WorldWideScience

Sample records for age-related cellular copper

  1. Cellular senescence in aging and age-related disease: from mechanisms to therapy

    NARCIS (Netherlands)

    Childs, B.G.; Durik, M.; Baker, D.J.; Deursen, J.M.A. van

    2015-01-01

    Cellular senescence, a process that imposes permanent proliferative arrest on cells in response to various stressors, has emerged as a potentially important contributor to aging and age-related disease, and it is an attractive target for therapeutic exploitation. A wealth of information about senesc

  2. Cellular and Molecular Pathology of Age-Related Macular Degeneration: Potential Role for Proteoglycans

    OpenAIRE

    Othman Al Gwairi; Lyna Thach; Wenhua Zheng; Narin Osman; Little, Peter J

    2016-01-01

    Age-related macular degeneration (AMD) is a retinal disease evident after the age of 50 that damages the macula in the centre of retina. It leads to a loss of central vision with retained peripheral vision but eventual blindness occurs in many cases. The initiation site of AMD development is Bruch’s membrane (BM) where multiple changes occur including the deposition of plasma derived lipids, accumulation of extracellular debris, changes in cell morphology, and viability and the formation of d...

  3. Resveratrol Attenuates Copper-Induced Senescence by Improving Cellular Proteostasis

    Science.gov (United States)

    2017-01-01

    Copper sulfate-induced premature senescence (CuSO4-SIPS) consistently mimetized molecular mechanisms of replicative senescence, particularly at the endoplasmic reticulum proteostasis level. In fact, disruption of protein homeostasis has been associated to age-related cell/tissue dysfunction and human disorders susceptibility. Resveratrol is a polyphenolic compound with proved antiaging properties under particular conditions. In this setting, we aimed to evaluate resveratrol ability to attenuate cellular senescence induction and to unravel related molecular mechanisms. Using CuSO4-SIPS WI-38 fibroblasts, resveratrol is shown to attenuate typical senescence alterations on cell morphology, senescence-associated beta-galactosidase activity, and cell proliferation. The mechanisms implicated in this antisenescence effect seem to be independent of senescence-associated genes and proteins regulation but are reliant on cellular proteostasis improvement. In fact, resveratrol supplementation restores copper-induced increased protein content, attenuates BiP level, and reduces carbonylated and polyubiquitinated proteins by autophagy induction. Our data provide compelling evidence for the beneficial effects of resveratrol by mitigating CuSO4-SIPS stressful consequences by the modulation of protein quality control systems. These findings highlight the importance of a balanced cellular proteostasis and add further knowledge on molecular mechanisms mediating resveratrol antisenescence effects. Moreover, they contribute to identifying specific molecular targets whose modulation will prevent age-associated cell dysfunction and improve human healthspan. PMID:28280523

  4. Age-related changes in the cellular composition and epithelial organization of the mouse trachea.

    Directory of Open Access Journals (Sweden)

    Carolien Wansleeben

    Full Text Available We report here senescent changes in the structure and organization of the mucociliary pseudostratified epithelium of the mouse trachea and main stem bronchi. We confirm previous reports of the gradual appearance of age-related, gland-like structures (ARGLS in the submucosa, especially in the intercartilage regions and carina. Immunohistochemistry shows these structures contain ciliated and secretory cells and Krt5+ basal cells, but not the myoepithelial cells or ciliated ducts typical of normal submucosal glands. Data suggest they arise de novo by budding from the surface epithelium rather than by delayed growth of rudimentary or cryptic submucosal glands. In old mice the surface epithelium contains fewer cells per unit length than in young mice and the proportion of Krt5+, p63+ basal cells is reduced in both males and females. However, there appears to be no significant difference in the ability of basal stem cells isolated from individual young and old mice to form clonal tracheospheres in culture or in the ability of the epithelium to repair after damage by inhaled sulfur dioxide. Gene expression analysis by Affymetrix microarray and quantitative PCR, as well as immunohistochemistry and flow sorting studies, are consistent with low-grade chronic inflammation in the tracheas of old versus young mice and an increase in the number of immune cells. The significance of these changes for ARGL formation are not clear since several treatments that induce acute inflammation in young mice did not result in budding of the surface epithelium.

  5. Cellular and Molecular Pathology of Age-Related Macular Degeneration: Potential Role for Proteoglycans

    Directory of Open Access Journals (Sweden)

    Othman Al Gwairi

    2016-01-01

    Full Text Available Age-related macular degeneration (AMD is a retinal disease evident after the age of 50 that damages the macula in the centre of retina. It leads to a loss of central vision with retained peripheral vision but eventual blindness occurs in many cases. The initiation site of AMD development is Bruch’s membrane (BM where multiple changes occur including the deposition of plasma derived lipids, accumulation of extracellular debris, changes in cell morphology, and viability and the formation of drusen. AMD manifests as early and late stage; the latter involves cell proliferation and neovascularization in wet AMD. Current therapies target the later hyperproliferative and invasive wet stage whilst none target early developmental stages of AMD. In the lipid deposition disease atherosclerosis modified proteoglycans bind and retain apolipoproteins in the artery wall. Chemically modified trapped lipids are immunogenic and can initiate a chronic inflammatory process manifesting as atherosclerotic plaques and subsequent artery blockages, heart attacks, or strokes. As plasma derived lipoprotein deposits are found in BM in early AMD, it is possible that they arise by a similar process within the macula. In this review we consider aspects of the pathological processes underlying AMD with a focus on the potential role of modifications to secreted proteoglycans being a cause and therefore a target for the treatment of early AMD.

  6. Cellular and Molecular Pathology of Age-Related Macular Degeneration: Potential Role for Proteoglycans.

    Science.gov (United States)

    Al Gwairi, Othman; Thach, Lyna; Zheng, Wenhua; Osman, Narin; Little, Peter J

    2016-01-01

    Age-related macular degeneration (AMD) is a retinal disease evident after the age of 50 that damages the macula in the centre of retina. It leads to a loss of central vision with retained peripheral vision but eventual blindness occurs in many cases. The initiation site of AMD development is Bruch's membrane (BM) where multiple changes occur including the deposition of plasma derived lipids, accumulation of extracellular debris, changes in cell morphology, and viability and the formation of drusen. AMD manifests as early and late stage; the latter involves cell proliferation and neovascularization in wet AMD. Current therapies target the later hyperproliferative and invasive wet stage whilst none target early developmental stages of AMD. In the lipid deposition disease atherosclerosis modified proteoglycans bind and retain apolipoproteins in the artery wall. Chemically modified trapped lipids are immunogenic and can initiate a chronic inflammatory process manifesting as atherosclerotic plaques and subsequent artery blockages, heart attacks, or strokes. As plasma derived lipoprotein deposits are found in BM in early AMD, it is possible that they arise by a similar process within the macula. In this review we consider aspects of the pathological processes underlying AMD with a focus on the potential role of modifications to secreted proteoglycans being a cause and therefore a target for the treatment of early AMD.

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

    Directory of Open Access Journals (Sweden)

    Shigehisa Yanagi

    2017-02-01

    Full Text Available 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.

  8. 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.

  9. Cellular and aqueous microcystin-LR following laboratory exposures of Microcystis aeruginosa to copper algaecides.

    Science.gov (United States)

    Iwinski, Kyla J; Calomeni, Alyssa J; Geer, Tyler D; Rodgers, John H

    2016-03-01

    Microcystin release from algal cells influences use of copper-algaecides in water resources. Accurate data regarding relationships between copper-algaecide exposures and responses of microcystin-producing algae are needed to make informed management decisions. Responses of Microcystis aeruginosa were measured in terms of cellular microcystin-LR (MC-LR), aqueous MC-LR, and chlorophyll-a following exposure to CuSO4 and copper-ethanolamine. Comparisons were made between treated and untreated samples, and copper formulations. EC50s and slopes for M. aeruginosa responses to copper exposures were calculated. Algal responses followed a sigmoidal exposure-response relationship, and cellular MC-LR and chlorophyll-a were negatively related to copper concentrations. Aqueous MC-LR increased with copper concentrations, although the increase in aqueous MC-LR was not proportional to decreases in cellular MC-LR and chlorophyll-a. Cellular MC-LR and chlorophyll a declined at a greater rate than aqueous MC-LR increased. Total MC-LR was less than untreated controls following copper exposure. Differences were measured between copper formulations in terms of aqueous and total MC-LR concentrations at concentrations of 0.5 and 1.0 mg Cu L-1. Aqueous and total MC-LR were greater (10-20%) following exposure to CuSO4 compared to copper-ethanolamine one day following exposure. The positive relationship between copper concentration and aqueous MC-LR at 0.07-1.0 mg Cu L-1 demonstrates that lower copper concentrations were as effective as higher concentrations in controlling M. aeruginosa while decreasing the total amount of MC-LR, and minimizing the proportion of MC-LR released to the aqueous-phase. Results serve to support more accurate risk evaluations of MC-LR concentrations when M. aeruginosa is exposed to copper-algaecides and when it is untreated.

  10. Copper transporters and chaperones: Their function on angiogenesis and cellular signalling

    Indian Academy of Sciences (India)

    SR BHARATHI DEVI; DHIVYA M ALOYSIUS; KN SULOCHANA

    2016-09-01

    Copper, although known as a micronutrient, has a pivotal role in modulating the cellular metabolism. Many studieshave reported the role of copper in angiogenesis. Copper chaperones are intracellular proteins that mediate coppertrafficking to various cell organelles. However, the role and function of copper chaperones in relation to angiogenesishas to be further explored. The intracellular copper levels when in excess are deleterious and certain mutations ofcopper chaperones have been shown to induce cell death and influence various cellular metabolisms. The study ofthese chaperones will be helpful in understanding the players in the cascade of events in angiogenesis and their role incellular metabolic pathways. In this review we have briefly listed the copper chaperones associated with angiogenicand metabolic signalling and their function.

  11. Dengue in Vietnamese infants--results of infection-enhancement assays correlate with age-related disease epidemiology, and cellular immune responses correlate with disease severity.

    Science.gov (United States)

    Chau, Tran Nguyen Bich; Quyen, Nguyen Than Ha; Thuy, Tran Thi; Tuan, Nguyen Minh; Hoang, Dang Minh; Dung, Nguyen Thi Phuong; Lien, Le Bich; Quy, Nguyen Thien; Hieu, Nguyen Trong; Hieu, Lu Thi Minh; Hien, Tran Tinh; Hung, Nguyen Thanh; Farrar, Jeremy; Simmons, Cameron P

    2008-08-15

    The pathogenesis of severe dengue is not well understood. Maternally derived subneutralizing levels of dengue virus-reactive IgG are postulated to be a critical risk factor for severe dengue during infancy. In this study, we found that, in healthy Vietnamese infants, there was a strong temporal association between the Fc-dependent, dengue virus infection-enhancing activity of neat plasma and the age-related epidemiology of severe dengue. We then postulated that disease severity in infants with primary infections would be associated with a robust immune response, possibly as a consequence of higher viral burdens in vivo. Accordingly, in infants hospitalized with acute dengue, the activation phenotype of peripheral-blood NK cells and CD8+ and CD4+ T cells correlated with overall disease severity, but HLA-A*1101-restricted NS3(133-142)-specific CD8+ T cells were not measurable until early convalescence. Plasma levels of cytokines/chemokines were generally higher in infants with dengue shock syndrome. Collectively, these data support a model of dengue pathogenesis in infants whereby antibody-dependent enhancement of infection explains the age-related case epidemiology and could account for antigen-driven immune activation and its association with disease severity. These results also highlight potential risks in the use of live attenuated dengue vaccines in infants in countries where dengue is endemic.

  12. In Absence of the Cellular Prion Protein, Alterations in Copper Metabolism and Copper-Dependent Oxidase Activity Affect Iron Distribution.

    Science.gov (United States)

    Gasperini, Lisa; Meneghetti, Elisa; Legname, Giuseppe; Benetti, Federico

    2016-01-01

    Essential elements as copper and iron modulate a wide range of physiological functions. Their metabolism is strictly regulated by cellular pathways, since dysregulation of metal homeostasis is responsible for many detrimental effects. Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and prion diseases are characterized by alterations of metal ions. These neurodegenerative maladies involve proteins that bind metals and mediate their metabolism through not well-defined mechanisms. Prion protein, for instance, interacts with divalent cations via multiple metal-binding sites and it modulates several metal-dependent physiological functions, such as S-nitrosylation of NMDA receptors. In this work we focused on the effect of prion protein absence on copper and iron metabolism during development and adulthood. In particular, we investigated copper and iron functional values in serum and several organs such as liver, spleen, total brain and isolated hippocampus. Our results show that iron content is diminished in prion protein-null mouse serum, while it accumulates in liver and spleen. Our data suggest that these alterations can be due to impairments in copper-dependent cerulopalsmin activity which is known to affect iron mobilization. In prion protein-null mouse total brain and hippocampus, metal ion content shows a fluctuating trend, suggesting the presence of homeostatic compensatory mechanisms. However, copper and iron functional values are likely altered also in these two organs, as indicated by the modulation of metal-binding protein expression levels. Altogether, these results reveal that the absence of the cellular prion protein impairs copper metabolism and copper-dependent oxidase activity, with ensuing alteration of iron mobilization from cellular storage compartments.

  13. In Absence of the Cellular Prion Protein, Alterations in Copper Metabolism and Copper-Dependent Oxidase Activity Affect Iron Distribution

    Science.gov (United States)

    Gasperini, Lisa; Meneghetti, Elisa; Legname, Giuseppe; Benetti, Federico

    2016-01-01

    Essential elements as copper and iron modulate a wide range of physiological functions. Their metabolism is strictly regulated by cellular pathways, since dysregulation of metal homeostasis is responsible for many detrimental effects. Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and prion diseases are characterized by alterations of metal ions. These neurodegenerative maladies involve proteins that bind metals and mediate their metabolism through not well-defined mechanisms. Prion protein, for instance, interacts with divalent cations via multiple metal-binding sites and it modulates several metal-dependent physiological functions, such as S-nitrosylation of NMDA receptors. In this work we focused on the effect of prion protein absence on copper and iron metabolism during development and adulthood. In particular, we investigated copper and iron functional values in serum and several organs such as liver, spleen, total brain and isolated hippocampus. Our results show that iron content is diminished in prion protein-null mouse serum, while it accumulates in liver and spleen. Our data suggest that these alterations can be due to impairments in copper-dependent cerulopalsmin activity which is known to affect iron mobilization. In prion protein-null mouse total brain and hippocampus, metal ion content shows a fluctuating trend, suggesting the presence of homeostatic compensatory mechanisms. However, copper and iron functional values are likely altered also in these two organs, as indicated by the modulation of metal-binding protein expression levels. Altogether, these results reveal that the absence of the cellular prion protein impairs copper metabolism and copper-dependent oxidase activity, with ensuing alteration of iron mobilization from cellular storage compartments. PMID:27729845

  14. IN ABSENCE OF THE CELLULAR PRION PROTEIN, ALTERATIONS IN COPPER METABOLISM AND COPPER-DEPENDENT OXIDASE ACTIVITY AFFECT IRON DISTRIBUTION

    OpenAIRE

    Lisa Gasperini; Elisa Meneghetti; Giuseppe Legname; Federico Benetti

    2016-01-01

    Essential elements as copper and iron modulate a wide range of physiological functions. Their metabolism is strictly regulated by cellular pathways, since dysregulation of metal homeostasis is responsible for many detrimental effects. Neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease and prion diseases are characterized by alterations of metal ions. These neurodegenerative maladies involve proteins that bind metals and mediate their metabolism through not well-defin...

  15. In Absence of the Cellular Prion Protein, Alterations in Copper Metabolism and Copper-Dependent Oxidase Activity Affect Iron Distribution

    OpenAIRE

    Gasperini, Lisa; Meneghetti, Elisa; Legname, Giuseppe; Benetti, Federico

    2016-01-01

    Essential elements as copper and iron modulate a wide range of physiological functions. Their metabolism is strictly regulated by cellular pathways, since dysregulation of metal homeostasis is responsible for many detrimental effects. Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and prion diseases are characterized by alterations of metal ions. These neurodegenerative maladies involve proteins that bind metals and mediate their metabolism through not well-defin...

  16. Cellular membrane accommodation of copper-induced oxidative conditions in the coral Seriatopora caliendrum

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Chuan-Ho, E-mail: chtang@nmmba.gov.tw [Institute of Marine Biodiversity and Evolutionary Biology, National Dong Hwa University, Pingtung, Taiwan, ROC (China); National Museum of Marine Biology and Aquarium, Pingtung, Taiwan, ROC (China); Lin, Ching-Yu [Institute of Environmental Health, National Taiwan University, Taipei City, Taiwan, ROC (China); Lee, Shu-Hui [Center of General Education, National Kaohsiung Marine University, Kaohsiung, Taiwan, ROC (China); Wang, Wei-Hsien [National Museum of Marine Biology and Aquarium, Pingtung, Taiwan, ROC (China); Department of Marine Biotechnology and Resources and Asia-Pacific Ocean Research Center, National Sun Yat-sen University, Kaohsiung, Taiwan, ROC (China)

    2014-03-01

    Highlights: • Coral cells alter membrane lipid to accommodate copper-induce oxidative conditions • Coral membrane repair occur due to lipid alterations • Zooxanthellae release results from membrane repair by symbiosome fusion • Copper-induced lipid alterations perturb membrane-related functions in coral cells • Copper chronic effect on coral fitness are related to long-term membrane perturbation - Abstract: Oxidative stress has been associated with copper-induced toxicity in scleractinian corals. To gain insight into the accommodation of the cellular membrane to oxidative conditions, a pocilloporid coral, Seriatopora caliendrum, was exposed to copper at distinct, environmentally relevant dose for various lengths of time. Glycerophosphocholine profiling of the response of the coral to copper exposure was characterized using a validated method. The results indicate that coral lipid metabolism is programmed to induce membrane alterations in response to the cellular deterioration that occurs during the copper exposure period. Decreasing lyso-phosphatidylcholines and exchanging polyunsaturated phosphatidylcholines for polyunsaturated plasmanylcholines were the initial actions taken to prevent membrane permeabilization. To relax/resist the resulting membrane strain caused by cell/organelle swelling, the coral cells inversely exchanged polyunsaturated plasmanylcholines for polyunsaturated phosphatidylcholines and further increased the levels of monounsaturated glycerophosphocholines. At the same time, the levels of saturated phosphatidylcholines were also increased to increase membrane rigidity and protect against oxidative attack. Interestingly, such alterations in lipid metabolism were also required for membrane fusion to repair the deteriorated membranes by repopulating them with proximal lipid reservoirs, similar to symbiosome membranes. Additionally, increasing saturated and monounsaturated plasmanylcholines and inhibiting the suppression of saturated lyso

  17. [Age related macular degeneration].

    Science.gov (United States)

    Sayen, Alexandra; Hubert, Isabelle; Berrod, Jean-Paul

    2011-02-01

    Age-related macular degeneration (ARMD) is a multifactorial disease caused by a combination of genetic and environmental factors. It is the first cause of blindness in patients over 50 in the western world. The disease has been traditionally classified into early and late stages with dry (atrophic) and wet (neovascular) forms: neovascular form is characterized by new blood vessels development under the macula (choroidal neovascularisation) which lead to a rapid decline of vision associated with metamorphopsia and requiring an urgent ophtalmological examination. Optical coherence tomography is now one of the most important part of the examination for diagnosis and treatment. Patient with age related maculopathy should consider taking a dietary supplement such that used in AREDS. The treatment of the wet ARMD has largely beneficied since year 2006 of anti-VEGF (vascular endothelial growth factor) molecules such as ranibizumab or bevacizumab given as repeated intravitreal injections. A systematic follow up each 4 to 8 week in required for several years. There is no effective treatment at the moment for dry AMD. For patients with binocular visual acuity under 60/200 rehabilitation includes low vision specialist, vision aids and psychological support.

  18. COPPER STRESS ON CELLULAR CONTENTS AND FATTY ACID PROFILES IN CHLORELLA SPECIES

    Directory of Open Access Journals (Sweden)

    G. Sibi

    2014-01-01

    Full Text Available Higher photosynthetic efficiency and biomass production with rapid growth makes microalgae as potential candidates over other energy crops in many applications. Heavy metals influence the production of secondary metabolites and lipd content of microalgae in particular. A study was conducted using six Chlorella species under heavy metal exposure to evaluate the copper stress on biomass, cellular and lipid contents. Preliminary growth studies indicated the growth tolerance levels of Chlorella in the presence of copper at 4.0 mg L-1 concentration. The total chlorophyll, protein and lipid content of the isolates were 1.7-3.45%, 0.43-0.70 mg g-1 and 0.02-0.11 mg g-1 respectively. Gas Chromatography-Mass Spectroscopy analysis revealed that the percent composition of fatty acids varied among the species studied and the major group of fatty acids were C16:0, C18:1 and C18:2. Highest percent of fatty acids were found in C. vulgaris, C. protothecoides and C. pyrenoidosa. Copper have an impact on Chlorella species where biomass content was directly proportional to the lipid productivity. The results reflects the fact that copper stress on Chlorella species as the evidence of lipid production in both qualitative and quantitative manner. In conclusion, Chlorella species can be used for the sustainable producion of renewable energy through copper stress and removal of copper from aqueous solutions.

  19. Age-related skin changes

    Directory of Open Access Journals (Sweden)

    Božanić Snežana

    2012-01-01

    Full Text Available Age-related skin changes can be induced by chronological ageing, manifested in subcutaneous fat reduction, and photo-ageing eliciting increased elastotic substance in the upper dermis, destruction of its fibrilar structure, augmented intercellular substance and moderate inflammatory infiltrate. Forty-five biopsy skin samples of the sun-exposed and sun-protected skin were analyzed. The patients were both males and females, aged from 17 to 81 years. The thickness of the epidermal layers and the number of cellular living layers is greater in younger skin. The amount of keratohyaline granules is enlarged in older skin. Dermoepidermal junction is flattened and the presence of elastotic material in the dermis is pronounced with age. The amount of inflammatory infiltrate is increased, the fibrous trabeculae are thickened in older skin and the atrophy of the hypodermis is observed. Chronological ageing alters the fibroblasts metabolism by reducing their life span, capacity to divide and produce collagen. During ageing, the enlargement of collagen fibrils diminishes the skin elasticity.

  20. Effects of rapamycin induced cellular autophagy in aging-related diseases%雷帕霉素诱导细胞自噬在衰老相关疾病中的作用

    Institute of Scientific and Technical Information of China (English)

    吴伯艳; 刘新光; 陈维春

    2015-01-01

    哺乳动物雷帕霉素靶蛋白( mammalian target of rapamy-cin, mTOR)是衰老和衰老相关疾病的一个关键调节因子。雷帕霉素( rapamycin, RAPA)可通过抑制mTOR通路,诱导和促进细胞自噬的发生。细胞自噬是维持细胞内稳态的主要方式与途径,通过降解多余的、受损的及衰老的蛋白与细胞器,为细胞重建、再生和修复提供必需原料。早老症( hutchinson-gil-ford progeria syndrome, HGPS )患者细胞中伴随早老蛋白( progerin)的异常聚集;此外,诸如亨廷顿病、帕金森病、阿尔茨海默病等神经退行性疾病细胞内同样出现异常蛋白质的聚集,而这些异常蛋白的清除正依赖于细胞的自噬作用。由此可见,雷帕霉素是潜在的抗衰老、治疗早老症及衰老相关疾病的重要药物。该文主要阐述雷帕霉素促进细胞自噬方面的功能及在HGPS、神经退行性疾病方面的应用。%Mammalian target of rapamycin( mTOR) is a key reg-ulator of aging and aging-related diseases. Rapamycin ( RAPA) induces and promotes the process of cell autophagy through in-hibiting mTOR pathway. Autophagy exerts a crucial role in main-taining the cellular meostasis, which provides essential materials for cell reconstruction, regeneration and repair via degradating the redundant, damaged, or senescent proteins and organelles. Hutchinson Gilford progeria syndrome ( HGPS ) patients are al-ways accompanied with abnormally accumulated progerin in cells. Similar to HGPS, abnormal protein accumulation is the common pathological feature of neurodegenerative diseases, in-cluding Huntington′s disease, Parkinson′s disease, Alzheimer′s disease and so on. Degradation of these abnormal proteins pre-dominantly depends on cell autophagy. Thus, rapamycin is a po-tential anti-aging drug for HGPS and aging-related diseases thera-py. This view focuses on the effects of rapamycin on cell autoph-agy and clinical application in HGPS and neurodegenerative

  1. Precursors of age-related macular degeneration

    DEFF Research Database (Denmark)

    Munch, Inger Christine; Toft, Ulla; Linneberg, Allan;

    2016-01-01

    PURPOSE: To investigate associations of very early age-related macular degeneration (AMD) with daily intake of vitamin A, beta-carotene, vitamin E, vitamin C, zinc and copper and interactions with AMD-associated polymorphisms in complement factor H (CFHY402H) and ARMS2/LOC387715. METHODS: Cross......: In this cross-sectional study, a higher intake of vitamin A increased the risk of macular drusen >63 μm in subjects with CFHY402H. The study supports that vitamin A may be a risk factor for early AMD....

  2. COX19 mediates the transduction of a mitochondrial redox signal from SCO1 that regulates ATP7A-mediated cellular copper efflux

    OpenAIRE

    Leary, Scot C; Cobine, Paul A.; Nishimura, Tamiko; Verdijk, Robert M; de Krijger, Ronald; Coo, René; Tarnopolsky, Mark A.; Winge, Dennis R; Eric A Shoubridge

    2013-01-01

    SCO1 and SCO2 are metallochaperones whose principal function is to add two copper ions to the catalytic core of cytochrome c oxidase (COX). However, affected tissues of SCO1 and SCO2 patients exhibit a combined deficiency in COX activity and total copper content, suggesting additional roles for these proteins in the regulation of cellular copper homeostasis. Here we show that both the redox state of the copper-binding cysteines of SCO1 and the abundance of SCO2 correlate with cellular copper ...

  3. Age-Related Macular Degeneration

    Science.gov (United States)

    ... version of this page please turn Javascript on. Age-related Macular Degeneration About AMD Click for more ... a leading cause of vision loss among people age 60 and older. It causes damage to the ...

  4. A differential genome-wide transcriptome analysis: impact of cellular copper on complex biological processes like aging and development.

    Directory of Open Access Journals (Sweden)

    Jörg Servos

    Full Text Available The regulation of cellular copper homeostasis is crucial in biology. Impairments lead to severe dysfunctions and are known to affect aging and development. Previously, a loss-of-function mutation in the gene encoding the copper-sensing and copper-regulated transcription factor GRISEA of the filamentous fungus Podospora anserina was reported to lead to cellular copper depletion and a pleiotropic phenotype with hypopigmentation of the mycelium and the ascospores, affected fertility and increased lifespan by approximately 60% when compared to the wild type. This phenotype is linked to a switch from a copper-dependent standard to an alternative respiration leading to both a reduced generation of reactive oxygen species (ROS and of adenosine triphosphate (ATP. We performed a genome-wide comparative transcriptome analysis of a wild-type strain and the copper-depleted grisea mutant. We unambiguously assigned 9,700 sequences of the transcriptome in both strains to the more than 10,600 predicted and annotated open reading frames of the P. anserina genome indicating 90% coverage of the transcriptome. 4,752 of the transcripts differed significantly in abundance with 1,156 transcripts differing at least 3-fold. Selected genes were investigated by qRT-PCR analyses. Apart from this general characterization we analyzed the data with special emphasis on molecular pathways related to the grisea mutation taking advantage of the available complete genomic sequence of P. anserina. This analysis verified but also corrected conclusions from earlier data obtained by single gene analysis, identified new candidates of factors as part of the cellular copper homeostasis system including target genes of transcription factor GRISEA, and provides a rich reference source of quantitative data for further in detail investigations. Overall, the present study demonstrates the importance of systems biology approaches also in cases were mutations in single genes are analyzed to

  5. A functional screen for copper homeostasis genes identifies a pharmacologically tractable cellular system

    OpenAIRE

    Schlecht, Ulrich; Suresh, Sundari; Xu, Weihong; Aparicio, Ana Maria; Chu, Angela; Proctor, Michael J; Davis, Ronald W.; Scharfe, Curt; St.Onge, Robert P.

    2014-01-01

    Background Copper is essential for the survival of aerobic organisms. If copper is not properly regulated in the body however, it can be extremely cytotoxic and genetic mutations that compromise copper homeostasis result in severe clinical phenotypes. Understanding how cells maintain optimal copper levels is therefore highly relevant to human health. Results We found that addition of copper (Cu) to culture medium leads to increased respiratory growth of yeast, a phenotype which we then system...

  6. COX19 mediates the transduction of a mitochondrial redox signal from SCO1 that regulates ATP7A-mediated cellular copper efflux

    Science.gov (United States)

    Leary, Scot C.; Cobine, Paul A.; Nishimura, Tamiko; Verdijk, Robert M.; de Krijger, Ronald; de Coo, René; Tarnopolsky, Mark A.; Winge, Dennis R.; Shoubridge, Eric A.

    2013-01-01

    SCO1 and SCO2 are metallochaperones whose principal function is to add two copper ions to the catalytic core of cytochrome c oxidase (COX). However, affected tissues of SCO1 and SCO2 patients exhibit a combined deficiency in COX activity and total copper content, suggesting additional roles for these proteins in the regulation of cellular copper homeostasis. Here we show that both the redox state of the copper-binding cysteines of SCO1 and the abundance of SCO2 correlate with cellular copper content and that these relationships are perturbed by mutations in SCO1 or SCO2, producing a state of apparent copper overload. The copper deficiency in SCO patient fibroblasts is rescued by knockdown of ATP7A, a trans-Golgi, copper-transporting ATPase that traffics to the plasma membrane during copper overload to promote efflux. To investigate how a signal from SCO1 could be relayed to ATP7A, we examined the abundance and subcellular distribution of several soluble COX assembly factors. We found that COX19 partitions between mitochondria and the cytosol in a copper-dependent manner and that its knockdown partially rescues the copper deficiency in patient cells. These results demonstrate that COX19 is necessary for the transduction of a SCO1-dependent mitochondrial redox signal that regulates ATP7A-mediated cellular copper efflux. PMID:23345593

  7. The Cellular Prion Protein Prevents Copper-Induced Inhibition of P2X4 Receptors

    Science.gov (United States)

    Lorca, Ramón A.; Varela-Nallar, Lorena; Inestrosa, Nibaldo C.; Huidobro-Toro, J. Pablo

    2011-01-01

    Although the physiological function of the cellular prion protein (PrPC) remains unknown, several evidences support the notion of its role in copper homeostasis. PrPC binds Cu2+ through a domain composed by four to five repeats of eight amino acids. Previously, we have shown that the perfusion of this domain prevents and reverses the inhibition by Cu2+ of the adenosine triphosphate (ATP)-evoked currents in the P2X4 receptor subtype, highlighting a modulatory role for PrPC in synaptic transmission through regulation of Cu2+ levels. Here, we study the effect of full-length PrPC in Cu2+ inhibition of P2X4 receptor when both are coexpressed. PrPC expression does not significantly change the ATP concentration-response curve in oocytes expressing P2X4 receptors. However, the presence of PrPC reduces the inhibition by Cu2+ of the ATP-elicited currents in these oocytes, confirming our previous observations with the Cu2+ binding domain. Thus, our observations suggest a role for PrPC in modulating synaptic activity through binding of extracellular Cu2+. PMID:22114745

  8. The Cellular Prion Protein Prevents Copper-Induced Inhibition of P2X4 Receptors

    Directory of Open Access Journals (Sweden)

    Ramón A. Lorca

    2011-01-01

    Full Text Available Although the physiological function of the cellular prion protein (PrPC remains unknown, several evidences support the notion of its role in copper homeostasis. PrPC binds Cu2+ through a domain composed by four to five repeats of eight amino acids. Previously, we have shown that the perfusion of this domain prevents and reverses the inhibition by Cu2+ of the adenosine triphosphate (ATP-evoked currents in the P2X4 receptor subtype, highlighting a modulatory role for PrPC in synaptic transmission through regulation of Cu2+ levels. Here, we study the effect of full-length PrPC in Cu2+ inhibition of P2X4 receptor when both are coexpressed. PrPC expression does not significantly change the ATP concentration-response curve in oocytes expressing P2X4 receptors. However, the presence of PrPC reduces the inhibition by Cu2+ of the ATP-elicited currents in these oocytes, confirming our previous observations with the Cu2+ binding domain. Thus, our observations suggest a role for PrPC in modulating synaptic activity through binding of extracellular Cu2+.

  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. Oral administration of copper to rats leads to increased lymphocyte cellular DNA degradation by dietary polyphenols: implications for a cancer preventive mechanism.

    Science.gov (United States)

    Khan, Husain Y; Zubair, Haseeb; Ullah, Mohd F; Ahmad, Aamir; Hadi, Sheikh M

    2011-12-01

    To account for the observed anticancer properties of plant polyphenols, we have earlier proposed a mechanism which involves the mobilization of endogenous copper ions by polyphenols leading to the generation of reactive oxygen species (ROS) that serve as proximal DNA cleaving agents and lead to cell death. Over the last decade we have proceeded to validate our hypothesis with considerable success. As a further confirmation of our hypothesis, in this paper we first show that oral administration of copper to rats leads to elevated copper levels in lymphocytes. When such lymphocytes with a copper overload were isolated and treated with polyphenols EGCG, genistein and resveratrol, an increased level of DNA breakage was observed. Further, preincubation of lymphocytes having elevated copper levels with the membrane permeable copper chelator neocuproine, resulted in inhibition of polyphenol induced DNA degradation. However, membrane impermeable chelator of copper bathocuproine, as well as iron and zinc chelators were ineffective in causing such inhibition in DNA breakage, confirming the involvement of endogenous copper in polyphenol induced cellular DNA degradation. It is well established that serum and tissue concentrations of copper are greatly increased in various malignancies. In view of this fact, the present results further confirm our earlier findings and strengthen our hypothesis that an important anticancer mechanism of plant polyphenols could be the mobilization of intracellular copper leading to ROS-mediated cellular DNA breakage. In this context, it may be noted that cancer cells are under considerable oxidative stress and increasing such stress to cytotoxic levels could be a successful anticancer approach.

  11. The S2 Cu(I) site in CupA from Streptococcus pneumoniae is required for cellular copper resistance†

    Science.gov (United States)

    Fu, Yue; Bruce, Kevin E.; Wu, Hongwei; Giedroc, David P.

    2015-01-01

    Pathogenic bacteria have evolved copper homeostasis and resistance systems for fighting copper toxicity imposed by the human immune system. Streptococcus pneumoniae is a respiratory pathogen that encodes an obligatorily membrane-anchored Cu(I) binding protein, CupA, and a P1B-type ATPase efflux transporter, CopA. The soluble, cytoplasmic domain of CupA (sCupA) contains a binuclear Cu(I) cluster consisting of S1 and S2 Cu(I) ions. The NMR solution structure of apo-sCupA reveals the same cupredoxin fold of Cu2-sCupA, except that the Cu(I) binding loop (residues 112–116, harboring S2 Cu ligands M113 and M115) is highly dynamic as documented by both backbone and side chain methionine methyl order parameters. In contrast to the more solvent exposed, lower affinity S2 Cu site, the high affinity S1 Cu-coordinating cysteines (C74, C111) are pre-organized in the apo-sCupA structure. Biological experiments reveal that the S1 site is largely dispensable for cellular Cu resistance and may be involved in buffering low cytoplasmic Cu(I). In contrast, the S2 site is essential for Cu resistance. Expression of a chimeric CopZ chaperone fused to the CupA transmembrane helix does not protect S. pneumoniae from copper toxicity and substitution of a predicted cytoplasm-facing Cu(I) entry metal-binding site (MBS) on CopA also gives rise to a Cu-sensitivity phenotype. These findings suggest that CupA and CopA may interact and filling of the CupA S2 site with Cu(I) results in stimulation of cellular copper efflux by CopA. PMID:26346139

  12. Green synthesis of peptide-templated fluorescent copper nanoclusters for temperature sensing and cellular imaging.

    Science.gov (United States)

    Huang, Hong; Li, Hua; Wang, Ai-Jun; Zhong, Shu-Xian; Fang, Ke-Ming; Feng, Jiu-Ju

    2014-12-21

    A simple and green approach was developed for the preparation of fluorescent Cu nanoclusters (NCs) using the artificial peptide CLEDNN as a template. The as-synthesized Cu NCs exhibited a high fluorescence quantum yield (7.3%) and good stability, along with excitation and temperature dependent fluorescent properties, which could be employed for temperature sensing. Further investigations demonstrated low toxicity of Cu NCs for cellular imaging.

  13. Genes, inflammation, and age-related diseases

    NARCIS (Netherlands)

    Trompet, Stella

    2010-01-01

    The general objective of this thesis was to investigate associations between genetic variants involved in inflammation and epigenetics and age-related diseases in an elderly cohort to get more insights in the patho-physiological mechanisms involved in age-related diseases, like cardiovascular diseas

  14. Copper changes the yield and cadmium/zinc accumulation and cellular distribution in the cadmium/zinc hyperaccumulator Sedum plumbizincicola

    Energy Technology Data Exchange (ETDEWEB)

    Li, Zhu [Key Laboratory of Soil Environment and Pollution Remediation, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008 (China); University of the Chinese Academy of Sciences, Beijing 100049 (China); Wu, Longhua, E-mail: lhwu@issas.ac.cn [Key Laboratory of Soil Environment and Pollution Remediation, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008 (China); Hu, Pengjie [Key Laboratory of Soil Environment and Pollution Remediation, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008 (China); Luo, Yongming [Key Laboratory of Soil Environment and Pollution Remediation, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008 (China); Yantai Institute of Coastal Zone Research, Yantai 264003 (China); Christie, Peter [Agri-Environment Branch, Agri-Food and Biosciences Institute, Newforge Lane, Belfast BT9 5PX (United Kingdom)

    2013-10-15

    Highlights: • Low Cu has no significant effect on Sedum plumbizincicola plant growth and Cd and Zn uptake. • Plant held Cu in unactive areas and insoluble forms as de-toxification mechanisms. • Influence of Cu on Zn and Cd uptake and translocation were different. • Cu accumulation in leaf veins may restrain Cd/Zn unloading to the leaves -- Abstract: Non-accumulated metals in mixed metal contaminated soils may affect hyperaccumulator growth and metal accumulation and thus remediation efficiency. Two hydroponics experiments were conducted to investigate the effects of copper (Cu) on cadmium (Cd) and zinc (Zn) accumulation by the Cd/Zn hyperaccumulator Sedum plumbizincicola, Cu toxicity and plant detoxification using chemical sequential extraction of metals, sub-cellular separation, micro synchrotron radiation based X-ray fluorescence, and transmission electron microscopy. Compared with the control (0.31 μM Cu), 5–50 μM Cu had no significant effect on Cd/Zn accumulation, but Cu at 200 μM induced root cell plasmolysis and disordered chloroplast structure. The plants held Cu in the roots and cell walls and complexed Cu in insoluble forms as their main detoxification mechanisms. Exposure to 200 μM Cu for 4 days inhibited plant Cd uptake and translocation but did not affect Zn concentrations in roots and stems. Moreover, unloading of Cd and Zn from stem to leaf was restrained compared to control plants, perhaps due to Cu accumulation in leaf veins. Copper may thus interfere with root Cd uptake and restrain Cd/Zn unloading to the leaves. Further investigation of how Cu affects plant metal uptake may help elucidate the Cd/Zn hyper-accumulating mechanisms of S. plumbizincicola.

  15. X-82 to Treat Age-related Macular Degeneration

    Science.gov (United States)

    2017-01-12

    Age-Related Macular Degeneration (AMD); Macular Degeneration; Exudative Age-related Macular Degeneration; AMD; Macular Degeneration, Age-related, 10; Eye Diseases; Retinal Degeneration; Retinal Diseases

  16. Genes, inflammation, and age-related diseases

    OpenAIRE

    Trompet, Stella

    2010-01-01

    The general objective of this thesis was to investigate associations between genetic variants involved in inflammation and epigenetics and age-related diseases in an elderly cohort to get more insights in the patho-physiological mechanisms involved in age-related diseases, like cardiovascular disease, cognitive decline and cancer. For all analyses we used data of the participants of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). We have shown that subjects carrying gen...

  17. Metabolic biotransformation of copper-benzo[a]pyrene combined pollutant on the cellular interface of Stenotrophomonas maltophilia.

    Science.gov (United States)

    Chen, Shuona; Yin, Hua; Tang, Shaoyu; Peng, Hui; Liu, Zehua; Dang, Zhi

    2016-03-01

    Previous studies have confirmed that Stenotrophomonas maltophilia can bind an appreciable amount of Cu(II) and degrade BaP. However, the removal mechanisms of Cu(II) coexisted with BaP by S. maltophilia are still unclear. In this study, the micro-interaction of contaminants on the cellular surface was investigated. The results indicated that carboxyl groups played an important role in the binding of copper to the thallus and that the cell walls were the main adsorption sites. Nevertheless, these reactive groups had no obvious effect on the uptake of BaP. Instead, the disruption and modification of cell walls accelerated transportation of BaP across the membrane into cells. The observation of SEM-EDS confirmed that Cu(II) would be adsorbed and precipitated onto the cell surface but would also be removed by extracellular precipitation when BaP coexisted. And the XPS analysis reflected that part of Cu(II) bound onto biosorbents changed into Cu(I) and Cu.

  18. Bioleaching of gold, copper and nickel from waste cellular phone PCBs and computer goldfinger motherboards by two Aspergillus nigerstrains.

    Science.gov (United States)

    Madrigal-Arias, Jorge Enrique; Argumedo-Delira, Rosalba; Alarcón, Alejandro; Mendoza-López, Ma Remedios; García-Barradas, Oscar; Cruz-Sánchez, Jesús Samuel; Ferrera-Cerrato, Ronald; Jiménez-Fernández, Maribel

    2015-01-01

    In an effort to develop alternate techniques to recover metals from waste electrical and electronic equipment (WEEE), this research evaluated the bioleaching efficiency of gold (Au), copper (Cu) and nickel (Ni) by two strains of Aspergillus niger in the presence of gold-plated finger integrated circuits found in computer motherboards (GFICMs) and cellular phone printed circuit boards (PCBs). These three metals were analyzed for their commercial value and their diverse applications in the industry. Au-bioleaching ranged from 42 to 1% for Aspergillus niger strain MXPE6; with the combination of Aspergillus niger MXPE6 + Aspergillus niger MX7, the Au-bioleaching was 87 and 28% for PCBs and GFICMs, respectively. In contrast, the bioleaching of Cu by Aspergillus niger MXPE6 was 24 and 5%; using the combination of both strains, the values were 0.2 and 29% for PCBs and GFICMs, respectively. Fungal Ni-leaching was only found for PCBs, but with no significant differences among treatments. Improvement of the metal recovery efficiency by means of fungal metabolism is also discussed.

  19. Bioleaching of gold, copper and nickel from waste cellular phone PCBs and computer goldfinger motherboards by two Aspergillus nigerstrains

    Directory of Open Access Journals (Sweden)

    Jorge Enrique Madrigal-Arias

    2015-09-01

    Full Text Available In an effort to develop alternate techniques to recover metals from waste electrical and electronic equipment (WEEE, this research evaluated the bioleaching efficiency of gold (Au, copper (Cu and nickel (Ni by two strains of Aspergillus niger in the presence of gold-plated finger integrated circuits found in computer motherboards (GFICMs and cellular phone printed circuit boards (PCBs. These three metals were analyzed for their commercial value and their diverse applications in the industry. Au-bioleaching ranged from 42 to 1% for Aspergillus niger strain MXPE6; with the combination of Aspergillus niger MXPE6 + Aspergillus niger MX7, the Au-bioleaching was 87 and 28% for PCBs and GFICMs, respectively. In contrast, the bioleaching of Cu by Aspergillus niger MXPE6 was 24 and 5%; using the combination of both strains, the values were 0.2 and 29% for PCBs and GFICMs, respectively. Fungal Ni-leaching was only found for PCBs, but with no significant differences among treatments. Improvement of the metal recovery efficiency by means of fungal metabolism is also discussed.

  20. Age-related changes in triathlon performances.

    Science.gov (United States)

    Lepers, R; Sultana, F; Bernard, T; Hausswirth, C; Brisswalter, J

    2010-04-01

    The aim of this study was two-fold: i) to analyse age-related declines in swimming, cycling, and running performances for Olympic and Ironman triathlons, and ii) to compare age-related changes in these three disciplines between the Olympic and Ironman triathlons. Swimming, cycling, running and total time performances of the top 10 males between 20 and 70 years of age (in 5 years intervals) were analysed for two consecutive world championships (2006 and 2007) for Olympic and Ironman distances. There was a lesser age-related decline in cycling performance (ptriathlon in cycling (>55 years) and running (>50 years), respectively. In contrast, an age-related decline in swimming performance seemed independent of triathlon distance. The age-related decline in triathlon performance is specific to the discipline, with cycling showing less declines in performance with age than swimming and running. The magnitude of the declines in cycling and running performance at Ironman distance is greater than at Olympic distance, suggesting that task duration exerts an important influence on the magnitude of the age-associated changes in triathlon performance.

  1. Model peptides provide new insights into the role of histidine residues as potential ligands in human cellular copper acquisition via Ctr1.

    Science.gov (United States)

    Haas, Kathryn L; Putterman, Allison B; White, Daniel R; Thiele, Dennis J; Franz, Katherine J

    2011-03-30

    Cellular acquisition of copper in eukaryotes is primarily accomplished through the Ctr family of copper transport proteins. In both humans and yeast, methionine-rich "Mets" motifs in the amino-terminal extracellular domain of Ctr1 are thought to be responsible for recruitment of copper at the cell surface. Unlike yeast, mammalian Ctr1 also contains extracellular histidine-rich motifs, although a role for these regions in copper uptake has not been explored in detail. Herein, synthetic model peptides containing the first 14 residues of the extracellular domain of human Ctr1 (MDHSHHMGMSYMDS) have been prepared and evaluated for their apparent binding affinity to both Cu(I) and Cu(II). These studies reveal a high affinity Cu(II) binding site (log K = 11.0 ± 0.3 at pH 7.4) at the amino-terminus of the peptide as well as a high affinity Cu(I) site (log K = 10.2 ± 0.2 at pH 7.4) that utilizes adjacent HH residues along with an additional His or Met ligand. These model studies suggest that the histidine domains may play a direct role in copper acquisition from serum copper-binding proteins and in facilitating the reduction of Cu(II) to the active Ctr1 substrate, Cu(I). We tested this hypothesis by expressing a Ctr1 mutant lacking only extracellular histidine residues in Ctr1-knockout mouse embryonic fibroblasts. Results from live cell studies support the hypothesis that extracellular amino-terminal His residues directly participate in the copper transport function of Ctr1.

  2. [New aspects in age related macular degeneration].

    Science.gov (United States)

    Turlea, C

    2012-01-01

    Being the leading cause of blindness in modern world Age Related Macular Degeneration has beneficiated in the last decade of important progress in diagnosis, classification and the discovery of diverse factors who contribute to the etiology of this disease. Treatments have arised who can postpone the irreversible evolution of the disease and thus preserve vision. Recent findings have identified predisposing genetic factors and also inflamatory and imunological parameters that can be modified trough a good and adequate prevention and therapy This articole reviews new aspects of patology of Age Related Macular Degeneration like the role of complement in maintaining inflamation and the role of oxidative stress on different structures of the retina.

  3. [Pathogenesis of age-related macular degeneration].

    Science.gov (United States)

    Kaarniranta, Kai; Seitsonen, Sanna; Paimela, Tuomas; Meri, Seppo; Immonen, Ilkka

    2009-01-01

    Age-related macular degeneration is a multiform disease of the macula, the region responsible for detailed central vision. In recent years, plenty of new knowledge of the pathogenesis of this disease has been obtained, and the treatment of exudative macular degeneration has greatly progressed. The number of patients with age-related macular degeneration will multiply in the following decades, because knowledge of mechanisms of development of macular degeneration that could be subject to therapeutic measures is insufficient. Central underlying factors are genetic inheritance, exposure of the retina to chronic oxidative stress and accumulation of inflammation-inducing harmful proteins into or outside of retinal cells.

  4. Paradoxical Condensation of Copper with Elevated β-Amyloid in Lipid Rafts under Cellular Copper Deficiency Conditions: IMPLICATIONS FOR ALZHEIMER DISEASE*

    OpenAIRE

    Hung, Ya Hui; Robb, Elysia L.; Volitakis, Irene; Ho, Michael; Evin, Genevieve; Li, Qiao-Xin; Janetta G Culvenor; Masters, Colin L.; Cherny, Robert A.; Bush, Ashley I.

    2009-01-01

    Redox-active copper is implicated in the pathogenesis of Alzheimer disease (AD), β-amyloid peptide (Aβ) aggregation, and amyloid formation. Aβ·copper complexes have been identified in AD and catalytically oxidize cholesterol and lipid to generate H2O2 and lipid peroxides. The site and mechanism of this abnormality is not known. Growing evidence suggests that amyloidogenic processing of the β-amyloid precursor protein (APP) occurs in lipid rafts, membrane microdomains enriched in cholesterol. ...

  5. Response differences between Ectocarpus siliculosus populations to copper stress involve cellular exclusion and induction of the phytochelatin biosynthetic pathway.

    Science.gov (United States)

    Roncarati, Francesca; Sáez, Claudio A; Greco, Maria; Gledhill, Martha; Bitonti, Maria B; Brown, Murray T

    2015-02-01

    Some populations of brown seaweed species inhabit metal-polluted environments and can develop tolerance to metal stress, but the mechanisms by which this is accomplished are still to be elucidated. To address this, the responses of two strains of the model brown alga Ectocarpus siliculosus isolated from sites with different histories of metal contamination exposed to total copper (CuT) concentrations ranging between 0 and 2.4 μM for 10 days were investigated. The synthesis of the metal-chelator phytochelatin (PCs) and relative levels of transcripts encoding the enzymes γ-glutamylcysteine synthetase (γ-GCS), glutathione synthase (GS) and phytochelatin synthase (PCS) that participate in the PC biosynthetic pathway were measured, along with the effects on growth, and adsorption and uptake of Cu. Growth of strain LIA, from a pristine site in Scotland, was inhibited to a greater extent, and at lower concentrations, than that of Es524, isolated from a Cu-contaminated site in Chile. Concentrations of intra-cellular Cu were higher and the exchangeable fraction was lower in LIA than Es524, especially at the highest exposure levels. Total glutathione concentrations increased in both strains with Cu exposure, whereas total PCs levels were higher in Es524 than LIA; PC2 and PC3 were detected in Es524 but PC2 only was found in LIA. The greater production and levels of polymerisation of PCs in Es524 can be explained by the up-regulation of genes encoding for key enzymes involved in the synthesis of PCs. In Es524 there was an increase in the transcripts of γ-GCS, GS and PCS, particularly under high Cu exposure, whereas in LIA4 transcripts of γ-GCS1 increased only slightly, γ-GCS2 and GS decreased and PCS did not change. The consequences of higher intra-cellular concentrations of Cu, lower production of PCs, and lower expression of enzymes involved in GSH-PCs synthesis may be contributing to an induced oxidative stress condition in LIA, which explains, at least in part, the

  6. Squalamine lactate for exudative age-related macular degeneration.

    Science.gov (United States)

    Connolly, Brian; Desai, Avinash; Garcia, Charles A; Thomas, Edgar; Gast, Michael J

    2006-09-01

    Squalamine lactate inhibits angiogenesis by a long-lived, intracellular mechanism of action. The drug is taken up into activated endothelial cells through caveolae, small invaginations in the cellular membrane. Subsequently, the drug binds to and "chaperones" calmodulin to an intracellular membrane compartment and blocks angiogenesis at several levels. A series of basic investigations, preclinical studies, and human clinical trials have begun to establish the proof of concept, efficacy, and safety parameters for use of squalamine lactate as a therapeutic agent for exudative age-related macular degeneration and several types of malignancies.

  7. Folate and age-related disease

    NARCIS (Netherlands)

    Durga, J.

    2004-01-01

    Aging is associated with increased risk of cardiovascular and neurodegenerative disorders and an increase in their risk factors, such as decreased concentrations of folate and increased concentrations of homocysteine. The association of folate and homocysteine with age-related disease and, most impo

  8. Depression in Age-Related Macular Degeneration

    Science.gov (United States)

    Casten, Robin; Rovner, Barry

    2008-01-01

    Age-related macular degeneration (AMD) is a major cause of disability in the elderly, substantially degrades the quality of their lives, and is a risk factor for depression. Rates of depression in AMD are substantially greater than those found in the general population of older people, and are on par with those of other chronic and disabling…

  9. Driving and Age-Related Macular Degeneration

    Science.gov (United States)

    Owsley, Cynthia; McGwin, Gerald, Jr.

    2008-01-01

    This article reviews the research literature on driving and age-related macular degeneration, which is motivated by the link between driving and the quality of life of older adults and their increased collision rate. It addresses the risk of crashes, driving performance, driving difficulty, self-regulation, and interventions to enhance, safety,…

  10. The effects of lead and copper on the cellular architecture and metabolism of the red alga Gracilaria domingensis.

    Science.gov (United States)

    Gouveia, Claudiane; Kreusch, Marianne; Schmidt, Éder C; Felix, Marthiellen R de L; Osorio, Luz K P; Pereira, Debora T; dos Santos, Rodrigo; Ouriques, Luciane C; Martins, Roberta de Paula; Latini, Alexandra; Ramlov, Fernanda; Carvalho, Tiago José G; Chow, Fungyi; Maraschin, Marcelo; Bouzon, Zenilda L

    2013-06-01

    The effect of lead and copper on apical segments of Gracilaria domingensis was examined. Over a period of 7 days, the segments were cultivated with concentrations of 5 and 10 ppm under laboratory conditions. The samples were processed for light, confocal, and electron microscopy, as well as histochemistry, to evaluate growth rates, mitochondrial activity, protein levels, chlorophyll a, phycobiliproteins, and carotenoids. After 7 days of exposure to lead and copper, growth rates were slower than control, and biomass loss was observed on copper-treated plants. Ultrastructural damage was primarily observed in the internal organization of chloroplasts and cell wall thickness. X-ray microanalysis detected lead in the cell wall, while copper was detected in both the cytoplasm and cell wall. Moreover, lead and copper exposure led to photodamage of photosynthetic pigments and, consequently, changes in photosynthesis. However, protein content and glutathione reductase activity decreased only in the copper treatments. In both treatments, decreased mitochondrial NADH dehydrogenase activity was observed. Taken together, the present study demonstrates that (1) heavy metals such as lead and copper negatively affect various morphological, physiological, and biochemical processes in G. domingensis and (2) copper is more toxic than lead in G. domingensis.

  11. 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...... stem cells (MSCs) that are present in the bone marrow and are able to differentiate into cell types such as osteoblasts, chondrocytes, endothelial cells, and probably also neuron-like cells. Because of the ease of their isolation and their extensive differentiation potential, MSCs are among the first...

  12. Mobilization of Nuclear Copper by Green Tea Polyphenol Epicatechin-3-Gallate and Subsequent Prooxidant Breakage of Cellular DNA: Implications for Cancer Chemotherapy

    Directory of Open Access Journals (Sweden)

    Mohd Farhan

    2016-12-01

    Full Text Available Epidemiological as well as experimental evidence exists in support of chemopreventive and anticancer properties of green tea and its constituents. The gallocatechin, epicatechin-3-gallate is a major polyphenol present in green tea, shown responsible for these effects. Plant-derived polyphenolic compounds are established natural antioxidants which are capable of catalyzing oxidative DNA degradation of cellular DNA, alone as well as in the presence of transition metal ions, such as copper. Here we present evidence to support that, similar to various other polyphenoic compounds, epicatechin-3-gallate also causes oxidative degradation of cellular DNA. Single cell alkaline gel electrophoresis (Comet assay was used to assess DNA breakage in lymphocytes that were exposed to various concentrations of epicatechin-3-gallate. Inhibition of DNA breakage in the presence of scavengers of reactive oxygen species (ROS suggested involvement of ROS generation. Addition of neocuproine (a cell membrane permeable Cu(I chelator inhibited DNA degradation, dose-dependently, in intact lymphocytes. In contrast, bathocuproine, which does not permeate cell membrane, was observed to be ineffective. We further show that epicatechin-3-gallate degrades DNA in cell nuclei, which can also be inhibited by neocuproine, suggesting mobilization of nuclear copper in this reaction as well. Our results are indicative of ROS generation, possibly through mobilization of endogenous copper ions, and support our long-standing hypothesis of a prooxidant activity of plant-derived polyphenols as a mechanism for their documented anticancer properties.

  13. 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....

  14. Evaluation of Age-Related Hearing Loss

    OpenAIRE

    2013-01-01

    Age-related hearing loss (presbycusis) is characterized by an increased hearing threshold and poor speech understanding in a noisy environment, slowed central processing of acoustic information, and impaired localization of sound sources. Presbycusis seriously affects the older people's quality of life. Particularly, hearing loss in the elderly contributes to social isolation, depression, and loss of self-esteem. Current amplification methods related to auditory rehabilitation can provide imp...

  15. Immunology of age related macular degeneration

    Institute of Scientific and Technical Information of China (English)

    Kijlstra Aize; Yang Peizeng

    2011-01-01

    @@ Age-related macular degeneration(AMD)is the most important cause of blindness in persons over 55 years of age in the Western world.In view of the increasing life expectancy we can assume that the problem will increase dramatically over the coming decades unless preventive or therapeutic measures are developed.Towards this goal many groups all over the world have performed epidemiological studies to identify potential risk factors for AMD.

  16. Depression in Age-Related Macular Degeneration

    OpenAIRE

    Casten,Robin; Rovner,Barry

    2008-01-01

    Age-related macular degeneration (AMD) is a major cause of disability in the elderly, substantially degrades the quality of their lives, and is a risk factor for depression. Rates of depression in AMD are substantially greater than those found in the general population of older people, and are on par with those of other chronic and disabling diseases. This article discusses the effect of depression on vision-related disability in patients with AMD, suggests methods for screening for depressio...

  17. Animal models of age related macular degeneration

    OpenAIRE

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

    2012-01-01

    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 ...

  18. Age-related synaptic loss of the medial olivocochlear efferent innervation

    Directory of Open Access Journals (Sweden)

    Schrader Angela

    2010-11-01

    Full Text Available Abstract Age-related functional decline of the nervous system is consistently observed, though cellular and molecular events responsible for this decline remain largely unknown. One of the most prevalent age-related functional declines is age-related hearing loss (presbycusis, a major cause of which is the loss of outer hair cells (OHCs and spiral ganglion neurons. Previous studies have also identified an age-related functional decline in the medial olivocochlear (MOC efferent system prior to age-related loss of OHCs. The present study evaluated the hypothesis that this functional decline of the MOC efferent system is due to age-related synaptic loss of the efferent innervation of the OHCs. To this end, we used a recently-identified transgenic mouse line in which the expression of yellow fluorescent protein (YFP, under the control of neuron-specific elements from the thy1 gene, permits the visualization of the synaptic connections between MOC efferent fibers and OHCs. In this model, there was a dramatic synaptic loss between the MOC efferent fibers and the OHCs in older mice. However, age-related loss of efferent synapses was independent of OHC status. These data demonstrate for the first time that age-related loss of efferent synapses may contribute to the functional decline of the MOC efferent system and that this synaptic loss is not necessary for age-related loss of OHCs.

  19. Age-related perspectives and emotion processing.

    Science.gov (United States)

    Lynchard, Nicholas A; Radvansky, Gabriel A

    2012-12-01

    Emotion is processed differently in younger and older adults. Older adults show a positivity effect, whereas younger adults show a negativity effect. Socioemotional selectivity theory suggests that these effects can be elicited in any age group when age-related perspectives are manipulated. To examine this, younger and older adults were oriented to actual and age-contrasting possible selves. Emotion activations were assessed using lexical decision. In line with socioemotional selectivity theory, shifts in emotion orientation varied according to perspective, with both younger and older adults showing a negativity effect when a younger adult perspective was taken and a positivity effect when an older adult perspective was taken.

  20. Evaluation of age-related hearing loss.

    Science.gov (United States)

    Kim, Tae Su; Chung, Jong Woo

    2013-09-01

    Age-related hearing loss (presbycusis) is characterized by an increased hearing threshold and poor speech understanding in a noisy environment, slowed central processing of acoustic information, and impaired localization of sound sources. Presbycusis seriously affects the older people's quality of life. Particularly, hearing loss in the elderly contributes to social isolation, depression, and loss of self-esteem. Current amplification methods related to auditory rehabilitation can provide improved communication ability to users. But, simple auditory rehabilitation is ineffective in managing the central auditory processing disorder and the psychosocial problem of presbycusis. The evaluation of central auditory processing disorder and psychosocial disorder in presbycusis should not be overlooked while providing auditory rehabilitation.

  1. [Age-related macular degeneration (AMD)].

    Science.gov (United States)

    Michels, Stephan; Kurz-Levin, Malaika

    2009-03-01

    Today age-related macular degeneration (AMD) is the most frequent cause for legal blindness in western industrialized countries. The prevalence of this disease rises with increasing age. A multifactorial pathogenesis of AMD is postulated including genetic predisposition and environmental risk factors. The most relevant modifiable risk factor is smoking. Up to today there is no cure of this chronic disease. Prophylaxis, including a healthy diet and antioxidants as nutrional supplements for selected patients, aims to slow down the disease progression. Significant progress has been made in the treatment of the neovascular form of the disease using inhibitors of the vascular endothelial growth factor (VEGF).

  2. Elevated glutathione levels confer cellular sensitization to cisplatin toxicity by up-regulation of copper transporter hCtr1.

    Science.gov (United States)

    Chen, Helen H W; Song, Im-Sook; Hossain, Anwar; Choi, Min-Koo; Yamane, Yoshiaki; Liang, Zheng D; Lu, Jia; Wu, Lily Y-H; Siddik, Zahid H; Klomp, Leo W J; Savaraj, Niramol; Kuo, Macus Tien

    2008-09-01

    Previous studies have demonstrated that treating cultured cells with cisplatin (CDDP) up-regulated the expression of glutathione (GSH) and its de novo rate-limiting enzyme glutamate-cysteine ligase (GCL), which consists of a catalytic (GCLC) and a modifier (GCLM) subunit. It has also been shown that many CDDP-resistant cell lines exhibit high levels of GCLC/GCLM and GSH. Because the GSH system is the major intracellular regulator of redox conditions that serve as an important detoxification cytoprotector, these results have been taken into consideration that elevated levels of GCL/GSH are responsible for the CDDP resistance. In contrast to this context, we demonstrated here that overexpression of GSH by transfection with an expression plasmid containing the GCLC cDNA conferred sensitization to CDDP through up-regulation of human copper transporter (hCtr) 1, which is also a transporter for CDDP. Depleting GSH levels in these transfected cells reversed CDDP sensitivity with concomitant reduction of hCtr1 expression. Although rates of copper transport were also up-regulated in the transfected cells, these cells exhibited biochemical signature of copper deficiency, suggesting that GSH functions as an intracellular copper-chelator and that overexpression of GSH can alter copper metabolism. More importantly, our results reveal a new role of GSH in the regulation of CDDP sensitivity. Overproduction of GSH depletes the bioavailable copper pool, leading to up-regulation of hCtr1 and sensitization of CDDP transport and cell killing. These findings also have important implications in that modulation of the intracellular copper pool may be a novel strategy for improving chemotherapeutic efficacy of platinum-based antitumor agents.

  3. SIRT1 ameliorates age-related senescence of mesenchymal stem cells via modulating telomere shelterin

    Directory of Open Access Journals (Sweden)

    Huiqiang eChen

    2014-06-01

    Full Text Available Age-related mesenchymal stem cells (MSCs senescence, which impairs its tissue repair capacity in vivo and hence compromises the effects of MSCs-based therapy in clinical applications, is closely related to aging and aging-related diseases. Here, we demonstrated the effect of SIRT1, a NAD+-dependent deacetylase, on age-related MSCs senescence. Knockdown of SIRT1 in young MSCs induces cellular senescence and inhibits cellular proliferation ability whereas overexpression of SIRT1 in aged MSCs reversed the cellular senescence and regained its proliferation capacity, suggesting that SIRT1 could modulate age-induced MSCs senescence. Aging-related proteins, P16 and P21, might be involved in SIRT1-mediated anti-aging effect on MSCs. SIRT1 could positively modulate age-related DNA damage in MSCs. In addition, SIRT1 could induce telomerase reverse transcriptase (TERT expression and consequently enhance telomerase activity, however, no significant change was observed in telomere length. Moreover, SIRT1 could positively regulate TPP1, an important member of telomere shelterin, expression. Together, these results demonstrate that SIRT1 dampens age-related MSCs senescence, which was correlated with the up-regulation of TPP1 expression, telomerase activity and down-regulation of DNA damage.

  4. Risk factors for age-related maculopathy.

    LENUS (Irish Health Repository)

    Connell, Paul P

    2012-02-01

    Age-related maculopathy (ARM) is the leading cause of blindness in the elderly. Although beneficial therapeutic strategies have recently begun to emerge, much remains unclear regarding the etiopathogenesis of this disorder. Epidemiologic studies have enhanced our understanding of ARM, but the data, often conflicting, has led to difficulties with drawing firm conclusions with respect to risk for this condition. As a consequence, we saw a need to assimilate the published findings with respect to risk factors for ARM, through a review of the literature appraising results from published cross-sectional studies, prospective cohort studies, case series, and case control studies investigating risk for this condition. Our review shows that, to date, and across a spectrum of epidemiologic study designs, only age, cigarette smoking, and family history of ARM have been consistently demonstrated to represent risk for this condition. In addition, genetic studies have recently implicated many genes in the pathogenesis of age-related maculopathy, including Complement Factor H, PLEKHA 1, and LOC387715\\/HTRA1, demonstrating that environmental and genetic factors are important for the development of ARM suggesting that gene-environment interaction plays an important role in the pathogenesis of this condition.

  5. 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.

  6. Inflammation and its role in age-related macular degeneration.

    Science.gov (United States)

    Kauppinen, Anu; Paterno, Jussi J; Blasiak, Janusz; Salminen, Antero; Kaarniranta, Kai

    2016-05-01

    Inflammation is a cellular response to factors that challenge the homeostasis of cells and tissues. Cell-associated and soluble pattern-recognition receptors, e.g. Toll-like receptors, inflammasome receptors, and complement components initiate complex cellular cascades by recognizing or sensing different pathogen and damage-associated molecular patterns, respectively. Cytokines and chemokines represent alarm messages for leukocytes and once activated, these cells travel long distances to targeted inflamed tissues. Although it is a crucial survival mechanism, prolonged inflammation is detrimental and participates in numerous chronic age-related diseases. This article will review the onset of inflammation and link its functions to the pathogenesis of age-related macular degeneration (AMD), which is the leading cause of severe vision loss in aged individuals in the developed countries. In this progressive disease, degeneration of the retinal pigment epithelium (RPE) results in the death of photoreceptors, leading to a loss of central vision. The RPE is prone to oxidative stress, a factor that together with deteriorating functionality, e.g. decreased intracellular recycling and degradation due to attenuated heterophagy/autophagy, induces inflammation. In the early phases, accumulation of intracellular lipofuscin in the RPE and extracellular drusen between RPE cells and Bruch's membrane can be clinically detected. Subsequently, in dry (atrophic) AMD there is geographic atrophy with discrete areas of RPE loss whereas in the wet (exudative) form there is neovascularization penetrating from the choroid to retinal layers. Elevations in levels of local and systemic biomarkers indicate that chronic inflammation is involved in the pathogenesis of both disease forms.

  7. Age-related macular degeneration: prevention and treatment. A review

    Directory of Open Access Journals (Sweden)

    K. A. Mirzabekova

    2014-01-01

    Full Text Available Age-related macular degeneration (AMD is a multifactorial disease. Age, light exposure, smoking, melanin levels and low-antioxidant diet are contributed to AMD development and progression. Cardiovascular disorders are of considerable importance as well. In macula, photoreceptor outer segments that are rich in polyunsaturated fatty acids (FA, particularly, docosahexaenoic acid (DHA, are susceptible to free radicals damage. High blood flow velocity and oxygen partial pressure as well as direct sunlight exposure induce oxidative processes. The source of free radicals in photoreceptor cells and retinal pigment epithelium (RPE is an extensive mitochondrial metabolism, photoreceptor outer segments phagocytosis, lipofuscin phototoxic activity and hemoglobin or protoporphyrin precursors photosensitization. Oxidative stress is considered as an universal component of cell depth in necrosis, apoptosis and toxic damage. Antioxidant protective system consists of enzymes (superoxide dismutase, glutathione peroxidase and catalase and non-enzymatic factors (ascorbic acid, alpha tocopherol, retinol, carotenoids. Specific antioxidant food supplement containing ascorbic acid (500 mg, vitamin E (400 IU and beta carotene (15 mg coupled with zinc (80 mg of zinc oxide and copper (2 mg of copper oxide results in 25 % decrease in late-stage AMD development rate. Amongst the agents that can protect retina from oxidative stress and AMD development, carotenoids are of special importance. Lutein and zeaxanthin containing in retina and lens screen blue light from central area of the retina. They also absorb blue light and inhibit free radicals generation thus preventing polyunsaturated FA light destruction. Association between lutein and zeaxanthin intake and late-stage AMD risk was revealed. Amongst the most important factors which deficiency favors macular degeneration are omega-3 FAs, i.e., DHA. DHA is the key component of visual pigment rhodopsin transformation. It

  8. Age-related macular degeneration: prevention and treatment. A review

    Directory of Open Access Journals (Sweden)

    K. A. Mirzabekova

    2014-07-01

    Full Text Available Age-related macular degeneration (AMD is a multifactorial disease. Age, light exposure, smoking, melanin levels and low-antioxidant diet are contributed to AMD development and progression. Cardiovascular disorders are of considerable importance as well. In macula, photoreceptor outer segments that are rich in polyunsaturated fatty acids (FA, particularly, docosahexaenoic acid (DHA, are susceptible to free radicals damage. High blood flow velocity and oxygen partial pressure as well as direct sunlight exposure induce oxidative processes. The source of free radicals in photoreceptor cells and retinal pigment epithelium (RPE is an extensive mitochondrial metabolism, photoreceptor outer segments phagocytosis, lipofuscin phototoxic activity and hemoglobin or protoporphyrin precursors photosensitization. Oxidative stress is considered as an universal component of cell depth in necrosis, apoptosis and toxic damage. Antioxidant protective system consists of enzymes (superoxide dismutase, glutathione peroxidase and catalase and non-enzymatic factors (ascorbic acid, alpha tocopherol, retinol, carotenoids. Specific antioxidant food supplement containing ascorbic acid (500 mg, vitamin E (400 IU and beta carotene (15 mg coupled with zinc (80 mg of zinc oxide and copper (2 mg of copper oxide results in 25 % decrease in late-stage AMD development rate. Amongst the agents that can protect retina from oxidative stress and AMD development, carotenoids are of special importance. Lutein and zeaxanthin containing in retina and lens screen blue light from central area of the retina. They also absorb blue light and inhibit free radicals generation thus preventing polyunsaturated FA light destruction. Association between lutein and zeaxanthin intake and late-stage AMD risk was revealed. Amongst the most important factors which deficiency favors macular degeneration are omega-3 FAs, i.e., DHA. DHA is the key component of visual pigment rhodopsin transformation. It

  9. Handling of Copper and Copper Oxide Nanoparticles by Astrocytes.

    Science.gov (United States)

    Bulcke, Felix; Dringen, Ralf

    2016-02-01

    Copper is an essential trace element for many important cellular functions. However, excess of copper can impair cellular functions by copper-induced oxidative stress. In brain, astrocytes are considered to play a prominent role in the copper homeostasis. In this short review we summarise the current knowledge on the molecular mechanisms which are involved in the handling of copper by astrocytes. Cultured astrocytes efficiently take up copper ions predominantly by the copper transporter Ctr1 and the divalent metal transporter DMT1. In addition, copper oxide nanoparticles are rapidly accumulated by astrocytes via endocytosis. Cultured astrocytes tolerate moderate increases in intracellular copper contents very well. However, if a given threshold of cellular copper content is exceeded after exposure to copper, accelerated production of reactive oxygen species and compromised cell viability are observed. Upon exposure to sub-toxic concentrations of copper ions or copper oxide nanoparticles, astrocytes increase their copper storage capacity by upregulating the cellular contents of glutathione and metallothioneins. In addition, cultured astrocytes have the capacity to export copper ions which is likely to involve the copper ATPase 7A. The ability of astrocytes to efficiently accumulate, store and export copper ions suggests that astrocytes have a key role in the distribution of copper in brain. Impairment of this astrocytic function may be involved in diseases which are connected with disturbances in brain copper metabolism.

  10. Age-related hearing loss or presbycusis.

    Science.gov (United States)

    Huang, Qi; Tang, Jianguo

    2010-08-01

    Aging is a natural consequence of a society developing process. Although many adults retain good hearing as they aging, hearing loss related with age-presbycusis which can vary in severity from mild to substantial is common among elderly persons. There are a number of pathophysiological processes underlying age-related changes in the auditory system as well as in the central nervous systems. Many studies have been dedicated to the illustration of risk factors accumulating presbycusis such as heritability, environment factors, medical conditions, free radical (reactive oxygen species, ROS) and damage of mitochondrial DNA. Left untreated, presbycusis can not only lead sufferers to reduced quality of life, isolation, dependence and frustration, but also affect the healthy people around. These can be partly corrected using hearing aids, but it is not enough, more and more strategies of treatment based on the findings associating with presbycusis should be added rather than using single hearing aids. We review here the pathophysiology; heritability, susceptibility genes and other risk factors including environmental, medical, especially free radical (ROS) and damage of mitochondrial DNA; and some strategies of treatment, as well as promising rehabilitations associating with presbycusis.

  11. Sarcopenia and Age-Related Endocrine Function

    Directory of Open Access Journals (Sweden)

    Kunihiro Sakuma

    2012-01-01

    Full Text Available Sarcopenia, the age-related loss of skeletal muscle, is characterized by a deterioration of muscle quantity and quality leading to a gradual slowing of movement, a decline in strength and power, and an increased risk of fall-related injuries. Since sarcopenia is largely attributed to various molecular mediators affecting fiber size, mitochondrial homeostasis, and apoptosis, numerous targets exist for drug discovery. In this paper, we summarize the current understanding of the endocrine contribution to sarcopenia and provide an update on hormonal intervention to try to improve endocrine defects. Myostatin inhibition seems to be the most interesting strategy for attenuating sarcopenia other than resistance training with amino acid supplementation. Testosterone supplementation in large amounts and at low frequency improves muscle defects with aging but has several side effects. Although IGF-I is a potent regulator of muscle mass, its therapeutic use has not had a positive effect probably due to local IGF-I resistance. Treatment with ghrelin may ameliorate the muscle atrophy elicited by age-dependent decreases in growth hormone. Ghrelin is an interesting candidate because it is orally active, avoiding the need for injections. A more comprehensive knowledge of vitamin-D-related mechanisms is needed to utilize this nutrient to prevent sarcopenia.

  12. Animal models of age related macular degeneration.

    Science.gov (United States)

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

    2012-08-01

    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.

  13. Accelerated features of age-related bone loss in zmpste24 metalloproteinase-deficient mice.

    Science.gov (United States)

    Rivas, Daniel; Li, Wei; Akter, Rahima; Henderson, Janet E; Duque, Gustavo

    2009-10-01

    Age-related bone loss is associated with changes in bone cellularity, which include marrow fat infiltration and decreasing levels of osteoblastogenesis. The mechanisms that explain these changes remain unclear. Although nuclear lamina alterations occur in premature aging syndromes that include changes in body fat and severe osteoporosis, the role of proteins of the nuclear lamina in age-related bone loss remains unknown. Using the Zmpste24-null progeroid mice (Zmpste24(-/-)), which exhibit nuclear lamina defects and accumulate unprocessed prelamin A, we identified several alterations in bone cellularity in vivo. We found that defective prelamin A processing induced accelerated features of age-related bone loss including lower osteoblast and osteocyte numbers and higher levels of marrow adipogenesis. In summary, processing of prelamin A could become a new approach to regulate osteoblastogenesis and bone turnover and thus for the prevention and treatment of senile osteoporosis.

  14. Age related macular degeneration and visual disability.

    Science.gov (United States)

    Christoforidis, John B; Tecce, Nicola; Dell'Omo, Roberto; Mastropasqua, Rodolfo; Verolino, Marco; Costagliola, Ciro

    2011-02-01

    Age-related macular degeneration (AMD) is the leading cause of central blindness or low vision among the elderly in industrialized countries. AMD is caused by a combination of genetic and environmental factors. Among modifiable environmental risk factors, cigarette smoking has been associated with both the dry and wet forms of AMD and may increase the likelihood of worsening pre-existing AMD. Despite advances, the treatment of AMD has limitations and affected patients are often referred for low vision rehabilitation to help them cope with their remaining eyesight. The characteristic visual impairment for both forms of AMD is loss of central vision (central scotoma). This loss results in severe difficulties with reading that may be only partly compensated by magnifying glasses or screen-projection devices. The loss of central vision associated with the disease has a profound impact on patient quality of life. With progressive central visual loss, patients lose their ability to perform the more complex activities of daily living. Common vision aids include low vision filters, magnifiers, telescopes and electronic aids. Low vision rehabilitation (LVR) is a new subspecialty emerging from the traditional fields of ophthalmology, optometry, occupational therapy, and sociology, with an ever-increasing impact on the usual concepts of research, education, and services for visually impaired patients. Relatively few ophthalmologists practise LVR and fewer still routinely use prismatic image relocation (IR) in AMD patients. IR is a method of stabilizing oculomotor functions with the purpose of promoting better function of preferred retinal loci (PRLs). The aim of vision rehabilitation therapy consists in the achievement of techniques designed to improve PRL usage. The use of PRLs to compensate for diseased foveae has offered hope to these patients in regaining some function. However, in a recently published meta-analysis, prism spectacles were found to be unlikely to be of

  15. Nut consumption and age-related disease.

    Science.gov (United States)

    Grosso, G; Estruch, R

    2016-02-01

    Current knowledge on the effects of nut consumption on human health has rapidly increased in recent years and it now appears that nuts may play a role in the prevention of chronic age-related diseases. Frequent nut consumption has been associated with better metabolic status, decreased body weight as well as lower body weight gain over time and thus reduce the risk of obesity. The effect of nuts on glucose metabolism, blood lipids, and blood pressure is still controversial. However, significant decreased cardiovascular risk has been reported in a number of observational and clinical intervention studies. Thus, findings from cohort studies show that increased nut consumption is associated with a reduced risk of cardiovascular disease and mortality (especially that due to cardiovascular-related causes). Similarly, nut consumption has been also associated with reduced risk of certain cancers, such as colorectal, endometrial, and pancreatic neoplasms. Evidence regarding nut consumption and neurological or psychiatric disorders is scarce, but a number of studies suggest significant protective effects against depression, mild cognitive disorders and Alzheimer's disease. The underlying mechanisms appear to include antioxidant and anti-inflammatory actions, particularly related to their mono- and polyunsaturated fatty acids (MUFA and PUFA, as well as vitamin and polyphenol content). MUFA have been demonstrated to improve pancreatic beta-cell function and regulation of postprandial glycemia and insulin sensitivity. PUFA may act on the central nervous system protecting neuronal and cell-signaling function and maintenance. The fiber and mineral content of nuts may also confer health benefits. Nuts therefore show promise as useful adjuvants to prevent, delay or ameliorate a number of chronic conditions in older people. Their association with decreased mortality suggests a potential in reducing disease burden, including cardiovascular disease, cancer, and cognitive impairments.

  16. 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.

  17. Oxidative modification of proteins: age-related changes.

    Science.gov (United States)

    Chakravarti, Bulbul; Chakravarti, Deb N

    2007-01-01

    Aging is a complex biological phenomenon which involves progressive loss of different physiological functions of various tissues of living organisms. It is the inevitable fate of life and is a major risk factor for death and different pathological disorders. Based on a wide variety of studies performed in humans as well as in various animal models and microbial systems, reactive oxygen species (ROS) are believed to play a key role in the aging process. The production of ROS is influenced by cellular metabolic activities as well as environmental factors. ROS can react with all major biological macromolecules such as carbohydrates, nucleic acids, lipids, and proteins. Since, in general, proteins are the key molecules that play the ultimate role in various structural and functional aspects of living organisms, this review will focus on the age-related oxidative modifications of proteins as well as on mechanism for removal or repair of the oxidized proteins. The topics covered include protein oxidation as a marker of oxidative stress, experimental evidence indicating the role of ROS in protein oxidation, protein carbonyl content, enzymatic degradation of oxidized proteins, and effects of caloric restriction on protein oxidation in the context of aging. Finally, we will discuss different strategies which have been or can be undertaken to slow down the oxidative damage of proteins and the aging process.

  18. Posttranslational regulation of copper transporters

    NARCIS (Netherlands)

    van den Berghe, P.V.E.

    2009-01-01

    The transition metal copper is an essential cofactor for many redox-active enzymes, but excessive copper can generate toxic reactive oxygen species. Copper homeostasis is maintained by highly conserved proteins, to balance copper uptake, distribution and export on the systemic and cellular level. Th

  19. Genetics Home Reference: age-related macular degeneration

    Science.gov (United States)

    ... Resources (3 links) BrightFocus Foundation: Macular Degeneration Treatment Macular Degeneration Partnership: Low Vision Rehabilitation Prevent Blindness America: Age-Related Macular Degeneration (AMD) ...

  20. Age-related macular degeneration: beyond anti-angiogenesis.

    Science.gov (United States)

    Kent, David L

    2014-01-06

    Recently, anti-vascular endothelial growth factor therapies for neovascular age-related macular degeneration have been developed. These agents, originally developed for their anti-angiogenic mechanism of action, probably also work through an anti-permeability effect in preventing or reducing the amount of leakage from submacular neovascular tissue. Other treatment modalities include laser photocoagulation, photodynamic therapy with verteporfin, and submacular surgery. In reality, these latter treatments can be similarly categorized as anti-angiogenic because their sole aim is destroying or removing choroidal neovascularization (CNV). At the cellular level, CNV resembles stereotypical tissue repair that consists of several matricellular components in addition to neovascularization. In the retina, the clinical term CNV is a misnomer since the term may more appropriately be referred to as aberrant submacular repair. Furthermore, CNV raises a therapeutic conundrum: To complete or correct any reparative process in the body, angiogenesis becomes an essential component. Anti-angiogenic therapy, in all its guises, arrests repair and causes the hypoxic environment to persist, thus fueling pro-angiogenesis and further development of CNV as a component of aberrant repair. However, we realize that anti-vascular endothelial growth factor therapy preserves vision in patients with age-related macular degeneration, albeit temporarily and therefore, repeated treatment is needed. More importantly, however, anti-angiogenic therapy demonstrates that we can at the very least tolerate neovascular tissue beneath the macula and preserve vision in contrast to our historical approach of total vascular destruction. In this clinical scenario, it may be possible to look beyond anti-angiogenesis if our goal is facilitating submacular repair without destroying the neurosensory retina. Thus, in this situation of neovascular tolerance, it may be timely to consider treatments that facilitate

  1. Age-related change of endocytic receptors megalin and cubilin in the kidney in rats.

    Science.gov (United States)

    Odera, Keiko; Goto, Sataro; Takahashi, Ryoya

    2007-10-01

    Megalin and cubilin are the major endocytic receptors responsible for resorption of glomerular filtrate proteins, particularly albumin, in the renal proximal tubule. In order to better understand the mechanism of the development of albuminuria with age in rats, we investigated age-related change of the amount and cellular localization of both receptors in the kidney. Immunoblot analysis of the kidney extracts showed that the amount of megalin significantly decreased with age. Although there was no age-related change in the amount of intact cubilin, the amount of cubilin fragments increased with age. Immunohistochemical study revealed that megalin and cubilin were predominantly localized in brush border membrane of proximal tubular cells in young rats, but the receptors tended to diffuse into the cytoplasm in the old rats. Interestingly, low but significant amounts of megalin and cubilin were present in the glomerular cells in addition to the proximal tubular cells. The quantity of receptors progressively increased in the glomerulus with age. This age-related increase might be to compensate for the age-related defect of the uptake of albumin by the proximal tubules. Thus, although it is unclear whether megalin and cubilin in the glomerulus contribute to the uptake of albumin in primary urine, the age-related increase in the amount of albumin in urine might at least partly be due to quantitative and qualitative alterations of both receptors in the proximal tubule.

  2. Preventing Age-Related Decline of Gut Compartmentalization Limits Microbiota Dysbiosis and Extends Lifespan.

    Science.gov (United States)

    Li, Hongjie; Qi, Yanyan; Jasper, Heinrich

    2016-02-10

    Compartmentalization of the gastrointestinal (GI) tract of metazoans is critical for health. GI compartments contain specific microbiota, and microbiota dysbiosis is associated with intestinal dysfunction. Dysbiosis develops in aging intestines, yet how this relates to changes in GI compartmentalization remains unclear. The Drosophila GI tract is an accessible model to address this question. Here we show that the stomach-like copper cell region (CCR) in the middle midgut controls distribution and composition of the microbiota. We find that chronic activation of JAK/Stat signaling in the aging gut induces a metaplasia of the gastric epithelium, CCR decline, and subsequent commensal dysbiosis and epithelial dysplasia along the GI tract. Accordingly, inhibition of JAK/Stat signaling in the CCR specifically prevents age-related metaplasia, commensal dysbiosis and functional decline in old guts, and extends lifespan. Our results establish a mechanism by which age-related chronic inflammation causes the decline of intestinal compartmentalization and microbiota dysbiosis, limiting lifespan.

  3. Superoxide Dismutase 1 Loss Disturbs Intracellular Redox Signaling, Resulting in Global Age-Related Pathological Changes

    Directory of Open Access Journals (Sweden)

    Kenji Watanabe

    2014-01-01

    Full Text Available Aging is characterized by increased oxidative stress, chronic inflammation, and organ dysfunction, which occur in a progressive and irreversible manner. Superoxide dismutase (SOD serves as a major antioxidant and neutralizes superoxide radicals throughout the body. In vivo studies have demonstrated that copper/zinc superoxide dismutase-deficient (Sod1−/− mice show various aging-like pathologies, accompanied by augmentation of oxidative damage in organs. We found that antioxidant treatment significantly attenuated the age-related tissue changes and oxidative damage-associated p53 upregulation in Sod1−/− mice. This review will focus on various age-related pathologies caused by the loss of Sod1 and will discuss the molecular mechanisms underlying the pathogenesis in Sod1−/− mice.

  4. Age-related Hearing Impairment and the Triad of Acquired Hearing Loss

    Directory of Open Access Journals (Sweden)

    Chao-Hui eYang

    2015-07-01

    Full Text Available Understanding underlying pathological mechanisms is prerequisite for a sensible design of protective therapies against hearing loss. The triad of age-related, noise-generated, and drug-induced hearing loss ¬¬displays intriguing similarities in some cellular responses of cochlear sensory cells such as a potential involvement of reactive oxygen species and apoptotic and necrotic cell death. On the other hand, detailed studies have revealed that molecular pathways are considerably complex and, importantly, it has become clear that pharmacological protection successful against one form of hearing loss will not necessarily protect against another. This review will summarize pathological and pathophysiological features of age-related hearing impairment (ARHI in human and animal models and address selected aspects of the commonality (or lack thereof of cellular responses in ARHI to drugs and noise.

  5. Prevalence of age-related macular degeneration in elderly Caucasians

    DEFF Research Database (Denmark)

    Erke, Maja G; Bertelsen, Geir; Peto, Tunde;

    2012-01-01

    To describe the sex- and age-specific prevalence of drusen, geographic atrophy, and neovascular age-related macular degeneration (AMD).......To describe the sex- and age-specific prevalence of drusen, geographic atrophy, and neovascular age-related macular degeneration (AMD)....

  6. Copper metabolism and copper-mediated alterations in the metabolism of cultured astrocytes

    OpenAIRE

    Scheiber, Ivo Florin

    2012-01-01

    Copper is an essential element that is required for a variety of important cellular functions. Since not only copper deficiency, but also excess of copper can seriously affect cellular functions, cellular copper metabolism is tightly regulated. Disturbances of copper homeostasis are the underlying defect of the inherited diseases Menkes and Wilson s disease and have also been linked to several neurodegenerative diseases including Alzheimer s disease and Parkinson s disease. Known astrocytes f...

  7. The relevance of aging-related changes in brain function to rehabilitation in aging-related disease

    Directory of Open Access Journals (Sweden)

    Bruce eCrosson

    2015-05-01

    Full Text Available The effects of aging on rehabilitation of aging-related diseases are rarely a design consideration in rehabilitation research. In this brief review we present strong coincidental evidence from these two fields suggesting that deficits in aging-related disease or injury are compounded by the interaction between aging-related brain changes and disease-related brain changes. Specifically, we hypothesize that some aphasia, motor, and neglect treatments using repetitive transcranial magnetic stimulation (rTMS or transcranial direct current stimulation (tDCS in stroke patients may address the aging side of this interaction. The importance of testing this hypothesis and addressing the larger aging by aging-related disease interaction is discussed. Underlying mechanisms in aging that most likely are relevant to rehabilitation of aging-related diseases also are covered.

  8. The relevance of aging-related changes in brain function to rehabilitation in aging-related disease.

    Science.gov (United States)

    Crosson, Bruce; McGregor, Keith M; Nocera, Joe R; Drucker, Jonathan H; Tran, Stella M; Butler, Andrew J

    2015-01-01

    The effects of aging on rehabilitation of aging-related diseases are rarely a design consideration in rehabilitation research. In this brief review we present strong coincidental evidence from these two fields suggesting that deficits in aging-related disease or injury are compounded by the interaction between aging-related brain changes and disease-related brain changes. Specifically, we hypothesize that some aphasia, motor, and neglect treatments using repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) in stroke patients may address the aging side of this interaction. The importance of testing this hypothesis and addressing the larger aging by aging-related disease interaction is discussed. Underlying mechanisms in aging that most likely are relevant to rehabilitation of aging-related diseases also are covered.

  9. 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

  10. Slowing down: age-related neurobiological predictors of processing speed

    Directory of Open Access Journals (Sweden)

    Mark A Eckert

    2011-03-01

    Full Text Available Processing speed, or the rate at which tasks can be performed, is a robust predictor of age-relatedcognitive decline and an indicator of independence among older adults. This review examines evidence for neurobiological predictors of age-related changes in processing speed, which is guided in part by our source based morphometry findings that unique patterns of frontal and cerebellar gray matter predict age-related variation in processing speed. These results, together with the extant literature on morphological predictors of age-related changes in processing speed, suggest that specific neural systems undergo declines and as a result slow processing speed. Future studies of processing speed - dependent neural systems will be important for identifying the etiologies for processing speed change and the development of interventions that mitigate gradual age-related declines in cognitive functioning and enhance healthy cognitive aging.

  11. New Clues to Age-Related Hearing Loss

    Science.gov (United States)

    ... fullstory_161359.html New Clues to Age-Related Hearing Loss Older people's brains have a harder time processing ... conversation, many older people chalk it up to hearing loss. But a new, small study finds that the ...

  12. CKD Increases the Risk of Age-Related Macular Degeneration

    OpenAIRE

    Liew, Gerald; Mitchell, Paul; Wong, Tien Yin; Iyengar, Sudha K; Wang, Jie Jin

    2008-01-01

    Age-related macular degeneration is the leading cause of irreversible blindness in the United States and often coexists with chronic kidney disease. Both conditions share common genetic and environmental risk factors. A total of 1183 participants aged 54+ were examined in the population-based, prospective cohort Blue Mountains Eye Study (Australia) to determine if chronic kidney disease increases the risk of age-related macular degeneration. Moderate chronic kidney disease (estimated glomerul...

  13. Abnormal Copper Homeostasis: Mechanisms and Roles in Neurodegeneration

    OpenAIRE

    Mario Manto

    2014-01-01

    As a cofactor of proteins and enzymes involved in critical molecular pathways in mammals and low eukaryotes, copper is a transition metal essential for life. The intra-cellular and extra-cellular metabolism of copper is under tight control, in order to maintain free copper concentrations at very low levels. Copper is a critical element for major neuronal functions, and the central nervous system is a major target of disorders of copper metabolism. Both the accumulation of copper and copper d...

  14. Polyphenol Stilbenes: Molecular Mechanisms of Defence against Oxidative Stress and Aging-Related Diseases

    Directory of Open Access Journals (Sweden)

    Mika Reinisalo

    2015-01-01

    Full Text Available Numerous studies have highlighted the key roles of oxidative stress and inflammation in aging-related diseases such as obesity, type 2 diabetes, age-related macular degeneration (AMD, and Alzheimer’s disease (AD. In aging cells, the natural antioxidant capacity decreases and the overall efficiency of reparative systems against cell damage becomes impaired. There is convincing data that stilbene compounds, a diverse group of natural defence phenolics, abundant in grapes, berries, and conifer bark waste, may confer a protective effect against aging-related diseases. This review highlights recent data helping to clarify the molecular mechanisms involved in the stilbene-mediated protection against oxidative stress. The impact of stilbenes on the nuclear factor-erythroid-2-related factor-2 (Nrf2 mediated cellular defence against oxidative stress as well as the potential roles of SQSTM1/p62 protein in Nrf2/Keap1 signaling and autophagy will be summarized. The therapeutic potential of stilbene compounds against the most common aging-related diseases is discussed.

  15. Life stress, glucocorticoid signaling, and the aging epigenome: Implications for aging-related diseases.

    Science.gov (United States)

    Gassen, Nils C; Chrousos, George P; Binder, Elisabeth B; Zannas, Anthony S

    2017-03-01

    Life stress has been associated with accelerated cellular aging and increased risk for developing aging-related diseases; however, the underlying molecular mechanisms remain elusive. A highly relevant process that may underlie this association is epigenetic regulation. In this review, we build upon existing evidence to propose a model whereby exposure to life stress, in part via its effects on the hypothalamic-pituitary axis and the glucocorticoid signaling system, may alter the epigenetic landscape across the lifespan and, consequently, influence genomic regulation and function in ways that are conducive to the development of aging-related diseases. This model is supported by recent studies showing that life stressors and stress-related phenotypes can accelerate epigenetic aging, a measure that is based on DNA methylation prediction of chronological age and has been associated with several aging-related disease phenotypes. We discuss the implications of this model for the prevention and treatment of aging-related diseases, as well as the challenges and limitations of this line of research.

  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. Redox cycling of endogenous copper by ferulic acid leads to cellular DNA breakage and consequent cell death: A putative cancer chemotherapy mechanism.

    Science.gov (United States)

    Sarwar, Tarique; Zafaryab, Md; Husain, Mohammed Amir; Ishqi, Hassan Mubarak; Rehman, Sayeed Ur; Rizvi, M Moshahid Alam; Tabish, Mohammad

    2015-12-01

    Ferulic acid (FA) is a plant polyphenol showing diverse therapeutic effects against cancer, diabetes, cardiovascular and neurodegenerative diseases. FA is a known antioxidant at lower concentrations, however at higher concentrations or in the presence of metal ions such as copper, it may act as a pro-oxidant. It has been reported that copper levels are significantly raised in different malignancies. Cancer cells are under increased oxidative stress as compared to normal cells. Certain therapeutic substances like polyphenols can further increase this oxidative stress and kill cancer cells without affecting the proliferation of normal cells. Through various in vitro experiments we have shown that the pro-oxidant properties of FA are enhanced in the presence of copper. Comet assay demonstrated the ability of FA to cause oxidative DNA breakage in human peripheral lymphocytes which was ameliorated by specific copper-chelating agent such as neocuproine and scavengers of ROS. This suggested the mobilization of endogenous copper in ROS generation and consequent DNA damage. These results were further validated through cytotoxicity experiments involving different cell lines. Thus, we conclude that such a pro-oxidant mechanism involving endogenous copper better explains the anticancer activities of FA. This would be an alternate non-enzymatic, and copper-mediated pathway for the cytotoxic activities of FA where it can selectively target cancer cells with elevated levels of copper and ROS.

  18. A Plasmodium falciparum copper-binding membrane protein with copper transport motifs

    OpenAIRE

    Choveaux David L; Przyborski Jude M; Goldring JP

    2012-01-01

    Abstract Background Copper is an essential catalytic co-factor for metabolically important cellular enzymes, such as cytochrome-c oxidase. Eukaryotic cells acquire copper through a copper transport protein and distribute intracellular copper using molecular chaperones. The copper chelator, neocuproine, inhibits Plasmodium falciparum ring-to-trophozoite transition in vitro, indicating a copper requirement for malaria parasite development. How the malaria parasite acquires or secretes copper st...

  19. Pharmacogenetics and nutritional supplementation in age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Hampton BM

    2015-05-01

    Full Text Available Blake M Hampton, Jaclyn L Kovach, Stephen G Schwartz Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA Abstract: The Age-Related Eye Disease Study (AREDS recommended treatment with antioxidants plus zinc in patients with intermediate or advanced age-related macular degeneration in order to reduce progression risks. Recent pharmacogenetic studies have reported differences in treatment outcomes with respect to variants in genes for CFH and ARMS2, although the treatment recommendations based on these differences are controversial. Different retrospective analyses of subsets of patients from the same AREDS trial have drawn different conclusions. The practicing clinician, who is not an expert on genetics, clinical trial design, or statistical analysis, may be uncertain how to interpret these results. Based on the balance of the available literature, we suggest not changing established practice recommendations until additional evidence from clinical trials becomes available. Keywords: Age-Related Eye Disease Study (AREDS, age-related macular degeneration, age-related maculopathy susceptibility 2 (ARMS2, complement factor H (CFH, pharmacogenetics, randomized clinical trial (RCT

  20. Age-related macular degeneration: current treatment and future options.

    Science.gov (United States)

    Moutray, Tanya; Chakravarthy, Usha

    2011-09-01

    Age-related macular degeneration is the leading cause of visual impairment among older adults in the developed world. Epidemiological studies have revealed a number of genetic, ocular and environmental risk factors for this condition, which can be addressed by disease reduction strategies. We discuss the various treatment options for dry and exudative age-related macular degeneration available and explain how the recommended treatment depends on the exact type, location and extent of the degeneration. Currently, vascular endothelial growth factor (VEGF) inhibition therapy is the best available treatment for exudative age-related macular degeneration but is limited by the need for repeated intravitreal injections. The current treatment regime is being refined through research on optimal treatment frequency and duration and type of anti-VEGF drug. Different modes of drug delivery are being developed and in the future other methods of VEGF inhibition may be used.

  1. Mouse models of age-related mitochondrial neurosensory hearing loss.

    Science.gov (United States)

    Han, Chul; Someya, Shinichi

    2013-07-01

    Hearing loss is the most common sensory disorder in the elderly population. Overall, 10% of the population has a hearing loss in the US, and this age-related hearing disorder is projected to afflict more than 28 million Americans by 2030. Age-related hearing loss is associated with loss of sensory hair cells (sensory hearing loss) and/or spiral ganglion neurons (neuronal hearing loss) in the cochlea of the inner ear. Many lines of evidence indicate that oxidative stress and associated mitochondrial dysfunction play a central role in age-related neurodegenerative diseases and are a cause of age-related neurosensory hearing loss. Yet, the molecular mechanisms of how oxidative stress and/or mitochondrial dysfunction lead to hearing loss during aging remain unclear, and currently there is no treatment for this age-dependent disorder. Several mouse models of aging and age-related diseases have been linked to age-related mitochondrial neurosensory hearing loss. Evaluation of these animal models has offered basic knowledge of the mechanism underlying hearing loss associated with oxidative stress, mitochondrial dysfunction, and aging. Here we review the evidence that specific mutations in the mitochondrial DNA or nuclear DNA that affect mitochondrial function result in increased oxidative damage and associated loss of sensory hair cells and/or spiral ganglion neurons in the cochlea during aging, thereby causing hearing loss in these mouse models. Future studies comparing these models will provide further insight into fundamental knowledge about the disordered process of hearing and treatments to improve the lives of individuals with communication disorders. This article is part of a Special Issue entitled 'Mitochondrial function and dysfunction in neurodegeneration'.

  2. Age-related changes in task related functional network connectivity.

    Directory of Open Access Journals (Sweden)

    Jason Steffener

    Full Text Available Aging has a multi-faceted impact on brain structure, brain function and cognitive task performance, but the interaction of these different age-related changes is largely unexplored. We hypothesize that age-related structural changes alter the functional connectivity within the brain, resulting in altered task performance during cognitive challenges. In this neuroimaging study, we used independent components analysis to identify spatial patterns of coordinated functional activity involved in the performance of a verbal delayed item recognition task from 75 healthy young and 37 healthy old adults. Strength of functional connectivity between spatial components was assessed for age group differences and related to speeded task performance. We then assessed whether age-related differences in global brain volume were associated with age-related differences in functional network connectivity. Both age groups used a series of spatial components during the verbal working memory task and the strength and distribution of functional network connectivity between these components differed across the age groups. Poorer task performance, i.e. slower speed with increasing memory load, in the old adults was associated with decreases in functional network connectivity between components comprised of the supplementary motor area and the middle cingulate and between the precuneus and the middle/superior frontal cortex. Advancing age also led to decreased brain volume; however, there was no evidence to support the hypothesis that age-related alterations in functional network connectivity were the result of global brain volume changes. These results suggest that age-related differences in the coordination of neural activity between brain regions partially underlie differences in cognitive performance.

  3. Counteracting age-related loss of skeletal muscle mass

    DEFF Research Database (Denmark)

    Bechshøft, Rasmus; Reitelseder, Søren; Højfeldt, Grith;

    2016-01-01

    to training, thereby attenuating the overall benefits of training. We hypothesize that light load resistance training is more efficient when both adherence and physical improvement are considered longitudinally. We launched the interdisciplinary project on Counteracting Age-related Loss of Skeletal Muscle...... Intervention Study will generate scientific evidence and recommendations to counteract age-related loss of skeletal muscle mass in elderly individuals.......Background Aging is associated with decreased muscle mass and functional capacity, which in turn decrease quality of life. The number of citizens over the age of 65 years in the Western world will increase by 50 % over the next four decades, and this demographic shift brings forth new challenges...

  4. On the definition of age-related norms for visual function testing.

    Science.gov (United States)

    Johnson, M A; Choy, D

    1987-04-15

    Cross-sectional psychophysical and electrophysiologic studies of aging indicate that visual function declines only slightly or not at all until age 50-60, at which time the decline in visual function rapidly accelerates. This accelerated loss of function may reflect an increased rate of natural cellular degradation, or it may reflect an increased proportion of subclinical pathology in the presumed normal older population. This paper provides a critical review of the changes in visual function that occur with age. The results of this review have implications for both the definition of age-matched control groups and for early detection of age-related pathology.

  5. Age-Related Differences in Worry and Related Processes

    Science.gov (United States)

    Basevitz, Paul; Pushkar, Dolores; Chaikelson, June; Conway, Michael; Dalton, Connie

    2008-01-01

    This study investigated the hypothesis that older adults would show age-related reductions in the tendency to worry in both their retrospective accounts and through cross-sectional age comparisons with a sample of younger adults. We also sought to determine whether age differences would be evident in psychological processes associated with a…

  6. Extrinsic Mechanisms Involved in Age-Related Defective Bone Formation

    DEFF Research Database (Denmark)

    Trinquier, Anne Marie-Pierre Emilie; Kassem, Moustapha

    2011-01-01

    the mechanisms involved in the age-related defective bone formation. Evidence Acquisition: The mechanisms discussed in this review are based on a PubMed search and knowledge of the authors in the field. Evidence Synthesis: Available basic and clinical studies indicate that multiple mechanisms are involved...

  7. Age-related effects in the neocortical organization of chimpanzees

    DEFF Research Database (Denmark)

    Autrey, Michelle M; Reamer, Lisa A; Mareno, Mary Catherine;

    2014-01-01

    Among primates, humans exhibit the most profound degree of age-related brain volumetric decline in particular regions, such as the hippocampus and the frontal lobe. Recent studies have shown that our closest living relatives, the chimpanzees, experience little to no volumetric decline in gray and...

  8. 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...

  9. Oxidation stress role in age-related cataractogenesis

    Directory of Open Access Journals (Sweden)

    Žorić Lepša

    2010-01-01

    Full Text Available Introduction. Age-related cataract not only diminishes human life quality but it also represents a big impact on healthcare budget of almost every country as the population ages globally. Hence, cataract prevention is a big and true challenge, but a very difficult task to be accomplished. Nowadays cataract is more than a routinely recognized and almost always successfully operated ophthalmologic disease. The diagnosis of age-related cataract diagnosis might alert doctors to some systemic disorders on the whole body level. Increasing age is certainly the most essential age-related cataract risk factor. However, it seems that cataract could be a multifactor disease because of its individual, familiar, racial and gender expression differences. Oxidation stress. Oxidation stress and its form caused by ultraviolet light-photo-oxidative stress - are considered to be crucial in the etiopatho­genesis of cataract. All biomolecules suffer damages during cataract formation. On the other side, the lens posses a range of antioxidant elements and mechanisms of their action, which enable long lasting maintenance of lens transparency and functioning. Although they are primary characteristics of the lens, these antioxidant elements also depend on their systemic availability and consumption. This paper is a short literature review of the relation between oxidation stress and age-related cataract.

  10. Age-related differences in women's foot shape

    NARCIS (Netherlands)

    Ansuategui Echeita, Jone; Hijmans, Juha M.; Smits, Sharon; Van der Woude, Lucas H. V.; Postema, Klaas

    2016-01-01

    Purpose: Describe age-related differences in women's foot shape using a wide range of measurements and ages. Study design: Cross-sectional, observational study. Main outcome measurements: Six foot-shape measurements of each foot: foot lengths, ball widths, ball circumferences, low instep circumferen

  11. The Experience of Age-Related Macular Degeneration

    Science.gov (United States)

    Wong, Elaine Y. H.; Guymer, Robyn H.; Hassell, Jennifer B.; Keeffe, Jill E.

    2004-01-01

    This qualitative article describes the impact of age-related macular degeneration (ARMD) among 15 participants: how a person makes sense of ARMD, the effect of ARMD on the person's quality of life, the psychological disturbances associated with the limitations of ARMD, and the influence of ARMD on social interactions. Such in-depth appreciation of…

  12. 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...

  13. 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…

  14. CKD increases the risk of age-related macular degeneration.

    Science.gov (United States)

    Liew, Gerald; Mitchell, Paul; Wong, Tien Yin; Iyengar, Sudha K; Wang, Jie Jin

    2008-04-01

    Age-related macular degeneration is the leading cause of irreversible blindness in the United States and often coexists with chronic kidney disease. Both conditions share common genetic and environmental risk factors. A total of 1183 participants aged 54+ were examined in the population-based, prospective cohort Blue Mountains Eye Study (Australia) to determine if chronic kidney disease increases the risk of age-related macular degeneration. Moderate chronic kidney disease (estimated glomerular filtration rate macular degeneration was 3.9% in participants with no/mild chronic kidney disease (35 of 897) and 17.5% in those with moderate chronic kidney disease (50 of 286). After adjusting for age, sex, cigarette smoking, hypertension, complement factor H polymorphism, and other risk factors, persons with moderate chronic kidney disease were 3 times more likely to develop early age-related macular degeneration than persons with no/mild chronic kidney disease (odds ratio = 3.2; 95% confidence interval, 1.8 to 5.7, P macular degeneration (odds ratio = 2.0; 95% confidence interval, 1.5 to 2.8, P chronic kidney disease have a higher risk of early age-related macular degeneration, suggesting the possibility of shared pathophysiologic mechanisms between the two conditions.

  15. Age-related differences in Second Language Acquisition

    Institute of Scientific and Technical Information of China (English)

    严爽

    2016-01-01

    There are many factors affecting second language acquisition such as motivation, personality, intelligence, ap-titude, learning styles and so on. This paper focuses on one crucial factor-age. The author tries to explore the age-related differences among second language learners. The main reasons behind the differences and the implications are also discussed.

  16. A Context for Teaching Aging-Related Public Policy.

    Science.gov (United States)

    Brown, David K.

    1999-01-01

    Describes two points of view regarding age-related public programs (Medicaid, Medicare, Social Security): that of devolutionists who would curtail them and safety netters who maintain the government's role is indispensable. Uses Relative Deprivation theory as a framework for teaching public policy about aging. (SK)

  17. Age-related maculopathy: A genetic and epidemiological approach

    NARCIS (Netherlands)

    J.J.M. Willemse-Assink (Jacqueline)

    2000-01-01

    textabstractIn the 19th century, age-related maculopathy (ARM) was described for the first time as an agerelated abnormality of the macula lutea. ARM consists of a variety of clinical signs, from the early stages with soft distinct drusen, indistinct drusen and pigment alterations up to the late st

  18. Lens Epithelial Cell Proliferation and Cell Density in Human Age-related Cataract

    Institute of Scientific and Technical Information of China (English)

    Xialin Liu; Yizhi Liu; Jianliang Zheng; Qiang Huang; Huling Zheng

    2000-01-01

    Purpose: To discuss the potential effect of the lens epithelial cell proliferation in age-related cataract.Methods: In vitro cell proliferation was assayed by MTT method to evaluate the lens epithelial cell density, index, and proliferation capacity in normal lens and all kinds of age-related cataract. Capsulotomy specimens from all kinds of patients who underwent cataract phacoemulsification extraction surgery were compared with the lens epithelial specimens from non-cataract lenses of Eye Bank eyes.Results: Lens epithelial cell density of central anterior capsule (LECD) in female normal lens was higher than that in male, LECD in nuclear cataract( > NⅢ ) was higher than that in normal lens, but in the mature cortical cataract, LF CD was lower. Mitotic index of three kinds of age-related cataracts in vivo had no statistical difference, neither did cell proliferation capacity of cultivated cells in vitro.Conclusion: The individual difference of lens epithelial cell density and proliferation capacity in vivo may be an important underlying cause for senile cataract in the cellular level, especially for nuclear cataract.

  19. Zinc and its role in age-related inflammation and immune dysfunction.

    Science.gov (United States)

    Wong, Carmen P; Ho, Emily

    2012-01-01

    Zinc is an essential micronutrient required for many cellular processes, especially for the normal development and function of the immune system. Zinc homeostasis and signaling are critical in immune activation, and an imbalance in zinc homeostasis is associated with the development of chronic diseases. Zinc deficiency causes significant impairment in both adaptive and innate immune responses, and promotes systemic inflammation. The elderly are a population particularly susceptible to zinc deficiency. National surveys indicate that a significant portion of the aged population has inadequate zinc intake, and a decline in zinc status is observed with age. There are remarkable similarities between the hallmarks of zinc deficiency and immunological dysfunction in aged individuals. Both zinc deficiency and the aging process are characterized by impaired immune responses and systemic low grade chronic inflammation. It has been hypothesized that age-related zinc deficiency may be an important factor contributing to immune dysfunction and chronic inflammation during the aging process. In this review, we discuss the effects of zinc status on aging, potential molecular and epigenetic mechanisms contributing to age-related decline in zinc status, and the role of zinc in age-related immune dysfunction and chronic inflammation.

  20. Ageism, age relations, and garment industry work in Montreal.

    Science.gov (United States)

    McMullin, J A; Marshall, V W

    2001-02-01

    This study examined the complexities of age relations at work. Garment workers believed that their fate was linked to ageism and that their work experience was discounted by management. Managers wanted to be rid of older workers because they commanded higher wages than younger workers. The issue was cost reduction, and age was implicated unintendedly. Still, managers seemed to use stereotypical images to discourage older workers and they did not organize work routines to facilitate the adaptation of them. Instead, they subcontracted the easy jobs, relying on the experience of the older employees for difficult work while not adapting the workplace. Theoretically, the authors argue that ageism and age discrimination can best be understood through a recognition of the importance of structured age relations and human agency.

  1. Mitochondrial aging and age-related dysfunction of mitochondria.

    Science.gov (United States)

    Chistiakov, Dimitry A; Sobenin, Igor A; Revin, Victor V; Orekhov, Alexander N; Bobryshev, Yuri V

    2014-01-01

    Age-related changes in mitochondria are associated with decline in mitochondrial function. With advanced age, mitochondrial DNA volume, integrity and functionality decrease due to accumulation of mutations and oxidative damage induced by reactive oxygen species (ROS). In aged subjects, mitochondria are characterized by impaired function such as lowered oxidative capacity, reduced oxidative phosphorylation, decreased ATP production, significant increase in ROS generation, and diminished antioxidant defense. Mitochondrial biogenesis declines with age due to alterations in mitochondrial dynamics and inhibition of mitophagy, an autophagy process that removes dysfunctional mitochondria. Age-dependent abnormalities in mitochondrial quality control further weaken and impair mitochondrial function. In aged tissues, enhanced mitochondria-mediated apoptosis contributes to an increase in the percentage of apoptotic cells. However, implementation of strategies such as caloric restriction and regular physical training may delay mitochondrial aging and attenuate the age-related phenotype in humans.

  2. 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.

  3. Humanin and Age-related diseases: A new link?

    Directory of Open Access Journals (Sweden)

    Zhenwei eGong

    2014-12-01

    Full Text Available Humanin (HN is 24-amino acid mitochondria-associated peptide. Since its initial discovery over a decade ago, a role for HN has been reported in many biological processes such as apoptosis, cell survival, substrate metabolism, inflammatory response and response to stressors such as oxidative stress, ischemia and starvation. HN and its potent analogs have been shown to have beneficial effects in many age-related diseases including Alzheimer’s disease (AD, stroke, diabetes, myocardial ischemia and reperfusion (MI-R, atherosclerosis, amyotrophic lateral sclerosis (ALS and certain types of cancer both in vitro and in vivo. More recently, an association between HN levels, growth hormone/ insulin-like growth factor-1 (GH/IGF axis and life span was demonstrated using various mouse models with mutations in the GH/IGF axis. The goal of this review is to summarize the current understanding of the role of HN in aging and age-related diseases.

  4. Mechanisms of age-related macular degeneration and therapeutic opportunities.

    Science.gov (United States)

    van Lookeren Campagne, Menno; LeCouter, Jennifer; Yaspan, Brian L; Ye, Weilan

    2014-01-01

    As the age of the population increases in many nations, age-related degenerative diseases pose significant socioeconomic challenges. One of the key degenerative diseases that compromise quality of life is age-related macular degeneration (AMD). AMD is a multi-faceted condition that affects the central retina, which ultimately leads to blindness in millions of people worldwide. The pathophysiology and risk factors for AMD are complex, and the symptoms manifest in multiple related but distinct forms. The ability to develop effective treatments for AMD will depend on a thorough understanding of the underlying pathophysiology, risk factors, and driver molecular pathways, as well as the ability to develop useful animal models. This review provides an overview of the aforementioned aspects in AMD.

  5. Species- and age-related variation in metal exposure and accumulation of two passerine bird species

    Energy Technology Data Exchange (ETDEWEB)

    Berglund, A.M.M., E-mail: asa.berglund@emg.umu.se [Section of Ecology, 20014 University of Turku (Finland); Koivula, M.J.; Eeva, T. [Section of Ecology, 20014 University of Turku (Finland)

    2011-10-15

    We measured the concentration of several elements (arsenic [As], calcium [Ca], cadmium [Cd], copper [Cu], nickel [Ni], lead [Pb], selenium [Se] and zinc [Zn]) in adult and nestling pied flycatchers (Ficedula hypoleuca) and great tits (Parus major) at different distances to a Cu-Ni smelter in 2009. Feces of nestlings generally failed to correspond with internal element concentrations but reflected the pollution exposure, indicating an increased stress by removal of excess metals. The uptake of Cu and Ni were regulated, but As, Cd, Pb and Se accumulated in liver tissue. Pied flycatchers had generally higher element concentrations than great tits. The higher accumulation of As and Pb in pied flycatcher livers was explained by a more efficient absorption, whereas the higher Cd concentration was primarily due to different intake of food items. Age-related differences occurred between the two species, though both Cd and Se accumulated with age. - Highlights: > We measured metal concentrations in feces and livers of two passerine species. > We examined species- and age-related differences in polluted environments. > Feces was evaluated as a useful non-destructive measure of increased stress. > Generally pied flycatchers accumulated higher concentrations than great tits. > Cadmium and selenium accumulated with age in both species. - Accumulation of metals in liver of two insectivorous passerines reflects inter-specific differences in diet, absorption rate and physiological requirements.

  6. EPHA2 is associated with age-related cortical cataract in mice and humans.

    Directory of Open Access Journals (Sweden)

    Gyungah Jun

    2009-07-01

    Full Text Available Age-related cataract is a major cause of blindness worldwide, and cortical cataract is the second most prevalent type of age-related cataract. Although a significant fraction of age-related cataract is heritable, the genetic basis remains to be elucidated. We report that homozygous deletion of Epha2 in two independent strains of mice developed progressive cortical cataract. Retroillumination revealed development of cortical vacuoles at one month of age; visible cataract appeared around three months, which progressed to mature cataract by six months. EPHA2 protein expression in the lens is spatially and temporally regulated. It is low in anterior epithelial cells, upregulated as the cells enter differentiation at the equator, strongly expressed in the cortical fiber cells, but absent in the nuclei. Deletion of Epha2 caused a significant increase in the expression of HSP25 (murine homologue of human HSP27 before the onset of cataract. The overexpressed HSP25 was in an underphosphorylated form, indicating excessive cellular stress and protein misfolding. The orthologous human EPHA2 gene on chromosome 1p36 was tested in three independent worldwide Caucasian populations for allelic association with cortical cataract. Common variants in EPHA2 were found that showed significant association with cortical cataract, and rs6678616 was the most significant in meta-analyses. In addition, we sequenced exons of EPHA2 in linked families and identified a new missense mutation, Arg721Gln, in the protein kinase domain that significantly alters EPHA2 functions in cellular and biochemical assays. Thus, converging evidence from humans and mice suggests that EPHA2 is important in maintaining lens clarity with age.

  7. An Immunologic Study on Age-related Macular Degeneration

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    Forty-one patients with age-related macular degeneration(AMD) were detected for serum autoantibodies against normal humanretinal protein by means of Western immunoblot analysis.Twenty-sevenout of the 41 patients showed positive response,with a rate of 66 percent.The positive rate of antiretinal antibody in the AMD patients wassignificantly higher than that in normal controls (18%) and in patients withother retinal diseases (24%) (p<0.0005).These antiretinal antibodies fromthe AMD patients partly reacted...

  8. Pinpointing the Earliest Defects in Age-Related Macular Degeneration

    OpenAIRE

    Magnusson, Kristinn P; Shan Duan; Haraldur Sigurdsson; Hjorvar Petursson; Zhenglin Yang; Yu Zhao; Bernstein, Paul S.; Jian Ge; Fridbert Jonasson; Einar Stefansson; Gudleif Helgadottir; Norman A Zabriskie; Thorlakur Jonsson; Asgeir Björnsson; Theodora Thorlacius

    2005-01-01

    BACKGROUND: Age-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in the developed world. The two forms of advanced AMD, geographic atrophy and neovascular AMD, represent different pathological processes in the macula that lead to loss of central vision. Soft drusen, characterized by deposits in the macula without visual loss, are considered to be a precursor of advanced AMD. Recently, it has been proposed that a common missense variant, Y402H, in t...

  9. Stereotactic radiotherapy in neovascular age-related macular degeneration

    OpenAIRE

    Ranjbar, Mahdy; Kurz, Maximilian; Holzhey, Annekatrin; Melchert, Corinna; Rades, Dirk; Grisanti, Salvatore

    2016-01-01

    Abstract Stereotactic radiotherapy (SRT) is a new approach to treat neovascular age-related macular degeneration (nAMD). The INTREPID trial suggested that SRT could reduce the frequency of regular intravitreal injections (IVIs) with antivascular endothelial growth factor drugs, which are necessary to control disease activity. However, the efficacy of SRT in nAMD and resulting morphological changes have not been validated under real-life circumstances, an issue, which we would like to address ...

  10. The role of epigenetics in age-related macular degeneration

    OpenAIRE

    Gemenetzi, M; Lotery, A.J.

    2014-01-01

    It is becoming increasingly evident that epigenetic mechanisms influence gene expression and can explain how interactions between genetics and the environment result in particular phenotypes during development. The extent to which this epigenetic effect contributes to phenotype heritability in age-related macular degeneration (AMD) is currently ill defined. However, emerging evidence suggests that epigenetic changes are relevant to AMD and as such provide an exciting new avenue of research fo...

  11. The Burden of Age-Related Macular Degeneration

    OpenAIRE

    Jordana K. Schmier; Mechelle L. Jones; Halpern, Michael T.

    2006-01-01

    As age-related macular degeneration (AMD) becomes more prevalent as a result of longer life expectancy and the number of elderly people worldwide, it will become increasingly important to understand its potential health and economic impact for appropriate healthcare planning. This review identified published literature on costs and resource use associated with AMD. Despite the increasing prevalence of AMD, the worldwide burden of illness is unknown. Several studies of direct medical costs, bo...

  12. Binocular Refraction in Patients with Age-Related Macular Degeneration

    OpenAIRE

    Skrbek, Matěj

    2013-01-01

    We’ve been finding possible association of central vision damage with binocular vision disorders in our clients suffering from age-related macular degeneration (ARMD), but whose visual acuity still allowed us to examine their binocular vision. Our findings show that there is a significant number of patients with heterophoria in horizontal, as well as vertical direction. The clients rate the vision with prismatic correction as more comfortable, clearer and long-term tolerable. Getting used ...

  13. Vitreomacular traction and age-related macular degeneration.

    Science.gov (United States)

    Green-Simms, Amy E; Bakri, Sophie J

    2011-05-01

    The interaction between the vitreous and the internal limiting membrane of the retina is important in the pathoetiology of numerous ocular disease processes. Recent studies have focused on the vitreo-retinal interface in the context of age-related macular degeneration (AMD), linking vitreo-retinal adhesion to exudative AMD in particular. This review summarizes our knowledge of vitreous anatomy and recent investigations regarding vitreomacular adhesion and AMD.

  14. Mitochondrial sirtuins as therapeutic targets for age-related disorders.

    Science.gov (United States)

    Shih, Jennifer; Donmez, Gizem

    2013-03-01

    Sirtuins are a class of histone deacetylases that have a wide range of regulatory roles in the cell. Three sirtuins, SIRT3 to SIRT5, localize to and function within the mitochondria. Mitochondrial dysfunction is thought to be the underlying mechanism of several age-related diseases, such as metabolic syndrome, cancer, and neurodegeneration. This review examines current evidence that mitochondrial sirtuins are involved in regulating mitochondrial function and pathogenesis.

  15. Smoking and Age-Related Macular Degeneration: Review and Update

    Science.gov (United States)

    Velilla, Sara; García-Medina, José Javier; García-Layana, Alfredo; Pons-Vázquez, Sheila; Pinazo-Durán, M. Dolores; Gómez-Ulla, Francisco; Arévalo, J. Fernando; Díaz-Llopis, Manuel; Gallego-Pinazo, Roberto

    2013-01-01

    Age-related macular degeneration (AMD) is one of the main socioeconomical health issues worldwide. AMD has a multifactorial etiology with a variety of risk factors. Smoking is the most important modifiable risk factor for AMD development and progression. The present review summarizes the epidemiological studies evaluating the association between smoking and AMD, the mechanisms through which smoking induces damage to the chorioretinal tissues, and the relevance of advising patients to quit smoking for their visual health. PMID:24368940

  16. Present and Possible Therapies for Age-Related Macular Degeneration

    OpenAIRE

    Muhammad Khan; Ketan Agarwal; Mohamed Loutfi; Ahmed Kamal

    2014-01-01

    Age-related macular degeneration (AMD) is the most common cause of blindness in the elderly population worldwide and is defined as a chronic, progressive disorder characterized by changes occurring within the macula reflective of the ageing process. At present, the prevalence of AMD is currently rising and is estimated to increase by a third by 2020. Although our understanding of the several components underpinning the pathogenesis of this condition has increased significantly, the treatment ...

  17. Smoking and Age-Related Macular Degeneration: Review and Update

    Directory of Open Access Journals (Sweden)

    Sara Velilla

    2013-01-01

    Full Text Available Age-related macular degeneration (AMD is one of the main socioeconomical health issues worldwide. AMD has a multifactorial etiology with a variety of risk factors. Smoking is the most important modifiable risk factor for AMD development and progression. The present review summarizes the epidemiological studies evaluating the association between smoking and AMD, the mechanisms through which smoking induces damage to the chorioretinal tissues, and the relevance of advising patients to quit smoking for their visual health.

  18. Early detection of age related macular degeneration: current status

    OpenAIRE

    Schwartz, Roy; Loewenstein, Anat

    2015-01-01

    Early diagnosis and treatment of choroidal neovascularization (CNV), a main cause of severe vision loss in age related macular degeneration (AMD), is crucial in order to preserve vision and the quality of life of patients. This review summarizes current literature on the subject of early detection of CNV, both in the clinic setting and mainly in the patient’s home. New technologies are evolving to allow for earlier detection and thus vision preservation in AMD patients.

  19. Early detection of age related macular degeneration: current status.

    Science.gov (United States)

    Schwartz, Roy; Loewenstein, Anat

    2015-01-01

    Early diagnosis and treatment of choroidal neovascularization (CNV), a main cause of severe vision loss in age related macular degeneration (AMD), is crucial in order to preserve vision and the quality of life of patients. This review summarizes current literature on the subject of early detection of CNV, both in the clinic setting and mainly in the patient's home. New technologies are evolving to allow for earlier detection and thus vision preservation in AMD patients.

  20. Results of submacular surgery in age-related macula degeneration

    OpenAIRE

    Laue, Jessica

    2010-01-01

    Due to a disruption of barrier function of the membrane Bruch and a change of the phagocities retinal pigment epithelial (rpe), exists possibility for progress of pathologist invasion of new vessels from the choroidea under the retina. On the position of the macula it will cause quick loss of central visual acuity. The most frequent cause for a choroidal neovascular membrane (CNV) is age-related macula degeneration (AMD); further causes are based on idiopathic or postinflammable reasons. ...

  1. Age-related differences in working memory updating components.

    Science.gov (United States)

    Linares, Rocío; Bajo, M Teresa; Pelegrina, Santiago

    2016-07-01

    The aim of this study was to investigate possible age-related changes throughout childhood and adolescence in different component processes of working memory updating (WMU): retrieval, transformation, and substitution. A set of numerical WMU tasks was administered to four age groups (8-, 11-, 14-, and 21-year-olds). To isolate the effect of each of the WMU components, participants performed different versions of a task that included different combinations of the WMU components. The results showed an expected overall decrease in response times and an increase in accuracy performance with age. Most important, specific age-related changes in the retrieval component were found, demonstrating that the effect of retrieval on accuracy was larger in children than in adolescents or young adults. These findings indicate that the availability of representations from outside the focus of attention may change with age. Thus, the retrieval component of updating could contribute to the age-related changes observed in the performance of many updating tasks.

  2. Telomere length variations in aging and age-related diseases.

    Science.gov (United States)

    Rizvi, Saliha; Raza, Syed Tasleem; Mahdi, Farzana

    2014-01-01

    Telomeres are gene sequences present at chromosomal ends and are responsible for maintaining genome integrity. Telomere length is maximum at birth and decreases progressively with advancing age and thus is considered as a biomarker of chronological aging. This age associated decrease in the length of telomere is linked to various ageing associated diseases like diabetes, hypertension, Alzheimer's disease, cancer etc. and their associated complications. Telomere length is a result of combined effect of oxidative stress, inflammation and repeated cell replication on it, and thus forming an association between telomere length and chronological aging and related diseases. Thus, decrease in telomere length was found to be important in determining both, the variations in longevity and age-related diseases in an individual. Ongoing and progressive research in the field of telomere length dynamics has proved that aging and age-related diseases apart from having a synergistic effect on telomere length were also found to effect telomere length independently also. Here a short description about telomere length variations and its association with human aging and age-related diseases is reviewed.

  3. Pathophysiology of age-related hearing loss (peripheral and central).

    Science.gov (United States)

    Lee, Kyu-Yup

    2013-09-01

    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. Extrinsic factors include noise, ototoxic medication and diet. However, presbycusis may not be related to the intrinsic and extrinsic factors separately. Presbycusis affects not only the physical, cognitive and emotional activities of patients, but also their social functioning. As a result, patients' quality of life deteriorates, compounded by various symptoms including depression, social isolation and lower self-esteem. Presbycusis is classified into six categories, as based on results of audiometric tests and temporal bone pathology, established by Schuknecht (1993): sensory, neural, metabolic or strial, cochlear conductive, mixed and indeterminate types. Among these, metabolic presbycusis is the mainstay of presbycusis types. Age-related changes also develop in the central hearing system. Functional decline of the central auditory system, caused by aging, reduces speech-understanding in noisy background and increase temporal processing deficits in gap-detection measures. This study reviews the literature on the age-related hearing loss.

  4. Soybean β-Conglycinin Prevents Age-Related Hearing Impairment.

    Directory of Open Access Journals (Sweden)

    Tohru Tanigawa

    Full Text Available Obesity-related complications are associated with the development of age-related hearing impairment. β-Conglycinin (β-CG, one of the main storage proteins in soy, offers multiple health benefits, including anti-obesity and anti-atherosclerotic effects. Here, to elucidate the potential therapeutic application of β-CG, we investigated the effect of β-CG on age-related hearing impairment. Male wild-type mice (age 6 months were randomly divided into β-CG-fed and control groups. Six months later, the body weight was significantly lower in β-CG-fed mice than in the controls. Consumption of β-CG rescued the hearing impairment observed in control mice. Cochlear blood flow also increased in β-CG-fed mice, as did the expression of eNOS in the stria vascularis (SV, which protects vasculature. β-CG consumption also ameliorated oxidative status as assessed by 4-HNE staining. In the SV, lipofuscin granules of marginal cells and vacuolar degeneration of microvascular pericytes were decreased in β-CG-fed mice, as shown by transmission electron microscopy. β-CG consumption prevented loss of spiral ganglion cells and reduced the frequencies of lipofuscin granules, nuclear invaginations, and myelin vacuolation. Our observations indicate that β-CG ameliorates age-related hearing impairment by preserving cochlear blood flow and suppressing oxidative stress.

  5. ROLE OF DIETARY SUPPLEMENTATION IN PREVENTING PROGRESSION OF AGE-RELATED MACULAR DEGENERATION

    Directory of Open Access Journals (Sweden)

    N. A. Ermakova

    2016-01-01

    Full Text Available Age-related macular degeneration (AMD is a chronic, progressive, degenerative eye disease affecting the central retina. It is the leading cause of blindness among individuals of 65 years and older. In the early stage patients have drusen and/or alterations of pigmentation in the macular region. This disease can progress to geographic atrophy and/or choroidal neovascularization. It has been shown that oxidative stress and hypoxia are important in the pathogenesis of AMD. Patients may gain some visual improvement with inhibitors of vascular endothelial growth factor, but complete restoration of visual function is achieved only in small cases. No effective therapies are known for atrophic AMD. Many large observational studies have shown that dietary antioxidant supplementation is beneficial in preventing the progression of AMD from early to late stages. The Age-Related Eye Disease Study (AREDS demonstrated that daily oral supplementation with vitamins C (500 mg and E (400 IU, beta carotene (15 mg, zinc (80 mg and copper (2 mg reduced the risk of progression to advanced AMD by 25% at 5 years. In primary analyses AREDS II failed to show further reduce of this risk by addition of lutein (10 mg and zeaxanthin (2mg, or/and omega-3 long-chain polyunsaturated fatty acids [docosahexaenoic acid (350 mg DHA and eicosapentaenoic acid 650 mg (EPA] to the AREDS formulation. But there was no true placebo group. The simultaneous administration of beta carotene, lutein and zeaxanthin may suppress tissue level of the both laters because of competitive absorption of carotenoids. Subgroup analyses revealed that dietary supplementation with lutein, zeaxanthin and AREDS formulation without beta carotene may reduce the risk of progression to advanced AMD.The LUNA (Lutein nutrition effects measured by autofluorescence study demonstrated that supplementation with lutein (12 mg, zeaxanthin (1 mg, vitamin C (120 mg, vitamin E (17,6 mg, zinc (10 mg, selenium (40 mg resulted

  6. Growth hormone action predicts age-related white adipose tissue dysfunction and senescent cell burden in mice

    Science.gov (United States)

    Pirtskhalava, Tamar; Palmer, Allyson K.; List, Edward O.; Berryman, Darlene E.; Lubbers, Ellen R.; Escande, Carlos; Spong, Adam; Masternak, Michal M.; Oberg, Ann L.; LeBrasseur, Nathan K.; Miller, Richard A.; Kopchick, John J.; Bartke, Andrzej; Kirkland, James L.

    2014-01-01

    The aging process is associated with the development of several chronic diseases. White adipose tissue (WAT) may play a central role in age-related disease onset and progression due to declines in adipogenesis with advancing age. Recent reports indicate that the accumulation of senescent progenitor cells may be involved in age-related WAT dysfunction. Growth hormone (GH) action has profound effects on adiposity and metabolism and is known to influence lifespan. In the present study we tested the hypothesis that GH activity would predict age-related WAT dysfunction and accumulation of senescent cells. We found that long-lived GH-deficient and -resistant mice have reduced age-related lipid redistribution. Primary preadipocytes from GH-resistant mice also were found to have greater differentiation capacity at 20 months of age when compared to controls. GH activity was also found to be positively associated with senescent cell accumulation in WAT. Our results demonstrate an association between GH activity, age-related WAT dysfunction, and WAT senescent cell accumulation in mice. Further studies are needed to determine if GH is directly inducing cellular senescence in WAT or if GH actions on other target organs or alternative downstream alterations in insulin-like growth factor-1, insulin or glucose levels are responsible. PMID:25063774

  7. Effect of Bcl-2 rs956572 polymorphism on age-related gray matter volume changes.

    Directory of Open Access Journals (Sweden)

    Mu-En Liu

    Full Text Available The anti-apoptotic protein B-cell CLL/lymphoma 2 (Bcl-2 gene is a major regulator of neural plasticity and cellular resilience. Recently, the Bcl-2 rs956572 single nucleotide polymorphism was proposed to be a functional allelic variant that modulates cellular vulnerability to apoptosis. Our cross-sectional study investigated the genetic effect of this Bcl-2 polymorphism on age-related decreases in gray matter (GM volume across the adult lifespan. Our sample comprised 330 healthy volunteers (191 male, 139 female with a mean age of 56.2±22.0 years (range: 21-92. Magnetic resonance imaging and genotyping of the Bcl-2 rs956572 were performed for each participant. The differences in regional GM volumes between G homozygotes and A-allele carriers were tested using optimized voxel-based morphometry. The association between the Bcl-2 rs956572 polymorphism and age was a predictor of regional GM volumes in the right cerebellum, bilateral lingual gyrus, right middle temporal gyrus, and right parahippocampal gyrus. We found that the volume of these five regions decreased with increasing age (all P<.001. Moreover, the downward slope was steeper among the Bcl-2 rs956572 A-allele carriers than in the G-homozygous participants. Our data provide convergent evidence for the genetic effect of the Bcl-2 functional allelic variant in brain aging. The rs956572 G-allele, which is associated with significantly higher Bcl-2 protein expression and diminished cellular sensitivity to stress-induced apoptosis, conferred a protective effect against age-related changes in brain GM volume, particularly in the cerebellum.

  8. The role of epigenetics in age-related macular degeneration.

    Science.gov (United States)

    Gemenetzi, M; Lotery, A J

    2014-12-01

    It is becoming increasingly evident that epigenetic mechanisms influence gene expression and can explain how interactions between genetics and the environment result in particular phenotypes during development. The extent to which this epigenetic effect contributes to phenotype heritability in age-related macular degeneration (AMD) is currently ill defined. However, emerging evidence suggests that epigenetic changes are relevant to AMD and as such provide an exciting new avenue of research for AMD. This review addresses information on the impact of posttranslational modification of the genome on the pathogenesis of AMD, such as DNA methylation changes affecting antioxidant gene expression, hypoxia-regulated alterations in chromatin structure, and histone acetylation status in relation to angiogenesis and inflammation. It also contains information on the role of non-coding RNA-mediated gene regulation in AMD at a posttranscriptional (before translation) level. Our aim was to review the epigenetic mechanisms that cause heritable changes in gene activity without changing the DNA sequence. We also describe some long-term alterations in the transcriptional potential of a cell, which are not necessarily heritable but remains to be defined in the future. Increasing understanding of the significance of common and rare genetic variants and their relationship to epigenetics and environmental influences may help in establishing methods to assess the risk of AMD. This in turn may allow new therapeutic interventions for the leading cause of central vision impairment in patients over the age of 50 years in developed countries. Search strategy We searched the MEDLINE/PubMed database following MeSH suggestions for articles including the terms: 'ocular epigenetic mechanisms', 'human disease epigenetics', and 'age-related macular degeneration genetics'. The headline used to locate related articles in PubMed was 'epigenetics in ocular disease', and to restrict search, we used the

  9. Aging related erectile dysfunction—potential mechanism to halt or delay its onset

    Science.gov (United States)

    Gonzalez-Cadavid, Nestor F.; Rajfer, Jacob

    2017-01-01

    Erectile dysfunction (ED) will visit every man at some time in his life. The age at when that knock on the door is heard is totally dependent on one’s genetics as well as other extrinsic factors. Unlike guests who come for a visit and then leave, once ED shows up it tends to hang around forever. To add insult to injury, the longer ED hangs around, the worse it will get. It is estimated that by the time a man is in his 40’s, he has about a 40% chance of having some form of ED and this prevalence increases about 10% per decade thereafter. This suggests that the aging related process that leads to ED begins early in life. It turns out that the most common cause of ED, regardless of the patient’s age, is due to a problem with the vascular system of the penis. However, this specific aging related vascular problem is not caused by arterial disease but due to a dysfunction and/or loss of the corporal smooth muscle cells (SMC), the main constituent of the corporal sinusoids. As one gets older, these SMC continue to degrade and disappear. When approximately 15% of these cells have been impacted, it results in an inability of the corporal tissue to retain and/or prevent the blood from “leaking” out of the corporal sinusoids into the systemic veins. However, the corporal SMC themselves begin to combat this aging process by expressing the inducible nitric oxide synthase (iNOS) enzyme to make nitric oxide (NO) in an attempt to quench the high intracellular oxidative stress responsible for the SMC apoptosis. When this iNOS pathway is then pharmacologically upregulated, reversal of these aging related changes in the corpora with correction of the venous leakage is observed. Since we believe that aging related ED is pathologically the same disorder as essential hypertension, the development of a therapeutic regimen that can halt, delay or possibly reverse the cellular processes that lead to aging related ED should also be applicable to those patients diagnosed with

  10. 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.

  11. Age-related macular degeneration: Complement in action.

    Science.gov (United States)

    van Lookeren Campagne, Menno; Strauss, Erich C; Yaspan, Brian L

    2016-06-01

    The complement system plays a key role in host-defense against common pathogens but must be tightly controlled to avoid inflammation and tissue damage. Polymorphisms in genes encoding two important negative regulators of the alternative complement pathway, complement factor H (CFH) and complement factor I (CFI), are associated with the risk for Age-Related Macular Degeneration (AMD), a leading cause of vision impairment in the ageing population. In this review, we will discuss the genetic basis of AMD and the potential impact of complement de-regulation on disease pathogenesis. Finally, we will highlight recent therapeutic approaches aimed at controlling complement activation in patients with AMD.

  12. Nutritional Modulation of Age-Related Macular Degeneration

    OpenAIRE

    Weikel, Karen A; Taylor, Allen

    2012-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. It affects 30–50 million individuals and clinical hallmarks of AMD are observed in at least one third of persons over the age of 75 in industrialized countries (Gehrs et al., 2006). Costs associated with AMD are in excess of $340 billion US (American-Health-Assistance-Foundation, 2012). The majority of AMD patients in the United States are not eligible for clinical treatments (Biarnes et al., 20...

  13. Vision rehabilitation of persons with age related macular degeneration.

    Science.gov (United States)

    Siemsen, Dennis W; Brown, William L

    2011-05-01

    As the population of the United States ages, there is an increase in the number of persons with age related macular degeneration (ARMD). Even as new prevention and treatment techniques are developed, the vision loss associated with ARMD may lead to loss of independence and quality of life. Low vision is a rehabilitative process designed to improve visual function and restore independence. This paper is a review of the current research related to low vision in the areas of magnification, contrast and illumination, reading, training, driving and outcomes assessment.

  14. Binocular refraction in patients with age-related macular degeneration.

    Science.gov (United States)

    Skrbek, Matej

    2013-04-01

    We've been finding possible association of central vision damage with binocular vision disorders in our clients suffering from age-related macular degeneration (ARMD), but whose visual acuity still allowed us to examine their binocular vision. Our findings show that there is a significant number of patients with heterophoria in horizontal, as well as vertical direction. The clients rate the vision with prismatic correction as more comfortable, clearer and long-term tolerable. Getting used to prismatic correction was spontaneous and non-problematic. Based on these results we expect to find possibly the most effective rehabilitation of vision in patients suffering from ARMD.

  15. New developments in age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Lyndon da Cruz

    2008-09-01

    Full Text Available The World Health Organization (WHO estimates that over 3 million people (9% of global blindness are blinded by age-related macular degeneration (AMD. AMD affects people over the age of 55. There are two main types of AMD, dry and wet. In dry AMD, patients slowly lose vision through progressive atrophy of the macular tissue. Wet, or exudative, AMD, is associated with new blood vessels called subretinal neovascular membranes (or SRNVM and affected patients lose vision more rapidly due to fluid leakage and haemorrhage at the macula.

  16. Future Therapies of Wet Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Makoto Ishikawa

    2015-01-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of blindness in the elderly population, and the prevalence of the disease increases exponentially with every decade after the age of 50 years. While VEGF inhibitors are promising drugs for treating patients with ocular neovascularization, there are limitations to their potential for improving vision in AMD patients. Thus, future therapies are required to have the potential to improve visual outcomes. This paper will summarize the future strategies and therapeutic targets that are aimed at enhancing the efficacy and duration of effect of antiangiogenic strategies.

  17. Microglia in the Outer Retina and their Relevance to Pathogenesis of Age-Related Macular Degeneration (AMD)

    OpenAIRE

    2012-01-01

    Age-related macular degeneration (AMD), the largest cause of legal blindness in the elderly in the Western world, is a disease whose pathogenesis is incompletely understood and for which therapeutic challenges remain. The etiology of AMD is thought to involve chronic neuroinflammation of the retina but the details of relevant cellular mechanisms are still not fully understood. Retinal microglia are the primary resident immune cell in the retina and are normally absent from the outer retina, t...

  18. [Age-related macular degeneration: paradigm shift from recent findings].

    Science.gov (United States)

    Yanagi, Yasuo

    2015-03-01

    This review describes recent advances in age-related macular degeneration (AMD), based mainly on our own research findings. First, we investigated the effect of choroidal abnormality and found that choroidal hyperpermeability was observed more often in eyes with polypoidal choroidal vasculopathy (PCV) than in eyes with typical AMD; however, even in eyes with typical AMD, substantial proportion of eyes showed hyperpermeability. Exudative AMD eyes with choroidal hyperpermeability showed thickened choroid more widely than previously demonstrated, and there were more frequent abnormalities with fundus autofluorescence examination. Thus, rather than classifying exudative AMD into PCV and typical AMD, AMD classification by choroidal hyperpermeability may be useful in illustrating the difference of certain clinical characteristics. Second, we investigated the importance of vitreomacular adhesion in the treatment outcome of exudative AMD. The currently prevailing hypothesis is that premacular VEGF concentration is lower in eyes with posterior vitreous detachment (PVD) than in eyes without PVD, thus leading to good treatment outcomes; however, in the current study, we showed that not only VEGF but also anti-angiogenic factor, interferon-inducible protein 10 (IP-10), is affected according to PVD. These results suggest that the effect of PVD on the intraocular environment is more complicated than previously thought, and may have diverse functions. Last, we explained the mechanism of AMD progression based mainly on our basic research. Our research showed that age-related decline of autophagic activity may, at least partly, contribute to the precursor lesion of AMD.

  19. Age-related changes to the production of linguistic prosody

    Science.gov (United States)

    Barnes, Daniel R.

    The production of speech prosody (the rhythm, pausing, and intonation associated with natural speech) is critical to effective communication. The current study investigated the impact of age-related changes to physiology and cognition in relation to the production of two types of linguistic prosody: lexical stress and the disambiguation of syntactically ambiguous utterances. Analyses of the acoustic correlates of stress: speech intensity (or sound-pressure level; SPL), fundamental frequency (F0), key word/phrase duration, and pause duration revealed that both young and older adults effectively use these acoustic features to signal linguistic prosody, although the relative weighting of cues differed by group. Differences in F0 were attributed to age-related physiological changes in the laryngeal subsystem, while group differences in duration measures were attributed to relative task complexity and the cognitive-linguistic load of these respective tasks. The current study provides normative acoustic data for older adults which informs interpretation of clinical findings as well as research pertaining to dysprosody as the result of disease processes.

  20. Age-related retinopathy in NRF2-deficient mice.

    Directory of Open Access Journals (Sweden)

    Zhenyang Zhao

    Full Text Available BACKGROUND: Cumulative oxidative damage is implicated in the pathogenesis of age-related macular degeneration (AMD. Nuclear factor erythroid 2-related factor 2 (NRF2 is a transcription factor that plays key roles in retinal antioxidant and detoxification responses. The purposes of this study were to determine whether NRF2-deficient mice would develop AMD-like retinal pathology with aging and to explore the underlying mechanisms. METHODS AND FINDINGS: Eyes of both wild type and Nrf2(-/- mice were examined in vivo by fundus photography and electroretinography (ERG. Structural changes of the outer retina in aged animals were examined by light and electron microscopy, and immunofluorescence labeling. Our results showed that Nrf2(-/- mice developed age-dependent degenerative pathology in the retinal pigment epithelium (RPE. Drusen-like deposits, accumulation of lipofuscin, spontaneous choroidal neovascularization (CNV and sub-RPE deposition of inflammatory proteins were present in Nrf2(-/- mice after 12 months. Accumulation of autophagy-related vacuoles and multivesicular bodies was identified by electron microscopy both within the RPE and in Bruch's membrane of aged Nrf2(-/- mice. CONCLUSIONS: Our data suggest that disruption of Nfe2l2 gene increased the vulnerability of outer retina to age-related degeneration. NRF2-deficient mice developed ocular pathology similar to cardinal features of human AMD and deregulated autophagy is likely a mechanistic link between oxidative injury and inflammation. The Nrf2(-/- mice can provide a novel model for mechanistic and translational research on AMD.

  1. NSAIDs may protect against age-related brain atrophy

    Directory of Open Access Journals (Sweden)

    Barbara B Bendlin

    2010-09-01

    Full Text Available The use of non-steroidal anti-inflammatory drugs (NSAIDs in humans is associated with brain differences including decreased number of activated microglia. In animals, NSAIDs are associated with reduced microglia, decreased amyloid burden, and neuronal preservation. Several studies suggest NSAIDs protect brain regions affected in the earliest stages of AD, including hippocampal and parahippocampal regions. In this cross-sectional study, we examined the protective effect of NSAID use on gray matter volume in a group of middle-aged and older NSAID users (n = 25 compared to non-user controls (n = 50. All participants underwent neuropsychological testing and T1-weighted magnetic resonance imaging. Non-user controls showed smaller volume in portions of the left hippocampus compared to NSAID users. Age-related loss of volume differed between groups, with controls showing greater medial temporal lobe volume loss with age compared to NSAID users. These results should be considered preliminary, but support previous reports that NSAIDs may modulate age-related loss of brain volume.

  2. Exploring age-related brain degeneration in meditation practitioners.

    Science.gov (United States)

    Luders, Eileen

    2014-01-01

    A growing body of research suggests that meditation practices are associated with substantial psychological as well as physiological benefits. In searching for the biological mechanisms underlying the beneficial impact of meditation, studies have revealed practice-induced alterations of neurotransmitters, brain activity, and cognitive abilities, just to name a few. These findings not only imply a close link between meditation and brain structure, but also suggest possible modulating effects of meditation on age-related brain atrophy. Given that normal aging is associated with significant loss of brain tissue, meditation-induced growth and/or preservation might manifest as a seemingly reduced brain age in meditators (i.e., cerebral measures characteristic of younger brains). Surprisingly, there are only three published studies that have addressed the question of whether meditation diminishes age-related brain degeneration. This paper reviews these three studies with respect to the brain attributes studied, the analytical strategies applied, and the findings revealed. The review concludes with an elaborate discussion on the significance of existing studies, implications and directions for future studies, as well as the overall relevance of this field of research.

  3. Radiation therapy for neovascular age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Robert Petrarca

    2011-01-01

    Full Text Available Robert Petrarca, Timothy L JacksonDepartment of Ophthalmology, King’s College Hospital NHS Foundation Trust, London, UKAbstract: Antivascular endothelial growth factor (anti-VEGF therapies represent the standard of care for most patients presenting with neovascular (wet age-related macular degeneration (neovascular AMD. Anti-VEGF drugs require repeated injections and impose a considerable burden of care, and not all patients respond. Radiation targets the proliferating cells that cause neovascular AMD, including fibroblastic, inflammatory, and endothelial cells. Two new neovascular AMD radiation treatments are being investigated: epimacular brachytherapy and stereotactic radiosurgery. Epimacular brachytherapy uses beta radiation, delivered to the lesion via a pars plana vitrectomy. Stereotactic radiosurgery uses low voltage X-rays in overlapping beams, directed onto the lesion. Feasibility data for epimacular brachytherapy show a greatly reduced need for anti-VEGF therapy, with a mean vision gain of 8.9 ETDRS letters at 12 months. Pivotal trials are underway (MERLOT, CABERNET. Preliminary stereotactic radiosurgery data suggest a mean vision gain of 8 to 10 ETDRS letters at 12 months. A large randomized sham controlled stereotactic radiosurgery feasibility study is underway (CLH002, with pivotal trials to follow. While it is too early to conclude on the safety and efficacy of epimacular brachytherapy and stereotactic radiosurgery, preliminary results are positive, and these suggest that radiation offers a more durable therapeutic effect than intraocular injections.Keywords: wet age-related macular degeneration, neovascular, radiation therapy, epimacular brachytherapy, stereotactic radiosurgery, anti-VEGF

  4. Nitroxide Pharmaceutical Development for Aging-Related Degeneration & Disease

    Directory of Open Access Journals (Sweden)

    Jacob A. Zarling

    2015-11-01

    Full Text Available Nitroxide small molecule agents are in development as preventative or therapeutic pharmaceutical drugs for age-related macular degeneration and cardiovascular disease, which are two major diseases of aging. These aging diseases are associated with patient genetics, smoking, diet, oxidative stress and chronic inflammation. Nitroxide drugs preventing aging-, smoking-, high sugar or high fat diet-, or radiation- and other environmental-induced pathophysiological conditions in aging disease are reviewed. Tempol (TP, Tempol Hydroxylamine (TP-H, and TP-H prodrug (OT-551 are evaluated in (1 nonsmokers versus smokers with cutaneous microvascular dysfunction, rapidly reversed by cutaneous TP; (2 elderly cancer patients at risk for radiation-induced skin burns or hair loss, prevented by topical TP; and (3 elderly smoker or nonsmoker Age-related Macular Degeneration (AMD patients at risk for vision loss, prevented by daily eye drops of OT-551. The human data indicates safety and efficacy for these nitroxide drugs. Both TP and TP-H topically penetrate and function in skin or mucosa, protecting and treating radiation burns and hair loss or smoking-induced cutaneous vascular dysfunction. TP and TP-H do not penetrate the cornea, while OT-551 does effectively penetrate and travels to the back of the eye, preserving visual acuity and reducing low luminance deficit and night vision loss in dry AMD smokers and non-smoker patients. Topical, oral or injectable drug formulations are discussed.

  5. KCNQ channels regulate age-related memory impairment.

    Directory of Open Access Journals (Sweden)

    Sonia Cavaliere

    Full Text Available In humans KCNQ2/3 heteromeric channels form an M-current that acts as a brake on neuronal excitability, with mutations causing a form of epilepsy. The M-current has been shown to be a key regulator of neuronal plasticity underlying associative memory and ethanol response in mammals. Previous work has shown that many of the molecules and plasticity mechanisms underlying changes in alcohol behaviour and addiction are shared with those of memory. We show that the single KCNQ channel in Drosophila (dKCNQ when mutated show decrements in associative short- and long-term memory, with KCNQ function in the mushroom body α/βneurons being required for short-term memory. Ethanol disrupts memory in wildtype flies, but not in a KCNQ null mutant background suggesting KCNQ maybe a direct target of ethanol, the blockade of which interferes with the plasticity machinery required for memory formation. We show that as in humans, Drosophila display age-related memory impairment with the KCNQ mutant memory defect mimicking the effect of age on memory. Expression of KCNQ normally decreases in aging brains and KCNQ overexpression in the mushroom body neurons of KCNQ mutants restores age-related memory impairment. Therefore KCNQ is a central plasticity molecule that regulates age dependent memory impairment.

  6. Glutathione maintenance mitigates age-related susceptibility to redox cycling agents

    Directory of Open Access Journals (Sweden)

    Nicholas O. Thomas

    2016-12-01

    Full Text Available Isolated hepatocytes from young (4–6 mo and old (24–26 mo F344 rats were exposed to increasing concentrations of menadione, a vitamin K derivative and redox cycling agent, to determine whether the age-related decline in Nrf2-mediated detoxification defenses resulted in heightened susceptibility to xenobiotic insult. An LC50 for each age group was established, which showed that aging resulted in a nearly 2-fold increase in susceptibility to menadione (LC50 for young: 405 μM; LC50 for old: 275 μM. Examination of the known Nrf2-regulated pathways associated with menadione detoxification revealed, surprisingly, that NAD(PH: quinone oxido-reductase 1 (NQO1 protein levels and activity were induced 9-fold and 4-fold with age, respectively (p=0.0019 and p=0.018; N=3, but glutathione peroxidase 4 (GPX4 declined by 70% (p=0.0043; N=3. These results indicate toxicity may stem from vulnerability to lipid peroxidation instead of inadequate reduction of menadione semi-quinone. Lipid peroxidation was 2-fold higher, and GSH declined by a 3-fold greater margin in old versus young rat cells given 300 µM menadione (p2-fold reduction in cell death, suggesting that the age-related increase in menadione susceptibility likely stems from attenuated GSH-dependent defenses. This data identifies cellular targets for intervention in order to limit age-related toxicological insults to menadione and potentially other redox cycling compounds.

  7. Age-related reduction of structural complexity in spleen hematopoietic tissue architecture in mice.

    Science.gov (United States)

    Pantic, Igor; Paunovic, Jovana; Basta-Jovanovic, Gordana; Perovic, Milan; Pantic, Senka; Milosevic, Nebojsa T

    2013-09-01

    The effects of aging on structural complexity in hematopoietic tissue are unknown. In this work, in a mouse experimental model, we report the age-related reduction of spleen hematopoietic tissue (SHT) complexity. Spleen tissue was obtained from the total of 64 male Swiss albino mice divided into 8 age groups: newborns (0 days old), 10 days, 20 days, 30 days, 120 days, 210 days, 300 and 390 days old. SHT was stained using conventional hematoxylin/eosin, and DNA-binding toluidine blue dyes. Fractal dimension as an indicator of cellular complexity, and lacunarity as indicator of tissue heterogeneity were determined based on the binarized SHT micrographs. Results indicate that fractal dimension of mice spleen hematopoietic tissue decreases with age, while lacunarity increases. These changes/trends have been detected in SHT stained both with toluidine blue and conventional hematoxylin/eosin. Fractal dimension was negatively correlated with lacunarity. The detected reduction in complexity suggests that age-related structural changes are present in mouse SHT both in general tissue architecture and progenitor cell DNA.

  8. Age-related dysfunctions of the autophagy lysosomal pathway in hippocampal pyramidal neurons under proteasome stress.

    Science.gov (United States)

    Gavilán, Elena; Pintado, Cristina; Gavilan, Maria P; Daza, Paula; Sánchez-Aguayo, Inmaculada; Castaño, Angélica; Ruano, Diego

    2015-05-01

    Autophagy plays a key role in the maintenance of cellular homeostasis, and autophagy deregulation gives rise to severe disorders. Many of the signaling pathways regulating autophagy under stress conditions are still poorly understood. Using a model of proteasome stress in rat hippocampus, we have characterized the functional crosstalk between the ubiquitin proteasome system and the autophagy-lysosome pathway, identifying also age-related modifications in the crosstalk between both proteolytic systems. Under proteasome inhibition, both autophagy activation and resolution were efficiently induced in young but not in aged rats, leading to restoration of protein homeostasis only in young pyramidal neurons. Importantly, proteasome stress inhibited glycogen synthase kinase-3β in young but activated in aged rats. This age-related difference could be because of a dysfunction in the signaling pathway of the insulin growth factor-1 under stress situations. Present data highlight the potential role of glycogen synthase kinase-3β in the coordination of both proteolytic systems under stress situation, representing a key molecular target to sort out this deleterious effect.

  9. Role of cancer stem cells in age-related rise in colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Pratima; Nangia-Makker; Yingjie; Yu; Adhip; PN; Majumdar

    2015-01-01

    Colorectal cancer(CRC) that comprises about 50% of estimated gastrointestinal cancers remains a high mortality malignancy. It is estimated that CRC will result in 9% of all cancer related deaths. CRC is the third leading malignancy affecting both males and females equally; with 9% of the estimated new cancer cases and 9% cancer related deaths. Sporadic CRC, whose incidence increases markedly with advancing age, occurs in 80%-85% patients diagnosed with CRC. Little is known about the precise biochemical mechanisms responsible for the rise in CRC with aging. However, many probable reasons for this increase have been suggested; among others they include altered carcinogen metabolism and the cumulative effects of long-term exposure to cancer-causing agents. Herein, we propose a role for self-renewing, cancer stem cells(CSCs) in regulating these cellular events. In this editorial, we have briefly described the recent work on the evolution of CSCs in gastro-intestinal track especially in the colon, and how they are involved in the age-related rise in CRC. Focus of this editorial is to provide a description of(1) CSC;(2) epigenetic and genetic mechanisms giving rise to CSCs;(3) markers of CSC;(4) characteristics; and(5) age-related increase in CSC in the colonic crypt.

  10. Role of cancer stem cells in age-related rise in colorectal cancer

    Science.gov (United States)

    Nangia-Makker, Pratima; Yu, Yingjie; Majumdar, Adhip PN

    2015-01-01

    Colorectal cancer (CRC) that comprises about 50% of estimated gastrointestinal cancers remains a high mortality malignancy. It is estimated that CRC will result in 9% of all cancer related deaths. CRC is the third leading malignancy affecting both males and females equally; with 9% of the estimated new cancer cases and 9% cancer related deaths. Sporadic CRC, whose incidence increases markedly with advancing age, occurs in 80%-85% patients diagnosed with CRC. Little is known about the precise biochemical mechanisms responsible for the rise in CRC with aging. However, many probable reasons for this increase have been suggested; among others they include altered carcinogen metabolism and the cumulative effects of long-term exposure to cancer-causing agents. Herein, we propose a role for self-renewing, cancer stem cells (CSCs) in regulating these cellular events. In this editorial, we have briefly described the recent work on the evolution of CSCs in gastro-intestinal track especially in the colon, and how they are involved in the age-related rise in CRC. Focus of this editorial is to provide a description of (1) CSC; (2) epigenetic and genetic mechanisms giving rise to CSCs; (3) markers of CSC; (4) characteristics; and (5) age-related increase in CSC in the colonic crypt. PMID:26600965

  11. Age-related differences in attentional bias for emotional faces.

    Science.gov (United States)

    Tomaszczyk, Jennifer C; Fernandes, Myra A

    2014-01-01

    Past research suggests an aging-related positivity effect in orienting to faces. However, these studies have eschewed direct comparison of orienting when positive and negative faces are presented simultaneously, thereby potentially underestimating the degree to which emotional valence influences such effects. In the current study younger and older adults viewed face pairs for 1000 ms, and upon face-pair offset indicated the location of a dot that appeared in the former location of one of the faces, to assess attentional orienting. When shown negative-neutral pairs, both age groups were biased to attend to negative faces, but when shown positive-negative pairs only younger adults showed a bias toward negative; older adults showed a lack of orienting toward either emotional face. Results suggest younger adults have a negativity bias in attention orienting regardless of the valence of nearby stimuli, whereas older adults show an absence of this bias when positive information is present.

  12. 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.

  13. [Etiology and pathogenesis of age-related macular degeneration].

    Science.gov (United States)

    Herrmann, P; Holz, F G; Charbel Issa, P

    2013-04-01

    Age-related macular degeneration (AMD) is the most common cause of blindness in Germany. Due to the demographic development a further increase of affected patients is to be expected. Improved understanding of AMD pathogenesis resulted from the molecular biological approaches in recent years and showed an association of genetic factors with AMD. The complement factor H gene and the second high-risk locus ARMS2 in particular were found to contribute a significant risk for development of the disease. Ageing and environmental factors, such as smoking, modulate the individual genetic risk profile. A detailed understanding of the complex AMD pathogenesis is also relevant in ophthalmological practice to understand new treatment strategies. In this review we aim to give an overview of the interplay of ageing, external environmental factors and genetic risk variants leading to AMD.

  14. 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.

  15. Counteracting age-related loss of skeletal muscle mass

    DEFF Research Database (Denmark)

    Bechshøft, Rasmus; Reitelseder, Søren; Højfeldt, Grith;

    2016-01-01

    at both societal and individual levels. Only a few longitudinal studies have been reported, but whey protein supplementation seems to improve muscle mass and function, and its combination with heavy strength training appears even more effective. However, heavy resistance training may reduce adherence...... to training, thereby attenuating the overall benefits of training. We hypothesize that light load resistance training is more efficient when both adherence and physical improvement are considered longitudinally. We launched the interdisciplinary project on Counteracting Age-related Loss of Skeletal Muscle....... Moreover, we will evaluate changes in physical performance, muscle fiber type and acute anabolic response to whey protein ingestion, sensory adaptation, gut microbiome, and a range of other measures, combined with questionnaires on life quality and qualitative interviews with selected subjects. The CALM...

  16. Metalloproteinases and metalloproteinase inhibitors in age-related diseases.

    Science.gov (United States)

    Gargiulo, Simona; Gamba, Paola; Poli, Giuseppe; Leonarduzzi, Gabriella

    2014-01-01

    Degradation of the extracellular matrix is an important feature of embryonic development, morphogenesis, angiogenesis, tissue repair and remodeling. It is precisely regulated under physiological conditions, but when dysregulated it becomes a cause of many diseases, including atherosclerosis, osteoarthritis, diabetic vascular complications, and neurodegeneration. Various types of proteinases are implicated in extracellular matrix degradation, but the major enzymes are considered to be metalloproteinases such as matrix metalloproteinases (MMPs) and disintegrin and metalloproteinase domain (ADAMs) that include ADAMs with a thrombospondin domain (ADAMTS). This review discusses involvement of the major metalloproteinases in some age-related chronic diseases, and examines what is currently known about the beneficial effects of their inhibitors, used as new therapeutic strategies for treating or preventing the development and progression of these diseases.

  17. The genetics of age-related macular degeneration.

    Science.gov (United States)

    Guymer, Robyn

    2001-07-01

    AIM: To review the genetics of age-related macular degeneration (AMD). The pathogenesis of AMD, the leading cause of severe visual disability and blindness in our community, remains unknown. However, AMD is regarded as a genetic disease where family history of AMD is a significant risk factor for the disease. Understanding the genetic factors associated with AMD offers the greatest chance for understanding the underlying disease processes. METHODS: Through a review of the literature and the use of original research findings, the current knowledge of the genetics of AMD is explored. CONCLUSION: AMD is increasing in prevalence and remains a major challenge for eye heath providers. Finding the genes that are associated with AMD offers the greatest chance for the development of preventative strategies and treatments.

  18. AMO Teledioptric System for age-related macular degeneration

    Science.gov (United States)

    Chou, Jim-Son; Ting, Albert C.

    1994-05-01

    A 2.5 X magnification system consisting of a two-zone intraocular implant and a spectacle was developed, tested, and clinically tried by fifty patients with cataract ad age-related macular degeneration. Optical bench testing results and clinical data confirmed that the field of view of the system was 2.6 times wider than an equivalent external telescope. The study also demonstrated that the implant itself was clinically equivalent to a standard monofocal intraocular lens for cataract. The clinical study indicated that higher magnification without compromising the compactness and optical quality was needed as the disease progressed. Also, a sound vision rehabilitation process is important to provide patients the full benefits of the system.

  19. [Future methods of treatment in age related macular degeneration].

    Science.gov (United States)

    Turlea, C

    2012-01-01

    In the present time the treatment of Age Related Macular Degeneration (ARMD) begins to develop. Many medical therapies are presently tested in the two types of ARMD, geographic atrophy and exudative ARMD. In atrophic ARMD, new drugs are aimed to spare photoreceptors and the retinal pigment epithelium, to prevent oxidative damage on the retina and to suppress the inflammation process. In exudative ARMD, new therapies are already in use and in progress, especially the anti-VEGF factors, and others try to improve visual prognosis in targeting other mechanism or cells involved in the angiogenesis process. This article reviews and summarizes the available data, presented in several scientific meetings, congresses or given directly by the companies involved.

  20. Wearable diagnostic system for age-related macular degeneration.

    Science.gov (United States)

    Mohaghegh, N; Zadeh, E Ghafar; Magierowski, S

    2016-08-01

    This paper presents a novel head-mounted point-of-care diagnostic system for detection and continuous monitoring of Age-related Macular Degeneration (AMD). This wearable embedded open-source platform enables accurate monitoring of AMD by taking advantage of multiple standard graphical interface techniques such as Amsler Grid, Threshold Amsler Grid, Macular Computerized Psychophysical Test and Preferential Hyperacuity Perimeter (PHP). Here, we describe the proposed multi-Grid or so-called NGRID software and elaborate on the hardware prototype. This prototype includes a commercially available Oculus HMD incorporated with a single board computer. As the first step towards a fully integrated wearable system, this paper successfully proves the functionality of head-mounted graphical interface device ready for a live demonstration. Participants can experience this device and take a 10-minute AMD eye-exam. Furthermore, NGRID has been approved and permitted for an in-hospital clinical trial.

  1. Age-related differences in arithmetic strategy sequential effects.

    Science.gov (United States)

    Lemaire, Patrick

    2016-03-01

    In this article, I review a series of new findings concerning how age-related changes in strategic variations are modulated by sequential effects. Sequential effects refer to how strategy selection and strategy execution on current problems are influenced by which strategy is used on immediately preceding problems. Two sequential effects during strategy selection (i.e., strategy revisions and strategy perseverations) and during strategy execution (i.e., strategy switch costs and modulations of poorer strategy effects) are presented. I also discuss how these effects change with age during adulthood. These phenomena are important, as they shed light on arithmetic processes and how these processes change with age during adulthood. In particular, they speak to the role of executive control while participants select and execute arithmetic strategies. Finally, I discuss the implications of sequential effects for theories of strategies and of arithmetic.

  2. Age-related decline in global form suppression

    DEFF Research Database (Denmark)

    Wiegand, Iris Michaela; Finke, Kathrin; Töllner, Thomas

    2015-01-01

    Visual selection of illusory ‘Kanizsa’ figures, an assembly of local elements that induce the percept of a whole object, is facilitated relative to configurations composed of the same local elements that do not induce a global form – an instance of ‘global precedence’ in visual processing....... Selective attention, i.e., the ability to focus on relevant and ignore irrelevant information, declines with increasing age; however, how this deficit affects selection of global vs. local configurations remains unknown. On this background, the present study examined for age-related differences in a global....... Electrophysiologically, this effect was accompanied by an early (150-225 ms) ‘positivity posterior contralateral’ (PPC), which was elicited for older, but not younger, participants, when the target was a non-Kanizsa configuration and the Kanizsa figure a distractor (rather than vice versa). In addition, timing...

  3. Ranibizumab vs. aflibercept for wet age-related macular degeneration

    DEFF Research Database (Denmark)

    Szabo, Shelagh M; Hedegaard, Morten; Chan, Keith;

    2015-01-01

    , a Bayesian network meta-analysis (NMA) was conducted to indirectly compare posologies of aflibercept and ranibizumab (0.5 mg). The efficacy outcome, mean change from baseline in best-corrected visual acuity (BCVA) on the ETDRS chart, was evaluated at 3 and 12 months; and safety data at 12 months. Standard...... for wet AMD. Reduced frequency aflibercept was associated with the poorest visual outcomes, and sample sizes were small. Findings from these analyses provide novel evidence of the comparative efficacy and safety of aflibercept and ranibizumab for wet AMD.......OBJECTIVE: Although a reduced aflibercept (2.0 mg) injection frequency relative to the approved dosing posology is included in national treatment guidelines for wet age-related macular degeneration (AMD), there is limited evidence of its comparative efficacy. The objective was to compare...

  4. Therapeutic Strategies for Mitochondrial Dysfunction and Oxidative Stress in Age-Related Metabolic Disorders.

    Science.gov (United States)

    Bhatti, J S; Kumar, S; Vijayan, M; Bhatti, G K; Reddy, P H

    2017-01-01

    Mitochondria are complex, intercellular organelles present in the cells and are involved in multiple roles including ATP formation, free radicals generation and scavenging, calcium homeostasis, cellular differentiation, and cell death. Many studies depicted the involvement of mitochondrial dysfunction and oxidative damage in aging and pathogenesis of age-related metabolic disorders and neurodegenerative diseases. Remarkable advancements have been made in understanding the structure, function, and physiology of mitochondria in metabolic disorders such as diabetes, obesity, cardiovascular diseases, and stroke. Further, much progress has been done in the improvement of therapeutic strategies, including lifestyle interventions, pharmacological, and mitochondria-targeted therapeutic approaches. These strategies were mainly focused to reduce the mitochondrial dysfunction caused by oxidative stress and to retain the mitochondrial health in various diseases. In this chapter, we have highlighted the involvement of mitochondrial dysfunction in the pathophysiology of various disorders and recent progress in the development of mitochondria-targeted molecules as therapeutic measures for metabolic disorders.

  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. 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.

  7. Models of accelerated sarcopenia: critical pieces for solving the puzzle of age-related muscle atrophy.

    Science.gov (United States)

    Buford, Thomas W; Anton, Stephen D; Judge, Andrew R; Marzetti, Emanuele; Wohlgemuth, Stephanie E; Carter, Christy S; Leeuwenburgh, Christiaan; Pahor, Marco; Manini, Todd M

    2010-10-01

    Sarcopenia, the age-related loss of skeletal muscle mass, is a significant public health concern that continues to grow in relevance as the population ages. Certain conditions have the strong potential to coincide with sarcopenia to accelerate the progression of muscle atrophy in older adults. Among these conditions are co-morbid diseases common to older individuals such as cancer, kidney disease, diabetes, and peripheral artery disease. Furthermore, behaviors such as poor nutrition and physical inactivity are well-known to contribute to sarcopenia development. However, we argue that these behaviors are not inherent to the development of sarcopenia but rather accelerate its progression. In the present review, we discuss how these factors affect systemic and cellular mechanisms that contribute to skeletal muscle atrophy. In addition, we describe gaps in the literature concerning the role of these factors in accelerating sarcopenia progression. Elucidating biochemical pathways related to accelerated muscle atrophy may allow for improved discovery of therapeutic treatments related to sarcopenia.

  8. Nutritional modulation of age-related macular degeneration.

    Science.gov (United States)

    Weikel, Karen A; Chiu, Chung-Jung; Taylor, Allen

    2012-08-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. It affects 30-50 million individuals and clinical hallmarks of AMD are observed in at least one third of persons over the age of 75 in industrialized countries (Gehrs et al., 2006). Costs associated with AMD are in excess of $340 billion US (American-Health-Assistance-Foundation, 2012). The majority of AMD patients in the United States are not eligible for clinical treatments (Biarnes et al., 2011; Klein et al., 2011). Preventive interventions through dietary modulation are attractive strategies because many studies suggest a benefit of micro- and macronutrients with respect to AMD, as well as other age-related debilities, and with few, if any, adverse effects (Chiu, 2011). Preservation of vision would enhance quality of life for millions of elderly people, and alleviate the personal and public health financial burden of AMD (Frick et al., 2007; Wood et al., 2011). Observational studies indicate that maintaining adequate levels of omega-3 fatty acids (i.e. with 2 servings/week of fish) or a low glycemic index diet may be particularly beneficial for early AMD and that higher levels of carotenoids may be protective, most probably, against neovascular AMD. Intervention trials are needed to better understand the full effect of these nutrients and/or combinations of nutrients on retinal health. Analyses that describe effects of a nutrient on onset and/or progress of AMD are valuable because they indicate the value of a nutrient to arrest AMD at the early stages. This comprehensive summary provides essential information about the value of nutrients with regard to diminishing risk for onset or progress of AMD and can serve as a guide until data from ongoing intervention trials are available.

  9. Age-Related Neurochemical Changes in the Vestibular Nuclei

    Directory of Open Access Journals (Sweden)

    Paul eSmith

    2016-03-01

    Full Text Available There is evidence that the normal aging process is associated with impaired vestibulo-ocular (VOR and vestibulo-spinal reflexes, causing reduced visual acuity and postural instability. Nonetheless, the available evidence is not entirely consistent, especially with respect to the VOR. Some recent studies have reported that VOR gain can be intact even above 80 years of age. Similarly, although there is evidence for age-related hair cell loss and neuronal loss in Scarpa’s ganglion and the vestibular nucleus complex (VNC, it is not entirely consistent. Whatever structural and functional changes occur in the VNC as a result of aging, either to cause vestibular impairment or to compensate for it, neurochemical changes must underlie them. However, the neurochemical changes that occur in the VNC with aging are poorly understood because the available literature is very limited. This review summarises and critically evaluates the available evidence relating to the noradrenaline, serotonin, dopamine, glutamate, GABA, glycine, and nitric oxide neurotransmitter systems in the aging VNC. It is concluded that, at present, it is difficult, if not impossible, to relate the neurochemical changes observed to the function of specific VNC neurons and whether the observed changes are the cause of a functional deficit in the VNC or an effect of it. A better understanding of the neurochemical changes that occur during aging may be important for the development of potential drug treatments for age-related vestibular disorders. However, this will require the use of more sophisticated methodology such as in vivo microdialysis with single neuron recording and perhaps new technologies such as optogenetics.

  10. Canine Models for Copper Homeostasis Disorders

    NARCIS (Netherlands)

    Wu, Xiaoyan; Leegwater, Peter A J; Fieten, Hille

    2016-01-01

    Copper is an essential trace nutrient metal involved in a multitude of cellular processes. Hereditary defects in copper metabolism result in disorders with a severe clinical course such as Wilson disease and Menkes disease. In Wilson disease, copper accumulation leads to liver cirrhosis and neurolog

  11. SATB2-Nanog axis links age-related intrinsic changes of mesenchymal stem cells from craniofacial bone

    Science.gov (United States)

    Xu, Rongyao; Ge, Jie; Fu, Yu; Zhang, Yuchao; Du, Yifei; Ye, Jinhai; Cheng, Jie; Jiang, Hongbing

    2016-01-01

    Bone mesenchymal stem cells (BMSCs) senescence contributes to age-related bone loss. The alveolar bone in jaws originates from neural crest cells and possesses significant site- and age-related properties. However, such intrinsic characteristics of BMSCs from alveolar bone (AB-BMSCs) and the underlying regulatory mechanisms still remain unknown. Here, we found that the expression of special AT-rich binding protein 2 (SATB2) in human AB-BMSCs significantly decreased with aging. SATB2 knockdown on AB-BMSCs from young donors displayed these aging-related phenotypes in vitro. Meanwhile, enforced SATB2 overexpression could rejuvenate AB-BMSCs from older donors. Importantly, satb2 gene- modified BMSCs therapy could prevent the alveolar bone loss during the aging of rats. Mechanistically, the stemness regulator Nanog was identified as the direct transcriptional target of SATB2 in BMSCs and functioned as a downstream mediator of SATB2. Collectively, our data reveal that SATB2 in AB-BMSCs associates with their age-related properties, and prevents AB-BMSCs senescence via maintaining Nanog expression. These findings highlight the translational potential of transcriptional factor-based cellular reprogramming for anti-aging therapy. PMID:27632702

  12. ROLE OF AUTOPHAGY IN AGE-RELATED MUSCLE LOSS

    OpenAIRE

    Lo Verso, Francesca

    2014-01-01

    Autophagy is an ubiquitous degradation system, that is conserved through species. Cells activate autophagy to degrade long-lived proteins, damaged organelles or portions of cytoplasm, that are engulfed in double-membrane vesicles called autophagosomes, that ultimately fuse to lysosomes, where the cargo is degraded and breakdown products are recycled to sustain cellular energetic demands. Skeletal muscle is the most abundant tissue in mammals and controls 80% of the blood glucose. We have r...

  13. The theory behind the age-related positivity effect

    Directory of Open Access Journals (Sweden)

    Andrew E Reed

    2012-09-01

    Full Text Available The positivity effect refers to an age-related trend that favors positive over negative stimuli in cognitive processing. Relative to their younger counterparts, older people attend to and remember more positive than negative information. Since the effect was initially identified and the conceptual basis articulated (Mather & Carstensen, 2005 scores of independent replications and related findings have appeared in the literature. Over the same period, a number of investigations have failed to observe age differences in the cognitive processing of emotional material. When findings are considered in theoretical context, a reliable pattern of evidence emerges that helps to refine conceptual tenets. In this article we articulate the operational definition and theoretical foundations of the positivity effect and review the empirical evidence based on studies of visual attention, memory, decision-making, and neural activation. We conclude with a discussion of future research directions with emphasis on the conditions where a focus on positive information may benefit and/or impair cognitive performance in older people.

  14. Age-related neuroinflammatory changes negatively impact on neuronal function

    Directory of Open Access Journals (Sweden)

    Marina A Lynch

    2010-01-01

    Full Text Available Neuroinflammatory changes, characterized by an increase in microglial activation and often accompanied by upregulation of inflammatory cytokines like interleukin-1β (IL-1β, are common to many, if not all, neurodegenerative diseases. Similar, though less dramatic neuroinflammatory changes are also known to occur with age. Among the consequences of these changes is an impairment in synaptic function and the evidence suggests that inflammatory cytokines may be the primary contributory factor responsible for the deficits in synaptic plasticity which have been identified in aged rodents. Specifically a decrease in the ability of aged rats to sustain long-term potentiation (LTP in perforant path-granule cells of the hippocampus is associated with increased microglial activation. This review considers the evidence which suggests a causal relationship between these changes and the factors which contribute to the age-related microglial activation, and reflects on data which demonstrate that agents which inhibit microglial activation also improve ability of rats to sustain LTP.

  15. The Chromospheric Activity-Age Relation for M Dwarf Stars

    Science.gov (United States)

    Silvestri, N. M.; Oswalt, T. D.; Hawley, S. L.

    2000-12-01

    We present preliminary results from our study in which we use moderate resolution spectroscopy to determine the correlation between the chromospheric activity and age of M dwarf stars in wide binary systems. We have observed ~50 M dwarf stars from our sample with the Apache Point Observatory 3.5-m telescope. We measure the ratio of Hα luminosity to the bolometric luminosity (LHα /Lbol) of the M dwarf---a measure of activity that is proven to correlate well with age. This project is unique in that it will extend the chromospheric activity-age relation of low-mass main sequence stars beyond the ages provided by cluster methods. The ages so determined are also independent of the uncertainties in cluster age determinations. The technique has the potential to improve by at least a factor of two the precision and the range over which ages can currently be determined for main sequence stars. Work on this project is supported by the NASA Graduate Student Researchers Program grant NGT-50290 (N.M.S.).

  16. eNOS-uncoupling in age-related erectile dysfunction

    Science.gov (United States)

    Johnson, JM; Bivalacqua, TJ; Lagoda, GA; Burnett, AL; Musicki, B

    2011-01-01

    Aging is associated with ED. Although age-related ED is attributed largely to increased oxidative stress and endothelial dysfunction in the penis, the molecular mechanisms underlying this effect are not fully defined. We evaluated whether endothelial nitric oxide synthase (eNOS) uncoupling in the aged rat penis is a contributing mechanism. Correlatively, we evaluated the effect of replacement with eNOS cofactor tetrahydrobiopterin (BH4) on erectile function in the aged rats. Male Fischer 344 ‘young’ (4-month-old) and ‘aged’ (19-month-old) rats were treated with a BH4 precursor sepiapterin (10 mg/kg intraperitoneally) or vehicle for 4 days. After 1-day washout, erectile function was assessed in response to electrical stimulation of the cavernous nerve. Endothelial dysfunction (eNOS uncoupling) and oxidative stress (thiobarbituric acid reactive substances, TBARS) were measured by conducting western blot in penes samples. Erectile response was significantly reduced in aged rats, whereas eNOS uncoupling and TBARS production were significantly increased in the aged rat penis compared with young rats. Sepiapterin significantly improved erectile response in aged rats and prevented increase in TBARS production, but did not affect eNOS uncoupling in the penis of aged rats. These findings suggest that aging induces eNOS uncoupling in the penis, resulting in increased oxidative stress and ED. PMID:21289638

  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. Fundus Autofluorescence in Age-related Macular Degeneration

    Science.gov (United States)

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

    2017-01-01

    ABSTRACT Fundus autofluorescence (FAF) provides detailed insight into the health of the retinal pigment epithelium (RPE). This is highly valuable in age-related macular degeneration (AMD) as RPE damage is a hallmark of the disease. The purpose of this paper is to critically appraise current clinical descriptions regarding the appearance of AMD using FAF and to integrate these findings into a chair-side reference. A wide variety of FAF patterns have been described in AMD, which is consistent with the clinical heterogeneity of the disease. In particular, FAF imaging in early to intermediate AMD has the capacity to reveal RPE alterations in areas that appear normal on funduscopy, which aids in the stratification of cases and may have visually significant prognostic implications. It can assist in differential diagnoses and also represents a reliable, sensitive method for distinguishing reticular pseudodrusen. FAF is especially valuable in the detection, evaluation, and monitoring of geographic atrophy and has been used as an endpoint in clinical trials. In neovascular AMD, FAF reveals distinct patterns of classic choroidal neovascularization noninvasively and may be especially useful for determining which eyes are likely to benefit from therapeutic intervention. FAF represents a rapid, effective, noninvasive imaging method that has been underutilized, and incorporation into the routine assessment of AMD cases should be considered. However, the practicing clinician should also be aware of the limitations of the modality, such as in the detection of foveal involvement and in the distinction of phenotypes (hypo-autofluorescent drusen from small areas of geographic atrophy). PMID:27668639

  19. Age-Related Deficits in Conjunctive Representation of Complex Objects

    Science.gov (United States)

    Scheerer, Nichole; Marrone, Diano F.

    2014-01-01

    Although some evidence is consistent with the notion that distinct cortical systems support memory and perception, mounting evidence supports a representational-hierarchical view of cognition, which posits that distinctions lie in simple feature representations versus more complex conjunctive representations of many stimulus features simultaneously. Thus, typical memory tasks engage different regions from typical perception tasks because they inherently test information on opposing ends of this continuum. Memory deficits are reliably reported with age, but the tasks used to make these conclusions predominantly rely on conjunctive representations. To test the extent to which age-related deficits may be accounted for by perceptual processing, this study investigated discriminations involving conjunctive representations in older adults. Results show that adults aged 50 to 77 are impaired, relative to their younger counterparts, on discriminations requiring feature conjunctions, but not simple feature representations. These findings support recent data showing an agerelated decline in the ability to form conjunctive representations. Furthermore, these data suggest that some ‘mnemonic’ deficits associated with age may in fact be the result of deficits in perception rather than memory. PMID:25308561

  20. Stereotactic radiotherapy in neovascular age-related macular degeneration

    Science.gov (United States)

    Ranjbar, Mahdy; Kurz, Maximilian; Holzhey, Annekatrin; Melchert, Corinna; Rades, Dirk; Grisanti, Salvatore

    2016-01-01

    Abstract Stereotactic radiotherapy (SRT) is a new approach to treat neovascular age-related macular degeneration (nAMD). The INTREPID trial suggested that SRT could reduce the frequency of regular intravitreal injections (IVIs) with antivascular endothelial growth factor drugs, which are necessary to control disease activity. However, the efficacy of SRT in nAMD and resulting morphological changes have not been validated under real-life circumstances, an issue, which we would like to address in this retrospective analysis. Patients who met the INTREPID criteria for best responders were eligible for SRT. A total of 32 eyes of 32 patients were treated. Thereafter, patients were examined monthly for 12 months and received pro re nata IVI of aflibercept or ranibizumab. Outcome measures were: mean number of injections, best-corrected visual acuity, and morphological changes of the outer retina-choroid complex as well as patient safety. Mean number of IVI decreased by almost 50% during the 12 months after SRT compared to the year before, whereas visual acuity increased by one line (logMAR). Morphological evaluation showed that most changes affect outer retinal layers. Stereotactic radiotherapy significantly reduced IVI retreatment in nAMD patients under real-life circumstances. Therefore, SRT might be the first step to stop visual loss as a result of IVI undertreatment, which is a major risk. PMID:28033280

  1. Age-related changes in the efficacy of crystalloid cardioplegia.

    Science.gov (United States)

    Magovern, J A; Pae, W E; Waldhausen, J A

    1991-09-01

    Recent work has shown that multi-dose St. Thomas' Hospital cardioplegia solution (STHC) may not provide reliable protection of the neonatal myocardium. We have used an isolated working heart model to study the age-related development of this observation. Sets of eight hearts from 2-, 4-, 6-, and 8-week-old rabbits were subjected to 90 min of ischemia at 10 degrees C. STHC was infused at 30-min intervals in a dose of 10 ml/kg. There were no differences in the preservation of ATP stores during ischemia among the groups. The percentage recovery of preischemic mean aortic pressure, left atrial pressure, and heart rate were not different among groups, but the percentage recovery of aortic flow (AF) (expressed as means +/- standard error of the mean) was significantly lower in the 2- and 4-week hearts (44.1 +/- 8.2 and 66.2 +/- 7.7%) than in the 6- and 8-week hearts (93.0 +/- 6.4 and 97.6 +/- 4.7%). We have confirmed that the use of multi-dose STHC impairs recovery of ventricular function in the neonatal rabbit heart. This effect, however, diminishes rapidly as the immature animal develops and is not present by 6 weeks of age. Additional experimentation is necessary to identify those aspects of the developing myocardium that account for these observations.

  2. Age-Related Changes in Trabecular Meshwork Imaging

    Directory of Open Access Journals (Sweden)

    Mark E. Gold

    2013-01-01

    Full Text Available Purpose. To evaluate the normal aging effects on trabecular meshwork (TM parameters using Fourier domain anterior segment optical coherence tomography (ASOCT images. Patients and Methods. One eye from 45 participants with open angles was imaged. Two independent readers measured TM area, TM length, and area and length of the TM interface shadow from 3 age groups (18–40, 41–60, and 61–80. Measurements were compared using stepwise regression analysis. Results. The average TM parameters were 0.0487 (±0.0092 mm2 for TM area, 0.5502 (±0.1033 mm for TM length, 0.1623 (±0.341 mm2 for TM interface shadow area, and 0.7755 (±0.1574 mm for TM interface shadow length. Interobserver reproducibility coefficients ranged from 0.45 (TM length to 0.82 (TM area. TM area and length were not correlated with age. While the TM interface shadow length did not correlate with age, the TM interface shadow area increased with age. Race, sex, intraocular pressure, and gonioscopy score were not correlated with any TM parameters. Conclusion. Although the TM measurements were not correlated with age, the TM interface shadow area increased with age. Further study is required to determine whether there is any relationship between the age-related ASOCT findings of the TM interface shadow area and physiologic function.

  3. Age-related hearing loss increases cross-modal distractibility.

    Science.gov (United States)

    Puschmann, Sebastian; Sandmann, Pascale; Bendixen, Alexandra; Thiel, Christiane M

    2014-10-01

    Recent electrophysiological studies have provided evidence that changes in multisensory processing in auditory cortex cannot only be observed following extensive hearing loss, but also in moderately hearing-impaired subjects. How the reduced auditory input affects audio-visual interactions is however largely unknown. Here we used a cross-modal distraction paradigm to investigate multisensory processing in elderly participants with an age-related high-frequency hearing loss as compared to young and elderly subjects with normal hearing. During the experiment, participants were simultaneously presented with independent streams of auditory and visual input and were asked to categorize either the auditory or visual information while ignoring the other modality. Unisensory sequences without any cross-modal input served as control conditions to assure that all participants were able to perform the task. While all groups performed similarly in these unisensory conditions, hearing-impaired participants showed significantly increased error rates when confronted with distracting cross-modal stimulation. This effect could be observed in both the auditory and the visual task. Supporting these findings, an additional regression analysis indicted that the degree of high-frequency hearing loss significantly modulates cross-modal visual distractibility in the auditory task. These findings provide new evidence that already a moderate sub-clinical hearing loss, a common phenomenon in the elderly population, affects the processing of audio-visual information.

  4. Activity loss and depression in age-related macular degeneration.

    Science.gov (United States)

    Rovner, Barry W; Casten, Robin J

    2002-01-01

    Age-related macular degeneration (AMD) is the most frequent cause of severe vision loss in older persons and is associated with high rates of disability and depression. The authors evaluated 51 patients with bilateral AMD to investigate the interrelationships of disease severity, disability, and depression and focused on loss of valued activities as an emblematic disabling consequence of AMD. They characterized depression by the Center for Epidemiologic Studies-Depression (CES-D) score, a syndromal state based on the CES-D, and as a level of distress (Index of Affective Suffering; IAS). Thirty subjects (58.8%) had loss of a valued, discretionary activity. They had worse visual acuity and more depressive symptoms and were represented in higher IAS levels than other subjects. Visual acuity was significantly correlated with IAS levels, but not with CES-D scores or syndromal depression. A regression model demonstrated that activity loss mediated the relationship between visual acuity and IAS level. Affective distress occurs in AMD, largely to the extent that valued activities are relinquished because of vision loss. IAS levels best illuminated this relationship, suggesting the value of this dimension of affective functioning in studies of the consequences of chronic disease.

  5. Age-related changes in skin topography and microcirculation.

    Science.gov (United States)

    Li, Li; Mac-Mary, Sophie; Marsaut, David; Sainthillier, Jean Marie; Nouveau, Stéphanie; Gharbi, Tijani; de Lacharriere, Olivier; Humbert, Philippe

    2006-03-01

    Skin topography and microvasculature undergo characteristic changes with age. Although several non-invasive bioengineering methods are currently available to measure them quantitatively, few publications have referred to their relationship with age in different anatomical sites. This study was carried out to observe the age-related changes of the skin topography and skin microcirculation. The microrelief was assessed with special processing software from scanning by interference fringe profilometry of silicone replicas performed on two sites (volar forearm and back of hand) on 50 female volunteers (aged 20-74 years who consisted of ten probands in each decade). The superficial vascular network of both sites was assessed by videocapillaroscopy, and the subpapillary vascular plexus was studied with laser Doppler flowmetry. Skin color, which is affected by blood flow, was observed by colorimeter. The skin roughness and the mean height between peak and valley increased with age. There were statistically significant differences between the evaluated sites. This study also shows that the capillary loops in the dermal papillae decrease but the subpapillary plexus increase with age. The interference fringe profilometry associated with videocapillaroscopy may be useful and accurate to measure the efficacy of medical or cosmetic products to delay skin aging.

  6. Effect of NCAM on aged-related deterioration in vision.

    Science.gov (United States)

    Luke, Margaret Po-Shan; LeVatte, Terry L; O'Reilly, Amanda M; Smith, Benjamin J; Tremblay, François; Brown, Richard E; Clarke, David B

    2016-05-01

    The neural cell adhesion molecule (NCAM) is involved in developmental processes and age-associated cognitive decline; however, little is known concerning the effects of NCAM in the visual system during aging. Using anatomical, electrophysiological, and behavioral assays, we analyzed age-related changes in visual function of NCAM deficient (-/-) and wild-type mice. Anatomical analyses indicated that aging NCAM -/- mice had fewer retinal ganglion cells, thinner retinas, and fewer photoreceptor cell layers than age-matched controls. Electroretinogram testing of retinal function in young adult NCAM -/- mice showed a 2-fold increase in a- and b-wave amplitude compared with wild-type mice, but the retinal activity dropped dramatically to control levels when the animals reached 10 months. In behavioral tasks, NCAM -/- mice had no visual pattern discrimination ability and showed premature loss of vision as they aged. Together, these findings demonstrate that NCAM plays significant roles in the adult visual system in establishing normal retinal anatomy, physiology and function, and in maintaining vision during aging.

  7. Treatment of neovascular age-related macular degeneration: Current therapies

    Directory of Open Access Journals (Sweden)

    Albert J Augustin

    2009-01-01

    Full Text Available Albert J Augustin, Stefan Scholl, Janna KirchhofDepartment of Ophthalmology, Klinikum Karlsruhe, GermanyAbstract: Choroidal neovascularization (CNV secondary to age-related macular degeneration (AMD is now the leading cause of blindness and severe vision loss among people over the age of 40 in the Western world. Its prevalence is certain to increase substantially as the population ages. Treatments currently available for the disease include laser photocoagulation, verteporfin photodynamic therapy, and intravitreal injections of corticosteroids and anti-angiogenic agents. Many studies have reported the benefits of each of these treatments, although none is without its risks. No intervention actually cures AMD, nor the neovascularization associated with it. However, its symptoms are treated with varying degrees of success. Some treatments stabilize or arrest the progress of the disease. Others have been shown to reverse some of the damage that has already been done. These treatments can even lead to visual improvement. This paper will review the major classes of drugs and therapies designed to treat this condition.Keywords: wet AMD, neovascularization, PDT, steroids, anti-angiogenesis

  8. 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.

  9. Nitroxide pharmaceutical development for age-related degeneration and disease.

    Science.gov (United States)

    Zarling, Jacob A; Brunt, Vienna E; Vallerga, Anne K; Li, Weixing; Tao, Albert; Zarling, David A; Minson, Christopher T

    2015-01-01

    Nitroxide small molecule agents are in development as preventative or therapeutic pharmaceutical drugs for age-related macular degeneration (AMD) and cardiovascular disease, which are two major diseases of aging. These aging diseases are associated with patient genetics, smoking, diet, oxidative stress, and chronic inflammation. Nitroxide drugs preventing aging-, smoking-, high sugar or high fat diet-, or radiation- and other environmental-induced pathophysiological conditions in aging disease are reviewed. Tempol (TP), Tempol Hydroxylamine (TP-H), and TP-H prodrug (OT-551) are evaluated in (1) non-smokers versus smokers with cutaneous microvascular dysfunction, rapidly reversed by cutaneous TP; (2) elderly cancer patients at risk for radiation-induced skin burns or hair loss, prevented by topical TP; and (3) elderly smoker or non-smoker AMD patients at risk for vision loss, prevented by daily eye drops of OT-551. The human data indicates safety and efficacy for these nitroxide drugs. Both TP and TP-H topically penetrate and function in skin or mucosa, protecting and treating radiation burns and hair loss or smoking-induced cutaneous vascular dysfunction. TP and TP-H do not penetrate the cornea, while OT-551 does effectively penetrate and travels to the back of the eye, preserving visual acuity and preserving normal and low light luminance in dry AMD smokers and non-smoker patients. Topical, oral, or injectable drug formulations are discussed.

  10. 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.

  11. 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.

  12. Breed- and age-related differences in canine mammary tumors.

    Science.gov (United States)

    Kim, Hyun-Woo; Lim, Ha-Young; Shin, Jong-Il; Seung, Byung-Joon; Ju, Jung-Hyung; Sur, Jung-Hyang

    2016-04-01

    Triple-negative breast cancer is a type of breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). It is an important and clinically relevant condition as it has a poor prognosis and is difficult to treat. Basal-like triple-negative cancer is highly prevalent in both African-Americans and adolescents. We therefore examined whether such a cancer likewise occurs in specific breeds and age groups in dogs, focusing on basal-like triple-negative cancer in particular. In this study, 181 samples from dogs with malignant mammary carcinoma from the 5 most common breeds and 2 age groups in Korea were analyzed. Histological classification and molecular subtyping, including assessment of immunohistochemical findings, were carried out. Twenty-five of 28 (89.3%) triple-negative carcinomas were identified as basal-like triple-negative carcinomas. Analysis of associations of classified factors revealed that the shih tzu breed (9/25, 36.0%) and advanced-age (19/25, 76.0%) groups were characterized by higher prevalence of basal-like triple-negative tumors with diverse histological types and of a higher grade. These results suggest that breed- and age-related differences can be identified in canine mammary carcinoma and, notably, in the shih tzu breed and at older ages. Further investigation of these distinguishing characteristics of the shih tzu breed is warranted.

  13. Oxidative Stress, Hypoxia, and Autophagy in the Neovascular Processes of Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Janusz Blasiak

    2014-01-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of severe and irreversible loss of vision in the elderly in developed countries. AMD is a complex chronic neurodegenerative disease associated with many environmental, lifestyle, and genetic factors. Oxidative stress and the production of reactive oxygen species (ROS seem to play a pivotal role in AMD pathogenesis. It is known that the macula receives the highest blood flow of any tissue in the body when related to size, and anything that can reduce the rich blood supply can cause hypoxia, malfunction, or disease. Oxidative stress can affect both the lipid rich retinal outer segment structure and the light processing in the macula. The response to oxidative stress involves several cellular defense reactions, for example, increases in antioxidant production and proteolysis of damaged proteins. The imbalance between production of damaged cellular components and degradation leads to the accumulation of detrimental products, for example, intracellular lipofuscin and extracellular drusen. Autophagy is a central lysosomal clearance system that may play an important role in AMD development. There are many anatomical changes in retinal pigment epithelium (RPE, Bruch’s membrane, and choriocapillaris in response to chronic oxidative stress, hypoxia, and disturbed autophagy and these are estimated to be crucial components in the pathology of neovascular processes in AMD.

  14. Oxidative stress, hypoxia, and autophagy in the neovascular processes of age-related macular degeneration.

    Science.gov (United States)

    Blasiak, Janusz; Petrovski, Goran; Veréb, Zoltán; Facskó, Andrea; Kaarniranta, Kai

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of severe and irreversible loss of vision in the elderly in developed countries. AMD is a complex chronic neurodegenerative disease associated with many environmental, lifestyle, and genetic factors. Oxidative stress and the production of reactive oxygen species (ROS) seem to play a pivotal role in AMD pathogenesis. It is known that the macula receives the highest blood flow of any tissue in the body when related to size, and anything that can reduce the rich blood supply can cause hypoxia, malfunction, or disease. Oxidative stress can affect both the lipid rich retinal outer segment structure and the light processing in the macula. The response to oxidative stress involves several cellular defense reactions, for example, increases in antioxidant production and proteolysis of damaged proteins. The imbalance between production of damaged cellular components and degradation leads to the accumulation of detrimental products, for example, intracellular lipofuscin and extracellular drusen. Autophagy is a central lysosomal clearance system that may play an important role in AMD development. There are many anatomical changes in retinal pigment epithelium (RPE), Bruch's membrane, and choriocapillaris in response to chronic oxidative stress, hypoxia, and disturbed autophagy and these are estimated to be crucial components in the pathology of neovascular processes in AMD.

  15. Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy.

    Science.gov (United States)

    Kovacs, Gabor G; Ferrer, Isidro; Grinberg, Lea T; Alafuzoff, Irina; Attems, Johannes; Budka, Herbert; Cairns, Nigel J; Crary, John F; Duyckaerts, Charles; Ghetti, Bernardino; Halliday, Glenda M; Ironside, James W; Love, Seth; Mackenzie, Ian R; Munoz, David G; Murray, Melissa E; Nelson, Peter T; Takahashi, Hitoshi; Trojanowski, John Q; Ansorge, Olaf; Arzberger, Thomas; Baborie, Atik; Beach, Thomas G; Bieniek, Kevin F; Bigio, Eileen H; Bodi, Istvan; Dugger, Brittany N; Feany, Mel; Gelpi, Ellen; Gentleman, Stephen M; Giaccone, Giorgio; Hatanpaa, Kimmo J; Heale, Richard; Hof, Patrick R; Hofer, Monika; Hortobágyi, Tibor; Jellinger, Kurt; Jicha, Gregory A; Ince, Paul; Kofler, Julia; Kövari, Enikö; Kril, Jillian J; Mann, David M; Matej, Radoslav; McKee, Ann C; McLean, Catriona; Milenkovic, Ivan; Montine, Thomas J; Murayama, Shigeo; Lee, Edward B; Rahimi, Jasmin; Rodriguez, Roberta D; Rozemüller, Annemieke; Schneider, Julie A; Schultz, Christian; Seeley, William; Seilhean, Danielle; Smith, Colin; Tagliavini, Fabrizio; Takao, Masaki; Thal, Dietmar Rudolf; Toledo, Jon B; Tolnay, Markus; Troncoso, Juan C; Vinters, Harry V; Weis, Serge; Wharton, Stephen B; White, Charles L; Wisniewski, Thomas; Woulfe, John M; Yamada, Masahito; Dickson, Dennis W

    2016-01-01

    Pathological accumulation of abnormally phosphorylated tau protein in astrocytes is a frequent, but poorly characterized feature of the aging brain. Its etiology is uncertain, but its presence is sufficiently ubiquitous to merit further characterization and classification, which may stimulate clinicopathological studies and research into its pathobiology. This paper aims to harmonize evaluation and nomenclature of aging-related tau astrogliopathy (ARTAG), a term that refers to a morphological spectrum of astroglial pathology detected by tau immunohistochemistry, especially with phosphorylation-dependent and 4R isoform-specific antibodies. ARTAG occurs mainly, but not exclusively, in individuals over 60 years of age. Tau-immunoreactive astrocytes in ARTAG include thorn-shaped astrocytes at the glia limitans and in white matter, as well as solitary or clustered astrocytes with perinuclear cytoplasmic tau immunoreactivity that extends into the astroglial processes as fine fibrillar or granular immunopositivity, typically in gray matter. Various forms of ARTAG may coexist in the same brain and might reflect different pathogenic processes. Based on morphology and anatomical distribution, ARTAG can be distinguished from primary tauopathies, but may be concurrent with primary tauopathies or other disorders. We recommend four steps for evaluation of ARTAG: (1) identification of five types based on the location of either morphologies of tau astrogliopathy: subpial, subependymal, perivascular, white matter, gray matter; (2) documentation of the regional involvement: medial temporal lobe, lobar (frontal, parietal, occipital, lateral temporal), subcortical, brainstem; (3) documentation of the severity of tau astrogliopathy; and (4) description of subregional involvement. Some types of ARTAG may underlie neurological symptoms; however, the clinical significance of ARTAG is currently uncertain and awaits further studies. The goal of this proposal is to raise awareness of

  16. Age-related decline in global form suppression.

    Science.gov (United States)

    Wiegand, Iris; Finke, Kathrin; Töllner, Thomas; Starman, Kornelija; Müller, Hermann J; Conci, Markus

    2015-12-01

    Visual selection of illusory 'Kanizsa' figures, an assembly of local elements that induce the percept of a whole object, is facilitated relative to configurations composed of the same local elements that do not induce a global form--an instance of 'global precedence' in visual processing. Selective attention, i.e., the ability to focus on relevant and ignore irrelevant information, declines with increasing age; however, how this deficit affects selection of global vs. local configurations remains unknown. On this background, the present study examined for age-related differences in a global-local task requiring selection of either a 'global' Kanizsa- or a 'local' non-Kanizsa configuration (in the presence of the respectively other configuration) by analyzing event-related lateralizations (ERLs). Behaviorally, older participants showed a more pronounced global-precedence effect. Electrophysiologically, this effect was accompanied by an early (150-225 ms) 'positivity posterior contralateral' (PPC), which was elicited for older, but not younger, participants, when the target was a non-Kanizsa configuration and the Kanizsa figure a distractor (rather than vice versa). In addition, timing differences in the subsequent (250-500 ms) posterior contralateral negativity (PCN) indicated that attentional resources were allocated faster to Kanizsa, as compared to non-Kanizsa, targets in both age groups, while the allocation of spatial attention seemed to be generally delayed in older relative to younger age. Our results suggest that the enhanced global-local asymmetry in the older age group originated from less effective suppression of global distracter forms on early processing stages--indicative of older observers having difficulties with disengaging from a global default selection mode and switching to the required local state of attentional resolution.

  17. Age-related loss of orexin/hypocretin neurons

    Science.gov (United States)

    Kessler, Brice A.; Stanley, Emily M.; Frederick-Duus, Danielle; Fadel, Jim

    2011-01-01

    Aging is associated with many physiological alterations—such as changes in sleep patterns, metabolism and food intake—suggestive of hypothalamic dysfunction, but the effects of senescence on specific hypothalamic nuclei and neuronal groups that mediate these alterations is unclear. The lateral hypothalamus and contiguous perifornical area (LH/PFA) contains several populations of neurons, including those that express the neuropeptides orexin (hypocretin) or melanin-concentrating hormone (MCH). Collectively, orexin and MCH neurons influence many integrative homeostatic processes related to wakefulness and energy balance. Here, we determined the effect of aging on numbers of orexin and MCH neurons in young adult (3–4 months) and old (26–28 months) Fisher 344/Brown Norway F1 hybrid rats. Aged rats exhibited a loss of greater than 40% of orexin-immunoreactive neurons in both the medial and lateral (relative to the fornix) sectors of the LH/PFA. MCH-immunoreactive neurons were also lost in aged rats, primarily in the medial LH/PFA. Neuronal loss in this area was not global as no change in cells immunoreactive for the pan-neuronal marker, NeuN, was observed in aged rats. Combined with other reports of altered receptor expression or behavioral responses to exogenously-administered neuropeptide, these data suggest that compromised orexin (and, perhaps, MCH) function is an important mediator of age-related homeostatic disturbances of hypothalamic origin. The orexin system may represent a crucial substrate linking homeostatic and cognitive dysfunction in aging, as well as a novel therapeutic target for pharmacological or genetic restoration approaches to preventing or ameliorating these disturbances. PMID:21262323

  18. 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.

  19. The burden of age-related macular degeneration.

    Science.gov (United States)

    Schmier, Jordana K; Jones, Mechelle L; Halpern, Michael T

    2006-01-01

    As age-related macular degeneration (AMD) becomes more prevalent as a result of longer life expectancy and the number of elderly people worldwide, it will become increasingly important to understand its potential health and economic impact for appropriate healthcare planning. This review identified published literature on costs and resource use associated with AMD. Despite the increasing prevalence of AMD, the worldwide burden of illness is unknown. Several studies of direct medical costs, both those associated with ophthalmic care and those associated with other care, have been conducted and have identified increased medical care associated with AMD. Direct non-medical costs include the cost for vision aids; while these costs may be substantial, they are difficult to quantify as no comprehensive sources track the distribution or use of vision aids. Because AMD is uncommon among people of working age, there is less concern regarding the impact of indirect (workplace) costs among AMD patients. However, indirect costs are incurred by caregivers who leave the workforce early or change their work patterns in order to provide assistance to AMD patients; the magnitude of caregiver-related costs is unknown. The cost effectiveness of some interventions for AMD has been explored. Supplementation with zinc and antioxidants for non-exudative (dry) AMD has been shown to result in an acceptable cost per QALY and is considered cost effective. Studies suggest that laser photocoagulation is cost effective but that photodynamic therapy with verteporfin appears to be cost effective only among patients with good visual acuity at baseline or when models extend longer than 5 years. Further research is needed to integrate the information on various components of AMD-related costs into a comprehensive burden of illness estimate and to evaluate basic utility assumptions in existing models.

  20. Systemic complement activation in age-related macular degeneration.

    Science.gov (United States)

    Scholl, Hendrik P N; Charbel Issa, Peter; Walier, Maja; Janzer, Stefanie; Pollok-Kopp, Beatrix; Börncke, Florian; Fritsche, Lars G; Chong, Ngaihang V; Fimmers, Rolf; Wienker, Thomas; Holz, Frank G; Weber, Bernhard H F; Oppermann, Martin

    2008-07-02

    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 (pAMD 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. Age related macular degeneration and drusen: neuroinflammation in the retina.

    Science.gov (United States)

    Buschini, Elisa; Piras, Antonio; Nuzzi, Raffaele; Vercelli, Alessandro

    2011-09-15

    Inflammation protects from dangerous stimuli, restoring normal tissue homeostasis. Inflammatory response in the nervous system ("neuroinflammation") has distinct features, which are shared in several diseases. The retina is an immune-privileged site, and the tight balance of immune reaction can be disrupted and lead to age-related macular disease (AMD) and to its peculiar sign, the druse. Excessive activation of inflammatory and immunological cascade with subsequent induction of damage, persistent activation of resident immune cells, accumulation of byproducts that exceeds the normal capacity of clearance giving origin to a chronic local inflammation, alterations in the activation of the complement system, infiltration of macrophages, T-lymphocytes and mast-cells from the bloodstream, participate in the mechanisms which originate the drusen. In addition, aging of the retina and AMD involve also para-inflammation, by which immune cells react to persistent stressful stimuli generating low-grade inflammation, aimed at restoring function and maintaining tissue homeostasis by varying the set point in relation to the new altered conditions. This mechanism is also seen in the normal aging retina, but, in the presence of noxious stimuli as in AMD, it can become chronic and have an adverse outcome. Finally, autophagy may provide new insights to understand AMD pathology, due to its contribution in the removal of defective proteins. Therefore, the AMD retina can represent a valuable model to study neuroinflammation, its mechanisms and therapy in a restricted and controllable environment. Targeting these pathways could represent a new way to treat and prevent both exudative and dry forms of AMD.

  2. 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.

  3. Wet age related macular degeneration management and follow-up.

    Science.gov (United States)

    Alexandru, Malciolu Radu; Alexandra, Nica Maria

    2016-01-01

    Age-related macular degeneration (AMD) is referred to as the leading cause of irreversible visual loss in developed countries, with a profound effect on the quality of life. The neovascular form of AMD is characterized by the formation of subretinal choroidal neovascularization, leading to sudden and severe visual loss. Research has identified the vascular endothelial growth factor (VEGF) as an important pathophysiological component in neovascular AMD and its intraocular inhibition as one of the most efficient therapies in medicine. The introduction of anti-VEGF as a standard treatment in wet AMD has led to a great improvement in the prognosis of patients, allowing recovery and maintenance of visual function in the vast majority of cases. However, the therapeutic benefit is accompanied by a difficulty in maintaining the treatment schedule due to the increase in the amount of patients, stress of monthly assessments, as well as the associated economic burden. Therefore, treatment strategies have evolved from fixed monthly dosing, to individualized regimens, aiming for comparable results, with fewer injections. One such protocol is called "pro re nata", or "treat and observe". Patients are given a loading dose of 3 monthly injections, followed by an as-needed decision to treat, based on the worsening of visual acuity, clinical evidence of the disease activity on fundoscopy, or OCT evidence of retinal thickening in the presence of intra or subretinal fluid. A different regimen is called "treat and extend", in which the interval between injections is gradually increased, once the disease stabilization is achieved. This paper aims to review the currently available anti-VEGF agents--bevacizumab, ranibizumab, aflibercept, and the aforementioned treatment strategies.

  4. Canine Models for Copper Homeostasis Disorders

    OpenAIRE

    Xiaoyan Wu; Leegwater, Peter A. J.; Hille Fieten

    2016-01-01

    Copper is an essential trace nutrient metal involved in a multitude of cellular processes. Hereditary defects in copper metabolism result in disorders with a severe clinical course such as Wilson disease and Menkes disease. In Wilson disease, copper accumulation leads to liver cirrhosis and neurological impairments. A lack in genotype-phenotype correlation in Wilson disease points toward the influence of environmental factors or modifying genes. In a number of Non-Wilsonian forms of copper me...

  5. 14-year incidence, progression, and visual morbidity of age-related maculopathy

    DEFF Research Database (Denmark)

    Hesgaard, Helena; Nielsen, Niels V; Vinding, Troels;

    2005-01-01

    To describe the 14-year incidence of age-related maculopathy (ARM) lesions and the related visual loss.......To describe the 14-year incidence of age-related maculopathy (ARM) lesions and the related visual loss....

  6. The impact of sleep on age-related sarcopenia: Possible connections and clinical implications.

    Science.gov (United States)

    Piovezan, Ronaldo D; Abucham, Julio; Dos Santos, Ronaldo Vagner Thomatieli; Mello, Marco Tulio; Tufik, Sergio; Poyares, Dalva

    2015-09-01

    Sarcopenia is a geriatric condition that comprises declined skeletal muscle mass, strength and function, leading to the risk of multiple adverse outcomes, including death. Its pathophysiology involves neuroendocrine and inflammatory factors, unfavorable nutritional habits and low physical activity. Sleep may play a role in muscle protein metabolism, although this hypothesis has not been studied extensively. Reductions in duration and quality of sleep and increases in prevalence of circadian rhythm and sleep disorders with age favor proteolysis, modify body composition and increase the risk of insulin resistance, all of which have been associated with sarcopenia. Data on the effects of age-related slow-wave sleep decline, circadian rhythm disruptions and obstructive sleep apnea (OSA) on hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary-gonadal (HPG), somatotropic axes, and glucose metabolism indicate that sleep disorder interventions may affect muscle loss. Recent research associating OSA with the risk of conditions closely related to the sarcopenia process, such as frailty and sleep quality impairment, indirectly suggest that sleep can influence skeletal muscle decline in the elderly. Several protein synthesis and degradation pathways are mediated by growth hormone (GH), insulin-like growth factor-1 (IGF-1), testosterone, cortisol and insulin, which act on the cellular and molecular levels to increase or reestablish muscle fiber, strength and function. Age-related sleep problems potentially interfere intracellularly by inhibiting anabolic hormone cascades and enhancing catabolic pathways in the skeletal muscle. Specific physical exercises combined or not with nutritional recommendations are the current treatment options for sarcopenia. Clinical studies testing exogenous administration of anabolic hormones have not yielded adequate safety profiles. Therapeutic approaches targeting sleep disturbances to normalize circadian rhythms and sleep homeostasis may

  7. 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

    2006-01-01

    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 of novel

  8. Influence of co-existed benzo[a]pyrene and copper on the cellular characteristics of Stenotrophomonas maltophilia during biodegradation and transformation.

    Science.gov (United States)

    Chen, Shuona; Yin, Hua; Ye, Jinshao; Peng, Hui; Liu, Zehua; Dang, Zhi; Chang, Jingjing

    2014-04-01

    Microbial remediation has been proposed as a promising technique to remove pollutions, however, its application has been hindered by the lack of understanding the mechanisms involved in contaminants conversion and the influence of pollutants on cellular characteristics. To address this problem, biodegradation and transformation of BaP-Cu(II) by Stenotrophomonas maltophilia, along with interactions of these pollutants with microbial cells through FCM assay were investigated. The results indicated that BaP and Cu(II) were rapidly removed by S. maltophilia on the 1st d, but only less than 10% BaP was broken down due to temporary store in cells, instead of being decomposed immediately. The key ATP enzymes in cells were then activated by BaP to promote bacteria to further decompose BaP. Stimulation of co-existed contaminants strengthened cell membrane permeability and altered cell structure, but a higher esterase activity and DNA in cells of S. maltophilia were still retained.

  9. Synthesis, DNA binding, cellular DNA lesion and cytotoxicity of a series of new benzimidazole-based Schiff base copper(II) complexes.

    Science.gov (United States)

    Paul, Anup; Anbu, Sellamuthu; Sharma, Gunjan; Kuznetsov, Maxim L; Koch, Biplob; Guedes da Silva, M Fátima C; Pombeiro, Armando J L

    2015-12-14

    A series of new benzimidazole containing compounds 2-((1-R-1-H-benzimidazol-2-yl)phenyl-imino)naphthol HL(1-3) (R = methyl, ethyl or propyl, respectively) have been synthesized by Schiff base condensation of 2-(1-R-1-H-benzo[d]imidazol-2-yl)aniline and 2-hydroxy-1-naphthaldehyde. The reactions of HL(1-3) with Cu(NO3)2·2.5H2O led to the corresponding copper(II) complexes [Cu(L)(NO3)] 1-3. All the compounds were characterized by conventional analytical techniques and, for 1 and 3, also by single-crystal X-ray analysis. The interactions of complexes 1-3 with calf thymus DNA were studied by absorption and fluorescence spectroscopic techniques and the calculated binding constants (K(b)) are in the range of 3.5 × 10(5) M(-1)-3.2 × 10(5) M(-1). Complexes 1-3 effectively bind DNA through an intercalative mode, as proved by molecular docking studies. The binding affinity of the complexes decreases with the size increase of the N-alkyl substituent, in the order of 1 > 2 > 3, which is also in accord with the calculated LUMO(complex) energies. They show substantial in vitro cytotoxic effect against human lung (A-549), breast (MDA-MB-231) and cervical (HeLa) cancer cell lines. Complex 1 exhibits a significant inhibitory effect on the proliferation of the A-549 cancer cells. The antiproliferative efficacy of 1 has also been analysed by a DNA fragmentation assay, fluorescence activated cell sorting (FACS) and nuclear morphology using a fluorescence microscope. The possible mode for the apoptosis pathway of 1 has also been evaluated by a reactive oxygen species (ROS) generation study.

  10. Oxidative stress, innate immunity, and age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Wei Fan

    2016-05-01

    Full Text Available 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

  11. 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

    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

  12. Influence of Age-Related Versus Non-Age-Related Renal Dysfunctionon Survival in Patients with Left Ventricular Dysfunction

    Science.gov (United States)

    Testani, Jeffrey M.; Brisco, Meredith A.; Han, Gang; Laur, Olga; Kula, Alexander J.; Cheng, Susan J.; Tang, W. H. Wilson; Parikh, Chirag R.

    2013-01-01

    Normal aging results in a predictable decline in glomerular filtration rate (GFR) and low GFR is associated with worsened survival. If this survival disadvantage is directly caused by the low GFR, as opposed to the disease causing the low GFR, the risk should be similar regardless of the underlying mechanism. Our objective was to determine if age related declines in estimated GFR (eGFR) carry the same prognostic importance as disease attributable losses in patients with ventricular dysfunction. We analyzed the Studies Of Left Ventricular Dysfunction (SOLVD) limited data set (n=6337). The primary analysis focused on determining if the eGFR mortality relationship differed by the extent the eGFR was consistent with normal ageing. Mean eGFR was 65.7 ± 19.0ml/min/1.73m2. Across the range of age in the population (27 to 80 years), baseline eGFR decreased by 0.67 ml/min/1.73m2 per year (95% CI 0.63 to 0.71). The risk of death associated with eGFR was strongly modified by the degree to which the low eGFR could be explained by aging (p interaction <0.0001). For example, in a model incorporating the interaction, uncorrected eGFR was no longer significantly related to mortality (adjusted HR=1.0 per 10 ml/min/1.73m2, 95% CI 0.97–1.1, p=0.53) whereas a disease attributable decrease in eGFR above the median carried significant risk (adjusted HR=2.8, 95% CI 1.6–4.7, p<0.001). In conclusion, in the setting of LV dysfunction, renal dysfunction attributable to normal aging had a limited risk for mortality, suggesting that the mechanism underlying renal dysfunction is critical in determining prognosis. PMID:24216124

  13. The copper metallome in prokaryotic cells.

    Science.gov (United States)

    Rensing, Christopher; McDevitt, Sylvia Franke

    2013-01-01

    As a trace element copper has an important role in cellular function like many other transition metals. Its ability to undergo redox changes [Cu(I) ↔ Cu(II)] makes copper an ideal cofactor in enzymes catalyzing electron transfers. However, this redox change makes copper dangerous for a cell since it is able to be involved in Fenton-like reactions creating reactive oxygen species (ROS). Cu(I) also is a strong soft metal and can attack and destroy iron-sulfur clusters thereby releasing iron which can in turn cause oxidative stress. Therefore, copper homeostasis has to be highly balanced to ensure proper cellular function while avoiding cell damage.Throughout evolution bacteria and archaea have developed a highly regulated balance in copper metabolism. While for many prokaryotes copper uptake seems to be unspecific, others have developed highly sophisticated uptake mechanisms to ensure the availability of sufficient amounts of copper. Within the cytoplasm copper is sequestered by various proteins and molecules, including specific copper chaperones, to prevent cellular damage. Copper-containing proteins are usually located in the cytoplasmic membrane with the catalytic domain facing the periplasm, in the periplasm of Gram-negative bacteria, or they are secreted, limiting the necessity of copper to accumulate in the cytoplasm. To prevent cellular damage due to excess copper, bacteria and archaea have developed various copper detoxification strategies. In this chapter we attempt to give an overview of the mechanisms employed by bacteria and archaea to handle copper and the importance of the metal for cellular function as well as in the global nutrient cycle.

  14. Vision rehabilitation for age-related macular degeneration.

    Science.gov (United States)

    Park, W

    1999-01-01

    Though the numbers of patients with ARMD are high, associated referrals for vision rehabilitation are not. Practitioners need to refer patients with age-related maculopathy when medical and surgical treatment are no longer possible, and patients need to be educated to that fact. The impact of improving activities of daily living may be monumental and benefits society as a whole. People who are visually impaired are often ill-prepared to deal with the substantial adjustment involved, further stressing their entire support system. It may not be safe for visual and systemic reasons for older adults to cook, clean, and maintain their home. Poor vision contributes to the already increased risk of falls and subsequent fractures in these patients. Individuals who may have already been told they can no longer drive now face the possibility of being unable to live in their houses. Their independence may be threatened dramatically and abruptly. All these circumstances contribute to anxiety and depression. Patients with ARMD need to be educated about their disease process (teaching that can never be assumed to have been initiated). They need to be educated that they will not go completely blind and that, with assistance, they can accomplish a great deal. With today's technology, it is not difficult to help visually impaired individuals with ARMD, unless they are not referred or lack motivation. The primary complaint of an individual with ARMD is recognition of central detail. This affects all activities of daily living, and patient performance is subject to the duration and severity of the disease (including the size, density, and location of the central scotoma) and to their understanding of the disease. Rubin and coworkers, found that slow reading performance of patients with a dense central scotoma might reflect inherent limitations of peripheral retina for complex visual tasks. ARMD in most cases lends itself to magnification that enlarges the object beyond the blind spot

  15. Copper hypersensitivity.

    Science.gov (United States)

    Fage, Simon W; Faurschou, Annesofie; Thyssen, Jacob P

    2014-10-01

    The world production of copper is steadily increasing. Although humans are widely exposed to copper-containing items on the skin and mucosa, allergic reactions to copper are only infrequently reported. To review the chemistry, biology and accessible data to clarify the implications of copper hypersensitivity, a database search of PubMed was performed with the following terms: copper, dermatitis, allergic contact dermatitis, contact hypersensitivity, contact sensitization, contact allergy, patch test, dental, IUD, epidemiology, clinical, and experimental. Human exposure to copper is relatively common. As a metal, it possesses many of the same qualities as nickel, which is a known strong sensitizer. Cumulative data on subjects with presumed related symptoms and/or suspected exposure showed that a weighted average of 3.8% had a positive patch test reaction to copper. We conclude that copper is a very weak sensitizer as compared with other metal compounds. However, in a few and selected cases, copper can result in clinically relevant allergic reactions.

  16. Membrane lipid rafts and neurobiology: age-related changes in membrane lipids and loss of neuronal function.

    Science.gov (United States)

    Egawa, Junji; Pearn, Matthew L; Lemkuil, Brian P; Patel, Piyush M; Head, Brian P

    2016-08-15

    A better understanding of the cellular physiological role that plasma membrane lipids, fatty acids and sterols play in various cellular systems may yield more insight into how cellular and whole organ function is altered during the ageing process. Membrane lipid rafts (MLRs) within the plasma membrane of most cells serve as key organizers of intracellular signalling and tethering points of cytoskeletal components. MLRs are plasmalemmal microdomains enriched in sphingolipids, cholesterol and scaffolding proteins; they serve as a platform for signal transduction, cytoskeletal organization and vesicular trafficking. Within MLRs are the scaffolding and cholesterol binding proteins named caveolin (Cav). Cavs not only organize a multitude of receptors including neurotransmitter receptors (NMDA and AMPA receptors), signalling proteins that regulate the production of cAMP (G protein-coupled receptors, adenylyl cyclases, phosphodiesterases (PDEs)), and receptor tyrosine kinases involved in growth (Trk), but also interact with components that modulate actin and tubulin cytoskeletal dynamics (e.g. RhoGTPases and actin binding proteins). MLRs are essential for the regulation of the physiology of organs such as the brain, and age-related loss of cholesterol from the plasma membrane leads to loss of MLRs, decreased presynaptic vesicle fusion, and changes in neurotransmitter release, all of which contribute to different forms of neurodegeneration. Thus, MLRs provide an active membrane domain that tethers and reorganizes the cytoskeletal machinery necessary for membrane and cellular repair, and genetic interventions that restore MLRs to normal cellular levels may be exploited as potential therapeutic means to reverse the ageing and neurodegenerative processes.

  17. Cellular senescence and the aging brain.

    Science.gov (United States)

    Chinta, Shankar J; Woods, Georgia; Rane, Anand; Demaria, Marco; Campisi, Judith; Andersen, Julie K

    2015-08-01

    Cellular senescence is a potent anti-cancer mechanism that arrests the proliferation of mitotically competent cells to prevent malignant transformation. Senescent cells accumulate with age in a variety of human and mouse tissues where they express a complex 'senescence-associated secretory phenotype' (SASP). The SASP includes many pro-inflammatory cytokines, chemokines, growth factors and proteases that have the potential to cause or exacerbate age-related pathology, both degenerative and hyperplastic. While cellular senescence in peripheral tissues has recently been linked to a number of age-related pathologies, its involvement in brain aging is just beginning to be explored. Recent data generated by several laboratories suggest that both aging and age-related neurodegenerative diseases are accompanied by an increase in SASP-expressing senescent cells of non-neuronal origin in the brain. Moreover, this increase correlates with neurodegeneration. Senescent cells in the brain could therefore constitute novel therapeutic targets for treating age-related neuropathologies.

  18. 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.

  19. Mitochondrial superoxide in osteocytes perturbs canalicular networks in the setting of age-related osteoporosis.

    Science.gov (United States)

    Kobayashi, Keiji; Nojiri, Hidetoshi; Saita, Yoshitomo; Morikawa, Daichi; Ozawa, Yusuke; Watanabe, Kenji; Koike, Masato; Asou, Yoshinori; Shirasawa, Takuji; Yokote, Koutaro; Kaneko, Kazuo; Shimizu, Takahiko

    2015-03-16

    Osteocytes are major bone cells that play a crucial role in maintaining the quality of and healing damage to bone tissue. The number of living osteocytes and canalicular networks declines in an age-dependent manner. However, the pathological effects of mitochondrial redox imbalances on osteocytes and bone metabolism have not been fully elucidated. We generated mice lacking mitochondrial superoxide dismutase 2 (Sod2) in osteocytes. Like an aged bone, Sod2 depletion in the osteocytes positively enhanced the production of cellular superoxide in vivo. A bone morphological analysis demonstrated that the Sod2-deficient femurs showed remarkable bone loss in an age-dependent manner. Interestingly, Sod2 loss induced markedly disorganized osteocytic canalicular networks and decreased the number of live osteocytes. Furthermore, Sod2 deficiency significantly suppressed bone formation and increased bone resorption concomitant with the upregulation of sclerostin and receptor activator of NF-κB ligand (RANKL). In vitro experiments also revealed that treatment with paraquat, a superoxide inducer in mitochondria, promoted the RANKL expression via, in part, ERK phosphorylation. These findings demonstrate that the mitochondrial superoxide induced in osteocytes by Sod2 ablation causes age-related bone loss due to the impairment of canalicular networks and bone metabolism via the deregulation of the sclerostin and RANKL expression.

  20. Copper transport.

    Science.gov (United States)

    Linder, M C; Wooten, L; Cerveza, P; Cotton, S; Shulze, R; Lomeli, N

    1998-05-01

    In adult humans, the net absorption of dietary copper is approximately 1 mg/d. Dietary copper joins some 4-5 mg of endogenous copper flowing into the gastrointestinal tract through various digestive juices. Most of this copper returns to the circulation and to the tissues (including liver) that formed them. Much lower amounts of copper flow into and out of other major parts of the body (including heart, skeletal muscle, and brain). Newly absorbed copper is transported to body tissues in two phases, borne primarily by plasma protein carriers (albumin, transcuprein, and ceruloplasmin). In the first phase, copper goes from the intestine to the liver and kidney; in the second phase, copper usually goes from the liver (and perhaps also the kidney) to other organs. Ceruloplasmin plays a role in this second phase. Alternatively, liver copper can also exit via the bile, and in a form that is less easily reabsorbed. Copper is also present in and transported by other body fluids, including those bathing the brain and central nervous system and surrounding the fetus in the amniotic sac. Ceruloplasmin is present in these fluids and may also be involved in copper transport there. The concentrations of copper and ceruloplasmin in milk vary with lactational stage. Parallel changes occur in ceruloplasmin messenger RNA expression in the mammary gland (as determined in pigs). Copper in milk ceruloplasmin appears to be particularly available for absorption, at least in rats.

  1. Copper hypersensitivity

    DEFF Research Database (Denmark)

    Fage, Simon W; Faurschou, Annesofie; Thyssen, Jacob P

    2014-01-01

    hypersensitivity, a database search of PubMed was performed with the following terms: copper, dermatitis, allergic contact dermatitis, contact hypersensitivity, contact sensitization, contact allergy, patch test, dental, IUD, epidemiology, clinical, and experimental. Human exposure to copper is relatively common...

  2. Trace elements in human physiology and pathology. Copper.

    Science.gov (United States)

    Tapiero, H; Townsend, D M; Tew, K D

    2003-11-01

    Copper is a trace element, important for the function of many cellular enzymes. Copper ions can adopt distinct redox states oxidized Cu(II) or reduced (I), allowing the metal to play a pivotal role in cell physiology as a catalytic cofactor in the redox chemistry of enzymes, mitochondrial respiration, iron absorption, free radical scavenging and elastin cross-linking. If present in excess, free copper ions can cause damage to cellular components and a delicate balance between the uptake and efflux of copper ions determines the amount of cellular copper. In biological systems, copper homeostasis has been characterized at the molecular level. It is coordinated by several proteins such as glutathione, metallothionein, Cu-transporting P-type ATPases, Menkes and Wilson proteins and by cytoplasmic transport proteins called copper chaperones to ensure that it is delivered to specific subcellular compartments and thereby to copper-requiring proteins.

  3. Age-related regulation of genes: slow homeostatic changes and age-dimension technology

    Science.gov (United States)

    Kurachi, Kotoku; Zhang, Kezhong; Huo, Jeffrey; Ameri, Afshin; Kuwahara, Mitsuhiro; Fontaine, Jean-Marc; Yamamoto, Kei; Kurachi, Sumiko

    2002-11-01

    Through systematic studies of pro- and anti-blood coagulation factors, we have determined molecular mechanisms involving two genetic elements, age-related stability element (ASE), GAGGAAG and age-related increase element (AIE), a unique stretch of dinucleotide repeats (AIE). ASE and AIE are essential for age-related patterns of stable and increased gene expression patterns, respectively. Such age-related gene regulatory mechanisms are also critical for explaining homeostasis in various physiological reactions as well as slow homeostatic changes in them. The age-related increase expression of the human factor IX (hFIX) gene requires the presence of both ASE and AIE, which apparently function additively. The anti-coagulant factor protein C (hPC) gene uses an ASE (CAGGAG) to produce age-related stable expression. Both ASE sequences (G/CAGAAG) share consensus sequence of the transcriptional factor PEA-3 element. No other similar sequences, including another PEA-3 consensus sequence, GAGGATG, function in conferring age-related gene regulation. The age-regulatory mechanisms involving ASE and AIE apparently function universally with different genes and across different animal species. These findings have led us to develop a new field of research and applications, which we named “age-dimension technology (ADT)”. ADT has exciting potential for modifying age-related expression of genes as well as associated physiological processes, and developing novel, more effective prophylaxis or treatments for age-related diseases.

  4. Comparative study of oxidative stress in individuals with and without age related hearing loss

    Directory of Open Access Journals (Sweden)

    Vineeth VK

    2015-08-01

    Conclusion: We found an association between the level of Glutathione and Super Oxide Dismutase in age related hearing loss. Thus the serum Glutathione and Super Oxide Dismutase level can be used as a biomarker for the assessment of age related hearing loss. [Int J Res Med Sci 2015; 3(8.000: 2020-2023

  5. Mechanistically linking age-related diseases and dietary carbohydrate via autophagy and the ubiquitin proteolytic systems

    Science.gov (United States)

    Epidemiological data indicate that consuming diets that deliver sugar to the blood rapidly (called high glycemic index, GI) is associated with enhanced risk for age-related diseases such as cardiovascular disease, type 2 diabetes, cataract and age-related macular degeneration (AMD). These debilities...

  6. Experience-Based Mitigation of Age-Related Performance Declines: Evidence from Air Traffic Control

    Science.gov (United States)

    Nunes, Ashley; Kramer, Arthur F.

    2009-01-01

    Previous research has found age-related deficits in a variety of cognitive processes. However, some studies have demonstrated age-related sparing on tasks where individuals have substantial experience, often attained over many decades. Here, the authors examined whether decades of experience in a fast-paced demanding profession, air traffic…

  7. Quality of Life and Health Economic Assessments of Age-Related Macular Degeneration

    OpenAIRE

    Covert, D.; Berdeaux, G; Mitchell, J; Bradley, Clare; Barnes, R.

    2007-01-01

    In this article, we review measures of patient-reported outcomes that can show whether a treatment for age-related macular degeneration also provides patient-perceived benefits. In addition, we look at health economic measurements currently being used to develop cost-effectiveness models for age-related macular degeneration.

  8. 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 ...

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

    Science.gov (United States)

    Damico, Francisco Max; Gasparin, Fabio; Scolari, Mariana Ramos; Pedral, Lycia Sampaio; Takahashi, Beatriz Sayuri

    2012-01-01

    Emerging treatments for dry age-related macular degeneration (AMD) and geographic 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.

  10. The stereotypical molecular cascade in neovascular age-related macular degeneration: the role of dynamic reciprocity.

    Science.gov (United States)

    Kent, D

    2015-11-01

    This review summarises our current understanding of the molecular basis of subretinal neovascularisation (SRNV) in age-related macular degeneration (AMD). The term neovascular AMD (NVAMD) is derived from the dominant early clinical features of haemorrhage, fluid, and lipid in the subretinal space (SRS) and the historical role of fluorescein angiography in detecting the presence of NV tissue. However, at the cellular level, SRNV resembles an aberrant but stereotypical tissue repair response that incorporates both an early inflammatory phase and a late fibrotic phase in addition to the neovascular (NV) component that dominates the early clinical presentation. This review will seek not only to highlight the important molecules involved in each of these components but to demonstrate that the development of SRNV has its origins in the earliest events in non-NV AMD pathogenesis. Current evidence suggests that this early-stage pathogenesis is characterised by complement-mediated immune dysregulation, leading to a state of chronic inflammation in the retinal pigment epithelium/Bruch's membrane/choriocapillaris complex. These initial events can be seamlessly and inextricably linked to late-stage development of SRNV in AMD by the process of dynamic reciprocity (DyR), the ongoing bidirectional communication between cells, and their surrounding matrix. Moreover, this correlation between disease onset and eventual outcome is reflected in the temporal and spatial correlation between chronic inflammation, NV, and fibrosis within the reparative microenvironment of the SRS. In summary, the downstream consequences of the earliest dysfunctional molecular events in AMD can result in the late-stage entity we recognize clinically as SRNV and is characterized by a spectrum of predictable, related, and stereotypical processes referred to as DyR.

  11. Identifying microRNAs involved in degeneration of the organ of corti during age-related hearing loss.

    Directory of Open Access Journals (Sweden)

    Qian Zhang

    Full Text Available MicroRNAs (miRNAs, a class of short non-coding RNAs that regulate the expression of mRNA targets, are important regulators of cellular senescence and aging. We questioned which miRNAs are involved in age-related degeneration of the organ of Corti (OC, the auditory sensory epithelium that transduces mechanical stimuli to electrical activity in the inner ear. Degeneration of the OC is generally accepted as the main cause of age-related hearing loss (ARHL, a progressive loss of hearing in individuals as they grow older. To determine which miRNAs are involved in the onset and progression of ARHL, miRNA gene expression in the OC of two mouse strains, C57BL/6J and CBA/J, was compared at three different ages using GeneChip miRNA microarray and was validated by real-time PCR. We showed that 111 and 71 miRNAs exhibited differential expression in the C57 and CBA mice, respectively, and that downregulated miRNAs substantially outnumbered upregulated miRNAs during aging. miRNAs that had approximately 2-fold upregulation included members of miR-29 family and miR-34 family, which are known regulators of pro-apoptotic pathways. In contrast, miRNAs that were downregulated by about 2-fold were members of the miR-181 family and miR-183 family, which are known to be important for proliferation and differentiation, respectively. The shift of miRNA expression favoring apoptosis occurred earlier than detectable hearing threshold elevation and hair cell loss. Our study suggests that changes in miRNA expression precede morphological and functional changes, and that upregulation of pro-apoptotic miRNAs and downregulation of miRNAs promoting proliferation and differentiation are both involved in age-related degeneration of the OC.

  12. Age-related variations of visuo-motor adaptation beyond explicit knowledge

    Directory of Open Access Journals (Sweden)

    Herbert eHeuer

    2014-07-01

    Full Text Available Visuo-motor adaptation suffers at older working age. The age-related decline of behavioural adjustments is accompanied by reduced explicit knowledge of the visuo-motor transformation. It disappears when explicit knowledge is kept constant across the age range, except for particularly high levels of explicit knowledge. According to these findings, at older adult age both the acquisition of explicit knowledge and its application for strategic corrections become poorer. Recently it has been posited that visuo-motor adaptation can involve model-free reinforcement mechanisms of learning in addition to model-based mechanisms. We tested whether age-related declines of reinforcement learning can also contribute to the age-related changes of visuo-motor adaptation. Therefore we enhanced the contribution of reinforcement learning to visuo-motor adaptation by way of introducing salient markers of success and failure during practice. With such modified practice conditions, there were residual age-related variations of behavioural adjustments at all levels of explicit knowledge, even when explicit knowledge was absent. The residual age-related variations were observed for practiced target directions only, but not for new target directions. These findings are consistent with an age-related decline of model-free reinforcement learning as a third factor in the age-related decline of visuo-motor adaptation. Under practice conditions, which spur model-free reward-based learning, this factor adds to the decrements of the acquisition of explicit knowledge and its use for strategic corrections.

  13. Role of antioxidant enzymes and small molecular weight antioxidants in the pathogenesis of age-related macular degeneration (AMD).

    Science.gov (United States)

    Tokarz, Paulina; Kaarniranta, Kai; Blasiak, Janusz

    2013-10-01

    Cells in aerobic condition are constantly exposed to reactive oxygen species (ROS), which may induce damage to biomolecules, including proteins, nucleic acids and lipids. In normal circumstances, the amount of ROS is counterbalanced by cellular antioxidant defence, with its main components-antioxidant enzymes, DNA repair and small molecular weight antioxidants. An imbalance between the production and neutralization of ROS by antioxidant defence is associated with oxidative stress, which plays an important role in the pathogenesis of many age-related and degenerative diseases, including age-related macular degeneration (AMD), affecting the macula-the central part of the retina. The retina is especially prone to oxidative stress due to high oxygen pressure and exposure to UV and blue light promoting ROS generation. Because oxidative stress has an established role in AMD pathogenesis, proper functioning of antioxidant defence may be crucial for the occurrence and progression of this disease. Antioxidant enzymes play a major role in ROS scavenging and changes of their expression or/and activity are reported to be associated with AMD. Therefore, the enzymes in the retina along with their genes may constitute a perspective target in AMD prevention and therapy.

  14. Mitochondrial decay in ageing: 'Qi-invigorating' schisandrin B as a hormetic agent for mitigating age-related diseases.

    Science.gov (United States)

    Leong, Pou K; Chen, Na; Ko, Kam M

    2012-03-01

    1. The mitochondrial free radical theory of ageing (MFRTA) proposes a primary role for mitochondrial reactive oxygen species (ROS) in the ageing process. The reductive hot spot hypothesis of mammalian ageing serves as a supplement to the MFRTA by explaining how the relatively few cells that have lost oxidative phosphorylation capacity due to mitochondrial DNA mutations can be toxic to the rest of the body and result in the development of age-related diseases. 2. Schisandrin B (SchB), which can induce both a glutathione anti-oxidant and a heat shock response via redox-sensitive signalling pathways, is a hormetic agent potentially useful for increasing the resistance of tissues to oxidative damage. The enhanced cellular/mitochondrial anti-oxidant status and heat shock response afforded by SchB can preserve the structural and functional integrity of mitochondria, suggesting a potential role for SchB in ameliorating age-related diseases. 3. Future studies will focus on investigating whether SchB can produce the hormetic response in humans.

  15. 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

  16. Progress and perspectives on the role of RPE cell inflammatory responses in the development of age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Suofu Qin

    2008-12-01

    Full Text Available Suofu Qin, Gerard A RodriguesRetinal Disease Research, Department of Biological Sciences, Allergan, Inc., Irvine, CA, USAAbstract: Age-related macular degeneration (AMD is the leading cause of blindness in developed countries. The etiology of AMD remains poorly understood and no treatment is currently available for the atrophic form of AMD. Atrophic AMD has been proposed to involve abnormalities of the retinal pigment epithelium (RPE, which lies beneath the photoreceptor cells and normally provides critical metabolic support to these light-sensing cells. Cumulative oxidative stress and local inflammation are thought to represent pathological processes involved in the etiology of atrophic AMD. Studies of tissue culture and animal models reveal that oxidative stress-induced injury to the RPE results in a chronic inflammatory response, drusen formation, and RPE atrophy. RPE degeneration in turn causes a progressive degeneration of photoreceptors, leading to the irreversible loss of vision. This review describes some of the potential major molecular and cellular events contributing to RPE death and inflammatory responses. In addition, potential target areas for therapeutic intervention will be discussed and new experimental therapeutic strategies for atrophic AMD will be presented.Keywords: age-related macular degeneration, danger signals, complement, inflammation, retinal pigment epithelial cells

  17. Drugs, nutrients, and phytoactive principles improving the health span of rodent models of human age-related diseases.

    Science.gov (United States)

    Lebel, Michel; Picard, Frédéric; Ferland, Guylaine; Gaudreau, Pierrette

    2012-02-01

    Rodents are often the species of choice to examine the effect of drugs on survival and on the progression of specific diseased tissues. This statement is also true for research laboratories working in the field of nutrition and aging. In addition to diets that can reduce the life expectancy of rodents, such as diabetogenic or high-fat diets, genetically modified rodents exhibiting different accelerated age-associated diseases also provide important biologic tools to decipher the impact of drugs, nutrients, or phytoactive compounds on their health and life span. This review covers some of the chemicals believed to decelerate the appearance of age-related diseases in different rodent models. Such chemicals include antioxidants, anti-inflammatory molecules, modulators of metabolic sensors, calorie restriction mimetics, and vegetal polyphenolic compounds that affect mitochondrial functions, cellular proliferation or differentiation as well as cell functionality.

  18. Biosorption of copper and zinc by immobilised and free algal biomass, and the effects of metal biosorption on the growth and cellular structure of Chlorella sp.and Chlamydomonas sp.isolated from rivers in Penang, Malaysia

    Institute of Scientific and Technical Information of China (English)

    W.O.Wan Maznah; A.T. Al-Fawwaz; Misni Surif

    2012-01-01

    In this study,the biosorption of copper and zinc ions by Chlorella sp.and Chlamydomonas sp.isolated from local environments in Malaysia was investigated in a batch system and by microscopic analyses.Under optimal biosorption conditions,the biosorption capacity of Chlorella sp.for copper and zinc ions was 33.4 and 28.5 mg/g,respectively,after 6 hr of biosorption in an immobilised system.Batch experiments showed that the biosorption capacity of algal biomass immobilised in the form of sodium alginate beads was higher than that of the free biomass.Scanning electron microscopy and energy-dispersive X-ray spectroscopy analyses revealed that copper and zinc were mainly sorbed at the cell surface during biosorption.Exposure to 5 mg/L of copper and zinc affected both the chlorophyll content and cell count of the algal cells after the first 12 hr of contact time.

  19. Biosorption of copper and zinc by immobilised and free algal biomass, and the effects of metal biosorption on the growth and cellular structure of Chlorella sp. and Chlamydomonas sp. isolated from rivers in Penang, Malaysia.

    Science.gov (United States)

    Maznah, W O Wan; Al-Fawwaz, A T; Surif, Misni

    2012-01-01

    In this study, the biosorption of copper and zinc ions by Chlorella sp. and Chlamydomonas sp. isolated from local environments in Malaysia was investigated in a batch system and by microscopic analyses. Under optimal biosorption conditions, the biosorption capacity of Chlorella sp. for copper and zinc ions was 33.4 and 28.5 mg/g, respectively, after 6 hr of biosorption in an immobilised system. Batch experiments showed that the biosorption capacity of algal biomass immobilised in the form of sodium alginate beads was higher than that of the free biomass. Scanning electron microscopy and energy-dispersive X-ray spectroscopy analyses revealed that copper and zinc were mainly sorbed at the cell surface during biosorption. Exposure to 5 mg/L of copper and zinc affected both the chlorophyll content and cell count of the algal cells after the first 12 hr of contact time.

  20. A Plasmodium falciparum copper-binding membrane protein with copper transport motifs

    Directory of Open Access Journals (Sweden)

    Choveaux David L

    2012-11-01

    Full Text Available Abstract Background Copper is an essential catalytic co-factor for metabolically important cellular enzymes, such as cytochrome-c oxidase. Eukaryotic cells acquire copper through a copper transport protein and distribute intracellular copper using molecular chaperones. The copper chelator, neocuproine, inhibits Plasmodium falciparum ring-to-trophozoite transition in vitro, indicating a copper requirement for malaria parasite development. How the malaria parasite acquires or secretes copper still remains to be fully elucidated. Methods PlasmoDB was searched for sequences corresponding to candidate P. falciparum copper-requiring proteins. The amino terminal domain of a putative P. falciparum copper transport protein was cloned and expressed as a maltose binding fusion protein. The copper binding ability of this protein was examined. Copper transport protein-specific anti-peptide antibodies were generated in chickens and used to establish native protein localization in P. falciparum parasites by immunofluorescence microscopy. Results Six P. falciparum copper-requiring protein orthologs and a candidate P. falciparum copper transport protein (PF14_0369, containing characteristic copper transport protein features, were identified in PlasmoDB. The recombinant amino terminal domain of the transport protein bound reduced copper in vitro and within Escherichia coli cells during recombinant expression. Immunolocalization studies tracked the copper binding protein translocating from the erythrocyte plasma membrane in early ring stage to a parasite membrane as the parasites developed to schizonts. The protein appears to be a PEXEL-negative membrane protein. Conclusion Plasmodium falciparum parasites express a native protein with copper transporter characteristics that binds copper in vitro. Localization of the protein to the erythrocyte and parasite plasma membranes could provide a mechanism for the delivery of novel anti-malarial compounds.

  1. Cellular automata

    CERN Document Server

    Codd, E F

    1968-01-01

    Cellular Automata presents the fundamental principles of homogeneous cellular systems. This book discusses the possibility of biochemical computers with self-reproducing capability.Organized into eight chapters, this book begins with an overview of some theorems dealing with conditions under which universal computation and construction can be exhibited in cellular spaces. This text then presents a design for a machine embedded in a cellular space or a machine that can compute all computable functions and construct a replica of itself in any accessible and sufficiently large region of t

  2. Validation of anti-aging drugs by treating age-related diseases.

    Science.gov (United States)

    Blagosklonny, Mikhail V

    2009-03-28

    Humans die from age-related diseases, which are deadly manifestations of the aging process. In order to extend life span, an anti-aging drug must delay age-related diseases. All together age-related diseases are the best biomarker of aging. Once a drug is used for treatment of any one chronic disease, its effect against other diseases (atherosclerosis, cancer, prostate enlargement, osteoporosis, insulin resistance, Alzheimer's and Parkinson's diseases, age-related macular degeneration) may be evaluated in the same group of patients. If the group is large, then the anti-aging effect could be validated in a couple of years. Startlingly, retrospective analysis of clinical and preclinical data reveals four potential anti-aging modalities.

  3. From mind wandering to involuntary retrieval: Age-related differences in spontaneous cognitive processes.

    Science.gov (United States)

    Maillet, David; Schacter, Daniel L

    2016-01-08

    The majority of studies that have investigated the effects of healthy aging on cognition have focused on age-related differences in voluntary and deliberately engaged cognitive processes. Yet many forms of cognition occur spontaneously, without any deliberate attempt at engaging them. In this article we review studies that have assessed age-related differences in four such types of spontaneous thought processes: mind-wandering, involuntary autobiographical memory, intrusive thoughts, and spontaneous prospective memory retrieval. These studies suggest that older adults exhibit a reduction in frequency of both mind-wandering and involuntary autobiographical memory, whereas findings regarding intrusive thoughts have been more mixed. Additionally, there is some preliminary evidence that spontaneous prospective memory retrieval may be relatively preserved in aging. We consider the roles of age-related differences in cognitive resources, motivation, current concerns and emotional regulation in accounting for these findings. We also consider age-related differences in the neural correlates of spontaneous cognitive processes.

  4. Blood pressure, atherosclerosis, and the incidence of age-related maculopathy: the Rotterdam Study

    NARCIS (Netherlands)

    R. van Leeuwen (Redmer); M.K. Ikram (Kamran); J.R. Vingerling (Hans); J.C.M. Witteman (Jacqueline); P.T.V.M. de Jong (Paulus); A. Hofman (Albert)

    2003-01-01

    textabstractPURPOSE: To determine whether blood pressure and subclinical atherosclerosis are associated with incident age-related maculopathy (ARM). METHODS: The study was performed within the Rotterdam Study, a population-based, prospective cohort study in Rotterdam, The Netherlan

  5. Verteporfin plus ranibizumab for choroidal neovascularization in age-related macular degeneration

    DEFF Research Database (Denmark)

    Larsen, Michael; Schmidt-Erfurth, Ursula; Lanzetta, Paolo;

    2012-01-01

    To compare the efficacy and safety of same-day verteporfin photodynamic therapy (PDT) and intravitreal ranibizumab combination treatment versus ranibizumab monotherapy in neovascular age-related macular degeneration....

  6. The Role of Copper Chaperone Atox1 in Coupling Redox Homeostasis to Intracellular Copper Distribution

    Science.gov (United States)

    Hatori, Yuta; Lutsenko, Svetlana

    2016-01-01

    Human antioxidant protein 1 (Atox1) is a small cytosolic protein with an essential role in copper homeostasis. Atox1 functions as a copper carrier facilitating copper transfer to the secretory pathway. This process is required for activation of copper dependent enzymes involved in neurotransmitter biosynthesis, iron efflux, neovascularization, wound healing, and regulation of blood pressure. Recently, new cellular roles for Atox1 have emerged. Changing levels of Atox1 were shown to modulate response to cancer therapies, contribute to inflammatory response, and protect cells against various oxidative stresses. It has also become apparent that the activity of Atox1 is tightly linked to the cellular redox status. In this review, we summarize biochemical information related to a dual role of Atox1 as a copper chaperone and an antioxidant. We discuss how these two activities could be linked and contribute to establishing the intracellular copper balance and functional identity of cells during differentiation. PMID:27472369

  7. Incidence of legal blindness from age-related macular degeneration in denmark: year 2000 to 2010

    DEFF Research Database (Denmark)

    Bloch, Sara Brandi; Larsen, Michael; Munch, Inger Christine

    2012-01-01

    To report incidence rates of legal blindness from age-related macular degeneration (AMD) and other causes in Denmark from years 2000 to 2010 in the age group at risk of AMD aged 50 years and older.......To report incidence rates of legal blindness from age-related macular degeneration (AMD) and other causes in Denmark from years 2000 to 2010 in the age group at risk of AMD aged 50 years and older....

  8. Moringa oleifera Mitigates Memory Impairment and Neurodegeneration in Animal Model of Age-Related Dementia

    OpenAIRE

    2013-01-01

    To date, the preventive strategy against dementia is still essential due to the rapid growth of its prevalence and the limited therapeutic efficacy. Based on the crucial role of oxidative stress in age-related dementia and the antioxidant and nootropic activities of Moringa oleifera, the enhancement of spatial memory and neuroprotection of M. oleifera leaves extract in animal model of age-related dementia was determined. The possible underlying mechanism was also investigated. Male Wistar rat...

  9. Update on Clinical Trials in Dry Age-related Macular Degeneration

    OpenAIRE

    Ibrahim Taskintuna; M.E. A. Abdalla Elsayed; Patrik Schatz

    2016-01-01

    This review article summarizes the most recent clinical trials for dry age.related macular degeneration (AMD), the most common cause of vision loss in the elderly in developed countries. A literature search through websites https://www.pubmed.org and https://www.clinicaltrials.gov/, both accessed no later than November 04, 2015, was performed. We identified three Phase III clinical trials that were completed over the recent 5 years Age.Related Eye Disease Study 2 (AREDS2), implantable miniatu...

  10. Comparison of life quality scores of ranibizumab-treated patients with age-related macular degeneration

    OpenAIRE

    Saadet Arslan; Merih Soylu; ilter Varinli

    2016-01-01

    Purpose: To evaluate the visual acuity, fluorescein angiography, optic coherence tomography and life quality of patients diagnosed with exudative age-related macular degeneration and administered with intravitreal Ranibizumab injection. Material and Methods: This study included of 48 different patients who were diagnosed as exudative age-related macular degeneration and administered with ranibizumab injection. In this study, demographic characteristics, pre- and post-injection corrected v...

  11. AGE-RELATED MACULAR DEGENERATION: CURRENT ASPECTS OF PATHOGENESIS AND TREATMENT

    Institute of Scientific and Technical Information of China (English)

    H; P; Heidenkummer

    1991-01-01

    About 1.1 million people are estimated to have age-related macular degeneration in West Germany. Anatomical aspects of the normal macula and physiological ageing processes in the retina will be discribed including alterations in the choroid, in Bruch's membrane, the pigment epithelium and the sensory retina. Risk factors for the development of age-related macular degeneration are age per se, perhaps ethnologic characteristics, ocular characteristics, and perhaps environmental factors. The histopathology...

  12. Multiple Brain Markers are Linked to Age-Related Variation in Cognition.

    Science.gov (United States)

    Hedden, Trey; Schultz, Aaron P; Rieckmann, Anna; Mormino, Elizabeth C; Johnson, Keith A; Sperling, Reisa A; Buckner, Randy L

    2016-04-01

    Age-related alterations in brain structure and function have been challenging to link to cognition due to potential overlapping influences of multiple neurobiological cascades. We examined multiple brain markers associated with age-related variation in cognition. Clinically normal older humans aged 65-90 from the Harvard Aging Brain Study (N = 186) were characterized on a priori magnetic resonance imaging markers of gray matter thickness and volume, white matter hyperintensities, fractional anisotropy (FA), resting-state functional connectivity, positron emission tomography markers of glucose metabolism and amyloid burden, and cognitive factors of processing speed, executive function, and episodic memory. Partial correlation and mediation analyses estimated age-related variance in cognition shared with individual brain markers and unique to each marker. The largest relationships linked FA and striatum volume to processing speed and executive function, and hippocampal volume to episodic memory. Of the age-related variance in cognition, 70-80% was accounted for by combining all brain markers (but only ∼20% of total variance). Age had significant indirect effects on cognition via brain markers, with significant markers varying across cognitive domains. These results suggest that most age-related variation in cognition is shared among multiple brain markers, but potential specificity between some brain markers and cognitive domains motivates additional study of age-related markers of neural health.

  13. Age-related changes in the macula. A histopathological study of fifty Indian donor eyes

    Directory of Open Access Journals (Sweden)

    Biswas Jyotirmay

    2002-01-01

    Full Text Available PURPOSE: Age-related macular degeneration (ARMD is clinically less common in India compared to the West. Therefore, clinicians are unfamiliar with histopathologic evidence of age-related macular changes in the Indian population. METHODS: Fifty consecutive human donor eyes removed for corneal grafting were studied for gross, microscopic and histochemical features of age-related changes in the macula in the Indian population. A horizontal block was cut from the globe including the optic disc, and the macula. Six sections, 6 microns thick, were cut from three levels in the macula at a distance of 140 microns. These were stained with haemotoxylin-eosin, periodic acid-Schiff, Mallory, Masson trichrome, alcian blue and von Kossa stains. The presence of basal laminar deposits, drusen and thickening and calcification of Bruch′s membrane in the macula were assessed at 400 x magnification using a modified version of Sark′s classification. RESULTS: Twenty-four donor eyes (48% had some form of age-related macular change. These included basal laminar deposits, hard drusen, soft drusen, extensive retinal pigment epithelium atrophy of the macula, and disciform degeneration of macula. A combination of changes was often seen. Age-related changes were more common in the seventh and eighth decade. CONCLUSION: Our study shows that histological changes characteristic of the early stages of age-related macular degeneration are fairly common in the Indian population. However, advanced macular changes are significantly rare.

  14. [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.

  15. EGFR Signaling Pathway and Related-miRNAs In Age-related Diseases: The Example of miR-221 and miR-222

    Directory of Open Access Journals (Sweden)

    Ana L Teixeira

    2012-12-01

    Full Text Available Presently, neurodegenerative diseases and cancer are the most clinically problematic age-related diseases worldwide. Although being distinct disorders, their developments share common cellular mechanisms. Oncogenesis and neurodegeneration arise from the deregulation of signaling pathways, as a consequence of the resulting imbalance in cellular homeostasis. The epidermal growth factor receptor (EGFR belongs to an important cellular signaling pathway, which regulates proliferation, differentiation, cell cycle and migration. As transcriptional targets of EGFR, the microRNAs-221/222 (miR-221/222 are important expression regulators. Dysfunctions in their networks are associated with cellular disruptions. The transcriptional activation of these miRNAs seems to be involved in cell cycle, apoptosis, metastization and in the acquisition of resistance to therapies. The up-regulation of miR-221/222 is associated with increased expression levels of matrix metalloproteinases (MMPs and repression of cell cycle inhibitors, which are key molecules in oncogenesis and neurodegeneration processes. The interaction loop between proliferative signaling pathways and miRNA expression could reveal new targets for controlling the molecular behavior of age-related diseases.

  16. Complement C3-Deficient Mice Fail to Display Age-Related Hippocampal Decline.

    Science.gov (United States)

    Shi, Qiaoqiao; Colodner, Kenneth J; Matousek, Sarah B; Merry, Katherine; Hong, Soyon; Kenison, Jessica E; Frost, Jeffrey L; Le, Kevin X; Li, Shaomin; Dodart, Jean-Cosme; Caldarone, Barbara J; Stevens, Beth; Lemere, Cynthia A

    2015-09-23

    The complement system is part of the innate immune response responsible for removing pathogens and cellular debris, in addition to helping to refine CNS neuronal connections via microglia-mediated pruning of inappropriate synapses during brain development. However, less is known about the role of complement during normal aging. Here, we studied the role of the central complement component, C3, in synaptic health and aging. We examined behavior as well as electrophysiological, synaptic, and neuronal changes in the brains of C3-deficient male mice (C3 KO) compared with age-, strain-, and gender-matched C57BL/6J (wild-type, WT) control mice at postnatal day 30, 4 months, and 16 months of age. We found the following: (1) region-specific and age-dependent synapse loss in aged WT mice that was not observed in C3 KO mice; (2) age-dependent neuron loss in hippocampal CA3 (but not in CA1) that followed synapse loss in aged WT mice, neither of which were observed in aged C3 KO mice; and (3) significantly enhanced LTP and cognition and less anxiety in aged C3 KO mice compared with aged WT mice. Importantly, CA3 synaptic puncta were similar between WT and C3 KO mice at P30. Together, our results suggest a novel and prominent role for complement protein C3 in mediating aged-related and region-specific changes in synaptic function and plasticity in the aging brain. Significance statement: The complement cascade, part of the innate immune response to remove pathogens, also plays a role in synaptic refinement during brain development by the removal of weak synapses. We investigated whether complement C3, a central component, affects synapse loss during aging. Wild-type (WT) and C3 knock-out (C3 KO) mice were examined at different ages. The mice were similar at 1 month of age. However, with aging, WT mice lost synapses in specific brain regions, especially in hippocampus, an area important for memory, whereas C3 KO mice were protected. Aged C3 KO mice also performed better on

  17. Mouse models of telomere dysfunction phenocopy skeletal changes found in human age-related osteoporosis

    Directory of Open Access Journals (Sweden)

    Tracy A. Brennan

    2014-05-01

    /−Terc−/− mice had a statistically significant increase in bone-marrow fat content compared with young WT mice, which remained elevated in aged double mutants. Taken together, our results suggest that Terc−/− and Wrn−/−Terc−/− mutants recapitulate the human bone aging phenotype and are useful models for studying age-related osteoporosis.

  18. Attenuating age-related learning deficits: emotional valenced feedback interacts with task complexity.

    Science.gov (United States)

    Gorlick, Marissa A; Giguère, Gyslain; Glass, Brian D; Nix, Brittany N; Mather, Mara; Maddox, W Todd

    2013-04-01

    Previous research reveals that older adults sometimes show enhanced processing of emotionally positive stimuli relative to negative stimuli, but that this positivity bias reverses to become a negativity bias when cognitive control resources are less available. In this study, we test the hypothesis that emotionally positive feedback will attenuate well-established age-related deficits in rule learning whereas emotionally negative feedback will amplify age deficits-but that this pattern will reverse when the task involves a high cognitive load. Experiment 1 used emotional face feedback and revealed an interaction among age, valence of the feedback, and task load. When the task placed minimal load on cognitive control resources, happy-face feedback attenuated age-related deficits in initial rule learning and angry-face feedback led to age-related deficits in initial rule learning and set shifting. However, when the task placed a high load on cognitive control resources, we found that angry-face feedback attenuated age-related deficits in initial rule learning and set shifting whereas happy-face feedback led to age-related deficits in initial rule learning and set shifting. Experiment 2 used less emotional point feedback and revealed age-related deficits in initial rule learning and set shifting under low and high cognitive load for point-gain and point-loss conditions. The research presented here demonstrates that emotional feedback can attenuate age-related learning deficits-but only positive feedback for tasks with a low cognitive load and negative feedback for tasks with high cognitive load.

  19. Novel therapeutic approaches to correct retinal metabolic abnormalities in primary open-angle glaucoma and age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    K. A. Mirzabekova

    2014-01-01

    Full Text Available Common pathogenic aspects of age-related macular degeneration (AMD and primary open-angle glaucoma (POAG, i.e., the role of free radicals inducing oxidative damage of the retina and optic nerve, are discussed. Factors that activate free radical reactions as well as multilevel antioxidant protection system are reviewed. Data derived from studies on current antioxidants that are used to treat and prevent dry AMD and glaucomatous optic nerve damage are compared. Neuroprotection for glaucoma will be considered soon as a basis for its treatment. B vitamins are generally included into therapeutic algorithms for glaucomatous optic neuropathy. While being metabolic therapeutics, they stimulate adaptive compensatory mechanisms and reduce the severity of various pathological processes, e.g., hypoxia, lipid peroxidation etc. Neurotrophic, antioxidant, and regenerative effects of B vitamins as wells as their involvement in metabolism, myelinsynthesis and other processes are of special importance for ophthalmologists. Currently, several vitamin and mineral supplements that differ in composition, dosage, and schedule are approved in Russia. SuperOptic, a biologically activeadditive, contains more free lutein (10 mg and zeaxanthin (500 μg as well as potent antioxidants (vitamin E and vitamin C, microelements (zinc and copper, and balanced vitamin B complex. These components play an important role in ocular health. SuperOptic can be recommended for the prevention and treatment of AMD and glaucomatous optic nerve damage.

  20. Novel therapeutic approaches to correct retinal metabolic abnormalities in primary open-angle glaucoma and age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    K. A. Mirzabekova

    2015-01-01

    Full Text Available Common pathogenic aspects of age-related macular degeneration (AMD and primary open-angle glaucoma (POAG, i.e., the role of free radicals inducing oxidative damage of the retina and optic nerve, are discussed. Factors that activate free radical reactions as well as multilevel antioxidant protection system are reviewed. Data derived from studies on current antioxidants that are used to treat and prevent dry AMD and glaucomatous optic nerve damage are compared. Neuroprotection for glaucoma will be considered soon as a basis for its treatment. B vitamins are generally included into therapeutic algorithms for glaucomatous optic neuropathy. While being metabolic therapeutics, they stimulate adaptive compensatory mechanisms and reduce the severity of various pathological processes, e.g., hypoxia, lipid peroxidation etc. Neurotrophic, antioxidant, and regenerative effects of B vitamins as wells as their involvement in metabolism, myelinsynthesis and other processes are of special importance for ophthalmologists. Currently, several vitamin and mineral supplements that differ in composition, dosage, and schedule are approved in Russia. SuperOptic, a biologically activeadditive, contains more free lutein (10 mg and zeaxanthin (500 μg as well as potent antioxidants (vitamin E and vitamin C, microelements (zinc and copper, and balanced vitamin B complex. These components play an important role in ocular health. SuperOptic can be recommended for the prevention and treatment of AMD and glaucomatous optic nerve damage.

  1. [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

  2. 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.

  3. Mesenchymal stem cells: a revolution in therapeutic strategies of age-related diseases.

    Science.gov (United States)

    Peng, Yan; Huang, Sha; Cheng, Biao; Nie, Xiaohu; Enhe, Jirigala; Feng, Changjiang; Fu, Xiaobing

    2013-01-01

    The great evolutionary biologist Theodosius Dobzhansky once said: "Nothing in biology makes sense except in the light of evolution". Aging is a complex biological phenomenon and the factors governing the process of aging and age-related diseases are only beginning to be understood, oxidative stress, telomere shortening in DNA components and genetic changes were shown to be the mainly regulating mechanisms during the recent decades. Although a considerable amount of both animal and clinical data that demonstrate the extensive and safe use of mesenchymal stromal cells (MSCs) is available, the precise summarization and identification of MSCs in age-related diseases remains a challenge. Along this line, this review discussed several typical age-related diseases for which MSCs have been proved to confer protection and put forward a hypothesis for the association among MSCs and age-related diseases from an evolutionary perspective. Above all, we hope further and more research efforts could be aroused to elucidate the role and mechanisms that MSCs involved in the age-related diseases.

  4. The potential preventive effects of vitamins for cataract and age-related macular degeneration.

    Science.gov (United States)

    Jacques, P F

    1999-05-01

    Age-related cataract and age-related macular degeneration (AMD) are important public health problems. Approximately 50% of the 30 to 50 million cases of blindness worldwide result from unoperated cataract. In the US and other developed countries AMD is the leading cause of blindness, but age-related cataract remains the leading cause of visual disability. Age-related cataract and AMD represent an enormous economic burden. In the United States more than 1.3 million cataract extractions are performed annually at a cost of approximately $3.5 billion. Much of the experimental research on the etiology of cataract and AMD has focused on the role of nutritional antioxidants (vitamin C, vitamin E, and carotenoids). Evidence from epidemiologic studies support a role for nutritional antioxidants in delaying the onset of these age-related vision disorders. Although it is not yet possible to conclude that antioxidant nutrients have a role in prevention of cataract or AMD, a summary of the epidemiologic evidence suggests that it is prudent to consume diets high in vitamins C and E and carotenoids, particularly the xanthophylls, as insurance against the development of cataract and AMD.

  5. 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.

  6. Aging assessment of reactor instrumentation and protection system components. Aging-related operating experiences

    Energy Technology Data Exchange (ETDEWEB)

    Gehl, A.C.; Hagen, E.W. [Oak Ridge National Lab., TN (United States)

    1992-07-01

    A study of the aging-related operating experiences throughout a five-year period (1984--1988) of six generic instrumentation modules (indicators, sensors, controllers, transmitters, annunciators, and recorders) was performed as a part of the Nuclear Plant Aging Research Program. The effects of aging from operational and environmental stressors were characterized from results depicted in Licensee Event Reports (LERs). The data are graphically displayed as frequency of events per plant year for operating plant ages from 1 to 28 years to determine aging-related failure trend patterns. Three main conclusions were drawn from this study: (1) Instrumentation and control (I&C) modules make a modest contribution to safety-significant events: 17% of LERs issued during 1984--1988 dealt with malfunctions of the six I&C modules studied, and 28% of the LERs dealing with these I&C module malfunctions were aging related (other studies show a range 25--50%); (2) Of the six modules studied, indicators, sensors, and controllers account for the bulk (83%) of aging-related failures; and (3) Infant mortality appears to be the dominant aging-related failure mode for most I&C module categories (with the exception of annunciators and recorders, which appear to fail randomly).

  7. Age-related changes in the transmission properties of the human lens and their relevance to circadian entrainment

    DEFF Research Database (Denmark)

    Kessel, Line; Lundeman, Jesper Holm; Herbst, Kristina;

    2010-01-01

    To characterize age-related changes in the transmission of light through noncataractous human lenses.......To characterize age-related changes in the transmission of light through noncataractous human lenses....

  8. Puzzles in modern biology. III.Two kinds of causality in age-related disease

    Science.gov (United States)

    Frank, Steven A.

    2017-01-01

    The two primary causal dimensions of age-related disease are rate and function. Change in rate of disease development shifts the age of onset. Change in physiological function provides necessary steps in disease progression. A causal factor may alter the rate of physiological change, but that causal factor itself may have no direct physiological role. Alternatively, a causal factor may provide a necessary physiological function, but that causal factor itself may not alter the rate of disease onset. The rate-function duality provides the basis for solving puzzles of age-related disease. Causal factors of cancer illustrate the duality between rate processes of discovery, such as somatic mutation, and necessary physiological functions, such as invasive penetration across tissue barriers. Examples from cancer suggest general principles of age-related disease.

  9. Age-related effects on the neural correlates of autobiographical memory retrieval.

    Science.gov (United States)

    St Jacques, Peggy L; Rubin, David C; Cabeza, Roberto

    2012-07-01

    Older adults recall less episodically rich autobiographical memories (AM), however, the neural basis of this effect is not clear. Using functional MRI, we examined the effects of age during search and elaboration phases of AM retrieval. Our results suggest that the age-related attenuation in the episodic richness of AMs is associated with difficulty in the strategic retrieval processes underlying recovery of information during elaboration. First, age effects on AM activity were more pronounced during elaboration than search, with older adults showing less sustained recruitment of the hippocampus and ventrolateral prefrontal cortex (VLPFC) for less episodically rich AMs. Second, there was an age-related reduction in the modulation of top-down coupling of the VLPFC on the hippocampus for episodically rich AMs. In sum, the present study shows that changes in the sustained response and coupling of the hippocampus and prefrontal cortex (PFC) underlie age-related reductions in episodic richness of the personal past.

  10. The rapidly evolving diagnosis and treatment of age-related macular degeneration.

    Science.gov (United States)

    2009-02-01

    Breakthrough research on age-related macular degeneration is stimulating the development of treatments, improving diagnosis, facilitating prevention through proper nutrition, and providing long-sought documentation on the effectiveness of low vision rehabilitation.Optometrists must take the lead in ensuring that patients reap the benefits. The February observance of Age-Related Macular Degeneration (AMD)/Low Vision Awareness Month provides a good time for optometrists to review their approach to age-related vision loss,ensure that they are ready to provide, or refer patients for, the best possible care, and prepare to conduct education efforts to ensure that their patients, communities, and other healthcare providers are aware of recent advancements.

  11.  Age-related changes of skeletal muscles: physiology, pathology and regeneration

    Directory of Open Access Journals (Sweden)

    Aleksandra Ławniczak

    2012-06-01

    Full Text Available  This review provides a short presentation of the aging-related changes of human skeletal muscles. The aging process is associated with the loss of skeletal muscle mass (sarcopenia and strength. This results from fibre atrophy and apoptosis, decreased regeneration capacity, mitochondrial dysfunction, gradual reduction of the number of spinal cord motor neurons, and local and systemic metabolic and hormonal alterations. The latter involve age-related decrease of the expression and activity of some mitochondrial and cytoplasmic enzymes, triacylglycerols and lipofuscin accumulation inside muscle fibres, increased proteolytic activity, insulin resistance and decreased serum growth hormone and IGF-1 concentrations. Aging of the skeletal muscles is also associated with a decreased number of satellite cells and their proliferative activity. The age-related reduction of skeletal muscle mass and function may be partially prevented by dietary restriction and systematic physical exercises.

  12. Age-related effects on the neural correlates of autobiographical memory retrieval

    Science.gov (United States)

    St. Jacques, Peggy L.; Rubin, David C.; Cabeza, Roberto

    2011-01-01

    Older adults recall less episodically rich autobiographical memories (AM), however, the neural basis of this effect is not clear. Using functional MRI, we examined the effects of age during search and elaboration phases of AM retrieval. Our results suggest that the age-related attenuation in the episodic richness of AMs is associated with difficulty in the strategic retrieval processes underlying recovery of information during elaboration. First, age effects on AM activity were more pronounced during elaboration than search, with older adults showing less sustained recruitment of the hippocampus and ventrolateral prefrontal cortex (VLPFC) for less episodically rich AMs. Second, there was an age-related reduction in the modulation of top-down coupling of the VLPFC on the hippocampus for episodically rich AMs. In sum, the present study shows that changes in the sustained response and coupling of the hippocampus and PFC underlie age-related reductions in episodic richness of the personal past. PMID:21190759

  13. Canine Models for Copper Homeostasis Disorders

    Directory of Open Access Journals (Sweden)

    Xiaoyan Wu

    2016-02-01

    Full Text Available Copper is an essential trace nutrient metal involved in a multitude of cellular processes. Hereditary defects in copper metabolism result in disorders with a severe clinical course such as Wilson disease and Menkes disease. In Wilson disease, copper accumulation leads to liver cirrhosis and neurological impairments. A lack in genotype-phenotype correlation in Wilson disease points toward the influence of environmental factors or modifying genes. In a number of Non-Wilsonian forms of copper metabolism, the underlying genetic defects remain elusive. Several pure bred dog populations are affected with copper-associated hepatitis showing similarities to human copper metabolism disorders. Gene-mapping studies in these populations offer the opportunity to discover new genes involved in copper metabolism. Furthermore, due to the relatively large body size and long life-span of dogs they are excellent models for development of new treatment strategies. One example is the recent use of canine organoids for disease modeling and gene therapy of copper storage disease. This review addresses the opportunities offered by canine genetics for discovery of genes involved in copper metabolism disorders. Further, possibilities for the use of dogs in development of new treatment modalities for copper storage disorders, including gene repair in patient-derived hepatic organoids, are highlighted.

  14. Progressive Bidirectional Age-Related Changes in Default Mode Network Effective Connectivity across Six Decades.

    Science.gov (United States)

    Li, Karl; Laird, Angela R; Price, Larry R; McKay, D Reese; Blangero, John; Glahn, David C; Fox, Peter T

    2016-01-01

    The default mode network (DMN) is a set of regions that is tonically engaged during the resting state and exhibits task-related deactivation that is readily reproducible across a wide range of paradigms and modalities. The DMN has been implicated in numerous disorders of cognition and, in particular, in disorders exhibiting age-related cognitive decline. Despite these observations, investigations of the DMN in normal aging are scant. Here, we used blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) acquired during rest to investigate age-related changes in functional connectivity of the DMN in 120 healthy normal volunteers comprising six, 20-subject, decade cohorts (from 20-29 to 70-79). Structural equation modeling (SEM) was used to assess age-related changes in inter-regional connectivity within the DMN. SEM was applied both using a previously published, meta-analytically derived, node-and-edge model, and using exploratory modeling searching for connections that optimized model fit improvement. Although the two models were highly similar (only 3 of 13 paths differed), the sample demonstrated significantly better fit with the exploratory model. For this reason, the exploratory model was used to assess age-related changes across the decade cohorts. Progressive, highly significant changes in path weights were found in 8 (of 13) paths: four rising, and four falling (most changes were significant by the third or fourth decade). In all cases, rising paths and falling paths projected in pairs onto the same nodes, suggesting compensatory increases associated with age-related decreases. This study demonstrates that age-related changes in DMN physiology (inter-regional connectivity) are bidirectional, progressive, of early onset and part of normal aging.

  15. Adverse Childhood Experiences and Adult Risk Factors for Age-Related Disease

    Science.gov (United States)

    Danese, Andrea; Moffitt, Terrie E.; Harrington, HonaLee; Milne, Barry J.; Polanczyk, Guilherme; Pariante, Carmine M.; Poulton, Richie; Caspi, Avshalom

    2013-01-01

    Objective To understand why children exposed to adverse psychosocial experiences are at elevated risk for age-related disease, such as cardiovascular disease, by testing whether adverse childhood experiences predict enduring abnormalities in stress-sensitive biological systems, namely, the nervous, immune, and endocrine/metabolic systems. Design A 32-year prospective longitudinal study of a representative birth cohort. Setting New Zealand. Participants A total of 1037 members of the Dunedin Multidisciplinary Health and Development Study. Main Exposures During their first decade of life, study members were assessed for exposure to 3 adverse psychosocial experiences: socioeconomic disadvantage, maltreatment, and social isolation. Main Outcome Measures At age 32 years, study members were assessed for the presence of 3 age-related-disease risks: major depression, high inflammation levels (high-sensitivity C-reactive protein level >3 mg/L), and the clustering of metabolic risk biomarkers (overweight, high blood pressure, high total cholesterol, low high-density lipoprotein cholesterol, high glycated hemoglobin, and low maximum oxygen consumption levels. Results Children exposed to adverse psychosocial experiences were at elevated risk of depression, high inflammation levels, and clustering of metabolic risk markers. Children who had experienced socioeconomic disadvantage (incidence rate ratio, 1.89; 95% confidence interval, 1.36–2.62), maltreatment (1.81; 1.38–2.38), or social isolation (1.87; 1.38–2.51) had elevated age-related-disease risks in adulthood. The effects of adverse childhood experiences on age-related-disease risks in adulthood were nonredundant, cumulative, and independent of the influence of established developmental and concurrent risk factors. Conclusions Children exposed to adverse psychosocial experiences have enduring emotional, immune, and metabolic abnormalities that contribute to explaining their elevated risk for age-related disease. The

  16. Caloric restriction extends yeast chronological lifespan by altering a pattern of age-related changes in trehalose concentration

    Directory of Open Access Journals (Sweden)

    Pavlo eKyryakov

    2012-07-01

    Full Text Available The nonreducing disaccharide trehalose has been long considered only as a reserve carbohydrate. However, recent studies in yeast suggested that this osmolyte can protect cells and cellular proteins from oxidative damage elicited by exogenously added reactive oxygen species (ROS. Trehalose has been also shown to affect stability, folding and aggregation of bacterial and firefly proteins heterologously expressed in heat-shocked yeast cells. Our recent investigation of how a lifespan-extending caloric restriction (CR diet alters the metabolic history of chronologically aging yeast suggested that their longevity is programmed by the level of metabolic capacity - including trehalose biosynthesis and degradation - that yeast cells developed prior to entry into quiescence. To investigate whether trehalose homeostasis in chronologically aging yeast may play a role in longevity extension by CR, in this study we examined how single-gene-deletion mutations affecting trehalose biosynthesis and degradation impact 1 the age-related dynamics of changes in trehalose concentration; 2 yeast chronological lifespan under CR conditions; 3 the chronology of oxidative protein damage, intracellular ROS level and protein aggregation; and 4 the timeline of thermal inactivation of a protein in heat-shocked yeast cells and its subsequent reactivation in yeast returned to low temperature. Our data imply that CR extends yeast chronological lifespan in part by altering a pattern of age-related changes in trehalose concentration. We outline a model for molecular mechanisms underlying the essential role of trehalose in defining yeast longevity by modulating protein folding, misfolding, unfolding, refolding, oxidative damage, solubility and aggregation throughout lifespan.

  17. Ophthalmology. Screening and treatment of age-related and pathologic vision changes.

    Science.gov (United States)

    Rosenthal, B P

    2001-12-01

    In the older adult, deterioration of normal vision is caused by age-related physiologic and pathologic changes. Vision impairment undermines quality of life by reducing independence, mobility, and the enjoyment that goes with seeing clearly. The most common causes of vision impairment are age-related macular degeneration (AMD), glaucoma, cataract, and diabetic retinopathy. Key to successful management of vision impairment is early detection of signs and symptoms, patient education regarding preventive strategies, and swift medical or surgical intervention for established or emerging conditions. Vision rehabilitation is an important management option.

  18. Age-related changes of the MR appearance of CNS involvement in neurocutaneous melanosis complex

    Energy Technology Data Exchange (ETDEWEB)

    Gondo, K.; Kira, R.; Tokunaga, Y.; Hara, T. [Dept. of Paediatrics, Kyushu Univ., Fukuoka (Japan)

    2000-12-01

    We report a case of giant congenital melanocytic nevi (GCMN) at risk of developing neurocutaneous melanosis (NCM) with age-related changes observable on MRI of the brain. However, although the usefulness of MR imaging in NCM is well known, age-related changes on MRI have rarely been reported. The prevalence of positive MRI findings and prognosis in GCMN accompanied by epilepsy and/or mental retardation awaits clarification. This case report may suggest the importance of serial brain MRI in cases of GCMN in assessing the risk of NCM. (orig.)

  19. Are chronic myeloproliferative neoplasms associated with age-related macular degeneration?

    DEFF Research Database (Denmark)

    Bak, M.; Sorensen, T. L.; Flachs, E. M.

    2015-01-01

    of the eye have not been thoroughly investigated in these patients. Previously reported studies show signs of systemic inflammation in patients with MPN as well as in patients with Age-Related Macular Degeneration (AMD). Our hypothesis is that the presence of MPN predisposes some individuals to develop AMD...... and this might be explained by the degree of systemic inflammation. Objective. To describe the prevalence of Age-Related Macular Degeneration in patients with Chronic Myeloproliferative cancer at time of diagnosis compared to the general population in Denmark. Materials and Methods. We conducted a retrospective...

  20. 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...... number of age-related signs with multifactorially adjusted hazard ratios up to 1.40 (95% confidence interval, 1.20-1.62) for IHD and 1.57 (1.28-1.93) for MI, in individuals with 3 to 4 versus no age-related signs at baseline (P for trend groups in both women and men, absolute 10-year...

  1. Flying Blind: Aeromedical Certification and Undiagnosed Age-Related Macular Degeneration

    Science.gov (United States)

    2011-09-01

    or becomes worse over time Vision loss may be severe and rapid with wet AMD compared to dry AMD Distorted vision (i.e., metamorphopsia) - A grid of...Although.vision.loss.can.occur,.it. is.usually.minimal.and.progresses.slowly.(12) . The.“ wet ”.form.of.macular.degeneration.is.responsible. for.10...564-72 . 14 .. Michels. S,. Kurz-Levin. M .. [Age-related. macu- lar. degeneration. ( AMD )]. Ther Umsch .. 2009. Mar;66(3):189-95 . 15 .. Age-Related

  2. "Older is always better": Age-related differences in vocabulary scores across 16 years.

    Science.gov (United States)

    Ben-David, Boaz M; Erel, Hadas; Goy, Huiwen; Schneider, Bruce A

    2015-12-01

    Cross-sectional studies of cognitive aging compare age groups at 1 time point. It is unclear from such studies whether age-related cognitive differences remain stable across time. We present a cross-sectional investigation of vocabulary scores of 2,000 younger and older adults collected across 16 years, using the same laboratory and protocol. We found a steady decrease with year of testing and an advantage for older adults. An additive relation between age group and year of testing implied that age-related differences in vocabulary are independent of changes over time, suggesting that younger and older adults are similarly affected by changes in word usage.

  3. Role of the human high-affinity copper transporter in copper homeostasis regulation and cisplatin sensitivity in cancer chemotherapy.

    Science.gov (United States)

    Kuo, Macus Tien; Fu, Siqing; Savaraj, Niramol; Chen, Helen H W

    2012-09-15

    The high-affinity copper transporter (Ctr1; SCLC31A1) plays an important role in regulating copper homeostasis because copper is an essential micronutrient and copper deficiency is detrimental to many important cellular functions, but excess copper is toxic. Recent research has revealed that human copper homeostasis is tightly controlled by interregulatory circuitry involving copper, Sp1, and human (hCtr1). This circuitry uses Sp1 transcription factor as a copper sensor in modulating hCtr1 expression, which in turn controls cellular copper and Sp1 levels in a 3-way mutual regulatory loop. Posttranslational regulation of hCtr1 expression by copper stresses has also been described in the literature. Because hCtr1 can also transport platinum drugs, this finding underscores the important role of hCtr1 in platinum-drug sensitivity in cancer chemotherapy. Consistent with this notion is the finding that elevated hCtr1 expression was associated with favorable treatment outcomes in cisplatin-based cancer chemotherapy. Moreover, cultured cell studies showed that elevated hCtr1 expression can be induced by depleting cellular copper levels, resulting in enhanced cisplatin uptake and its cell-killing activity. A phase I clinical trial using a combination of trientine (a copper chelator) and carboplatin has been carried out with encouraging results. This review discusses new insights into the role of hCtr1 in regulating copper homeostasis and explains how modulating cellular copper availability could influence treatment efficacy in platinum-based cancer chemotherapy through hCtr1 regulation.

  4. NPY antagonism reduces adiposity and attenuates age-related imbalance of adipose tissue metabolism.

    Science.gov (United States)

    Park, Seongjoon; Fujishita, Chika; Komatsu, Toshimitsu; Kim, Sang Eun; Chiba, Takuya; Mori, Ryoichi; Shimokawa, Isao

    2014-12-01

    An orexigenic hormone, neuropeptide Y (NPY), plays a role not only in the hypothalamic regulation of appetite, but also in the peripheral regulation of lipid metabolism. However, the intracellular mechanisms triggered by NPY to regulate lipid metabolism are poorly understood. Here we report that NPY deficiency reduces white adipose tissue (WAT) mass and ameliorates the age-related imbalance of adipose tissue metabolism in mice. Gene expression involved in adipogenesis/lipogenesis was found to decrease, whereas proteins involved in lipolysis increased in gonadal WAT (gWAT) of NPY-knockout mice. These changes were associated with an activated SIRT1- and PPARγ-mediated pathway. Moreover, the age-related decrease of de novo lipogenesis in gWAT and thermogenesis in inguinal WAT was inhibited by NPY deficiency. Further analysis using 3T3-L1 cells showed that NPY inhibited lipolysis through the Y1 receptor and enhanced lipogenesis following a reduction in cAMP response element-binding protein (CREB) and SIRT1 protein expression. Therefore, NPY appears to act as a key regulator of adipose tissue metabolism via the CREB-SIRT1 signaling pathway. Taken together, NPY deficiency reduces adiposity and ameliorates the age-related imbalance of adipose tissue metabolism, suggesting that antagonism of NPY may be a promising target for drug development to prevent age-related metabolic diseases.

  5. Single-Chain Antibody Fragment VEGF Inhibitor RTH258 for Neovascular Age-Related Macular Degeneration

    DEFF Research Database (Denmark)

    Holz, Frank G; Dugel, Pravin U; Weissgerber, Georges

    2016-01-01

    PURPOSE: To assess the safety and efficacy of different doses of RTH258 applied as single intravitreal administration compared with ranibizumab 0.5 mg in patients with neovascular age-related macular degeneration (AMD). DESIGN: Six-month, phase 1/2, prospective, multicenter, double-masked, random...

  6. Age-related spatial working memory deficits in homing pigeons (Columba livia).

    Science.gov (United States)

    Coppola, Vincent J; Hough, Gerald; Bingman, Verner P

    2014-12-01

    The hippocampus is particularly susceptible to age-related degeneration that, like hippocampal lesions, is thought to lead to age-related decline in spatial memory and navigation. Lesions to the avian hippocampal formation (HF) also result in impaired spatial memory and navigation, but the relationship between aging and HF-dependent spatial cognition is unknown. To investigate possible age-related decline in avian spatial cognition, the current study investigated spatial working memory performance in older homing pigeons (10+ years of age). Pigeons completed a behavioral procedure nearly identical to the delayed spatial, win-shift procedure in a modified radial arm maze that has been previously used to study spatial working memory in rats and pigeons. The results revealed that the older pigeons required a greater number of choices to task completion and were less accurate with their first 4 choices as compared to younger pigeons (1-2 years of age). In addition, older pigeons were more likely to adopt a stereotyped sampling strategy, which explained in part their impaired performance. To the best of our knowledge, this study is the first to demonstrate an age-related impairment of HF-dependent, spatial memory in birds. Implications and future directions of the findings are discussed.

  7. Age-related decline in associative learning in healthy Chinese adults.

    Science.gov (United States)

    Lee, Annie; Archer, Jo; Wong, Caroline Kai Yun; Chen, Shen-Hsing Annabel; Qiu, Anqi

    2013-01-01

    Paired associates learning (PAL) has been widely used in aging-related research, suggesting an age-related decline in associative learning. However, there are several cognitive processes (attention, spatial and recognition memory, strategy, and associative learning) involved in PAL. It is unclear which component contributes to the decline in PAL performance associated with age effects. The present study determines whether age effects on associative learning are independent of other cognitive processes involved in PAL. Using a validated computerized cognitive program (CANTAB), we examined cognitive performance of associative learning, spatial and recognition memory, attention and strategy use in 184 Singaporean Chinese adults aged from 21 to 80 years old. Linear regression revealed significant age-related decline in associative learning, spatial and recognition memory, and the level of strategy use. This age-related decline in associative learning remains even after adjusting for attention, spatial and recognition memory, and strategy use. These results show that age effects on associative learning are independent of other cognitive processes involved in PAL.

  8. Zooming in on the hippocampus in aging and age-related diseases

    NARCIS (Netherlands)

    Wisse, L.E.M.

    2014-01-01

    The hippocampal formation is a brain structure important for memory and emotion regulation. The hippocampal formation is susceptible to aging and age-related diseases, which is manifested as volume loss, visible on MRI scans. The hippocampal formation consists of several subfields with different cel

  9. Guidelines for the Evaluation of Dementia and Age-Related Cognitive Change

    Science.gov (United States)

    American Psychologist, 2012

    2012-01-01

    Dementia in its many forms is a leading cause of functional limitation among older adults worldwide and will continue to ascend in global health importance as populations continue to age and effective cures remain elusive. The following guidelines were developed for psychologists who perform evaluations of dementia and age-related cognitive…

  10. Age-Related Hearing Loss: Quality of Care for Quality of Life

    Science.gov (United States)

    Li-Korotky, Ha-Sheng

    2012-01-01

    Age-related hearing loss (ARHL), known as presbycusis, is characterized by progressive deterioration of auditory sensitivity, loss of the auditory sensory cells, and central processing functions associated with the aging process. ARHL is the third most prevalent chronic condition in older Americans, after hypertension and arthritis, and is a…

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

    NARCIS (Netherlands)

    Friedman, R.A.; Laer, L. van; Huentelman, M.J.; Sheth, S.S.; Eyken, E. van; Corneveaux, J.J.; Tembe, W.D.; Halperin, R.F.; Thorburn, A.Q.; Thys, S.; Bonneux, S.; Fransen, E.; Huyghe, J.; Pyykko, I.; Cremers, C.W.R.J.; Kremer, H.; Dhooge, I.J.; Stephens, D.; Orzan, E.; Pfister, M.; Bille, M.; Parving, A.; Sorri, M.; Heyning, P. van de; Makmura, L.; Ohmen, J.D.; Linthicum Jr, F.H.; Fayad, J.N.; Pearson, J.V.; Craig, D.W.; Stephan, D.A.; Camp, G. van

    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 study w

  12. 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 study...

  13. The Psychosocial Impact of Closed-Circuit Televisions on Persons with Age-Related Macular Degeneration

    Science.gov (United States)

    Huber, Jessica G.; Jutai, Jeffrey W.; Strong, J. Graham; Plotkin, Ann D.

    2008-01-01

    Closed-circuit televisions (CCTVs) are used by many elderly people who have age-related macular degeneration (AMD). The functional vision of 68 participants, which was measured immediately after they adopted CCTVs, suggested successful outcomes, but the psychosocial impact of the use of CCTVs did not peak until a month later. The findings help…

  14. Age-Related Differences in Restricted Repetitive Behaviors in Autism Spectrum Disorders

    Science.gov (United States)

    Esbensen, Anna J.; Seltzer, Marsha Mailick; Lam, Kristen S. L.; Bodfish, James W.

    2009-01-01

    Restricted repetitive behaviors (RRBs) were examined in a large group of children, adolescents and adults with ASD in order to describe age-related patterns of symptom change and association with specific contextual factors, and to examine if the patterns of change are different for the various types of RRBs. Over 700 individuals with ASD were…

  15. Use of a robotic device to measure age-related decline in finger proprioception.

    Science.gov (United States)

    Ingemanson, Morgan L; Rowe, Justin B; Chan, Vicky; Wolbrecht, Eric T; Cramer, Steven C; Reinkensmeyer, David J

    2016-01-01

    Age-related changes in proprioception are known to affect postural stability, yet the extent to which such changes affect the finger joints is poorly understood despite the importance of finger proprioception in the control of skilled hand movement. We quantified age-related changes in finger proprioception in 37 healthy young, middle-aged, and older adults using two robot-based tasks wherein participants' index and middle fingers were moved by an exoskeletal robot. The first task assessed finger position sense by asking participants to indicate when their index and middle fingers were directly overlapped during a passive crisscross movement; the second task assessed finger movement detection by asking participants to indicate the onset of passive finger movement. When these tasks were completed without vision, finger position sense errors were 48 % larger in older adults compared to young participants (p proprioceptive reaction time was 78 % longer in older adults compared to young adults (p proprioception, these age-related differences were no longer apparent. No difference between dominant and non-dominant hand performance was found for either proprioception task. These findings demonstrate that finger proprioception is impaired in older adults, and visual feedback can be used to compensate for this deficit. The findings also support the feasibility and utility of the FINGER robot as a sensitive tool for detecting age-related decline in proprioception.

  16. Association of diabetes with age-related macular degeneration in the EUREYE study

    NARCIS (Netherlands)

    Topouzis, F.; Anastasopoulos, E.; Augood, C.; Bentham, G.C.; Chakravarthy, U.; de Jong, P.T.V.M.; Rahu, M.; Seland, J.; Soubrane, G.; Tomazzoli, L.; Vingerling, J.R.; Vioque, J.; Young, I.S.; Fletcher, A.E.

    2009-01-01

    Objective: To examine the association between self-reported diabetes history and early or late age-related macular degeneration (AMD) in the European population. Methods: Participants aged 65 years and over in the cross-sectional population-based EUREYE study underwent an eye examination including d

  17. Raspberry supplementation alleviates age-related motor dysfunction in select populations

    Science.gov (United States)

    Age-related declines in balance, muscle strength and coordination often lead to a higher incidence of falling. Among older adults, falls are the leading cause of distress, pain, injury, loss of confidence, and ultimately, loss of independence and death. Previous studies in our laboratory have demons...

  18. Age and age-related differences in internet usage of cancer patients

    NARCIS (Netherlands)

    van Weert, J.C.M.; Bolle, S.; Muusses, L.D.; Stephanidis, C.; Antona, M.

    2014-01-01

    This study investigates age and age-related differences in Internet usage of 952 cancer patients treated with chemotherapy. Older patients (> 65 years) reported significantly less Internet usage to find treatment-related information than younger ones (< 65 years). Still, 40.1% of the older patients

  19. What the Age-Related Eye Disease Studies Mean for You (AREDS2)

    Science.gov (United States)

    ... the AREDS Means for You For the Public: What the AREDS Means for You What the Age-Related Eye Disease Studies Mean for ... related nutritional supplements with a health care professional. What is the original AREDS formulation? 500 milligrams (mg) ...

  20. The changing face of emotion: age-related patterns of amygdala activation to salient faces

    NARCIS (Netherlands)

    Todd, R.M.; Evans, J.W.; Morris, D.; Lewis, M.D.; Taylor, M.J.

    2011-01-01

    The present study investigated age-related differences in the amygdala and other nodes of face-processing networks in response to facial expression and familiarity. fMRI data were analyzed from 31 children (3.5–8.5 years) and 14 young adults (18–33 years) who viewed pictures of familiar (mothers) an

  1. Knowledge and Use of Low Vision Services Among Persons with Age-Related Macular Degeneration

    Science.gov (United States)

    Casten, Robin J.; Maloney, Eileen K.; Rovner, Barry W.

    2005-01-01

    Visual impairment (blindness or low vision) is a leading cause of disability among older adults and is most often due to age-related macular degeneration (AMD). It is predicted that 2.95 million people will have AMD by 2020 (Eye Diseases Prevalence Research Group, 2004). Unfortunately, there is no cure for AMD, nor can lost vision be restored.…

  2. Multiple gait parameters derived from iPod accelerometry predict age-related gait changes

    NARCIS (Netherlands)

    Kosse, Nienke; Vuillerme, Nicolas; Hortobagyi, Tibor; Lamoth, Claude

    2016-01-01

    Introduction Normative data of how natural aging affects gait can serve as a frame of reference for changes in gait dynamics due to pathologies. Therefore, the present study aims (1) to identify gait variables sensitive to age-related changes in gait over the adult life span using the iPod and (2) t

  3. 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…

  4. Obesity and Age-Related Changes in Markers of Oxidative Stress and Inflammation Across Four Generations

    NARCIS (Netherlands)

    Hulsegge, Gerben; Herber-Gast, Gerrie-Cor M; Spijkerman, Annemieke M W; Susan, H; Picavet, J; van der Schouw, Yvonne T; Bakker, Stephan J L; Gansevoort, Ron T; Dollé, Martijn E T; Smit, Henriette A; Monique Verschuren, W M

    2016-01-01

    OBJECTIVE: The prevalence of obesity increases with age and is higher in each younger generation (unfavorable generation shift). This may influence patterns of oxidative stress and inflammation. Age-related changes and generation shifts in markers of oxidative stress and inflammation were investigat

  5. A Qualitative Analysis of Reading Rehabilitation of Persons with Age-Related Macular Degeneration

    Science.gov (United States)

    Feely, Mary; Vetere, Arlene; Myers, Lynn B.

    2007-01-01

    One of the most prevalent visual impairments of people aged 60 and older is age-related macular degeneration (AMD), which ranks third globally as a cause of visual impairment (World Health Organization, 2006). The purpose of this study was to conduct a tentative subjective assessment of eccentric viewing by persons with AMD. The authors recruited…

  6. 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.

  7. Identification of MOAG-4/SERF as a regulator of age-related proteotoxicity

    NARCIS (Netherlands)

    van Ham, Tjakko J; Holmberg, Mats A; van der Goot, Annemieke T; Teuling, Eva; Garcia-Arencibia, Moises; Kim, Hyun-eui; Du, Deguo; Thijssen, Karen L; Wiersma, Marit; Burggraaff, Rogier; van Bergeijk, Petra; van Rheenen, Jeroen; Jerre van Veluw, G; Hofstra, Robert M W; Rubinsztein, David C; Nollen, Ellen A. A.

    2010-01-01

    Fibrillar protein aggregates are the major pathological hallmark of several incurable, age-related, neurodegenerative disorders. These aggregates typically contain aggregation-prone pathogenic proteins, such as amyloid-beta in Alzheimer's disease and alpha-synuclein in Parkinson's disease. It is, ho

  8. Identification of MOAG-4/SERF as a Regulator of Age-Related Proteotoxicity

    NARCIS (Netherlands)

    van Ham, Tjakko J.; Holmberg, Mats A.; van der Goot, Annemieke T.; Teuling, Eva; Garcia-Arencibia, Moises; Kim, Hyun-eui; Du, Deguo; Thijssen, Karen L.; Wiersma, Marit; Burggraaff, Rogier; van Bergeijk, Petra; van Rheenen, Jeroen; van Veluw, G. Jerre; Hofstra, Robert M. W.; Rubinsztein, David C.; Nollen, Ellen A. A.

    2010-01-01

    Fibrillar protein aggregates are the major pathological hallmark of several incurable, age-related, neurodegenerative disorders. These aggregates typically contain aggregation-prone pathogenic proteins, such as amyloid-beta in Alzheimer's disease and alpha-synuclein in Parkinson's disease. It is, ho

  9. The short-wavelength mechanisms of Stiles in age-related macular degeneration.

    Science.gov (United States)

    Hubschman, J P; Vola, J L; Conrath, J; Berros, P; Hougrand, F

    1998-11-01

    Clinical measurements by the increment-threshold technique of W.S. Stiles are reported in five cases of age-related macular degeneration. Measurements were made on a modified Tübingen perimeter using 1 degree, short-wavelength targets presented on a red field.

  10. Ability of university-level education to prevent age-related decline in emotional intelligence

    Directory of Open Access Journals (Sweden)

    Rosario eCabello

    2014-03-01

    Full Text Available Numerous studies have suggested that educational history, as a proxy measure of active cognitive reserve, protects against age-related cognitive decline and risk of dementia. Whether educational history also protects against age-related decline in emotional intelligence (EI is unclear. The present study examined ability EI in 310 healthy adults ranging in age from 18 to 76 years using the Mayer–Salovey–Caruso Emotional Intelligence Test (MSCEIT. We found that older people had lower scores than younger people for total EI and for the EI branches of perceiving, facilitating and understanding emotions, whereas age was not associated with the EI branch of managing emotions. We also found that educational history protects against this age-related EI decline by mediating the relationship between age and EI. In particular, the EI scores of older adults with a university education were higher than those of older adults with primary or secondary education, and similar to those of younger adults of any education level. These findings suggest that the cognitive reserve hypothesis, which states that individual differences in cognitive processes as a function of lifetime intellectual activities explain differential susceptibility to functional impairment in the presence of age-related changes and brain pathology, applies also to EI, and that education can help preserve cognitive-emotional structures during aging.

  11. Ability of university-level education to prevent age-related decline in emotional intelligence.

    Science.gov (United States)

    Cabello, Rosario; Navarro Bravo, Beatriz; Latorre, José Miguel; Fernández-Berrocal, Pablo

    2014-01-01

    Numerous studies have suggested that educational history, as a proxy measure of active cognitive reserve, protects against age-related cognitive decline and risk of dementia. Whether educational history also protects against age-related decline in emotional intelligence (EI) is unclear. The present study examined ability EI in 310 healthy adults ranging in age from 18 to 76 years using the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). We found that older people had lower scores than younger people for total EI and for the EI branches of perceiving, facilitating, and understanding emotions, whereas age was not associated with the EI branch of managing emotions. We also found that educational history protects against this age-related EI decline by mediating the relationship between age and EI. In particular, the EI scores of older adults with a university education were higher than those of older adults with primary or secondary education, and similar to those of younger adults of any education level. These findings suggest that the cognitive reserve hypothesis, which states that individual differences in cognitive processes as a function of lifetime intellectual activities explain differential susceptibility to functional impairment in the presence of age-related changes and brain pathology, applies also to EI, and that education can help preserve cognitive-emotional structures during aging.

  12. HISTORY OF SUNLIGHT EXPOSURE IS A RISK FACTOR FOR AGE-RELATED MACULAR DEGENERATION

    NARCIS (Netherlands)

    Schick, T.; Ersoy, L.; Lechanteur, Y.T.; Saksens, N.T.; Hoyng, C.B.; Hollander, A.I. den; Kirchhof, B.; Fauser, S.

    2016-01-01

    PURPOSE: To evaluate effects of current and past sunlight exposure and iris color on early and late age-related macular degeneration (AMD). METHODS: Of 3,701 individuals from the EUGENDA database, 752 (20.3%) showed early AMD, 1,179 (31.9%) late AMD, and 1,770 (47.8%) were controls. Information abou

  13. Genetic Determinants of Cognitive Function and Age-Related Brain Changes

    NARCIS (Netherlands)

    M. Schuur (Maaike)

    2010-01-01

    textabstractThe brain is by far the most complicated structure of the human being, and its malfunction is characterized by various degrees and types of morbidity. Several brain functions deteriorate with increasing age during life. Cognitive decline and age-related brain pathology are common in the

  14. The potential effects of meditation on age-related cognitive decline: a systematic review.

    Science.gov (United States)

    Gard, Tim; Hölzel, Britta K; Lazar, Sara W

    2014-01-01

    With a rapidly aging society it becomes increasingly important to counter normal age-related decline in cognitive functioning. Growing evidence suggests that cognitive training programs may have the potential to counteract this decline. On the basis of a growing body of research that shows that meditation has positive effects on cognition in younger and middle-aged adults, meditation may be able to offset normal age-related cognitive decline or even enhance cognitive function in older adults. In this paper, we review studies investigating the effects of meditation on age-related cognitive decline. We searched the Web of Science (1900 to present), PsycINFO (1597 to present), MEDLINE (1950 to present), and CABI (1910 to present) to identify original studies investigating the effects of meditation on cognition and cognitive decline in the context of aging. Twelve studies were included in the review, six of which were randomized controlled trials. Studies involved a wide variety of meditation techniques and reported preliminary positive effects on attention, memory, executive function, processing speed, and general cognition. However, most studies had a high risk of bias and small sample sizes. Reported dropout rates were low and compliance rates high. We conclude that meditation interventions for older adults are feasible, and preliminary evidence suggests that meditation can offset age-related cognitive decline.

  15. 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, recognize

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

    OpenAIRE

    Francisco Max Damico; Fabio Gasparin; Mariana Ramos Scolari; Lycia Sampaio Pedral; Beatriz Sayuri Takahashi

    2012-01-01

    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, ...

  17. Prevalence of age-related maculopathy in older Europeans: The European Eye Study (EUREYE)

    NARCIS (Netherlands)

    C. Augood (Cristina); J.R. Vingerling (Hans); P.T.V.M. de Jong (Paulus); U. Chakravarthy (Usha); J.H. Seland (Johan ); G. Soubrane; L. Tomazzoli (Laura); F. Topouzis (Fotis); G.C. Bentham (Graham ); M. Rahu; J. Vioque (Jesus); I.S. Young (Ian ); A.E. Fletcher (Astrid E.)

    2006-01-01

    textabstractObjective: To estimate the prevalence of age-related maculopathy in an older population from 7 European countries. Methods: Randomly sampled people 65 years and older were invited to an eye examination in centers across 7 European countries (Norway, Estonia, United Kingdom, France, Italy

  18. Cognitive Abilities Explaining Age-Related Changes in Time Perception of Short and Long Durations

    Science.gov (United States)

    Zelanti, Pierre S.; Droit-Volet, Sylvie

    2011-01-01

    The current study investigated how the development of cognitive abilities explains the age-related changes in temporal judgment over short and long duration ranges from 0.5 to 30 s. Children (5- and 9-year-olds) as well as adults were given a temporal bisection task with four different duration ranges: a duration range shorter than 1 s, two…

  19. Assessment of the quality of life of patients with age-related macular degeneration

    OpenAIRE

    BAKHRITDINOVA FAZILAT ARIFOVNA; YUSUPOV AZAMAT FARKHADOVICH; MUKHANOV SHAVKAT ABDUVALIYEVICH

    2016-01-01

    This article is dedicated to the study of the quality of life of patients with the help of an adapted questionnaire VFQ-25 in Uzbek language and assessment of complex treatment of early and late manifestations of age-related macular degeneration.

  20. Heritability of Anxious-Depressive and Withdrawn Behavior: Age-Related Changes during Adolescence

    Science.gov (United States)

    Lamb, Diane J.; Middeldorp, Christel M.; van Beijsterveldt, Catarina E. M.; Bartels, Meike; van der Aa, Niels; Polderman, Tinca J. C.; Boomsma, Dorret I.

    2010-01-01

    Objective: To explain the differential course of anxiety and depression in individuals from childhood to adulthood by examining age-related changes in the genetic and environmental etiology of anxious and depressive symptoms. Method: A sample of 1470, 1839, and 2023 Dutch twins aged 12, 14, and 16 years reported on symptoms of anxious depression…

  1. 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.

  2. Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans

    NARCIS (Netherlands)

    Rahimi, Mehran; Vinciguerra, Manlio; Daghighi, Mojtaba; Oezcan, Behiye; Akbarkhanzadeh, Vishtaseb; Sheedfar, Fareeba; Amini, Marzyeh; Mazza, Tommaso; Pazienza, Valerio; Motazacker, Mahdi M.; Mahmoudi, Morteza; De Rooij, Felix W. M.; Sijbrands, Eric; Peppelenbosch, Maikel P.; Rezaee, Farhad

    2015-01-01

    Despite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (AT) and pancr

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

    Directory of Open Access Journals (Sweden)

    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. Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans.

    NARCIS (Netherlands)

    Rahimi, M.; Vinciguerra, M.; Daghighi, M.; Ozcan, B.; Akbarkhanzadeh, V.; Sheedfar, F.; Amini, M.; Mazza, T.; Pazienza, V.; Motazacker, M.M.; Mahmoudi, M.; Rooij, F.W. De; Sijbrands, E.; Peppelenbosch, M.P.; Rezaee, F.

    2015-01-01

    Despite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (AT) and pancr

  5. Age-related obesity and type 2 diabetes dysregulate neuronal associated genes and proteins in humans

    NARCIS (Netherlands)

    M. Rahimi (Mehran); M. Vinciguerra (Manlio); M. Daghighi (Mojtaba); B. Özcan (Behiye); V. Akbarkhanzadeh (Vishtaseb); F. Sheedfar (Fareeba); M. Amini (Marzyeh); T. Mazza (Tommaso); V. Pazienza (Valerio); M.M. Motazacker (Mohammad); T. Mahmoudi (Tokameh); F.W.M. de Rooij (Felix); E.J.G. Sijbrands (Eric); M.P. Peppelenbosch (Maikel); F. Rezaee (Farhad)

    2015-01-01

    textabstractDespite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (A

  6. Age-related changes in 100-km ultra-marathon running performance

    OpenAIRE

    Beat, Knechtlee; Rüst, Christoph Alexander; Rosemann, Thomas; Lepers, Romuald

    2011-01-01

    International audience; The aims of this study were (1) to investigate the participation and performance trends at the '100 km Lauf Biel' in Switzerland from 1998 to 2010, and (2) to compare the age-related changes in 100-km running performance between males and females. For both sexes, the percent of finishers significantly (P 

  7. Predicting Non-response to Ranibizumab in Patients with Neovascular Age-related Macular Degeneration

    NARCIS (Netherlands)

    Asten, F. van; Rovers, M.M.; Lechanteur, Y.T.E.; Smailhodzic, D.; Muether, P.S.; Chen, J.; Hollander, A.I. den; Fauser, S.; Hoyng, C.B.; Wilt, G.J. van der; Klevering, B.J.

    2014-01-01

    Abstract Purpose: To validate known and determine new predictors of non-response to ranibizumab in patients with neovascular age-related macular degeneration (AMD) and to incorporate these factors into a prediction rule. METHODS: This multicenter, observational cohort study included 391 patients tre

  8. Clinical characteristics of familial and sporadic age-related macular degeneration: differences and similarities

    NARCIS (Netherlands)

    Saksens, N.T.M.; Kersten, E.; Groenewoud, J.M.M.; Grinsven, M.J.J.P. van; Ven, J.P.H. van de; Sanchez, C.I.; Schick, T.; Fauser, S.; Hollander, A.I. den; Hoyng, C.B.; Boon, C.J.F.

    2014-01-01

    PURPOSE: We describe the differences and similarities in clinical characteristics and phenotype of familial and sporadic patients with age-related macular degeneration (AMD). METHODS: We evaluated data of 1828 AMD patients and 1715 controls enrolled in the European Genetic Database. All subjects und

  9. 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

  10. Age-related differences in cognition across the adult lifespan in autism spectrum disorder.

    Science.gov (United States)

    Lever, Anne G; Geurts, Hilde M

    2016-06-01

    It is largely unknown how age impacts cognition in autism spectrum disorder (ASD). We investigated whether age-related cognitive differences are similar, reduced or increased across the adult lifespan, examined cognitive strengths and weaknesses, and explored whether objective test performance is related to subjective cognitive challenges. Neuropsychological tests assessing visual and verbal memory, generativity, and theory of mind (ToM), and a self-report measure assessing cognitive failures were administered to 236 matched participants with and without ASD, aged 20-79 years (IQ > 80). Group comparisons revealed that individuals with ASD had higher scores on visual memory, lower scores on generativity and ToM, and similar performance on verbal memory. However, ToM impairments were no longer present in older (50+ years) adults with ASD. Across adulthood, individuals with ASD demonstrated similar age-related effects on verbal memory, generativity, and ToM, while age-related differences were reduced on visual memory. Although adults with ASD reported many cognitive failures, those were not associated with neuropsychological test performance. Hence, while some cognitive abilities (visual and verbal memory) and difficulties (generativity and semantic memory) persist across adulthood in ASD, others become less apparent in old age (ToM). Age-related differences characteristic of typical aging are reduced or parallel, but not increased in individuals with ASD, suggesting that ASD may partially protect against an age-related decrease in cognitive functioning. Despite these findings, adults with ASD experience many cognitive daily challenges, which highlights the need for adequate social support and the importance of further research into this topic, including longitudinal studies. Autism Res 2016, 9: 666-676. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

  11. Age-related changes of task-specific brain activity in normal aging.

    Science.gov (United States)

    Ho, Ming-Chung; Chou, Chia-Yi; Huang, Chin-Fei; Lin, Yu-Te; Shih, Ching-Sen; Han, Shiang-Yi; Shen, Ming-Hsun; Chen, Tsung-Ching; Liang, Chi-lin; Lu, Ming-Chi; Liu, Chia-Ju

    2012-01-17

    An important question in healthcare for older patients is whether age-related changes in cortical reorganization can be measured with advancing age. This study investigated the factors behind such age-related changes, using time-frequency analysis of event-related potentials (ERPs). We hypothesized that brain rhythms was affected by age-related changes, which could be reflected in the ERP indices. An oddball task was conducted in two experimental groups, namely young participants (N=15; mean age 23.7±2.8 years) and older participants (N=15; mean age 70.1±7.9 years). Two types of stimuli were used: the target (1 kHz frequency) and standard (2 kHz frequency). We scrutinized three ERP indices: event-related spectral power (ERPSP), inter-trial phase-locking (ITPL), and event-related cross-phase coherence (ERPCOH). Both groups performed equally well for correct response rate. However, the results revealed a statistically significant age difference for inter-trial comparison. Compared with the young, the older participants showed the following age-related changes: (a) power activity decreased; however, an increase was found only in the late (P3, 280-450 ms) theta (4-7 Hz) component over the bilateral frontal and temporo-frontal areas; (b) low phase-locking in the early (N1, 80-140 ms) theta band over the parietal/frontal (right) regions appeared; (c) the functional connections decreased in the alpha (7-13 Hz) and beta (13-30 Hz) bands, but no difference emerged in the theta band between the two groups. These results indicate that age-related changes in task-specific brain activity for a normal aging population can be depicted using the three ERP indices.

  12. Cellular Telephone

    Institute of Scientific and Technical Information of China (English)

    杨周

    1996-01-01

    Cellular phones, used in automobiles, airliners, and passenger trains, are basically low-power radiotelephones. Calls go through radio transmitters that are located within small geographical units called cells. Because each cell’s signals are too weak to interfere with those of other cells operating on the same fre-

  13. PGC-1α Modulates Telomere Function and DNA Damage in Protecting against Aging-Related Chronic Diseases

    Directory of Open Access Journals (Sweden)

    Shiqin Xiong

    2015-09-01

    Full Text Available Cellular senescence and organismal aging predispose age-related chronic diseases, such as neurodegenerative, metabolic, and cardiovascular disorders. These diseases emerge coincidently from elevated oxidative/electrophilic stress, inflammation, mitochondrial dysfunction, DNA damage, and telomere dysfunction and shortening. Mechanistic linkages are incompletely understood. Here, we show that ablation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α accelerates vascular aging and atherosclerosis, coinciding with telomere dysfunction and shortening and DNA damage. PGC-1α deletion reduces expression and activity of telomerase reverse transcriptase (TERT and increases p53 levels. Ectopic expression of PGC-1α coactivates TERT transcription and reverses telomere malfunction and DNA damage. Furthermore, alpha lipoic acid (ALA, a non-dispensable mitochondrial cofactor, upregulates PGC-1α-dependent TERT and the cytoprotective Nrf-2-mediated antioxidant/electrophile-responsive element (ARE/ERE signaling cascades, and counteracts high-fat-diet-induced, age-dependent arteriopathy. These results illustrate the pivotal importance of PGC-1α in ameliorating senescence, aging, and associated chronic diseases, and may inform novel therapeutic approaches involving electrophilic specificity.

  14. Cell surgery and growth factors in dry age-related macular degeneration: visual prognosis and morphological study

    Science.gov (United States)

    Limoli, Paolo Giuseppe; Limoli, Celeste; Vingolo, Enzo Maria; Scalinci, Sergio Zaccaria; Nebbioso, Marcella

    2016-01-01

    Background The aim of this research was to study the overall restoration effect on residual retinal cells through surgically grafted autologous cells onto the surrounding tissue, choroid and retina in order to produce a constant secretion of growth factors (GFs) in dry age-related macular degeneration (AMD) patients. Results 6 months after surgery, several values were statistically significant in the group with higher RTA. Also patient compliance analysis (PCA) in relation to functional change perception appeared to be very good. Methods Thirty-six eyes of 25 patients (range 64-84 years of age) affected by dry AMD were included in study, and divided in two groups by spectral domain-optical coherence tomography (SD-OCT): group A with retinal thickness average (RTA) less than 250 microns (μm) and group B with RTA equal to or more than 250 μm. Adipocytes, adipose-derived stem cells from the stromal-vascular fraction, and platelets from platelet-rich plasma were implanted in the suprachoroidal space. Particularly, the following parameters were evaluated: best corrected visual acuity (BCVA) for far and near distance, retinal thickness maps, scotopic and photopic electroretinogram (ERG), and microperimetry (MY). All statistical analyses were performed with STATA 14.0 (Collage Station, Texas, USA). Conclusions The available set of GFs allowed biological retinal neuroenhancement. After 6 months it improved visual performance (VP), but the increase was better if RTA recorded by OCT was higher, probably in relation to the presence of areas with greater cellularity. PMID:27391437

  15. Role of microRNAs in the age-related changes in skeletal muscle and diet or exercise interventions to promote healthy aging in humans.

    Science.gov (United States)

    McGregor, Robin A; Poppitt, Sally D; Cameron-Smith, David

    2014-09-01

    Progressive age-related changes in skeletal muscle mass and composition, underpin decreases in muscle function, which can inturn lead to impaired mobility and quality of life in older adults. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression in skeletal muscle and are associated with aging. Accumulating evidence suggests that miRNAs play an important role in the age-related changes in skeletal muscle mass, composition and function. At the cellular level, miRNAs have been demonstrated to regulate muscle cell proliferation and differentiation. Furthermore, miRNAs are involved in the transitioning of muscle stem cells from a quiescent, to either an activated or senescence state. Evidence from animal and human studies has shown miRNAs are modulated in muscle atrophy and hypertrophy. In addition, miRNAs have been implicated in changes in muscle fiber composition, fat infiltration and insulin resistance. Both exercise and dietary interventions can combat age-related changes in muscle mass, composition and function, which may be mediated by miRNA modulation in skeletal muscle. Circulating miRNA species derived from myogenic cell populations represent potential biomarkers of aging muscle and the molecular responses to exercise or diet interventions, but larger validation studies are required. In future therapeutic approaches targeting miRNAs, either through exercise, diet or drugs may be able to slow down or prevent the age-related changes in skeletal muscle mass, composition, function, hence help maintain mobility and quality of life in old age.

  16. Molecular responses of mouse macrophages to copper and copper oxide nanoparticles inferred from proteomic analyses.

    Science.gov (United States)

    Triboulet, Sarah; Aude-Garcia, Catherine; Carrière, Marie; Diemer, Hélène; Proamer, Fabienne; Habert, Aurélie; Chevallet, Mireille; Collin-Faure, Véronique; Strub, Jean-Marc; Hanau, Daniel; Van Dorsselaer, Alain; Herlin-Boime, Nathalie; Rabilloud, Thierry

    2013-11-01

    The molecular responses of macrophages to copper-based nanoparticles have been investigated via a combination of proteomic and biochemical approaches, using the RAW264.7 cell line as a model. Both metallic copper and copper oxide nanoparticles have been tested, with copper ion and zirconium oxide nanoparticles used as controls. Proteomic analysis highlighted changes in proteins implicated in oxidative stress responses (superoxide dismutases and peroxiredoxins), glutathione biosynthesis, the actomyosin cytoskeleton, and mitochondrial proteins (especially oxidative phosphorylation complex subunits). Validation studies employing functional analyses showed that the increases in glutathione biosynthesis and in mitochondrial complexes observed in the proteomic screen were critical to cell survival upon stress with copper-based nanoparticles; pharmacological inhibition of these two pathways enhanced cell vulnerability to copper-based nanoparticles, but not to copper ions. Furthermore, functional analyses using primary macrophages derived from bone marrow showed a decrease in reduced glutathione levels, a decrease in the mitochondrial transmembrane potential, and inhibition of phagocytosis and of lipopolysaccharide-induced nitric oxide production. However, only a fraction of these effects could be obtained with copper ions. In conclusion, this study showed that macrophage functions are significantly altered by copper-based nanoparticles. Also highlighted are the cellular pathways modulated by cells for survival and the exemplified cross-toxicities that can occur between copper-based nanoparticles and pharmacological agents.

  17. Molecular Responses of Mouse Macrophages to Copper and Copper Oxide Nanoparticles Inferred from Proteomic Analyses*

    Science.gov (United States)

    Triboulet, Sarah; Aude-Garcia, Catherine; Carrière, Marie; Diemer, Hélène; Proamer, Fabienne; Habert, Aurélie; Chevallet, Mireille; Collin-Faure, Véronique; Strub, Jean-Marc; Hanau, Daniel; Van Dorsselaer, Alain; Herlin-Boime, Nathalie; Rabilloud, Thierry

    2013-01-01

    The molecular responses of macrophages to copper-based nanoparticles have been investigated via a combination of proteomic and biochemical approaches, using the RAW264.7 cell line as a model. Both metallic copper and copper oxide nanoparticles have been tested, with copper ion and zirconium oxide nanoparticles used as controls. Proteomic analysis highlighted changes in proteins implicated in oxidative stress responses (superoxide dismutases and peroxiredoxins), glutathione biosynthesis, the actomyosin cytoskeleton, and mitochondrial proteins (especially oxidative phosphorylation complex subunits). Validation studies employing functional analyses showed that the increases in glutathione biosynthesis and in mitochondrial complexes observed in the proteomic screen were critical to cell survival upon stress with copper-based nanoparticles; pharmacological inhibition of these two pathways enhanced cell vulnerability to copper-based nanoparticles, but not to copper ions. Furthermore, functional analyses using primary macrophages derived from bone marrow showed a decrease in reduced glutathione levels, a decrease in the mitochondrial transmembrane potential, and inhibition of phagocytosis and of lipopolysaccharide-induced nitric oxide production. However, only a fraction of these effects could be obtained with copper ions. In conclusion, this study showed that macrophage functions are significantly altered by copper-based nanoparticles. Also highlighted are the cellular pathways modulated by cells for survival and the exemplified cross-toxicities that can occur between copper-based nanoparticles and pharmacological agents. PMID:23882024

  18. An age-related deficit in spatial-feature reference memory in homing pigeons (Columba livia).

    Science.gov (United States)

    Coppola, Vincent J; Flaim, Mary E; Carney, Samantha N; Bingman, Verner P

    2015-03-01

    Age-related memory decline in mammals has been well documented. By contrast, very little is known about memory decline in birds as they age. In the current study we trained younger and older homing pigeons on a reference memory task in which a goal location could be encoded by spatial and feature cues. Consistent with a previous working memory study, the results revealed impaired acquisition of combined spatial-feature reference memory in older compared to younger pigeons. Following memory acquisition, we used cue-conflict probe trials to provide an initial assessment of possible age-related differences in cue preference. Both younger and older pigeons displayed a similarly modest preference for feature over spatial cues.

  19. Impact of Endothelial Microparticles on Coagulation, Inflammation, and Angiogenesis in Age-Related Vascular Diseases

    Directory of Open Access Journals (Sweden)

    Margaret Markiewicz

    2013-01-01

    Full Text Available Endothelial microparticles (EMPs are complex vesicular structures that originate from plasma membranes of activated or apoptotic endothelial cells. EMPs play a significant role in vascular function by altering the processes of inflammation, coagulation, and angiogenesis, and they are key players in the pathogenesis of several vascular diseases. Circulating EMPs are increased in many age-related vascular diseases such as coronary artery disease, peripheral vascular disease, cerebral ischemia, and congestive heart failure. Their elevation in plasma has been considered as both a biomarker and bioactive effector of vascular damage and a target for vascular diseases. This review focuses on the pleiotropic roles of EMPs and the mechanisms that trigger their formation, particularly the involvement of decreased estrogen levels, thrombin, and PAI-1 as major factors that induce EMPs in age-related vascular diseases.

  20. Glycation: the angiogenic paradox in aging and age-related disorders and diseases.

    Science.gov (United States)

    Roca, F; Grossin, N; Chassagne, P; Puisieux, F; Boulanger, E

    2014-05-01

    Angiogenesis is generally a quiescent process which, however, may be modified by different physiological and pathological conditions. The "angiogenic paradox" has been described in diabetes because this disease impairs the angiogenic response in a manner that differs depending on the organs involved and disease evolution. Aging is also associated with pro- and antiangiogenic processes. Glycation, the post-translational modification of proteins, increases with aging and the progression of diabetes. The effect of glycation on angiogenesis depends on the type of glycated proteins and cells involved. This complex link could be responsible for the "angiogenic paradox" in aging and age-related disorders and diseases. Using diabetes as a model, the present work has attempted to review the age-related angiogenic paradox, in particular the effects of glycation on angiogenesis during aging.

  1. Age-related plasma chemistry findings in the buff-crested bustard (Eupodotis ruficrista gindiana).

    Science.gov (United States)

    Bailey, T A; Wernery, U; Howlett, J; Naldo, J; Samour, J H

    1998-12-01

    Blood samples were obtained from adult (> 1.5 years) and juvenile (2-8 weeks, 9-16 weeks and 17-24 weeks) captive buff-crested bustards (Eupodotis ruficrista gindiana) to study age-related changes. A total of twelve different tests were conducted using a Hitachi 90011 wet chemistry analyzer. A comparison of the values obtained was made between adult and juvenile buff-crested bustards and from the literature with other bustard species. Significant differences between adult and juvenile buff-crested bustards were found for glucose, uric acid, total protein, alkaline phosphatase, asparatate amino transferase and calcium. The results obtained from this study provide blood chemistry values for this species and demonstrate age-related differences between adult and juvenile birds.

  2. 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.

  3. Diminishing risk for age-related macular degeneration with nutrition: a current view.

    Science.gov (United States)

    Schleicher, Molly; Weikel, Karen; Garber, Caren; Taylor, Allen

    2013-07-02

    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.

  4. Nanotechnology-based drug delivery treatments and specific targeting therapy for age-related macular degeneration.

    Science.gov (United States)

    Lin, Tai-Chi; Hung, Kuo-Hsuan; Peng, Chi-Hsien; Liu, Jorn-Hon; Woung, Lin-Chung; Tsai, Ching-Yao; Chen, Shih-Jen; Chen, Yan-Ting; Hsu, Chih-Chien

    2015-11-01

    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.

  5. Digital histologic analysis reveals morphometric patterns of age-related involution in breast epithelium and stroma.

    Science.gov (United States)

    Sandhu, Rupninder; Chollet-Hinton, Lynn; Kirk, Erin L; Midkiff, Bentley; Troester, Melissa A

    2016-02-01

    Complete age-related regression of mammary epithelium, often termed postmenopausal involution, is associated with decreased breast cancer risk. However, most studies have qualitatively assessed involution. We quantitatively analyzed epithelium, stroma, and adipose tissue from histologically normal breast tissue of 454 patients in the Normal Breast Study. High-resolution digital images of normal breast hematoxylin and eosin-stained slides were partitioned into epithelium, adipose tissue, and nonfatty stroma. Percentage area and nuclei per unit area (nuclear density) were calculated for each component. Quantitative data were evaluated in association with age using linear regression and cubic spline models. Stromal area decreased (P = 0.0002), and adipose tissue area increased (P epithelium. Epithelial nuclear density is a quantitative measure of age-related breast involution that begins to decline in the early premenopausal period.

  6. Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson's Disease.

    Science.gov (United States)

    Sepe, Sara; Milanese, Chiara; Gabriels, Sylvia; Derks, Kasper W J; Payan-Gomez, Cesar; van IJcken, Wilfred F J; Rijksen, Yvonne M A; Nigg, Alex L; Moreno, Sandra; Cerri, Silvia; Blandini, Fabio; Hoeijmakers, Jan H J; Mastroberardino, Pier G

    2016-05-31

    The underlying relation between Parkinson's disease (PD) etiopathology and its major risk factor, aging, is largely unknown. In light of the causative link between genome stability and aging, we investigate a possible nexus between DNA damage accumulation, aging, and PD by assessing aging-related DNA repair pathways in laboratory animal models and humans. We demonstrate that dermal fibroblasts from PD patients display flawed nucleotide excision repair (NER) capacity and that Ercc1 mutant mice with mildly compromised NER exhibit typical PD-like pathological alterations, including decreased striatal dopaminergic innervation, increased phospho-synuclein levels, and defects in mitochondrial respiration. Ercc1 mouse mutants are also more sensitive to the prototypical PD toxin MPTP, and their transcriptomic landscape shares important similarities with that of PD patients. Our results demonstrate that specific defects in DNA repair impact the dopaminergic system and are associated with human PD pathology and might therefore constitute an age-related risk factor for PD.

  7. Resistance to antivascular endothelial growth factor treatment in age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Tranos P

    2013-06-01

    Full Text Available Paris Tranos,1 Athanasios Vacalis,1 Solon Asteriadis,1 Stavrenia Koukoula,1 Athanasios Vachtsevanos,1 Georgia Perganta,1 Ilias Georgalas21Retina Centre, Thessaloniki, Greece; 2Department of Ophthalmology, "G Gennimatas" Hospital of Athens, University of Athens, Athens, GreeceAbstract: Age-related macular degeneration (AMD is the main cause of visual impairment and blindness in people aged over 65 years in developed countries. Vascular endothelial growth factor (VEGF is a positive regulator of angiogenesis and its proven role in the pathological neovascularization in wet AMD has provided evidence for the use of anti-VEGF agents as potential therapies. In this study, we review the literature for the possible causes of failure after treatment with anti-VEGF agents and attempt to propose an algorithm of suggestive actions to increase the chances of successful management of such difficult cases.Keywords: antiVEGF, age related macular degeneration, treatment

  8. Classification of wet aged related macular degeneration using optical coherence tomographic images

    Science.gov (United States)

    Haq, Anam; Mir, Fouwad Jamil; Yasin, Ubaid Ullah; Khan, Shoab A.

    2013-12-01

    Wet Age related macular degeneration (AMD) is a type of age related macular degeneration. In order to detect Wet AMD we look for Pigment Epithelium detachment (PED) and fluid filled region caused by choroidal neovascularization (CNV). This form of AMD can cause vision loss if not treated in time. In this article we have proposed an automated system for detection of Wet AMD in Optical coherence tomographic (OCT) images. The proposed system extracts PED and CNV from OCT images using segmentation and morphological operations and then detailed feature set are extracted. These features are then passed on to the classifier for classification. Finally performance measures like accuracy, sensitivity and specificity are calculated and the classifier delivering the maximum performance is selected as a comparison measure. Our system gives higher performance using SVM as compared to other methods.

  9. Age-related increase in top-down activation of visual features

    Science.gov (United States)

    Madden, David J.; Spaniol, Julia; Bucur, Barbara; Whiting, Wythe L.

    2007-01-01

    Previous research suggests that, during visual search and discrimination tasks, older adults place greater emphasis than younger adults on top-down attention. This experiment investigated the relative contribution of target activation and distractor inhibition to this age difference. Younger and older adults performed a singleton discrimination task in which either an E or an R target (colour singleton) was present among distractor letters. Relative to a baseline condition in which the colours of the targets and distractors remained constant, an age-related slowing of performance was evident when either the colour of the target or that of the distractors varied across trials. The age-related slowing was more pronounced in response to target colour variation, suggesting that older adults place relatively greater emphasis on the top-down activation of target features. PMID:17455072

  10. Age-related changes in human posture control: Sensory organization tests

    Science.gov (United States)

    Peterka, R. J.; Black, F. O.

    1989-01-01

    Postural control was measured in 214 human subjects ranging in age from 7 to 81 years. Sensory organization tests measured the magnitude of anterior-posterior body sway during six 21 s trials in which visual and somatosensory orientation cues were altered (by rotating the visual surround and support surface in proportion to the subject's sway) or vision eliminated (eyes closed) in various combinations. No age-related increase in postural sway was found for subjects standing on a fixed support surface with eyes open or closed. However, age-related increases in sway were found for conditions involving altered visual or somatosensory cues. Subjects older than about 55 years showed the largest sway increases. Subjects younger than about 15 years were also sensitive to alteration of sensory cues. On average, the older subjects were more affected by altered visual cues whereas younger subjects had more difficulty with altered somatosensory cues.

  11. Combined treatment of exudative age related macular degeneration with photodynamic therapy and intravitreal triamcinolone

    Directory of Open Access Journals (Sweden)

    José Mª Ruiz-Moreno

    2008-03-01

    Full Text Available José Mª Ruiz-Moreno1,2, Javier A Montero21Department of Ophthalmology, Miguel Hernández University School of Medicine, Alicante, Spain; 2Vitreo-Retinal Unit, Alicante Institute of Ophthalmology, Alicante, SpainAbstract: Choroidal neovascularization (CNV secondary to age related macular degeneration is among the leading causes of legal blindness in developed countries. Photodynamic therapy (PDT with verteporfin induces CNV closure causing little damage to healthy tissue, but the need to re-treat may lead to low final visual acuity at an unacceptable cost. The association of intravitreous triamcinolone or antiangiogenic drugs with PDT has been used in order to reduce these limitations of the therapy. The combination of PDT and intravitreous triamcinolone, its complications and outcome at one and two-year follow-up are discussed.Keywords: age related macular degeneration, choroidal neovascularization, photodynamic therapy, steroid, triamcinolone

  12. A neglected requirement for optimizing treatment of age-related osteoporosis: Replenishing the skeleton's base reservoir with net base-producing diets.

    Science.gov (United States)

    Sebastian, Anthony; Frassetto, Lynda A

    2016-06-01

    Osteoporosis is a disorder of bone in which the mass of the bone is reduced and the bone's architecture at the microscopic level is disordered. Together those abnormalities predispose affected individuals to experience fractures despite only minimal trauma (i.e., fragility fractures). Age related osteoporosis is a common type of osteoporosis that occurs with aging in both men and women usually beginning after the age of peak bone mass. Research has found that the disorder can be partially reversed by reducing the net amount of acid that is produced when consuming typical Western diets. However, the amelioration that results has not been so dramatic or so consistent that physicians have adopted the procedure as part of the standard treatment for age-related osteoporosis. We propose that reducing the net acid load from the diet is not sufficient to reverse age related osteoporosis because it fails to supply base needed to restore the large amount of base in bone that had been lost by reacting with the net acid load of the diet that had been consumed for years or decades. Reducing the net acid load from the diet might be expected to have little ameliorative effect or merely slow the progression of the disorder. We hypothesize that both to restore osteoporotic bone to, or nearly to, its pre-disease state, as well as to eliminate the risk of fragility fractures, requires consuming diets that produce net amounts of base to restore the base lost from years to decades of consuming diets that produce net amounts of acid. We hypothesize also that the excess base and attendant subclinical metabolic alkalosis will both stimulate the cellular process of bone formation and suppress the cellular process of bone resorption, and thereby implement the restorative process.

  13. Structural and functional findings in exudative age-related long-term macular degeneration

    OpenAIRE

    Riusala, Aila

    2013-01-01

    Age-related macular degeneration (AMD) is the leading cause of visual disability. During past years, new treatments have been studied frequently. However, only some studies have examined its long-term natural outcome. In the future, these kinds of studies are no longer possible because all the AMD lesions are treated. The purpose of this project was to investigate the end-stage structural and functional components of wet AMD and their connection to the fresh exudative lesion stage. The s...

  14. Treatment with dexamethasone and vitamin D3 attenuates neuroinflammatory age-related changes in rat hippocampus.

    Science.gov (United States)

    Moore, Michelle; Piazza, Alessia; Nolan, Yvonne; Lynch, Marina A

    2007-10-01

    Among the changes which occur in the brain with age is an increase in hippocampal concentration of proinflammatory cytokines like interleukin-1beta (IL-1beta) and an increase in IL-1beta-induced signaling. Here we demonstrate that the increase in IL-1beta concentration is accompanied by an increase in expression of IL-1 type I receptor (IL-1RI) and an age-related increase in microglial activation, as shown by increased expression of the cell surface marker, major histocompatibility complex II (MHCII) and increased MHCII staining. The evidence indicates that these age-related changes were abrogated in hippocampus of aged rats treated with dexamethasone and vitamin D3. Similarly, the age-related increases in activation of the stress-activated protein kinase, c-Jun N-terminal kinase (JNK), as well as caspase-3 and PARP were all attenuated in hippocampal tissue prepared from rats that received dexamethasone and vitamin D3. The data indicate that dexamethasone and vitamin D3 ameliorated the age-related increase in IFNgamma and suggest that IFNgamma may be the trigger leading to microglial activation, since it increases MHCII mRNA and IL-1beta release from cultured glia. In parallel with its ability to decrease microglial activation in vivo, we report that treatment of cultured glia with dexamethasone and vitamin D3 blocked the lipopolysaccharide increased MHCII mRNA and IL-1beta concentration, while the IL-1beta-induced increases in activation of JNK and caspase 3 in cultured neurons were also reversed by treatment with dexamethasone and vitamin D3. The data suggest that the antiinflammatory effect of dexamethasone and vitamin D3 derives from their ability to downreguate microglial activation.

  15. Tachyphylaxis during ranibizumab treatment of exudative age-related macular degeneration

    Institute of Scientific and Technical Information of China (English)

    Sibel; Doguizi; Sengul; Ozdek; Selcen; Yuksel

    2015-01-01

    <正>Dear Editor,We are intestigators from Turkey primarily studying exudative age-related macular degeneration(AMD).Here we present the results of our retrospective clinical study on tachyphylaxis development during the treatment of exudative AMD with ranibizumab,which,we believe,will form a basis for further prospective studies to predict the drug response in anti-vascular endothelial growth factor

  16. Aging-related changes in respiratory system mechanics and morphometry in mice.

    Science.gov (United States)

    Elliott, Jonathan E; Mantilla, Carlos B; Pabelick, Christina M; Roden, Anja C; Sieck, Gary C

    2016-07-01

    Previous work investigating respiratory system mechanics in mice has reported an aging-related increase in compliance and mean linear intercept (Lm). However, these changes were assessed using only a young (2-mo-old) and old (20- and 26-mo-old) group yet were interpreted to reflect a linear evolution across the life span. Therefore, to investigate respiratory system mechanics and lung morphometry across a more complete spectrum of ages, we utilized 2 (100% survival, n = 6)-, 6 (100% survival, n = 12)-, 18 (90% survival, n = 12)-, 24 (75% survival, n = 12)-, and 30 (25% survival, n = 12)-mo-old C57BL/6 mice. We found a nonlinear aging-related decrease in respiratory system resistance and increase in dynamic compliance and hysteresis between 2- and 24-mo-old mice. However, in 30-mo-old mice, respiratory system resistance increased, and dynamic compliance and hysteresis decreased relative to 24-mo-old mice. Respiratory system impedance spectra were measured between 1-20.5 Hz at positive end-expiratory pressures (PEEP) of 1, 3, 5, and 7 cmH2O. Respiratory system resistance and reactance at each level of PEEP were increased and decreased, respectively, only in 2-mo-old animals. No differences in the respiratory system impedance spectra were observed in 6-, 18-, 24-, and 30-mo-old mice. Additionally, lungs were fixed following tracheal instillation of 4% paraformaldehyde at 25 cmH2O and processed for Lm and airway collagen deposition. There was an aging-related increase in Lm consistent with emphysematous-like changes and no evidence of increased airway collagen deposition. Accordingly, we demonstrate nonlinear aging-related changes in lung mechanics and morphometry in C57BL/6 mice.

  17. The Impact of Age-Related Dysregulation of the Angiotensin System on Mitochondrial Redox Balance

    Directory of Open Access Journals (Sweden)

    Ramya eVajapey

    2014-11-01

    Full Text Available Aging is associated with the accumulation of various deleterious changes in cells. According to the free radical and mitochondrial theory of aging, mitochondria initiate most of the deleterious changes in aging and govern life span. The failure of mitochondrial reduction-oxidation (redox homeostasis and the formation of excessive free radicals are tightly linked to dysregulation in the Renin Angiotensin System (RAS. A main rate-controlling step in RAS is renin, an enzyme that hydrolyzes angiotensinogen to generate angiotensin I. Angiotensin I is further converted to Angiotensin II (Ang II by angiotensin-converting enzyme (ACE. Ang II binds with equal affinity to two main angiotensin receptors—type 1 (AT1R and type 2 (AT2R. The binding of Ang II to AT1R activates NADPH oxidase, which leads to increased generation of cytoplasmic reactive oxygen species (ROS. This Ang II-AT1R–NADPH-ROS signal triggers the opening of mitochondrial KATP channels and mitochondrial ROS production in a positive feedback loop. Furthermore, RAS has been implicated in the decrease of many of ROS scavenging enzymes, thereby leading to detrimental levels of free radicals in the cell.AT2R is less understood, but evidence supports an anti-oxidative and mitochondria-protective function for AT2R. The overlap between age related changes in RAS and mitochondria, and the consequences of this overlap on age-related diseases are quite complex. RAS dysregulation has been implicated in many pathological conditions due to its contribution to mitochondrial dysfunction. Decreased age-related, renal and cardiac mitochondrial dysfunction was seen in patients treated with angiotensin receptor blockers. The aim of this review is to: (a report the most recent information elucidating the role of RAS in mitochondrial redox hemostasis and (b discuss the effect of age-related activation of RAS on generation of free radicals.

  18. 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.

  19. A Corpus Analysis of Patterns of Age-Related Change in Conversational Speech

    OpenAIRE

    2010-01-01

    Conversational speech from over three hundred speakers aged 17 to 68 years old was analyzed for age-related changes in the timing and content of spoken language production. Overall, several relationships between the lexical content, timing, and fluency of speech emerged, such that more novel and lower frequency words are associated with slower speech and higher levels of disfluencies. Speaker age was associated with slower speech and more filled pauses, particularly those associated with lexi...

  20. Nutritional and Lifestyle Interventions for Age-Related Macular Degeneration: A Review

    OpenAIRE

    Carneiro, Ângela; Andrade, José Paulo

    2017-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world. In this narrative review, we will summarize the nutritional interventions evaluated in numerous observational studies and a few randomized clinical trials. The AREDS and AREDS2 studies demonstrated that supplements including vitamins C and E, beta-carotene, and zinc may reduce the progression to advanced AMD, in some patients, by 25% in five years. This is one of the few nutritional supplements kn...

  1. Evaluation of real-world mobility in age-related macular degeneration

    OpenAIRE

    Sengupta, Sabyasachi; Nguyen, Angeline M.; van Landingham, Suzanne W.; Solomon, Sharon D.; Do, Diana V.; Ferrucci, Luigi; David S Friedman; Ramulu, Pradeep Y.

    2015-01-01

    Background Previous research has suggested an association between poor vision and decreased mobility, including restricted levels of physical activity and travel away from home. We sought to determine the impact of age-related macular degeneration (AMD) on these measures of mobility. Methods Fifty-seven AMD patients with bilateral, or severe unilateral, visual impairment were compared to 59 controls with normal vision. All study subjects were between the ages of 60 and 80. Subjects wore accel...

  2. Long-term effectiveness of ranibizumab for age-related macular degeneration and diabetic macular edema

    OpenAIRE

    Lai, Timothy Y. Y.; Fong

    2013-01-01

    Angie HC Fong,1 Timothy YY Lai1,2 1Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Eye Hospital, Kowloon, Hong Kong; 22010 Retina and Macula Centre, Tsimshatsui, Kowloon, Hong Kong Abstract: Neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME) are major causes of visual impairment in the elderly population worldwide. With the aging population, the prevalence of neovascular AMD and DME has increased substantially o...

  3. The chronic care for wet age related macular degeneration (CHARMED) study: a randomized controlled trial

    OpenAIRE

    Markun, Stefan; Dishy, Avraham; Neuner-Jehle, Stefan; Rosemann, Thomas; Frei, Anja

    2015-01-01

    BACKGROUND: In real life, outcomes in wet age related macular degeneration (W-AMD) continue to fall behind the results from randomized controlled trials. The aim of this trial was to assess if outcomes can be improved by an intervention in healthcare organization following recommendations of the Chronic Care Model (CCM). METHODS: Multi-centered randomized controlled clinical trial. The multifaceted intervention consisted in reorganization of care (delivery by trained chronic care coaches, ...

  4. Relationship between macular pigment and visual function in subjects with early age-related macular degeneration

    OpenAIRE

    Akuffo, Kwadwo Owusu; Nolan, John M.; Peto, Tunde; Stack, Jim; Leung, Irene; Corcoran, Laura; Beatty, Stephen

    2016-01-01

    Purpose To investigate the relationship between macular pigment (MP) and visual function in subjects with early age-related macular degeneration (AMD). Methods 121 subjects with early AMD enrolled as part of the Central Retinal Enrichment Supplementation Trial (CREST; ISRCTN13894787) were assessed using a range of psychophysical measures of visual function, including best corrected visual acuity (BCVA), letter contrast sensitivity (CS), mesopic and photopic CS, mesopic and photopic glare disa...

  5. The Chronic Care for Wet Age Related Macular Degeneration (CHARMED) Study: A Randomized Controlled Trial

    OpenAIRE

    Stefan Markun; Avraham Dishy; Stefan Neuner-Jehle; Thomas Rosemann; Anja Frei

    2015-01-01

    Background In real life, outcomes in wet age related macular degeneration (W-AMD) continue to fall behind the results from randomized controlled trials. The aim of this trial was to assess if outcomes can be improved by an intervention in healthcare organization following recommendations of the Chronic Care Model (CCM). Methods Multi-centered randomized controlled clinical trial. The multifaceted intervention consisted in reorganization of care (delivery by trained chronic care coaches, using...

  6. Genome-wide age-related changes in DNA methylation and gene expression in human PBMCs.

    Science.gov (United States)

    Steegenga, Wilma T; Boekschoten, Mark V; Lute, Carolien; Hooiveld, Guido J; de Groot, Philip J; Morris, Tiffany J; Teschendorff, Andrew E; Butcher, Lee M; Beck, Stephan; Müller, Michael

    2014-06-01

    Aging is a progressive process that results in the accumulation of intra- and extracellular alterations that in turn contribute to a reduction in health. Age-related changes in DNA methylation have been reported before and may be responsible for aging-induced changes in gene expression, although a causal relationship has yet to be shown. Using genome-wide assays, we analyzed age-induced changes in DNA methylation and their effect on gene expression with and without transient induction with the synthetic transcription modulating agent WY14,643. To demonstrate feasibility of the approach, we isolated peripheral blood mononucleated cells (PBMCs) from five young and five old healthy male volunteers and cultured them with or without WY14,643. Infinium 450K BeadChip and Affymetrix Human Gene 1.1 ST expression array analysis revealed significant differential methylation of at least 5 % (ΔYO > 5 %) at 10,625 CpG sites between young and old subjects, but only a subset of the associated genes were also differentially expressed. Age-related differential methylation of previously reported epigenetic biomarkers of aging including ELOVL2, FHL2, PENK, and KLF14 was confirmed in our study, but these genes did not display an age-related change in gene expression in PBMCs. Bioinformatic analysis revealed that differentially methylated genes that lack an age-related expression change predominantly represent genes involved in carcinogenesis and developmental processes, and expression of most of these genes were silenced in PBMCs. No changes in DNA methylation were found in genes displaying transiently induced changes in gene expression. In conclusion, aging-induced differential methylation often targets developmental genes and occurs mostly without change in gene expression.

  7. Diabetic macular edema, retinopathy and age-related macular degeneration as inflammatory conditions

    OpenAIRE

    Das, Undurti N

    2016-01-01

    Diabetic macular edema (DME) and diabetic retinopathy (DR) are complications affecting about 25% of all patients with long-standing type 1 and type 2 diabetes mellitus and are a major cause of significant decrease in vision and quality of life. Age-related macular degeneration (AMD) is not uncommon, and diabetes mellitus affects the incidence and progression of AMD through altering hemodynamics, increasing oxidative stress, accumulating advanced glycation end products, etc. Recent studies sug...

  8. he Effects of Glaucoma and Age-Related Macular Degeneration on Quality of Life

    OpenAIRE

    Nilüfer Koçak; Behice Elif Onur; Hüseyin Aslankara; Hasan Can Cimilli; Süleyman Kaynak

    2014-01-01

    Objectives: The aim of the study was to assess the depressive and anxiety symptoms and the quality of life (QofL) in patients treated for glaucoma and age-related macular degeneration (AMD). Materials and Methods: Between March 1 and June 30, 2008, 60 outpatients with glaucoma and AMD were included into the study. As controls, sixty patients with similar sociodemographic features and who applied to the Ophthalmology Clinics with refractive errors only were taken. All patients and ...

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

    Science.gov (United States)

    Blokh, David; Stambler, Ilia

    2016-03-19

    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.

  10. Cost effectiveness of treatments for wet age-related macular degeneration

    OpenAIRE

    Mitchell, Paul; Annemans, Lieven; White, Richard; Gallagher, Meghan; Thomas, Simu

    2011-01-01

    Age-related macular degeneration (AMD) is a leading cause of blindness in people aged >= 50 years. Wet AMD in particular has a major impact on patient quality of life and imposes substantial burdens on healthcare systems. This systematic review examined the cost-effectiveness data for current therapeutic options for wet AMD. PubMed and EMBASE databases were searched for all articles reporting original cost-effectiveness analyses of wet AMD treatments. The Centre for Reviews and Dissemination ...

  11. Long-term effectiveness of ranibizumab for age-related macular degeneration and diabetic macular edema

    OpenAIRE

    Fong, Angie HC; Lai, Timothy YY

    2013-01-01

    Neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME) are major causes of visual impairment in the elderly population worldwide. With the aging population, the prevalence of neovascular AMD and DME has increased substantially over the recent years. Vascular endothelial growth factor (VEGF) has been implicated as playing an important role in the pathogenesis of both neovascular AMD and DME. Since its introduction in 2006, ranibizumab, a recombinant, humanized, mon...

  12. Cost Effectiveness of Treatments for Wet Age-Related Macular Degeneration

    OpenAIRE

    Paul Mitchell; Lieven Annemans; Richard White; Meghan Gallagher; Simu Thomas

    2011-01-01

    Age-related macular degeneration (AMD) is a leading cause of blindness in people aged ≥50 years. Wet AMD in particular has a major impact on patient quality of life and imposes substantial burdens on healthcare systems. This systematic review examined the cost-effectiveness data for current therapeutic options for wet AMD. PubMed and EMBASE databases were searched for all articles reporting original cost-effectiveness analyses of wet AMD treatments. The Centre for Reviews and Dissemination an...

  13. Management of neovascular Age-related macular degeneration: A review on landmark randomized controlled trials

    OpenAIRE

    Aniruddha Agarwal; Kanika Aggarwal; Vishali Gupta

    2016-01-01

    In the last decade, a number of prospective clinical trials with carefully designed study protocols have been conducted for the treatment of neovascular age-related macular degeneration (AMD). These landmark clinical trials such as ANCHOR and MARINA and, more recently, the Comparison of AMD Treatment Trials and VIEW studies have revolutionized the management of neovascular AMD. While AMD continues to remain a leading cause of severe visual loss worldwide, advances in pharmacotherapeutics have...

  14. Economic Burden of Bilateral Neovascular Age-Related Macular Degeneration: Multi-Country Observational Study

    OpenAIRE

    Alan F. Cruess; Gergana Zlateva; Xiao Xu; Gisele Soubrane; Daniel Pauleikhoff; Andrew Lotery; Jordi Mones; Ronald Buggage; Caroline Schaefer; Tyler Knight; Goss, Thomas F

    2008-01-01

    Background: There is limited previous research examining the healthcare costs of neovascular age-related macular degeneration (NV-AMD), which constrains our understanding of the economic impact of this condition. With aging populations, this leading cause of rapid vision loss in Western countries is expected to become a pressing health predicament, requiring decision makers to evaluate alternative treatment strategies for AMD. Objective: To document the economic burden of bilateral NV-AMD, th...

  15. Dry age-related macular degeneration: A currently unmet clinical need

    OpenAIRE

    Girmens, Jean-François; Sahel, José-Alain; Marazova, Katia

    2012-01-01

    Age-related macular degeneration (AMD) is a leading cause of severe visual impairment and disability in older people worldwide. Although considerable advances in the management of the neovascular form of AMD have been made in the last decade, no therapy is yet available for the advanced dry form of AMD (geographic atrophy). This review focuses on current trends in the development of new therapies targeting specific pathophysiological pathways of dry AMD. Increased understanding of the complex...

  16. Further Evidence for an Association of ABCR Alleles with Age-Related Macular Degeneration

    OpenAIRE

    Allikmets, Rando

    2000-01-01

    Age-related macular degeneration (AMD) accounts for >50% of the registered visual disability among North American and Western European populations and has been associated both with environmental factors, such as smoking, and with genetic factors. Previously we have reported disease-associated variants in the ABCR (also called ABCA4) gene in a subset of patients affected with this complex disorder. We have now tested our original hypothesis, that ABCR is a dominant susceptibility locus for AMD...

  17. Prevalence of depression and its effect on disability in patients with age-related macular degeneration

    OpenAIRE

    Banerjee Anindya; Kumar Suresh; Kulhara Parmanand; Gupta Amod

    2008-01-01

    Aims: To estimate depression in patients with age-related macular degeneration (AMD) and study the relationships among depression, visual acuity, and disability. Materials and Methods: It was a cross-sectional study with consecutive sampling (n = 53) of patients with AMD aged 50 years and above attending the retina clinic of a tertiary care hospital in North India. Depression, general disability and vision-specific disability were assessed in subjects meeting selection criteria. Assessment...

  18. Enhanced low vision rehabilitation for people with age related macular degeneration: a randomised controlled trial

    OpenAIRE

    Reeves, B C; Harper, R. A.; Russell, W B

    2004-01-01

    Aim: To compare the effectiveness of three models of low vision rehabilitation for people with age related macular degeneration (AMD) referred for low vision rehabilitation (LVR): (a) an enhanced low vision rehabilitation model (ELVR) including supplementary home based low vision rehabilitation; (b) conventional low vision rehabilitation (CLVR) based in a hospital clinic; (c) CLVR with home visits that did not include rehabilitation (CELVR), intended to act as a control for the additional con...

  19. Quality of life in age-related macular degeneration: a review of the literature

    OpenAIRE

    Mitchell, Jan; Bradley, Clare

    2006-01-01

    The Age-related Macular Degeneration Alliance International commissioned a review of the literature on quality of life (QoL) in macular degeneration (MD) with a view to increasing awareness of MD, reducing its impact and improving services for people with MD worldwide. Method: A systematic review was conducted using electronic databases, conference proceedings and key journal hand search checks. The resulting 'White Paper' was posted on the AMD Alliance website and is reproduced here. ...

  20. CCR3 is a therapeutic and diagnostic target for neovascular age-related macular degeneration

    OpenAIRE

    2009-01-01

    Age-related macular degeneration (AMD), a leading cause of blindness worldwide, is as prevalent as cancer in industrialized nations. Most blindness in AMD results from invasion of the retina by choroidal neovascularization (CNV). We report that the eosinophil/mast cell chemokine receptor CCR3 is specifically expressed in CNV endothelial cells in humans with AMD, and that, despite the expression of its ligands eotaxin-1, -2, and -3, neither eosinophils nor mast cells are present in human CNV. ...

  1. Mediterranean diet and age-related cognitive decline: a randomized clinical trial

    OpenAIRE

    Valls Pedret, Cinta; Sala Vila, Aleix; Serra Mir, Mercè; Corella, Dolores; Torre Fornell, Rafael de la; Martínez-González, Miguel A.; Martínez Lapiscina, Elena H.; Fitó Colomer, Montserrat; Pérez Heras, Ana; Salas-Salvadó, Jordi; Estruch, Ramón; Ros, Emilio

    2015-01-01

    IMPORTANCE: Oxidative stress and vascular impairment are believed to partly mediate age-related cognitive decline, a strong risk factor for development of dementia. Epidemiologic studies suggest that a Mediterranean diet, an antioxidant-rich cardioprotective dietary pattern, delays cognitive decline, but clinical trial evidence is lacking. OBJECTIVE: To investigate whether a Mediterranean diet supplemented with antioxidant-rich foods influences cognitive function compared with a control diet....

  2. Oxidative Stress, Hypoxia, and Autophagy in the Neovascular Processes of Age-Related Macular Degeneration

    OpenAIRE

    Blasiak, Janusz; Petrovski, Goran; Veréb, Zoltán; Facskó, Andrea; Kaarniranta, Kai

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of severe and irreversible loss of vision in the elderly in developed countries. AMD is a complex chronic neurodegenerative disease associated with many environmental, lifestyle, and genetic factors. Oxidative stress and the production of reactive oxygen species (ROS) seem to play a pivotal role in AMD pathogenesis. It is known that the macula receives the highest blood flow of any tissue in the body when related to size, and anythin...

  3. Is Age-Related Macular Degeneration Associated with Stroke Among Elderly Americans?§

    OpenAIRE

    Liao, Duanping; Mo, Jingping; Duan, Yinkang; Klein, Ronald; Scott, Ingrid U.; Huang, Kui A; Zhou, Haibo

    2008-01-01

    Objective: To investigate whether age-related macular degeneration (AMD) is associated with the development of ischemic and hemorrhagic stroke among elderly Americans. Design: Population-based cohort study. Participants: The five percent random sample of 2000-2003 Medicare enrollees was obtained. The cohort (n=1,519,086) consisted of enrollees who were aged 65 or older at the first two-year (January 1, 2000 to December 31, 2001). Methods: Baseline demographic variables and chronic conditions ...

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

    OpenAIRE

    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, photorecept...

  5. Genetics of Immunological and Inflammatory Components in Age-related Macular Degeneration

    OpenAIRE

    Tuo, Jingsheng; Grob, Seanna; Zhang, Kang; Chan, Chi-Chao

    2012-01-01

    Age-related macular degeneration (AMD), affecting 30 to 50 million elder individuals worldwide, is a disease affecting the macular retina and choroid that can lead to irreversible central vision loss and blindness. Recent findings support a role for immunologic processes in AMD pathogenesis, including generation of inflammatory related molecules in the Bruch’s membrane, recruitment of macrophages, complement activation, microglial activation and accumulation in the macular lesions. Pro-inflam...

  6. Combined treatment of exudative age related macular degeneration with photodynamic therapy and intravitreal triamcinolone

    OpenAIRE

    Ruiz-Moreno , Jose

    2008-01-01

    José Mª Ruiz-Moreno1,2, Javier A Montero21Department of Ophthalmology, Miguel Hernández University School of Medicine, Alicante, Spain; 2Vitreo-Retinal Unit, Alicante Institute of Ophthalmology, Alicante, SpainAbstract: Choroidal neovascularization (CNV) secondary to age related macular degeneration is among the leading causes of legal blindness in developed countries. Photodynamic therapy (PDT) with verteporfin induces CNV closure causing little damage to healt...

  7. Age-Related Macular Degeneration: Clinical Findings following Treatment with Antiangiogenic Drugs

    OpenAIRE

    Ricardo Casaroli-Marano; Roberto Gallego-Pinazo; Clemencia Torrón Fernández-Blanco; Figueroa, Marta S.; Begoña Pina Marín; Gustavo Fernández-Baca Vaca; Antonio Piñero-Bustamante; Juan Donate López; José García-Arumí; Jordi Farrés Martí

    2014-01-01

    Purpose. To survey the management of patients with neovascular age-related macular degeneration (nvAMD) in Spain. Methods. An observational retrospective multicenter study was conducted. The variables analyzed were sociodemographic characteristics, foveal and macular thickness, visual acuity (VA), type of treatment, number of injections, and the initial administration of a loading dose of an antiangiogenic drug. Results. 208 patients were followed up during 23.4 months in average. During the ...

  8. Comparison of life quality scores of ranibizumab-treated patients with age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Saadet Arslan

    2016-03-01

    Full Text Available Purpose: To evaluate the visual acuity, fluorescein angiography, optic coherence tomography and life quality of patients diagnosed with exudative age-related macular degeneration and administered with intravitreal Ranibizumab injection. Material and Methods: This study included of 48 different patients who were diagnosed as exudative age-related macular degeneration and administered with ranibizumab injection. In this study, demographic characteristics, pre- and post-injection corrected visual acuity, angiography, optic coherence tomography alteration and the scores of quality of life questionnaire were prospectively analyzed. Results: The patients were followed up for 20+/-1 months on average. After ranibizumab injection, 12 patients (25% gained and #8805;3 lines of visual acuity, 28 patients (58.3% gained and #8804;3 lines of visual acuity, 6 patients (12.5% lost and #8804;3 lines of visual acuity and 2 patients (4.2% lost and #8805;3 lines of visual acuity. The increase in Early Treatment Diabetic Retinopathy Study was lower in patients with Hypertension and positive family history In this study, it was determined that The National Eye Institute Visual Function Questionnaire score increased in patients with improving visual acuity after ranibizumab injection and the difference was statistically significant. Conclusion: Visual acuity was found to improve in patients with exudative age-related macular degeneration and treated with intravitreal ranibizumab injection. The National Eye Institute Visual Function Questionnaire provided reliable results in patients with age-related macular degeneration and the questionnaire score was determined to increase following the treatment. [Cukurova Med J 2016; 41(1.000: 61-68

  9. Epidemiology and quality of life of patients with age-related macular degeneration.

    Science.gov (United States)

    Synek, Svatopluk; Vojniković, Bozo; Pahor, Dana

    2010-04-01

    It is well known that age-related macular degeneration (AMD), besides glaucoma and diabetic retinopathy, represents a major cause of low vision and blindness throughout the world. In this study, specific causal factors of AMD are analyzed, emphasizing the causal role and effects of sunlight, no matter which part of its spectrum, in a longer exposition through life. The accent is also put on the influence of lifestyle as well as vitamin and antioxidants supplementation in development or prevention of AMD.

  10. Epidemiology and Quality of Life of Patients with Age-Related Macular Degeneration

    OpenAIRE

    Synek, Svatopluk; Vojniković, Božo; Pahor, Đana

    2010-01-01

    It is well known that age-related macular degeneration (AMD), besides glaucoma and diabetic retinopathy, represents a major cause of low vision and blindness throughout the world. In this study, specific causal factors of AMD are analyzed, emphasizing the causal role and effects of sunlight, no matter which part of its spectrum, in a longer exposition through life. The accent is also put on the influence of lifestyle as well as vitamin and antioxidants supplementation in development or preven...

  11. Device for fluorescent control and photodynamic therapy of age-related macula degeneration

    Science.gov (United States)

    Loschenov, Victor B.; Meerovich, Gennadii A.; Budzinskaya, M. V.; Ermakova, N. A.; Shevchik, S. A.; Kharnas, Sergey S.

    2004-07-01

    Age-related macula degeneration (AMD) is a wide spread disease the appearance of which leads to poor eyesight and blindness. A method of treatment is not determined until today. Traditional methods, such as laser coagulation and surgical operations are rather traumatic for eye and often bring to complications. That's why recently a photodynamic method of AMD treatment is studied. Based on photodynamic occlusion of choroidal neovascularization (CNV) with minimal injury to overlying neurosensory retina what increases the efficiency.

  12. Age-related changes in conventional road versus off-road triathlon performance.

    Science.gov (United States)

    Lepers, Romuald; Stapley, Paul J

    2011-08-01

    The aims of this study were: (i) to analyze age-related declines in swimming, cycling, and running performances for road-based and off-road triathlons, and (ii) to compare age-related changes in these three disciplines between road-based and off-road triathlons. Swimming, cycling, running and total time performances of the top five males between 20 and 70 years of age (in 5-year intervals) were analyzed for short distance road-based (1.5 km swim, 40 km cycle, and 10 km run) and off-road (1.5 km swim, 30 km mountain bike, and 11 km trail run) triathlons at the 2009 World Championships. Independently of age, there was a lesser age-related decline in cycling performance (P triathlon. In contrast, age-related decline did not differ between the three locomotion modes for off-road triathlon. With advancing age, the performance decline was less pronounced (P triathlon in swimming (≥65 years), cycling (≥50 years), running (≥60 years), and total event (≥55 years) times, respectively. These results suggest that the rate of the decline in performance for off-road triathlon is greater than for road-based triathlon, indicating that the type of discipline (road vs. mountain bike cycling and road vs. trail running) exerts an important influence on the magnitude of the age-associated changes in triathlon performance.

  13. Premature Aging-related Peripheral Neuropathy in a Mouse Model of Progeria

    Science.gov (United States)

    Goss, James R.; Stolz, Donna Beer; Robinson, Andria Rasile; Zhang, Mingdi; Arbujas, Norma; Robbins, Paul D.; Glorioso, Joseph C.; Niedernhofer, Laura J.

    2011-01-01

    Peripheral neuropathy is a common aging-related degenerative disorder that interferes with daily activities and leads to increased risk of falls and injury in the elderly. The etiology of most aging-related peripheral neuropathy is unknown. Inherited defects in several genome maintenance mechanisms cause tissue-specific accelerated aging, including neurodegeneration. We tested the hypothesis that a murine model of XFE progeroid syndrome, caused by reduced expression of ERCC1-XPF DNA repair endonuclease, develops peripheral neuropathy. Nerve conduction studies revealed normal nerve function in young adult (8 week) Ercc1−/Δ mice, but significant abnormalities in 20 week-old animals. Morphologic and ultrastructural analysis of the sciatic nerve from mutant mice revealed significant alterations at 20 but not 8 weeks of age. We conclude that Ercc1−/Δ mice have accelerated spontaneous peripheral neurodegeneration that mimics aging-related disease. This provides strong evidence that DNA damage can drive peripheral neuropathy and offers a rapid and novel model to test therapies. PMID:21596054

  14. Age-related differences in emotion recognition ability: a cross-sectional study.

    Science.gov (United States)

    Mill, Aire; Allik, Jüri; Realo, Anu; Valk, Raivo

    2009-10-01

    Experimental studies indicate that recognition of emotions, particularly negative emotions, decreases with age. However, there is no consensus at which age the decrease in emotion recognition begins, how selective this is to negative emotions, and whether this applies to both facial and vocal expression. In the current cross-sectional study, 607 participants ranging in age from 18 to 84 years (mean age = 32.6 +/- 14.9 years) were asked to recognize emotions expressed either facially or vocally. In general, older participants were found to be less accurate at recognizing emotions, with the most distinctive age difference pertaining to a certain group of negative emotions. Both modalities revealed an age-related decline in the recognition of sadness and -- to a lesser degree -- anger, starting at about 30 years of age. Although age-related differences in the recognition of expression of emotion were not mediated by personality traits, 2 of the Big 5 traits, openness and conscientiousness, made an independent contribution to emotion-recognition performance. Implications of age-related differences in facial and vocal emotion expression and early onset of the selective decrease in emotion recognition are discussed in terms of previous findings and relevant theoretical models.

  15. Age-related changes in the integration of gaze direction and facial expressions of emotion.

    Science.gov (United States)

    Slessor, Gillian; Phillips, Louise H; Bull, Rebecca

    2010-08-01

    Gaze direction influences younger adults' perception of emotional expressions, with direct gaze enhancing the perception of anger and joy, while averted gaze enhances the perception of fear. Age-related declines in emotion recognition and eye-gaze processing have been reported, indicating that there may be age-related changes in the ability to integrate these facial cues. As there is evidence of a positivity bias with age, age-related difficulties integrating these cues may be greatest for negative emotions. The present research investigated age differences in the extent to which gaze direction influenced explicit perception (e.g., anger, fear and joy; Study 1) and social judgments (e.g., of approachability; Study 2) of emotion faces. Gaze direction did not influence the perception of fear in either age group. In both studies, age differences were found in the extent to which gaze direction influenced judgments of angry and joyful faces, with older adults showing less integration of gaze and emotion cues than younger adults. Age differences were greatest when interpreting angry expressions. Implications of these findings for older adults' social functioning are discussed.

  16. Age-Related Differences in Gait Kinematics, Kinetics, and Muscle Function: A Principal Component Analysis.

    Science.gov (United States)

    Schloemer, Sarah A; Thompson, Julie A; Silder, Amy; Thelen, Darryl G; Siston, Robert A

    2017-03-01

    Age-related increased hip extensor recruitment during gait is a proposed compensation strategy for reduced ankle power generation and may indicate a distal-to-proximal shift in muscle function with age. Extending beyond joint level analyses, identifying age-related changes at the muscle level could capture more closely the underlying mechanisms responsible for movement. The purpose of this study was to characterize and compare muscle forces and induced accelerations during gait in healthy older adults with those of young adults. Simulations of one gait cycle for ten older (73.9 ± 5.3 years) and six young (21.0 ± 2.1 years) adults walking at their self-selected speed were analyzed. Muscle force and induced acceleration waveforms, along with kinematic, kinetic, and muscle activation waveforms, were compared between age-groups using principal component analysis. Simulations of healthy older adults had greater gluteus maximus force and vertical support contribution, but smaller iliacus force, psoas force, and psoas vertical support contribution. There were no age-group differences in distal muscle force, contribution, or ankle torque magnitudes. Later peak dorsiflexion and peak ankle angular velocity in older adults may have contributed to their greater ankle power absorption during stance. These findings reveal the complex interplay between age-related changes in neuromuscular control, kinematics, and muscle function during gait.

  17. Therapeutic potential of eccentric exercises for age-related muscle atrophy

    Directory of Open Access Journals (Sweden)

    Jae-Young Lim

    2016-09-01

    Full Text Available Recent studies have focused on evidence-based interventions to prevent mobility decline and enhance physical performance in older adults. Several modalities, in addition to traditional strengthening programs, have been designed to manage age-related functional decline more effectively. In this study, we reviewed the current relevant literatures to assess the therapeutic potential of eccentric exercises for age-related muscle atrophy (sarcopenia. Age-related changes in human skeletal muscle, and their relationship with physical performance, are discussed with reference to in vitro physiologic and human biomechanics studies. An overview of issues relevant to sarcopenia is provided in the context of the recent consensus on the diagnosis and management of the condition. A decline in mobility among the aging population is closely linked with changes in the muscle force–velocity relationship. Interventions based specifically on increasing velocity and eccentric strength can improve function more effectively compared with traditional strengthening programs. Eccentric strengthening programs are introduced as a specific method for improving both muscle force and velocity. To be more effective, exercise interventions for older adults should focus on enhancing the muscle force–velocity relationship. Exercises that can be performed easily, and that utilize eccentric strength (which is relatively spared during the aging process, are needed to improve both muscle force and velocity.

  18. Middle ear impedance studies in elderly patients implications on age-related hearing loss

    Directory of Open Access Journals (Sweden)

    Olusola Ayodele Sogebi

    2015-04-01

    Full Text Available INTRODUCTION: Controversies arise with respect to functioning of the middle ear over time.OBJECTIVE: To assess changes in middle ear impedance that may be related to aging, and/or if there was an association of these changes with those of the inner ear in the elderly patients.METHODS: Cross-sectional, comparative study of elderly patients managed in ear, nose and throat clinics. A structured questionnaire was administered to obtain clinical information. Pure tone audiometry, tympanometry, and acoustic reflexes were performed. Comparative analyses were performed to detect intergroup differences between clinico-audiometric findings and middle ear measures, viz. tympanograms and acoustic reflexes.RESULTS: One hundred and three elderly patients participated in the study; 52.4% were male, averagely 70.0 ± 6.3 years old, age-related hearing loss in 59.2%, abnormal tympanograms in 39.3%, absent acoustic reflex in 37.9%. There was no association between age and gender in patients with abnormal tympanograms and absent acoustic reflex. Significantly more patients with different forms and grades of age-related hearing loss had abnormal tympanometry and absent acoustic reflex.CONCLUSION: Some abnormalities were observed in the impedance audiometric measures of elderly patients, which were significantly associated with parameters connected to age-related hearing loss.

  19. Developmental improvement and age-related decline in unfamiliar face matching.

    Science.gov (United States)

    Megreya, Ahmed M; Bindemann, Markus

    2015-01-01

    Age-related changes have been documented widely in studies of face recognition and eyewitness identification. However, it is not clear whether these changes arise from general developmental differences in memory or occur specifically during the perceptual processing of faces. We report two experiments to track such perceptual changes using a 1-in- 10 (experiment 1) and 1-in-1 (experiment 2) matching task for unfamiliar faces. Both experiments showed improvements in face matching during childhood and adult-like accuracy levels by adolescence. In addition, face-matching performance declined in adults of the age of 65 years. These findings indicate that developmental improvements and aging-related differences in face processing arise from changes in the perceptual encoding of faces. A clear face inversion effect was also present in all age groups. This indicates that those age-related changes in face matching reflect a quantitative effect, whereby typical face processes are engaged but do not operate at the best-possible level. These data suggest that part of the problem of eyewitness identification in children and elderly persons might reflect impairments in the perceptual processing of unfamiliar faces.

  20. Magnetic resonance fiber density mapping of age-related white matter changes

    Energy Technology Data Exchange (ETDEWEB)

    Stadlbauer, Andreas, E-mail: andi@nmr.at [MR Physics Group, Department of Radiology, Landesklinikum St. Poelten, Propst Fuehrer Strasse 4, A-3100 St. Poelten (Austria); Department of Neurosurgery, University of Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen (Germany); Ganslandt, Oliver [Department of Neurosurgery, University of Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen (Germany); Salomonowitz, Erich [MR Physics Group, Department of Radiology, Landesklinikum St. Poelten, Propst Fuehrer Strasse 4, A-3100 St. Poelten (Austria); Buchfelder, Michael [Department of Neurosurgery, University of Erlangen-Nuremberg, Schwabachanlage 6, 91054 Erlangen (Germany); Hammen, Thilo [Department of Neurology, Epilepsy Center, University of Erlangen-Nuremberg, Schwabachanlage 6, D-90429 Erlangen (Germany); Bachmair, Johanna [MR Physics Group, Department of Radiology, Landesklinikum St. Poelten, Propst Fuehrer Strasse 4, A-3100 St. Poelten (Austria); Eberhardt, Knut [Krankenhaus Schloss Werneck, MRT-Kompetenzzentrum, Balthasar-Neumann-Platz 1, D-97440 Werneck (Germany)

    2012-12-15

    Objectives: To introduce fiber density mapping (FDM) for investigation of age-related white matter (WM) changes and to compare its capabilities with conventional diffusion tensor imaging (DTI) post-processing. Methods: DTI data with 1.9 mm{sup 3} isotropic voxels were acquired from 44 healthy volunteers (18–88 years) at 3 T. FDM is a 3-step approach which includes diagonalization of the diffusion tensor, fiber reconstruction for the whole brain, and calculation of fiber density (FD) values. Maps of fractional anisotropy (FA) and mean diffusivity (MD) were additionally calculated. Voxel-based analyses were performed to determine volume clusters of significant correlation with age. Bivariate linear regression models and Hotelling–Williams tests were used to detect significant differences between correlations. Results: FDM detected a larger WM volume affected by age-related changes concomitant with fewer significant clusters compared to FA and MD. This indicates that WM alterations due to normal aging occur rather globally than locally. FD values showed a significant stronger correlation with age in frontal lobes (prefrontal and precentral gyrus), limbic lobes (cingulate and parahippocampal gyrus), the corpus callosum (genu) and temporal lobes. Conclusions: FDM shows higher sensitivity for detection of age-related WM changes because it includes all surrounding fiber structures into the evaluation of each DTI data voxel.

  1. Influence of anti-VEGF about cardiovascular biomarkers in age related macular degeneration.

    Science.gov (United States)

    Manresa, N; Mulero, J; Losada, M; Zafrilla, P

    2015-02-01

    Systemic VEGF inhibition disrupts endothelial homeostasis and accelerates the atherogenesis, suggesting that these events contribute to the clinical cardiovascular adverse events of VEGF-inhibiting therapies. The objective of the current study was to analyze the effect of anti-VEGF therapy on cardiovascular risk factors in patients with exudative age related macular degeneration. A total of 73 patients with exudative age related macular degeneration (without previous anti-VEGF therapy) were treated with two anti-VEGF: Ranibizumab and Pegaptanib sodium. The follow up was 6 months. The following parameters were determined before and after treatment: homocysteine, lipids (total cholesterol, triglycerides, HDL-c, LDL-c), C-Reactive Protein and fibrinogen. There were not statistically significant differences in parameters studied before and after treatment with both Pegaptanib sodium and Ranibizumab, except C-Reactive Protein. Of all patients analyzed, only 3 of them have initially C-Reactive Protein levels above normal levels and after antiangiogenic therapy, there was a significant increase in C-Reactive Protein. We have not found results in our study who to suspect that treatment with anti-VEGF in the patients with exudative age related macular degeneration increases cardiovascular risk predictors. However, after therapy was increased the CRP and fibrinogen may mean that anti-VEGF contribute an alteration of endothelial homeostasis in exudative AMD.

  2. AGE-RELATED DIFFERENCES IN SLEEP-WAKE SYMPTOMS OF ADULTS UNDERGOING POLYSOMNOGRAPHY

    Science.gov (United States)

    Vaz Fragoso, Carlos A.; Van Ness, Peter H.; Araujo, Katy L.B; Iannone, Lynne P.; Yaggi, H. Klar

    2017-01-01

    OBJECTIVES To evaluate age-related differences in sleep-wake symptoms. DESIGN Cross-sectional. SETTING Technologist-attended, laboratory-based polysomnography (PSG). PARTICIPANTS 201 community-dwelling adults aged 20–89, including 52 aged 18–39, 72 aged 40–59, and 77 aged ≥60. MEASUREMENTS 1) Medical burden: Charlson Comorbidity Index, medications, and health status; 2) PSG-defined sleep disorders: sleep-disordered breathing (SDB), sleep-associated hypoxemia, and periodic limb movements in sleep (PLMS); 3) sleep-wake symptoms: Epworth Sleepiness Scale (ESS), Insomnia Severity Index (ISI), and fatigue (Facit-F Scale). RESULTS Medical burden increased significantly across the age groups of 18–39, 40–59 and ≥60 (psleep disorders increased significantly across the age groups of 18–39, 40–59 and ≥60 (psleep-wake symptoms across the age groups of 18–39, 40–59 and ≥60 (p=.020 for daytime drowsiness [ESS≥10]; p=.036 for insomnia [ISI≥8]; psleep-wake symptoms (daytime drowsiness, insomnia and fatigue), despite an age-related increase in disease severity (medical burden and sleep disorders). Because the increase in disease severity included well-established risk factors for having sleep-wake symptoms, we posit that the age-related decrease in sleep-wake symptoms may reflect reduced symptom awareness. PMID:26389988

  3. Detection of age-related duplications in mtDNA from human muscles and bones.

    Science.gov (United States)

    Lacan, Marie; Thèves, Catherine; Keyser, Christine; Farrugia, Audrey; Baraybar, Jose-Pablo; Crubézy, Eric; Ludes, Bertrand

    2011-03-01

    Several studies have demonstrated the age-related accumulation of duplications in the D-loop of mitochondrial DNA (mtDNA) extracted from skeletal muscle. This kind of mutation had not yet been studied in bone. The detection of age-related mutations in bone tissue could help to estimate age at death within the context of legal medicine or/and anthropological identification procedures, when traditional osteological markers studied are absent or inefficient. As we detected an accumulation of a point mutation in mtDNA from an older individual's bones in a previous study, we tried here to identify if three reported duplications (150, 190, 260 bp) accumulate in this type of tissue. We developed a sensitive method which consists in the use of back-to-back primers during amplification followed by an electrophoresis capillary analysis. The aim of this study was to confirm that at least one duplication appears systematically in muscle tissue after the age of 20 and to evaluate the duplication age appearance in bones extracted from the same individuals. We found that the number of duplications increase from 38 years and that at least one duplicated fragment is present in 50% of cases after 70 years in this tissue. These results confirm that several age-related mutations can be detected in the D-loop of mtDNA and open the way for the use of molecular markers for age estimation in forensic and/or anthropological identification.

  4. Age-Related Reduced Somatosensory Gating Is Associated with Altered Alpha Frequency Desynchronization

    Directory of Open Access Journals (Sweden)

    Chia-Hsiung Cheng

    2015-01-01

    Full Text Available Sensory gating (SG, referring to an attenuated neural response to the second identical stimulus, is considered as preattentive processing in the central nervous system to filter redundant sensory inputs. Insufficient somatosensory SG has been found in the aged adults, particularly in the secondary somatosensory cortex (SII. However, it remains unclear which variables leading to the age-related somatosensory SG decline. There has been evidence showing a relationship between brain oscillations and cortical evoked excitability. Thus, this study used whole-head magnetoencephalography to record responses to paired-pulse electrical stimulation to the left median nerve in healthy young and elderly participants to test whether insufficient stimulus 1- (S1- induced event-related desynchronization (ERD contributes to a less-suppressed stimulus 2- (S2- evoked response. Our analysis revealed that the minimum norm estimates showed age-related reduction of SG in the bilateral SII regions. Spectral power analysis showed that the elderly demonstrated significantly reduced alpha ERD in the contralateral SII (SIIc. Moreover, it was striking to note that lower S1-induced alpha ERD was associated with higher S2-evoked amplitudes in the SIIc among the aged adults. Conclusively, our findings suggest that age-related decline of somatosensory SG is partially attributed to the altered S1-induced oscillatory activity.

  5. Age-related differences in sleep-based memory consolidation: A meta-analysis.

    Science.gov (United States)

    Gui, Wen-Jun; Li, Hui-Jie; Guo, Yu-Hua; Peng, Peng; Lei, Xu; Yu, Jing

    2017-02-02

    A period of post-learning sleep benefits memory consolidation compared with an equal-length wake interval. However, whether this sleep-based memory consolidation changes as a function of age remains controversial. Here we report a meta-analysis that investigates the age differences in the sleep-based memory consolidation in two types of memory: declarative memory and procedural memory. The meta-analysis included 22 comparisons of the performance between young adults (N =640) and older adults (N =529) on behavioral tasks measuring sleep-based memory consolidation. Our results showed a significant overall sleep-based beneficial effect in young adults but not in older adults. However, further analyses suggested that the age differences were mainly manifested in sleep-based declarative memory consolidation but not in procedural memory consolidation. We discussed the possible underlying mechanisms for the age-related degradation in sleep-based memory consolidation. Further research is needed to determine the crucial components for sleep-related memory consolidation in older adults such as age-related changes in neurobiological and cardiovascular functions, which may play an important role in this context and have the potential to delineate the interrelationships between age-related changes in sleep and memory.

  6. Stereotactic radiotherapy for wet age-related macular degeneration: current perspectives

    Directory of Open Access Journals (Sweden)

    Neffendorf JE

    2015-09-01

    Full Text Available James E Neffendorf, Timothy L Jackson Department of Ophthalmology, School of Medicine, King’s College London, London, United Kingdom Abstract: Neovascular age-related macular degeneration is a leading cause of blindness in the developed world. Currently, the treatment of choice is intravitreal injections of anti-VEGF medications. These require frequent dosing, up to monthly, and impose a substantial burden on patients and the health economy. Ionizing radiation was proposed as a possible treatment for age-related macular degeneration due to its anti-inflammatory and anti-fibrotic properties. Stereotactic radiotherapy is an outpatient-based radiotherapy platform that provides stereotactic application of low energy X-ray to the retina in three highly collimated beams that cross the inferior sclera to overlap at the macula. A randomized, double-masked, sham-controlled trial of 230 patients (INTREPID showed that a single dose of stereotactic radiotherapy significantly reduces the number of intravitreal anti-VEGF injections needed over 2 years. A larger randomized controlled trial (STAR is underway. Keywords: wet age-related macular degeneration, radiation therapy, stereotactic radiotherapy, vascular endothelial growth factor

  7. Age-related structural and functional changes in the cochlear nucleus.

    Science.gov (United States)

    Frisina, Robert D; Walton, Joseph P

    2006-01-01

    Presbycusis - age-related hearing loss - is a key communication disorder and chronic medical condition of our aged population. The cochlear nucleus is the major site of projections from the auditory portion of the inner ear. Relative to other levels of the peripheral and central auditory systems, relatively few studies have been conducted examining age-related changes in the cochlear nucleus. The neurophysiological investigations suggest declines in glycine-mediated inhibition, reflected in increased firing rates in cochlear nucleus neurons from old animals relative to young adults. Biochemical investigations of glycine inhibition in the cochlear nucleus are consistent with the functional aging declines of this inhibitory neurotransmitter system that affect complex sound processing. Anatomical reductions in neurons of the cochlear nucleus and their output pathways can occur due to aging changes in the brain, as well as due to age-dependent plasticity of the cochlear nucleus in response to the age-related loss of inputs from the cochlea, particularly from the basal, high-frequency regions. Novel preventative and curative biomedical interventions in the future aimed at alleviating the hearing loss that comes with age, will likely emanate from increasing our knowledge and understanding of its neural and molecular bases. To the extent that this sensory deficit resides in the central auditory system, including the cochlear nucleus, future neural therapies will be able to improve hearing in the elderly.

  8. The relevance of chemokine signalling in modulating inherited and age-related retinal degenerations.

    Science.gov (United States)

    Luhmann, Ulrich Fo; Robbie, Scott J; Bainbridge, James Wb; Ali, Robin R

    2014-01-01

    Systemic monocytes, tissue resident macrophages, dendritic cells and microglia have specific roles in immune surveillance and maintenance of tissue homeostasis and are key regulator and effector cells of the local immune response to acute and chronic tissue injury.Two major signalling pathways that differentially define trafficking behaviour and activation of systemic and local myeloid cell populations in response to exogenous and endogenous inflammatory stimuli are the Ccl2-Ccr2 and the Cx3cl1-Cx3cr1 chemokine pathways.Alterations in these pathways have been implicated in controlling myeloid cell activation during normal ageing and in age-related retinal degenerations, including age-related macular degeneration (AMD).We review the evidence for how altered chemokine signalling in acute and chronic inflammatory conditions regulate local and systemic myeloid cell responses in the retina and how this may contribute to or attenuate pathology in inherited and age-related retinal diseases. We discuss the role of environmental factors (e.g. light exposure) and the influence of genetic factors on the manifestation of pathology in experimental models and in human patients and how we envisage harnessing this knowledge for the development of targeted, more broadly applicable anti-inflammatory treatment strategies for a wide range of retinal degenerations.

  9. Gender differences in age-related decline in regional cerebral glucose metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Bang, Seong Ae; Cho, Sang Soo; Yoon, Eun Jin; Park, Hyun Soo; Lee, Eun Ju; Kim, Yu Kyeong; Kim, Sang Sun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    In this study, we investigated gender differences in age-related declines in regional cerebral glucose metabolism using FDG-PET in a large population sample with a broad age range. 230 healthy subjects (90 male; age: 34-80 y, 140 females; age: 33-82 y) participated. Correlation maps showing age related declines in glucose uptake were created separately for each gender in SPM2. Using population-based probabilistic volume of interests (VOIs), VOIs were defined for the regions showing significant decline with aging. Age related declines were separately assessed within each age range using analysis of covariate in SPSS 13.0. In the total population without gender effect, age-related negative correlation of glucose metabolism was found in the bilateral inferior frontal gyri, bilateral caudate, bilateral thalamus, left insula, left superior frontal gyrus, left uncus, right superior temporal gyrus, right medial frontal gyrus, right parahippocampal gyrus, right anterior cingulate gyrus (P < 0.001 corrected, extent threshold k = 100). 14 VOIs values of brain regions were calculated based on this negative correlation results. The rate of decline across all defined VOIs assessed in the age category of 'more than 70' referenced to the category of '30- 39years' were 7.85% in the entire sample; 7.62% in male and 8.09% in female. Detailed analyses of declines in each age range showed separable patterns of declines across gender. In males, greater decline was observed after the age 60 (20.45%) than the ages of 30 and 50(7.98%). Whereas in females, greater declines were found in age 60s (20.15%) compared to 50s, and in 40(14.84%) compared to 30s. Age-related decline in cerebral glucose metabolism was found in both genders. We further observed that males show a relatively constant pattern of decline across a life span; whereas, females show a pattern of steep changes aging to 60s and to 40s, which may be related to changes in sex hormone levels after menopause.

  10. Bioavailable copper modulates oxidative phosphorylation and growth of tumors.

    Science.gov (United States)

    Ishida, Seiko; Andreux, Pénélope; Poitry-Yamate, Carole; Auwerx, Johan; Hanahan, Douglas

    2013-11-26

    Copper is an essential trace element, the imbalances of which are associated with various pathological conditions, including cancer, albeit via largely undefined molecular and cellular mechanisms. Here we provide evidence that levels of bioavailable copper modulate tumor growth. Chronic exposure to elevated levels of copper in drinking water, corresponding to the maximum allowed in public water supplies, stimulated proliferation of cancer cells and de novo pancreatic tumor growth in mice. Conversely, reducing systemic copper levels with a chelating drug, clinically used to treat copper disorders, impaired both. Under such copper limitation, tumors displayed decreased activity of the copper-binding mitochondrial enzyme cytochrome c oxidase and reduced ATP levels, despite enhanced glycolysis, which was not accompanied by increased invasiveness of tumors. The antiproliferative effect of copper chelation was enhanced when combined with inhibitors of glycolysis. Interestingly, larger tumors contained less copper than smaller tumors and exhibited comparatively lower activity of cytochrome c oxidase and increased glucose uptake. These results establish copper as a tumor promoter and reveal that varying levels of copper serves to regulate oxidative phosphorylation in rapidly proliferating cancer cells inside solid tumors. Thus, activation of glycolysis in tumors may in part reflect insufficient copper bioavailability in the tumor microenvironment.

  11. Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation.

    Science.gov (United States)

    Wang, Jing; Luo, Cheng; Shan, Changliang; You, Qiancheng; Lu, Junyan; Elf, Shannon; Zhou, Yu; Wen, Yi; Vinkenborg, Jan L; Fan, Jun; Kang, Heebum; Lin, Ruiting; Han, Dali; Xie, Yuxin; Karpus, Jason; Chen, Shijie; Ouyang, Shisheng; Luan, Chihao; Zhang, Naixia; Ding, Hong; Merkx, Maarten; Liu, Hong; Chen, Jing; Jiang, Hualiang; He, Chuan

    2015-12-01

    Copper is a transition metal that plays critical roles in many life processes. Controlling the cellular concentration and trafficking of copper offers a route to disrupt these processes. Here we report small molecules that inhibit the human copper-trafficking proteins Atox1 and CCS, and so provide a selective approach to disrupt cellular copper transport. The knockdown of Atox1 and CCS or their inhibition leads to a significantly reduced proliferation of cancer cells, but not of normal cells, as well as to attenuated tumour growth in mouse models. We show that blocking copper trafficking induces cellular oxidative stress and reduces levels of cellular ATP. The reduced level of ATP results in activation of the AMP-activated protein kinase that leads to reduced lipogenesis. Both effects contribute to the inhibition of cancer cell proliferation. Our results establish copper chaperones as new targets for future developments in anticancer therapies.

  12. Inhibition of human copper trafficking by a small molecule significantly attenuates cancer cell proliferation

    Science.gov (United States)

    Wang, Jing; Luo, Cheng; Shan, Changliang; You, Qiancheng; Lu, Junyan; Elf, Shannon; Zhou, Yu; Wen, Yi; Vinkenborg, Jan L.; Fan, Jun; Kang, Heebum; Lin, Ruiting; Han, Dali; Xie, Yuxin; Karpus, Jason; Chen, Shijie; Ouyang, Shisheng; Luan, Chihao; Zhang, Naixia; Ding, Hong; Merkx, Maarten; Liu, Hong; Chen, Jing; Jiang, Hualiang; He, Chuan

    2015-12-01

    Copper is a transition metal that plays critical roles in many life processes. Controlling the cellular concentration and trafficking of copper offers a route to disrupt these processes. Here we report small molecules that inhibit the human copper-trafficking proteins Atox1 and CCS, and so provide a selective approach to disrupt cellular copper transport. The knockdown of Atox1 and CCS or their inhibition leads to a significantly reduced proliferation of cancer cells, but not of normal cells, as well as to attenuated tumour growth in mouse models. We show that blocking copper trafficking induces cellular oxidative stress and reduces levels of cellular ATP. The reduced level of ATP results in activation of the AMP-activated protein kinase that leads to reduced lipogenesis. Both effects contribute to the inhibition of cancer cell proliferation. Our results establish copper chaperones as new targets for future developments in anticancer therapies.

  13. DRYAD and ADH: Further comments on explaining age-related differences in memory.

    Science.gov (United States)

    Naveh-Benjamin, Moshe; Smyth, Andrea C

    2016-02-01

    Recently, Smyth and Naveh-Benjamin (2016) questioned some of the main assumptions/hypotheses of DRYAD (or density of representations yields age-related deficits), a global-deficit model of aging and memory judgments (Benjamin, 2010; Benjamin et al., 2012). Smyth and Naveh-Benjamin (2016) provided empirical evidence that seems incompatible with DRYAD, but that fits the associative deficit hypothesis (ADH; Naveh-Benjamin, 2000), 1 specific-deficit theoretical view. In response, Aaron Benjamin (2016) offered a discussion of the complementary strengths and weaknesses of the DRYAD and the ADH, and the potential ways they might work together. We agree with many of his comments, but are not convinced that DRYAD is able to explain basic replicable empirical evidence of the type mentioned in Smyth and Naveh-Benjamin (2016). We discuss the reasons why we are not fully convinced by the demonstration of DRYAD's simulation of results presented in Benjamin (2016) and then present an implementation of ADH in a computationally based age-related impaired neuromodulation approach that was shown to simulate the basic empirical results of age-related associative memory deficits. We also discuss the issues of parsimony of theories and the appropriate type of representation, in the context of global versus specific deficits theoretical views. Finally, we show that the ADH's take on the distinction between items and associations has been adopted by some global computational models of memory. We believe that considerations of the above issues and others raised by Benjamin (2016) can lead to fruitful discussions that will benefit both theory development and existing knowledge of aging and memory.

  14. Age-related structural and functional changes of low back muscles.

    Science.gov (United States)

    Hiepe, Patrick; Gussew, Alexander; Rzanny, Reinhard; Kurz, Eduard; Anders, Christoph; Walther, Mario; Scholle, Hans-Christoph; Reichenbach, Jürgen R

    2015-05-01

    During aging declining maximum force capacity with more or less unchanged fatigability is observed with the underlying mechanisms still not fully understood. Therefore, we compared morphology and function of skeletal muscles between different age groups. Changes in high-energy phosphate turnover (PCr, Pi and pH) and muscle functional MRI (mfMRI) parameters, including proton transverse relaxation time (T2), diffusion (D) and vascular volume fraction (f), were investigated in moderately exercised low back muscles of young and late-middle-aged healthy subjects with (31)P-MR spectroscopy, T2- and diffusion-weighted MRI at 3T. In addition, T1-weighted MRI data were acquired to determine muscle cross-sectional areas (CSA) and to assess fat infiltration into muscle tissue. Except for pH, both age groups showed similar load-induced MR changes and rates of perceived exertion (RPE), which indicates comparable behavior of muscle activation at moderate loads. Changes of mfMRI parameters were significantly associated with RPE in both cohorts. Age-related differences were observed, with lower pH and higher Pi/ATP ratios as well as lower D and f values in the late-middle-aged subjects. These findings are ascribed to age-related changes of fiber type composition, fiber size and vascularity. Interestingly, post exercise f was negatively associated with fat infiltration with the latter being significantly higher in late-middle-aged subjects. CSA of low back muscles remained unchanged, while CSA of inner back muscle as well as mean T2 at rest were associated with maximum force capacity. Overall, applying the proposed MR approach provides evidence of age-related changes in several muscle tissue characteristics and gives new insights into the physiological processes that take place during aging.

  15. Results of Intravitreal Ranibizumab Treatment for Exudative Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Umut Karaca

    2012-01-01

    Full Text Available Pur po se: To evaluate the efficacy and safety of intravitreal ranibizumab injection for exudative age-related macular degeneration. Ma te ri al and Met hod: In this study, we included forty-eight eyes of 43 age-related macular degeneration patients followed for at least twelve months. Mean age was 73.65±8.93 years and mean follow-up time was 14.2 months. All patients received three consecutive monthly intravitreal ranibizumab injections and then were followed up with clinical examination and optic coherence tomography monthly. Re-injection was executed as needed. Re sults: Twenty patients were male (46.5% and twenty-three patients were female (53.5%. The average number of ranibizumab injection was 3.7 (3-7 per eye. Twenty-six lesions (54.2% were classic (predominantly and minimally and twenty-two (45.8% were occult. Mean best-corrected visual acuity was 46.8 letters with ETDRS chart at the initial examination and 55.5 letters at twelfth month. Mean central foveal thickness decreased from 320 microns to 269 microns. There was a statistically significant improvement in visual acuity and central foveal thickness. On the other hand, this improvement was not significant between lesion types. During follow-up, there were no systemic or serious ocular complications determined. Dis cus si on: Intravitreal ranibizumab injection is safe and effective, both anatomically and functionally, for age-related macular degeneration. (Turk J Ophthalmol 2012; 42: 25-9

  16. 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.

  17. Innate immunity and inflammation in ageing: a key for understanding age-related diseases

    Directory of Open Access Journals (Sweden)

    Colonna-Romano Giuseppina

    2005-05-01

    Full Text Available Abstract The process of maintaining life for the individual is a constant struggle to preserve his/her integrity. This can come at a price when immunity is involved, namely systemic inflammation. Inflammation is not per se a negative phenomenon: it is the response of the immune system to the invasion of viruses or bacteria and other pathogens. During evolution the human organism was set to live 40 or 50 years; today, however, the immune system must remain active for much a longer time. This very long activity leads to a chronic inflammation that slowly but inexorably damages one or several organs: this is a typical phenomenon linked to ageing and it is considered the major risk factor for age-related chronic diseases. Alzheimer's disease, atherosclerosis, diabetes and even sarcopenia and cancer, just to mention a few – have an important inflammatory component, though disease progression seems also dependent on the genetic background of individuals. Emerging evidence suggests that pro-inflammatory genotypes are related to unsuccessful ageing, and, reciprocally, controlling inflammatory status may allow a better chance of successful ageing. In other words, age-related diseases are "the price we pay" for a life-long active immune system: this system has also the potential to harm us later, as its fine tuning becomes compromised. Our immune system has evolved to control pathogens, so pro-inflammatory responses are likely to be evolutionarily programmed to resist fatal infections with pathogens aggressively. Thus, inflammatory genotypes are an important and necessary part of the normal host responses to pathogens in early life, but the overproduction of inflammatory molecules might also cause immune-related inflammatory diseases and eventually death later. Therefore, low responder genotypes involved in regulation of innate defence mechanisms, might better control inflammatory responses and age-related disease development, resulting in an increased

  18. A PROSPECTIVE CLINICAL STUDY TO EVALUATE RISK FACTORS FOR AGE RELATED MACULAR DEGENERATION IN CENTRAL INDIA

    Directory of Open Access Journals (Sweden)

    Kavita

    2013-10-01

    Full Text Available Age related macular degeneration (AMD is a leadi ng cause of irreversible blindness among the elderly worldwide affecting 30 - 50 million individuals. AMD is more common in developed world. AMD is characterized by central visual loss. Advanced AMD can be classified in broadly into two types: dry and wet fo rm. Several clear risk factors for the development and progression of age related macular degeneration have been established are advancing age, genetic factors, history of smoking ,white race, obesity, high dietary intake of vegetable fat, low dietary inta ke of antioxidants and zinc. This prospective non - interventional study was conducted from February 2011 to October 2012 in the Regional Institute of Ophthalmology, Hamidia Hospital, Bhopal, included patients who attended the eye OPD, retina clinic and eye ward and were diagnosed as a case of AMD. Present study included 174 patients out of which patients 79(45.39% were above the age of 70 years, with 51 (29.31% patients between 61 - 70 years and 44 cases (25.28% in the sixth decade. Male: female ratio was 0 .75: 1. 21 (12.06% patients have a positive family history of AMD. Most common risk factor identified in our study was chronic sun exposure (49.42% followed by hypertension in 41.8% patients. 25.26% cases gave history of smoking and raised serum cholest erol levels were seen in 14.28% cases. History of alcoholism was positive in 19.54% patients. Of the 174 cases in our present study 90 patients (51.72% were hypermetropic. Conclusion: Age related macular degeneration is a disease of elderly with risk fact ors, most of them are preventable. If timely proper measures are taken, a major cause of blindness can be prevented in elderly age group.

  19. Subfoveal choroidal thickness changes after intravitreal bevacizumab therapy for neovascular age-related macular degeneration

    Institute of Scientific and Technical Information of China (English)

    Cihan; ünlü; Gurkan; Erdogan; Betul; Onal; Gunay; Betul; Ilkay; Sezgin; Akcay; Esra; Kardes

    2015-01-01

    <正>Dear Sir,Iam Dr.Cihanünlü,from the Department of Opthalmology,ümraniye Training and Research Hospital,Istanbul,Turkey.I write to present our study findings on subfoveal choroidal thickness(SFCT)changes after intravitreal bevacizumab(IVB)therapy for neovascular age-related macular degeneration(AMD).AMD is the leading cause of severe visual loss in adults older than 60y[1].Visual loss in late stages of AMD may be the result of one of the two processes:geographic atrophy(GA)or choroidal neovascularization(CNV).Many types of

  20. Resveratrol and novel potent activators of SIRT1: effects on aging and age-related diseases.

    Science.gov (United States)

    Knutson, Mitchell D; Leeuwenburgh, Christiaan

    2008-10-01

    Studies show that the plant polyphenol resveratrol can extend the life span of yeast, worms, flies, and fish. It also mitigates the metabolic dysfunction of mice fed high-fat diets. Resveratrol appears to mediate these effects partly by activating SIRT1, a deacetylase enzyme that regulates the activity of several transcriptional factors and enzymes responsive to nutrient availability. However, few foods contain resveratrol and humans metabolize it extensively, resulting in very low systemic bioavailability. Substantial research effort now focuses on identifying and testing more bioavailable and potent activators of SIRT1 for use as pharmacologic interventions in aging and age-related disorders.

  1. The association between Neovascular Age-related Macular Degeneration and Regulatory T cells in peripheral blood

    DEFF Research Database (Denmark)

    Madelung, Christopher Fugl; Falk, Mads; Sørensen, Torben Lykke

    2015-01-01

    PURPOSE: To investigate regulatory T cells (Tregs) and subsets of the Treg population in patients with neovascular age-related macular degeneration (AMD). PATIENTS AND METHODS: Twenty-one neovascular AMD cases and 12 age-matched controls without retinal pathology were selected. Patients were recr...... were found in the percentages of CD4(+) lymphocytes, CD25(high)CD127(low) Tregs, CD45RA(+) naïve Tregs, or CD31(+) recent thymic emigrant Tregs. CONCLUSION: Our data does not indicate an altered state of systemic Treg cells in neovascular AMD....

  2. Age-related differences in control of a visuomotor coordination task: a preliminary study

    OpenAIRE

    2016-01-01

    [Purpose] The purpose of the current study was to examine age-related differences in control of a perception-action coordination skill. We adapted a visuomotor tracking experiment requiring various coordination patterns between a limb’s motion and an external signal. [Subjects and Methods] A total of 12 subjects (6 elderly and 6 young) voluntarily participated in the study. The experimental session consisted of 3 trials for 3 different relative phase patterns: 0°, 90°, and 180°, defined by th...

  3. Brain protein oxidation in age-related neurodegenerative disorders that are associated with aggregated proteins.

    Science.gov (United States)

    Butterfield, D A; Kanski, J

    2001-07-15

    Protein oxidation, one of a number of brain biomarkers of oxidative stress, is increased in several age-related neurodegenerative disorders or animal models thereof, including Alzheimer's disease, Huntington's disease, prion disorders, such as Creutzfeld-Jakob disease, and alpha-synuclein disorders, such as Parkinson's disease and frontotemporal dementia. Each of these neurodegenerative disorders is associated with aggregated proteins in brain. However, the relationship among protein oxidation, protein aggregation, and neurodegeneration remain unclear. The current rapid progress in elucidation of mechanisms of protein oxidation in neuronal loss should provide further insight into the importance of free radical oxidative stress in these neurodegenerative disorders.

  4. Age-related differences in recall for words using semantics and prosody.

    Science.gov (United States)

    Sober, Jonathan D; VanWormer, Lisa A; Arruda, James E

    2016-01-01

    The positivity effect is a developmental shift seen in older adults to be increasingly influenced by positive information in areas such as memory, attention, and decision-making. This study is the first to examine the age-related differences of the positivity effect for emotional prosody. Participants heard a factorial combination of words that were semantically positive or negative said with either positive or negative intonation. Results showed a semantic positivity effect for older adults, and a prosody positivity effect for younger adults. Additionally, older adults showed a significant decrease in recall for semantically negative words said in an incongruent prosodically positive tone.

  5. [Progression of treatment and researches in dry age related macular degeneration].

    Science.gov (United States)

    Zhang, Kaiyan; Tang, Shibo

    2015-03-01

    Age related macular degeneration (AMD) is the leading cause of blindness and visual disability among old patients in Europe and North America. AMD has been divided into two broad clinical categories depending on whether there is a presence of abnormal neovascularization: neovascular (exudative or wet) AMD and dry (or geographic atrophic) AMD. VEGF has been understood as a pathogenesis of wet AMD which allows us to get breakthroughs in treatment. While the progression of dry AMD treatment is very slow because the lack of pathogenesis, no acute loss of vision, and without appropriate standards for treatment. This review tries to introduce about the recent researches and progressions for dry AMD treatment.

  6. Dry age-related macular degeneration: A currently unmet clinical need.

    Science.gov (United States)

    Girmens, Jean-François; Sahel, José-Alain; Marazova, Katia

    2012-08-01

    Age-related macular degeneration (AMD) is a leading cause of severe visual impairment and disability in older people worldwide. Although considerable advances in the management of the neovascular form of AMD have been made in the last decade, no therapy is yet available for the advanced dry form of AMD (geographic atrophy). This review focuses on current trends in the development of new therapies targeting specific pathophysiological pathways of dry AMD. Increased understanding of the complex mechanisms that underlie dry AMD will help to address this largely unmet clinical need.

  7. Perceptual and Social Attributes Underlining Age-Related Preferences for Faces.

    Science.gov (United States)

    Kiiski, Hanni S M; Cullen, Brendan; Clavin, Sarah L; Newell, Fiona N

    2016-01-01

    Although aesthetic preferences are known to be important in person perception and can play a significant role in everyday social decisions, the effect of the age of the observer on aesthetic preferences for faces of different ages has not yet been fully investigated. In the present study we investigated whether aesthetic preferences change with aging, with an age-related bias in favoring faces from one's own age group. In addition, we examined the role of age on both the perceptual qualities and the social attributes of faces that may influence these aesthetic judgements. Both younger and older adult observers provided ratings to images of younger, middle-aged and older unfamiliar faces. As well as attractiveness, the rating dimensions included other perceptual (distinctiveness, familiarity) and social (competence, trustworthiness and dominance) factors. The results suggested a consistent aesthetic preference for youthful faces across all ages of the observers but, surprisingly, no evidence for an age-related bias in attractiveness ratings. Older adults tended to provide higher ratings of attractiveness, competence and trustworthiness to the unfamiliar faces, consistent with the positivity effect previously reported. We also tested whether perceptual factors such as face familiarity or distinctiveness affected aesthetic ratings. Only ratings of familiarity, but not distinctiveness, were positively associated with the attractiveness of the faces. Moreover, ratings of familiarity decreased with increasing age of the face. With regard to the social characteristics of the faces, we found that the age of the face negatively correlated with ratings of trustworthiness provided by all observers, but with the competence ratings of older observers only. Interestingly, older adults provided higher ratings of perceived competence and trustworthiness to younger than older faces. However, our results also suggest that higher attractiveness ratings, together with older aged faces

  8. Perceptual and social attributes underlining age-related preferences for faces

    Directory of Open Access Journals (Sweden)

    Hanni SM Kiiski

    2016-08-01

    Full Text Available Although aesthetic preferences are known to be important in person perception and can play a significant role in everyday social decisions, the effect of the age of the observer on aesthetic preferences for faces of different ages has not yet been fully investigated. In the present study we investigated whether aesthetic preferences change with ageing, with an age-related bias in favouring faces from one’s own age group. In addition, we examined the role of age on both the perceptual qualities and the social attributes of faces that may influence these aesthetic judgements. Both younger and older adult observers provided ratings to images of younger, middle-aged and older unfamiliar faces. As well as attractiveness, the rating dimensions included other perceptual (distinctiveness, familiarity and social (competence, trustworthiness and dominance factors. The results suggested a consistent aesthetic preference for youthful faces across all ages of the observers but, surprisingly, no evidence for an age-related bias in attractiveness ratings. Older adults tended to provide higher ratings of attractiveness, competence and trustworthiness to the unfamiliar faces, consistent with the positivity effect previously reported. We also tested whether perceptual factors such as face familiarity or distinctiveness affected aesthetic ratings. Only ratings of familiarity, but not distinctiveness, were positively associated with the attractiveness of the faces. Moreover, ratings of familiarity decreased with increasing age of the face. With regard to the social characteristics of the faces, we found that the age of the face negatively correlated with ratings of trustworthiness provided by all observers, but with the competence ratings of older observers only. Interestingly, older adults provided higher ratings of perceived competence and trustworthiness to younger than older faces. However, our results also suggest that higher attractiveness ratings, together

  9. VISUAL REHABILITATION IN LOW VISION PATIENTS WITH AGE-RELATED MACULAR DEGENERATION

    Institute of Scientific and Technical Information of China (English)

    1991-01-01

    Using optical visual aids, visual rehabilitation was performed in 14 low vision patients(25 eyes) with age-related macular degeneration. With distance aids, visual acuity improvement appeared in 24 eyes(95%) out of the 25 eyes. Twelve eyes(48%) obtained a visual acuity equal to or better than 0.4. With near visual aids, near acuity of all eyes(100%) was improved. Thirteen eyes(52%) got the near vision equal to or better than 0.5. Ten patients could read No.5 Chinese Reading Card. The reading success rat...

  10. Age-Related Decline in Cardiorespiratory Fitness among Career Firefighters: Modification by Physical Activity and Adiposity

    Directory of Open Access Journals (Sweden)

    Dorothee M. Baur

    2012-01-01

    We found as expected that CRF declines with advancing age; however, the decline is greatly attenuated among leaner firefighters who report more physical activity. Furthermore, in a linear regression model including age, BMI, and variables describing physical activity behaviors, we could predict CRF (R2=0.6286. The total weekly duration of aerobic exercise as well as the duration of weight lifting sessions both had significant impacts on age-related decline. We conclude that firefighters are more likely to maintain the high levels of CRF needed to safely perform their duties if they engage in frequent exercise and maintain healthy weights.

  11. Depressive symptoms and quality of life in people with age-related macular degeneration

    OpenAIRE

    Mathew, Remy Sheena; Delbaere, Kim; Lord, Stephen R; Beaumont, Paul; Vaegan; Madigan, Michele C.

    2011-01-01

    Purpose: To examine quality of life and associated factors in people with Age-Related Macular Degeneration (AMD). Methods: One hundred and forty-five AMD participants (mean age 78.0 +/- 7.7 years) and 104 age- and gender- matched controls (mean age 78.1 +/- 5.8 years) comprised the study populations for this case-control study. Depressive symptoms were measured with the Goldberg Anxiety and Depression (GAD) scale; general health and daily functioning was assessed with the Medical Outcomes Stu...

  12. Hippocampus age-related microstructural changes in schizophrenia: a case-control mean diffusivity study.

    Science.gov (United States)

    Chiapponi, Chiara; Piras, Fabrizio; Fagioli, Sabrina; Girardi, Paolo; Caltagirone, Carlo; Spalletta, Gianfranco

    2014-08-01

    Macrostructural-volumetric abnormalities of the hippocampus have been described in schizophrenia. Here, we characterized age-related changes of hippocampal mean diffusivity as an index of microstructural damage by carrying out a neuroimaging study in 85 patients with a DSM-IV-TR diagnosis of schizophrenia and 85 age- and gender-matched healthy controls. We performed analyses of covariance, with diagnosis as fixed factor, mean diffusivity as dependent variable and age as covariate. Patients showed an early increase in mean diffusivity in the right and left hippocampus that increased with age. Thus, microstructural hippocampal changes associated with schizophrenia cannot be confined to a specific time window.

  13. No evidence of age-related increases in unconscious plagiarism during free recall.

    Science.gov (United States)

    Perfect, Timothy John; Defeldre, Anne-Catherine; Elliman, Rachel; Dehon, Hedwige

    2011-07-01

    In three experiments younger and older participants took part in a group generation task prior to a delayed recall task. In each, participants were required to recall the items that they had generated, avoiding plagiarism errors. All studies showed the same pattern: older adults did not plagiarise their partners any more than younger adults did. However, older adults were more likely than younger adults to intrude with entirely novel items not previously generated by anyone. These findings stand in opposition to the single previous demonstration of age-related increases in plagiarism during recall.

  14. The Role of Sensory Modality in Age-Related Distraction: A Critical Review and a Renewed View

    Science.gov (United States)

    Guerreiro, Maria J. S.; Murphy, Dana R.; Van Gerven, Pascal W. M.

    2010-01-01

    Selective attention requires the ability to focus on relevant information and to ignore irrelevant information. The ability to inhibit irrelevant information has been proposed to be the main source of age-related cognitive change (e.g., Hasher & Zacks, 1988). Although age-related distraction by irrelevant information has been extensively…

  15. Inspection Time and Cognitive Abilities in Twins Aged 7 to 17 Years: Age-Related Changes, Heritability and Genetic Covariance

    Science.gov (United States)

    Edmonds, Caroline J.; Isaacs, Elizabeth B.; Visscher, Peter M.; Rogers, Mary; Lanigan, Julie; Singhal, Atul; Lucas, Alan; Gringras, Paul; Denton, Jane; Deary, Ian J.

    2008-01-01

    We studied the age-related differences in inspection time and multiple cognitive domains in a group of monozygotic (MZ) and dizygotic (DZ) twins aged 7 to 17 years. Data from 111 twin pairs and 19 singleton siblings were included. We found clear age-related trends towards more efficient visual information processing in older participants. There…

  16. Age-related macular degeneration is associated with increased proportion of CD56(+) T cells in peripheral blood

    DEFF Research Database (Denmark)

    Faber, Carsten; Singh, Amardeep; Krüger Falk, Mads;

    2013-01-01

    PURPOSE: To examine the association between age-related changes in the T-cell compartment and prevalence of age-related macular degeneration (AMD). DESIGN: Case-control study. PARTICIPANTS: A total of 117 AMD cases and 106 controls were included prospectively. METHODS: Fresh-drawn peripheral bloo...

  17. Moringa oleifera Mitigates Memory Impairment and Neurodegeneration in Animal Model of Age-Related Dementia

    Directory of Open Access Journals (Sweden)

    Chatchada Sutalangka

    2013-01-01

    Full Text Available To date, the preventive strategy against dementia is still essential due to the rapid growth of its prevalence and the limited therapeutic efficacy. Based on the crucial role of oxidative stress in age-related dementia and the antioxidant and nootropic activities of Moringa oleifera, the enhancement of spatial memory and neuroprotection of M. oleifera leaves extract in animal model of age-related dementia was determined. The possible underlying mechanism was also investigated. Male Wistar rats, weighing 180–220 g, were orally given M. oleifera leaves extract at doses of 100, 200, and 400 mg/kg at a period of 7 days before and 7 days after the intracerebroventricular administration of AF64A bilaterally. Then, they were assessed memory, neuron density, MDA level, and the activities of SOD, CAT, GSH-Px, and AChE in hippocampus. The results showed that the extract improved spatial memory and neurodegeneration in CA1, CA2, CA3, and dentate gyrus of hippocampus together with the decreased MDA level and AChE activity but increased SOD and CAT activities. Therefore, our data suggest that M. oleifera leaves extract is the potential cognitive enhancer and neuroprotectant. The possible mechanism might occur partly via the decreased oxidative stress and the enhanced cholinergic function. However, further explorations concerning active ingredient(s are still required.

  18. Age relations of cardiovascular risk factors in a traditional Melanesian society: the Kitava Study.

    Science.gov (United States)

    Lindeberg, S; Berntorp, E; Nilsson-Ehle, P; Terént, A; Vessby, B

    1997-10-01

    This study examined cross-sectional age relations of blood pressure, anthropometric indexes, serum lipids, and hemostatic variables in 203 subsistence horticulturists aged 20-86 y in Kitava, Trobriand Islands, Papua New Guinea. The population is characterized by extreme leanness (despite food abundance), low blood pressure, low plasma plasminogen activator inhibitor 1 activity, and rarity of cardiovascular disease. Tubers, fruit, fish, and coconut are dietary staples whereas dairy products, refined fat and sugar, cereals, and alcohol are absent and salt intake is low. Although diastolic blood pressure was not associated with age in Kitavans, systolic blood pressure increased linearly after 50 y of age in both sexes. Body mass index decreased with age in both sexes. Serum total cholesterol, triacylglycerol, low-density-lipoprotein cholesterol, and apolipoprotein B increased in males between 20 and 50 y of age, whereas high-density-lipoprotein cholesterol and apolipoprotein A-I decreased. There were no significant differences in these indexes with age in the few females studied. A slight linear age-related increase of lipoprotein(a) was present in males. Plasma fibrinogen, factor VII clotting activity, factor VIII clotting activity, and von Willebrand factor antigen increased with age in both sexes but plasminogen activator inhibitor 1 activity did not. The modest or absent relations between the indexes measured and age are apparently important explanations of the virtual nonexistence of stroke and ischemic heart disease in Kitava.

  19. A STUDY TO COMPARE FUNDUS FLUORESCEIN ANGIOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY IN AGE RELATED MACULAR DEGENERATION

    Directory of Open Access Journals (Sweden)

    Rani Sujatha

    2016-02-01

    Full Text Available PURPOSE To compare the diagnostic accuracy of optical coherence tomography with Fundus Fluorescein Angiography in diagnosing Age related macular degeneration. METHODS A total 25 patients newly diagnosed as Age related macular degeneration were included in the study. The study was done during the time period between August 2013 to November 2015 this is a prospective randomized hospital based study. RESULTS Maximum no of patients affected belonged to the age group of 50-70 years and 60% were females. The most common symptom was defective vision accounting for 92%. Hypertension and hyperlipidemia were the most common risk factors. 12% of the cases had unilateral disease and 88% had bilateral disease. 6% of eyes were normal in both FFA and OCT. 62% of the eyes by FFA and 61% of the eyes by OCT had dry ARMD and 32 % of the eye by FFA and 33 % by OCT had wet ARMD. CONCLUSION Fundus Fluorescein Angiography is the gold standard tool for screening ARMD and OCT is more specific in detecting early subretinal neovascular membrane and also to assess the activity of the neovascular membranes. Hence OCT is superior to FFA in diagnosing early wet ARMD and thus helps in early management of patients with ARMD.

  20. Primary Raynaud's phenomenon and nailfold videocapillaroscopy: age-related changes in capillary morphology.

    Science.gov (United States)

    Pizzorni, Carmen; Sulli, Alberto; Smith, Vanessa; Ruaro, Barbara; Trombetta, Amelia Chiara; Cutolo, Maurizio; Paolino, Sabrina

    2016-10-08

    This study aimed to detect by nailfold videocapillaroscopy (NVC) the presence of age-related capillary morphological patterns in a large cohort of subjects affected by primary Raynaud's phenomenon (PRP). NVC was performed in 877 patients affected by PRP, divided into three age groups: 55 years. The following qualitative parameters were assessed and compared in the three groups of patients: apical dilations, irregular (non-homogeneous) dilations, venous branch dilations, microhaemorrhages, tortuosities and subpapillary venous plexus visibility. Patients with either irregular dilations or venous branch dilations were found significantly younger than those without (p  55 years (p < 0.0001). A statistically significant negative correlation was found between presence of apical and irregular dilations (p < 0.0001), apical dilations and venous branch dilations (p = 0.02), apical dilations and tortuosities (p = 0.0005), microhaemorrhages and tortuosities (p < 0.0001) and venous branch dilations and tortuosities (p = 0.02). Finally, a statistically significant positive correlation was found between irregular and venous branch dilations (p < 0.0001), irregular dilations and microhaemorrhages (p < 0.0001) and venous branch dilations and microhaemorrhages (p < 0.0001). In conclusion, our study detected different age-related morphological capillary changes mainly in younger patients with PRP, as well as statistically significant correlations between the presence of different capillary variables.

  1. Age-Related Response Bias in the Decoding of Sad Facial Expressions

    Directory of Open Access Journals (Sweden)

    Mara Fölster

    2015-10-01

    Full Text Available Recent studies have found that age is negatively associated with the accuracy of decoding emotional facial expressions; this effect of age was found for actors as well as for raters. Given that motivational differences and stereotypes may bias the attribution of emotion, the aim of the present study was to explore whether these age effects are due to response bias, that is, the unbalanced use of response categories. Thirty younger raters (19–30 years and thirty older raters (65–81 years viewed video clips of younger and older actors representing the same age ranges, and decoded their facial expressions. We computed both raw hit rates and bias-corrected hit rates to assess the influence of potential age-related response bias on decoding accuracy. Whereas raw hit rates indicated significant effects of both the actors’ and the raters’ ages on decoding accuracy for sadness, these age effects were no longer significant when response bias was corrected. Our results suggest that age effects on the accuracy of decoding facial expressions may be due, at least in part, to age-related response bias.

  2. Modulation of age-related insulin sensitivity by VEGF-dependent vascular plasticity in adipose tissues.

    Science.gov (United States)

    Honek, Jennifer; Seki, Takahiro; Iwamoto, Hideki; Fischer, Carina; Li, Jingrong; Lim, Sharon; Samani, Nilesh J; Zang, Jingwu; Cao, Yihai

    2014-10-14

    Mechanisms underlying age-related obesity and insulin resistance are generally unknown. Here, we report age-related adipose vascular changes markedly modulated fat mass, adipocyte functions, blood lipid composition, and insulin sensitivity. Notably, VEGF expression levels in various white adipose tissues (WATs) underwent changes uninterruptedly in different age populations. Anti-VEGF and anti- VEGF receptor 2 treatment in different age populations showed marked variations of vascular regression, with midaged mice exhibiting modest sensitivity. Interestingly, anti-VEGF treatment produced opposing effects on WAT adipocyte sizes in different age populations and affected vascular density and adipocyte sizes in brown adipose tissue. Consistent with changes of vasculatures and adipocyte sizes, anti-VEGF treatment increased insulin sensitivity in young and old mice but had no effects in the midaged group. Surprisingly, anti-VEGF treatment significantly improved insulin sensitivity in midaged obese mice fed a high-fat diet. Our findings demonstrate that adipose vasculatures show differential responses to anti-VEGF treatment in various age populations and have therapeutic implications for treatment of obesity and diabetes with anti-VEGF-based antiangiogenic drugs.

  3. Age-related changes in brain hemodynamics; A calibrated MRI study

    DEFF Research Database (Denmark)

    De Vis, J B; Hendrikse, J; Bhogal, A;

    2015-01-01

    calculated. RESULTS: Whole brain CBF was 49 ± 14 and 40 ± 9 ml/100 g/min in young and older subjects respectively (P Age-related differences in CBF decreased to the point of nonsignificance (B=-4.1, SE=3.8) when EtCO2 was added as a confounder. BOLD CVR was lower in the whole brain, in the frontal......, in the temporal, and in the occipital of the older subjects (Pbrain OEF was 43 ± 8% in the young and 39 ± 6% in the older subjects (P = 0.066). Whole brain CMRO2 was 181 ± 60 and 133 ± 43 µmol/100 g/min in young and older subjects, respectively (PAge-related differences in CBF......INTRODUCTION: Blood oxygenation-level dependent (BOLD) magnetic resonance imaging signal changes in response to stimuli have been used to evaluate age-related changes in neuronal activity. Contradictory results from these types of experiments have been attributed to differences in cerebral blood...

  4. Mechanisms of age-related decline in memory search across the adult life span.

    Science.gov (United States)

    Hills, Thomas T; Mata, Rui; Wilke, Andreas; Samanez-Larkin, Gregory R

    2013-12-01

    Three alternative mechanisms for age-related decline in memory search have been proposed, which result from either reduced processing speed (global slowing hypothesis), overpersistence on categories (cluster-switching hypothesis), or the inability to maintain focus on local cues related to a decline in working memory (cue-maintenance hypothesis). We investigated these 3 hypotheses by formally modeling the semantic recall patterns of 185 adults between 27 to 99 years of age in the animal fluency task (Thurstone, 1938). The results indicate that people switch between global frequency-based retrieval cues and local item-based retrieval cues to navigate their semantic memory. Contrary to the global slowing hypothesis that predicts no qualitative differences in dynamic search processes and the cluster-switching hypothesis that predicts reduced switching between retrieval cues, the results indicate that as people age, they tend to switch more often between local and global cues per item recalled, supporting the cue-maintenance hypothesis. Additional support for the cue-maintenance hypothesis is provided by a negative correlation between switching and digit span scores and between switching and total items recalled, which suggests that cognitive control may be involved in cue maintenance and the effective search of memory. Overall, the results are consistent with age-related decline in memory search being a consequence of reduced cognitive control, consistent with models suggesting that working memory is related to goal perseveration and the ability to inhibit distracting information.

  5. Less efficient pattern separation may contribute to age-related spatial memory deficits

    Directory of Open Access Journals (Sweden)

    Heather M. Holden

    2012-05-01

    Full Text Available Spatial memory deficits have been well documented in older adults and may serve as an early indicator of mild cognitive impairment or Alzheimer’s disease in some individuals. Pattern separation is a critical mechanism for reducing potential interference among similar memory representations to enhance memory accuracy. A small but growing literature indicates that spatial pattern separation may become less efficient as a result of normal aging, possibly due to age-related changes in subregions of the hippocampus. This decreased efficiency in spatial pattern separation may be a critical processing deficit that could be a contributing factor to spatial memory deficits and episodic memory impairment associated with aging. The present paper will review recently published studies in humans, nonhuman primates, and rodents that have examined age-related changes in spatial pattern separation. The potential basic science, translational, and clinical implications from these studies are discussed to illustrate the need for future research to further examine the relationship between spatial pattern separation and brain changes associated with aging and neurodegenerative disease.

  6. Age-related hearing decline in individuals with and without occupational noise exposure

    Directory of Open Access Journals (Sweden)

    Christina Hederstierna

    2016-01-01

    Full Text Available This study was conducted to compare the pattern of age-related hearing decline in individuals with and without self-reported previous occupational noise exposure. This was a prospective, population-based, longitudinal study of individuals aged 70-75 years, from an epidemiological investigation, comprising three age cohorts. In total there were 1013 subjects (432 men and 581 women. Participants were tested with pure tone audiometry, and they answered a questionnaire to provide information regarding number of years of occupational noise exposure. There were no significant differences in hearing decline, at any frequency, for those aged 70-75 years between the noise-exposed (N= 62 men, 22 women and the nonexposed groups (N = 96 men, 158 women. This study supports the additive model of noise-induced hearing loss (NIHL and age-related hearing loss (ARHL. The concept of different patterns of hearing decline between persons exposed and not exposed to noise could not be verified.

  7. Highway crash rates and age-related driver limitations: Literature review and evaluation of data bases

    Energy Technology Data Exchange (ETDEWEB)

    Hu, P.S. [Oak Ridge National Lab., TN (United States); Young, J.R. [Tennessee Univ., Knoxville, TN (United States); Lu, An [Oak Ridge Associated Universities, Inc., TN (United States)

    1993-08-01

    American society is undergoing a major demographic transformation that is resulting in a larger proportion of older individuals in the population. Moreover, recent travel surveys show that an increasing number of older individuals are licensed to drive and that they drive more than their same age cohort a decade ago. However, they continue to take shorter trips than younger drivers and they avoid driving during congested hours. This recent demographic transformation in our society, the graying of America, coupled with the increasing mobility of the older population impose a serious highway safety issue that cannot be overlooked. Some of the major concerns are the identification of ``high-risk`` older drivers and the establishment of licensing guidelines and procedures that are based on conclusive scientific evidence. Oak Ridge National Laboratory`s (ORNL) objectives in this project can be characterized by the following tasks: Review and evaluate the 1980 American Association of Motor Vehicle Administrators (AAMVA) and National Highway Traffic Safety Administration (NHTSA) licensing guidelines. Determine whether the license restriction recommended in the 1980 AAMVA and NHTSA guidelines was based on scientific evidence or on judgement of medical advisors. Identify in the scientific literature any medical conditions which are found to be highly associated with highway crashes, and which are not mentioned in the 1980 guidelines. Summarize States` current licensing practices for drivers with age-related physical and mental limitations. Identify potential data sources to establish conclusive evidence on age-related functional impairments and highway crashes.

  8. The NLRP3 Inflammasome Promotes Age-Related Thymic Demise and Immunosenescence

    Directory of Open Access Journals (Sweden)

    Yun-Hee Youm

    2012-01-01

    Full Text Available The collapse of thymic stromal cell microenvironment with age and resultant inability of the thymus to produce naive T cells contributes to lower immune-surveillance in the elderly. Here we show that age-related increase in ‘lipotoxic danger signals’ such as free cholesterol (FC and ceramides, leads to thymic caspase-1 activation via the Nlrp3 inflammasome. Elimination of Nlrp3 and Asc, a critical adaptor required for inflammasome assembly, reduces age-related thymic atrophy and results in an increase in cortical thymic epithelial cells, T cell progenitors and maintenance of T cell repertoire diversity. Using a mouse model of irradiation and hematopoietic stem cell transplantation (HSCT, we show that deletion of the Nlrp3 inflammasome accelerates T cell reconstitution and immune recovery in middle-aged animals. Collectively, these data demonstrate that lowering inflammasome-dependent caspase-1 activation increases thymic lymphopoiesis and suggest that Nlrp3 inflammasome inhibitors may aid the re-establishment of a diverse T cell repertoire in middle-aged or elderly patients undergoing HSCT.

  9. Modulation of age-related NF-kappaB activation by dietary zingerone via MAPK pathway.

    Science.gov (United States)

    Kim, Mi Kyung; Chung, Sang Woon; Kim, Dae Hyun; Kim, Ji Min; Lee, Eun Kyeong; Kim, Ji Young; Ha, Young Mi; Kim, Yun Hee; No, Jae-Kyung; Chung, Hye Sun; Park, Kun-Young; Rhee, Sook Hee; Choi, Jae Sue; Yu, Byung Pal; Yokozawa, Takako; Kim, Young Jin; Chung, Hae Young

    2010-06-01

    Zingerone, a major component found in ginger root, has been known as anti-mutagenic and anti-carcinogenic activities that are often associated with its anti-oxidative and anti-inflammatory activities. In recent studies, we examined molecular mechanism of zingerone treatment on pro-inflammatory NF-kappaB activation via the redox-related NIK/IKK and MAPK pathways. Action mechanism of zingerone on NF-kappaB signaling was investigated in aged rat kidney and endothelial cells. The results showed that zingerone had not only the antioxidant effect by constitutive suppression of ROS, but also anti-inflammatory effects by suppression of nuclear factor (NF)-kappaB activation in aged rat. In addition, zingerone treatment suppressed gene activation of pro-inflammatory enzymes, COX-2 and iNOS, which were upregulated with aging through NF-kappaB activation and IKK/MAPK signaling pathway. These experiments strongly indicate that zingerone treatment exerts a beneficial efficacy by suppressing both oxidative stress and age-related inflammation through the modulation of several key pro-inflammatory genes and transcription factors. Thus, the significance of our findings is that the zingerone treatment may provide some preventive measure against chronic inflammatory conditions that underlie many age-related inflammatory diseases, such as metabolic syndrome, cardiovascular disease, dementia, arthritis, diabetes, osteoprosis, and cancers.

  10. Pharmacogenetics of antiangiogenic and antineovascular therapies of age-related macular degeneration.

    Science.gov (United States)

    Agosta, Elisa; Lazzeri, Stefano; Orlandi, Paola; Figus, Michele; Fioravanti, Anna; Di Desidero, Teresa; Sartini, Maria Sole; Nardi, Marco; Danesi, Romano; Bocci, Guido

    2012-07-01

    Age-related macular degeneration (AMD), the most common age-related disease causing irreversible visual loss in industrialized countries, is a complex and multifactorial illness. Researchers have found components of the complement alternative pathway inside drusen and Bruch's membrane of AMD patients, underlying a possible important role of complement factor H in the pathogenesis of AMD. The neovascular (wet) AMD is the most destructive form and it is characterized by invasion of new blood vessels into subretinal spaces with subsequent exudation and bleeding, resulting in scarring of the macular region and loss of the central vision. The hallmark of the neovascular form is the choroidal neovascularization, where VEGF-A has an important role in the pathogenesis of the disease. SNPs of these genes have recently been investigated as potential pharmacogenetic markers of the antiangiogenic and antineovascular therapy of AMD, which includes verteporfin photodynamic therapy and anti-VEGF-A drugs, such as pegaptanib, bevacizumab and ranibizumab. The CFH rs1061170 CT and TT genotypes have been associated with an improvement of visual acuity in bevacizumab or ranibizumab treated patients, whereas patients harboring VEGF-A rs699946 G allele responded better to bevacizumab-based therapy if compared with patients carrying the A allele. In conclusion, the discovery of pharmacogenetic markers for the personalization of the antiangiogenic and/or antineovascular therapy could be, in the future, a key issue in ophthalmology to obtain a personalization of the therapy and to avoid unnecessary costs and adverse drug reactions.

  11. Enriched Childhood Experiences Moderate Age-related Motor and Cognitive Decline

    Directory of Open Access Journals (Sweden)

    Megan J. Metzler

    2013-02-01

    Full Text Available Aging is associated with deterioration of skilled manual movement. Specifically, aging corresponds with increased reaction time, greater movement duration, segmentation of movement, increased movement variability, and reduced ability to adapt to external forces and inhibit previously learned sequences. Moreover, it is thought that decreased lateralization of neural function in older adults may point to increased neural recruitment as a compensatory response to deterioration of key frontal and intra-hemispheric networks, particularly of callosal structures. However, factors that mediate age-related motor decline are not well understood. Here we show that music training in childhood is associated with reduced age-related decline of bimanual and unimanual motor skills in a MIDI keyboard motor learning task. Compared to older adults without music training, older adults with more than a year of music training demonstrated proficient bimanual and unimanual movement, evidenced by enhanced speed and decreased movement errors. Further, this group demonstrated significantly better implicit learning in the weather prediction task, a non-motor task. The performance of older adults with music training in those tasks was comparable to young adults. Older adults, however, displayed greater verbal ability compared to young adults irrespective of a past history of music training. Our results indicate that music training early in life may reduce age-associated decline of neural motor and cognitive networks.

  12. The role of DNA methylation in aging, rejuvenation, and age-related disease.

    Science.gov (United States)

    Johnson, Adiv A; Akman, Kemal; Calimport, Stuart R G; Wuttke, Daniel; Stolzing, Alexandra; de Magalhães, João Pedro

    2012-10-01

    DNA methylation is a major control program that modulates gene expression in a plethora of organisms. Gene silencing through methylation occurs through the activity of DNA methyltransferases, enzymes that transfer a methyl group from S-adenosyl-L-methionine to the carbon 5 position of cytosine. DNA methylation patterns are established by the de novo DNA methyltransferases (DNMTs) DNMT3A and DNMT3B and are subsequently maintained by DNMT1. Aging and age-related diseases include defined changes in 5-methylcytosine content and are generally characterized by genome-wide hypomethylation and promoter-specific hypermethylation. These changes in the epigenetic landscape represent potential disease biomarkers and are thought to contribute to age-related pathologies, such as cancer, osteoarthritis, and neurodegeneration. Some diseases, such as a hereditary form of sensory neuropathy accompanied by dementia, are directly caused by methylomic changes. Epigenetic modifications, however, are reversible and are therefore a prime target for therapeutic intervention. Numerous drugs that specifically target DNMTs are being tested in ongoing clinical trials for a variety of cancers, and data from finished trials demonstrate that some, such as 5-azacytidine, may even be superior to standard care. DNMTs, demethylases, and associated partners are dynamically shaping the methylome and demonstrate great promise with regard to rejuvenation.

  13. Moringa oleifera mitigates memory impairment and neurodegeneration in animal model of age-related dementia.

    Science.gov (United States)

    Sutalangka, Chatchada; Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Thukham-mee, Wipawee

    2013-01-01

    To date, the preventive strategy against dementia is still essential due to the rapid growth of its prevalence and the limited therapeutic efficacy. Based on the crucial role of oxidative stress in age-related dementia and the antioxidant and nootropic activities of Moringa oleifera, the enhancement of spatial memory and neuroprotection of M. oleifera leaves extract in animal model of age-related dementia was determined. The possible underlying mechanism was also investigated. Male Wistar rats, weighing 180-220 g, were orally given M. oleifera leaves extract at doses of 100, 200, and 400 mg/kg at a period of 7 days before and 7 days after the intracerebroventricular administration of AF64A bilaterally. Then, they were assessed memory, neuron density, MDA level, and the activities of SOD, CAT, GSH-Px, and AChE in hippocampus. The results showed that the extract improved spatial memory and neurodegeneration in CA1, CA2, CA3, and dentate gyrus of hippocampus together with the decreased MDA level and AChE activity but increased SOD and CAT activities. Therefore, our data suggest that M. oleifera leaves extract is the potential cognitive enhancer and neuroprotectant. The possible mechanism might occur partly via the decreased oxidative stress and the enhanced cholinergic function. However, further explorations concerning active ingredient(s) are still required.

  14. Neuron volumes in hippocampal subfields in delayed poststroke and aging-related dementias.

    Science.gov (United States)

    Gemmell, Elizabeth; Tam, Edward; Allan, Louise; Hall, Roslyn; Khundakar, Ahmad; Oakley, Arthur E; Thomas, Alan; Deramecourt, Vincent; Kalaria, Raj N

    2014-04-01

    Hippocampal atrophy is widely recognized in Alzheimer disease (AD). Whether neurons within hippocampal subfields are similarly affected in other aging-related dementias, particularly after stroke, remains an open question. We investigated hippocampal CA3 and CA4 pyramidal neuron volumes and densities using 3-dimensional stereologic techniques in postmortem samples from a total of 67 subjects: poststoke demented (PSD; n = 11), nondemented stroke survivors (PSND) and PSD patients from the CogFAST (Cognitive Function After Stroke) cohort (n = 13), elderly controls (n = 12), and subjects diagnosed as having vascular dementia (n = 11), AD (n = 10), and mixed AD and vascular dementia (n = 10). We found that CA3 and CA4 neuron volumes were reduced in PSD samples compared with those in PSND samples. The CA3 and CA4 neuron volumes were positively correlated with poststroke global cognitive function but were not associated with the burden of AD pathology. There were no differences in total neuron densities in either subfield in any of the groups studied. Our results indicate that selective reductions in CA4 and to a lesser extent CA3 neuron volumes may be related to post stroke cognitive impairment and aging-related dementias. These data suggest that CA4 neurons are vulnerable to disease processes and support our previous finding that a reduction in hippocampal neuron volume predominantly reflects vascular mechanisms as contributing to dementia after stroke.

  15. Reversing Age Related Changes of the Laryngeal Muscles by Chronic Electrostimulation of the Recurrent Laryngeal Nerve

    Science.gov (United States)

    Karbiener, Michael; Jarvis, Jonathan C.; Perkins, Justin D.; Lanmüller, Hermann; Schmoll, Martin; Rode, Hanna S.; Gerstenberger, Claus; Gugatschka, Markus

    2016-01-01

    Age related atrophy of the laryngeal muscles -mainly the thyroarytenoid muscle (TAM)- leads to a glottal gap and consequently to a hoarse and dysphonic voice that significantly affects quality of life. The aim of our study was to reverse this atrophy by inducing muscular hypertrophy by unilateral functional electrical stimulation (FES) of the recurrent laryngeal nerve (RLN) in a large animal model using aged sheep (n = 5). Suitable stimulation parameters were determined by fatiguing experiments of the thyroarytenoid muscle in an acute trial. For the chronic trial an electrode was placed around the right RLN and stimulation was delivered once daily for 29 days. We chose a very conservative stimulation pattern, total stimulation time was two minutes per day, or 0.14% of total time. Overall, the mean muscle fiber diameter of the stimulated right TAM was significantly larger than the non-stimulated left TAM (30μm±1.1μm vs. 28μm±1.1 μm, p<0.001). There was no significant shift in fiber type distribution as judged by immunohistochemistry. The changes of fiber diameter could not be observed in the posterior cricoarytenoid muscle (PCAM). FES is a possible new treatment option for reversing the effects of age related laryngeal muscle atrophy. PMID:27893858

  16. Structural invariance and age-related performance differences in face cognition.

    Science.gov (United States)

    Hildebrandt, Andrea; Sommer, Werner; Herzmann, Grit; Wilhelm, Oliver

    2010-12-01

    Perceiving and memorizing faces swiftly and correctly are important social competencies. The organization of these interpersonal abilities and how they change across the life span are still poorly understood. We investigated changes in the mean and covariance structure of face cognition abilities across the adult life span. A sample of 448 participants, with age ranging from 18 to 88 years, completed a battery of 15 face cognition tasks. After establishing a measurement model of face cognition that distinguishes between face perception, face memory, and the speed of face cognition, we used multiple group models and age-weighted measurement models to explore age-related changes. The modeling showed that the loadings and intercepts of all measures are age invariant. The factor means showed substantial decrements with increasing age. Age-related decrements in performance were strongest for the speed of face cognition but were also salient for face perception and face memory. The onset of age decrements is apparent in the 60s for face perception, in the late 40s for face memory, and in the early 30s for speed of face cognition. Implications of these findings on a theoretical and methodological level are discussed, and potential consequences for applied settings are considered.

  17. Age-related changes in the prostate and testes of the Beagle dog

    Energy Technology Data Exchange (ETDEWEB)

    Lowseth, L.A.; Gerlach, R.F.; Gillett, N.A.; Muggenburg, B.A. (Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM (United States))

    1990-01-01

    Age-related changes in the histologic morphology of the Beagle dog prostate have been used as a model for similar changes that occur in human beings. Previous studies of the aging changes in Beagle dogs have been limited to animals less than 10 years of age. In this study, the prostate, testes, and serum testosterone levels were evaluated in healthy Beagle dogs that were grouped by age to provide five groups of dogs that ranged from 3 to 14 years of age. Tissue sections from the prostate and testes were examined qualitatively and quantitatively by light microscopy. All animals 6 years of age and older had histologic characteristics of complex benign prostatic hyperplasia. A mean statistically significant increase in prostatic weight with increased age was noted. Morphometric analysis of the prostatic tissue suggested that similar to the change observed in human males, the increase in size was primarily due to an increase in the absolute volume of interstitial tissues. The epithelial component did not contribute to the increase noted, with the exception that the percentage of glandular lumen did increase with age, indicating progressive cystic dilatation of the glands. Stereologic analysis of the testes showed a decrease in the relative percentage of germ cells with increasing age. No distinct age-related trend was detected in serum testosterone concentrations. These findings indicate that the progression of benign prostatic hyperplasia occurs throughout the entire life span of the dog; an association with changes in the testes was not identified.

  18. Dynamical network model for age-related health deficits and mortality

    Science.gov (United States)

    Taneja, Swadhin; Mitnitski, Arnold B.; Rockwood, Kenneth; Rutenberg, Andrew D.

    2016-02-01

    How long people live depends on their health, and how it changes with age. Individual health can be tracked by the accumulation of age-related health deficits. The fraction of age-related deficits is a simple quantitative measure of human aging. This quantitative frailty index (F ) is as good as chronological age in predicting mortality. In this paper, we use a dynamical network model of deficits to explore the effects of interactions between deficits, deficit damage and repair processes, and the connection between the F and mortality. With our model, we qualitatively reproduce Gompertz's law of increasing human mortality with age, the broadening of the F distribution with age, the characteristic nonlinear increase of the F with age, and the increased mortality of high-frailty individuals. No explicit time-dependence in damage or repair rates is needed in our model. Instead, implicit time-dependence arises through deficit interactions—so that the average deficit damage rates increase, and deficit repair rates decrease, with age. We use a simple mortality criterion, where mortality occurs when the most connected node is damaged.

  19. Lifelong expression of apolipoprotein D in the human brainstem: correlation with reduced age-related neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Ana Navarro

    Full Text Available The lipocalin apolipoprotein D (Apo D is upregulated in peripheral nerves following injury and in regions of the central nervous system, such as the cerebral cortex, hippocampus, and cerebellum, during aging and progression of certain neurological diseases. In contrast, few studies have examined Apo D expression in the brainstem, a region necessary for survival and generally less prone to age-related degeneration. We measured Apo D expression in whole human brainstem lysates by slot-blot and at higher spatial resolution by quantitative immunohistochemistry in eleven brainstem nuclei (the 4 nuclei of the vestibular nuclear complex, inferior olive, hypoglossal nucleus, oculomotor nucleus, facial motor nucleus, nucleus of the solitary tract, dorsal motor nucleus of the vagus nerve, and Roller`s nucleus. In contrast to cortex, hippocampus, and cerebellum, apolipoprotein D was highly expressed in brainstem tissue from subjects (N = 26, 32-96 years of age with no history of neurological disease, and expression showed little variation with age. Expression was significantly stronger in somatomotor nuclei (hypoglossal, oculomotor, facial than visceromotor or sensory nuclei. Both neurons and glia expressed Apo D, particularly neurons with larger somata and glia in the periphery of these brainstem centers. Immunostaining was strongest in the neuronal perinuclear region and absent in the nucleus. We propose that strong brainstem expression of Apo D throughout adult life contributes to resistance against neurodegenerative disease and age-related degeneration, possibly by preventing oxidative stress and ensuing lipid peroxidation.

  20. Update on clinical trials in dry Age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Ibrahim Taskintuna

    2016-01-01

    Full Text Available This review article summarizes the most recent clinical trials for dry age.related macular degeneration (AMD, the most common cause of vision loss in the elderly in developed countries. A literature search through websites https://www.pubmed.org and https://www.clinicaltrials.gov/, both accessed no later than November 04, 2015, was performed. We identified three Phase III clinical trials that were completed over the recent 5 years Age.Related Eye Disease Study 2 (AREDS2, implantable miniature telescope and tandospirone, and several other trials targeting a variety of mechanisms including, oxidative stress, complement inhibition, visual cycle inhibition, retinal and choroidal blood flow, stem cells, gene therapy, and visual rehabilitation. To date, none of the biologically oriented therapies have resulted in improved vision. Vision improvement was reported with an implantable mini telescope. Stem cells therapy holds a potential for vision improvement. The AREDS2 formulas did not add any further reduced risk of progression to advanced AMD, compared to the original AREDS formula. Several recently discovered pathogenetic mechanisms in dry AMD have enabled development of new treatment strategies, and several of these have been tested in recent clinical trials and are currently being tested in ongoing trials. The rapid development and understanding of pathogenesis holds promise for the future.

  1. Update on Clinical Trials in Dry Age-related Macular Degeneration.

    Science.gov (United States)

    Taskintuna, Ibrahim; Elsayed, M E A Abdalla; Schatz, Patrik

    2016-01-01

    This review article summarizes the most recent clinical trials for dry age-related macular degeneration (AMD), the most common cause of vision loss in the elderly in developed countries. A literature search through websites https://www.pubmed.org and https://www.clinicaltrials.gov/, both accessed no later than November 04, 2015, was performed. We identified three Phase III clinical trials that were completed over the recent 5 years Age-Related Eye Disease Study 2 (AREDS2), implantable miniature telescope and tandospirone, and several other trials targeting a variety of mechanisms including, oxidative stress, complement inhibition, visual cycle inhibition, retinal and choroidal blood flow, stem cells, gene therapy, and visual rehabilitation. To date, none of the biologically oriented therapies have resulted in improved vision. Vision improvement was reported with an implantable mini telescope. Stem cells therapy holds a potential for vision improvement. The AREDS2 formulas did not add any further reduced risk of progression to advanced AMD, compared to the original AREDS formula. Several recently discovered pathogenetic mechanisms in dry AMD have enabled development of new treatment strategies, and several of these have been tested in recent clinical trials and are currently being tested in ongoing trials. The rapid development and understanding of pathogenesis holds promise for the future.

  2. Update on current and future novel therapies for dry age-related macular degeneration.

    Science.gov (United States)

    Leung, Ella; Landa, Gennady

    2013-09-01

    Age-related macular degeneration (ARMD) is the leading cause of irreversible blindness in developed countries. There are currently no cures, but there are promising potential therapies that target the underlying disease mechanisms of dry ARMD. Stem cells, ciliary neurotrophic factor, rheopheresis, ozonated autohemotherapy and prostaglandins show promise in stabilizing or improving visual acuity. Age-Related Eye Disease Study vitamins may reduce progression to severe ARMD. Adjuvant therapy like low vision rehabilitation and implantable miniature telescopes may help patients adjust to the sequelae of their disease, and herbal supplementation with saffron, zinc monocysteine and phototrop may be helpful. Therapies that are currently in clinical trials include brimonidine, doxycycline, anti-amyloid antibodies (GSK933776 and RN6G), RPE65 inhibitor (ACU-4429), complement inhibitors (ARC1905, FCFD4514S), hydroxychloroquine, intravitreal fluocinolone acetate and vasodilators like sildenafil, moxaverine and MC-1101. Therapies that have not been shown to be effective include POT-4, eculizumab, tandospirone, anecortave acetate, the antioxidant OT-551, sirolimus and vitamin E.

  3. Obesity and medicare expenditure: accounting for age-related height loss.

    Science.gov (United States)

    Onwudiwe, Nneka C; Stuart, Bruce; Zuckerman, Ilene H; Sorkin, John D

    2011-01-01

    To determine the relationship between BMI and Medicare expenditure for adults 65-years and older and determine whether this relationship changes after accounting for misclassification due to age-related height loss. Using a cross sectional study design, the relationship between BMI and fee-for-service Medicare expenditure was examined among beneficiaries who completed the Medicare Current Beneficiary Survey (MCBS) in 2002, were not enrolled in Medicare Health Maintenance Organization, had a self-reported height and weight, and were 65 and older (n = 7,706). Subjects were classified as underweight, normal weight, overweight, obese (obese I), and severely obese (obese II/III). To adjust BMI for the artifactual increase associated with age-related height loss, the reported height was transformed by adding the sex-specific age-associated height loss to the reported height in MCBS. The main outcome variable was total Medicare expenditure. There was a significant U-shaped pattern between unadjusted BMI and Medicare expenditure: underweight $4,581 (P accounting for height loss: underweight $4,640 (P cost is not found at "normal" BMI, but rather in overweight subjects with higher spending in the obese and underweight categories. Adjusting for loss-of-height with aging had little affect on cost estimates.

  4. Age-related changes in muscle strength and spinal kyphosis angles in an elderly Japanese population.

    Science.gov (United States)

    Kasukawa, Yuji; Miyakoshi, Naohisa; Hongo, Michio; Ishikawa, Yoshinori; Kudo, Daisuke; Suzuki, Masazumi; Mizutani, Takashi; Kimura, Ryouta; Ono, Yuichi; Shimada, Yoichi

    2017-01-01

    Lumbar kyphosis and the decreased mobility of the lumbar spine increase the risk of falls and impair both the quality of life and the ability to perform activities of daily living. However, in the elderly Japanese population, little is known about the age-related changes and sex-related differences in muscle strength, including of the upper and lower extremities and back extensors. An adequate kyphotic or lordotic angle has also not been determined. In this study, we evaluated the age-related changes in muscle strength and spinal kyphosis in 252 males and 320 females ≥50 years of age. Grip, back extensor, hip flexor, and knee extensor strength; thoracic and lumbar kyphosis; and spinal inclination in the neutral standing position were assessed, together with the range of motion of the thoracic and lumbar spine and spinal inclination. Grip strength, back extensor strength, and the strength of the hip flexors and knee extensors decreased significantly with aging, both in males (Pstrength and the thoracic kyphosis angle were significant variables influencing the lumbar kyphosis angle in both sexes. Spinal inclination correlated significantly with both the lumbar kyphosis angle and hip flexor strength in males, as well as with the lumbar kyphosis angle in females.

  5. Aging-related gains and losses associated with word production in connected speech.

    Science.gov (United States)

    Dennis, Paul A; Hess, Thomas M

    2016-11-01

    Older adults have been observed to use more nonnormative, or atypical, words than younger adults in connected speech. We examined whether aging-related losses in word-finding abilities or gains in language expertise underlie these age differences. Sixty younger and 60 older adults described two neutral photographs. These descriptions were processed into word types, and textual analysis was used to identify interrupted speech (e.g., pauses), reflecting word-finding difficulty. Word types were assessed for normativeness, with nonnormative word types defined as those used by six (5%) or fewer participants to describe a particular picture. Accuracy and precision ratings were provided by another sample of 48 high-vocabulary younger and older adults. Older adults produced more interrupted and, as predicted, nonnormative words than younger adults. Older adults were more likely than younger adults to use nonnormative language via interrupted speech, suggesting a compensatory process. However, older adults' nonnormative words were more precise and trended for having higher accuracy, reflecting expertise. In tasks offering response flexibility, like connected speech, older adults may be able to offset instances of aging-related deficits by maximizing their expertise in other instances.

  6. Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Sara Sepe

    2016-05-01

    Full Text Available The underlying relation between Parkinson’s disease (PD etiopathology and its major risk factor, aging, is largely unknown. In light of the causative link between genome stability and aging, we investigate a possible nexus between DNA damage accumulation, aging, and PD by assessing aging-related DNA repair pathways in laboratory animal models and humans. We demonstrate that dermal fibroblasts from PD patients display flawed nucleotide excision repair (NER capacity and that Ercc1 mutant mice with mildly compromised NER exhibit typical PD-like pathological alterations, including decreased striatal dopaminergic innervation, increased phospho-synuclein levels, and defects in mitochondrial respiration. Ercc1 mouse mutants are also more sensitive to the prototypical PD toxin MPTP, and their transcriptomic landscape shares important similarities with that of PD patients. Our results demonstrate that specific defects in DNA repair impact the dopaminergic system and are associated with human PD pathology and might therefore constitute an age-related risk factor for PD.

  7. Age-related bone loss in the LOU/c rat model of healthy ageing.

    Science.gov (United States)

    Duque, Gustavo; Rivas, Daniel; Li, Wei; Li, Ailian; Henderson, Janet E; Ferland, Guylaine; Gaudreau, Pierrette

    2009-03-01

    Inbred albino Louvain (LOU) rats are considered a model of healthy aging due to their increased longevity in the absence of obesity and with a low incidence of common age-related diseases. In this study, we characterized the bone phenotype of male and female LOU rats at 4, 20 and 27 months of age using quantitative micro computed tomographic (mCT) imaging, histology and biochemical analysis of circulating bone biomarkers. Bone quality and morphometry of the distal femora, assessed by mCT, was similar in male and female rats at 4 months of age and deteriorated over time. Histochemical staining of undecalcified bone showed a significant reduction in cortical and trabecular bone by 20 months of age. The reduction in mineralized tissue was accompanied by reduced numbers of osteoblasts and osteoclasts and a significant increase in marrow adiposity. Biochemical markers of bone turnover, C-telopeptide and osteocalcin, correlated with the age-related bone loss whereas the calciotropic hormones PTH and vitamin D remained unchanged over time. In summary, aged LOU rats exhibit low-turnover bone loss and marrow fat infiltration, which are the hallmarks of senile osteoporosis, and thus represent a novel model in which to study the molecular mechanisms leading to this disorder.

  8. Age-Related Impairment of Quality of Joint Motion in Vibroarthrographic Signal Analysis

    Directory of Open Access Journals (Sweden)

    Dawid Bączkowicz

    2015-01-01

    Full Text Available Aging is associated with degenerative changes in articular surfaces leading to quantitative and qualitative impairment of joint motion. Therefore, the aim of this study is to evaluate an age-related quality of the patellofemoral joint (PFJ motion in the vibroarthrographic (VAG signal analysis. Two hundred and twenty individuals were enrolled in this study and divided into five groups according to age. The VAG signals were collected during flexion/extension knee motion using an acceleration sensor and described using four parameters (VMS, P1, P2, and H. We observed that values of parameters VMS, P1, and P2 increase in accordance with the age, but H level decreases. The most significant differences were achieved between the youngest and the oldest participants’ groups. Moreover, we show that parameters VMS, P1, and P2 positively correlate with age, contrary to negatively associated H parameter. Our results suggest that the impairment of joint motion is a result of age-related osteoarticular degenerative changes.

  9. Age-related changes in postural control to the demands of a precision task.

    Science.gov (United States)

    Yeh, Ting-Ting; Cinelli, Michael E; Lyons, James L; Lee, Timothy D

    2015-12-01

    Optimal sensorimotor integration is needed to maintain the precision of a visuomotor postural task. Furthermore, cognitive resources have been suggested to be involved in maintaining balance, especially in older adults. This study investigated how older and younger adults differed in employing sensorimotor strategies in a dual-task situation. Older (age 65-84 years) and younger adults (age 19-30 years) performed a visually-based, postural tracking task in different body orientations (from 0° to 45°), which necessitated slightly different task goals. On some trials, participants performed a concurrent silent arithmetic task with the visuomotor tracking task. The results demonstrated that sensorimotor control declined with age. Older adults showed greater medial-lateral center of pressure variability compared to younger adults in the precision task. Younger adults displayed a trend to decrease anterior-posterior variability, but older adults exhibited an opposite trend when the body orientation changed from 0° to 45°. The addition of a dual-task situation decreased overall postural variability in both age groups. Age-related changes in postural control may degrade the flexible coordination of the sensory feedback and motor execution. This study suggested that medial-lateral stability may be more sensitive to this age-related decline and may be closely associated with postural instability and falls.

  10. Is age-related macular degeneration a problem in Ibadan, Sub-Saharan Africa?

    Directory of Open Access Journals (Sweden)

    Oluleye TS

    2012-04-01

    Full Text Available Tunji Sunday OluleyeRetina and Vitreous Unit, Department of Ophthalmology, University College Hospital, Ibadan, Nigeria, West AfricaBackground: Age-related macular degeneration (AMD is considered uncommon in black populations including those of Sub-Saharan Africa. The aim of this review was to determine the pattern of presentation of AMD in our hospital located in Ibadan, the largest city in Sub-Saharan Africa.Methods: A retrospective review of all cases with AMD presenting to the Eye and Retinal Clinic of the University College Hospital, Ibadan, West Africa was undertaken between October 2007 and September 2010.Results: In the 3 years reviewed, 768 retinal cases were seen in the hospital, 101 (14% of which were diagnosed with AMD. The peak age was 60–79 years. The male to female ratio was approximately 2:3. More males presented with the advanced form of dry AMD than females (odds ratio = 2.33. However, more females had advanced wet AMD than males (odds ratio = 1.85. Wet AMD was seen in 40 cases (40%.Conclusion: The review determined that, as AMD is not uncommon and wet AMD is relatively more common in our hospital than has been reported previously, this is probably true of Ibadan in general.Keywords: age-related maculopathy, choroidal neovascular membrane, retinal, vitreoretinal, drusen

  11. An overview on age related macular degeneration and recent advances in its management

    Directory of Open Access Journals (Sweden)

    SOBIA N.

    2014-03-01

    Full Text Available Age-related macular degeneration (AMD is a condition characterized, in the early stages, by slow development and progression, absence of symptoms over a number of years, and extensive retinal deposits called drusen, often associated with pigmentary abnormalities (early AMD.There is strong and consistent evidence that increasing age, family history, obesity/high body mass index, and cataract surgery are associated with late AMD. Smoking is the strongest and most consistently found modifiable risk factor for late AMD.Age-related macular degeneration remains one of the most severe and profound disabilities encountered in medicine, particularly due to the loss of the central vision and the high economic burden it places on patients and societies.Recent advances in management of AMD is anti-angiogenic drugs. The identification of the crucial role played by vascular endothelial growth factor (VEGF in the pathogenesis of wet AMD hasallowed the development of VEGF-blocking agents such as bevacizumab, pegaptanib and ranibizumab.

  12. Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review

    Directory of Open Access Journals (Sweden)

    Yang S

    2016-06-01

    Full Text Available Shiqi Yang,1 Jingke Zhao,1 Xiaodong Sun1–3 1Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 2Eye Research Institute of Shanghai Jiao Tong University, 3Shanghai Key Laboratory of Fundus Disease, Shanghai, People’s Republic of China Abstract: As a progressive chronic disease, age-related macular degeneration (AMD is the leading cause of irreversible vision impairment worldwide. Experimental and clinical evidence has demonstrated that vascular endothelial growth factor (VEGF plays a vital role in the formation of choroidal neovascularization. Intravitreal injections of anti-VEGF agents have been recommended as a first-line treatment for neovascular AMD. However, persistent fluid or recurrent exudation still occurs despite standardized anti-VEGF therapy. Patients suffering from refractory or recurrent neovascular AMD may develop mechanisms of resistance to anti-VEGF therapy, which results in a diminished therapeutic effect. Until now, there has been no consensus on the definitions of refractory neovascular AMD and recurrent neovascular AMD. This article aims at clarifying these concepts to evaluate the efficacy of switching drugs, which contributes to making clinical decision more scientifically. Furthermore, insight into the causes of resistance to anti-VEGF therapy would be helpful for developing possible therapeutic approaches, such as combination therapy and multi-target treatment that can overcome this resistance. Keywords: age-related macular degeneration, vascular endothelial growth factor, choroidal neovascularization, resistance

  13. Aging is not a disease: distinguishing age-related macular degeneration from aging.

    Science.gov (United States)

    Ardeljan, Daniel; Chan, Chi-Chao

    2013-11-01

    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.

  14. Neuroprotective effects of behavioural training and nicotine on age-related deficits in spatial learning.

    Science.gov (United States)

    Carrasco, Carmen; Vicens, Paloma; Redolat, Rosa

    2006-09-01

    Studies in humans and animals show a clear decline in spatial memory with age and several approaches have been adopted to alleviate this impairment. The purpose of our review is to assess the studies that have suggested the possible neuroprotective actions of behavioural training and nicotine-applied both independently and in conjunction-on age-related deficits in spatial learning. Both spatial pretraining and nonspatial experiences influence an animal's performance in spatial tasks. In aged rats, the experience of training in the water maze task increases the number of newly generated neurons in the hippocampus. The neuroprotective effects of nicotine have been demonstrated in both in-vitro and in-vivo models, although the molecular mechanisms underlying these actions are not yet fully understood. It had been concluded in different studies that nicotine can improve, impair or have no effect on performance in the water maze. Neurobiological data also suggest an interaction between nicotine and prior experience in complex tasks, although few studies have raised the question of whether nicotine treatment and training in spatial tasks may contribute in an interactive manner to alleviate spatial cognition impairment associated with the ageing process. Different findings suggest that past experience could be a confounding variable in longitudinal studies that aim to evaluate the neuroprotective effects of nicotine on age-related deficits in spatial learning.

  15. Age-related changes in 100-km ultra-marathon running performance.

    Science.gov (United States)

    Knechtle, Beat; Rüst, Christoph Alexander; Rosemann, Thomas; Lepers, Romuald

    2012-08-01

    The aims of this study were (1) to investigate the participation and performance trends at the '100 km Lauf Biel' in Switzerland from 1998 to 2010, and (2) to compare the age-related changes in 100-km running performance between males and females. For both sexes, the percent of finishers significantly (P running time for the top ten finishers remained stable for females, while it significantly (P = 0.001) increased by 2.4 min per annum for males. There was a significant (P running times for both sexes. The best 100-km running times was observed for the age comprised between 30 and 49 years for males, and between 30 and 54 years for females, respectively. The age-related decline in running performance was similar until 60-64 years between males and females, but was greater for females compared to males after 65 years. Future studies should investigate the lifespan from 65 to 75 years to better understand the performance difference between male and female master ultra-marathoners.

  16. Protraction of anaphase B in lymphocyte mitosis with ageing: possible contribution to age-related cancer risk.

    Science.gov (United States)

    Ford, Judith H

    2013-05-01

    Ageing is associated with a reduction in the fidelity of cell division as shown by increases in trisomic and polyploid cells; however, to date, the underlying age-specific changes in cell division have not been identified. Understanding these specific changes in cell division could give insight into the aetiology some age-related illnesses, especially cancer. Using blood collected from 72 women aged 18-53 years, this study recorded the frequencies of cells in each of the stages of mitosis in synchronised lymphocyte cultures harvested at controlled temperature without microtubule inhibitors. Factor analysis identified four components that accounted for >67.5% of the variance in the data. The component we named 'Spindle elongation efficiency', which was primarily influenced by the time taken to complete anaphase B, showed a major change with age: women aged ≥36 showed a highly statistically significant protraction of anaphase B compared with those aged ≤35 (t = -2.74, df = 70, P = 0.006) and linear regression showed a logarithmic change in this component with age (R = 0.297, P = 0.011). This phosphorylation-dependent phase of the cycle is responsible for increasing the distance between the two sets of daughter chromosomes and in older subjects the daughter nuclei at telophase were often poorly separated. Inefficient spindle elongation with ageing probably results from decreased cellular energy. Insufficient force at anaphase B might fail to resolve merotelic kinetochore attachments such that lagging at anaphase would be uncorrected and lead to trisomy and polyploidy in daughter cells.

  17. Complement factor H and age-related macular degeneration: the role of glycosaminoglycan recognition in disease pathology.

    Science.gov (United States)

    Clark, Simon J; Bishop, Paul N; Day, Anthony J

    2010-10-01

    AMD (age-related macular degeneration) is the major cause of blindness in the western world, associated with the formation of extracellular deposits called drusen in the macula, i.e. the central region of the retina. These drusen contain cellular debris and proteins, including components of the complement system such as the regulator CFH (complement factor H); dysregulation of complement is thought to play a major role in the development of AMD. CFH acts through its capacity to recognize polyanionic structures [e.g. sulfated GAGs (glycosaminoglycans)] found on host tissues, and thereby inactivates any C3b that becomes deposited. Importantly, a common polymorphism in CFH (Y402H) has been strongly associated with an increased risk of AMD. This polymorphism, which causes a tyrosine to histidine coding change, has been shown to alter the binding of CFH to sulfated GAGs, as well as to other ligands including C-reactive protein, necrotic cells and bacterial coat proteins. Of these, the change in the GAG-recognition properties of CFH is likely to be of most significance to AMD. Recent research has revealed that the disease-associated 402H allotype interacts less well (compared with 402Y) with binding sites within the macula (e.g. Bruch's membrane), where the GAGs heparan sulfate and dermatan sulfate play a major role in mediating the interaction with CFH. Reduced binding of the 402H allotype could result in impaired regulation of complement leading to chronic local inflammation that may contribute to the accumulation of drusen and thus the initiation, development and progression of AMD.

  18. Heat shock proteins as gatekeepers of proteolytic pathways-Implications for age-related macular degeneration (AMD).

    Science.gov (United States)

    Kaarniranta, Kai; Salminen, Antero; Eskelinen, Eeva-Liisa; Kopitz, Jürgen

    2009-04-01

    Age-related macular degeneration (AMD) is the major diagnosis for severe and irreversible central loss of vision in elderly people in the developed countries. The loss of vision involves primarily a progressive degeneration and cell death of postmitotic retinal pigment epithelial cells (RPE), which secondarily evokes adverse effects on photoreceptor cells. The RPE cells are exposed to chronic oxidative stress from three sources: their high levels of oxygen consumption, their exposure to the high levels of lipid peroxidation derived from the photoreceptor outer segments and their exposure to constant light stimuli. Cells increase the expression of heat shock proteins (HSPs) in order to normalize their growth conditions in response to various environmental stress factors, e.g. oxidative stress. The HSPs function as molecular chaperones by preventing the accumulation of cellular cytotoxic protein aggregates and assisting in correct folding of both nascent and misfolded proteins. Increased HSPs levels are observed in the retina of AMD patients, evidence of stressed tissue. A hallmark of RPE cell aging is lysosomal lipofuscin accumulation reflecting a weakened capacity to degrade proteins in lysosomes. The presence of lipofuscin increases the misfolding of intracellular proteins, which evokes additional stress in the RPE cells. If the capacity of HSPs to repair protein damages is overwhelmed, then the proteins are mainly cleared in proteasomes or in lysosomes. In this review, we discuss the role of heat shock proteins, proteasomes, and lysosomes and autophagic processes in RPE cell proteolysis and how these might be involved in development of AMD. In addition to classical lysosomal proteolysis, we focus on the increasing evidence that, HSPs, proteasomes and autophagy regulate protein turnover in the RPE cells and thus have important roles in AMD disease.

  19. Copper Products Capacity Expansion Stimulate the Copper Consumption

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    <正>The dramatic growth of copper consumption in China can directly be seen from the expansion of copper products capacity.According to sta- tistics,in the past 4 years,the improvement on the balance of trade on copper bar,copper,and copper alloy and copper wire & cable has driven the growth of copper consumption a lot.

  20. What associates Charles Bonnet syndrome with age-related macular degeneration?

    Science.gov (United States)

    Vojniković, Bozo; Radeljak, Sanja; Dessardo, Sandro; Zarković-Palijan, Tija; Bajek, Goran; Linsak, Zeljko

    2010-04-01

    Charles Bonnet syndrome (CBS) is a condition related to patients with visual loss due to age related macular degeneration or glaucoma that are having complex visual hallucinations. The CBS was first described by Swiss physician Charles Bonnet in 1760. Affected patients, who are otherwise mentally healthy people with significant visual loss, have vivid, complex recurrent visual hallucinations (VHs). One characteristic of these hallucinations is that they usually are "Lilliputian hallucinations" as patients experience micropsia (hallucinations in which the characters or objects are distorted and much smaller than normal). The prevalence of Charles Bonnet Syndrome has been reported to be between 10% and 40%; a recent Australian study has found the prevalence to be 17.5%. The high incidence of non-reported CBS is thought to be as a result of patient's fear to report the symptoms as they could be labeled as mentally insane since those type of visual hallucinations could be found in variety of psychiatric and neurological disorders such as drug or alcohol abuse (delirium tremens), Alice in Wonderland syndrome (AIWS), psychosis, schizophrenia, dementia, narcolepsy, epilepsy, Parkinson disease, brain tumors, migraine, as well as, in long term sleep deprivation. VHs can also be presented as the initial sign of the Epstein-Barr virus infection in infectious mononucleosis. Patients who suffer from CBS usually possess insight into the unreality of their visual experiences, which are commonly pleasant but may sometimes cause distress. The hallucinations consist of well-defined, organized, and clear images over which the subject has little control. It is believed that they represent release phenomena due to deafferentiation of the visual association areas of the cerebral cortex, leading to a form of phantom vision. Cognitive defects, social isolation, and sensory deprivation have also been implicated in the etiology of this condition. This study was conducted on 350 patients