. In this study, we found that one human year is equivalent to nine mice days, although this is not the case when comparing the lifespan of mice versus humans taking the entire life at the same time without considering each phase separately. Therefore, the precise correlation of age at every point in their lifespan must be determined. Determining the age relation between mice and humans is necessary for setting up experimental murine models more analogous in age to humans. Thus, more accuracy can be obtained in the research outcome for humans of a specific age group, although current outcomes are based on mice of an approximate age. To fill this gap between approximation and accuracy, this review article is the first to establish a precise relation between mice age and human age, following our previous article, which explained the relation in ages of laboratory rats with humans in detail. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Effective gene therapy in an authentic model of Tay-Sachs-related diseases.

    Science.gov (United States)

    Cachón-González, M Begoña; Wang, Susan Z; Lynch, Andrew; Ziegler, Robin; Cheng, Seng H; Cox, Timothy M

    2006-07-05

    Tay-Sachs disease is a prototypic neurodegenerative disease. Lysosomal storage of GM2 ganglioside in Tay-Sachs and the related disorder, Sandhoff disease, is caused by deficiency of beta-hexosaminidase A, a heterodimeric protein. Tay-Sachs-related diseases (GM2 gangliosidoses) are incurable, but gene therapy has the potential for widespread correction of the underlying lysosomal defect by means of the secretion-recapture cellular pathway for enzymatic complementation. Sandhoff mice, lacking the beta-subunit of hexosaminidase, manifest many signs of classical human Tay-Sachs disease and, with an acute course, die before 20 weeks of age. We treated Sandhoff mice by stereotaxic intracranial inoculation of recombinant adeno-associated viral vectors encoding the complementing human beta-hexosaminidase alpha and beta subunit genes and elements, including an HIV tat sequence, to enhance protein expression and distribution. Animals survived for >1 year with sustained, widespread, and abundant enzyme delivery in the nervous system. Onset of the disease was delayed with preservation of motor function; inflammation and GM2 ganglioside storage in the brain and spinal cord was reduced. Gene delivery of beta-hexosaminidase A by using adeno-associated viral vectors has realistic potential for treating the human Tay-Sachs-related diseases.

  5. Dynamic relationships between age, amyloid-β deposition, and glucose metabolism link to the regional vulnerability to Alzheimer’s disease

    Science.gov (United States)

    Madison, Cindee; Baker, Suzanne; Rabinovici, Gil; Jagust, William

    2016-01-01

    Abstract See Hansson and Gouras (doi:10.1093/aww146) for a scientific commentary on this article. Although some brain regions such as precuneus and lateral temporo-parietal cortex have been shown to be more vulnerable to Alzheimer’s disease than other areas, a mechanism underlying the differential regional vulnerability to Alzheimer’s disease remains to be elucidated. Using fluorodeoxyglucose and Pittsburgh compound B positron emission tomography imaging glucose metabolism and amyloid-β deposition, we tested whether and how life-long changes in glucose metabolism relate to amyloid-β deposition and Alzheimer’s disease-related hypometabolism. Nine healthy young adults (age range: 20–30), 96 cognitively normal older adults (age range: 61–96), and 20 patients with Alzheimer’s disease (age range: 50–90) were scanned using fluorodeoxyglucose and Pittsburgh compound B positron emission tomography. Among cognitively normal older subjects, 32 were further classified as amyloid-positive, with 64 as amyloid-negative. To assess the contribution of glucose metabolism to the regional vulnerability to amyloid-β deposition, we defined the highest and lowest metabolic regions in young adults and examined differences in amyloid deposition between these regions across groups. Two-way analyses of variance were conducted to assess regional differences in age and amyloid-β-related changes in glucose metabolism. Multiple regressions were applied to examine the association between amyloid-β deposition and regional glucose metabolism. Both region of interest and whole-brain voxelwise analyses were conducted to complement and confirm the results derived from the other approach. Regional differences in glucose metabolism between the highest and lowest metabolism regions defined in young adults (T = 12.85, P glucose metabolism regions defined in young adults (T = 2.05, P glucose metabolism were found such that frontal glucose metabolism was reduced with age, while glucose

  6. Bodacious Berry, Potency Wood and the Aging Monster: Gender and Age Relations in Anti-Aging Ads

    Science.gov (United States)

    Calasanti, Toni

    2007-01-01

    This paper situates age discrimination within a broader system of age relations that intersects with other inequalities, and then uses that framework to analyze internet advertisements for the anti-aging industry. Such ads reinforce age and gender relations by positing old people as worthwhile only to the extent that they look and act like those…

  7. Age-related changes in core body temperature and activity in triple-transgenic Alzheimer's disease (3xTgAD) mice.

    Science.gov (United States)

    Knight, Elysse M; Brown, Timothy M; Gümüsgöz, Sarah; Smith, Jennifer C M; Waters, Elizabeth J; Allan, Stuart M; Lawrence, Catherine B

    2013-01-01

    Alzheimer's disease (AD) is characterised, not only by cognitive deficits and neuropathological changes, but also by several non-cognitive behavioural symptoms that can lead to a poorer quality of life. Circadian disturbances in core body temperature and physical activity are reported in AD patients, although the cause and consequences of these changes are unknown. We therefore characterised circadian patterns of body temperature and activity in male triple transgenic AD mice (3xTgAD) and non-transgenic (Non-Tg) control mice by remote radiotelemetry. At 4 months of age, daily temperature rhythms were phase advanced and by 6 months of age an increase in mean core body temperature and amplitude of temperature rhythms were observed in 3xTgAD mice. No differences in daily activity rhythms were seen in 4- to 9-month-old 3xTgAD mice, but by 10 months of age an increase in mean daily activity and the amplitude of activity profiles for 3xTgAD mice were detected. At all ages (4-10 months), 3xTgAD mice exhibited greater food intake compared with Non-Tg mice. The changes in temperature did not appear to be solely due to increased food intake and were not cyclooxygenase dependent because the temperature rise was not abolished by chronic ibuprofen treatment. No β-amyloid (Aβ) plaques or neurofibrillary tangles were noted in the hypothalamus of 3xTgAD mice, a key area involved in temperature regulation, although these pathological features were observed in the hippocampus and amygdala of 3xTgAD mice from 10 months of age. These data demonstrate age-dependent changes in core body temperature and activity in 3xTgAD mice that are present before significant AD-related neuropathology and are analogous to those observed in AD patients. The 3xTgAD mouse might therefore be an appropriate model for studying the underlying mechanisms involved in non-cognitive behavioural changes in AD.

  8. The Age-Related Changes in Cartilage and Osteoarthritis

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    YongPing Li

    2013-01-01

    Full Text Available Osteoarthritis (OA is closely associated with aging, but its underlying mechanism is unclear. Recent publications were reviewed to elucidate the connection between aging and OA. With increasing OA incidence, more senior people are facing heavy financial and social burdens. Age-related OA pathogenesis is not well understood. Recently, it has been realized that age-related changes in other tissues besides articular cartilage may also contribute to OA development. Many factors including senescence-related secretory phenotypes, chondrocytes’ low reactivity to growth factors, mitochondrial dysfunction and oxidative stress, and abnormal accumulation of advanced glycation end products (AGEs may all play key roles in the pathogenesis of age-related OA. Lately, epigenetic regulation of gene expression was recognized for its impact on age-related OA pathogenesis. Up to now, few studies have been reported about the role of miRNA and long-noncoding RNA (lncRNA in age-related OA. Research focusing on this area may provide valuable insights into OA pathogenesis. OA-induced financial and social burdens have become an increasingly severe threat to older population. Age-related changes in noncartilage tissue should be incorporated in the understanding of OA development. Growing attention on oxidative stress and epigenetics will provide more important clues for the better understanding of the age-related OA.

  9. Age-related decrease in the mitochondrial sirtuin deacetylase Sirt3 expression associated with ROS accumulation in the auditory cortex of the mimetic aging rat model.

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    Lingling Zeng

    Full Text Available Age-related dysfunction of the central auditory system, also known as central presbycusis, can affect speech perception and sound localization. Understanding the pathogenesis of central presbycusis will help to develop novel approaches to prevent or treat this disease. In this study, the mechanisms of central presbycusis were investigated using a mimetic aging rat model induced by chronic injection of D-galactose (D-Gal. We showed that malondialdehyde (MDA levels were increased and manganese superoxide dismutase (SOD2 activity was reduced in the auditory cortex in natural aging and D-Gal-induced mimetic aging rats. Furthermore, mitochondrial DNA (mtDNA 4834 bp deletion, abnormal ultrastructure and cell apoptosis in the auditory cortex were also found in natural aging and D-Gal mimetic aging rats. Sirt3, a mitochondrial NAD+-dependent deacetylase, has been shown to play a crucial role in controlling cellular reactive oxygen species (ROS homeostasis. However, the role of Sirt3 in the pathogenesis of age-related central auditory cortex deterioration is still unclear. Here, we showed that decreased Sirt3 expression might be associated with increased SOD2 acetylation, which negatively regulates SOD2 activity. Oxidative stress accumulation was likely the result of low SOD2 activity and a decline in ROS clearance. Our findings indicate that Sirt3 might play an essential role, via the mediation of SOD2, in central presbycusis and that manipulation of Sirt3 expression might provide a new approach to combat aging and oxidative stress-related diseases.

  10. Incentive relativity in middle aged rats.

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    Justel, N; Mustaca, A; Boccia, M; Ruetti, E

    2014-01-24

    Response to a reinforcer is affected by prior experience with different reward values of that reward, a phenomenon known as incentive relativity. Two different procedures to study this phenomenon are the incentive downshift (ID) and the consummatory anticipatory negative contrast (cANC), the former is an emotional-cognitive protocol and the latter cognitive one. Aged rodents, as also well described in aged humans, exhibit alterations in cognitive functions. The main goal of this work was to evaluate the effect of age in the incentive' assessment using these two procedures. The results indicated that aged rats had an adequate assessment of the rewards but their performance is not completely comparable to that of young subjects. They recover faster from the ID and they had a cognitive impairment in the cANC. The results are discussed in relation to age-related changes in memory and emotion. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. A risk score for the prediction of advanced age-related macular degeneration: Development and validation in 2 prospective cohorts

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    We aimed to develop an eye specific model which used readily available information to predict risk for advanced age-related macular degeneration (AMD). We used the Age-Related Eye Disease Study (AREDS) as our training dataset, which consisted of the 4,507 participants (contributing 1,185 affected v...

  12. A 2-d classification of diseases based on age-specific death rates

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    Richmond, Peter; Roehner, Bertrand M.

    2018-02-01

    Age specific mortality curves exhibit an age tc (about 10 years) which plays a crucial role in that the mortality curve decreases hyperbolically in the age interval A before tc and increases exponentially in the interval B following tc. For those familiar with reliability theory, region A is called the "burn in" phase and B is the "wear out" phase. Using the exponents of the hyperbolic and exponential phases, we introduce a new 2 dimensional map of diseases. This permits the classification of diseases into three broad classes: AS1, AS2 and S. Class AS1 includes all diseases arising from congenital malformations which dominate infant and child mortality; class AS2 includes degenerative diseases such as dementia and Alzheimer's which dominate old age mortality. In class S, which includes most infectious and metabolic diseases, the exponents from both aging phases contribute to positions on the map. Cancer is one of these mixed cases but is closer to class AS2 than AS1. A second line classification is needed to resolve S cases and to this end we introduce a 3rd dimension, namely (calendar) time. Using historical data we show that in their response to treatment (particularly vaccination), S diseases fall into three sub-classes. (i) Class E diseases (e.g. measles or meningococcal disease) which have been almost eliminated at all ages (ii) class C diseases (e.g. tuberculosis) which can be cured but whose cure becomes less effective at old age. (iii) Class U diseases for which radical cures are still unknown. Regarding the future, the fact that the wear-out process of numerous diseases already starts around the age of 25 means that a major extension of the human lifespan beyond 120 certainly also requires to uncover the secret of the "elixir of eternal youth" which has driven timeless human efforts and still seems unlikely in the foreseeable future.

  13. The AGE-RAGE Axis: Implications for Age-Associated Arterial Diseases

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    Laura M. Senatus

    2017-12-01

    Full Text Available The process of advanced glycation leads to the generation and accumulation of an heterogeneous class of molecules called advanced glycation endproducts, or AGEs. AGEs are produced to accelerated degrees in disorders such as diabetes, renal failure, inflammation, neurodegeneration, and in aging. Further, AGEs are present in foods and in tobacco products. Hence, through both endogenous production and exogenous consumption, AGEs perturb vascular homeostasis by a number of means; in the first case, AGEs can cause cross-linking of long-lived molecules in the basement membranes such as collagens, thereby leading to “vascular stiffening” and processes that lead to hyperpermeability and loss of structural integrity. Second, AGEs interaction with their major cell surface signal transduction receptor for AGE or RAGE sets off a cascade of events leading to modulation of gene expression and loss of vascular and tissue homeostasis, processes that contribute to cardiovascular disease. In addition, it has been shown that an enzyme, which plays key roles in the detoxification of pre-AGE species, glyoxalase 1 (GLO1, is reduced in aged and diabetic tissues. In the diabetic kidney devoid of Ager (gene encoding RAGE, higher levels of Glo1 mRNA and GLO1 protein and activity were observed, suggesting that in conditions of high AGE accumulation, natural defenses may be mitigated, at least in part through RAGE. AGEs are a marker of arterial aging and may be detected by both biochemical means, as well as measurement of “skin autofluorescence.” In this review, we will detail the pathobiology of the AGE-RAGE axis and the consequences of its activation in the vasculature and conclude with potential avenues for therapeutic interruption of the AGE-RAGE ligand-RAGE pathways as means to forestall the deleterious consequences of AGE accumulation and signaling via RAGE.

  14. Cellular models and therapies for age-related macular degeneration

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    David L. Forest

    2015-05-01

    Full Text Available Age-related macular degeneration (AMD is a complex neurodegenerative visual disorder that causes profound physical and psychosocial effects. Visual impairment in AMD is caused by the loss of retinal pigmented epithelium (RPE cells and the light-sensitive photoreceptor cells that they support. There is currently no effective treatment for the most common form of this disease (dry AMD. A new approach to treating AMD involves the transplantation of RPE cells derived from either human embryonic or induced pluripotent stem cells. Multiple clinical trials are being initiated using a variety of cell therapies. Although many animal models are available for AMD research, most do not recapitulate all aspects of the disease, hampering progress. However, the use of cultured RPE cells in AMD research is well established and, indeed, some of the more recently described RPE-based models show promise for investigating the molecular mechanisms of AMD and for screening drug candidates. Here, we discuss innovative cell-culture models of AMD and emerging stem-cell-based therapies for the treatment of this vision-robbing disease.

  15. Development of Obesity and Related Diseases in African Refugees After Resettlement to United States.

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    Rhodes, Corinne M; Chang, Yuchiao; Percac-Lima, Sanja

    2016-12-01

    Despite increases in obesity and related diseases in developing nations, initial refugee clinical visits do not address these issues. We explored the development of obesity and related diseases in a longitudinal prospective cohort of African refugees resettling in northeastern US. Using state Department of Health data, refugees were linked to a health system. Body mass index, diabetes, hypertension, and hyperlipidemia status were extracted from charts. US regional controls from NAMCS/NHAMCS data were matched by age, sex, race, and visit year. African refugee BMI increased after resettlement at 1 (1.7 ± 2.9, p resettlement to prevent development of obesity and related disease in this vulnerable population.

  16. Widespread recent increases in county-level heart disease mortality across age groups.

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    Vaughan, Adam S; Ritchey, Matthew D; Hannan, Judy; Kramer, Michael R; Casper, Michele

    2017-12-01

    Recent national trends show decelerating declines in heart disease mortality, especially among younger adults. National trends may mask variation by geography and age. We examined recent county-level trends in heart disease mortality by age group. Using a Bayesian statistical model and National Vital Statistics Systems data, we estimated overall rates and percent change in heart disease mortality from 2010 through 2015 for four age groups (35-44, 45-54, 55-64, and 65-74 years) in 3098 US counties. Nationally, heart disease mortality declined in every age group except ages 55-64 years. County-level trends by age group showed geographically widespread increases, with 52.3%, 58.5%, 69.1%, and 42.0% of counties experiencing increases with median percent changes of 0.6%, 2.2%, 4.6%, and -1.5% for ages 35-44, 45-54, 55-64, and 65-74 years, respectively. Increases were more likely in counties with initially high heart disease mortality and outside large metropolitan areas. Recent national trends have masked local increases in heart disease mortality. These increases, especially among adults younger than age 65 years, represent challenges to communities across the country. Reversing these trends may require intensification of primary and secondary prevention-focusing policies, strategies, and interventions on younger populations, especially those living in less urban counties. Published by Elsevier Inc.

  17. Repressed SIRT1/PGC-1α pathway and mitochondrial disintegration in iPSC-derived RPE disease model of age-related macular degeneration.

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    Golestaneh, Nady; Chu, Yi; Cheng, Shuk Kei; Cao, Hong; Poliakov, Eugenia; Berinstein, Daniel M

    2016-12-20

    Study of age related macular degeneration (AMD) has been hampered by lack of human models that represent the complexity of the disease. Here we have developed a human in vitro disease model of AMD to investigate the underlying AMD disease mechanisms. Generation of iPSCs from retinal pigment epithelium (RPE) of AMD donors, age-matched normal donors, skin fibroblasts of a dry AMD patient, and differentiation of iPSCs into RPE (AMD RPE-iPSC-RPE, normal RPE-iPSC-RPE and AMD Skin-iPSC-RPE, respectively). Immunostaining, cell viability assay and reactive oxygen species (ROS) production under oxidative stress conditions, electron microscopy (EM) imaging, ATP production and glycogen concentration assays, quantitative real time PCR, western blot, karyotyping. The AMD RPE-iPSC-RPE and AMD Skin-iPSC-RPE present functional impairment and exhibit distinct disease phenotypes compared to RPE-iPSC-RPE generated from normal donors (Normal RPE-iPSC-RPE). The AMD RPE-iPSC-RPE and AMD Skin-iPSC-RPE show increased susceptibility to oxidative stress and produced higher levels of reactive oxygen species (ROS) under stress in accordance with recent reports. The susceptibility to oxidative stress-induced cell death in AMD RPE-iPSC-RPE and Skin-iPSC-RPE was consistent with inability of the AMD RPE-iPSC-RPE and Skin-iPSC-RPE to increase SOD2 expression under oxidative stress. Phenotypic analysis revealed disintegrated mitochondria, accumulation of autophagosomes and lipid droplets in AMD RPE-iPSC-RPE and AMD Skin-iPSC-RPE. Mitochondrial activity was significantly lower in AMD RPE-iPSC-RPE and AMD Skin-iPSC-RPE compared to normal cells and glycogen concentration was significantly increased in the diseased cells. Furthermore, Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a regulator of mitochondrial biogenesis and function was repressed, and lower expression levels of NAD-dependent deacetylase sirtuin1 (SIRT1) were found in AMD RPE-iPSC-RPE and AMD Skin

  18. Age-related mortality trends in Italy from 1901 to 2008.

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    Marina Vercelli

    Full Text Available We stratified the Italian population according to age and gender in order to evaluate mortality trends over more than one century. Data covering the 1901-2008 period were used to study the yearly variations in mortality. Fluctuations in age-adjusted mortality curves were analyzed by Join Point Regression Models, identifying Join Points and Annual Percent Changes. A consistent decline in all-cause mortality occurred across the whole period, the most striking variations being observed in the 0-49 years population. In 1901, other and undefined diseases were the main causes of death, followed by infectious, digestive, and respiratory diseases in the 0-49 years population and by respiratory, cardiovascular, and cerebrovascular diseases in the ≥ 50 years population groups. In 2008 the main causes of death were accidents (males and tumors (females in the 0-49 age class, tumors in the 50-69 age class (both genders, and tumors (males and cardiovascular diseases (females in the elderly. The results highlight the interplay between age and gender in affecting mortality trends and reflect the dramatic progress in nutritional, lifestyle, socioeconomic, medical, and hygienic conditions.

  19. Smoking-attributable medical expenditures by age, sex, and smoking status estimated using a relative risk approach☆

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    Maciosek, Michael V.; Xu, Xin; Butani, Amy L.; Pechacek, Terry F.

    2015-01-01

    Objective To accurately assess the benefits of tobacco control interventions and to better inform decision makers, knowledge of medical expenditures by age, gender, and smoking status is essential. Method We propose an approach to distribute smoking-attributable expenditures by age, gender, and cigarette smoking status to reflect the known risks of smoking. We distribute hospitalization days for smoking-attributable diseases according to relative risks of smoking-attributable mortality, and use the method to determine national estimates of smoking-attributable expenditures by age, sex, and cigarette smoking status. Sensitivity analyses explored assumptions of the method. Results Both current and former smokers ages 75 and over have about 12 times the smoking-attributable expenditures of their current and former smoker counterparts 35–54 years of age. Within each age group, the expenditures of formers smokers are about 70% lower than current smokers. In sensitivity analysis, these results were not robust to large changes to the relative risks of smoking-attributable mortality which were used in the calculations. Conclusion Sex- and age-group-specific smoking expenditures reflect observed disease risk differences between current and former cigarette smokers and indicate that about 70% of current smokers’ excess medical care costs is preventable by quitting. PMID:26051203

  20. Energy metabolism and inflammation in brain aging and Alzheimer's disease.

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    Yin, Fei; Sancheti, Harsh; Patil, Ishan; Cadenas, Enrique

    2016-11-01

    The high energy demand of the brain renders it sensitive to changes in energy fuel supply and mitochondrial function. Deficits in glucose availability and mitochondrial function are well-known hallmarks of brain aging and are particularly accentuated in neurodegenerative disorders such as Alzheimer's disease. As important cellular sources of H 2 O 2 , mitochondrial dysfunction is usually associated with altered redox status. Bioenergetic deficits and chronic oxidative stress are both major contributors to cognitive decline associated with brain aging and Alzheimer's disease. Neuroinflammatory changes, including microglial activation and production of inflammatory cytokines, are observed in neurodegenerative diseases and normal aging. The bioenergetic hypothesis advocates for sequential events from metabolic deficits to propagation of neuronal dysfunction, to aging, and to neurodegeneration, while the inflammatory hypothesis supports microglia activation as the driving force for neuroinflammation. Nevertheless, growing evidence suggests that these diverse mechanisms have redox dysregulation as a common denominator and connector. An independent view of the mechanisms underlying brain aging and neurodegeneration is being replaced by one that entails multiple mechanisms coordinating and interacting with each other. This review focuses on the alterations in energy metabolism and inflammatory responses and their connection via redox regulation in normal brain aging and Alzheimer's disease. Interaction of these systems is reviewed based on basic research and clinical studies. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Parental Problem-Solving Abilities and the Association of Sickle Cell Disease Complications with Health-related Quality of Life for School-age Children

    Science.gov (United States)

    Barakat, Lamia P.; Daniel, Lauren C.; Smith, Kelsey; Robinson, M. Renée; Patterson, Chavis A.

    2013-01-01

    Children with sickle cell disease (SCD) are at risk for poor health-related quality of life (HRQOL). The current analysis sought to explore parent problem-solving abilities/skills as a moderator between SCD complications and HRQOL to evaluate applicability to pediatric SCD. At baseline, 83 children ages 6–12 years and their primary caregiver completed measures of the child HRQOL. Primary caregivers also completed a measure of social problem-solving. A SCD complications score was computed from medical record review. Parent problem-solving abilities significantly moderated the association of SCD complications with child self-report psychosocial HRQOL (p = .006). SCD complications had a direct effect on parent proxy physical and psychosocial child HRQOL. Enhancing parent problem-solving abilities may be one approach to improve HRQOL for children with high SCD complications; however, modification of parent perceptions of HRQOL may require direct intervention to improve knowledge and skills involved in disease management. PMID:24222378

  2. The influence of age and gender on motor and non-motor features of early Parkinson's disease: initial findings from the Oxford Parkinson Disease Center (OPDC) discovery cohort.

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    Szewczyk-Krolikowski, Konrad; Tomlinson, Paul; Nithi, Kannan; Wade-Martins, Richard; Talbot, Kevin; Ben-Shlomo, Yoav; Hu, Michele T M

    2014-01-01

    Identifying factors influencing phenotypic heterogeneity in Parkinson's Disease is crucial for understanding variability in disease severity and progression. Age and gender are two most basic epidemiological characteristics, yet their effect on expression of PD symptoms is not fully defined. We aimed to delineate effects of age and gender on the phenotype in an incident cohort of PD patients and healthy controls from the Oxford Parkinson Disease Centre (OPDC). Clinical features, including demographic and medical characteristics and non-motor and motor symptoms, were analyzed in a group of PD patients within 3 years of diagnosis and a group of healthy controls from the OPDC cohort. Disease features were stratified according to age and compared between genders, controlling for effects of common covariates. 490 PD patients and 176 healthy controls were analyzed. Stratification by age showed increased disease severity with age on motor scales. Some non-motor features showed similar trend, including cognition and autonomic features. Comparison across genders highlighted a pattern of increased severity and greater symptom symmetricality in the face, neck and arms in men with women having more postural problems. Amongst the non-motor symptoms, men had more cognitive impairment, greater rate of REM behavior disorder (RBD), more orthostatic hypotension and sexual dysfunction. Age in PD is a strong factor contributing to disease severity even after controlling for the effect of disease duration. Gender-related motor phenotype can be defined by a vertical split into more symmetrical upper-body disease in men and disease dominated by postural symptoms in women. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Glio-vascular changes during ageing in wild-type and Alzheimer's disease-like APP/PS1 mice.

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    Janota, C S; Brites, D; Lemere, C A; Brito, M A

    2015-09-16

    Vascular and glial involvement in the development of neurodegenerative disorders, such as Alzheimer's disease (AD), and age-related brain vulnerabilities have been suggested. Therefore, we sought to: (i) investigate which vascular and glial events are evident in ageing and/or AD, (ii) to establish the temporal evolution of vascular and glial changes in AD-like and wild-type (WT) mice and (iii) to relate them to amyloid-β (Aβ) peptide accumulation. We examined immunohistochemically hippocampi and cortex from APP/PS1dE9 and WT C57BL/6 mice along ageing and disease progression (young-adulthood, middle- and old-age). Ageing resulted in the increase in receptor for advanced glycation endproducts expression, as well as the entrance of thrombin and albumin in hippocampal parenchyma. In contrast, the loss of platelet-derived growth factor receptor-β (PDGFR-β) positive cells, in both regions, was only related to AD pathogenesis. Hypovascularization was affected by both ageing and AD in the hippocampus, but resulted from the interaction between both factors in the cortex. Astrogliosis was a result of AD in hippocampus and of both factors in cortex, while microgliosis was associated with fibrillar amyloid plaques in AD-like mice and with the interaction between both factors in each of the studied regions. In sum, these data show that senile plaques precede vascular and glial alterations only in hippocampus, whereas in cortex, vascular and glial alterations, namely the loss of PDGFR-β-positive cells and astrogliosis, accompanied the first senile plaques. Hence, this study points to vascular and glial events that co-exist in AD pathogenesis and age-related brain vulnerabilities. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Relation between visual function index and falls-related factors in patients with age-related cataract

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    Mei-Na Huang

    2016-01-01

    Full Text Available AIM:To investigate the relation between vision function index and falls-related factors in patients with age-related cataract.METHODS:Ninety-six patients with age-related cataract were interviewed using a seven-item visual function questionnaire(VF-7, then classified into poor, moderate, or good visual function group. The differences of the three groups on visual acuity, balance and mobility function, cognition, depressive symptoms, self-reported fear of falling were analyzed. RESULTS:The patients in poor visual function group had older age, tendency to depression, was more afraid of falling, compared with groups with higher score in VF-7, and they had worse visual acuity, performed worse on all balance and mobility tests. CONCLUSION:Poor visual function is related to worse visual acuity, weaker balance and mobility performance in patients with age-related cataract. The VF-7, as a simple and convenient self-reported method, can be used as a falling risk monitoring in patients with age-related cataract.

  5. Pharmacologic Treatment of Wet Type Age-related Macular Degeneration; Current and Evolving Therapies.

    Science.gov (United States)

    Shams Najafabadi, Hoda; Daftarian, Narsis; Ahmadieh, Hamid; Soheili, Zahra-Soheila

    2017-08-01

    Age-related macular degeneration as the major cause of blindness in the elderly population has remained at the epicenter of clinical research in ophthalmology. This retinal disorder is characterized by the photoreceptor and retinal pigment epithelial cells loss, occurring within the macula. The disease represents a spectrum of clinical manifestations. It is a multifactorial disease resulting from a combination of genetic predispositions and environmental risk factors. AMD is classified into two different types, dry and wet. Wet AMD is in close relation with angiogenesis and inflammatory processes.A variety of anti-angiogenesis and anti-inflammatory drugs have been proposed for the treatment of the disease. The purpose of this paper is to briefly review the pharmacological therapies of the wet form of AMD and focus on new drugs that are currently in different stages of research and development.

  6. Hippocampal sclerosis of aging, a prevalent and high-morbidity brain disease

    Science.gov (United States)

    Smith, Charles D.; Abner, Erin L.; Wilfred, Bernard J.; Wang, Wang-Xia; Neltner, Janna H.; Baker, Michael; Fardo, David W.; Kryscio, Richard J.; Scheff, Stephen W.; Jicha, Gregory A.; Jellinger, Kurt A.; Van Eldik, Linda J.; Schmitt, Frederick A.

    2013-01-01

    Hippocampal sclerosis of aging (HS-Aging) is a causative factor in a large proportion of elderly dementia cases. The current definition of HS-Aging rests on pathologic criteria: neuronal loss and gliosis in the hippocampal formation that is out of proportion to AD-type pathology. HS-Aging is also strongly associated with TDP-43 pathology. HS-Aging pathology appears to be most prevalent in the oldest-old: autopsy series indicate that 5–30 % of nonagenarians have HS-Aging pathology. Among prior studies, differences in study design have contributed to the study-to-study variability in reported disease prevalence. The presence of HS-Aging pathology correlates with significant cognitive impairment which is often misdiagnosed as AD clinically. The antemortem diagnosis is further confounded by other diseases linked to hippocampal atrophy including frontotemporal lobar degeneration and cerebrovascular pathologies. Recent advances characterizing the neurocognitive profile of HS-Aging patients have begun to provide clues that may help identify living individuals with HS-Aging pathology. Structural brain imaging studies of research subjects followed to autopsy reveal hippocampal atrophy that is substantially greater in people with eventual HS-Aging pathology, compared to those with AD pathology alone. Data are presented from individuals who were followed with neurocognitive and neuroradiologic measurements, followed by neuropathologic evaluation at the University of Kentucky. Finally, we discuss factors that are hypothesized to cause or modify the disease. We conclude that the published literature on HS-Aging provides strong evidence of an important and under-appreciated brain disease of aging. Unfortunately, there is no therapy or preventive strategy currently available. PMID:23864344

  7. Immunology of age-related macular degeneration

    Science.gov (United States)

    Ambati, Jayakrishna; Atkinson, John P.; Gelfand, Bradley D.

    2014-01-01

    Age-related macular degeneration (AMD) is a leading cause of blindness in aged individuals. Recent advances have highlighted the essential role of immune processes in the development, progression and treatment of AMD. In this Review we discuss recent discoveries related to the immunological aspects of AMD pathogenesis. We outline the diverse immune cell types, inflammatory activators and pathways that are involved. Finally, we discuss the future of inflammation-directed therapeutics to treat AMD in the growing aged population. PMID:23702979

  8. Nucleotide Excision DNA Repair is Associated with Age-Related Vascular Dysfunction

    Science.gov (United States)

    Durik, Matej; Kavousi, Maryam; van der Pluijm, Ingrid; Isaacs, Aaron; Cheng, Caroline; Verdonk, Koen; Loot, Annemarieke E.; Oeseburg, Hisko; Musterd-Bhaggoe, Usha; Leijten, Frank; van Veghel, Richard; de Vries, Rene; Rudez, Goran; Brandt, Renata; Ridwan, Yanto R.; van Deel, Elza D.; de Boer, Martine; Tempel, Dennie; Fleming, Ingrid; Mitchell, Gary F.; Verwoert, Germaine C.; Tarasov, Kirill V.; Uitterlinden, Andre G.; Hofman, Albert; Duckers, Henricus J.; van Duijn, Cornelia M.; Oostra, Ben A.; Witteman, Jacqueline C.M.; Duncker, Dirk J.; Danser, A.H. Jan; Hoeijmakers, Jan H.; Roks, Anton J.M.

    2012-01-01

    Background Vascular dysfunction in atherosclerosis and diabetes, as observed in the aging population of developed societies, is associated with vascular DNA damage and cell senescence. We hypothesized that cumulative DNA damage during aging contributes to vascular dysfunction. Methods and Results In mice with genomic instability due to the defective nucleotide excision repair genes ERCC1 and XPD (Ercc1d/− and XpdTTD mice), we explored age-dependent vascular function as compared to wild-type mice. Ercc1d/− mice showed increased vascular cell senescence, accelerated development of vasodilator dysfunction, increased vascular stiffness and elevated blood pressure at very young age. The vasodilator dysfunction was due to decreased endothelial eNOS levels as well as impaired smooth muscle cell function, which involved phosphodiesterase (PDE) activity. Similar to Ercc1d/− mice, age-related endothelium-dependent vasodilator dysfunction in XpdTTD animals was increased. To investigate the implications for human vascular disease, we explored associations between single nucleotide polymorphisms (SNPs) of selected nucleotide excision repair genes and arterial stiffness within the AortaGen Consortium, and found a significant association of a SNP (rs2029298) in the putative promoter region of DDB2 gene with carotid-femoral pulse wave velocity. Conclusions Mice with genomic instability recapitulate age-dependent vascular dysfunction as observed in animal models and in humans, but with an accelerated progression, as compared to wild type mice. In addition, we found associations between variations in human DNA repair genes and markers for vascular stiffness which is associated with aging. Our study supports the concept that genomic instability contributes importantly to the development of cardiovascular disease. PMID:22705887

  9. Olfactory disfunction and its relation olfactory bulb volume in Parkinson's disease.

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    Altinayar, S; Oner, S; Can, S; Kizilay, A; Kamisli, S; Sarac, K

    2014-01-01

    Olfactory dysfunction is the most frequently seen non-motor symptom of Idiopathic Parkinson's disease (IPD). The aim of this study is to analyze selective olfactory dysfunction, and olfactory bulb volume (OBV) in subtypes of IPD, and compare them with those of the healthy controls. Our study included 41 patients with IPD and age and gender matched 19 healthy controls. IPD patients were either tremor dominant (65.9%; TDPD) or non-tremor dominant (34.1%; NTDPD) type. All patients underwent neurological, ear, nose, and throat examinations, and orthonasal olfaction testing. Magnetic resonance imaging (MRI) technique was used to measure the volume of the olfactory bulb. A significant decrease in olfactory identification scores was found in the patient group. The patients had difficulty in discriminating between odors of mothballs, chocolate, Turkish coffee and soap. OBV did not differ between the patient, and the control groups. In the TDPD group, odor identification ability was decreased when compared to the control group. However, odor test results of NTDPD, control and TDPD groups were similar. OBV estimates of the TDPD group were not different from those of the control group, while in the NTDPD group OBVs were found to be decreased. In all patients with Parkinson's disease OBV values did not vary with age of the patients, duration of the disease, age at onset of the disease, and Unified Parkinson's Disease Rating Scale motor scores (UPDRS-m). Olfactory function is a complex process involving olfactory, and cortical structures as well. In Idiopathic Parkinson's disease, changes in OBV do not seem to be directly related to olfactory dysfunction.

  10. Arterial Ventricular Uncoupling with Age and Disease and Recoupling with Exercise

    Science.gov (United States)

    Chantler, Paul D

    2017-01-01

    The deterioration in arterial and cardiac function with aging impairs arterial ventricular coupling, an important determinant of cardiovascular performance. However, exercise training improves arterial ventricular coupling especially during exercise during the age and disease process. This review examines the concept of arterial-ventricular coupling, and how age, and disease uncouples but exercise training recouples the heart and arterial system. PMID:28072585

  11. Influence of obesity, age, and comorbidities on the multi-biomarker disease activity test in rheumatoid arthritis.

    Science.gov (United States)

    Curtis, Jeffrey R; Greenberg, Jeffrey D; Harrold, Leslie R; Kremer, Joel M; Palmer, J Lynn

    2018-02-01

    Traditional markers of inflammation are often required for inclusion in rheumatoid arthritis trials, yet patients with active disease may have normal lab tests. The potential use of the multi-biomarker disease activity (MBDA) test in this setting is unclear, as is understanding of whether it is influenced by patient characteristics (e.g., age, BMI, and comorbidities). Using data from the Corrona registry, we conducted a cross-sectional analysis of RA patients with MBDA tests. Patients were classified as low (44) and by clinical and RA-related factors. Regression was used to evaluate the association between MBDA score and age, body mass index, comorbidities, and RA-related factors. Of 357 eligible patients, 76% (n = 273) had normal CRP (BMI, age, CDAI, and SJC. There was no association between MBDA score and fibromyalgia, diabetes, smoking, or COPD; none were confounders between MBDA score and either SJC or CDAI. For patients in CDAI remission, older age (2.6 units per decade; p = 0.03) and obesity (β = 10.5 for BMI > 30, referent to <25; p = 0.02) were independently associated with MBDA score. An adjusted MBDA score was proposed that was highly correlated with the original MBDA (r = 0.91). In this real-world analysis, the MBDA score was associated with RA disease activity, obesity, and age, and was negligibly affected by common comorbidities. Almost one-third of patients with normal CRP had high MBDA scores. An adjustment to the MBDA score to account for body mass index and age is proposed. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Case-control study of factors associated with chronic Chagas heart disease in patients over 50 years of age

    Directory of Open Access Journals (Sweden)

    Silvana de Araújo Silva

    2007-11-01

    Full Text Available A case-control study on chronic Chagas heart disease (CCHD was carried out between 1997 and 2005. Ninety patients over 50 years of age were examined for factors related to (CCHD. Fourty-six patients (51.1% with Chagas heart disease (anomalous ECG were assigned to the case group and 44 (48.9% were included in the control group as carriers of undetermined forms of chronic disease. Social, demographic (age, gender, skin color, area of origin, epidemiological (permanence within an endemic zone, family history of Chagas heart disease or sudden death, physical strain, alcoholism, and smoking, and clinical (systemic hypertension variables were analyzed. The data set was assessed through single-variable and multivariate analysis. The two factors independently associated with heart disease were age - presence of heart disease being three times higher in patients over 60 years of age (odds ratio, OR: 2.89; confidence interval of 95%: 1.09-7.61 - and family history of Chagas heart disease (OR: 2.833, CI 95%: 1.11-7.23. Systemic hypertension and gender did not prove to hold any association with heart disease, as neither did skin color, but this variable showed low statistical power due to reduced sample size.

  13. Current Concept of IgG4-Related Disease.

    Science.gov (United States)

    Okazaki, Kazuichi; Umehara, Hisanori

    2017-01-01

    IgG4-related disease (IgG4-RD) is a fibroinflammatory disease of unknown etiology, which is characterized by a tendency to form tumefactive lesions, increased serum levels of IgG4, and massive infiltration of IgG4-positive plasma cells with storiform fibrosis and/or obliterative phlebitis. Patients with IgG4-RD have frequently multiorgan involvements such as the pancreas, biliary tree, salivary glands, periorbital tissues, kidneys, lungs, lymph nodes, and retroperitoneum. IgG4-RD mainly affects middle-aged to elderly men except for involvement in lachrymal and salivary glands, so-called Mikulicz's disease. The clinical manifestations of IgG4-RD depend on individually involved organs and respond well to steroid, but the prognosis still remains unclear. Some patients develop serious complications such as obstructive jaundice due to hepatic, gallbladder, or pancreatic lesions; hydronephrosis due to retroperitoneal fibrosis; or respiratory symptoms due to pulmonary lesions. Nomenclatures of individual organ manifestation of IgG4-RD have been internationally consented.

  14. Higher serum cholesterol is associated with intensified age-related neural network decoupling and cognitive decline in early- to mid-life.

    Science.gov (United States)

    Spielberg, Jeffrey M; Sadeh, Naomi; Leritz, Elizabeth C; McGlinchey, Regina E; Milberg, William P; Hayes, Jasmeet P; Salat, David H

    2017-06-01

    Mounting evidence indicates that serum cholesterol and other risk factors for cardiovascular disease intensify normative trajectories of age-related cognitive decline. However, the neural mechanisms by which this occurs remain largely unknown. To understand the impact of cholesterol on brain networks, we applied graph theory to resting-state fMRI in a large sample of early- to mid-life Veterans (N = 206, Mean age  = 32). A network emerged (centered on the banks of the superior temporal sulcus) that evidenced age-related decoupling (i.e., decreased network connectivity with age), but only in participants with clinically-elevated total cholesterol (≥180 mg/dL). Crucially, decoupling in this network corresponded to greater day-to-day disability and mediated age-related declines in psychomotor speed. Finally, examination of network organization revealed a pattern of age-related dedifferentiation for the banks of the superior temporal sulcus, again present only with higher cholesterol. More specifically, age was related to decreasing within-module communication (indexed by Within-Module Degree Z-Score) and increasing between-module communication (indexed by Participation Coefficient), but only in participants with clinically-elevated cholesterol. Follow-up analyses indicated that all findings were driven by low-density lipoprotein (LDL) levels, rather than high-density lipoprotein (HDL) or triglycerides, which is interesting as LDL levels have been linked to increased risk for cardiovascular disease, whereas HDL levels appear inversely related to such disease. These findings provide novel insight into the deleterious effects of cholesterol on brain health and suggest that cholesterol accelerates the impact of age on neural trajectories by disrupting connectivity in circuits implicated in integrative processes and behavioral control. Hum Brain Mapp 38:3249-3261, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  15. High Prevalence of Gallstone Disease in Rheumatoid Arthritis: A New Comorbidity Related to Dyslipidemia?

    Science.gov (United States)

    García-Gómez, María Carmen; de Lama, Eugenia; Ordoñez-Palau, Sergi; Nolla, Joan Miquel; Corbella, Emili; Pintó, Xavier

    2017-08-01

    To assess the prevalence of gallstone disease and identify associated risk factors in rheumatoid arthritis (RA) patients compared to the general population. Eighty-four women with rheumatoid arthritis were included in the study. Each patient was assessed via a structured interview, physical examination, abdominal ultrasound and blood test including lipid profile. The prevalence of gallstone disease in rheumatoid arthritis was compared with data from a study of the Spanish population matched by age groups. Twenty-eight of the 84 women had gallstone disease (33.3%). RA women with and without gallstone disease were similar in most of the variables assessed, except for older age and menopausal status in the former. A greater prevalence of gallstone disease was seen in rheumatoid arthritis patients compared to the general population of the same age; however, the differences were significant only in women aged 60 or older (45.5% versus 23.1% respectively, P-value .008). The age-adjusted OR of developing gallstone disease in RA women compared with general population women was 2,3 (95% CI: 1.3-4.1). A significantly higher HDL3-c subfraction and higher apoA-I/HDL and HDL3-c/TC ratios were observed in patients with gallstone disease. Women with rheumatoid arthritis may have a predisposition to gallstones that can manifest in middle or older age compared with women in the general population. This situation could be related to chronic inflammation and HDL metabolism. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  16. Aging with HIV-1 Infection: Motor Functions, Cognition, and Attention--A Comparison with Parkinson's Disease.

    Science.gov (United States)

    DeVaughn, S; Müller-Oehring, E M; Markey, B; Brontë-Stewart, H M; Schulte, T

    2015-12-01

    Recent advances in highly active anti-retroviral therapy (HAART) in their various combinations have dramatically increased the life expectancies of HIV-infected persons. People diagnosed with HIV are living beyond the age of 50 but are experiencing the cumulative effects of HIV infection and aging on brain function. In HIV-infected aging individuals, the potential synergy between immunosenescence and HIV viral loads increases susceptibility to HIV-related brain injury and functional brain network degradation similar to that seen in Parkinson's disease (PD), the second most common neurodegenerative disorder in the aging population. Although there are clear diagnostic differences in the primary pathology of both diseases, i.e., death of dopamine-generating cells in the substantia nigra in PD and neuroinflammation in HIV, neurotoxicity to dopaminergic terminals in the basal ganglia (BG) has been implied in the pathogenesis of HIV and neuroinflammation in the pathogenesis of PD. Similar to PD, HIV infection affects structures of the BG, which are part of interconnected circuits including mesocorticolimbic pathways linking brainstem nuclei to BG and cortices subserving attention, cognitive control, and motor functions. The present review discusses the combined effects of aging and neuroinflammation in HIV individuals on cognition and motor function in comparison with age-related neurodegenerative processes in PD. Despite the many challenges, some HIV patients manage to age successfully, most likely by redistribution of neural network resources to enhance function, as occurs in healthy elderly; such compensation could be curtailed by emerging PD.

  17. Three-dimensional anatomy of equine incisors: tooth length, enamel cover and age related changes

    Science.gov (United States)

    2013-01-01

    Background Equine incisors are subjected to continuous occlusal wear causing multiple, age related changes of the extragingival crown. It is assumed that the occlusal wear is compensated by continued tooth elongation at the apical ends of the teeth. In this study, μCT-datasets offered the opportunity to analyze the three-dimensional appearance of the extra- and intraalveolar parts of the enamel containing dental crown as well as of the enamel-free dental root. Multiple morphometric measurements elucidated age related, morphological changes within the intraalveolar part of the incisors. Results Equine incisors possess a unique enamel cover displaying large indentations on the mesial and distal sides. After eruption tooth elongation at the apical end outbalances occlusal wear for two to four years resulting in increasing incisor length in this period of time. Remarkably, this maximum length is maintained for about ten years, up to a tooth age of 13 to 15 years post eruption. Variances in the total length of individual teeth are related to different Triadan positions (central-, middle- and corner incisors) as well as to the upper and lower arcades. Conclusion Equine incisors are able to fully compensate occlusal wear for a limited period of time. However, after this ability ceases, it is expected that a diminished intraalveolar tooth length will cause massive changes in periodontal biomechanics. The time point of these morphodynamic and biomechanical changes (13 to 15 years post eruption) occurs in coincidence with the onset of a recently described destructive disease of equine incisor (equine odontoclastic tooth resorption and hypercementosis) in aged horses. However, further biomechanical, cell biological and microbiological investigations are needed to elucidate a correlation between age related changes of incisor morphology and this disease. PMID:24321365

  18. SORL1 rs1699102 polymorphism modulates age-related cognitive decline and gray matter volume reduction in non-demented individuals.

    Science.gov (United States)

    Li, He; Lv, Chenlong; Yang, Caishui; Wei, Dongfeng; Chen, Kewei; Li, Shaowu; Zhang, Zhanjun

    2017-01-01

    SORL1 rs1699102 is associated with the risk of late-onset Alzheimer's disease. However, the effects of this single nucleotide polymorphism on cognition and brain structure during normal aging are unclear. This study aimed to examine the effects of the rs1699102 polymorphism on age-related cognitive decline and cortical gray matter reduction in the Chinese Han population. A total of 780 non-demented adults completed a battery of neuropsychological tests. High-resolution T1-weighted structural magnetic resonance imaging data from 89 of these subjects were also collected using a Siemens Trio 3.0 Tesla scanner. The T allele carriers displayed an accelerated age-related change in episodic memory and processing speed tests relative to the CC genotype. A similar pattern was observed in the age-related gray matter volume (GMV) reduction of the right middle temporal pole. The GMV in this region was significantly positively correlated with the episodic memory scores. The SORL1 gene rs1699102 polymorphism has been found to be associated with age-related cognitive decline and GMV reduction of the right middle temporal pole in older adults. These findings elucidate how the SORL1 variants shape the neural system to modulate age-related cognitive decline and support the hypothesis that SORL1 may represent a candidate gene for late-onset Alzheimer's disease. © 2016 EAN.

  19. Gluten-free diet may improve obstructive sleep apnea-related symptoms in children with celiac disease.

    Science.gov (United States)

    Yerushalmy-Feler, Anat; Tauman, Riva; Derowe, Ari; Averbuch, Eran; Ben-Tov, Amir; Weintraub, Yael; Weiner, Dror; Amir, Achiya; Moran-Lev, Hadar; Cohen, Shlomi

    2018-02-07

    Enlarged tonsils and adenoids are the major etiology of obstructive sleep apnea (OSA) in children. Lymphatic hyperplasia is common to both OSA and celiac disease. We aimed to investigate the effect of a gluten-free diet on OSA symptoms in children with celiac disease. Children with celiac disease aged 2-18 years were prospectively recruited before the initiation of a gluten-free diet. Children with negative celiac serology who underwent gastrointestinal endoscopies for other indications served as controls. All participants completed a validated OSA-related symptoms questionnaire and the pediatric sleep questionnaire (PSQ) at baseline and 6 months later. Thirty-four children with celiac disease (mean age 6.6 ± 3.5 years) and 24 controls (mean age 7.3 ± 4.6 years, P = 0.5) were recruited. There were no significant differences in gender, body mass index or season at recruitment between the two groups. The rate of positive PSQ scores was higher (more OSA-related symptoms) in the control group compared to the celiac group, both at recruitment and at the 6-month follow-up (33.3% vs. 11.8%, P = 0.046, and 16.7% vs. 0, P = 0.014, respectively). PSQ scores improved significantly in both groups at the 6-month follow-up (P celiac group compared to controls (0.1 ± 0.09 vs.0.06 ± 0.06, respectively, P = 0.04). Children with celiac disease had fewer OSA-related symptoms than controls, but the degree of improvement following the initiation of a gluten-free diet was significantly higher. These findings suggest that a gluten-free diet may improve OSA-related symptoms in children with celiac disease.

  20. Systemic complement activation in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Hendrik P N Scholl

    Full Text Available Dysregulation of the alternative pathway (AP of complement cascade has been implicated in the pathogenesis of age-related macular degeneration (AMD, the leading cause of blindness in the elderly. To further test the hypothesis that defective control of complement activation underlies AMD, parameters of complement activation in blood plasma were determined together with disease-associated genetic markers in AMD patients. Plasma concentrations of activation products C3d, Ba, C3a, C5a, SC5b-9, substrate proteins C3, C4, factor B and regulators factor H and factor D were quantified in patients (n = 112 and controls (n = 67. Subjects were analyzed for single nucleotide polymorphisms in factor H (CFH, factor B-C2 (BF-C2 and complement C3 (C3 genes which were previously found to be associated with AMD. All activation products, especially markers of chronic complement activation Ba and C3d (p<0.001, were significantly elevated in AMD patients compared to controls. Similar alterations were observed in factor D, but not in C3, C4 or factor H. Logistic regression analysis revealed better discriminative accuracy of a model that is based only on complement activation markers Ba, C3d and factor D compared to a model based on genetic markers of the complement system within our study population. In both the controls' and AMD patients' group, the protein markers of complement activation were correlated with CFH haplotypes.This study is the first to show systemic complement activation in AMD patients. This suggests that AMD is a systemic disease with local disease manifestation at the ageing macula. Furthermore, the data provide evidence for an association of systemic activation of the alternative complement pathway with genetic variants of CFH that were previously linked to AMD susceptibility.

  1. The Burden of Human Papillomavirus Infections and Related Diseases in Sub-Saharan Africa

    Science.gov (United States)

    De Vuyst, Hugo; Alemany, Laia; Lacey, Charles; Chibwesha, Carla J.; Sahasrabuddhe, Vikrant; Banura, Cecily; Denny, Lynette; Parham, Groesbeck P.

    2014-01-01

    Despite the scarcity of high quality cancer registries and lack of reliable mortality data, it is clear that human papillomavirus (HPV)-associated diseases, particularly cervical cancer, are major causes of morbidity and mortality in sub-Saharan Africa (SSA). Cervical cancer incidence rates in SSA are the highest in the world and the disease is the most common cause of cancer death among women in the region. The high incidence of cervical cancer is a consequence of the inability of most countries to either initiate or sustain cervical cancer prevention services. In addition, it appears that the prevalence of HPV in women with normal cytology is higher than in more developed areas of the world, at an average of 24%. There is, however, significant regional variation in SSA, with the highest incidence of HPV infection and cervical cancer found in Eastern and Western Africa. It is expected that, due to aging and growth of the population, but also to lack of access to appropriate prevention services and the concomitant human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemic, cervical cancer incidence and mortality rates in SSA will rise over the next 20 years. HPV16 and 18 are the most common genotypes in cervical cancer in SSA, although other carcinogenic HPV types, such as HPV45 and 35, are also relatively more frequent compared with other world regions. Data on other HPV-related anogenital cancers including those of the vulva, vagina, anus, and penis, are limited. Genital warts are common and associated with HPV types 6 and 11. HIV infection increases incidence and prevalence of all HPV-associated diseases. Sociocultural determinants of HPV-related disease, as well as the impact of forces that result in social destabilization, demand further study. Strategies to reduce the excessive burden of HPV-related diseases in SSA include age-appropriate prophylactic HPV vaccination, cervical cancer prevention services for women of the reproductive

  2. Physical activity attenuates age-related biomarker alterations in preclinical AD.

    Science.gov (United States)

    Okonkwo, Ozioma C; Schultz, Stephanie A; Oh, Jennifer M; Larson, Jordan; Edwards, Dorothy; Cook, Dane; Koscik, Rebecca; Gallagher, Catherine L; Dowling, N M; Carlsson, Cynthia M; Bendlin, Barbara B; LaRue, Asenath; Rowley, Howard A; Christian, Brad T; Asthana, Sanjay; Hermann, Bruce P; Johnson, Sterling C; Sager, Mark A

    2014-11-04

    To examine whether engagement in physical activity might favorably alter the age-dependent evolution of Alzheimer disease (AD)-related brain and cognitive changes in a cohort of at-risk, late-middle-aged adults. Three hundred seventeen enrollees in the Wisconsin Registry for Alzheimer's Prevention underwent T1 MRI; a subset also underwent (11)C-Pittsburgh compound B-PET (n = 186) and (18)F-fluorodeoxyglucose-PET (n = 152) imaging. Participants' responses on a self-report measure of current physical activity were used to classify them as either physically active or physically inactive based on American Heart Association guidelines. They also completed a comprehensive neuropsychological battery. Covariate-adjusted regression analyses were used to test whether the adverse effect of age on imaging and cognitive biomarkers was modified by physical activity. There were significant age × physical activity interactions for β-amyloid burden (p = 0.014), glucose metabolism (p = 0.015), and hippocampal volume (p = 0.025) such that, with advancing age, physically active individuals exhibited a lesser degree of biomarker alterations compared with the physically inactive. Similar age × physical activity interactions were also observed on cognitive domains of Immediate Memory (p = 0.042) and Visuospatial Ability (p = 0.016). In addition, the physically active group had higher scores on Speed and Flexibility (p = 0.002) compared with the inactive group. In a middle-aged, at-risk cohort, a physically active lifestyle is associated with an attenuation of the deleterious influence of age on key biomarkers of AD pathophysiology. However, because our observational, cross-sectional design cannot establish causality, randomized controlled trials/longitudinal studies will be necessary for determining whether midlife participation in structured physical exercise forestalls the development of AD and related disorders in later life. © 2014 American Academy of Neurology.

  3. Role of growth factors and the wound healing response in age-related macular degeneration

    NARCIS (Netherlands)

    Schlingemann, Reinier O.

    2004-01-01

    Growth factors (GF) are important in several stages of the pathogenesis of age-related macular disease (AMD). In choroidal neovascularization (CNV) in exudative AMD, the GF involved are similar to those involved in wound healing of the skin. Like granulation tissue of skin, CNV is characterized by

  4. Neuromelanin-related contrast in the substantia nigra semiquantitatively evaluated by magnetic resonance imaging at 3T. Comparison between normal aging and Parkinson disease

    International Nuclear Information System (INIS)

    Tanaka, Makoto; Aihara, Yuko; Ikeda, Sachie; Aihara, Yoshiaki

    2011-01-01

    Fast spin-echo (FSE) T 1 -weighted magnetic resonance imaging (MRI) at 3T, which was optimized to detect neuromelanin-related contrast (NRC), was applied to quantitative estimation of signal alterations in the substantia nigra pars compacta (SNc) of 72 normal volunteers and 59 patients with Parkinson disease (PD). We examined relationship between NRC in SNc and clinical parameters. The NRC showed significant positive correlation with normal aging and was slightly but significantly higher in women than in men. Significant reduction in the NRC was found in PD as compared with 59 age- and sex-matched normal volunteers. The NRC in PD was negatively and significantly correlated with duration of illness and disease severity assessed by unified Parkinoson's disease rating scale (UPDRS) and Hoehn and Yahr stage. Significant reduction of the NRC was demonstrated in patients with visual hallucinations as compare with patients without the symptoms. Rapid eye movement (REM) sleep behavior disorder also contributed reduction of NRC although it did more mildly than visual hallucination. Anosmia or hyposmia had no statistical relationship with the amount of NRC in PD. The overall visual inspection indicated that the reduction of the NRC in PD should start at the ventrolateral portion of SNc and advance medially. Additionally, we studied dementia with Lewy body disease (DLB). The NRC was reduced more significantly in DLB patients with PD symptoms than in those without them who also showed a significant reduction compared with normal controls. Quantification and distribution of the NRC obtained by 3T MRI was well correlated with pathological findings reported previously and clinical parameters in this study. Visualization and quantification of the NRC provide some parts of clinical and diagnostic information about pathologic condition of SNc. (author)

  5. Nanotechnology-based drug delivery treatments and specific targeting therapy for age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Tai-Chi Lin

    2015-11-01

    Full Text Available Nanoparticles combined with cells, drugs, and specially designed genes provide improved therapeutic efficacy in studies and clinical setting, demonstrating a new era of treatment strategy, especially in retinal diseases. Nanotechnology-based drugs can provide an essential platform for sustaining, releasing and a specific targeting design to treat retinal diseases. Poly-lactic-co-glycolic acid is the most widely used biocompatible and biodegradable polymer approved by the Food and Drug Administration. Many studies have attempted to develop special devices for delivering small-molecule drugs, proteins, and other macromolecules consistently and slowly. In this article, we first review current progress in the treatment of age-related macular degeneration. Then, we discuss the function of vascular endothelial growth factor (VEGF and the pharmacological effects of anti-VEGF-A antibodies and soluble or modified VEGF receptors. Lastly, we summarize the combination of antiangiogenic therapy and nanomedicines, and review current potential targeting therapy in age-related macular degeneration.

  6. Retinal pigment epithelium, age-related macular degeneration and neurotrophic keratouveitis.

    Science.gov (United States)

    Bianchi, Enrica; Scarinci, Fabio; Ripandelli, Guido; Feher, Janos; Pacella, Elena; Magliulo, Giuseppe; Gabrieli, Corrado Balacco; Plateroti, Rocco; Plateroti, Pasquale; Mignini, Fiorenzo; Artico, Marco

    2013-01-01

    Age-related macular degeneration (AMD) is the leading cause of impaired vision and blindness in the aging population. The aims of our studies were to identify qualitative and quantitative alterations in mitochondria in human retinal pigment epithelium (RPE) from AMD patients and controls and to test the protective effects of pigment epithelium-derived factor (PEDF), a known neurotrophic and antiangiogenic substance, against neurotrophic keratouveitis. Histopathological alterations were studied by means of morphometry, light and electron microscopy. Unexpectedly, morphometric data showed that the RPE alterations noted in AMD may also develop in normal aging, 10-15 years later than appearing in AMD patients. Reduced tear secretion, corneal ulceration and leukocytic infiltration were found in capsaicin (CAP)-treated rats, but this effect was significantly attenuated by PEDF. These findings suggest that PEDF accelerated the recovery of tear secretion and also prevented neurotrophic keratouveitis and vitreoretinal inflammation. PEDF may have a clinical application in inflammatory and neovascular diseases of the eye.

  7. AGE-RAGE Stress, Stressors, and Antistressors in Health and Disease.

    Science.gov (United States)

    Prasad, Kailash; Mishra, Manish

    2018-03-01

    Adverse effects of advanced glycation end-products (AGEs) on the tissues are through nonreceptor- and receptor-mediated mechanisms. In the receptor-mediated mechanism, interaction of AGEs with its cell-bound receptor of AGE (RAGE) increases generation of oxygen radicals, activates nuclear factor-kappa B, and increases expression and release of pro-inflammatory cytokines resulting in the cellular damage. The deleterious effects of AGE and AGE-RAGE interaction are coined as "AGE-RAGE stress." The body is equipped with defense mechanisms to counteract the adverse effects of AGE and RAGE through endogenous enzymatic (glyoxalase 1, glyoxalase 2) and AGE receptor-mediated (AGER1, AGER2) degradation of AGE, and through elevation of soluble receptor of AGE (sRAGE). Exogenous defense mechanisms include reduction in consumption of AGE, prevention of AGE formation, and downregulation of RAGE expression. We have coined AGE and RAGE as "stressors" and the defense mechanisms as "anti-stressors." AGE-RAGE stress is defined as a shift in the balance between stressors and antistressors in the favor of stressors. Measurements of stressors or antistressors alone would not assess AGE-RAGE stress. For true assessment of AGE-RAGE stress, the equation should include all the stressors and antistressors. The equation for AGE-RAGE stress, therefore, would be the ratio of AGE + RAGE/sRAGE + glyoxalase1 + glyoxalase 2 + AGER1 +AGER2. This is, however, not practical in patients. AGE-RAGE stress may be assessed simply by the ratio of AGE/sRAGE. A high ratio of AGE/sRAGE indicates a relative shift in stressors from antistressors, suggesting the presence of AGE-RAGE stress, resulting in tissue damage, initiation, and progression of the diseases and their complications.

  8. Systematic age-related differences in chronic disease management in a population-based cohort study: a new paradigm of primary care is required.

    Directory of Open Access Journals (Sweden)

    Alessandra Buja

    Full Text Available BACKGROUND: Our interest in chronic conditions is due to the fact that, worldwide, chronic diseases have overtaken infectious diseases as the leading cause of death and disability, so their management represents an important challenge for health systems. The aim of this study was to compare the performance of primary health care services in managing diabetes, congestive heart failure (CHF and coronary heart disease (CHD, by age group. METHODS: This population-based retrospective cohort study was conducted in Italy, enrolling 1,948,622 residents ≥ 16 years old. A multilevel regression model was applied to analyze compliance to care processes with explanatory variables at both patient and district level, using age group as an independent variable, and adjusting for sex, citizenship, disease duration, and Charlson index on the first level, and for District Health Unit on the second level. RESULTS: The quality of chronic disease management showed an inverted U-shaped relationship with age. In particular, our findings indicate lower levels for young adults (16-44 year-olds, adults (45-64, and oldest old (+85 than for patients aged 65-74 in almost all quality indicators of CHD, CHF and diabetes management. Young adults (16-44 y, adults (45-64 y, the very old (75-84 y and the oldest old (+85 y patients with CHD, CHF and diabetes are less likely than 65-74 year-old patients to be monitored and treated using evidence-based therapies, with the exceptions of echocardiographic monitoring for CHF in young adult patients, and renal monitoring for CHF and diabetes in the very old. CONCLUSION: Our study shows that more effort is needed to ensure that primary health care systems are sensitive to chronic conditions in the young and in the very elderly.

  9. Diminishing Risk for Age-Related Macular Degeneration with Nutrition: A Current View

    Directory of Open Access Journals (Sweden)

    Allen Taylor

    2013-07-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of blindness in the elderly. Clinical hallmarks of AMD are observed in one third of the elderly in industrialized countries. Preventative interventions through dietary modification are attractive strategies, because they are more affordable than clinical therapies, do not require specialists for administration and many studies suggest a benefit of micro- and macro-nutrients with respect to AMD with few, if any, adverse effects. The goal of this review is to provide information from recent literature on the value of various nutrients, particularly omega-3 fatty acids, lower glycemic index diets and, perhaps, some carotenoids, with regard to diminishing risk for onset or progression of AMD. Results from the upcoming Age-Related Eye Disease Study (AREDS II intervention trial should be particularly informative.

  10. Diminishing Risk for Age-Related Macular Degeneration with Nutrition: A Current View

    Science.gov (United States)

    Schleicher, Molly; Weikel, Karen; Garber, Caren; Taylor, Allen

    2013-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Clinical hallmarks of AMD are observed in one third of the elderly in industrialized countries. Preventative interventions through dietary modification are attractive strategies, because they are more affordable than clinical therapies, do not require specialists for administration and many studies suggest a benefit of micro- and macro-nutrients with respect to AMD with few, if any, adverse effects. The goal of this review is to provide information from recent literature on the value of various nutrients, particularly omega-3 fatty acids, lower glycemic index diets and, perhaps, some carotenoids, with regard to diminishing risk for onset or progression of AMD. Results from the upcoming Age-Related Eye Disease Study (AREDS) II intervention trial should be particularly informative. PMID:23820727

  11. The etiology of human age-related cataract. Proteins don't last forever.

    Science.gov (United States)

    Truscott, Roger J W; Friedrich, Michael G

    2016-01-01

    It is probable that the great majority of human cataract results from the spontaneous decomposition of long-lived macromolecules in the human lens. Breakdown/reaction of long-lived proteins is of primary importance and recent proteomic analysis has enabled the identification of the particular crystallins, and their exact sites of amino acid modification. Analysis of proteins from cataractous lenses revealed that there are sites on some structural proteins that show a consistently greater degree of deterioration than age-matched normal lenses. The most abundant posttranslational modification of aged lens proteins is racemization. Deamidation, truncation and crosslinking, each arising from the spontaneous breakdown of susceptible amino acids within proteins, are also present. Fundamental to an understanding of nuclear cataract etiology, it is proposed that once a certain degree of modification at key sites occurs, that protein-protein interactions are disrupted and lens opacification ensues. Since long-lived proteins are now recognized to be present in many other sites of the body, such as the brain, the information gleaned from detailed analyses of degraded proteins from aged lenses will apply more widely to other age-related human diseases. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Effect of aging and Alzheimer's disease-like pathology on brain monoamines in mice.

    Science.gov (United States)

    Von Linstow, C U; Severino, M; Metaxas, A; Waider, J; Babcock, A A; Lesch, K P; Gramsbergen, J B; Finsen, B

    2017-09-01

    Aging is the greatest single risk factor of the neurodegenerative disorder Alzheimer's disease (AD). The monoaminergic system, including serotonin (5-HT), dopamine (DA) and noradrenaline (NA) modulates cognition, which is affected in AD. Changes in monoamine levels have been observed in AD, but these can both be age- and/or disease-related. We examined whether brain monoamine levels change as part of physiological aging and/or AD-like disease in APP SWE /PS1 ΔE9 (APP/PS1) transgenic mice. The neocortex, hippocampus, striatum, brainstem and cerebellum of 6-, 12-, 18- and 24-month-old B6C3 wild-type (WT) mice and of 18-month old APP/PS1 and WT mice were analysed for 5-HT, DA and NA contents by high pressure liquid chromatography (HPLC), along with neocortex from 14-month-old APP/PS1 and WT mice. While, we observed no aging effect in WT mice, we detected region-specific changes in the levels of all monoamines in 18-month-old transgenic compared with WT mice. This included reductions in 5-HT (-30%), DA (-47%) and NA (-32%) levels in the neocortex and increases of 5-HT in the brainstem (+18%). No changes were observed in any of the monoamines in the neocortex from 14-month-old APP/PS1 mice. In combination, these findings indicate that aging alone is not sufficient to affect brain monoamine levels, unlike the APP SWE /PS1 ΔE9 genotype. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Clinical study of infectious diseases on aged A-bomb survivors in Hiroshima Welfare Home for aged A-bomb survivors

    International Nuclear Information System (INIS)

    Aisaka, Tadakazu; Orimen, Akio; Niimi, Masanobu; Simizu, Kiyoshi.

    1978-01-01

    Infections, especially urinary passage and respiratory infections of aged A-bomb survivers under special protective care was examined. Urinary passage infections have recently shown an increasing tendency. These infections are related to the factors such as their basic diseases and wearing napkins rather than a severe degree of protective care. In the case of respiratory infection, diseases such as influenza are observed rather in patients who can walk, but they tend to be aggravated in bedridden patients. It cannot be said that more urinary passage infections are observed in A-bomb survivers than non A-bomb survivers. Both urinary passage infection and respiratory infection tend to recur repeatedly. Aged A-bomb survivers show no significant difference of acquired immunity from that of non A-bomb survivers group. However, a maintenance of neutralizing antibody by vaccination of influenza in the former is worse than in the latter. Bedridden patients show a higher rate of infection to potential urinary passage diseases than patients who can walk, irrespective of sex. Moreover, bedridden patients have a large number of bacteria, but other significant host reaction couldn't be observed. In bedridden patients with potential urinary passage infection, a variety of bacteria, most of which are bacteria resistant to rutinely used broad spectrum antibiotics, is detected. As a main disease or a direct cause of death, pyelonephritis in women and bronchopneumonia are often observed. (Iwagami, H.)

  14. "Lipid raft aging" in the human frontal cortex during nonpathological aging: gender influences and potential implications in Alzheimer's disease.

    Science.gov (United States)

    Díaz, Mario; Fabelo, Noemí; Ferrer, Isidre; Marín, Raquel

    2018-07-01

    Lipid rafts are highly dynamic membrane domains featured by distinctive biochemical composition and physicochemical properties compared with the surrounding plasma membrane. These microstructures are associated not only with cellular signaling and communication in normal nerve cells but also with pathological processing of amyloid precursor protein in Alzheimer's disease. Using lipid rafts isolated from human frontal cortex in nondemented subjects aging 24 to 85 years, we demonstrate here that lipid structure of lipid rafts undergo significant alterations of specific lipid classes and phospholipid-bound fatty acids as brain cortex correlating with aging. Main changes affect levels of plasmalogens, polyunsaturated fatty acids (especially docosahexaenoic acid and arachidonic acid), total polar lipids (mainly phosphatidylinositol, sphingomyelin, sulfatides, and cerebrosides), and total neutral lipids (particularly cholesterol and sterol esters). Besides, relevant relationships between main fatty acids and/or lipid classes were altered in an age-related manner. This "lipid raft aging" exhibits clear gender differences and appear to be more pronounced in women than in men, especially in older (postmenopausal) women. The outcomes led us to conclude that human cortical lipid rafts are modified by aging in a gender-dependent fashion. Given the central role of bilayer lipid matrix in lipid rafts functionality and neuronal signaling, we hypothesize that these findings might underlie the higher prevalence of cognitive decline evolving toward Alzheimer's disease in postmenopausal women. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Conceptions of Healthy Aging Held by Relatives of Older Persons in Isan-Thai Culture: A Phenomenographic Study.

    Science.gov (United States)

    Manasatchakun, Pornpun; Roxberg, Åsa; Asp, Margareta

    2018-01-01

    In Thailand, family nurses are expected to provide support for older persons and their family members to promote healthy aging. Family bonds are strong, and relatives are expected to take care of their older family members. However, there is limited research on how older persons' family members perceive healthy aging. This study aimed to describe the conceptions of healthy aging held by the children and grandchildren of older persons in northeast Thailand. In a phenomenographic study, 14 interviews were performed to qualitatively analyze different conceptions of healthy aging. Four descriptive categories emerged: being independent, not being afflicted by diseases or illnesses, being a giver and a receiver, and being wise. The conceptions of healthy aging entail both autonomy and interdependence. The relative's perspective needs to be considered when policies relating to healthy aging are implemented in the community and when family nurses provide support to families to promote healthy aging.

  16. Coenzyme Q10 Supplementation in Aging and Disease

    Directory of Open Access Journals (Sweden)

    Juan D. Hernández-Camacho

    2018-02-01

    Full Text Available Coenzyme Q (CoQ is an essential component of the mitochondrial electron transport chain and an antioxidant in plasma membranes and lipoproteins. It is endogenously produced in all cells by a highly regulated pathway that involves a mitochondrial multiprotein complex. Defects in either the structural and/or regulatory components of CoQ complex or in non-CoQ biosynthetic mitochondrial proteins can result in a decrease in CoQ concentration and/or an increase in oxidative stress. Besides CoQ10 deficiency syndrome and aging, there are chronic diseases in which lower levels of CoQ10 are detected in tissues and organs providing the hypothesis that CoQ10 supplementation could alleviate aging symptoms and/or retard the onset of these diseases. Here, we review the current knowledge of CoQ10 biosynthesis and primary CoQ10 deficiency syndrome, and have collected published results from clinical trials based on CoQ10 supplementation. There is evidence that supplementation positively affects mitochondrial deficiency syndrome and the symptoms of aging based mainly on improvements in bioenergetics. Cardiovascular disease and inflammation are alleviated by the antioxidant effect of CoQ10. There is a need for further studies and clinical trials involving a greater number of participants undergoing longer treatments in order to assess the benefits of CoQ10 treatment in metabolic syndrome and diabetes, neurodegenerative disorders, kidney diseases, and human fertility.

  17. Metabolic syndrome but not obesity measures are risk factors for accelerated age-related glomerular filtration rate decline in the general population.

    Science.gov (United States)

    Stefansson, Vidar T N; Schei, Jørgen; Solbu, Marit D; Jenssen, Trond G; Melsom, Toralf; Eriksen, Bjørn O

    2018-05-01

    Rapid age-related glomerular filtration rate (GFR) decline increases the risk of end-stage renal disease, and a low GFR increases the risk of mortality and cardiovascular disease. High body mass index and the metabolic syndrome are well-known risk factors for patients with advanced chronic kidney disease, but their role in accelerating age-related GFR decline independent of cardiovascular disease, hypertension and diabetes is not adequately understood. We studied body mass index, waist circumference, waist-hip ratio and metabolic syndrome as risk factors for accelerated GFR decline in 1261 middle-aged people representative of the general population without diabetes, cardiovascular disease or kidney disease. GFR was measured as iohexol clearance at baseline and repeated after a median of 5.6 years. Metabolic syndrome was defined as fulfilling three out of five criteria, based on waist circumference, blood pressure, glucose, high-density lipoprotein cholesterol and triglycerides. The mean GFR decline rate was 0.95 ml/min/year. Neither the body mass index, waist circumference nor waist-hip ratio predicted statistically significant changes in age-related GFR decline, but individuals with baseline metabolic syndrome had a significant mean of 0.30 ml/min/year faster decline than individuals without metabolic syndrome in a multivariable adjusted linear regression model. This association was mainly driven by the triglyceride criterion of metabolic syndrome, which was associated with a significant 0.36 ml/min/year faster decline when analyzed separately. Results differed significantly when GFR was estimated using creatinine and/or cystatin C. Thus, metabolic syndrome, but not the body mass index, waist circumference or waist-hip ratio, is an independent risk factor for accelerated age-related GFR decline in the general population. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  18. Age-related hair pigment loss.

    Science.gov (United States)

    Tobin, Desmond J

    2015-01-01

    Humans are social animals that communicate disproportionately via potent genetic signals imbued in the skin and hair, including racial, ethnic, health, gender, and age status. For the vast majority of us, age-related hair pigment loss becomes the inescapable signal of our disappearing youth. The hair follicle (HF) pigmentary unit is a wonderful tissue for studying mechanisms generally regulating aging, often before this becomes evident elsewhere in the body. Given that follicular melanocytes (unlike those in the epidermis) are regulated by the hair growth cycle, this cycle is likely to impact the process of aging in the HF pigmentary unit. The formal identification of melanocyte stem cells in the mouse skin has spurred a flurry of reports on the potential involvement of melanocyte stem cell depletion in hair graying (i.e., canities). Caution is recommended, however, against simple extrapolation of murine data to humans. Regardless, hair graying in both species is likely to involve an age-related imbalance in the tissue's oxidative stress handling that will impact not only melanogenesis but also melanocyte stem cell and melanocyte homeostasis and survival. There is some emerging evidence that the HF pigmentary unit may have regenerative potential, even after it has begun to produce white hair fibers. It may therefore be feasible to develop strategies to modulate some aging-associated changes to maintain melanin production for longer. © 2015 S. Karger AG, Basel.

  19. White Matter Lipids as a Ketogenic Fuel Supply in Aging Female Brain: Implications for Alzheimer's Disease.

    Science.gov (United States)

    Klosinski, Lauren P; Yao, Jia; Yin, Fei; Fonteh, Alfred N; Harrington, Michael G; Christensen, Trace A; Trushina, Eugenia; Brinton, Roberta Diaz

    2015-12-01

    White matter degeneration is a pathological hallmark of neurodegenerative diseases including Alzheimer's. Age remains the greatest risk factor for Alzheimer's and the prevalence of age-related late onset Alzheimer's is greatest in females. We investigated mechanisms underlying white matter degeneration in an animal model consistent with the sex at greatest Alzheimer's risk. Results of these analyses demonstrated decline in mitochondrial respiration, increased mitochondrial hydrogen peroxide production and cytosolic-phospholipase-A2 sphingomyelinase pathway activation during female brain aging. Electron microscopic and lipidomic analyses confirmed myelin degeneration. An increase in fatty acids and mitochondrial fatty acid metabolism machinery was coincident with a rise in brain ketone bodies and decline in plasma ketone bodies. This mechanistic pathway and its chronologically phased activation, links mitochondrial dysfunction early in aging with later age development of white matter degeneration. The catabolism of myelin lipids to generate ketone bodies can be viewed as a systems level adaptive response to address brain fuel and energy demand. Elucidation of the initiating factors and the mechanistic pathway leading to white matter catabolism in the aging female brain provides potential therapeutic targets to prevent and treat demyelinating diseases such as Alzheimer's and multiple sclerosis. Targeting stages of disease and associated mechanisms will be critical.

  20. White Matter Lipids as a Ketogenic Fuel Supply in Aging Female Brain: Implications for Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Lauren P. Klosinski

    2015-12-01

    Full Text Available White matter degeneration is a pathological hallmark of neurodegenerative diseases including Alzheimer's. Age remains the greatest risk factor for Alzheimer's and the prevalence of age-related late onset Alzheimer's is greatest in females. We investigated mechanisms underlying white matter degeneration in an animal model consistent with the sex at greatest Alzheimer's risk. Results of these analyses demonstrated decline in mitochondrial respiration, increased mitochondrial hydrogen peroxide production and cytosolic-phospholipase-A2 sphingomyelinase pathway activation during female brain aging. Electron microscopic and lipidomic analyses confirmed myelin degeneration. An increase in fatty acids and mitochondrial fatty acid metabolism machinery was coincident with a rise in brain ketone bodies and decline in plasma ketone bodies. This mechanistic pathway and its chronologically phased activation, links mitochondrial dysfunction early in aging with later age development of white matter degeneration. The catabolism of myelin lipids to generate ketone bodies can be viewed as a systems level adaptive response to address brain fuel and energy demand. Elucidation of the initiating factors and the mechanistic pathway leading to white matter catabolism in the aging female brain provides potential therapeutic targets to prevent and treat demyelinating diseases such as Alzheimer's and multiple sclerosis. Targeting stages of disease and associated mechanisms will be critical.

  1. The Hayflick Limit and Age-Related Adaptive Immune Deficiency.

    Science.gov (United States)

    Gill, Zoe; Nieuwoudt, Martin; Ndifon, Wilfred

    2018-01-01

    The adaptive immune system (AIS) acquires significant deficiency during chronological ageing, making older individuals more susceptible to infections and less responsive to vaccines compared to younger individuals. At the cellular level, one of the most striking features of this ageing-related immune deficiency is the dramatic loss of T-cell diversity that occurs in elderly humans. After the age of 70 years, there is a sharp decline in the diversity of naïve T cells, including a >10-fold decrease in the CD4+ compartment and a >100-fold decrease in the CD8+ compartment. Such changes are detrimental because the AIS relies on a diverse naïve T-cell pool to respond to novel pathogens. Recent work suggests that this collapse of naïve T-cell diversity results from T cells reaching the Hayflick limit and being eliminated through both antigen-dependent and -independent pathways. The progressive attrition of telomeres is the molecular mechanism that underlies this Hayflick limit. Therefore, we propose that by measuring the telomere lengths of T cells with high resolution, it is possible to develop a unique biomarker of immune deficiency, potentially much better correlated with individual susceptibility to diseases compared to chronological age alone. © 2017 S. Karger AG, Basel.

  2. Effects of age, replicative lifespan and growth rate of human nucleus pulposus cells on selecting age range for cell-based biological therapies for degenerative disc diseases.

    Science.gov (United States)

    Lee, J S; Lee, S M; Jeong, S W; Sung, Y G; Lee, J H; Kim, K W

    2016-07-01

    Autologous disc cell implantation, growth factors and gene therapy appear to be promising therapies for disc regeneration. Unfortunately, the replicative lifespan and growth kinetics of human nucleus pulposus (NP) cells related to host age are unclear. We investigated the potential relations among age, replicative lifespan and growth rate of NP cells, and determined the age range that is suitable for cell-based biological therapies for degenerative disc diseases. We used NP tissues classified by decade into five age groups: 30s, 40s, 50s, 60s and 70s. The mean cumulative population doubling level (PDL) and population doubling rate (PDR) of NP cells were assessed by decade. We also investigated correlations between cumulative PDL and age, and between PDR and age. The mean cumulative PDL and PDR decreased significantly in patients in their 60s. The mean cumulative PDL and PDR in the younger groups (30s, 40s and 50s) were significantly higher than those in the older groups (60s and 70s). There also were significant negative correlations between cumulative PDL and age, and between PDR and age. We found that the replicative lifespan and growth rate of human NP cells decreased with age. The replicative potential of NP cells decreased significantly in patients 60 years old and older. Young individuals less than 60 years old may be suitable candidates for NP cell-based biological therapies for treating degenerative disc diseases.

  3. Superior cervical gangliectomy induces non-exudative age-related macular degeneration in mice

    Directory of Open Access Journals (Sweden)

    Hernán H. Dieguez

    2018-02-01

    Full Text Available Non-exudative age-related macular degeneration, a prevalent cause of blindness, is a progressive and degenerative disease characterized by alterations in Bruch's membrane, retinal pigment epithelium, and photoreceptors exclusively localized in the macula. Although experimental murine models exist, the vast majority take a long time to develop retinal alterations and, in general, these alterations are ubiquitous, with many resulting from non-eye-specific genetic manipulations; additionally, most do not always reproduce the hallmarks of human age-related macular degeneration. Choroid vessels receive sympathetic innervation from the superior cervical ganglion, which, together with the parasympathetic system, regulates blood flow into the choroid. Choroid blood flow changes have been involved in age-related macular degeneration development and progression. At present, no experimental models take this factor into account. The aim of this work was to analyze the effect of superior cervical gangliectomy (also known as ganglionectomy on the choroid, Bruch's membrane, retinal pigment epithelium and retina. Adult male C57BL/6J mice underwent unilateral superior cervical gangliectomy and a contralateral sham procedure. Although superior cervical gangliectomy induced ubiquitous choroid and choriocapillaris changes, it induced Bruch's membrane thickening, loss of retinal pigment epithelium melanin content and retinoid isomerohydrolase, the appearance of drusen-like deposits, and retinal pigment epithelium and photoreceptor atrophy, exclusively localized in the temporal side. Moreover, superior cervical gangliectomy provoked a localized increase in retinal pigment epithelium and photoreceptor apoptosis, and a decline in photoreceptor electroretinographic function. Therefore, superior cervical gangliectomy recapitulated the main features of human non-exudative age-related macular degeneration, and could become a new experimental model of dry age-related

  4. Ursodeoxycholic acid decreases age-related adiposity and inflammation in mice

    Science.gov (United States)

    Oh, Ah-Reum; Bae, Jin-Sik; Lee, Junghoon; Shin, Eunji; Oh, Byung-Chul; Park, Sang-Chul; Cha, Ji-Young

    2016-01-01

    Ursodeoxycholic acid (UDCA), a natural, hydrophilic nontoxic bile acid, is clinically effective for treating cholestatic and chronic liver diseases. We investigated the chronic effects of UDCA on age-related lipid homeostasis and underlying molecular mechanisms. Twenty-week-old C57BL/6 male and female mice were fed a diet with or without 0.3% UDCA supplementation for 25 weeks. UDCA significantly reduced weight gain, adiposity, hepatic triglyceride, and hepatic cholesterol without incidental hepatic injury. UDCA-mediated hepatic triglyceride reduction was associated with downregulated hepatic expression of peroxisome proliferator-activated receptor-γ, and of other genes involved in lipogenesis (Chrebp, Acaca, Fasn, Scd1, and Me1) and fatty acid uptake (Ldlr, Cd36). The inflammatory cytokines Tnfa, Ccl2, and Il6 were significantly decreased in liver and/or white adipose tissues of UDCA-fed mice. These data suggest that UDCA exerts beneficial effects on age-related metabolic disorders by lowering the hepatic lipid accumulation, while concurrently reducing hepatocyte and adipocyte susceptibility to inflammatory stimuli. [BMB Reports 2016; 49(2): 105-110] PMID:26350747

  5. Macular xanthophylls, lipoprotein-related genes, and age-related macular degeneration1234

    Science.gov (United States)

    Koo, Euna; Neuringer, Martha; SanGiovanni, John Paul

    2014-01-01

    Plant-based macular xanthophylls (MXs; lutein and zeaxanthin) and the lutein metabolite meso-zeaxanthin are the major constituents of macular pigment, a compound concentrated in retinal areas that are responsible for fine-feature visual sensation. There is an unmet need to examine the genetics of factors influencing regulatory mechanisms and metabolic fates of these 3 MXs because they are linked to processes implicated in the pathogenesis of age-related macular degeneration (AMD). In this work we provide an overview of evidence supporting a molecular basis for AMD-MX associations as they may relate to DNA sequence variation in AMD- and lipoprotein-related genes. We recognize a number of emerging research opportunities, barriers, knowledge gaps, and tools offering promise for meaningful investigation and inference in the field. Overviews on AMD- and high-density lipoprotein (HDL)–related genes encoding receptors, transporters, and enzymes affecting or affected by MXs are followed with information on localization of products from these genes to retinal cell types manifesting AMD-related pathophysiology. Evidence on the relation of each gene or gene product with retinal MX response to nutrient intake is discussed. This information is followed by a review of results from mechanistic studies testing gene-disease relations. We then present findings on relations of AMD with DNA sequence variants in MX-associated genes. Our conclusion is that AMD-associated DNA variants that influence the actions and metabolic fates of HDL system constituents should be examined further for concomitant influence on MX absorption, retinal tissue responses to MX intake, and the capacity to modify MX-associated factors and processes implicated in AMD pathogenesis. PMID:24829491

  6. Effect of aging and Alzheimer's disease-like pathology on brain monoamines in mice

    DEFF Research Database (Denmark)

    Von Linstow, C. U.; Severino, Maurizio; Metaxas, Athanasios

    2017-01-01

    , but these can both be age- and/or disease-related. We examined whether brain monoamine levels change as part of physiological aging and/or AD-like disease in APPSWE/PS1δE9 (APP/PS1) transgenic mice. The neocortex, hippocampus, striatum, brainstem and cerebellum of 6-, 12-, 18- and 24-month-old B6C3 wild......-type (WT) mice and of 18-month old APP/PS1 and WT mice were analysed for 5-HT, DA and NA contents by high pressure liquid chromatography (HPLC), along with neocortex from 14-month-old APP/PS1 and WT mice. While, we observed no aging effect in WT mice, we detected region-specific changes in the levels...... of all monoamines in 18-month-old transgenic compared with WT mice. This included reductions in 5-HT (-30%), DA (-47%) and NA (-32%) levels in the neocortex and increases of 5-HT in the brainstem (+18%). No changes were observed in any of the monoamines in the neocortex from 14-month-old APP/PS1 mice...

  7. Association of Aging-Related Endophenotypes With Mortality in 2 Cohort Studies: the Long Life Family Study and the Health, Aging and Body Composition Study.

    Science.gov (United States)

    Singh, Jatinder; Schupf, Nicole; Boudreau, Robert; Matteini, Amy M; Prasad, Tanushree; Newman, Anne B; Liu, YongMei; Christensen, Kaare; Kammerer, Candace M

    2015-12-01

    One method by which to identify fundamental biological processes that may contribute to age-related disease and disability, instead of disease-specific processes, is to construct endophenotypes comprising linear combinations of physiological measures. Applying factor analyses methods to phenotypic data (2006-2009) on 28 traits representing 5 domains (cognitive, cardiovascular, metabolic, physical, and pulmonary) from 4,472 US and Danish individuals in 574 pedigrees from the Long Life Family Study (United States and Denmark), we constructed endophenotypes and assessed their relationship with mortality. The most dominant endophenotype primarily reflected the physical activity and pulmonary domains, was heritable, was significantly associated with mortality, and attenuated the association of age with mortality by 24.1%. Using data (1997-1998) on 1,794 Health, Aging and Body Composition Study participants from Memphis, Tennessee, and Pittsburgh, Pennsylvania, we obtained strikingly similar endophenotypes and relationships to mortality. We also reproduced the endophenotype constructs, especially the dominant physical activity and pulmonary endophenotype, within demographic subpopulations of these 2 cohorts. Thus, this endophenotype construct may represent an underlying phenotype related to aging. Additional genetic studies of this endophenotype may help identify genetic variants or networks that contribute to the aging process. © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. Age-related changes in core body temperature and activity in triple-transgenic Alzheimer’s disease (3xTgAD mice

    Directory of Open Access Journals (Sweden)

    Elysse M. Knight

    2013-01-01

    Alzheimer’s disease (AD is characterised, not only by cognitive deficits and neuropathological changes, but also by several non-cognitive behavioural symptoms that can lead to a poorer quality of life. Circadian disturbances in core body temperature and physical activity are reported in AD patients, although the cause and consequences of these changes are unknown. We therefore characterised circadian patterns of body temperature and activity in male triple transgenic AD mice (3xTgAD and non-transgenic (Non-Tg control mice by remote radiotelemetry. At 4 months of age, daily temperature rhythms were phase advanced and by 6 months of age an increase in mean core body temperature and amplitude of temperature rhythms were observed in 3xTgAD mice. No differences in daily activity rhythms were seen in 4- to 9-month-old 3xTgAD mice, but by 10 months of age an increase in mean daily activity and the amplitude of activity profiles for 3xTgAD mice were detected. At all ages (4–10 months, 3xTgAD mice exhibited greater food intake compared with Non-Tg mice. The changes in temperature did not appear to be solely due to increased food intake and were not cyclooxygenase dependent because the temperature rise was not abolished by chronic ibuprofen treatment. No β-amyloid (Aβ plaques or neurofibrillary tangles were noted in the hypothalamus of 3xTgAD mice, a key area involved in temperature regulation, although these pathological features were observed in the hippocampus and amygdala of 3xTgAD mice from 10 months of age. These data demonstrate age-dependent changes in core body temperature and activity in 3xTgAD mice that are present before significant AD-related neuropathology and are analogous to those observed in AD patients. The 3xTgAD mouse might therefore be an appropriate model for studying the underlying mechanisms involved in non-cognitive behavioural changes in AD.

  9. Age-related changes in core body temperature and activity in triple-transgenic Alzheimer’s disease (3xTgAD) mice

    Science.gov (United States)

    Knight, Elysse M.; Brown, Timothy M.; Gümüsgöz, Sarah; Smith, Jennifer C. M.; Waters, Elizabeth J.; Allan, Stuart M.; Lawrence, Catherine B.

    2013-01-01

    SUMMARY Alzheimer’s disease (AD) is characterised, not only by cognitive deficits and neuropathological changes, but also by several non-cognitive behavioural symptoms that can lead to a poorer quality of life. Circadian disturbances in core body temperature and physical activity are reported in AD patients, although the cause and consequences of these changes are unknown. We therefore characterised circadian patterns of body temperature and activity in male triple transgenic AD mice (3xTgAD) and non-transgenic (Non-Tg) control mice by remote radiotelemetry. At 4 months of age, daily temperature rhythms were phase advanced and by 6 months of age an increase in mean core body temperature and amplitude of temperature rhythms were observed in 3xTgAD mice. No differences in daily activity rhythms were seen in 4- to 9-month-old 3xTgAD mice, but by 10 months of age an increase in mean daily activity and the amplitude of activity profiles for 3xTgAD mice were detected. At all ages (4–10 months), 3xTgAD mice exhibited greater food intake compared with Non-Tg mice. The changes in temperature did not appear to be solely due to increased food intake and were not cyclooxygenase dependent because the temperature rise was not abolished by chronic ibuprofen treatment. No β-amyloid (Aβ) plaques or neurofibrillary tangles were noted in the hypothalamus of 3xTgAD mice, a key area involved in temperature regulation, although these pathological features were observed in the hippocampus and amygdala of 3xTgAD mice from 10 months of age. These data demonstrate age-dependent changes in core body temperature and activity in 3xTgAD mice that are present before significant AD-related neuropathology and are analogous to those observed in AD patients. The 3xTgAD mouse might therefore be an appropriate model for studying the underlying mechanisms involved in non-cognitive behavioural changes in AD. PMID:22864021

  10. Adipocyte-derived factors in age-related dementia and their contribution to vascular and Alzheimer pathology.

    Science.gov (United States)

    Ishii, Makoto; Iadecola, Costantino

    2016-05-01

    Age-related dementia is increasingly recognized as having a mixed pathology, with contributions from both cerebrovascular factors and pathogenic factors associated with Alzheimer's disease (AD). Furthermore, there is accumulating evidence that vascular risk factors in midlife, e.g., obesity, diabetes, and hypertension, increase the risk of developing late-life dementia. Since obesity and changes in body weight/adiposity often drive diabetes and hypertension, understanding the relationship between adiposity and age-related dementia may reveal common underlying mechanisms. Here we offer a brief appraisal of how changes in body weight and adiposity are related to both AD and dementia on vascular basis, and examine the involvement of two key adipocyte-derived hormones: leptin and adiponectin. The evidence suggests that in midlife increased body weight/adiposity and subsequent changes in adipocyte-derived hormones may increase the long-term susceptibility to dementia. On the other hand, later in life, decreases in body weight/adiposity and related hormonal changes are early manifestations of disease that precede the onset of dementia and may promote AD and vascular pathology. Understanding the contribution of adiposity to age-related dementia may help identify the underlying pathological mechanisms common to both vascular dementia and AD, and provide new putative targets for early diagnosis and therapy. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Subclinical Coronary Plaque Burden in Asymptomatic Relatives of Patients With Documented Premature Coronary Artery Disease

    DEFF Research Database (Denmark)

    Christiansen, Morten Krogh; Jensen, Jesper Møller; Bøtker, Hans Erik

    Introduction: A family history of premature coronary artery disease (CAD) is a well-known risk factor for adverse coronary events with age of onset being inversely related to the degree of heritability. Hypothesis: We hypothesized that asymptomatic first degree relatives, of patients with premature...... CAD, suffer a high burden of subclinical coronary atherosclerosis. Methods: First degree relatives, aged 30-65 years, of patients with a documented coronary revascularization procedure before the age of 40 years, were invited to participate in the study. Participants were matched by age, sex...... and absence of a family history, with patients referred for coronary CT angiography (CTA) because of atypical angina or non-anginal chest pain. A pooled blinded analysis was performed. The main outcome measure was the number of plaque-affected coronary segments. Results: 88 relatives and 88 symptomatic...

  12. Effects of normal aging and Alzheimer's disease on emotional memory.

    Science.gov (United States)

    Kensinger, Elizabeth A; Brierley, Barbara; Medford, Nick; Growdon, John H; Corkin, Suzanne

    2002-06-01

    Recall is typically better for emotional than for neutral stimuli. This enhancement is believed to rely on limbic regions. Memory is also better for neutral stimuli embedded in an emotional context. The neural substrate supporting this effect has not been thoroughly investigated but may include frontal lobe, as well as limbic circuits. Alzheimer's disease (AD) results in atrophy of limbic structures, whereas normal aging relatively spares limbic regions but affects prefrontal areas. The authors hypothesized that AD would reduce all enhancement effects, whereas aging would disproportionately affect enhancement based on emotional context. The results confirmed the authors' hypotheses: Young and older adults, but not AD patients, showed better memory for emotional versus neutral pictures and words. Older adults and AD patients showed no benefit from emotional context, whereas young adults remembered more items embedded in an emotional versus neutral context.

  13. Optic nerve head biomechanics in aging and disease.

    Science.gov (United States)

    Downs, J Crawford

    2015-04-01

    This nontechnical review is focused upon educating the reader on optic nerve head biomechanics in both aging and disease along two main themes: what is known about how mechanical forces and the resulting deformations are distributed in the posterior pole and ONH (biomechanics) and what is known about how the living system responds to those deformations (mechanobiology). We focus on how ONH responds to IOP elevations as a structural system, insofar as the acute mechanical response of the lamina cribrosa is confounded with the responses of the peripapillary sclera, prelaminar neural tissues, and retrolaminar optic nerve. We discuss the biomechanical basis for IOP-driven changes in connective tissues, blood flow, and cellular responses. We use glaucoma as the primary framework to present the important aspects of ONH biomechanics in aging and disease, as ONH biomechanics, aging, and the posterior pole extracellular matrix (ECM) are thought to be centrally involved in glaucoma susceptibility, onset and progression. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Tour leaders with detailed knowledge of travel-related diseases play a key role in disease prevention.

    Science.gov (United States)

    Hsu, Shu-Hua; Huang, Hsien-Liang; Lu, Chia-Wen; Cheng, Shao-Yi; Lee, Long-Teng; Chiu, Tai-Yuan; Huang, Kuo-Chin

    2018-02-01

    In Taiwan, group tours are a popular mode of international travel; hence, group tour leaders must ensure traveler safety and health. This study identified factors influencing tour leaders' willingness to recommend pretravel medical consultation and vaccination.A cross-sectional questionnaire survey was administered to tour leaders from January 2011 to December 2012. Multivariate logistic regression analyses were performed to estimate the odds ratios of having a positive attitude and willingness based on different knowledge scores of the tour leaders after adjustments for age, sex, education level, and seniority.Tour leaders with a more detailed knowledge of both travel-related infectious and noninfectious diseases demonstrated a higher willingness to receive vaccination. They believed that consultation at travel clinics before travel can improve travelers' health (P educating tour leaders' knowledge about travel-related diseases to improve health care for travelers.

  15. Clinical Factors and Disease Course Related to Diagnostic Delay in Korean Crohn's Disease Patients: Results from the CONNECT Study.

    Directory of Open Access Journals (Sweden)

    Chang Mo Moon

    Full Text Available Diagnostic delay frequently occurs in Crohn's disease (CD patients because of diagnostic limitations. However, diagnostic delay and its related factors remain poorly defined. Therefore, we aimed to identify the predictors associated with diagnostic delay and to evaluate the impact of diagnostic delay on clinical course in a Korean CD patient cohort. We performed a multicenter retrospective analysis of 1,047 CD patients registered in the Crohn's Disease Clinical Network and Cohort study in Korea. The mean interval of diagnostic delay was 16.0 ± 33.1 months. Multivariate analysis showed that older age at diagnosis (≥40 years (p = 0.014, concomitant upper gastrointestinal (UGI disease (p = 0.012 and penetrating disease behavior at diagnosis (p = 0.001 were positively associated with long diagnostic delay (≥18 months. During the longitudinal follow-up, long diagnostic delay was independently predictive of further development of intestinal stenosis (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.07-1.93; p = 0.017, internal fistulas (HR, 1.62; 95% CI, 1.12-2.33; p = 0.011, and perianal fistulas (HR, 1.38; 95% CI, 1.06-1.80; p = 0.016. However, as for the risk of abscess formation, bowel perforation, and CD-related abdominal surgery, no significant association with diagnostic delay was observed. Older age at diagnosis, UGI involvement, and penetrating behavior are associated with long diagnostic delay in Korean CD patients. Moreover, diagnostic delay is associated with an increased risk of CD-related complications such as intestinal stenosis, internal fistulas, and perianal fistulas.

  16. Age-related collagen turnover of the interstitial matrix and basement membrane: Implications of age- and sex-dependent remodeling of the extracellular matrix

    DEFF Research Database (Denmark)

    Kehlet, Stephanie N.; Willumsen, Nicholas; Armbrecht, Gabriele

    2018-01-01

    The extracellular matrix (ECM) plays a vital role in maintaining normal tissue function. Collagens are major components of the ECM and there is a tight equilibrium between degradation and formation of these proteins ensuring tissue health and homeostasis. As a consequence of tissue turnover, small...... collagen fragments are released into the circulation, which act as important biomarkers in the study of certain tissue-related remodeling factors in health and disease. The aim of this study was to establish an age-related collagen turnover profile of the main collagens of the interstitial matrix (type I...... an increased turnover. In summary, collagen turnover is affected by age and sex with the interstitial matrix and the basement membrane being differently regulated. The observed changes needs to be accounted for when measuring ECM related biomarkers in clinical studies....

  17. Increased White Matter Inflammation in Aging- and Alzheimer’s Disease Brain

    Directory of Open Access Journals (Sweden)

    Divya Raj

    2017-06-01

    Full Text Available Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia activity in various brain regions upon healthy aging and Alzheimer’s disease (AD-related pathology in both human and mouse samples. In purified microglia isolated from aging mouse brains, we found a profound gene expression pattern related to pro-inflammatory processes, phagocytosis, and lipid homeostasis. Particularly in white matter microglia of 24-month-old mice, abundant expression of phagocytic markers including Mac-2, Axl, CD16/32, Dectin1, CD11c, and CD36 was detected. Interestingly, in white matter of human brain tissue the first signs of inflammatory activity were already detected during middle age. Thus quantification of microglial proteins, such as CD68 (commonly associated with phagocytosis and HLA-DR (associated with antigen presentation, in postmortem human white matter brain tissue showed an age-dependent increase in immunoreactivity already in middle-aged people (53.2 ± 2.0 years. This early inflammation was also detectable by non-invasive positron emission tomography imaging using [11C]-(R-PK11195, a ligand that binds to activated microglia. Increased microglia activity was also prominently present in the white matter of human postmortem early-onset AD (EOAD brain tissue. Interestingly, microglia activity in the white matter of late-onset AD (LOAD CNS was similar to that of the aged clinically silent AD cases. These data indicate that microglia-induced neuroinflammation is predominant in the white matter of aging mice and humans as well as in EOAD brains. This white matter inflammation may contribute to the progression of neurodegeneration, and have prognostic value for detecting the onset and progression of aging and neurodegeneration.

  18. NAD+ in Aging

    DEFF Research Database (Denmark)

    Fang, Evandro F.; Lautrup, Sofie; Hou, Yujun

    2017-01-01

    The coenzyme NAD+ is critical in cellular bioenergetics and adaptive stress responses. Its depletion has emerged as a fundamental feature of aging that may predispose to a wide range of chronic diseases. Maintenance of NAD+ levels is important for cells with high energy demands and for proficient...... neuronal function. NAD+ depletion is detected in major neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, cardiovascular disease and muscle atrophy. Emerging evidence suggests that NAD+ decrements occur in various tissues during aging, and that physiological and pharmacological...... interventions bolstering cellular NAD+ levels might retard aspects of aging and forestall some age-related diseases. Here, we discuss aspects of NAD+ biosynthesis, together with putative mechanisms of NAD+ action against aging, including recent preclinical and clinical trials. Recent discoveries have...

  19. Feasibility of telemedicine in detecting diabetic retinopathy and age-related macular degeneration.

    Science.gov (United States)

    Vaziri, Kamyar; Moshfeghi, Darius M; Moshfeghi, Andrew A

    2015-03-01

    Age-related macular degeneration and diabetic retinopathy are important causes of visual impairment and blindness in the world. Because of recent advances and newly available treatment modalities along with the devastating consequences associated with late stages of these diseases, much attention has been paid to the importance of early detection and improving patient access to specialist care. Telemedicine or, more specifically, digital retinal imaging utilizing telemedical technology has been proposed as an important alternative screening and management strategy to help meet this demand. In this paper, we perform a literature review and analysis that evaluates the validity and feasibility of telemedicine in detecting diabetic retinopathy and age-related macular degeneration. Understanding both the progress and barriers to progress that have been demonstrated in these two areas is important for future telemedicine research projects and innovations in telemedicine technology.

  20. Age-Related Alterations in Signaling Pathways in Articular Chondrocytes: Implications for the Pathogenesis and Progression of Osteoarthritis - A Mini-Review.

    Science.gov (United States)

    van der Kraan, Peter; Matta, Csaba; Mobasheri, Ali

    2017-01-01

    Musculoskeletal conditions are a major burden on individuals, healthcare systems, and social care systems throughout the world, with indirect costs having a predominant economic impact. Aging is a major contributing factor to the development and progression of arthritic and musculoskeletal diseases. Indeed, aging and inflammation (often referred to as 'inflammaging') are critical risk factors for the development of osteoarthritis (OA), which is one of the most common forms of joint disease. The term 'chondrosenescence' has recently been introduced to define the age-dependent deterioration of chondrocyte function and how it undermines cartilage function in OA. An important component of chondrosenescence is the age-related deregulation of subcellular signaling pathways in chondrocytes. This mini-review discusses the role of age-related alterations in chondrocyte signaling pathways. We focus our attention on two major areas: age-dependent alterations in transforming growth factor-β signaling and changes in protein kinase and phosphoprotein phosphatase activities in aging chondrocytes. A better understanding of the basic signaling mechanisms underlying aging in chondrocytes is likely to facilitate the development of new therapeutic and preventive strategies for OA and a range of other age-related osteoarticular disorders. © 2016 The Author(s) Published by S. Karger AG, Basel.

  1. Beyond chronological age: examining time and health as age-related mediators in relations to work motives

    NARCIS (Netherlands)

    Kooij, T.A.M.; de Lange, A.H.; Jansen, P.G.W.; Dikkers, J.S.E.

    2013-01-01

    Since workforces across the world are aging, researchers and organizations need more insight into how and why occupational well-being, together with work-related attitudes and motivations, change with age. Lifespan theories point to subjective health and future time perspective (i.e. an individual's

  2. The mouse as a model for understanding chronic diseases of aging: the histopathologic basis of aging in inbred mice

    Directory of Open Access Journals (Sweden)

    David Harrison

    2011-06-01

    Full Text Available Inbred mice provide a unique tool to study aging populations because of the genetic homogeneity within an inbred strain, their short life span, and the tools for analysis which are available. A large-scale longitudinal and cross-sectional aging study was conducted on 30 inbred strains to determine, using histopathology, the type and diversity of diseases mice develop as they age. These data provide tools that when linked with modern in silico genetic mapping tools, can begin to unravel the complex genetics of many of the common chronic diseases associated with aging in humans and other mammals. In addition, novel disease models were discovered in some strains, such as rhabdomyosarcoma in old A/J mice, to diseases affecting many but not all strains including pseudoxanthoma elasticum, pulmonary adenoma, alopecia areata, and many others. This extensive data set is now available online and provides a useful tool to help better understand strain-specific background diseases that can complicate interpretation of genetically engineered mice and other manipulatable mouse studies that utilize these strains.

  3. Age-Related Differences in Multiple Task Monitoring

    OpenAIRE

    Todorov, Ivo; Del Missier, Fabio; Mäntylä, Timo

    2014-01-01

    Coordinating multiple tasks with narrow deadlines is particularly challenging for older adults because of age related decline in cognitive control functions. We tested the hypothesis that multiple task performance reflects age- and gender-related differences in executive functioning and spatial ability. Young and older adults completed a multitasking session with four monitoring tasks as well as separate tasks measuring executive functioning and spatial ability. For both age groups, men excee...

  4. Evolving Knowledge in Pharmacologic Treatments of Age-Related Macular Degeneration.

    Science.gov (United States)

    Soubrane Daguet, Gisèle; Risard-Gasiorowski, Sarah; Massamba, Nathalie

    2016-01-01

    Modern retinal drug therapy is a result of the recent challenges and breakthroughs in chemistry, physics, genetics, cell biology and biotechnologies. Specific pharmaceutical and pharmacokinetic characteristics of a drug are of major importance and contribute to its ability to penetrate targeted ocular tissues in order to result in effective therapeutic concentrations. In addition, the drugs should maintain a prolonged time of activity and be safe with minimal local and systemic toxicity. The transporter vehicle or drug delivery system is crucial in order to enhance ocular tissue penetration and establish controlled drug release. Administration methods should be local, thereby reducing systemic side effects, and, ideally, treatment should be noninvasive. Within the group of so-called classic therapies, the use of pharmacologic treatments has become widespread for most severe retinal diseases. Thereby, ocular therapy of diseases like exudative age-related macular degeneration has improved markedly. Moreover, new metabolic pathways have been identified, new molecules have emerged, new synthesis technologies have been discovered, and new formulae conceived. These developments have opened new avenues for limiting disease progression. © 2016 S. Karger AG, Basel.

  5. Imaging of macrophage-related lung diseases

    International Nuclear Information System (INIS)

    Marten, Katharina; Hansell, David M.

    2005-01-01

    Macrophage-related pulmonary diseases are a heterogeneous group of disorders characterized by macrophage accumulation, activation or dysfunction. These conditions include smoking-related interstitial lung diseases, metabolic disorders such as Niemann-Pick or Gaucher disease, and rare primary lung tumors. High-resolution computed tomography abnormalities include pulmonary ground-glass opacification secondary to infiltration by macrophages, centrilobular nodules or interlobular septal thickening reflecting peribronchiolar or septal macrophage accumulation, respectively, emphysema caused by macrophage dysfunction, and honeycombing following macrophage-related lung matrix remodeling. (orig.)

  6. Energy Metabolism and Inflammation in Brain Aging and Alzheimer’s Disease

    Science.gov (United States)

    Yin, Fei; Sancheti, Harsh; Patil, Ishan; Cadenas, Enrique

    2016-01-01

    The high energy demand of the brain renders it sensitive to changes in energy fuel supply and mitochondrial function. Deficits in glucose availability and mitochondrial function are well-known hallmarks of brain aging and are particularly accentuated in neurodegenerative disorders such as Alzheimer’s disease. As important cellular sources of H2O2, mitochondrial dysfunction is usually associated with altered redox status. Bioenergetic deficits and chronic oxidative stress are both major contributors to cognitive decline associated with brain aging and Alzheimer’s disease. Neuroinflammatory changes, including microglial activation and production of inflammatory cytokines, are observed in neurodegenerative diseases and normal aging. The bioenergetic hypothesis advocates for sequential events from metabolic deficits to propagation of neuronal dysfunction, to aging, and to neurodegeneration, while the inflammatory hypothesis supports microglia activation as the driving force for neuroinflammation. Nevertheless, growing evidence suggests that these diverse mechanisms have redox dysregulation as a common denominator and connector. An independent view of the mechanisms underlying brain aging and neurodegeneration is being replaced by one that entails multiple mechanisms coordinating and interacting with each other. This review focuses on the alterations in energy metabolism and inflammatory responses and their connection via redox regulation in normal brain aging and Alzheimer’s disease. Interactions of these systems is reviewed based on basic research and clinical studies. PMID:27154981

  7. Age-related differences in multiple task monitoring.

    Science.gov (United States)

    Todorov, Ivo; Del Missier, Fabio; Mäntylä, Timo

    2014-01-01

    Coordinating multiple tasks with narrow deadlines is particularly challenging for older adults because of age related decline in cognitive control functions. We tested the hypothesis that multiple task performance reflects age- and gender-related differences in executive functioning and spatial ability. Young and older adults completed a multitasking session with four monitoring tasks as well as separate tasks measuring executive functioning and spatial ability. For both age groups, men exceeded women in multitasking, measured as monitoring accuracy. Individual differences in executive functioning and spatial ability were independent predictors of young adults' monitoring accuracy, but only spatial ability was related to sex differences. For older adults, age and executive functioning, but not spatial ability, predicted multitasking performance. These results suggest that executive functions contribute to multiple task performance across the adult life span and that reliance on spatial skills for coordinating deadlines is modulated by age.

  8. Age-related differences in multiple task monitoring.

    Directory of Open Access Journals (Sweden)

    Ivo Todorov

    Full Text Available Coordinating multiple tasks with narrow deadlines is particularly challenging for older adults because of age related decline in cognitive control functions. We tested the hypothesis that multiple task performance reflects age- and gender-related differences in executive functioning and spatial ability. Young and older adults completed a multitasking session with four monitoring tasks as well as separate tasks measuring executive functioning and spatial ability. For both age groups, men exceeded women in multitasking, measured as monitoring accuracy. Individual differences in executive functioning and spatial ability were independent predictors of young adults' monitoring accuracy, but only spatial ability was related to sex differences. For older adults, age and executive functioning, but not spatial ability, predicted multitasking performance. These results suggest that executive functions contribute to multiple task performance across the adult life span and that reliance on spatial skills for coordinating deadlines is modulated by age.

  9. Calpain 1 inhibitor BDA-410 ameliorates α-klotho-deficiency phenotypes resembling human aging-related syndromes.

    Science.gov (United States)

    Nabeshima, Yoko; Washida, Miwa; Tamura, Masaru; Maeno, Akiteru; Ohnishi, Mutsuko; Shiroishi, Toshihiko; Imura, Akihiro; Razzaque, M Shawkat; Nabeshima, Yo-ichi

    2014-08-01

    Taking good care of elderly is a major challenge of our society, and thus identification of potential drug targets to reduce age-associated disease burden is desirable. α-klotho(-/-) (α-kl) is a short-lived mouse model that displays multiple phenotypes resembling human aging-related syndromes. Such ageing phenotype of α-kl(-/-) mice is associated with activation of a proteolytic enzyme, Calpain-1. We hypothesized that uncontrolled activation of calpain-1 might be causing age-related phenotypes in α-kl-deficient mice. We found that daily administration of BDA-410, a calpain-1 inhibitor, strikingly ameliorated multiple aging-related phenotypes. Treated mice showed recovery of reproductive ability, increased body weight, reduced organ atrophy, and suppression of ectopic calcifications, bone mineral density reduction, pulmonary emphysema and senile atrophy of skin. We also observed ectopic expression of FGF23 in calcified arteries of α-kl(-/-) mice, which might account for the clinically observed association of increased FGF23 level with increased risk of cardiovascular mortality. These findings allow us to propose that modulation of calpain-1 activity is a potential therapeutic option for delaying age-associated organ pathology, particularly caused by the dysregulation of mineral ion homeostasis.

  10. Methods for structuring scientific knowledge from many areas related to aging research.

    Science.gov (United States)

    Zhavoronkov, Alex; Cantor, Charles R

    2011-01-01

    Aging and age-related disease represents a substantial quantity of current natural, social and behavioral science research efforts. Presently, no centralized system exists for tracking aging research projects across numerous research disciplines. The multidisciplinary nature of this research complicates the understanding of underlying project categories, the establishment of project relations, and the development of a unified project classification scheme. We have developed a highly visual database, the International Aging Research Portfolio (IARP), available at AgingPortfolio.org to address this issue. The database integrates information on research grants, peer-reviewed publications, and issued patent applications from multiple sources. Additionally, the database uses flexible project classification mechanisms and tools for analyzing project associations and trends. This system enables scientists to search the centralized project database, to classify and categorize aging projects, and to analyze the funding aspects across multiple research disciplines. The IARP is designed to provide improved allocation and prioritization of scarce research funding, to reduce project overlap and improve scientific collaboration thereby accelerating scientific and medical progress in a rapidly growing area of research. Grant applications often precede publications and some grants do not result in publications, thus, this system provides utility to investigate an earlier and broader view on research activity in many research disciplines. This project is a first attempt to provide a centralized database system for research grants and to categorize aging research projects into multiple subcategories utilizing both advanced machine algorithms and a hierarchical environment for scientific collaboration.

  11. MORPHOLOGICAL STUDY OF THE AGE RELATED CHANGES OF THE CERVIX

    Directory of Open Access Journals (Sweden)

    Monjushree Chakravarty

    2016-07-01

    Full Text Available BACKGROUND Disease of the cervix is a common clinical condition in females, worldwide and especially in a developing country like India. The study was undertaken in Guwahati Medical College to see the age related changes in the morphology of the cervix. AIM The study was done to observe the age related changes in the cervix and compare the same with the different studies done by the previous workers around the world so as to help clinicians to diagnose the pathologies of this part of the female reproductive system better. MATERIALS AND METHOD The specimens were divided into three groups viz. pre-reproductive, reproductive and post-menopausal. Twenty specimens were collected of each group. The results were statistically analysed and ‘t’ test was employed to find out the significant difference between the mean value. SUMMARY A study of the 60 specimens collected were done to find the morphological parameters of each group viz. pre-reproductive, reproductive and post-menopausal and the findings of each group were compared to one another and were related to the finding of previous workers. CONCLUSION The study showed that there were certain differences in the morphology of the three groups and these differences tallied with that of the previous workers.

  12. Astrocytes in physiological aging and Alzheimer's disease.

    Science.gov (United States)

    Rodríguez-Arellano, J J; Parpura, V; Zorec, R; Verkhratsky, A

    2016-05-26

    Astrocytes are fundamental for homoeostasis, defence and regeneration of the central nervous system. Loss of astroglial function and astroglial reactivity contributes to the aging of the brain and to neurodegenerative diseases. Changes in astroglia in aging and neurodegeneration are highly heterogeneous and region-specific. In animal models of Alzheimer's disease (AD) astrocytes undergo degeneration and atrophy at the early stages of pathological progression, which possibly may alter the homeostatic reserve of the brain and contribute to early cognitive deficits. At later stages of AD reactive astrocytes are associated with neurite plaques, the feature commonly found in animal models and in human diseased tissue. In animal models of the AD reactive astrogliosis develops in some (e.g. in the hippocampus) but not in all regions of the brain. For instance, in entorhinal and prefrontal cortices astrocytes do not mount gliotic response to emerging β-amyloid deposits. These deficits in reactivity coincide with higher vulnerability of these regions to AD-type pathology. Astroglial morphology and function can be regulated through environmental stimulation and/or medication suggesting that astrocytes can be regarded as a target for therapies aimed at the prevention and cure of neurodegenerative disorders. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Smoking, health and ageing

    Directory of Open Access Journals (Sweden)

    Nicita-Mauro Claudio

    2008-09-01

    Full Text Available Abstract On March 19, 2008 a Symposium on Pathophysiology of Ageing and Age-Related diseases was held in Palermo, Italy. Here, the lecture of V. Nicita-Mauro on Smoking, health and ageing is summarized. Smoking represents an important ageing accelerator, both directly by triggering an inflammatory responses, and indirectly by favoring the occurrence of several diseases where smoking is a recognized risk factor. Hence, non-smokers can delay the appearance of diseases and of ageing process, so attaining longevity.

  14. Superior cervical gangliectomy induces non-exudative age-related macular degeneration in mice.

    Science.gov (United States)

    Dieguez, Hernán H; Romeo, Horacio E; González Fleitas, María F; Aranda, Marcos L; Milne, Georgia A; Rosenstein, Ruth E; Dorfman, Damián

    2018-02-07

    Non-exudative age-related macular degeneration, a prevalent cause of blindness, is a progressive and degenerative disease characterized by alterations in Bruch's membrane, retinal pigment epithelium, and photoreceptors exclusively localized in the macula. Although experimental murine models exist, the vast majority take a long time to develop retinal alterations and, in general, these alterations are ubiquitous, with many resulting from non-eye-specific genetic manipulations; additionally, most do not always reproduce the hallmarks of human age-related macular degeneration. Choroid vessels receive sympathetic innervation from the superior cervical ganglion, which, together with the parasympathetic system, regulates blood flow into the choroid. Choroid blood flow changes have been involved in age-related macular degeneration development and progression. At present, no experimental models take this factor into account. The aim of this work was to analyze the effect of superior cervical gangliectomy (also known as ganglionectomy) on the choroid, Bruch's membrane, retinal pigment epithelium and retina. Adult male C57BL/6J mice underwent unilateral superior cervical gangliectomy and a contralateral sham procedure. Although superior cervical gangliectomy induced ubiquitous choroid and choriocapillaris changes, it induced Bruch's membrane thickening, loss of retinal pigment epithelium melanin content and retinoid isomerohydrolase, the appearance of drusen-like deposits, and retinal pigment epithelium and photoreceptor atrophy, exclusively localized in the temporal side. Moreover, superior cervical gangliectomy provoked a localized increase in retinal pigment epithelium and photoreceptor apoptosis, and a decline in photoreceptor electroretinographic function. Therefore, superior cervical gangliectomy recapitulated the main features of human non-exudative age-related macular degeneration, and could become a new experimental model of dry age-related macular degeneration, and

  15. Role of Stromal Paracrine Signals in Proliferative Diseases of the Aging Human Prostate

    Directory of Open Access Journals (Sweden)

    Kenichiro Ishii

    2018-04-01

    Full Text Available Androgens are essential for the development, differentiation, growth, and function of the prostate through epithelial–stromal interactions. However, androgen concentrations in the hypertrophic human prostate decrease significantly with age, suggesting an inverse correlation between androgen levels and proliferative diseases of the aging prostate. In elderly males, age- and/or androgen-related stromal remodeling is spontaneously induced, i.e., increased fibroblast and myofibroblast numbers, but decreased smooth muscle cell numbers in the prostatic stroma. These fibroblasts produce not only growth factors, cytokines, and extracellular matrix proteins, but also microRNAs as stromal paracrine signals that stimulate prostate epithelial cell proliferation. Surgical or chemical castration is the standard systemic therapy for patients with advanced prostate cancer. Androgen deprivation therapy induces temporary remission, but the majority of patients eventually progress to castration-resistant prostate cancer, which is associated with a high mortality rate. Androgen deprivation therapy-induced stromal remodeling may be involved in the development and progression of castration-resistant prostate cancer. In the tumor microenvironment, activated fibroblasts stimulating prostate cancer cell proliferation are called carcinoma-associated fibroblasts. In this review, we summarize the role of stromal paracrine signals in proliferative diseases of the aging human prostate and discuss the potential clinical applications of carcinoma-associated fibroblast-derived exosomal microRNAs as promising biomarkers.

  16. Visual cortex in aging and Alzheimer’s disease: Changes in visual field maps and population receptive fields

    Directory of Open Access Journals (Sweden)

    Alyssa A. Brewer

    2014-02-01

    Full Text Available Although several studies have suggested that cortical alterations underlie such age-related visual deficits as decreased acuity, little is known about what changes actually occur in visual cortex during healthy aging. Two recent studies showed changes in primary visual cortex (V1 during normal aging; however, no studies have characterized the effects of aging on visual cortex beyond V1, important measurements both for understanding the aging process and for comparison to changes in age-related diseases. Similarly, there is almost no information about changes in visual cortex in Alzheimer’s disease (AD, the most common form of dementia. Because visual deficits are often reported as one of the first symptoms of AD, measurements of such changes in the visual cortex of AD patients might improve our understanding of how the visual system is affected by neurodegeneration as well as aid early detection, accurate diagnosis and timely treatment of AD. Here we use fMRI to first compare the visual field map (VFM organization and population receptive fields (pRFs between young adults and healthy aging subjects for occipital VFMs V1, V2, V3, and hV4. Healthy aging subjects do not show major VFM organizational deficits, but do have reduced surface area and increased pRF sizes in the foveal representations of V1, V2, and hV4 relative to healthy young control subjects. These measurements are consistent with behavioral deficits seen in healthy aging. We then demonstrate the feasibility and first characterization of these measurements in two patients with mild AD, which reveal potential changes in visual cortex as part of the pathophysiology of AD. Our data aid in our understanding of the changes in the visual processing pathways in normal aging and provide the foundation for future research into earlier and more definitive detection of AD.

  17. Impact of Age at Smoking Initiation on Smoking-Related Morbidity and All-Cause Mortality.

    Science.gov (United States)

    Choi, Seung Hee; Stommel, Manfred

    2017-07-01

    Using a nationally representative sample of U.S. adults, the aims of this study were to examine the impact of early smoking initiation on the development of self-reported smoking-related morbidity and all-cause mortality. National Health Interview Survey data from 1997 through 2005 were linked to the National Death Index with follow-up to December 31, 2011. Two primary dependent variables were smoking-related morbidity and all-cause mortality; the primary independent variable was age of smoking initiation. The analyses included U.S. population of current and former smokers aged ≥30 years (N=90,278; population estimate, 73.4 million). The analysis relied on fitting logistic regression and Cox proportional hazards models. Among the U.S. population of smokers, 7.3% started smoking before age 13 years, 11.0% at ages 13-14 years, 24.2% at ages 15-16 years, 24.5% at ages 17-18 years, 14.5% at ages 19-20 years, and 18.5% at ages ≥21 years. Early smoking initiation before age 13 years was associated with increased risks for cardiovascular/metabolic (OR=1.67) and pulmonary (OR=1.79) diseases as well as smoking-related cancers (OR=2.1) among current smokers; the risks among former smokers were cardiovascular/metabolic (OR=1.38); pulmonary (OR=1.89); and cancers (OR=1.44). Elevated mortality was also related to early smoking initiation among both current (hazard ratio, 1.18) and former smokers (hazard ratio, 1.19). Early smoking initiation increases risks of experiencing smoking-related morbidities and all-cause mortality. These risks are independent of demographic characteristics, SES, health behaviors, and subsequent smoking intensity. Comprehensive tobacco control programs should be implemented to prevent smoking initiation and promote cessation among youth. Copyright © 2017 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  18. Targeting modifiable risk factors in age-related macular degeneration in optometric practice in Sweden

    Directory of Open Access Journals (Sweden)

    Martin L

    2017-04-01

    Full Text Available Lene Martin1,2 1School of Health, Care and Social Welfare, Mälardalen University, Eskilstuna, Sweden; 2School of Health Sciences, City, University of London, London, UK Purpose: The purpose of this study was to investigate the extent to which ophthalmologists and optometrists in Sweden recommend the use of nutritional supplements, changes in diet, or smoking cessation to patients who are at risk of or with signs of age-related macular degeneration (AMD. In addition, this study also examined how these practitioners rate the strength of evidence for nutritional supplements in AMD management and which sources of information they consult to determine supplement recommendations for the prevention or treatment of AMD. Methods: This study implemented a cross-sectional design using data from a questionnaire. All Swedish optometrists and ophthalmologists who were registered in the membership databases of their respective professional organizations were invited to participate. The questionnaire contained 18 forced choice questions and one free text question and was organized into the following four sections: use of nutritional supplements, dietary advice, smoking and eye diseases, and strength of evidence and the sources of information regarding nutritional supplement interventions. Results: The response rate was 40.3% for optometrists and 5% for ophthalmologists. Optometrists were more likely than ophthalmologists to recommend nutritional supplements in AMD and provided significantly more advice about diet than did the ophthalmologists for both patients at risk for AMD and those with established disease. The ophthalmologists were more likely than the optometrists to rely on the findings from the age-related eye disease studies of AMD regarding treatment with and selection of supplements and to recommend smoking cessation. Conclusion: Common evidence-based strategies for AMD management among eye care professionals would presumably be beneficial for AMD

  19. Genetic mouse models of brain ageing and Alzheimer's disease.

    Science.gov (United States)

    Bilkei-Gorzo, Andras

    2014-05-01

    Progression of brain ageing is influenced by a complex interaction of genetic and environmental factors. Analysis of genetically modified animals with uniform genetic backgrounds in a standardised, controlled environment enables the dissection of critical determinants of brain ageing on a molecular level. Human and animal studies suggest that increased load of damaged macromolecules, efficacy of DNA maintenance, mitochondrial activity, and cellular stress defences are critical determinants of brain ageing. Surprisingly, mouse lines with genetic impairment of anti-oxidative capacity generally did not show enhanced cognitive ageing but rather an increased sensitivity to oxidative challenge. Mouse lines with impaired mitochondrial activity had critically short life spans or severe and rapidly progressing neurodegeneration. Strains with impaired clearance in damaged macromolecules or defects in the regulation of cellular stress defences showed alterations in the onset and progression of cognitive decline. Importantly, reduced insulin/insulin-like growth factor signalling generally increased life span but impaired cognitive functions revealing a complex interaction between ageing of the brain and of the body. Brain ageing is accompanied by an increased risk of developing Alzheimer's disease. Transgenic mouse models expressing high levels of mutant human amyloid precursor protein showed a number of symptoms and pathophysiological processes typical for early phase of Alzheimer's disease. Generally, therapeutic strategies effective against Alzheimer's disease in humans were also active in the Tg2576, APP23, APP/PS1 and 5xFAD lines, but a large number of false positive findings were also reported. The 3xtg AD model likely has the highest face and construct validity but further studies are needed. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Predictors of health-related quality of life in children with chronic heart disease.

    Science.gov (United States)

    Niemitz, Mandy; Gunst, Diana C M; Hövels-Gürich, Hedwig H; Hofbeck, Michael; Kaulitz, Renate; Galm, Christoph; Berger, Felix; Nagdyman, Nicole; Stiller, Brigitte; Borth-Bruhns, Thomas; Konzag, Ines; Balmer, Christian; Goldbeck, Lutz

    2017-10-01

    Chronic paediatric heart disease is often associated with residual symptoms, persisting functional restrictions, and late sequelae for psychosocial development. It is, therefore, increasingly important to evaluate the health-related quality of life of children and adolescents with chronic heart disease. The aim of this study was to determine medical and socio-demographic variables affecting health-related quality of life in school-aged children and adolescents with chronic heart disease. Patients and methods The Pediatric Cardiac Quality of Life Inventory was administered to 375 children and adolescents and 386 parental caregivers. Medical information was obtained from the charts. The socio-demographic information was provided by the patients and caregivers. Greater disease severity, low school attendance, current cardiac medication, current parental employment, uncertain or limited prognosis, history of connection to a heart-lung machine, number of nights spent in a hospital, and need for treatment in a paediatric aftercare clinic independently contributed to lower health-related quality of life (self-report: R2=0.41; proxy-report: R2=0.46). High correlations between self-reports and parent-proxy reports indicated concordance regarding the evaluation of a child's health-related quality of life. Beyond medical treatment, integration into school is important to increase health-related quality of life in children and adolescents surviving with chronic heart disease. Regular screening of health-related quality of life is recommended to identify patients with special needs.

  1. Differential age-related effects on conjunctive and relational visual short-term memory binding.

    Science.gov (United States)

    Bastin, Christine

    2017-12-28

    An age-related associative deficit has been described in visual short-term binding memory tasks. However, separate studies have suggested that ageing disrupts relational binding (to associate distinct items or item and context) more than conjunctive binding (to integrate features within an object). The current study directly compared relational and conjunctive binding with a short-term memory task for object-colour associations in 30 young and 30 older adults. Participants studied a number of object-colour associations corresponding to their individual object span level in a relational task in which objects were associated to colour patches and a conjunctive task where colour was integrated into the object. Memory for individual items and for associations was tested with a recognition memory test. Evidence for an age-related associative deficit was observed in the relational binding task, but not in the conjunctive binding task. This differential impact of ageing on relational and conjunctive short-term binding is discussed by reference to two underlying age-related cognitive difficulties: diminished hippocampally dependent binding and attentional resources.

  2. ALGORITHM OF DIAGNOSTICS AND TREATMENT OF AN AGE-RELATED MACULAR DEGENERATION AT PATIENTS WITH CHRONIC PERIPHERAL UVEITIS

    Directory of Open Access Journals (Sweden)

    Yu. I. Khoroshikh

    2014-01-01

    Full Text Available The results of clinical trial of various approaches in treatment the exudative forms of macular degenerations, including age-related, against chronic slow intensity inflammatory process on the extreme retinal periphery of an eye are described in represented material. There were 91 patients (105 eyes in the research with different types of an exudative macular degeneration. The general criteria of inclusion were: age of 18–80 years old, complaints to discomfort in eyes, a spot before an eye, distortions and decrease in the central sight, ophthalmoscopic symptoms of hypostasis in the central and peripheral areas of a retina. It is analyzed the general criteria of diagnostics and treatment of the disease in the article. Considering defeat of the chorioretinal structures located near the ora serrata at persons of young and advanced age. Practical recommendations to a choice of methods of diagnostics and treatment of various clinical and morphological forms of the disease are made. Screening methods of identification of patients with the peripheral uveitis are offered. The scheme of risk calculation of development the macular pathology at persons with changes on the extreme periphery of a retina, that can be used as a method of prevention of development predictively adverse of “wet" forms of an age-related macular degeneration, by means of timely sparing treatment at patients with chronic inflammatory diseases of eyes is given.

  3. Update on the role of genetics in the onset of age-related macular degeneration

    Science.gov (United States)

    Francis, Peter James; Klein, Michael L

    2011-01-01

    Age-related macular degeneration (AMD), akin to other common age-related diseases, has a complex pathogenesis and arises from the interplay of genes, environmental factors, and personal characteristics. The past decade has seen very significant strides towards identification of those precise genetic variants associated with disease. That genes encoding proteins of the (alternative) complement pathway (CFH, C2, CFB, C3, CFI) are major players in etiology came as a surprise to many but has already lead to the development of therapies entering human clinical trials. Other genes replicated in many populations ARMS2, APOE, variants near TIMP3, and genes involved in lipid metabolism have also been implicated in disease pathogenesis. The genes discovered to date can be estimated to account for approximately 50% of the genetic variance of AMD and have been discovered by candidate gene approaches, pathway analysis, and latterly genome-wide association studies. Next generation sequencing modalities and meta-analysis techniques are being employed with the aim of identifying the remaining rarer but, perhaps, individually more significant sequence variations, linked to disease status. Complementary studies have also begun to utilize this genetic information to develop clinically useful algorithms to predict AMD risk and evaluate pharmacogenetics. In this article, contemporary commentary is provided on rapidly progressing efforts to elucidate the genetic pathogenesis of AMD as the field stands at the end of the first decade of the 21st century. PMID:21887094

  4. The mechanobiology of obesity and related diseases

    CERN Document Server

    Benayahu, Dafna

    2015-01-01

    This volume describes the state-of-knowledge in the study of the relationships between mechanical loading states in tissues and common pathophysiologies related to increase in mass of adipose tissues and/or hyperglycemia which eventually lead to obesity, diabetes, insulin resistance, hyperlipidemia, metabolic inflammations, certain types of cancer and other related diseases. There appears to be an interaction between the loading states in tissues and cells and these chronic conditions, as well as with factors such as age, gender and genetics of the individual. Bioengineering has made key contributions to this research field in providing technologies for cell biomechanics experimentation, microscopy and image processing, tissue engineering and multi-scale, multi-physics computational modeling. Topics at the frontier of this field of study include: the continuous monitoring of cell growth, proliferation and differentiation in response to mechanical factors such as stiffness of the extracellular matrix (ECM) and...

  5. Impacts of age-related failures on nuclear systems

    International Nuclear Information System (INIS)

    Meale, B.M.; Satterwhite, D.G.; Krantz, E.A.; MacDonald, P.E.

    1986-01-01

    Aging-related failure data from nine light water reactor safety, support, and power conversion systems have been extracted from an operational data base. Systems and components within the systems that are most affected by aging are identified. In addition, information on aging-related root causes of component failures has been extracted for service water and Class 1E electrical power distribution systems. Engineering insights are presented, and preliminary quantification of the importance of aging-related root causes for a service water system is provided

  6. Relation between small airways disease and parenchymal destruction in surgical lung specimens.

    Science.gov (United States)

    Willems, L N; Kramps, J A; Stijnen, T; Sterk, P J; Weening, J J; Dijkman, J H

    1990-01-01

    The relation between small airways disease and parenchymal destruction was investigated in lungs and lobes removed at surgery from 27 patients aged 15-70 years. Eight of the 27 patients were life-long non-smokers. The degree of small airways disease was assessed by semi-quantitative grading (SAD score) and by measuring diameter and wall thickness of membranous bronchioles. Parenchymal destruction was measured in three ways. Firstly, the number of alveolar attachments on membranous bronchioles per millimetre of circumference (AA/mm) was counted; the number of broken attachments was subtracted from the total AA/mm to give the numbers of intact attachments (normal AA/mm). Secondly, a point counting technique was used to give a destructive index (DI). Thirdly, the mean linear intercept (Lm) was determined. Total and normal AA/mm correlated negatively with the SAD score of membranous bronchioles (rs = -0.48 and -0.51) and with wall thickness (rs = -0.37 and -0.45) and DI correlated with wall thickness (rs = 0.5) and with the SAD score of respiratory bronchioles (rs = 0.53). Lm did not correlate with indices of small airway disease and total and normal AA/mm did not correlate with diameter. Multiple regression analyses showed that the correlation of total AA/mm with the SAD score of membranous and respiratory bronchioles and with wall thickness were not confounded by age or smoking. It is concluded that small airways disease is related to destruction of peribronchiolar alveoli, and it is postulated that small airways disease has a direct role in the causation of centrilobular emphysema. PMID:2315880

  7. Maternal periodontal disease in early pregnancy and risk for a small-for-gestational-age infant.

    Science.gov (United States)

    Boggess, Kim A; Beck, James D; Murtha, Amy P; Moss, Kevin; Offenbacher, Steven

    2006-05-01

    The objective of the study was to determine whether periodontal disease is associated with delivery of a small-for-gestational-age infant. In a prospective study of oral health, periodontal disease was categorized as health, mild, or moderate/severe on the basis of clinical criteria. Small for gestational age was defined as birth weight less than the 10th percentile for gestational age. A risk ratio (95th percentile confidence interval) for a small-for-gestational-age infant among women with moderate or severe periodontal disease was calculated. Sixty-seven of 1017 women (6.6%) delivered a small-for-gestational-age infant, and 143 (14.3%) had moderate or severe periodontal disease. The small-for-gestational-age rate was higher among women with moderate or severe periodontal disease, compared with those with health or mild disease (13.8% versus 3.2% versus 6.5%, P periodontal disease was associated with a small-for-gestational-age infant, a risk ratio of 2.3 (1.1 to 4.7), adjusted for age, smoking, drugs, marital and insurance status, and pre-eclampsia. Moderate or severe periodontal disease early in pregnancy is associated with delivery of a small-for-gestational-age infant. Understanding the mechanism of periodontal disease-associated adverse pregnancy outcomes could lead to interventions to improve fetal growth.

  8. Age-related Deterioration of Hematopoietic Stem Cells.

    Science.gov (United States)

    Kim, Mi Jung; Kim, Min Hwan; Kim, Seung Ah; Chang, Jae Suk

    2008-11-01

    Aging is the process of system deterioration over time in the whole body. Stem cells are self-renewing and therefore have been considered exempt from the aging process. Earlier studies by Hayflick showed that there is an intrinsic limit to the number of divisions that mammalian somatic cells can undergo, and cycling kinetics and ontogeny-related studies strongly suggest that even the most primitive stem cell functions exhibit a certain degree of aging. Despite these findings, studies on the effects of aging on stem cell functions are inconclusive. Here we review the age-related properties of hematopoietic stem cells in terms of intrinsic and extrinsic alterations, proliferative potential, signaling molecules, telomere and telomerase, senescence and cancer issues, regenerative potential and other indications of stem cell aging are discussed in detail.

  9. The Digital Ageing Atlas: integrating the diversity of age-related changes into a unified resource.

    Science.gov (United States)

    Craig, Thomas; Smelick, Chris; Tacutu, Robi; Wuttke, Daniel; Wood, Shona H; Stanley, Henry; Janssens, Georges; Savitskaya, Ekaterina; Moskalev, Alexey; Arking, Robert; de Magalhães, João Pedro

    2015-01-01

    Multiple studies characterizing the human ageing phenotype have been conducted for decades. However, there is no centralized resource in which data on multiple age-related changes are collated. Currently, researchers must consult several sources, including primary publications, in order to obtain age-related data at various levels. To address this and facilitate integrative, system-level studies of ageing we developed the Digital Ageing Atlas (DAA). The DAA is a one-stop collection of human age-related data covering different biological levels (molecular, cellular, physiological, psychological and pathological) that is freely available online (http://ageing-map.org/). Each of the >3000 age-related changes is associated with a specific tissue and has its own page displaying a variety of information, including at least one reference. Age-related changes can also be linked to each other in hierarchical trees to represent different types of relationships. In addition, we developed an intuitive and user-friendly interface that allows searching, browsing and retrieving information in an integrated and interactive fashion. Overall, the DAA offers a new approach to systemizing ageing resources, providing a manually-curated and readily accessible source of age-related changes. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. Identifying coronary artery disease in asymptomatic middle-aged sportsmen : The additional value of pulse wave velocity

    NARCIS (Netherlands)

    Braber, Thijs L.; Prakken, Niek H J; Mosterd, Arend; Mali, Willem P Th M; Doevendans, Pieter A F M; Bots, Michiel L.; Velthuis, Birgitta K.

    2015-01-01

    Background: Cardiovascular screening may benefit middle-aged sportsmen, as coronary artery disease (CAD) is the main cause of exercise-related sudden cardiac death. Arterial stiffness, as measured by pulse wave velocity (PWV), may help identify sportsmen with subclinical CAD. We examined the

  11. Differential patterns of implicit emotional processing in Alzheimer's disease and healthy aging.

    Science.gov (United States)

    García-Rodríguez, Beatriz; Fusari, Anna; Rodríguez, Beatriz; Hernández, José Martín Zurdo; Ellgring, Heiner

    2009-01-01

    Implicit memory for emotional facial expressions (EFEs) was investigated in young adults, healthy old adults, and mild Alzheimer's disease (AD) patients. Implicit memory is revealed by the effect of experience on performance by studying previously encoded versus novel stimuli, a phenomenon referred to as perceptual priming. The aim was to assess the changes in the patterns of priming as a function of aging and dementia. Participants identified EFEs taken from the Facial Action Coding System and the stimuli used represented the emotions of happiness, sadness, surprise, fear, anger, and disgust. In the study phase, participants rated the pleasantness of 36 faces using a Likert-type scale. Subsequently, the response to the 36 previously studied and 36 novel EFEs was tested when they were randomly presented in a cued naming task. The results showed that implicit memory for EFEs is preserved in AD and aging, and no specific age-related effects on implicit memory for EFEs were observed. However, different priming patterns were evident in AD patients that may reflect pathological brain damage and the effect of stimulus complexity. These findings provide evidence of how progressive neuropathological changes in the temporal and frontal areas may affect emotional processing in more advanced stages of the disease.

  12. Dietary lactoferrin alleviates age-related lacrimal gland dysfunction in mice.

    Directory of Open Access Journals (Sweden)

    Motoko Kawashima

    Full Text Available BACKGROUND: Decrease in lacrimal gland secretory function is related to age-induced dry eye disease. Lactoferrin, the main glycoprotein component of tears, has multiple functions, including anti-inflammatory effects and the promotion of cell growth. We investigated how oral administration of lactoferrin affects age-related lacrimal dysfunction. METHODS AND FINDINGS: Twelve-month-old male C57BL/6Cr Slc mice were randomly divided into a control fed group and an oral lactoferrin treatment group. Tear function was measured at a 6-month time-point. After euthanasia, the lacrimal glands were subjected to histological examination with 8-hydroxy-2'-deoxyguanosine (8-OHdG antibodies, and serum concentrations of 8-OHdG and hexanoyl-lysine adduct (HEL were evaluated. Additionally, monocyte chemotactic protein-1(MCP-1 and tumor necrosis factor-α (TNF-α gene expression levels were determined by real-time PCR. The volume of tear secretion was significantly larger in the treated group than in the control. Lactoferrin administration reduced inflammatory cell infiltration and the MCP-1 and TNF-α expression levels. Serum concentrations of 8-OHdG and HEL in the lactoferrin group were lower than those in the control group and were associated with attenuated 8-OHdG immunostaining of the lacrimal glands. CONCLUSION: Oral lactoferrin administration preserves lacrimal gland function in aged mice by attenuating oxidative damage and suppressing subsequent gland inflammation.

  13. The Age-Specific Quantitative Effects of Metabolic Risk Factors on Cardiovascular Diseases and Diabetes: A Pooled Analysis

    Science.gov (United States)

    Farzadfar, Farshad; Stevens, Gretchen A.; Woodward, Mark; Wormser, David; Kaptoge, Stephen; Whitlock, Gary; Qiao, Qing; Lewington, Sarah; Di Angelantonio, Emanuele; vander Hoorn, Stephen; Lawes, Carlene M. M.; Ali, Mohammed K.; Mozaffarian, Dariush; Ezzati, Majid

    2013-01-01

    Background The effects of systolic blood pressure (SBP), serum total cholesterol (TC), fasting plasma glucose (FPG), and body mass index (BMI) on the risk of cardiovascular diseases (CVD) have been established in epidemiological studies, but consistent estimates of effect sizes by age and sex are not available. Methods We reviewed large cohort pooling projects, evaluating effects of baseline or usual exposure to metabolic risks on ischemic heart disease (IHD), hypertensive heart disease (HHD), stroke, diabetes, and, as relevant selected other CVDs, after adjusting for important confounders. We pooled all data to estimate relative risks (RRs) for each risk factor and examined effect modification by age or other factors, using random effects models. Results Across all risk factors, an average of 123 cohorts provided data on 1.4 million individuals and 52,000 CVD events. Each metabolic risk factor was robustly related to CVD. At the baseline age of 55–64 years, the RR for 10 mmHg higher SBP was largest for HHD (2.16; 95% CI 2.09–2.24), followed by effects on both stroke subtypes (1.66; 1.39–1.98 for hemorrhagic stroke and 1.63; 1.57–1.69 for ischemic stroke). In the same age group, RRs for 1 mmol/L higher TC were 1.44 (1.29–1.61) for IHD and 1.20 (1.15–1.25) for ischemic stroke. The RRs for 5 kg/m2 higher BMI for ages 55–64 ranged from 2.32 (2.04–2.63) for diabetes, to 1.44 (1.40–1.48) for IHD. For 1 mmol/L higher FPG, RRs in this age group were 1.18 (1.08–1.29) for IHD and 1.14 (1.01–1.29) for total stroke. For all risk factors, proportional effects declined with age, were generally consistent by sex, and differed by region in only a few age groups for certain risk factor-disease pairs. Conclusion Our results provide robust, comparable and precise estimates of the effects of major metabolic risk factors on CVD and diabetes by age group. PMID:23935815

  14. Productivity losses attributable to untreated chlamydial infection and associated pelvic inflammatory disease in reproductive-aged women.

    Science.gov (United States)

    Blandford, John M; Gift, Thomas L

    2006-10-01

    The productivity losses attributable to disease-related morbidity and mortality impose a burden on society in general and on employers in particular. A reliable assessment of the productivity losses associated with untreated infection with Chlamydia trachomatis (Ct) would complement earlier work on direct medical costs and contribute to an estimate of the full cost of chlamydial disease. The goal of this study was to estimate the discounted lifetime productivity losses attributable to untreated chlamydial infection in reproductive-aged women. We developed a cost model using Monte Carlo methods to estimate the lifetime discounted productivity losses attributable to untreated lower genital tract Ct infection among reproductive-aged women. The model considered the impact of disability resulting from acute pelvic inflammatory disease (PID) associated with untreated Ct infection and from the sequelae of acute PID, including chronic pelvic pain, ectopic pregnancy, and infertility. To accommodate disparate Ct infection rates and labor market characteristics across age groups, we matched age-based risk factors for Ct infection with labor market patterns. Data sources included the 2001 National Chlamydia Surveillance Data, the 2001 Current Population Survey, and published literature. Estimates indicate that the mean weighted productivity losses per untreated Ct infection were approximately US dollars 130 (in year 2001 dollars). Mean weighted productivity losses per case of acute PID were estimated at US dollars 649. Estimated productivity losses were highly correlated with age, reflecting age-dependent differences in labor market characteristics. The productivity losses attributable to untreated infection with Ct and to sequelae of this infection form a substantial portion of the total economic burden of disease. Effective programs to prevent chlamydial infection and effective screening, diagnosis, and treatment of Ct-infected women may reduce productivity losses and

  15. Shared Ageing Research Models (ShARM) : a new facility to support ageing research

    NARCIS (Netherlands)

    Duran, Adele L.; Potter, Paul; Wells, Sara; Kirkwood, Tom; von Zglinicki, Thomas; McArdle, Anne; Scudamore, Cheryl; Meng, Qing-Jun; de Haan, Gerald; Corcoran, Anne; Bellantuono, Ilaria

    2013-01-01

    In order to manage the rise in life expectancy and the concomitant increased occurrence of age-related diseases, research into ageing has become a strategic priority. Mouse models are commonly utilised as they share high homology with humans and show many similar signs and diseases of ageing.

  16. Risk factors of age-related macular degeneration in Argentina

    Directory of Open Access Journals (Sweden)

    María Eugenia Nano

    2013-04-01

    Full Text Available PURPOSES: To assess the risk factors of age-related macular degeneration in Argentina using a case-control study. METHODS: Surveys were used for subjects' antioxidant intake, age/gender, race, body mass index, hypertension, diabetes (and type of treatment, smoking, sunlight exposure, red meat consumption, fish consumption, presence of age-related macular degeneration and family history of age-related macular degeneration. Main effects models for logistic regression and ordinal logistic regression were used to analyze the results. RESULTS: There were 175 cases and 175 controls with a mean age of 75.4 years and 75.5 years, respectively, of whom 236 (67.4% were female. Of the cases with age-related macular degeneration, 159 (45.4% had age-related macular degeneration in their left eyes, 154 (44.0% in their right eyes, and 138 (39.4% in both eyes. Of the cases with age-related macular degeneration in their left eyes, 47.8% had the dry type, 40.3% had the wet type, and the type was unknown for 11.9%. The comparable figures for right eyes were: 51.9%, 34.4%, and 13.7%, respectively. The main effects model was dominated by higher sunlight exposure (OR [odds ratio]: 3.3 and a family history of age-related macular degeneration (OR: 4.3. Other factors included hypertension (OR: 2.1, smoking (OR: 2.2, and being of the Mestizo race, which lowered the risk of age-related macular degeneration (OR: 0.40. Red meat/fish consumption, body mass index, and iris color did not have an effect. Higher age was associated with progression to more severe age-related macular degeneration. CONCLUSION: Sunlight exposure, family history of age-related macular degeneration, and an older age were the significant risk factors. There may be other variables, as the risk was not explained very well by the existing factors. A larger sample may produce different and better results.

  17. Molecular and Chemical Genetic Approaches to Developmental Origins of Aging and Disease in Zebrafish

    Science.gov (United States)

    Sasaki, Tomoyuki; Kishi, Shuji

    2013-01-01

    The incidence of diseases increases rapidly with age, accompanied by progressive deteriorations of physiological functions in organisms. Aging-associated diseases are sporadic but mostly inevitable complications arising from senescence. Senescence is often considered the antithesis of early development, but yet there may be factors and mechanisms in common between these two phenomena over the dynamic process of aging. The association between early development and late-onset disease with advancing age is thought to come from a consequence of developmental plasticity, the phenomenon by which one genotype can give rise to a range of physiologically and/or morphologically adaptive states in response to different environmental or genetic perturbations. On the one hand, we hypothesized that the future aging process can be predictive based on adaptivity during the early developmental period. Modulating the thresholds of adaptive plasticity by chemical genetic approaches, we have been investigating whether any relationship exists between the regulatory mechanisms that function in early development and in senescence using the zebrafish (Danio rerio), a small freshwater fish and a useful model animal for genetic studies. We have successfully conducted experiments to isolate zebrafish mutants expressing apparently altered senescence phenotypes during embryogenesis (“embryonic senescence”), subsequently showing shortened lifespan in adulthoods. We anticipate that previously uncharacterized developmental genes may mediate the aging process and play a pivotal role in senescence. On the other hand, unexpected senescence-related genes might also be involved in the early developmental process and regulation. The ease of manipulation using the zebrafish system allows us to conduct an exhaustive exploration of novel genes and small molecular compounds that can be linked to the senescence phenotype, and thereby facilitates searching for the evolutionary and developmental origins

  18. Hemostasis and ageing

    OpenAIRE

    Mari, D.; Ogliari, G.; Castaldi, D.; Vitale, G.; Bollini, E.M.; Lio, D.

    2008-01-01

    Abstract On March 19, 2008 a Symposium on Pathophysiology of Ageing and Age-Related Diseases was held in Palermo, Italy. The lecture of D. Mari on Hemostasis and ageing is summarized herein. Physiological ageing is associated with increased plasma levels of many proteins of blood coagulation together with fibrinolysis impairment. This may be of great concern in view of the known association between vascular and thromboembolic diseases and ageing. On the other hand, centenarians are characteri...

  19. Mechanical properties of the normal human cartilage-bone complex in relation to age

    DEFF Research Database (Denmark)

    Ding, Ming; Dalstra, M; Linde, F

    1998-01-01

    OBJECTIVE: This study investigates the age-related variations in the mechanical properties of the normal human tibial cartilage-bone complex and the relationships between cartilage and bone. DESIGN: A novel technique was applied to assess the mechanical properties of the cartilage and bone by mea...... that are of importance for the understanding of the etiology and pathogenesis of degenerative joint diseases, such as arthrosis....

  20. A Mitochondrial Paradigm of Metabolic and Degenerative Diseases, Aging, and Cancer: A Dawn for Evolutionary Medicine

    Science.gov (United States)

    Wallace, Douglas C.

    2005-01-01

    Life is the interplay between structure and energy, yet the role of energy deficiency in human disease has been poorly explored by modern medicine. Since the mitochondria use oxidative phosphorylation (OXPHOS) to convert dietary calories into usable energy, generating reactive oxygen species (ROS) as a toxic by-product, I hypothesize that mitochondrial dysfunction plays a central role in a wide range of age-related disorders and various forms of cancer. Because mitochondrial DNA (mtDNA) is present in thousands of copies per cell and encodes essential genes for energy production, I propose that the delayed-onset and progressive course of the age-related diseases results from the accumulation of somatic mutations in the mtDNAs of post-mitotic tissues. The tissue-specific manifestations of these diseases may result from the varying energetic roles and needs of the different tissues. The variation in the individual and regional predisposition to degenerative diseases and cancer may result from the interaction of modern dietary caloric intake and ancient mitochondrial genetic polymorphisms. Therefore the mitochondria provide a direct link between our environment and our genes and the mtDNA variants that permitted our forbears to energetically adapt to their ancestral homes are influencing our health today. PMID:16285865