Du, Heng; Guo, Lan; Zhang, Wensheng; Rydzewska, Monika; Yan, Shidu
Mitochondrial stress is one of the early features of Alzheimer disease (AD). Mitochondrial Aβ has been linked to mitochondrial toxicity. Our recent study demonstrated that cyclophilin D (CypD) mediated mitochondrial permeability transition pore (mPTP) is an important mechanism for neuronal and synaptic stress induced by both Aβ and oxidative stress. In transgenic AD-type mice overexpressing mutant amyloid precursor protein (APP) and Aβ (mAPP), CypD deficiency improves mitochondrial and synaptic function and learning/memory up to 12 months old. Here we provide evidence of the protective effects of CypD deficiency in aged AD mice (22-24 months). Cyp D deficient mAPP mice demonstrate less calcium-induced mitochondrial swelling, increased mitochondrial calcium uptake capacity, preserved mitochondrial respiratory function and improved spatial learning/memory even in old age (known to be the age for late stage AD pathology and synaptic dysfunction). These data demonstrate that abrogation of CypD results in persistent life-long protection against Aβ toxicity in an Alzheimer's disease mouse model, thereby suggesting that blockade of CypD may be of benefit for Alzheimer disease treatment.
Full Text Available Strong links between music and motor functions suggest that music could represent an interesting aid for motor learning. The present study aims for the first time to test the potential of music to assist in the learning of sequences of gestures in normal and pathological aging. Participants with mild Alzheimer's disease (AD and healthy older adults (Controls learned sequences of meaningless gestures that were either accompanied by music or a metronome. We also manipulated the learning procedure such that participants had to imitate the gestures to-be-memorized in synchrony with the experimenter or after the experimenter during encoding. Results show different patterns of performance for the two groups. Overall, musical accompaniment had no impact on the Controls' performance, but improved those of AD participants. Conversely, synchronization of gestures during learning helped Controls but seemed to interfere with retention in AD. We discuss these findings regarding their relevance for a better understanding of auditory-motor memory, and we propose recommendations to maximize the mnemonic effect of music for motor sequence learning for dementia care.
Hung, Chia-Wei; Chen, Yu-Chih; Hsieh, Wan-Ling; Chiou, Shih-Hwa; Kao, Chung-Lan
Ageing, which all creatures must encounter, is a challenge to every living organism. In the human body, it is estimated that cell division and metabolism occurs exuberantly until about 25 years of age. Beyond this age, subsidiary products of metabolism and cell damage accumulate, and the phenotypes of ageing appear, causing disease formation. Among these age-related diseases, neurodegenerative diseases have drawn a lot of attention due to their irreversibility, lack of effective treatment, and accompanied social and economical burdens. In seeking to ameliorate ageing and age-related diseases, the search for anti-ageing drugs has been of much interest. Numerous studies have shown that the plant polyphenol, resveratrol (3,5,4'-trihydroxystilbene), extends the lifespan of several species, prevents age-related diseases, and possesses anti-inflammatory, and anti-cancer properties. The beneficial effects of resveratrol are believed to be associated with the activation of a longevity gene, SirT1. In this review, we discuss the pathogenesis of age-related neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and cerebrovascular disease. The therapeutic potential of resveratrol, diet and the roles of stem cell therapy are discussed to provide a better understanding of the ageing mystery.
... genetic terms used on this page. Learning About Crohn's Disease What is Crohn's disease? What are the symptoms ... disease Additional Resources for Crohn's Disease What is Crohn's disease? Crohn's disease, an idiopathic (of unknown cause), chronic ...
... Mouse Models Of Huntington's Disease 1998 News Release Learning About Huntington's Disease What do we know about ... and treatment information. Hosted by the Dolan DNA Learning Center at Cold Spring Harbor Laboratory. Huntington's Outreach ...
... Glucocerebrosidase providing a molecular link between Parkinson and Gaucher diseases Journal of Biological Chemistry , June 9, 2011 Learning ... Glucocerebrosidase providing a molecular link between Parkinson and Gaucher diseases Journal of Biological Chemistry , June 9, 2011 Get ...
Timmons, James A
As average life expectancy increases there is a greater focus on health-span and, in particular, how to treat or prevent chronic age-associated diseases. Therapies which were able to control 'biological age' with the aim of postponing chronic and costly diseases of old age require an entirely new approach to drug development. Molecular technologies and machine-learning methods have already yielded diagnostics that help guide cancer treatment and cardiovascular procedures. Discovery of valid and clinically informative diagnostics of human biological age (combined with disease-specific biomarkers) has the potential to alter current drug-discovery strategies, aid clinical trial recruitment and maximize healthy ageing. I will review some basic principles that govern the development of 'ageing' diagnostics, how such assays could be used during the drug-discovery or development process. Important logistical and statistical considerations are illustrated by reviewing recent biomarker activity in the field of Alzheimer's disease, as dementia represents the most pressing of priorities for the pharmaceutical industry, as well as the chronic disease in humans most associated with age.
Scott F Gilbert
Cancer and ageing are often said to be diseases of development. During the past fifty years, the genetic components of cancer and ageing have been intensely investigated since development, itself, was seen to be an epiphenomenon of the genome. However, as we have learned more about the expression of the genome, we find that differences in expression can be as important as differences in alleles. It is easier to inactivate a gene by methylation than by mutation, and given that appropriate methylation is essential for normal development, one can immediately see that diseases would result as a consequence of inappropriate epigenetic methylation. While first proposed by Boris Vanyushin in 1973, recent studies have confirmed that inappropriate methylation not only causes diseases, and it also may be the critical factor in ageing and cancers.
... genetic terms used on this page Learning About Sickle Cell Disease What do we know about heredity and ... Information What do we know about heredity and sickle cell disease? Sickle cell disease is the most common ...
... Inherited and Endocrine Myopathies Metabolic Diseases of Muscle Mitochondrial Myopathies (MM) Myotonic Muscular Dystrophy (MMD) Spinal-Bulbar Muscular ... Deficient Congenital Muscular Dystrophy Metabolic Diseases of Muscle Mitochondrial Myopathy Miyoshi Distal Myopathy Motor Neurone Disease Muscle-Eye- ...
In this paper, I described clinical and basic problems on neurology of the aged patients. These studies have been done in various institutions with many co-workers. 1) A PET study revealed some age differences on CBF, CMRO2, or CMRgl. But these results are not so rigid in which much of individual variations should be considered in interpretation. Calendar age is not always compatible to biological age. 2) Saccular aneurysms in the brain artery were found in 7.3% of 1200 routine autopsy series of the aged subjects. Aneurysms with external diameter exceeding 6 mm had been fatally ruptured in 14 (78%) of 18 subjects. 3) Variations of the pyramidal crossing are found responsible for bizarre clinical manifestations. Non-crossing component was more prominent in the right pyramidal tract; consequently, right pyramidal tracts including ventral and lateral one seemed to have more extensive representation in the spinal cord level. 4) I123-IMP SPECT study showed a reduced uptake in the area 4 or area 4-6 of the ALS patients. 5) I introduced a new simplified Wartenberg's maneuver, which is useful for detection of subtle pyramidal dysfunctions. 6) Cases with central pontine myelinolysis and those of paraneoplastic syndrome were presented with an emphasis on their patho-chemical mechanisms. 7) Lewis-Sumner syndrome showing multifocal persistent conduction block is not rare in the aged, in which we have already had some useful therapeutic methods. 8) Dementia complicated with neurodegenerative disease was discussed on its clinical and chemical features of mental disturbances. In ALS-dementia, CSF-homovanilic acid reduced significantly than in the control and L-dopa was effective in some patients. 9) Vascular and Alzheimer-type dementias were presented and discussed on their pathogenetic mechanism according to our recent studies with review of literature.
Foerde, Karin; Braun, Erin Kendall; Higgins, E Tory; Shohamy, Daphna
Learning and motivation are intrinsically related, and both have been linked to dopamine. Parkinson's disease results from a progressive loss of dopaminergic inputs to the striatum and leads to impairments in motivation and learning from feedback. However, the link between motivation and learning in Parkinson's disease is not well understood. To address this gap, we leverage a well-established psychological theory of motivation, regulatory mode theory, which distinguishes between two functionally independent motivational concerns in regulating behavior: a concern with having an effect by initiating and maintaining movement (Locomotion) and a concern with establishing what is correct by critically evaluating goal pursuit means and outcomes (Assessment). We examined Locomotion and Assessment in patients with Parkinson's disease and age-matched controls. Parkinson's disease patients demonstrated a selective decrease in Assessment motivation but no change in Locomotion motivation, suggesting that Parkinson's disease leads to a reduced tendency to evaluate and monitor outcomes. Moreover, weaker Assessment motivation was correlated with poorer performance on a feedback-based learning task previously shown to depend on the striatum. Together, these findings link a questionnaire-based personality inventory with performance on a well-characterized experimental task, advancing our understanding of how Parkinson's disease affects motivation with implications for well-being and treatment outcomes.
Peled, Shir; Schocken, Shimon
The ability to develop engaging simulations and constructive learning experiences using mobile devices is unprecedented, presenting a disruption in educational practices of historical proportions. In this paper we describe some of the unique virtues that mobile learning hold for early age mathematics education. In particular, we describe how…
Examines the various stages of human development (as outlined by Erik Erikson and others) with their psychological stresses of recurring crises of identity and expectation and explores some of the implications for education's best serving human needs. Focuses on early childhood, late adolescence, middle age, and old age. (JT)
Foster, Liam; Boxall, Kathy
Background: People (with and without learning disabilities) are living longer. Demographic ageing creates challenges and the leading policy response to these challenges is "active ageing". "Active" does not just refer to the ability to be physically and economically active, but also includes ongoing social and civic engagement…
Rizvi, Saliha; Raza, Syed Tasleem; Mahdi, Farzana
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.
Hoozemans, J.J.M.; Rozemuller, A.J.M.; van Haastert, E.S.; Eikelenboom, P.; van Gool, W.A.
ABSTRACT: BACKGROUND: Inflammation is a prominent feature in Alzheimer's disease (AD). It has been proposed that aging has an effect on the function of inflammation in the brain, thereby contributing to the development of age-related diseases like AD. However, the age-dependent relationship between
Skip Navigation Bar Home Current Issue Past Issues Heart Disease Affects Women of All Ages Past Issues / Winter ... weeks of a heart attack. For Women with Heart Disease: About 6 million American women have coronary heart ...
This volume contains papers presented at the conference on "Law and Learning in the Middle Ages" held at the Carlsberg Academy in Copenhagen in May 2005. Here, a group of European and American scholars give their contribution to the examination of the theological and legal schooling that the 'cre......This volume contains papers presented at the conference on "Law and Learning in the Middle Ages" held at the Carlsberg Academy in Copenhagen in May 2005. Here, a group of European and American scholars give their contribution to the examination of the theological and legal schooling...
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
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...
Swerdlow, Russell H.
The relationship between brain aging and Alzheimer’s disease (AD) is contentious. One view holds AD results when brain aging surpasses a threshold. The other view postulates AD is not a consequence of brain aging. This review discusses this conundrum from the perspective of different investigative lines that have tried to address it, as well as from the perspective of the mitochondrion, an organelle that appears to play a role in both AD and brain aging. Specific issues addressed include the ...
Figueira, Inês; Fernandes, Adelaide; Mladenovic Djordjevic, Aleksandra;
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....
Wang, Jiguang; Zhang, Shihua; Wang, Yong; Chen, Luonan; Zhang, Xiang-Sun
One of the challenging problems in biology and medicine is exploring the underlying mechanisms of genetic diseases. Recent studies suggest that the relationship between genetic diseases and the aging process is important in understanding the molecular mechanisms of complex diseases. Although some intricate associations have been investigated for a long time, the studies are still in their early stages. In this paper, we construct a human disease-aging network to study the relationship among aging genes and genetic disease genes. Specifically, we integrate human protein-protein interactions (PPIs), disease-gene associations, aging-gene associations, and physiological system-based genetic disease classification information in a single graph-theoretic framework and find that (1) human disease genes are much closer to aging genes than expected by chance; and (2) diseases can be categorized into two types according to their relationships with aging. Type I diseases have their genes significantly close to aging genes, while type II diseases do not. Furthermore, we examine the topological characters of the disease-aging network from a systems perspective. Theoretical results reveal that the genes of type I diseases are in a central position of a PPI network while type II are not; (3) more importantly, we define an asymmetric closeness based on the PPI network to describe relationships between diseases, and find that aging genes make a significant contribution to associations among diseases, especially among type I diseases. In conclusion, the network-based study provides not only evidence for the intricate relationship between the aging process and genetic diseases, but also biological implications for prying into the nature of human diseases.
Lassen, Aske Juul
How are the boundaries of disease and health, age, life and death negotiated through technology and active aging? The paper focuses on how disease and age are dealt with by active elderly at activity centres in the Copenhagen area. New health technologies lead to new expectations to the longevity...... of life. A new ethics is emerging, focused on longevity and spreading through healthcare policies and technologies . At activity centres active elderly talk about health in old age, share experiences with health technologies and reflect on longevity, while working out. Chronic diseases are common in old...... age, but this does not mean that you give up or accept decreased quality of life. Ends change as new means emerge . The technological and medical abilities change the reflexive longevity. One expects to live a long and healthy life. Thus, technology can be conceived as a world-changing mediation. What...
Wang, Shengzheng; Tao, Dacheng; Yang, Jie
When estimating age, human experts can provide privileged information that encodes the facial attributes of aging, such as smoothness, face shape, face acne, wrinkles, and bags under-eyes. In automatic age estimation, privileged information is unavailable to test images. To overcome this problem, we hypothesize that asymmetric information can be explored and exploited to improve the generalizability of the trained model. Using the learning using privileged information (LUPI) framework, we tested this hypothesis by carefully defining relative attributes for support vector machine (SVM+) to improve the performance of age estimation. We term this specific setting as relative attribute SVM+ (raSVM+), in which the privileged information enables separation of outliers from inliers at the training stage and effectively manipulates slack variables and age determination errors during model training, and thus guides the trained predictor toward a generalizable solution. Experimentally, the superiority of raSVM+ was confirmed by comparing it with state-of-the-art algorithms on the face and gesture recognition research network (FG-NET) and craniofacial longitudinal morphological face aging databases. raSVM+ is a promising development that improves age estimation, with the mean absolute error reaching 4.07 on FG-NET.
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
Children's English learning in China attracts more and more people's attention and is on the teidency of starting at an early age. Under the trend of "learning English from childhood", the author has explored the Criical Period Hypothesis and discussed the younger learners' dsadvantages and older learners'advantages when learning Englsh. and concludes that early-age English learning is not feasible.
Underwood, Jonathan; Caan, Matthan W.A.; De Francesco, Davide; van Zoest, Rosan A.; Leech, Robert; Wit, Ferdinand W.N.M.; Portegies, Peter; Geurtsen, Gert J.; Schmand, Ben A.; Schim van der Loeff, Maarten F.; Franceschi, Claudio; Sabin, Caroline A.; Majoie, Charles B.L.M.; Winston, Alan; Reiss, Peter; Sharp, David J.
Objective: To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. Methods: A large sample of virologically suppressed HIV-positive adults (n = 162, age 45–82 years) and highly comparable HIV-negative controls (n = 105) were recruited as part of the Comorbidity in Relation to AIDS (COBRA) collaboration. Using T1-weighted MRI scans, a machine-learning model of healthy brain aging was defined in an independent cohort (n = 2,001, aged 18–90 years). Neuroimaging data from HIV-positive and HIV-negative individuals were then used to estimate brain-predicted age; then brain-predicted age difference (brain-PAD = brain-predicted brain age − chronological age) scores were calculated. Neuropsychological and clinical assessments were also carried out. Results: HIV-positive individuals had greater brain-PAD score (mean ± SD 2.15 ± 7.79 years) compared to HIV-negative individuals (−0.87 ± 8.40 years; b = 3.48, p < 0.01). Increased brain-PAD score was associated with decreased performance in multiple cognitive domains (information processing speed, executive function, memory) and general cognitive performance across all participants. Brain-PAD score was not associated with age, duration of HIV infection, or other HIV-related measures. Conclusion: Increased apparent brain aging, predicted using neuroimaging, was observed in HIV-positive adults, despite effective viral suppression. Furthermore, the magnitude of increased apparent brain aging related to cognitive deficits. However, predicted brain age difference did not correlate with chronological age or duration of HIV infection, suggesting that HIV disease may accentuate rather than accelerate brain aging. PMID:28258081
Woodruff-Pak, D S
Eyeblink classical conditioning is a useful paradigm for the study of the neurobiology of learning, memory, and aging, which also has application in the differential diagnosis of neurodegenerative diseases expressed in advancing age. Converging evidence from studies of eyeblink conditioning in neurological patients and brain imaging in normal adults document parallels in the neural substrates of this form of associative learning in humans and non-human mammals. Age differences in the short-delay procedure (400 ms CS-US interval) appear in middle age in humans and may be caused at least in part by cerebellar cortical changes such as loss of Purkinje cells. Whereas the hippocampus is not essential for conditioning in the delay procedure, disruption of hippocampal cholinergic neurotransmission impairs acquisition and slows the rate of learning. Alzheimer's disease (AD) profoundly disrupts the hippocampaL cholinergic system, and patients with AD consistently perform poorly in eyeblink conditioning. We hypothesize that disruption of hippocampal cholinergic pathways in AD in addition to age-associated Purkinje cell loss results in severely impaired eyeblink conditioning. The earliest pathology in AD occurs in entorhinal cortical input to hippocampus, and eyeblink conditioning may detect this early disruption before declarative learning and memory circuits become impaired. A case study is presented in which eyeblink conditioning detected impending dementia six years before changes on other screening tests indicated impairment. Because eyeblink conditioning is simple, non-threatening, and non-invasive, it may become a useful addition to test batteries designed to differentiate normal aging from mild cognitive impairment that progresses to AD and AD from other types of dementia.
Li-qiang HE; Jia-hong LU; Zhen-yu YUE
Autophagy is a cell self-digestion process via lysosomes that clears "cellular waste",including aberrantly modified proteins or protein aggregates and damaged organelles.Therefore,autophagy is considered a protein and organelle quality control mechanism that maintains normal cellular homeostasis.Dysfunctional autophagy has been observed in ageing tissues and several ageing-associated diseases.Lifespan of model organisms such as yeast,worms,flies,and mice can be extended through promoting autophagy,either by genetic manipulations such as over-expression of Sirtuin 1,or by administrations of rapamycin,resveratrol or spermidine.The evidence supports that autophagy may play an important role in delaying ageing or extending lifespan.In this review,we summarize the current knowledge about autophagy and its regulation,outline recent developments ie the genetic and pharmacological manipulations of autophagy that affects the lifespan,and discuss the role of autophagy in the ageing-related diseases.ow in Center for Neurodegenerative and Neuroimmunologic Diseases,Department of Neurology,University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School,Piscataway,NJ 08854,USA
Marziano, Mariagrazia; Rungratanawanich, Wiramon; Memo, Maurizio
Recently, the role of food and nutrition in preventing or delaying chronic disability in the elderly population has received great attention. Thanks to their ability to influence biochemical and biological processes, bioactive nutrients are considered modifiable factors capable of preserving a healthy brain status. A diet rich in vitamins and polyphenols and poor in saturated fatty acids has been recommended. In the prospective of a healthy diet, cooking methods should be also considered. In fact, cooking procedures can modify the original dietary content, contributing not only to the loss of healthy nutrients, but also to the formation of toxins, including advanced glycation end products (AGEs). These harmful compounds are adsorbed at intestinal levels and can contribute to the ageing process. The accumulation of AGEs in ageing (“AGE-ing”) is further involved in the exacerbation of neurodegenerative and many other chronic diseases. In this review, we discuss food's dual role as both source of bioactive nutrients and reservoir for potential toxic compounds—paying particular attention to the importance of proper nutrition in preventing/delaying Alzheimer's disease. In addition, we focus on the importance of a good education in processing food in order to benefit from the nutritional properties of an optimal diet. PMID:28168012
Adrianna Z Herskovits; Leonard Guarente
Sirtuin enzymes are a family of highly conserved protein deacetylases that depend on nicotinamide adenine dinucleotide (NAD+) for their activity.There are seven sirtuins in mammals and these proteins have been linked with caloric restriction and aging by modulating energy metabolism,genomic stability and stress resistance.Sirtuin enzymes are potential therapeutic targets in a variety of human diseases including cancer,diabetes,inflammatory disorders and neurodegenerative disease.Modulation of sirtuin activity has been shown to impact the course of several aggregate-forming neurodegenerative disorders including Alzheimer's disease,Parkinson's disease,Huntington's disease,amyotrophic lateral sclerosis and spinal and bulbar muscular atrophy.Sirtuins can influence the progression of neurodegenerative disorders by modulating transcription factor activity and directly deacetylating proteotoxic species.Here,we describe sirtuin protein targets in several aggregate-forming neurodegenerative diseases and discuss the therapeutic potential of compounds that modulate sirtuin activity in these disorders.
Katherine R Gamble
Full Text Available Implicit sequence learning involves learning about dependencies in sequences of events without intent to learn or awareness of what has been learned. Sequence learning is related to striatal dopamine levels, striatal activation, and integrity of white matter connections. People with Parkinson’s disease (PD have degeneration of dopamine-producing neurons, leading to dopamine deficiency and therefore striatal deficits, and they have difficulties with sequencing, including complex language comprehension and postural stability. Most research on implicit sequence learning in PD has used motor-based tasks. However, because PD presents with motor deficits, it is difficult to assess whether learning itself is impaired in these tasks. The present study used an implicit sequence learning task with a reduced motor component, the Triplets Learning Task (TLT. People with PD and age- and education-matched healthy older adults completed three sessions (each consisting of 10 blocks of 50 trials of the TLT. Results revealed that the PD group was able to learn the sequence, however, when learning was examined using a Half Blocks analysis (Nemeth et al., 2013, which compared learning in the 1st 25/50 trials of all blocks to that in the 2nd 25/50 trials, the PD group showed significantly less learning than Controls in the 2nd Half Blocks, but not in the 1st. Nemeth et al. hypothesized that the 1st Half Blocks involve recall and reactivation of the sequence learned, thus reflecting hippocampal-dependent learning, while the 2nd Half Blocks involve proceduralized behavior of learned sequences, reflecting striatal-based learning. The present results suggest that the PD group had intact hippocampal-dependent implicit sequence learning, but impaired striatal-dependent learning. Thus, sequencing deficits in PD are likely due to striatal impairments, but other brain systems, such as the hippocampus, may be able to partially compensate for striatal decline to improve
Hoozemans Jeroen JM
Full Text Available Abstract Background Inflammation is a prominent feature in Alzheimer's disease (AD. It has been proposed that aging has an effect on the function of inflammation in the brain, thereby contributing to the development of age-related diseases like AD. However, the age-dependent relationship between inflammation and clinical phenotype of AD has never been investigated. Methods In this study we have analysed features of the neuroinflammatory response in clinically and pathologically confirmed AD and control cases in relation to age (range 52-97 years. The mid-temporal cortex of 19 controls and 19 AD cases was assessed for the occurrence of microglia and astrocytes by immunohistochemistry using antibodies directed against CD68 (KP1, HLA class II (CR3/43 and glial fibrillary acidic protein (GFAP. Results By measuring the area density of immunoreactivity we found significantly more microglia and astrocytes in AD cases younger than 80 years compared to older AD patients. In addition, the presence of KP1, CR3/43 and GFAP decreases significantly with increasing age in AD. Conclusion Our data suggest that the association between neuroinflammation and AD is stronger in relatively young patients than in the oldest patients. This age-dependent relationship between inflammation and clinical phenotype of AD has implications for the interpretation of biomarkers and treatment of the disease.
Marr, Celia M
Respiratory and cardiac diseases are common in older horses. Advancing age is a specific risk factor for cardiac murmurs and these are more likely in males and small horses. Airway inflammation is the most common respiratory diagnosis. Recurrent airway obstruction can lead to irreversible structural change and bronchiectasis; with chronic hypoxia, right heart dysfunction and failure can develop. Valvular heart disease most often affects the aortic and/or the mitral valve. Management of comorbidity is an essential element of the therapeutic approach to cardiac and respiratory disease in older equids.
Full Text Available Purpose: Analyzing the influence of nursing students’ learning initiative in the course reform of aged caring. Discuss the way of the aged care reform. Method: To reform the course of aged care in our school level 2013 88 nursing undergraduate. The specific content: learning aged care theory, learning Japanese care technology basic knowledge, adding Japanese and Taiwan’s nursing concepts to the traditional aged care teaching, performing sitcoms about old people’s disease and nursing way , reporting the plan of aged care by PowerPoint, organizing student volunteers to visit the nursing home and so on. The specific content lasted four months. Adopting the learning initiative (ALS scale developed by Zang Yuli and others after course reform. Measure the students’ learning initiative before and after the teaching. Result: Nursing student’s self-study ability was in the middle and lower level before the course reform(59.26±7.38; After the course reform, nursing student gain higher score than before learning on the three aspects contain “Learning motivation”,“Learning goals” and “Solid study”. The difference has statistically significant.(P<0.05.Conclusion: Through the aged care course reform, nursing students strengthen the study enthusiasm and initiative; enhance nursing student’s self-study ability. It is conducive to improve the learning interest of aged care course for nursing students.
Vernooij, Meike W.; Smits, Marion
The role of structural neuroimaging in the diagnosis of Alzheimer's disease (AD) is becoming increasingly important. As a consequence, a basic understanding of what are normal brain changes in aging is key to be able to recognize what is abnormal. The first part of this article discusses normal vers
Balasubramanian, Priya; Longo, Valter D
Simple organisms including yeast and flies with mutations in the IGF-1 and Tor-S6K pathways are dwarfs, are highly protected from toxins, and survive up to 3 times longer. Similarly, dwarf mice with deficiencies in the growth hormone-IGF-I axis are also long lived and protected from diseases. We recently reported that humans with Growth Hormone Receptor Deficiency (GHRD) rarely develop cancer or diabetes. These findings are in agreement with the effect of defects in the Tor-S6K pathways in causing dwarfism and protection of DNA. Because protein restriction reduces both GHR-IGF-1 axis and Tor-S6K activity, we examined links between protein intake, disease, and mortality in over 6000 US subjects in the NHANES CDC database. Respondents aged 50-65 reporting a high protein intake displayed an increase in IGF-I levels, a 75% increased risk of overall mortality and a 3-4 fold increased risk of cancer mortality in agreement with findings in mouse experiments. These studies point to a conserved link between proteins and amino acids, GHR-IGF-1/insulin, Tor-S6k signaling, aging, and diseases.
Ke, Fengfeng; Kwak, Dean
This mixed-method study examined whether online learning interaction participation, perception, and learning satisfaction would be consistent across varied age and ethnicity groups. Data were collected from students enrolled in 28 online courses via content analysis with online interaction transcripts, structural equation modeling with the…
Sadeghi, Karim; Khonbi, Zainab Abolfazli
This study investigated the use of language learning strategies (LLS) and reasons for learning English among Iranian EFL students who began learning English at different ages. The participants (N = 33, both male and female) were divided into two groups of younger beginners (who began learning English before age 9; N = 16) and older beginners (who…
Tonelli, Marcello; Riellae, Miguel
Youth, which is forgiven everything, forgives itself nothing: age, which forgives itself everything, is forgiven nothing. George Bernard Shaw The proportion of older people in the general population is steadily increasing worldwide, with the most rapid growth in low-and middle-income countries . This demographic change is to be celebrated, because it is the consequence of socioeconomic development and better life expectancy. However, population aging also has important implications for society - in diverse areas including health systems, labor markets, public policy, social programs, and family dynamics . A successful response to the aging population will require capitalizing on the opportunities that this transition offers, as well as effectively addressing its challenges. Chronic kidney disease (CKD) is an important public health problem that is characterized by poor health outcomes and very high health care costs. CKD is a major risk multiplier in patients with diabetes, hypertension, heart disease and stroke - all of which are key causes of death and disability in older people . Since the prevalence of CKD is higher in older people, the health impact of population aging will depend in part on how the kidney community responds. March 13, 2014 will mark the celebration of the 9th World Kidney Day (WKD), an annual event jointly sponsored by the International Society of Nephrology and the International Federation of Kidney Foundations. Since its inception in 2006, WKD has become the most successful effort to raise awareness among policymakers and the general public about the importance of kidney disease. The topic for WKD 2014 is "CKD in older people". This article reviews the key links between kidney function, age, health and illness - and discusses the implications of the aging population for the care of people with CKD.
De Diego-Balaguer, R; Couette, M; Dolbeau, G; Dürr, A; Youssov, K; Bachoud-Lévi, A-C
Although the role of the striatum in language processing is still largely unclear, a number of recent proposals have outlined its specific contribution. Different studies report evidence converging to a picture where the striatum may be involved in those aspects of rule-application requiring non-automatized behaviour. This is the main characteristic of the earliest phases of language acquisition that require the online detection of distant dependencies and the creation of syntactic categories by means of rule learning. Learning of sequences and categorization processes in non-language domains has been known to require striatal recruitment. Thus, we hypothesized that the striatum should play a prominent role in the extraction of rules in learning a language. We studied 13 pre-symptomatic gene-carriers and 22 early stage patients of Huntington's disease (pre-HD), both characterized by a progressive degeneration of the striatum and 21 late stage patients Huntington's disease (18 stage II, two stage III and one stage IV) where cortical degeneration accompanies striatal degeneration. When presented with a simplified artificial language where words and rules could be extracted, early stage Huntington's disease patients (stage I) were impaired in the learning test, demonstrating a greater impairment in rule than word learning compared to the 20 age- and education-matched controls. Huntington's disease patients at later stages were impaired both on word and rule learning. While spared in their overall performance, gene-carriers having learned a set of abstract artificial language rules were then impaired in the transfer of those rules to similar artificial language structures. The correlation analyses among several neuropsychological tests assessing executive function showed that rule learning correlated with tests requiring working memory and attentional control, while word learning correlated with a test involving episodic memory. These learning impairments significantly
Petoumenos, Kathy; Worm, Signe W
In the developed world, HIV infection is now well managed with very effective and less toxic antiretroviral treatment. HIV-positive patients therefore are living longer, but are now faced by challenges associated with aging. Several non-AIDS associated morbidities are increased in this population......, including cardiovascular disease (CVD). It is suggested that CVD occurs earlier among HIV-positive patients compared with HIV-negative patients, and at a higher rate. Several factors have been proposed to contribute to this. First, the traditional CVD risk factors are highly prevalent in this population....... High rates of smoking, dyslipidaemia and a family history of CVD have been reported. This population is also aging, with estimates of more than 25% of HIV-positive patients in the developed world being over the age of 50. Antiretroviral treatment, both through its effect on lipids and through other...
Ardeljan, Daniel; Chan, Chi-Chao
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...
Li, Xue-Yuan; Men, Wei-Wei; Zhu, Hua; Lei, Jian-Feng; Zuo, Fu-Xing; Wang, Zhan-Jing; Zhu, Zhao-Hui; Bao, Xin-Jie; Wang, Ren-Zhi
Alzheimer’s disease (AD) is a leading cause of dementia worldwide, associated with cognitive deficits and brain glucose metabolic alteration. However, the associations of glucose metabolic changes with cognitive dysfunction are less detailed. Here, we examined the brains of APP/presenilin 1 (PS1) transgenic (Tg) mice aged 2, 3.5, 5 and 8 months using 18F-labed fluorodeoxyglucose (18F-FDG) microPET to assess age- and brain region-specific changes of glucose metabolism. FDG uptake was calculated as a relative standardized uptake value (SUVr). Morris water maze (MWM) was used to evaluate learning and memory dysfunction. We showed a glucose utilization increase in multiple brain regions of Tg mice at 2 and 3.5 months but not at 5 and 8 months. Comparisons of SUVrs within brains showed higher glucose utilization than controls in the entorhinal cortex, hippocampus, and frontal cortex of Tg mice at 2 and 3.5 months but in the thalamus and striatum at 3.5, 5 and 8 months. By comparing SUVrs in the entorhinal cortex and hippocampus, Tg mice were distinguished from controls at 2 and 3.5 months. In MWM, Tg mice aged 2 months shared a similar performance to the controls (prodromal-AD). By contrast, Tg mice failed training tests at 3.5 months but failed all MWM tests at 5 and 8 months, suggestive of partial or complete cognitive deficits (symptomatic-AD). Correlation analyses showed that hippocampal SUVrs were significantly correlated with MWM parameters in the symptomatic-AD stage. These data suggest that glucose metabolic disorder occurs before onset of AD signs in APP/PS1 mice with the entorhinal cortex and hippocampus affected first, and that regional FDG uptake increase can be an early biomarker for AD. Furthermore, hippocampal FDG uptake is a possible indicator for progression of Alzheimer’s cognition after cognitive decline, at least in animals. PMID:27763550
Full Text Available Alzheimer’s disease (AD is a leading cause of dementia worldwide, associated with cognitive deficits and brain glucose metabolic alteration. However, the associations of glucose metabolic changes with cognitive dysfunction are less detailed. Here, we examined the brains of APP/presenilin 1 (PS1 transgenic (Tg mice aged 2, 3.5, 5 and 8 months using 18F-labed fluorodeoxyglucose (18F-FDG microPET to assess age- and brain region-specific changes of glucose metabolism. FDG uptake was calculated as a relative standardized uptake value (SUVr. Morris water maze (MWM was used to evaluate learning and memory dysfunction. We showed a glucose utilization increase in multiple brain regions of Tg mice at 2 and 3.5 months but not at 5 and 8 months. Comparisons of SUVrs within brains showed higher glucose utilization than controls in the entorhinal cortex, hippocampus, and frontal cortex of Tg mice at 2 and 3.5 months but in the thalamus and striatum at 3.5, 5 and 8 months. By comparing SUVrs in the entorhinal cortex and hippocampus, Tg mice were distinguished from controls at 2 and 3.5 months. In MWM, Tg mice aged 2 months shared a similar performance to the controls (prodromal-AD. By contrast, Tg mice failed training tests at 3.5 months but failed all MWM tests at 5 and 8 months, suggestive of partial or complete cognitive deficits (symptomatic-AD. Correlation analyses showed that hippocampal SUVrs were significantly correlated with MWM parameters in the symptomatic-AD stage. These data suggest that glucose metabolic disorder occurs before onset of AD signs in APP/PS1 mice with the entorhinal cortex and hippocampus affected first, and that regional FDG uptake increase can be an early biomarker for AD. Furthermore, hippocampal FDG uptake is a possible indicator for progression of Alzheimer’s cognition after cognitive decline, at least in animals.
Li, Xue-Yuan; Men, Wei-Wei; Zhu, Hua; Lei, Jian-Feng; Zuo, Fu-Xing; Wang, Zhan-Jing; Zhu, Zhao-Hui; Bao, Xin-Jie; Wang, Ren-Zhi
Alzheimer's disease (AD) is a leading cause of dementia worldwide, associated with cognitive deficits and brain glucose metabolic alteration. However, the associations of glucose metabolic changes with cognitive dysfunction are less detailed. Here, we examined the brains of APP/presenilin 1 (PS1) transgenic (Tg) mice aged 2, 3.5, 5 and 8 months using (18)F-labed fluorodeoxyglucose ((18)F-FDG) microPET to assess age- and brain region-specific changes of glucose metabolism. FDG uptake was calculated as a relative standardized uptake value (SUVr). Morris water maze (MWM) was used to evaluate learning and memory dysfunction. We showed a glucose utilization increase in multiple brain regions of Tg mice at 2 and 3.5 months but not at 5 and 8 months. Comparisons of SUVrs within brains showed higher glucose utilization than controls in the entorhinal cortex, hippocampus, and frontal cortex of Tg mice at 2 and 3.5 months but in the thalamus and striatum at 3.5, 5 and 8 months. By comparing SUVrs in the entorhinal cortex and hippocampus, Tg mice were distinguished from controls at 2 and 3.5 months. In MWM, Tg mice aged 2 months shared a similar performance to the controls (prodromal-AD). By contrast, Tg mice failed training tests at 3.5 months but failed all MWM tests at 5 and 8 months, suggestive of partial or complete cognitive deficits (symptomatic-AD). Correlation analyses showed that hippocampal SUVrs were significantly correlated with MWM parameters in the symptomatic-AD stage. These data suggest that glucose metabolic disorder occurs before onset of AD signs in APP/PS1 mice with the entorhinal cortex and hippocampus affected first, and that regional FDG uptake increase can be an early biomarker for AD. Furthermore, hippocampal FDG uptake is a possible indicator for progression of Alzheimer's cognition after cognitive decline, at least in animals.
Price, Amanda; Shin, Jacqueline C.
The current study examined the contribution of brain areas affected by Parkinson's disease (PD) to sequence learning, with a specific focus on response-related processes, spatial attentional control, and executive functioning. Patients with mild PD, patients with moderate PD, and healthy age-matched participants performed three tasks--a sequence…
Chang, Timothy S; Coen, Michael H; La Rue, Asenath; Jonaitis, Erin; Koscik, Rebecca L; Hermann, Bruce; Sager, Mark A
Identification of preclinical Alzheimer's disease (AD) is an essential first step in developing interventions to prevent or delay disease onset. In this study, we examine the hypothesis that deeper analyses of traditional cognitive tests may be useful in identifying subtle but potentially important learning and memory differences in asymptomatic populations that differ in risk for developing Alzheimer's disease. Subjects included 879 asymptomatic higher-risk persons (middle-aged children of parents with AD) and 355 asymptotic lower-risk persons (middle-aged children of parents without AD). All were administered the Rey Auditory Verbal Learning Test at baseline. Using machine learning approaches, we constructed a new measure that exploited finer differences in memory strategy than previous work focused on serial position and subjective organization. The new measure, based on stochastic gradient descent, provides a greater degree of statistical separation (p = 1.44 × 10-5) than previously observed for asymptomatic family history and non-family history groups, while controlling for apolipoprotein epsilon 4, age, gender, and education level. The results of our machine learning approach support analyzing memory strategy in detail to probe potential disease onset. Such distinct differences may be exploited in asymptomatic middle-aged persons as a potential risk factor for AD.
Tam, Maureen; Chui, Ernest
This paper is about a quantitative study which has examined and elucidated the conceptualizations of ageing and learning by a group of elders in Hong Kong. In more specific terms, the study has investigated how this group of older people understood the meaning of successful ageing and elder learning in the context of their later lives. Based on…
Yoshida, Katherine A.; Pons, Ferran; Maye, Jessica; Werker, Janet F.
Infant phonetic perception reorganizes in accordance with the native language by 10 months of age. One mechanism that may underlie this perceptual change is distributional learning, a statistical analysis of the distributional frequency of speech sounds. Previous distributional learning studies have tested infants of 6-8 months, an age at which…
Palmer, Shekeila D; Havelka, Jelena
Two experiments examined whether the age of acquisition (AoA) of a concept influences the speed at which native English speakers are able to name pictures using a newly acquired second language (L2) vocabulary. In Experiment 1, participants were taught L2 words associated with pictures. In Experiment 2 a second group of participants were taught the same words associated with L1 translations. Following training both groups performed a picture naming task in which they were asked to name pictures using the newly acquired words. Significant AoA effects were observed only in Experiment 1, in that participants were faster at naming pictures representing early acquired relative to late acquired concepts. The results suggest that the AoA of a concept can exert influence over processing which is independent of the AoA of the word form. The results also indicate that different training methods may lead to qualitative differences in the nature of the links formed between words and concepts during the earliest stages of second language learning.
Dijk, van Henk
Learning motor skills is fundamental to human life. One of the most critical variables affecting motor learning, aside from practice itself, is augmented feedback (performance-related information). Although there is abundance of research on how young adults use augmented feedback to learn motor skil
Hodes, Georgia E; Shors, Tracey J.
Acute stressful experience enhances subsequent learning in males and impairs learning in females. These sex differences emerge soon after puberty in adulthood. Whether these opposite effects of stress on learning extend into older age is unknown. To examine this, young adult (2–3 months) and middle aged (17–18 months) Fischer 344 rats of both sexes were exposed to an acute stress or of brief tail shocks and trained 24 h later with classical eyeblink conditioning using a trace paradigm. Wherea...
Hori, Shigeo; Cusack, Sandra
Lifelong learning is essential to participation in society, and presents important challenges for educational gerontology. This study compares Canadian and Japanese perspectives on (a) attitudes toward aging, (b) the learning needs of older adults, and (c) the role of centers of learning. Surveys were conducted of sample populations in two elder…
Grosso, G; Estruch, R
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.
Full Text Available Ageing is often accompanied by a decline in learning and memory abilities across the animal kingdom. Understanding age-related changes in cognitive abilities is therefore a major goal of current research. The honey bee is emerging as a novel model organism for age-related changes in brain function, because learning and memory can easily be studied in bees under controlled laboratory conditions. In addition, genetically similar workers naturally display life expectancies from six weeks (summer bees to six months (winter bees. We studied whether in honey bees, extreme longevity leads to a decline in cognitive functions. Six-month-old winter bees were conditioned either to odours or to tactile stimuli. Afterwards, long-term memory and discrimination abilities were analysed. Winter bees were kept under different conditions (flight /no flight opportunity to test for effects of foraging activity on learning performance. Despite their extreme age, winter bees did not display an age-related decline in learning or discrimination abilities, but had a slightly impaired olfactory long-term memory. The opportunity to forage indoors led to a slight decrease in learning performance. This suggests that in honey bees, unlike in most other animals, age per se does not impair associative learning. Future research will show which mechanisms protect winter bees from age-related deficits in learning.
Boulton-Lewis, Gillian M.; Buys, Laurie
This paper reports on the findings of qualitative, semistructured interviews conducted with 40 older Australian participants who either did or did not engage in organized learning. Phenomenology was used to guide the interviews and analysis to explore the lived learning experiences and perspectives of these older people. Their experiences of…
McGeer, Patrick L; McGeer, Edith G
Chronic inflammation is associated with a broad spectrum of neurodegenerative diseases of aging. Included are such disorders as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis, the Parkinson-dementia complex of Guam, all of the tauopathies, and age-related macular degeneration. Also included are such peripheral conditions as osteoarthritis, rheumatoid arthritis, atherosclerosis, and myocardial infarction. Inflammation is a two-edged sword. In acute situations, or at low levels, it deals with the abnormality and promotes healing. When chronically sustained at high levels, it can seriously damage viable host tissue. We describe this latter phenomenon as autotoxicity to distinguish it from autoimmunity. The latter involves a lymphocyte-directed attack against self proteins. Autotoxicity, on the other hand, is determined by the concentration and degree of activation of tissue-based monocytic phagocytes. Microglial cells are the brain representatives of the monocyte phagocytic system. Biochemically, the intensity of their activation is related to a spectrum of inflammatory mediators generated by a variety of local cells. The known spectrum includes, but is not limited to, prostaglandins, pentraxins, complement components, anaphylotoxins, cytokines, chemokines, proteases, protease inhibitors, adhesion molecules, and free radicals. This spectrum offers a huge variety of targets for new anti-inflammatory agents. It has been suggested, largely on the basis of transgenic mouse models, that stimulating inflammation rather than inhibiting it can be beneficial in such diseases as AD. If this were the case, administration of NSAIDs, or other anti-inflammatory drugs, would be expected to exacerbate conditions such as AD, PD, and atherosclerosis. However, epidemiological evidence overwhelmingly demonstrates that the reverse is true. This indicates that, at least in these diseases, the inflammation is harmful. So far, advantage has not been taken
Brian T Harel
Full Text Available Associate learning is fundamental to the acquisition of knowledge and plays a critical role in the everyday functioning of the developing child, though the developmental course is still unclear. This study investigated the development of visual associate learning in 125 school age children using the Continuous Paired Associate Learning task. As hypothesized, younger children made more errors than older children across all memory loads and evidenced decreased learning efficiency as memory load increased. Results suggest that age-related differences in performance largely reflect continued development of executive function in the context of relatively developed memory processes.
Praag, Henriette van; Shubert, Tiffany; Zhao, Chunmei; Gage, Fred H.
Aging causes changes in the hippocampus that may lead to cognitive decline in older adults. In young animals, exercise increases hippocampal neurogenesis and improves learning. We investigated whether voluntary wheel running would benefit mice that were sedentary until 19 months of age. Specifically, young and aged mice were housed with or without a running wheel and injected with bromodeoxyuridine or retrovirus to label newborn cells. After 1 month, learning was tested in the Morris water maze. Aged runners showed faster acquisition and better retention of the maze than age-matched controls. The decline in neurogenesis in aged mice was reversed to 50% of young control levels by running. Moreover, fine morphology of new neurons did not differ between young and aged runners, indicating that the initial maturation of newborn neurons was not affected by aging. Thus, voluntary exercise ameliorates some of the deleterious morphological and behavioral consequences of aging. PMID:16177036
Pendt, Lisa Katharina; Reuter, Iris; Müller, Hermann
Parkinson's disease, which affects the basal ganglia, is known to lead to various impairments of motor control. Since the basal ganglia have also been shown to be involved in learning processes, motor learning has frequently been investigated in this group of patients. However, results are still inconsistent, mainly due to skill levels and time scales of testing. To bridge across the time scale problem, the present study examined de novo skill learning over a long series of practice sessions that comprised early and late learning stages as well as retention. 19 non-demented, medicated, mild to moderate patients with Parkinson's disease and 19 healthy age and gender matched participants practiced a novel throwing task over five days in a virtual environment where timing of release was a critical element. Six patients and seven control participants came to an additional long-term retention testing after seven to nine months. Changes in task performance were analyzed by a method that differentiates between three components of motor learning prominent in different stages of learning: Tolerance, Noise and Covariation. In addition, kinematic analysis related the influence of skill levels as affected by the specific motor control deficits in Parkinson patients to the process of learning. As a result, patients showed similar learning in early and late stages compared to the control subjects. Differences occurred in short-term retention tests; patients' performance constantly decreased after breaks arising from poorer release timing. However, patients were able to overcome the initial timing problems within the course of each practice session and could further improve their throwing performance. Thus, results demonstrate the intact ability to learn a novel motor skill in non-demented, medicated patients with Parkinson's disease and indicate confounding effects of motor control deficits on retention performance.
Lisa Katharina Pendt
Full Text Available Parkinson's disease, which affects the basal ganglia, is known to lead to various impairments of motor control. Since the basal ganglia have also been shown to be involved in learning processes, motor learning has frequently been investigated in this group of patients. However, results are still inconsistent, mainly due to skill levels and time scales of testing. To bridge across the time scale problem, the present study examined de novo skill learning over a long series of practice sessions that comprised early and late learning stages as well as retention. 19 non-demented, medicated, mild to moderate patients with Parkinson's disease and 19 healthy age and gender matched participants practiced a novel throwing task over five days in a virtual environment where timing of release was a critical element. Six patients and seven control participants came to an additional long-term retention testing after seven to nine months. Changes in task performance were analyzed by a method that differentiates between three components of motor learning prominent in different stages of learning: Tolerance, Noise and Covariation. In addition, kinematic analysis related the influence of skill levels as affected by the specific motor control deficits in Parkinson patients to the process of learning. As a result, patients showed similar learning in early and late stages compared to the control subjects. Differences occurred in short-term retention tests; patients' performance constantly decreased after breaks arising from poorer release timing. However, patients were able to overcome the initial timing problems within the course of each practice session and could further improve their throwing performance. Thus, results demonstrate the intact ability to learn a novel motor skill in non-demented, medicated patients with Parkinson's disease and indicate confounding effects of motor control deficits on retention performance.
Geng, Xin; Yin, Chao; Zhou, Zhi-Hua
One of the main difficulties in facial age estimation is that the learning algorithms cannot expect sufficient and complete training data. Fortunately, the faces at close ages look quite similar since aging is a slow and smooth process. Inspired by this observation, instead of considering each face image as an instance with one label (age), this paper regards each face image as an instance associated with a label distribution. The label distribution covers a certain number of class labels, representing the degree that each label describes the instance. Through this way, one face image can contribute to not only the learning of its chronological age, but also the learning of its adjacent ages. Two algorithms, named IIS-LLD and CPNN, are proposed to learn from such label distributions. Experimental results on two aging face databases show remarkable advantages of the proposed label distribution learning algorithms over the compared single-label learning algorithms, either specially designed for age estimation or for general purpose.
Ager, J.W.; Balooch, G.; Ritchie, R.O.
fracture resistance, whereas regulating the level of the cytokine TGF-beta can offer significant improvements in the stiffness, strength and toughness of bone, and as such may be considered as a therapeutic target to treat increased bone fragility induced by aging, drugs, and disease.
Aging is the most significant risk factor for a range of degenerative disease such as cardiovascular, neurodegenerative and metabolic disorders. While the cause of aging and its associated diseases is multifactorial, mitochondrial dysfunction has been implicated in the aging process and the onset and progression of age-associated disorders. Recent studies indicate that maintenance of mitochondrial function is beneficial in the prevention or delay of age-associated diseases. A central molecule...
Children are thought to learn second languages (L2s) using primarily implicit mechanisms, in contrast to adults, who primarily rely on explicit language learning. This difference is usually attributed to cognitive maturation, but adults also receive more explicit instruction than children, which may influence their learning strategies. This study crosses instruction condition with age, teaching forty children aged 5;3 to 7;11 and forty adults an artificial mini-language under implicit or explicit training conditions. Participants produced novel sentences and judged sentence grammaticality equally well in either condition, but both children and adults in the explicit training condition developed greater awareness of the mini-language's structures - and greater awareness was associated with better performance for both age groups. Results show that explicit instruction affects children and adults in the same way, supporting the hypothesis that age differences in implicit vs. explicit L2 learning are not exclusively caused by maturation, but also influenced by instruction.
He, Zhouzhou; Li, Xi; Zhang, Zhongfei; Wu, Fei; Geng, Xin; Zhang, Yaqing; Yang, Ming-Hsuan; Zhuang, Yueting
As an important and challenging problem in computer vision, face age estimation is typically cast as a classification or regression problem over a set of face samples with respect to several ordinal age labels, which have intrinsically cross-age correlations across adjacent age dimensions. As a result, such correlations usually lead to the age label ambiguities of the face samples. Namely, each face sample is associated with a latent label distribution that encodes the cross-age correlation information on label ambiguities. Motivated by this observation, we propose a totally data-driven label distribution learning approach to adaptively learn the latent label distributions. The proposed approach is capable of effectively discovering the intrinsic age distribution patterns for cross-age correlation analysis on the basis of the local context structures of face samples. Without any prior assumptions on the forms of label distribution learning, our approach is able to flexibly model the sample-specific context aware label distribution properties by solving a multi-task problem, which jointly optimizes the tasks of age-label distribution learning and age prediction for individuals. Experimental results demonstrate the effectiveness of our approach.
Petyaev, Ivan M
Lycopene is a hydrocarbon phytochemical belonging to the tetraterpene carotenoid family and is found in red fruit and vegetables. Eleven conjugated double bonds predetermine the antioxidant properties of lycopene and its ability to scavenge lipid peroxyl radicals, reactive oxygen species, and nitric oxide. Lycopene has a low bioavailability rate and appears in the blood circulation incorporated into chylomicrons and other apo-B containing lipoproteins. The recent body of evidence suggests that plasma concentration of lycopene is not only a function of intestinal absorption rate but also lycopene breakdown via enzymatic and oxidative pathways in blood and tissues. Oxidative stress and the accumulation of reactive oxygen species and nitric oxide may represent a major cause of lycopene depletion in ageing, cardiovascular disease, and type 2 diabetes mellitus. It has been shown recently that low carotenoid levels, and especially decreased serum lycopene levels, are strongly predictive of all-cause mortality and poor outcomes of cardiovascular disease. However, there is a poor statistical association between dietary and serum lycopene levels which occurs due to limited bioavailability of lycopene from dietary sources. Hence, it is very unlikely that nutritional intervention alone could be instrumental in the correction of lycopene and carotenoid deficiency. Therefore, new nutraceutical formulations of carotenoids with enhanced bioavailability are urgently needed.
Ram Pande; Mayur Bagad; Vinay Dubey; Asit Ranjan Ghosh
In India food reflects the warmth, hospitality, status, symbol of wealth and aesthetics. The synergistic combination of pre and probiotics is known as synbiotics. Regular consumption of synbiotics in diets imparts health benefits like improved immune response, maintain intestinal integrity, decrease intestinal infections and down regulate the allergic response, influence digestion and gastric motility. Because of the changes in life styles due to globalization, unhealthy diets, lack of physical activity and exposure to tobacco smoke or harmful use of alcohol non communicable diseases are disproportionately affecting the 80% of low and middle income countries. This review covers the mechanism of probiotic action, use of probiotics in treatment and prevention of diseases of modern age, progress in delivery systems for the administration and finally some regulatory considerations. In conclusion, combined skills of the microbiologist, food technologist and clinician are necessary to sustain effect of probiotics. The role of probiotic organisms as alternative or complementary therapy in combating a large number of disorders can be achieved with balance and healthy life style as well as clean external environmental conditions. It is hoped that more detailed research will be conducted regarding the efficacy of probiotics so that clinically well documented and simplest formulation will be developed and can be regarded as effective for everyone. With validated results strong market will be formed and expanded in near future.
Fabris, Fabio; Magalhães, João Pedro de; Freitas, Alex A
Broadly speaking, supervised machine learning is the computational task of learning correlations between variables in annotated data (the training set), and using this information to create a predictive model capable of inferring annotations for new data, whose annotations are not known. Ageing is a complex process that affects nearly all animal species. This process can be studied at several levels of abstraction, in different organisms and with different objectives in mind. Not surprisingly, the diversity of the supervised machine learning algorithms applied to answer biological questions reflects the complexities of the underlying ageing processes being studied. Many works using supervised machine learning to study the ageing process have been recently published, so it is timely to review these works, to discuss their main findings and weaknesses. In summary, the main findings of the reviewed papers are: the link between specific types of DNA repair and ageing; ageing-related proteins tend to be highly connected and seem to play a central role in molecular pathways; ageing/longevity is linked with autophagy and apoptosis, nutrient receptor genes, and copper and iron ion transport. Additionally, several biomarkers of ageing were found by machine learning. Despite some interesting machine learning results, we also identified a weakness of current works on this topic: only one of the reviewed papers has corroborated the computational results of machine learning algorithms through wet-lab experiments. In conclusion, supervised machine learning has contributed to advance our knowledge and has provided novel insights on ageing, yet future work should have a greater emphasis in validating the predictions.
Verneau, M.; Kamp, J. van der; Savelsbergh, G.J.P.; Looze, M.P. de
Study Context: It has been proposed that effects of aging are more pronounced for explicit than for implicit motor learning. The authors evaluated this claim by comparing the efficacy of explicit and implicit learning of a movement sequence in young and older adults, and by testing the resilience ag
The purpose of the study was to investigate language learning strategies used by English as a Foreign Language (EFL) learners at different educational levels and explored the influence of age on the use of language learning strategies. A total of 1,023 students participated in the study. Out of the participants, there were 250 primary students…
Fleming, Julie; Becker, Karen; Newton, Cameron
Purpose: The purpose of this paper is to examine the factors affecting employees' overall acceptance, satisfaction and future use of e-learning, specifically exploring the impact that age has on the intended future use of e-learning relative to the other potential predictors. Design/Methodology/Approach: The project developed an online survey and…
Blagosklonny, Mikhail V
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.
There has been a shift in interest from ‘lifelong education’ to ‘lifelong learning’ in the Western world since the 1990s. This shift is closely related to strategies for securing the competitiveness of national economies. For this purpose one of the tools applied by educational policy makers has...... been to invoke ‘the golden standard(s)’ of evidence based research into the domain of learning. A number of problems with this approach are that the very conception of learning is broad, vague, ambiguous and does not in itself give us a normative handle which can help us with education. There might...... be one particular area, however, where evidence based learning research might be thought to have a strong foothold: in the brain sciences. And certainly a rapidly growing interest in ‘educational neuroscience’ has emerged within the last 10 years. But is it possible to bridge the gap between ‘studying...
Ye, Dong Hye; Desjardins, Benoit; Hamm, Jihun; Litt, Harold; Pohl, Kilian M
While manifold learning from images itself has become widely used in medical image analysis, the accuracy of existing implementations suffers from viewing each image as a single data point. To address this issue, we parcellate images into regions and then separately learn the manifold for each region. We use the regional manifolds as low-dimensional descriptors of high-dimensional morphological image features, which are then fed into a classifier to identify regions affected by disease. We produce a single ensemble decision for each scan by the weighted combination of these regional classification results. Each weight is determined by the regional accuracy of detecting the disease. When applied to cardiac magnetic resonance imaging of 50 normal controls and 50 patients with reconstructive surgery of Tetralogy of Fallot, our method achieves significantly better classification accuracy than approaches learning a single manifold across the entire image domain.
As a result of the general improvement in living conditions in industrialised Western countries, people aged over 60 years usually reach the third age in good mental and physical condition. Contemporary society has thus had to endeavour to offer the new old not only social services but also pastimes, leisure, social, cultural and educational…
Background: Growing numbers of people with learning disabilities are now living into older age. This study aims to examine the state of knowledge about their lives and the challenges that ageing has for both family carers and policymakers and practitioners. Materials and Methods: The article synthesises existing research in the fields of learning…
Zhu, Haidong; Belcher, Matthew; van der Harst, Pim
Aging is a biological process that affects most cells, organisms and species. Human aging is associated with increased susceptibility to a variety of chronic diseases, including cardiovascular disease, Type 2 diabetes, neurological diseases and cancer. Despite the remarkable progress made during the
Full Text Available [Excerpt] We offer a different approach to delaying or preventing age-related diseases. To understand the necessity for a new approach we have plotted the mortality rates in Israelis in relation to specific age groups and diseases. With the common phenomenon of aging of Western populations it is of utmost importance to follow time-dependent and age-dependent mortality patterns to predict future needs of Western health systems. Age-specific, gender-specific, and cause-of-death-specific mortality rates were extracted from the statistical abstract of Israel1 and include data for the period of 1975–2010; these are presented in Figure 1, separately for men (A and women (B. Detailed age-specific causes of death data were available for the year 2009. Data presented were restricted to 5-year age groups starting at age 50, and for cause-specific mortality to the following age groups: 45–54, 55–64, 65–74, 75–84, and 85+. Causes of mortality were separated into malignant diseases, acute myocardial infarction, other ischemic heart diseases, other forms of heart diseases, cerebrovascular disease, diabetes mellitus, respiratory diseases, diseases of kidney, infectious diseases, all external causes, signs/symptoms and ill-defined conditions, and all other diseases. Figure 1 is similar to the one posted on the National Institute of Aging website and similar to data across the industrial world. The striking feature of this graph is that aging is a major log scale risk for most diseases, including the major killers: heart disease, cancer, diabetes, and Alzheimer’s. For example, while aging is a 100-fold risk for cardiovascular disease (CVD according to Figure 1, hypercholesterolemia is known to carry only a three-fold risk for CVD. For each of the mentioned diseases, aging is a log risk greater than the most important known risk factor for that disease.
Ana Luiza Andrade
Full Text Available It is known that learning refers to how beings acquire new knowledge, develop skills and change behavior. Thus, knowing the learning styles of individuals is important, both for those who learn how to teach. In this sense, this research project aimed to describe the sociodemographic characteristics of the sample, identify the predominant learning styles of these individuals and see if there is a correlation between learning styles with sociodemographic variables. The sample consisted of 248 elderly participants in the study "Continuing Education - Benefits of the Open University of the Third Age EACH USP", funded by the National Institute for Educational Studies and Research Teixeira (INEP| Ministry of Education. We used a protocol that included sociodemographic questionnaire and the Learning Style Inventory (Learning Style Inventory - LSI by David A. Kolb. Descriptive analysis and inferential analysis. The dominant learning style was the assimilator and identified the association between learning styles of older people and sex (p = 0.0372, age (p = 0.0450, schooling for males (p = 0.0155 and sex for seniors with even the elementary school level (p = 0.0166. The results of this study are in line with theoretical perspectives and findings in the literature with regard to sample characteristics and learning styles identified. Future studies should be conducted in order to investigate more about the topic of learning in the elderly.
Full Text Available Peptic ulcer disease is one of the most widespread diseases. 6-10 % of adult population in Russia suffer from it. Demographic processes in the Russian Federation determine the increase of patients' number aged over 60 with peptic ulcer disease. It counts 10-35 % of all patients with this disease. The modern views on pathogenesis of peptic ulcer disease, including factor of Helicobacter pylori, in patients of different age groups have been highlighted in the article. Pathogenetic features and clinical morphological manifestations of peptic ulcer disease in young and aged patients have been considered
Ardeljan, Daniel; Chan, Chi-Chao
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.
Full Text Available Personal development throughout the course of life is at the core of several important policy documents that have shaped European cooperation in economic, social and educational sciences over the last decade. The paradigm of Lifelong Learning implies learning at any age of life and underlines the importance of achieving continuous knowledge and self-care. Pedagogy has started taking into account the age of older adults only in recent years. The European project we are going to illustrate sought to test how well peer to peer learning can be useful to define new training and learning models for older adults. The HiHtaST (Hand in Hand to a Social Tomorrow project provides an example of peer to peer learning among older adults. We provided training for adult learners to teach IT among other older adults as a means for social inclusion in five European countries. Each country had 20 learners / trainers who had other older students in turn. Multiple choice questionnaires and focus groups were used to collect data. The project was run in the theoretical framework of active ageing, considering the paradigm of Vygotsky’s zone of proximal development and co-construction of knowledge. The project results showed that adults can acquire knowledge in peer to peer group situations with no drop-outs especially when learning real and practical tasks, which suggests that peer to peer learning works better than a frontal class in formal as well as non-formal or informal situations
Lou, Zhongyu; Alnajar, Fares; Alvarez, Jose; Hu, Ninghang; Gevers, Theo
In this paper, we investigate and exploit the influence of facial expressions on automatic age estimation. Different from existing approaches, our method jointly learns the age and expression by introducing a new graphical model with a latent layer between the age/expression labels and the features. This layer aims to learn the relationship between the age and expression and captures the face changes which induce the aging and expression appearance, and thus obtaining expression-invariant age estimation. Conducted on three age-expression datasets (FACES , Lifespan  and NEMO ), our experiments illustrate the improvement in performance when the age is jointly learnt with expression in comparison to expression-independent age estimation. The age estimation error is reduced by 14.43%, 37.75% and 9.30% for the FACES, Lifespan and NEMO datasets respectively. The results obtained by our graphical model, without prior-knowledge of the expressions of the tested faces, are better than the best reported ones for all datasets. The flexibility of the proposed model to include more cues is explored by incorporating gender together with age and expression. The results show performance improvements for all cues.
Farkas, E; Luiten, PGM
The aging of the central nervous system and the development of incapacitating neurological diseases like Alzheimer's disease (AD) are generally associated with a wide range of histological and pathophysiological changes eventually leading to compromised cognitive status. Although the diverse trigger
U.S. Department of Health & Human Services — NNDSS - Table II. Invasive Pneumococcal Diseases, All Ages - 2017. In this Table, provisional cases of selected notifiable diseases (â¥1,000 cases reported during...
U.S. Department of Health & Human Services — NNDSS - Table II. Invasive Pneumococcal Diseases, Age <5 - 2017. In this Table, provisional cases of selected notifiable diseases (â¥1,000 cases reported during...
McGovern, John P.
The author examines the problems of chronic respiratory disease in school-age children from a medical viewpoint, including recognition and diagnosis, commonly encountered diseases, their effect on participation in physical exercise, emotional factors, medication, and emergency care. (MB)
Full Text Available Learning analytics (LA has been applied to various learning environments, though it is quite new in the field of computer assisted language learning (CALL. This article attempts to examine the application of learning analytics in the upcoming big data age. It starts with an introduction and application of learning analytics in other fields, followed by a retrospective review of historical interaction between learning and media in CALL, and a penetrating analysis on why people would go to learning analytics to increase the efficiency of foreign language education. As approved in previous research, new technology, including big data mining and analysis, would inevitably enhance the learning of foreign languages. Potential changes that learning analytics would bring to Chinese foreign language education and researches are also presented in the article.
Ban, T A; Guy, W
Of the two generally recognized processes through which learning occurs--imprinting and conditioning--only the latter with its two paradigms, classical and operant, has both practical and heuristic implications for disease. From the classical conditioning experiments of Pavlov's laboratory over 100 years ago to the later work in operant conditioning by Skinner and others in the past four decades has evolved much of the basis of modern learning theory and its applications to disease in the form of behavior therapy. Variants of behavior therapy have been employed in the treatment of wide variety of medical and psychiatric illnesses. Recent developments in the study of brain function and biochemistry have led to renewed interest in the conditioning paradigm and its value as tool in these areas of research.
... of your heart. Preventing heart disease (and all cardiovascular diseases ) means making smart choices now that will pay off the rest of your life. Lack of exercise, a poor diet and other unhealthy habits can ...
Fristrup, Tine; Grut, Sara
In this article, we develop a framework that demonstrates how older adults need to develop diverse capabilities in relation to their educational life course through engagements in Nordic museums, archives and street art activities. We discuss how European museums have taken up UNESCO’s approach...... to lifelong learning as a way to conceptualise activities for older adults’ in museums, as we emphasise an approach to adult education for active ageing articulated as ‘lifelong learning for active ageing’. To illustrate this framing, we outline a number of activities taken from publications, cultural sites...... and conferences in which we have been involved over the last decade in the context of the Nordic Centre of Heritage Learning and Creativity in Östersund, Sweden. We argue that lifelong learning for active ageing in cultural heritage institutions can contribute to the development of older adults’ civic...
Mata, Rui; von Helversen, Bettina; Rieskamp, Jörg
Decision makers often have to learn from experience. In these situations, people must use the available feedback to select the appropriate decision strategy. How does the ability to select decision strategies on the basis of experience change with age? We examined younger and older adults' strategy selection learning in a probabilistic inference task using a computational model of strategy selection learning. Older adults showed poorer decision performance compared with younger adults. In particular, older adults performed poorly in an environment favoring the use of a more cognitively demanding strategy. The results suggest that the impact of cognitive aging on strategy selection learning depends on the structure of the decision environment.
Geifman, Nophar; Cohen, Raphael; Rubin, Eitan
Age is an important factor when considering phenotypic changes in health and disease. Currently, the use of age information in medicine is somewhat simplistic, with ages commonly being grouped into a small number of crude ranges reflecting the major stages of development and aging, such as childhood or adolescence. Here, we investigate the possibility of redefining age groups using the recently developed Age-Phenome Knowledge-base (APK) that holds over 35,000 literature-derived entries describing relationships between age and phenotype. Clustering of APK data suggests 13 new, partially overlapping, age groups. The diseases that define these groups suggest that the proposed divisions are biologically meaningful. We further show that the number of different age ranges that should be considered depends on the type of disease being evaluated. This finding was further strengthened by similar results obtained from clinical blood measurement data. The grouping of diseases that share a similar pattern of disease-related reports directly mirrors, in some cases, medical knowledge of disease-age relationships. In other cases, our results may be used to generate new and reasonable hypotheses regarding links between diseases.
Noble, Daniel W A; Byrne, Richard W; Whiting, Martin J
Evidence of social learning, whereby the actions of an animal facilitate the acquisition of new information by another, is taxonomically biased towards mammals, especially primates, and birds. However, social learning need not be limited to group-living animals because species with less interaction can still benefit from learning about potential predators, food sources, rivals and mates. We trained male skinks (Eulamprus quoyii), a mostly solitary lizard from eastern Australia, in a two-step foraging task. Lizards belonging to 'young' and 'old' age classes were presented with a novel instrumental task (displacing a lid) and an association task (reward under blue lid). We did not find evidence for age-dependent learning of the instrumental task; however, young males in the presence of a demonstrator learnt the association task faster than young males without a demonstrator, whereas old males in both treatments had similar success rates. We present the first evidence of age-dependent social learning in a lizard and suggest that the use of social information for learning may be more widespread than previously believed.
Aging of biological systems occurs in spite of numerous complex pathways of maintenance, repair and defense. There are no gerontogenes which have the specific evolutionary function to cause aging. Although aging is the common cause of all age-related diseases, aging in itself cannot be considered...... a disease. This understanding of aging as a process should transform our approach towards interventions from developing illusory anti-aging treatments to developing realistic and practical methods for maintaining health throughout the lifespan. The concept of homeodynamic space can be a useful one in order...... to identify a set of measurable, evidence-based and demonstratable parameters of health, robustness and resilience. Age-induced health problems, for which there are no other clear-cut causative agents, may be better tackled by focusing on health mechanisms and their maintenance, rather than only disease...
Sheedfar, Fareeba; Di Biase, Stefano; Koonen, Debby; Vinciguerra, Manlio
The liver is the only internal human organ capable of natural regeneration of lost tissue, as little as 25% of a liver can regenerate into a whole liver. The process of aging predisposes to hepatic functional and structural impairment and metabolic risk. Therefore, understanding how aging could affe
Schneider, N G; Gritz, E R; Jarvik, M E
In an initial study, differences in learning and immediate recall were observed for groups of young and aged subjects on several measures. Retest date showed some differential loss for aged subjects after 1 week. Conclusions regarding long-term retention per se were not possible due to the nature of the design. In a second study, additional aged and young groups of subjects were run under delayed recall conditions. The data from these two groups were combined with data from the first study, with care taken to match subjects on a number of variables (health, education, intelligence). The results showed age-related differences for measures of learning and immediate recall but not for delayed 1 week retention.
Mapstone, Mark; Dickerson, Kathryn; Duffy, Charles J.
Similar manifestations of functional decline in ageing and Alzheimer's disease obscure differences in the underlying cognitive mechanisms of impairment. We sought to examine the contributions of top-down attentional and bottom-up perceptual factors to visual self-movement processing in ageing and Alzheimer's disease. We administered a novel…
Bousquet, J; Anto, J M; Berkouk, K; Gergen, P; Antunes, J Pinto; Augé, P; Camuzat, T; Bringer, J; Mercier, J; Best, N; Bourret, R; Akdis, M; Arshad, S H; Bedbrook, A; Berr, C; Bush, A; Cavalli, G; Charles, M A; Clavel-Chapelon, F; Gillman, M; Gold, D R; Goldberg, M; Holloway, J W; Iozzo, P; Jacquemin, S; Jeandel, C; Kauffmann, F; Keil, T; Koppelman, G H; Krauss-Etschmann, S; Kuh, D; Lehmann, S; Carlsen, K C Lodrup; Maier, D; Méchali, M; Melén, E; Moatti, J P; Momas, I; Nérin, P; Postma, D S; Ritchie, K; Robine, J M; Samolinski, B; Siroux, V; Slagboom, P E; Smit, H A; Sunyer, J; Valenta, R; Van de Perre, P; Verdier, J M; Vrijheid, M; Wickman, M; Yiallouros, P; Zins, M
Prenatal and peri-natal events play a fundamental role in health, development of diseases and ageing (Developmental Origins of Health and Disease (DOHaD)). Research on the determinants of active and healthy ageing is a priority to: (i) inform strategies for reducing societal and individual costs of
Staja Q. Booker
Full Text Available Background: The unprecedented global growth in older adults merits high-quality gerontological nursing care. As gerontological nursing grows in visibility in developed and developing countries, nurses must possess a broader worldview of ageing with knowledge of physiological, psychosocial, and cultural issues.Purpose: The purpose of this article is to: (1 highlight lessons learned on differences and similarities in ageing and care of older adults in the United States of America (USA and South Africa (SA; and (2 provide recommendations on how to advance gerontological nursingeducation in SA.Methods: A two-week international service-learning project was undertaken by visiting SA and learning about their nursing system and care of older adults. Service-learning is an innovative teaching-learning-service method that provided reflective and hands-on experience of gerontological nursing. This article provides a personal reflection of lessons learned about ageing and gerontological nursing during the service-learning project.Findings: Care of older adults in SA is in many ways different from and similar to that in the USA. Consequently global nurses should recognise those differences and provide culturally appropriate care. This service-learning experience also demonstrated the need for gerontological nursing education in SA. Based on this, recommendations on how to infuse and advance gerontological nursing education in SA are provided.Conclusion: Caring for older adults in a global context requires knowledge and understanding of cultures and their values and practices. With a growing population of diverse older adults, there is a need for incorporation
Lisa B. Boyette
Full Text Available Preservation of adult stem cells pools is critical for maintaining tissue homeostasis into old age. Exhaustion of adult stem cell pools as a result of deranged metabolic signaling, premature senescence as a response to oncogenic insults to the somatic genome, and other causes contribute to tissue degeneration with age. Both progeria, an extreme example of early-onset aging, and heritable longevity have provided avenues to study regulation of the aging program and its impact on adult stem cell compartments. In this review, we discuss recent findings concerning the effects of aging on stem cells, contributions of stem cells to age-related pathologies, examples of signaling pathways at work in these processes, and lessons about cellular aging gleaned from the development and refinement of cellular reprogramming technologies. We highlight emerging therapeutic approaches to manipulation of key signaling pathways corrupting or exhausting adult stem cells, as well as other approaches targeted at maintaining robust stem cell pools to extend not only lifespan but healthspan.
Full Text Available The paper presents outcomes of a longitudinal study on learning motivation in children of early school age. The aim was to reveal the leading motives in first, second, third and fourth grades and to explore the dynamics of some learning motives in children over the whole period of elementary school. As it was found, the learning activity in the children was mostly motivated by social motives, among which the leading ones were the motives of selfdetermination and wellbeing. As for learning motives, over the course of all four years the children were for the most part motivated by the content of the learning activity, and not by its process. The dynamics of certain social motives of the learning activity varied across the sample, with some going through the periods of increase and decrease and others having a oneway dynamics. The study also revealed a decrease in the motivation rooted in the learning activity itself between the second and third year; at the same time, in the second, third and fourth years the children were more motivated by the content of the learning activity than by its process
Full Text Available Aging is the most significant risk factor for a range of degenerative disease such as cardiovascular, neurodegenerative and metabolic disorders. While the cause of aging and its associated diseases is multifactorial, mitochondrial dysfunction has been implicated in the aging process and the onset and progression of age-associated disorders. Recent studies indicate that maintenance of mitochondrial function is beneficial in the prevention or delay of age-associated diseases. A central molecule seems to be the peroxisome proliferator-activated receptor γ coactivator α (PGC-1α, which is the key regulator of mitochondrial biogenesis. Besides regulating mitochondrial function, PGC-1α targets several other cellular processes and thereby influences cell fate on multiple levels. This paper discusses how mitochondrial function and PGC-1α are affected in age-associated diseases and how modulation of PGC-1α might offer a therapeutic potential for age-related pathology.
Aging is the most significant risk factor for a range of degenerative disease such as cardiovascular, neurodegenerative and metabolic disorders. While the cause of aging and its associated diseases is multifactorial, mitochondrial dysfunction has been implicated in the aging process and the onset and progression of age-associated disorders. Recent studies indicate that maintenance of mitochondrial function is beneficial in the prevention or delay of age-associated diseases. A central molecule seems to be the peroxisome proliferator-activated receptor γ coactivator α (PGC-1α), which is the key regulator of mitochondrial biogenesis. Besides regulating mitochondrial function, PGC-1α targets several other cellular processes and thereby influences cell fate on multiple levels. This paper discusses how mitochondrial function and PGC-1α are affected in age-associated diseases and how modulation of PGC-1α might offer a therapeutic potential for age-related pathology.
Sanders, Y. V.; Giezenaar, M. A.; Laros-van Gorkom, B. A. P.; Meijer, K.; van der Bom, J. G.; Cnossen, M. H.; Nijziel, M. R.; Ypma, P. F.; Fijnvandraat, K.; Eikenboom, J.; Mauser-Bunschoten, E. P.; Leebeek, F. W. G.
Background: Because the number of elderly von Willebrand disease (VWD) patients is increasing, the pathophysiology of aging in VWD has become increasingly relevant. Objectives: To assess age-related changes in von Willebrand factor (VWF) and factor VIII (FVIII) levels and to compare age-related diff
Full Text Available To explore the relationship between category and perceptual learning, we examined both category and perceptual learning in patients with treated Wilson's disease (WD, whose basal ganglia, known to be important in category learning, were damaged by the disease. We measured their learning rate and accuracy in rule-based and information-integration category learning, and magnitudes of perceptual learning in a wide range of external noise conditions, and compared the results with those of normal controls. The WD subjects exhibited deficits in both forms of category learning and in perceptual learning in high external noise. However, their perceptual learning in low external noise was relatively spared. There was no significant correlation between the two forms of category learning, nor between perceptual learning in low external noise and either form of category learning. Perceptual learning in high external noise was, however, significantly correlated with information-integration but not with rule-based category learning. The results suggest that there may be a strong link between information-integration category learning and perceptual learning in high external noise. Damage to brain structures that are important for information-integration category learning may lead to poor perceptual learning in high external noise, yet spare perceptual learning in low external noise. Perceptual learning in high and low external noise conditions may involve separate neural substrates.
Lalovic, Dejan; Gvozdenovic, Vasilije
Efficient memory is one of the necessary cognitive potentials required for virtually every form of lifelong learning. In this contribution we first briefly review and summarize state of the art of knowledge on memory and related cognitive functions in normal aging. Then we critically discuss a relatively short inventory of clinical, psychometric,…
Altamura, Sandro; Muckenthaler, Martina U
Excess free iron generates oxidative stress that hallmarks diseases of aging. The observation that patients with Alzheimer's disease or Parkinson's disease show a dramatic increase in their brain iron content has opened the possibility that disturbances in brain iron homeostasis may contribute to the pathogenesis of these disorders. While the reason for iron accumulation is unknown, iron localization correlates with the production of reactive oxygen species in those areas of the brain that are prone to neurodegeneration. A role for iron is also proposed in atherosclerosis, a further frequent disorder of aging. We will review experimental evidences for an involvement of iron in these diseases and discuss some mouse models with impairment in iron-related genes that may be useful to study the role of iron in these disorders.
Full Text Available Brain aging-related neurological diseases including Alzheimer's disease (AD, Parkinson's disease (PD and cerebral amyloid angiopathy (CAA have become one of the major diseases endangering the health of old people in China. Although the mechanism of brain aging and pathogenesis of its related neurodegenerative diseases remain unclear, protein pathological studies such as tau, α-synuclein (α-Syn, TDP-43 and amyloid-β protein (Aβ based on brain tissue bank and case registration database are opening the door to solve the mystery in the brain aging process and unlock pathogenesis of aging-related neurodegenerative diseases. Research on functional neuroimaging including 11C-PIB PET and 18F-FDDNP PET in Alzheimer's disease and 18F-FDG PET in Parkinson's disease, and biomarkers such as total-tau, phosphorylated-tau, and the 42 amino acid fragment of β-amyloid in cerebrospinal fluid (CSF in the preclinical stages of Alzheimer's disease now become hot topics in the field of elderly dementia and movement disorders. Clinicopathological correlation research of Alzheimer's disease, Parkinson's disease and cerebral amyloid angiopathy is also one of focuses in the geriatric neurological diseases. doi: 10.3969/j.issn.1672-6731.2014.03.004
Astle, Andrew T.; Blighe, Alan J.; Webb, Ben S.; McGraw, Paul V.
We investigated whether perceptual learning could be used to improve peripheral word identification speed. The relationship between the magnitude of learning and age was established in normal participants to determine whether perceptual learning effects are age invariant. We then investigated whether training could lead to improvements in patients with age-related macular degeneration (AMD). Twenty-eight participants with normal vision and five participants with AMD trained on a word identification task. They were required to identify three-letter words, presented 10° from fixation. To standardize crowding across each of the letters that made up the word, words were flanked laterally by randomly chosen letters. Word identification performance was measured psychophysically using a staircase procedure. Significant improvements in peripheral word identification speed were demonstrated following training (71% ± 18%). Initial task performance was correlated with age, with older participants having poorer performance. However, older adults learned more rapidly such that, following training, they reached the same level of performance as their younger counterparts. As a function of number of trials completed, patients with AMD learned at an equivalent rate as age-matched participants with normal vision. Improvements in word identification speed were maintained at least 6 months after training. We have demonstrated that temporal aspects of word recognition can be improved in peripheral vision with training across a range of ages and these learned improvements are relatively enduring. However, training targeted at other bottlenecks to peripheral reading ability, such as visual crowding, may need to be incorporated to optimize this approach. PMID:26605694
Blokh, David; Stambler, Ilia
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.
B. Klijs (Bart)
textabstractHealthy ageing of individuals is crucial to prevent strong increases in the burden of disease and disability due to population ageing. We aimed to quantify the current burden of disease and disability and assessed which determinants explain the burden of disability. The occurrence of dis
Full Text Available BACKGROUND: Similarities between mice and humans lead to generation of many mouse models of human disease. However, differences between the species often result in mice being unreliable as preclinical models for human disease. One difference that might play a role in lowering the predictivity of mice models to human diseases is age. Despite the important role age plays in medicine, it is too often considered only casually when considering mouse models. METHODS: We developed the mouse-Age Phenotype Knowledgebase, which holds knowledge about age-related phenotypic patterns in mice. The knowledgebase was extensively populated with literature-derived data using text mining techniques. We then mapped between ages in humans and mice by comparing the age distribution pattern for 887 diseases in both species. RESULTS: The knowledgebase was populated with over 9800 instances generated by a text-mining pipeline. The quality of the data was manually evaluated, and was found to be of high accuracy (estimated precision >86%. Furthermore, grouping together diseases that share similar age patterns in mice resulted in clusters that mirror actual biomedical knowledge. Using these data, we matched age distribution patterns in mice and in humans, allowing for age differences by shifting either of the patterns. High correlation (r(2>0.5 was found for 223 diseases. The results clearly indicate a difference in the age mapping between different diseases: age 30 years in human is mapped to 120 days in mice for Leukemia, but to 295 days for Anemia. Based on these results we generated a mice-to-human age map which is publicly available. CONCLUSIONS: We present here the development of the mouse-APK, its population with literature-derived data and its use to map ages in mice and human for 223 diseases. These results present a further step made to bridging the gap between humans and mice in biomedical research.
Taridi, Nursiati Mohamad; Abd Rani, Nazirah; Abd Latiff, Azian; Ngah, Wan Zurinah Wan; Mazlan, Musalmah
Little is known about the effect of vitamin E on brain function. Therefore, in this study we evaluated the effect of tocotrienol rich fraction (TRF) on behavioral impairment and oxidative stress in aged rats. Thirty-six male Wistar rats (young: 3-months-old; aged: 21-months-old) were treated with either the control (olive oil) or TRF (200 mg/kg) for 3 months. Behavioral studies were performed using the open field test and Morris water maze (MWM) task. Blood was taken for assessment of DNA damage, plasma malondialdehyde (MDA) and vitamin E, and erythrocyte antioxidant enzyme activity. Brains were also collected to measure vitamin E levels. Results showed that aged rats exhibited reduced exploratory activity, enhanced anxiety and decreased spatial learning and memory compared with young rats. DNA damage and plasma MDA were increased, and vitamin E levels in plasma and brain were reduced in aged rats. Aged rats supplemented with TRF showed a markedly reduced level of anxiety, improved spatial learning and memory, reduced amount and severity of DNA damage, a reduced level of MDA, and increased levels of antioxidant enzyme activity and plasma/brain vitamin E compared with age-matched controls. In conclusion, TRF supplementation reverses spatial learning and memory decline and decreases oxidative stress in aged rats.
Karin Bakračevič Vukman
Full Text Available The present research is focused on the development of different fields of self-regulation during adolescence and early adulthood. The study included participants from the following age groups: the pupils in the final classes of the primary school, aged 14–15 years, the youngsters in the secondary school (grammar school, aged 17–18 years, and the students, aged 22–23 years. To gain information on cognitive, metacognitive and motivational self-regulation of learning, we applied the Motivated Strategies for Learning Questionnaire (MSLQ; Pintrich, 1991. We also measured the metacognitive accuracy at problem solving, which should indicate the actual ability of metacognitive self-regulation. The results showed the following differences between the age groups: the perceived ability of self-regulation decreased within the high school period compared to the primary school group, and increased again into study years. The described tendency was not obtained with respect to metacognitive accuracy. Results showed an increase in the metacognitive accuracy throughout the entire age-span studied. There are also interesting differences between the sexes. The differences in the perceived ability of self-regulation between boys and girls were distinctive within the early adolescence period, diminished during the growing age, and disappeared almost completely in the period of late adolescence/early adulthood. The reason for this could most probably be the different tempo of self-regulation development between boys and girls.
Moyse, Evelyne; Bastin, Christine; Salmon, Eric; Brédart, Serge
A prerequisite for any function in social cognition is the perception and processing of social cues. Age estimation is a skill that is used in everyday life and is fundamental in social interactions. This study evaluated whether facial age estimation is impaired in patients with mild to moderate Alzheimer's disease (AD). The current age of faces is known to have an impact on age estimation, and therefore stimuli belonging to different age groups (young, middle-aged, and older adults' faces) were used. As expected, an impairment of age estimation from faces was observed in mild to moderate AD patients. However, the profile of impairment depended on the age of faces and stage of the disease. Mild AD patients presented difficulties mainly in assessing the age of middle-aged adults. In moderate disease stage, these difficulties also affected the age estimation of young adult faces. Interestingly, AD patients remained relatively good at estimating the age of older adults' faces, compared to healthy controls.
Evron, Lotte; Ulrich, Anita; Tanggaard, Lene
This study presents a discourse analysis of falls prevention among older people in a context of a falls clinic. Data are based on an empirical study of the ways in which fall prevention was realized and managed in a falls clinic at the political, recruitment and treatment level. Despite massive...... information and investment in falls prevention programs, many still drop out or decline to participate in such programs. The study explores how discourses cross swords in the domain of falls prevention. We identify two main discourses in the field: Discourses of active aging opposed to discourses of old age...... as disease. In discourses of active aging falls are constructed as preventable and not necessarily related to old age; in discourses of old age as disease falls are constructed as a disease of old age. Specific agent positions are created within discourses. Discourses of active aging construct self...
J.W. Roos-Hesselink (Jolien)
markdownabstract__Abstract__ Congenital cardiac defects are by far the most common congenital anomalies. Of all live births around the world, approximately 1% is born with congenital heart disease.1 This number is even higher if patients with a bicuspid aortic valve are included.2 Accordingly, in t
Brewer, George J
In this review, we point out that natural selection does not act to lessen human diseases after the reproductive and caregiving period and that normal levels of iron and copper that may be healthy during the reproductive years appear to be contributing to diseases of aging and possibly the aging process itself. It is clear that oxidant damage contributes to many of the diseases of aging, such as atherosclerosis, Alzheimer's disease, Parkinson's diseases, diabetes, diseases of inflammation, diseases of fibrosis, diseases of autoimmunity, and so on. It is equally clear that both iron and copper can contribute to excess production of damaging reactive oxygen species through Fenton chemistry. Here, we examine the evidence that "normal" levels of iron and copper contribute to various diseases of aging.
Roca, F; Grossin, N; Chassagne, P; Puisieux, F; Boulanger, E
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.
Kasza, K.E.; Diercks, D.R.; Holland, J.W.; Choi, S.U. [and others
The purpose of this generic aging lessons learned (GALL) review is to provide a systematic review of plant aging information in order to assess materials and component aging issues related to continued operation and license renewal of operating reactors. Literature on mechanical, structural, and thermal-hydraulic components and systems reviewed consisted of 97 Nuclear Plant Aging Research (NPAR) reports, 23 NRC Generic Letters, 154 Information Notices, 29 Licensee Event Reports (LERs), 4 Bulletins, and 9 Nuclear Management and Resources Council Industry Reports (NUMARC IRs) and literature on electrical components and systems reviewed consisted of 66 NPAR reports, 8 NRC Generic Letters, 111 Information Notices, 53 LERs, 1 Bulletin, and 1 NUMARC IR. More than 550 documents were reviewed. The results of these reviews were systematized using a standardized GALL tabular format and standardized definitions of aging-related degradation mechanisms and effects. The tables are included in volume s 1 and 2 of this report. A computerized data base has also been developed for all review tables and can be used to expedite the search for desired information on structures, components, and relevant aging effects. A survey of the GALL tables reveals that all ongoing significant component aging issues are currently being addressed by the regulatory process. However, the aging of what are termed passive components has been highlighted for continued scrutiny. This report consists of Volume 2, which consists of the GALL literature review tables for the NUMARC Industry Reports reviewed for the report.
Heidi N. Fridolfsson; Hemal H. Patel
It is estimated that the elderly (> 65 years of age) will increase from 13%-14% to 25% by 2035. If this trend continues, > 50% of the United States population and more than two billion people worldwide will be "aged" in the next 50 years. Aged individuals face formidable challenges to their health, as aging is associated with a myriad of diseases. Cardiovascular disease is the leading cause of morbidity and mortality in the United States with > 50% of mortality attributed to coronary artery disease and > 80% of these deaths occurring in those age 65 and older. Therefore, age is an important predictor of cardiovascular disease. The efficiency of youth is built upon cellular signaling scaffolds that provide tight and coordinated signaling. Lipid rafts are one such scaffold of which caveolae are a subset. In this review, we consider the importance of caveolae in common cardiovascular diseases of the aged and as potential therapeutic targets. We specifically address the role of caveolin in heart failure, myocardial ischemia, and pulmonary hypertension.
龙大宏; 冷水龙; 姚志彬
背景:神经生长因子(nerve growthfactor,NGF)能促进青年痴呆鼠的学习记忆能力的恢复,但老年痴呆鼠对NGF是否敏感?目的:探讨NGF对老年痴呆鼠学习记忆能力的影响.设计:以动物实验为依托,与对照组比较分析.地点和材料:实验在广州医学院解剖学教研室完成.材料:24个月龄雄性SD大鼠30只,NGF(人工脑脊液配制,3.0 g/L,军事医学院提供),人工脑脊液配制细胞色素C溶液.方法:切断老年SD大鼠左侧穹窿海马伞(fimbria-fomix,FF),侧脑室注射NGF,用Morris水迷宫和Y迷宫测试正常组、损伤组和治疗组大鼠的学习记忆能力.主要观察指标:Morris水迷宫行为测试中大鼠平台平均潜伏期的变化及撤除平台后3组大鼠120 s内在各象限游泳距离占总距离的百分比和跨过原平台位置数;Y迷宫检测中大鼠的学习和记忆能力的改变.结果:治疗组大鼠与损伤组相比较,治疗组平均逃避潜伏期缩短,原平台象限游泳距离和穿环次数增多,学会Y迷宫所需训练次数减少和正确反应次数增多,但未完全达到正常水平.结论:NGF能够改善老年FF损伤鼠学习记忆能力.%BACKGROUND: Nerve growth factor(NGF) has been shown to improve the ability of spatial learning and memory in young rats with fimbria-fornix(F-F) transection. But it is by far not known whether aged rats with F-F transection respond to NGF treatment in view of spatial learning and memory.OBJECTIVE: To study the effect of NGF on spatial learning and memory abilities in aged rats with unilateral F-F transection.SETTING and MATERIALS: A controlled animal experiment completed in the Anatomy Department of Guangzhou Medical College. Thirty male SD rats aged 24 months, NGF(3.0 g/L, resolved in artificial cerebrospinal fluid kindly presented by Academy of Military Medicine) and cytochrome C(Cyt C)(artificially confected by cerebrospinal fluid).infusion of NGF or Cyt C into the cerebroventricular space. One month
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...
Christoffersen, Mette; Tybjærg-Hansen, Anne
Association of common aging signs (i.e., male pattern baldness, hair graying, and facial wrinkles) as well as other age-related appearance factors (i.e., arcus corneae, xanthelasmata, and earlobe crease) with increased risk of ischemic heart disease was initially described in anecdotal reports from...
Rattan, Suresh I S
Aging of biological systems occurs in spite of numerous complex pathways of maintenance, repair and defense. There are no gerontogenes which have the specific evolutionary function to cause aging. Although aging is the common cause of all age-related diseases, aging in itself cannot be considered a disease. This understanding of aging as a process should transform our approach towards interventions from developing illusory anti-aging treatments to developing realistic and practical methods for maintaining health throughout the lifespan. The concept of homeodynamic space can be a useful one in order to identify a set of measurable, evidence-based and demonstratable parameters of health, robustness and resilience. Age-induced health problems, for which there are no other clear-cut causative agents, may be better tackled by focusing on health mechanisms and their maintenance, rather than only disease management and treatment. Continuing the disease-oriented research and treatment approaches, as opposed to health-oriented and preventive strategies, are economically, socially and psychologically unsustainable.
Full Text Available The aging process worsens the human body functions at multiple levels, thus causing its gradual decrease to resist stress, damage, and disease. Besides changes in gene expression and metabolic control, the aging rate has been associated with the production of high levels of Reactive Oxygen Species (ROS and/or Reactive Nitrosative Species (RNS. Specific increases of ROS level have been demonstrated as potentially critical for induction and maintenance of cell senescence process. Causal connection between ROS, aging, age-related pathologies, and cell senescence is studied intensely. Senescent cells have been proposed as a target for interventions to delay the aging and its related diseases or to improve the diseases treatment. Therapeutic interventions towards senescent cells might allow restoring the health and curing the diseases that share basal processes, rather than curing each disease in separate and symptomatic way. Here, we review observations on ROS ability of inducing cell senescence through novel mechanisms that underpin aging processes. Particular emphasis is addressed to the novel mechanisms of ROS involvement in epigenetic regulation of cell senescence and aging, with the aim to individuate specific pathways, which might promote healthy lifespan and improve aging.
Baelum, Vibeke; López, Rodrigo
The notion of periodontal disease being the major cause of tooth loss among adults was rooted in the focal infection paradigm that dominated the first half of the 20th century. This paradigm was established largely by personal opinions, and it was not until the development of periodontal indices in the mid-1950s that periodontal epidemiology gained momentum. Unfortunately, the indices used suffered from a number of flaws, whereby the interpretation of the research results took the form of circular reasoning. It was under this paradigm that therapeutic and preventive intervention for periodontal diseases became entirely devoted to oral hygiene, as poor oral hygiene and older age were understood to explain nearly all the variation in disease occurrence. In the early 1980s, studies appeared that contradicted the concepts of poor oral hygiene as the inevitable trigger of periodontitis and of linear and ubiquitous periodontitis progression, whereby periodontal epidemiology was led into a relatively short-lived high-risk era. At this time, it became evident that old scourges continue to haunt periodontology: the inability to agree in operational clinical criteria for a periodontitis diagnosis and the inability to devise both a meaningful and a useful classification of periodontal diseases based on nominalist principles. The meager outcome of the high-risk era led researchers to resurrect the focal infection paradigm, which is now dressed up as periodontal medicine. Unfortunately, these developments have left the core of periodontology somewhat disheveled and deserted.
This paper focuses on the effects of age on second language learning, specifically in foreign language settings. It begins by pointing out that the effects of learners' initial age of learning in foreign language learning settings are partially different from those in naturalistic language learning settings and, furthermore, that studies in the…
Horan, Martin P; Pichaud, Nicolas; Ballard, J William O
There is accumulating evidence that mitochondrial respiratory malfunction is associated with aging-associated complex diseases. However, progress in our understanding of these diseases has been hampered by the sensitivity and throughput of systems employed to quantify dysfunction and inherent limitations of the biological systems studied. In this review, we describe and contrast two methodologies that have been developed for measuring mitochondrial function to address the need for improved sensitivity and increased throughput. We then consider the utility of each methodology in studying three biological systems: isolated mitochondria, cultured cells, and cell fibers and tissues. Finally, we discuss the application of each methodology in the study of mitochondrial dysfunction in Alzheimer's disease, type 2 diabetes mellitus, and aging-associated autophagy impairment and mitochondrial malfunction. We conclude that the methodologies are complementary, and researchers may need to examine multiple biological systems to unravel complex diseases of aging.
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
Childs, B.G.; Durik, M.; Baker, D.J.; Deursen, J.M.A. van
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
Jacob A. Zarling
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.
Roncal-Jimenez, Carlos A; Ishimoto, Takuji; Lanaspa, Miguel A; Milagres, Tamara; Hernando, Ana Andres; Jensen, Thomas; Miyazaki, Makoto; Doke, Tomohito; Hayasaki, Takahiro; Nakagawa, Takahiko; Marumaya, Shoichi; Long, David A; Garcia, Gabriela E; Kuwabara, Masanari; Sánchez-Lozada, Laura G; Kang, Duk-Hee; Johnson, Richard J
Aging-associated kidney disease is usually considered a degenerative process associated with aging. Recently, it has been shown that animals can produce fructose endogenously, and that this can be a mechanism for causing kidney damage in diabetic nephropathy and in association with recurrent dehydration. We therefore hypothesized that low-level metabolism of endogenous fructose might play a role in aging-associated kidney disease. Wild-type and fructokinase knockout mice were fed a normal diet for 2 yr that had minimal (fructose content. At the end of 2 yr, wild-type mice showed elevations in systolic blood pressure, mild albuminuria, and glomerular changes with mesangial matrix expansion, variable mesangiolysis, and segmental thrombi. The renal injury was amplified by provision of high-salt diet for 3 wk, as noted by the presence of glomerular hypertrophy, mesangial matrix expansion, and alpha smooth muscle actin expression, and with segmental thrombi. Fructokinase knockout mice were protected from renal injury both at baseline and after high salt intake (3 wk) compared with wild-type mice. This was associated with higher levels of active (phosphorylated serine 1177) endothelial nitric oxide synthase in their kidneys. These studies suggest that aging-associated renal disease might be due to activation of specific metabolic pathways that could theoretically be targeted therapeutically, and raise the hypothesis that aging-associated renal injury may represent a disease process as opposed to normal age-related degeneration.
Gassen, Nils C; Chrousos, George P; Binder, Elisabeth B; Zannas, Anthony S
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.
Birch, Leann L; Doub, Allison E
During the first 2 y of life, development is rapid and includes dramatic changes in eating behavior. Individual patterns of food preferences and eating behaviors emerge and differ depending on the foods offered and on the contexts of feeding during this early period of dietary transition. In this review, we discuss evidence on ways in which early learning influences food preferences and eating behavior, which, in turn, shape differences in dietary patterns, growth, and health. Although the evidence reviewed indicates that this early period of transition provides opportunities to influence children's developing intake patterns, there is no consistent, evidence-based guidance for caregivers who are feeding infants and toddlers; the current Dietary Guidelines are intended to apply to Americans over the age of 2 y. At present, the evidence base with regard to how and what children learn about food and eating behavior during these first years is limited. Before developing guidance for parents and caregivers, more scholarship and research is necessary to understand how infants and toddlers develop the food preferences and self-regulatory processes necessary to promote healthy growth, particularly in today's environment. By the time they reach 2 y of age, children have essentially completed the transition to "table foods" and are consuming diets similar to those of other family members. This article discusses parenting and feeding approaches that may facilitate or impede the development of self-regulation of intake and the acceptance of a variety of foods and flavors necessary for a healthy diet. We review the limited evidence on how traditional feeding practices, familiarization, associative learning, and observational learning affect the development of eating behavior in the context of the current food environment. Areas for future research that could inform the development of anticipatory guidance for parents and caregivers responsible for the care and feeding of young
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.
Full Text Available Age is the strongest risk factor for sporadic Alzheimer disease (AD, yet the effects of age on rates of clinical decline and brain atrophy in AD have been largely unexplored. Here, we examined longitudinal rates of change as a function of baseline age for measures of clinical decline and structural MRI-based regional brain atrophy, in cohorts of AD, mild cognitive impairment (MCI, and cognitively healthy (HC individuals aged 65 to 90 years (total n = 723. The effect of age was modeled using mixed effects linear regression. There was pronounced reduction in rates of clinical decline and atrophy with age for AD and MCI individuals, whereas HCs showed increased rates of clinical decline and atrophy with age. This resulted in convergence in rates of change for HCs and patients with advancing age for several measures. Baseline cerebrospinal fluid densities of AD-relevant proteins, Aβ(1-42, tau, and phospho-tau(181p (ptau, showed a similar pattern of convergence with advanced age across cohorts, particularly for ptau. In contrast, baseline clinical measures did not differ by age, indicating uniformity of clinical severity at baseline. These results imply that the phenotypic expression of AD is relatively mild in individuals older than approximately 85 years, and this may affect the ability to distinguish AD from normal aging in the very old. Our findings show that inclusion of older individuals in clinical trials will substantially reduce the power to detect disease-modifying therapeutic effects, leading to dramatic increases in required clinical trial sample sizes with age of study sample.
Head, Elizabeth; Rofina, Jaime; Zicker, Steven
Decline in cognitive functions that accompany aging in dogs may have a biologic basis, and many of the disorders associated with aging in dogs may be mitigated through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of laboratory and clinical studies, antioxidants may be one class of nutraceutical that provides benefits to aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which may lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes may lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs.
The article presents longitudinal data of the survey of 212 Šiauliai Petras Avižonis Visual Centre’s 6–7-year-old pre-school children’s motives to attend school. A brief theoretical analysis of significance of motives for learning in child’s development is displayed. Analysing research results, a positive experience on development of positive motives for school attendance in pre-school age children attending Šiauliai Petras Avižonis Visual Centre is rendered in a generalising way.
Zarling, Jacob A; Brunt, Vienna E; Vallerga, Anne K; Li, Weixing; Tao, Albert; Zarling, David A; Minson, Christopher T
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.
Stoian, Dana; Craciunescu, Mihalea; Timar, Romulus; Schiller, Adalbert; Pater, Liana; Craina, Marius
Thyroid autoimmune disease, a widespread phenomenon in female population, impairs thyroid function during pregnancy. Identifying cases, which will develop hypothyroidism during pregnancy, is crucial in the follow-up process. The study group comprised 108 females, with ages between 20-40 years; with known inactive autoimmune thyroid disease, before pregnancy that became pregnant in the study follow-up period. They were monitored by means of clinical, hormonal and immunological assays. Supplemental therapy with thyroid hormones was used, where needed. Maternal age and level of anti-thyroid antibodies were used to predict thyroid functional impairment.
de Lores Arnaiz, Georgina Rodríguez; Ordieres, María Graciela López
, enzyme changes in diverse neurological diseases as well as during aging, have been summarized. Issues refer mainly to Na+, K+-ATPase studies in ischemia, brain injury, depression and mood disorders, mania, stress, Alzheimer´s disease, learning and memory, and neuronal hyperexcitability and epilepsy. PMID:25018677
Lu, Tao; Aron, Liviu; Zullo, Joseph; Pan, Ying; Kim, Haeyoung; Chen, Yiwen; Yang, Tun-Hsiang; Kim, Hyun-Min; Drake, Derek; Liu, X. Shirley; Bennett, David A.; Colaiácovo, Monica P.; Yankner, Bruce A.
Human neurons are functional over an entire lifetime, yet the mechanisms that preserve function and protect against neurodegeneration during ageing are unknown. Here we show that induction of the repressor element 1-silencing transcription factor (REST; also known as neuron-restrictive silencer factor, NRSF) is a universal feature of normal ageing in human cortical and hippocampal neurons. REST is lost, however, in mild cognitive impairment and Alzheimer's disease. Chromatin immunoprecipitation with deep sequencing and expression analysis show that REST represses genes that promote cell death and Alzheimer's disease pathology, and induces the expression of stress response genes. Moreover, REST potently protects neurons from oxidative stress and amyloid β-protein toxicity, and conditional deletion of REST in the mouse brain leads to age-related neurodegeneration. A functional orthologue of REST, Caenorhabditis elegans SPR-4, also protects against oxidative stress and amyloid β-protein toxicity. During normal ageing, REST is induced in part by cell non-autonomous Wnt signalling. However, in Alzheimer's disease, frontotemporal dementia and dementia with Lewy bodies, REST is lost from the nucleus and appears in autophagosomes together with pathological misfolded proteins. Finally, REST levels during ageing are closely correlated with cognitive preservation and longevity. Thus, the activation state of REST may distinguish neuroprotection from neurodegeneration in the ageing brain.
Hurley, P J; Elsworth, J D; Whittaker, M C; Roth, R H; Redmond, D E
Parkinson's Disease (PD) and the natural aging process share a number of biochemical mechanisms, including reduced function of dopaminergic systems. The present study aims to determine the extent that motor and behavioral changes in aged monkeys resemble parkinsonism induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The behavioral and physiological changes in PD are believed to result largely from selective depletion of dopamine in the nigrostriatal system. In the present study, ten aged female monkeys were compared with three groups: 9 untreated young adult female monkeys, 10 young adult male monkeys and 13 older male monkeys that had been exposed to MPTP. Trained observers, blind as to age and drug condition and without knowledge of the hypotheses, scored the monkeys using the Parkinson's factor score (Parkscore), which has been validated by a high correlation with post mortem striatal dopamine (DA) concentrations. The aged animals had higher scores on the Parkscore compared with the young adults, with most of its component behavioral items showing significance (tremor, Eating Problems, Delayed initiation of movement, and Poverty of Movement). L-Dopa and DA-agonists did not clearly reverse the principal measure of parkinsonism. DA concentrations post mortem were 63% lower in 3 aged monkeys in the ventral putamen compared with 4 young adults, with greater reductions in putamen than in caudate (45%). We conclude that aged monkeys, unexposed to MPTP, show a similar profile of parkinsonism to that seen after the neurotoxin exposure to MPTP in young adult monkeys. The pattern of greater DA depletion in putamen than in caudate in aged monkeys is the same as in human Parkinson's disease and contrasts with the greater depletion in caudate seen after MPTP. Aged monkeys of this species reflect many facets of Parkinson's disease, but like older humans do not improve with standard dopamine replacement pharmacotherapies.
Full Text Available Cellular senescence is viewed as an irreversible cell-cycle arrest mechanism involving a complexity of biological progressive processes and the acquisition of diverse cellular phenotypes. Several cell-intrinsic and extrinsic causes (stresses may lead to diverse cellular signaling cascades that include oxidative stress, mitochondrial dysfunction, DNA damage, excessive accumulation of misfolded proteins, impaired microRNA processing and inflammation. Here we review recent advances in the causes and consequences of brain cell ageing, including the senescence of endothelial cells at the central nervous system barriers, as well as of neurons and glial cells. We address what makes ageing an important risk factor for neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and cerebrovascular disease. In particular, we highlight the importance of defects in mitochondrial dynamics, in the cathepsin activity imbalance, in cell-cell communication, in the accumulation of misfolded and unfolded proteins and in the microRNA profiling as having potential impact on cellular ageing processes. Another important aspect is that the absence of specific senescence biomarkers has hampered the characterization of senescent cells in ageing and age-associated diseases. In accordance, the senescence-associated secretory phenotype (SASP or secretome was shown to vary in distinct cell types and upon different stressors, and SASP heterogeneity is believed to create subsets of senenescent cells. In addition to secreted proteins, we then place extracellular vesicles (exosomes and ectosomes as important mediators of intercellular communication with pathophysiological roles in disease spreading, and as emerging targets for therapeutic intervention. We also discuss the application of engineered extracellular vesicles as vehicles for drug delivery. Finally, we summarize current knowledge on methods to rejuvenate senescent cells
Fay Michael P
Full Text Available Abstract Fay, Pfeiffer, Cronin, Le, and Feuer (Statistics in Medicine 2003; 22; 1837–1848 developed a formula to calculate the age-conditional probability of developing a disease for the first time (ACPDvD for a hypothetical cohort. The novelty of the formula of Fay et al (2003 is that one need not know the rates of first incidence of disease per person-years alive and disease-free, but may input the rates of first incidence per person-years alive only. Similarly the formula uses rates of death from disease and death from other causes per person-years alive. The rates per person-years alive are much easier to estimate than per person-years alive and disease-free. Fay et al (2003 used simple piecewise constant models for all three rate functions which have constant rates within each age group. In this paper, we detail a method for estimating rate functions which does not have jumps at the beginning of age groupings, and need not be constant within age groupings. We call this method the mid-age group joinpoint (MAJ model for the rates. The drawback of the MAJ model is that numerical integration must be used to estimate the resulting ACPDvD. To increase computational speed, we offer a piecewise approximation to the MAJ model, which we call the piecewise mid-age group joinpoint (PMAJ model. The PMAJ model for the rates input into the formula for ACPDvD described in Fay et al (2003 is the current method used in the freely available DevCan software made available by the National Cancer Institute.
George M. Weisz
Full Text Available Two paintings of older men by Rembrandt (1609–1669 are examined to demonstrate that historical attitudes toward diseases of old age and the ageing person’s response to illness can be investigated in paintings. The works selected are of different genres and date from different stages of Rembrandt’s own life, one from his youth and one from his old age. Both paintings show figures who have joint pathologies typically associated with the ageing process, the first involving the subject’s foot and the second involving the subject’s hand. Despite the sometimes painful nature of these conditions, the subjects are shown accommodating their illnesses while maintaining both their intellectual and social engagement and their emotional composure. Although the seventeenth century offered older people very little effective medical treatment in comparison with what is presently available, these paintings nevertheless present a view of illness as a subsidiary rather than a dominant feature of old age.
LeBrasseur, Nathan K; Tchkonia, Tamara; Kirkland, James L
Population aging simultaneously highlights the remarkable advances in science, medicine, and public policy, and the formidable challenges facing society. Indeed, aging is the primary risk factor for many of the most common chronic diseases and frailty, which result in profound social and economic costs. Population aging also reveals an opportunity, i.e. interventions to disrupt the fundamental biology of aging could significantly delay the onset of age-related conditions as a group, and, as a result, extend the healthy life span, or health span. There is now considerable evidence that cellular senescence is an underlying mechanism of aging and age-related conditions. Cellular senescence is a process in which cells lose the ability to divide and damage neighboring cells by the factors they secrete, collectively referred to as the senescence-associated secretory phenotype (SASP). Herein, we discuss the concept of cellular senescence, review the evidence that implicates cellular senescence and SASP in age-related deterioration, hyperproliferation, and inflammation, and propose that this underlying mechanism of aging may play a fundamental role in the biology of frailty.
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
Rosenblatt, Adam; Kumar, Brahma V; Mo, Alisa; Welsh, Claire S; Margolis, Russell L; Ross, Christopher A
The objective of this study was to further explore the effect of CAG repeat length on the rate of clinical progression in patients with Huntington's disease. The dataset included records for 569 subjects followed prospectively at the Baltimore Huntington's Disease Center. Participants were seen for a mean of 7.1 visits, with a mean follow-up of 8.2 years. Subjects were evaluated using the Quantified Neurologic Examination and its Motor Impairment subscale, the Mini-Mental State Examination, and the Huntington's disease Activities of Daily Living Scale. By itself, CAG repeat length showed a statistically significant but small effect on the progression of all clinical measures. Contrary to our previous expectations, controlling for age of onset increased the correlation between CAG repeat length and progression of all variables by 69% to 159%. Graphical models further supported the idea that individuals with smaller triplet expansions experience a more gradual decline. CAG repeat length becomes an important determinant of clinical prognosis when accounting for age of onset. This suggests that the aging process itself influences clinical outcomes in Huntington's disease. Inconsistent results in prior studies examining CAG repeat length and progression may indeed reflect a lack of age adjustment.
We show in this thesis that different subtypes of astrocytes comprise specialized GFAP-IF networks, that change during development, aging and Alzheimer’s disease. The novel functions that have emerged for the IF network suggest these changes can play an important part in the specialized function of
Valcárcel-Ocete, Leire; Alkorta-Aranburu, Gorka; Iriondo, Mikel;
Age of onset (AO) of Huntington disease (HD) is mainly determined by the length of the CAG repeat expansion (CAGexp) in exon 1 of the HTT gene. Additional genetic variation has been suggested to contribute to AO, although the mechanism by which it could affect AO is presently unknown. The aim of ...
Nassar, Matthew R; Bruckner, Rasmus; Gold, Joshua I; Li, Shu-Chen; Heekeren, Hauke R; Eppinger, Ben
Healthy aging can lead to impairments in learning that affect many laboratory and real-life tasks. These tasks often involve the acquisition of dynamic contingencies, which requires adjusting the rate of learning to environmental statistics. For example, learning rate should increase when expectations are uncertain (uncertainty), outcomes are surprising (surprise) or contingencies are more likely to change (hazard rate). In this study, we combine computational modelling with an age-comparative behavioural study to test whether age-related learning deficits emerge from a failure to optimize learning according to the three factors mentioned above. Our results suggest that learning deficits observed in healthy older adults are driven by a diminished capacity to represent and use uncertainty to guide learning. These findings provide insight into age-related cognitive changes and demonstrate how learning deficits can emerge from a failure to accurately assess how much should be learned.
Rebecca M. C. Spencer; Pace-Schott, Edward F.
Improvements in motor sequence learning come about via goal-based learning of the sequence of visual stimuli and muscle-based learning of the sequence of movement responses. In young adults, consolidation of goal-based learning is observed after intervals of sleep but not following wake, whereas consolidation of muscle-based learning is greater following intervals with wake compared to sleep. While the benefit of sleep on motor sequence learning has been shown to decline with age, how sleep c...
Kitada, Munehiro; Kume, Shinji; Takeda-Watanabe, Ai; Kanasaki, Keizo; Koya, Daisuke
Sirtuins are members of the Sir2 (silent information regulator 2) family, a group of class III deacetylases. Mammals have seven different sirtuins, SIRT1-SIRT7. Among them, SIRT1, SIRT3 and SIRT6 are induced by calorie restriction conditions and are considered anti-aging molecules. SIRT1 has been the most extensively studied. SIRT1 deacetylates target proteins using the coenzyme NAD+ and is therefore linked to cellular energy metabolism and the redox state through multiple signalling and survival pathways. SIRT1 deficiency under various stress conditions, such as metabolic or oxidative stress or hypoxia, is implicated in the pathophysiologies of age-related diseases including diabetes, cardiovascular diseases, neurodegenerative disorders and renal diseases. In the kidneys, SIRT1 may inhibit renal cell apoptosis, inflammation and fibrosis, and may regulate lipid metabolism, autophagy, blood pressure and sodium balance. Therefore the activation of SIRT1 in the kidney may be a new therapeutic target to increase resistance to many causal factors in the development of renal diseases, including diabetic nephropathy. In addition, SIRT3 and SIRT6 are implicated in age-related disorders or longevity. In the present review, we discuss the protective functions of sirtuins and the association of sirtuins with the pathophysiology of renal diseases, including diabetic nephropathy.
Downs, J Crawford
This nontechnical review is focused upon educating the reader on optic nerve head biomechanics in both aging and disease along two main themes: what is known about how mechanical forces and the resulting deformations are distributed in the posterior pole and ONH (biomechanics) and what is known about how the living system responds to those deformations (mechanobiology). We focus on how ONH responds to IOP elevations as a structural system, insofar as the acute mechanical response of the lamina cribrosa is confounded with the responses of the peripapillary sclera, prelaminar neural tissues, and retrolaminar optic nerve. We discuss the biomechanical basis for IOP-driven changes in connective tissues, blood flow, and cellular responses. We use glaucoma as the primary framework to present the important aspects of ONH biomechanics in aging and disease, as ONH biomechanics, aging, and the posterior pole extracellular matrix (ECM) are thought to be centrally involved in glaucoma susceptibility, onset and progression.
Full Text Available Abstract Aging is associated with a greatly increased incidence of a number of neurodegenerative disorders, including Alzheimer's disease (AD, Parkinson's disease (PD and amyotrophic lateral sclerosis (ALS. These conditions are associated with chronic inflammation, which generates oxygen reactive species, ultimately responsible for a process known as oxidative stress. It is well established that this process is the culprit of neurodegeneration, and there are also mounting evidences that it is not restricted to the central nervous system. Indeed, several studies, including some by our group, have demonstrated that increased peripheral oxidative stress markers are associated to aging and, more specifically, to AD. Therefore, it is very instigating to regard aging and AD as systemic conditions that might be determined by studying peripheral markers of oxidative stress.
Kallery, Maria; Loupidou, Thomais
The present study examines how the overall cognitive achievements in science of the younger children in a class where the students work in small multi-age groups are influenced by the number of older children in the groups. The context of the study was early-years education. The study has two parts: The first part involved classes attended by pre-primary children aged 4-6. The second part included one primary class attended by students aged 6-8 in addition to the pre-primary classes. Students were involved in inquiry-based science activities. Two sources of data were used: Lesson recordings and children's assessments. The data from both sources were separately analyzed and the findings plotted. The resulting graphs indicate a linear relationship between the overall performance of the younger children in a class and the number of older ones participating in the groups in each class. It seems that the age composition of the groups can significantly affect the overall cognitive achievements of the younger children and preferentially determines the time within which this factor reaches its maximum value. The findings can be utilized in deciding the age composition of small groups in a class with the aim of facilitating the younger children's learning in science.
Fjell, Anders M.; McEvoy, Linda; Holland, Dominic; Dale, Anders M; Walhovd, Kristine B.
What can be expected in normal aging, and where does normal aging stop and pathological neurodegeneration begin? With the slow progression of age-related dementias such as Alzheimer's disease (AD), it is difficult to distinguish age-related changes from effects of undetected disease. We review recent research on changes of the cerebral cortex and the hippocampus in aging and the borders between normal aging and AD. We argue that prominent cortical reductions are evident in fronto-temporal reg...
Cellular damage and deregulated apoptotic cell death lead to functional impairment, and a main consequence of these events is aging. Cellular damage is initiated by different stress/risk factors such as oxidative stress, inflammation, and heavy metals. These stress/risk factors affect the cellular homeostasis by altering methylation status of several aging and Alzheimer's disease associated genes; these effects can be manifested immediately after exposure to stress and at later stages of life. However, when cellular damage exceeds certain threshold levels apoptosis is initiated. This review discusses the stress factors involved in cellular damage and the role and potential of TSPO-mediated cell death in aging as well as in Alzheimer's disease, which is also characterized by extensive cell death. Mitochondrial-mediated apoptotic death through the release of cytochrome c is regulated by TSPO, and increased expression of this protein is observed in both elderly people and in patients with Alzheimer's disease. TSPO forms and mediates opening of the mitochondrial membrane pore, mPTP and oxidizes cardiolipin, and these events lead to the leakage of apoptotic death mediators, such as cytochrome c, resulting in cell death. However, TSPO has many proposed functions and can also increase steroid synthesis, which leads to inhibition of inflammation and inhibition of the release of apoptotic factors, thereby decreasing cell damage and promoting cell survival. Thus, TSPO mediates apoptosis and decreases the cell damage, which in turn dictates the process of aging as well as the functionality of organs such as the brain. TSPO modulation with ligands in the Alzheimer's disease mouse model showed improvement in behavioral symptoms, and studies in Drosophila species showed increased cell survival and prolonged lifespan in flies after TSPO inhibition. These data suggest that since effects/signs of stress can manifest at any time, prevention through change in lifestyle and TSPO
Smits, Fenne Margreeth; Porcaro, Camillo; Cottone, Carlo; Cancelli, Andrea; Rossini, Paolo Maria; Tecchio, Franca
Brain activity is complex; a reflection of its structural and functional organization. Among other measures of complexity, the fractal dimension is emerging as being sensitive to neuronal damage secondary to neurological and psychiatric diseases. Here, we calculated Higuchi's fractal dimension (HFD) in resting-state eyes-closed electroencephalography (EEG) recordings from 41 healthy controls (age: 20-89 years) and 67 Alzheimer's Disease (AD) patients (age: 50-88 years), to investigate whether HFD is sensitive to brain activity changes typical in healthy aging and in AD. Additionally, we considered whether AD-accelerating effects of the copper fraction not bound to ceruloplasmin (also called "free" copper) are reflected in HFD fluctuations. The HFD measure showed an inverted U-shaped relationship with age in healthy people (R2 = .575, p < .001). Onset of HFD decline appeared around the age of 60, and was most evident in central-parietal regions. In this region, HFD decreased with aging stronger in the right than in the left hemisphere (p = .006). AD patients demonstrated reduced HFD compared to age- and education-matched healthy controls, especially in temporal-occipital regions. This was associated with decreasing cognitive status as assessed by mini-mental state examination, and with higher levels of non-ceruloplasmin copper. Taken together, our findings show that resting-state EEG complexity increases from youth to maturity and declines in healthy, aging individuals. In AD, brain activity complexity is further reduced in correlation with cognitive impairment. In addition, elevated levels of non-ceruloplasmin copper appear to accelerate the reduction of neural activity complexity. Overall, HDF appears to be a proper indicator for monitoring EEG-derived brain activity complexity in healthy and pathological aging.
Stephan, Marianne A.; Meier, Beat; Zaugg, Sabine Weber; Kaelin-Lang, Alain
It is still unclear, whether patients with Parkinson's disease (PD) are impaired in the incidental learning of different motor sequences in short succession, although such a deficit might greatly impact their daily life. The aim of this study was thus to clarify the relation between disease parameters of PD and incidental motor learning of two…
Jahanshahi, Marjan; Wilkinson, Leonora; Gahir, Harpreet; Dharminda, Angeline; Lagnado, David A.
In Parkinson's disease (PD), it is possible that tonic increase of dopamine associated with levodopa medication overshadows phasic release of dopamine, which is essential for learning. Thus while the motor symptoms of PD are improved with levodopa medication, learning would be disrupted. To test this hypothesis, we investigated the effect of…
Gawi, Elsadig Mohamed Khalifa
The purpose of this study is to investigate the effect of age on learning English in Saudi Arabia. It aims at encouraging the learning of English as a foreign language at an early age in KSA. The populations of the study are English language teachers and Saudi students in elementary schools compared with intermediate school students in Dawadmi…
Full Text Available Abstract Background Heat shock proteins (Hsp are ubiquitously synthesised in virtually all species and it is hypothesised that they might have beneficial health effects. Recent studies have identified circulating Hsp as an important mediator in inflammation - the effects of low-grade inflammation in the aging process are overwhelming. While much is known about intracellular Hsp70, scant data exist on circulating Hsp70 in the aging context. Therefore, the objectives of this study were to investigate the effect of age and disease on circulating Hsp70 and, in particular, to evaluate the association between circulating Hsp70 and inflammatory parameters. Results Serum Hsp70, Interleukin (IL -10, IL-6 and Tumor Necrosis Factor (TNF alpha concentrations were determined in 90 hospitalised geriatric patients (aged 83 ± 6 years and in 200 community-dwelling control subjects (100 elderly, aged 74 ± 5 years, and 100 young, aged 23 ± 3 years. In the community-dwelling elderly, serum Hsp70 and IL-10 concentrations were significantly lower and IL-6 was significantly higher when compared to healthy young control subjects. Elderly patients presenting inflammation (CRP serum levels ≥5 mg/L showed significantly (p = 0.007 higher Hsp70 values; and Hsp70 correlated positively (p Conclusions The present data provide new evidence that serum concentration of Hsp70 decreases with age in a normal population. Our study also shows that higher levels of Hsp70 are associated with inflammation and frailty in elderly patients.
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.
Crosson, Bruce; McGregor, Keith M; Nocera, Joe R; Drucker, Jonathan H; Tran, Stella M; Butler, Andrew J
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.
Zapata, Heidi J; Quagliarello, Vincent J
Advances in bacterial deoxyribonucleic acid sequencing allow for characterization of the human commensal bacterial community (microbiota) and its corresponding genome (microbiome). Surveys of healthy adults reveal that a signature composite of bacteria characterizes each unique body habitat (e.g., gut, skin, oral cavity, vagina). A myriad of clinical changes, including a basal proinflammatory state (inflamm-aging), that directly interface with the microbiota of older adults and enhance susceptibility to disease accompany aging. Studies in older adults demonstrate that the gut microbiota correlates with diet, location of residence (e.g., community dwelling, long-term care settings), and basal level of inflammation. Links exist between the microbiota and a variety of clinical problems plaguing older adults, including physical frailty, Clostridium difficile colitis, vulvovaginal atrophy, colorectal carcinoma, and atherosclerotic disease. Manipulation of the microbiota and microbiome of older adults holds promise as an innovative strategy to influence the development of comorbidities associated with aging.
Martin-Iguacel, R; Llibre, J M; Friis-Moller, N
With more effective and widespread antiretroviral treatment, the overall incidence of AIDS- or HIV-related death has decreased dramatically. Consequently, as patients are aging, cardiovascular disease (CVD) has emerged as an important cause of morbidity and mortality in the HIV population....... The incidence of CVD overall in HIV is relatively low, but it is approximately 1.5-2-fold higher than that seen in age-matched HIV-uninfected individuals. Multiple factors are believed to explain this excess in risk such as overrepresentation of traditional cardiovascular risk factors (particularly smoking...
C Sőti; Péter Csermely
Environmantal stress induces damage that activates an adaptive response in any organism. The cellular stress response is based on the induction of cytoprotective proteins, the so called stress or heat shock proteins. The stress response as well as stress proteins are ubiquitous, highly conserved mechanism, and genes, respectively, already present in prokaryotes. Chaperones protect the proteome against conformational damage, promoting the function of protein networks. Protein damage takes place during aging and in several degenerative diseases, and presents a threat to overload the cellular defense mechanisms. The preservation of a robust stress response and protein disposal is indispensable for health and longevity. This review summarizes the present knowledge of protein damage, turnover, and the stress response in aging and degenerative diseases.
Rattan, Suresh Is
Aging is characterized by stochastic accumulation of molecular damage, progressive failure of maintenance and repair, and consequent onset of age-related diseases. Applying hormesis in aging research and therapy is based on the principle of stimulation of maintenance and repair pathways by repeated exposure to mild stress. Studies on the beneficial biological effects of repeated mild heat shock on human cells in culture, and other studies on the anti-aging and life-prolonging effects of proxidants, hypergravity, irradiation and ethanol on cells and organisms suggest that hormesis as an antiaging and gerontomodulatory approach has a promising future. Its clinical applications include prevention and treatment of diabetes, cataract, osteoporosis, dementia and some cancers.
Kholodnyak, O. V.
Under modern condotions the problem of prevention and treatment of periodontal does not lose its relevance, This is significant prevalence of periodontal lesions, including young people. One of the promising areas that help to reduce the incidence and intensity of periodontal disease is the development and implementation of objective methods for predicting and preventing their development. Data on periodontal status in young aged adults are contradictory, and rates of prevalence of periodonta...
Joaquin Hinojosa del Val
Inflammatory bowel disease (IBD) in patients aged > 60 accounts for 10%-15% of cases of the disease. Diganostic methods are the same as for other age groups. Care has to be taken to distinguish an IBD colitis from other forms of colitis that can mimick clinically, endoscopically and even histologically the IBD entity. The clinical pattern in ulcerative colitis (UC) is proctitis and left-sided UC,while granulomatous colitis with an inflammatory pattern is more common in Crohn's disease (CD). The treatment options are those used in younger patients, but a series of considerations related to potential pharmacological interactions and side effects of the drugs must be taken into account. The safety profile of conventional immunomodulators and biological therapy is acceptable but more data are required on the safety of use of these drugs in the elderly population. Biological therapy has risen question on the possibility of increased side effects, however this needs to be confirmed. Adherence to performing all the test prior to biologic treatment administration is very important. The overall response to treatment is similar in the different patient age groups but elderly patients have fewer recurrences. The number of hospitalizations in patients > 65 years is greater than in younger group,accounting for 25% of all admissions for IBD. Mortality is similar in UC and slightly higher in CD, but significantly increased in hospitalized patients. Failure of medical treatment continues to be the most common indication for surgery in patients aged > 60 years. Age is not considered a contraindication for performing restorative proctocolectomy with an ileal pouch-anal anastomosis.However, incontinence evaluation should be taken into account an individualized options should be considered
Kathleen H. Miao
Full Text Available Globally, heart disease is the leading cause of death for both men and women. One in every four people is afflicted with and dies of heart disease. Early and accurate diagnoses of heart disease thus are crucial in improving the chances of long-term survival for patients and saving millions of lives. In this research, an advanced ensemble machine learning technology, utilizing an adaptive Boosting algorithm, is developed for accurate coronary heart disease diagnosis and outcome predictions. The developed ensemble learning classification and prediction models were applied to 4 different data sets for coronary heart disease diagnosis, including patients diagnosed with heart disease from Cleveland Clinic Foundation (CCF, Hungarian Institute of Cardiology (HIC, Long Beach Medical Center (LBMC, and Switzerland University Hospital (SUH. The testing results showed that the developed ensemble learning classification and prediction models achieved model accuracies of 80.14% for CCF, 89.12% for HIC, 77.78% for LBMC, and 96.72% for SUH, exceeding the accuracies of previously published research. Therefore, coronary heart disease diagnoses derived from the developed ensemble learning classification and prediction models are reliable and clinically useful, and can aid patients globally, especially those from developing countries and areas where there are few heart disease diagnostic specialists.
Vidak, Sandra; Foisner, Roland
Hutchinson-Gilford progeria syndrome (HGPS) is an extremely rare premature aging disease presenting many features resembling the normal aging process. HGPS patients die before the age of 20 years due to cardiovascular problems and heart failure. HGPS is linked to mutations in the LMNA gene encoding the intermediate filament protein lamin A. Lamin A is a major component of the nuclear lamina, a scaffold structure at the nuclear envelope that defines mechanochemical properties of the nucleus and is involved in chromatin organization and epigenetic regulation. Lamin A is also present in the nuclear interior where it fulfills lamina-independent functions in cell signaling and gene regulation. The most common LMNA mutation linked to HGPS leads to mis-splicing of the LMNA mRNA and produces a mutant lamin A protein called progerin that tightly associates with the inner nuclear membrane and affects the dynamic properties of lamins. Progerin expression impairs many important cellular processes providing insight into potential disease mechanisms. These include changes in mechanosignaling, altered chromatin organization and impaired genome stability, and changes in signaling pathways, leading to impaired regulation of adult stem cells, defective extracellular matrix production and premature cell senescence. In this review, we discuss these pathways and their potential contribution to the disease pathologies as well as therapeutic approaches used in preclinical and clinical tests.
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...
Eichhoff, Gerhard; Busche, Marc A.; Garaschuk, Olga [Technical University of Munich, Institute of Neuroscience, Munich (Germany)
Over the last decade, in vivo calcium imaging became a powerful tool for studying brain function. With the use of two-photon microscopy and modern labelling techniques, it allows functional studies of individual living cells, their processes and their interactions within neuronal networks. In vivo calcium imaging is even more important for studying the aged brain, which is hard to investigate in situ due to the fragility of neuronal tissue. In this article, we give a brief overview of the techniques applicable to image aged rodent brain at cellular resolution. We use multicolor imaging to visualize specific cell types (neurons, astrocytes, microglia) as well as the autofluorescence of the ''aging pigment'' lipofuscin. Further, we illustrate an approach for simultaneous imaging of cortical cells and senile plaques in mouse models of Alzheimer's disease. (orig.)
Jové, Mariona; Portero-Otín, Manuel; Naudí, Alba; Ferrer, Isidre; Pamplona, Reinald
Neurons in the mature human central nervous system (CNS) perform a wide range of motor, sensory, regulatory, behavioral, and cognitive functions. Such diverse functional output requires a great diversity of CNS neuronal and non-neuronal populations. Metabolomics encompasses the study of the complete set of metabolites/low-molecular-weight intermediates (metabolome), which are context-dependent and vary according to the physiology, developmental state, or pathologic state of the cell, tissue, organ, or organism. Therefore, the use of metabolomics can help to unravel the diversity-and to disclose the specificity-of metabolic traits and their alterations in the brain and in fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of aging and neurodegenerative diseases. Here, we review the current applications of metabolomics in studies of CNS aging and certain age-related neurodegenerative diseases such as Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. Neurometabolomics will increase knowledge of the physiologic and pathologic functions of neural cells and will place the concept of selective neuronal vulnerability in a metabolic context.
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.
Longworth, Norman; Osborne, Michael
Learning Cities and Learning Regions are terms now in common use as a result of the growing importance of lifelong learning concepts to the economic, social and environmental future of people and places. Why "learning" regions? Why not intelligent, creative, clever, smart or knowledge regions? In truth, all of these can, and some do,…
Longworth, Norman; Osborne, Michael
Learning Cities and Learning Regions are terms now in common use as a result of the growing importance of lifelong learning concepts to the economic, social and environmental future of people and places. Why "learning" regions? Why not intelligent, creative, clever, smart or knowledge regions? In truth, all of these can, and some do, also exist,…
Gargiulo, Simona; Gamba, Paola; Poli, Giuseppe; Leonarduzzi, Gabriella
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.
Chen, Jia; Li, Cheng-Ren; Yang, Heng; Liu, Juan; Zhang, Tao; Jiao, Shu-Sheng; Wang, Yan-Jiang; Xu, Zhi-Qiang
Mature brain-derived neurotrophic factor has shown promotive effect on neural cells in rodents, including neural proliferation, differentiation, survival, and synaptic formation. Conversely, the precursor of brain-derived neurotrophic factor (proBDNF) has been emerging as a differing protein against its mature form, for its critical role in aging process and neurodegenerative diseases. In the present study, we investigated the role of proBDNF in neurogenesis in the hippocampal dentate gyrus of aged mice and examined the changes in mice learning and memory functions. The results showed that the newborn cells in the hippocampus revealed a significant decline in proBDNF-treated group compared with bovine serum albumin group, but an elevated level in anti-proBDNF group. During the maturation period, no significant change was observed in the proportions of phenotype of the newborn cells among the three groups. In water maze, proBDNF-treated mice had poorer scores in place navigation test and probe test, compared with those from any other group. Thus, we conclude that proBDNF attenuates neurogenesis in the hippocampus and induces the deficits in learning and memory functions of aged mice.
Full Text Available Hyperhomocysteinemia is a widely recognized, although not yet entirely understood, risk factor for cardiovascular disease. Particularly, the complex relationships between age, hyperhomocysteinemia, predisposing genetic factors and peripheral vascular diseases have not been fully evaluated. Our contribution to this issue is a retrospective analysis of a large series of patients with peripheral arterial, venous and lymphatic disease, and of their blood relatives, with special reference to homocysteine plasma levels, age and methylenetetrahydrofolate reductase (MTHFR polymorphisms. Serum homocysteine was measured in 477 patients (286 males, 191 females, age range 19-78 years with various vascular clinical conditions: postphlebitic syndrome (46 recurrent venous ulcers (78, arterial diseases (101 primary lymphoedema (87, secondary lymphoedema (161 and outlet thoracic syndrome (4, and in 50 normal controls. A MTHFR study for polymorphisms was carried on in the subjects with homocysteine values exceeding 15 mol/L. Serum homocysteine determination and MTHFR polymorphism studies were performed also in 1430 healthy blood related relatives (mainly siblings, descendents and sibling descendents of the subjects with hyperhomocysteinemia and MTHFR polymorphisms. We found MTHFR polymorphisms in 20% of controls and in 69.3%, 69.5% and 53.8% of hyperhomocysteinemic subjects with arterial diseases, postphlebitic syndrome and venous ulcers, respectively. As expected, the percentage of hyperhomocysteinemia in patients with secondary lymphoedema and with thoracic outlet syndrome did not show significant differences compared to the control group. A MTHFR polymorphism was found in 116 out of the 214 hyperhomocysteinemic patients, i.e., in the 54% of the overall patient population with hyperhomocysteinemia (214 patients. Interestingly 750 (52% out of the 1430 blood relatives of the 116 patients with hyperhomocysteinemia and MTHFR polymorphisms showed at least one
Vinciguerra, Manlio; Musaro, Antonio; Rosenthal, Nadia
Muscle aging is characterized by a decline in functional performance and restriction of adaptability, due to progressive loss of muscle tissue coupled with a decrease in strength and force output. Together with selective activation ofapoptotic pathways, a hallmark of age-related muscle loss or sarcopenia is the progressive incapacity of regeneration machinery to replace damaged muscle. These characteristics are shared by pathologies involving muscle wasting, such as muscular dystrophies or amyotrophic lateral sclerosis, cancer and AIDS, all characterized by alterations in metabolic and physiological parameters, progressive weakness in specific muscle groups. Modulation ofextracellular agonists, receptors, protein kinases, intermediate molecules, transcription factors and tissue-specific gene expression collectively compromise the functionality of skeletal muscle tissue, leading to muscle degeneration and persistent protein degradation through activation ofproteolytic systems, such as calpain, ubiquitin-proteasome and caspase. Additional decrements in muscle growth factors compromise skeletal muscle growth, differentiation, survival and regeneration. A better understanding of the mechanisms underlying the pathogenesis of muscle atrophy and wasting associated with different diseases has been the objective of numerous studies and represents an important first step for the development of therapeutic approaches. Among these, insulin-like growth factor-1 (IGF-1) has emerged as a growth factor with a remarkably wide range of actions and a tremendous potential as a therapeutic in attenuating the atrophy and frailty associated with muscle aging and diseases. In this chapter we provide an overview of current concepts in muscle atrophy, focusing specifically on the molecular basis of IGF-1 action and survey current gene and cell therapeutic approaches to rescue muscle atrophy in aging and disease.
This podcast discusses prion diseases and the risk of exposure associated with some common activities. Created: 5/23/2011 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID). Date Released: 5/23/2011.
Johnson, Adiv A; Akman, Kemal; Calimport, Stuart R G; Wuttke, Daniel; Stolzing, Alexandra; de Magalhães, João Pedro
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.
Tommasini, Alberto; Not, Tarcisio; Ventura, Alessandro
From the time of Gee's landmark writings, the recent history of celiac disease (CD) can be divided into many ages, each driven by a diagnostic advance and a deeper knowledge of disease pathogenesis. At the same time, these advances were paralleled by the identification of new clinical patterns associated with CD and by a continuous redefinition of the prevalence of the disease in population. In the beginning, CD was considered a chronic indigestion, even if the causative food was not known; later, the disease was proven to depend on an intolerance to wheat gliadin, leading to typical mucosal changes in the gut and to a malabsorption syndrome. This knowledge led to curing the disease with a gluten-free diet. After the identification of antibodies to gluten (AGA) in the serum of patients and the identification of gluten-specific lymphocytes in the mucosa, CD was described as an immune disorder, resembling a chronic "gluten infection". The use of serological testing for AGA allowed identification of the higher prevalence of this disorder, revealing atypical patterns of presentation. More recently, the characterization of autoantibodies to endomysium and to transglutaminase shifted the attention to a complex autoimmune pathogenesis and to the increased risk of developing autoimmune disorders in untreated CD. New diagnostic assays, based on molecular technologies, will introduce new changes, with the promise of better defining the spectrum of gluten reactivity and the real burden of gluten related-disorders in the population. Herein, we describe the different periods of CD experience, and further developments for the next celiac age will be proposed.
Natalia Casagrande Brabo
Full Text Available The objective of this study was to determine the frequency of occurrence and to characterize the typology of dysfluencies in individuals with Parkinson’s disease (PD, including the variables age, gender, schooling, disease duration, score on the Hoehn and Yahr scale and cognitive status (score on Mini-Mental State Examination. A cross-sectional study of a sample comprising 60 adults matched for gender, age and schooling was conducted. Group I comprised 30 adults with idiopathic PD, and Group II comprised 30 healthy adults. For assessment of fluency of speech, subjects were asked to utter a narrative based on a sequence of drawings and a transcription of 200 fluent syllables was performed to identify speech dysfluencies. PD patients exhibited a higher overall number of dysfluencies in speech with a large number of atypical dysfluencies. Additionally, results showed an influence of the variables cognitive status, disease duration and age on occurrence of dysfluencies.
Gavazzi, Gaëtan; Herrmann, Francois; Krause, Karl-Heinz
Although demographic aging does not remain restricted to industrialized countries, the medical challenge arising from the aging population will be distinct in the developing world. This is particularly true with respect to infectious diseases, which have a distinct spectrum in the elderly population, as well as a greater overall relevance in the developing world. Tropical diseases have a specific presentation and epidemiology in elderly patients. Infectious diseases with a worldwide distribution impact elderly patients in the developing world in a specific manner, which is most obvious with respect to human immunodeficiency virus and tuberculosis but is also true with respect to "trivial" manifestations of infection, such as diarrhea and pneumonia. Malnutrition contributes in a major way to the immunodeficiency of elderly patients in the developing world. Poorly controlled use of antimicrobial drugs leads to multidrug-resistant microorganisms, which, together with the limited resources available for drug treatment, makes appropriate treatment of infections in elderly patients in developing countries very difficult. Infections in elderly patients will have an increasing impact on the public health and economy of developing countries.
Indo, Hiroko P; Yen, Hsiu-Chuan; Nakanishi, Ikuo; Matsumoto, Ken-Ichiro; Tamura, Masato; Nagano, Yumiko; Matsui, Hirofumi; Gusev, Oleg; Cornette, Richard; Okuda, Takashi; Minamiyama, Yukiko; Ichikawa, Hiroshi; Suenaga, Shigeaki; Oki, Misato; Sato, Tsuyoshi; Ozawa, Toshihiko; Clair, Daret K St; Majima, Hideyuki J
Fridovich identified CuZnSOD in 1969 and manganese superoxide dismutase (MnSOD) in 1973, and proposed "the Superoxide Theory," which postulates that superoxide (O2 (•-)) is the origin of most reactive oxygen species (ROS) and that it undergoes a chain reaction in a cell, playing a central role in the ROS producing system. Increased oxidative stress on an organism causes damage to cells, the smallest constituent unit of an organism, which can lead to the onset of a variety of chronic diseases, such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis and other neurological diseases caused by abnormalities in biological defenses or increased intracellular reactive oxygen levels. Oxidative stress also plays a role in aging. Antioxidant systems, including non-enzyme low-molecular-weight antioxidants (such as, vitamins A, C and E, polyphenols, glutathione, and coenzyme Q10) and antioxidant enzymes, fight against oxidants in cells. Superoxide is considered to be a major factor in oxidant toxicity, and mitochondrial MnSOD enzymes constitute an essential defense against superoxide. Mitochondria are the major source of superoxide. The reaction of superoxide generated from mitochondria with nitric oxide is faster than SOD catalyzed reaction, and produces peroxynitrite. Thus, based on research conducted after Fridovich's seminal studies, we now propose a modified superoxide theory; i.e., superoxide is the origin of reactive oxygen and nitrogen species (RONS) and, as such, causes various redox related diseases and aging.
Wei, Ke; Díaz-Trelles, Ramon; Liu, Qiaozhen; Diez-Cuñado, Marta; Scimia, Maria-Cecilia; Cai, Wenqing; Sawada, Junko; Komatsu, Masanobu; Boyle, Joseph J.; Zhou, Bin; Ruiz-Lozano, Pilar; Mercola, Mark
Aim Age and injury cause structural and functional changes in coronary artery smooth muscle cells (caSMCs) that influence the pathogenesis of coronary artery disease. Although paracrine signalling is widely believed to drive phenotypic changes in caSMCs, here we show that developmental origin within the fetal epicardium can have a profound effect as well. Methods and results Fluorescent dye and transgene pulse-labelling techniques in mice revealed that the majority of caSMCs are derived from Wt1+, Gata5-Cre+ cells that migrate before E12.5, whereas a minority of cells are derived from a later-emigrating, Wt1+, Gata5-Cre− population. We functionally evaluated the influence of early emigrating cells on coronary artery development and disease by Gata5-Cre excision of Rbpj, which prevents their contribution to coronary artery smooth muscle cells. Ablation of the Gata5-Cre+ population resulted in coronary arteries consisting solely of Gata5-Cre− caSMCs. These coronary arteries appeared normal into early adulthood; however, by 5–8 months of age, they became progressively fibrotic, lost the adventitial outer elastin layer, were dysfunctional and leaky, and animals showed early mortality. Conclusion Taken together, these data reveal heterogeneity in the fetal epicardium that is linked to coronary artery integrity, and that distortion of the coronaries epicardial origin predisposes to adult onset disease. PMID:26054850
Phillipson, Oliver T
The aging risk factor for Parkinson's disease is described in terms of specific disease markers including mitochondrial and gene dysfunctions relevant to energy metabolism. This review details evidence for the ability of nutritional agents to manage these aging risk factors. The combination of alpha lipoic acid, acetyl-l-carnitine, coenzyme Q10, and melatonin supports energy metabolism via carbohydrate and fatty acid utilization, assists electron transport and adenosine triphosphate synthesis, counters oxidative and nitrosative stress, and raises defenses against protein misfolding, inflammatory stimuli, iron, and other endogenous or xenobiotic toxins. These effects are supported by gene expression via the antioxidant response element (ARE; Keap/Nrf2 pathway), and by peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1 alpha), a transcription coactivator, which regulates gene expression for energy metabolism and mitochondrial biogenesis, and maintains the structural integrity of mitochondria. The effectiveness and synergies of the combination against disease risks are discussed in relation to gene action, dopamine cell loss, and the accumulation and spread of pathology via misfolded alpha-synuclein. In addition there are potential synergies to support a neurorestorative role via glial derived neurotrophic factor expression.
Mohanty, Sharada P; Hughes, David P; Salathé, Marcel
Crop diseases are a major threat to food security, but their rapid identification remains difficult in many parts of the world due to the lack of the necessary infrastructure. The combination of increasing global smartphone penetration and recent advances in computer vision made possible by deep learning has paved the way for smartphone-assisted disease diagnosis. Using a public dataset of 54,306 images of diseased and healthy plant leaves collected under controlled conditions, we train a deep convolutional neural network to identify 14 crop species and 26 diseases (or absence thereof). The trained model achieves an accuracy of 99.35% on a held-out test set, demonstrating the feasibility of this approach. Overall, the approach of training deep learning models on increasingly large and publicly available image datasets presents a clear path toward smartphone-assisted crop disease diagnosis on a massive global scale.
Mohanty, Sharada P.; Hughes, David P.; Salathé, Marcel
Crop diseases are a major threat to food security, but their rapid identification remains difficult in many parts of the world due to the lack of the necessary infrastructure. The combination of increasing global smartphone penetration and recent advances in computer vision made possible by deep learning has paved the way for smartphone-assisted disease diagnosis. Using a public dataset of 54,306 images of diseased and healthy plant leaves collected under controlled conditions, we train a deep convolutional neural network to identify 14 crop species and 26 diseases (or absence thereof). The trained model achieves an accuracy of 99.35% on a held-out test set, demonstrating the feasibility of this approach. Overall, the approach of training deep learning models on increasingly large and publicly available image datasets presents a clear path toward smartphone-assisted crop disease diagnosis on a massive global scale. PMID:27713752
Maddox, W. Todd; Pacheco, Jennifer; Reeves, Maia; Zhu, Bo; Schnyer, David M.
The basal ganglia and prefrontal cortex play critical roles in category learning. Both regions evidence age-related structural and functional declines. The current study examined rule-based and information-integration category learning in a group of older and younger adults. Rule-based learning is thought to involve explicit, frontally mediated…
Vijver, I. van de; Ridderinkhof, K.R.; Wit, S. de
Feedback-based learning declines with age. Because older adults are generally biased toward positive information (“positivity effect”), learning from positive feedback may be less impaired than learning from negative outcomes. The literature documents mixed results, due possibly to variability betwe
van de Vijver, I.; Ridderinkhof, K.R.; de Wit, S.
Feedback-based learning declines with age. Because older adults are generally biased toward positive information ("positivity effect"), learning from positive feedback may be less impaired than learning from negative outcomes. The literature documents mixed results, due possibly to variability betwe
Kliegel, Matthias; Altgassen, Mareike
The present study investigated fluid and crystallized intelligence as well as strategic task approaches as potential sources of age-related differences in adult learning performance. Therefore, 45 young and 45 old adults were asked to learn pictured objects. Overall, young participants outperformed old participants in this learning test. However,…
Lee, Annie; Archer, Jo; Wong, Caroline Kai Yun; Chen, Shen-Hsing Annabel; Qiu, Anqi
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.
As a third age PhD candidate with a passion for learning, I wanted to explore the learning of other rural third age women who live on the Lower Eyre Peninsula (LEP) of South Australia. This reflects the methodological stance of heuristic inquiry, which requires the researcher to have a passionate interest in the phenomena under investigation, and…
The aim of this study is to determine whether the approaches to learning and age are significantly correlated to grade point average (GPA) in early childhood education students. In addition, another purpose of this study is to determine whether approaches to learning and age predicted students' GPAs in the Early Childhood Education Department. The…
Toner, Chelsea K; Reese, Bruce E; Neargarder, Sandy; Riedel, Tatiana M; Gilmore, Grover C; Cronin-Golomb, Alice
We examined performance of healthy older and younger adults and individuals with Alzheimer's disease (AD) and Parkinson's disease (PD) on digit cancellation, a task putatively sensitive to cognitive impairment, but possibly affected by visual impairment, particularly in contrast sensitivity. Critical contrast thresholds were established to create custom stimulus arrays that were proximally matched across individuals. Age- and PD-related differences in search were fully accounted for by the sensory deficit. Increased contrast benefited AD patients, but could not override cognitive impairment. We conclude that visually fair neuropsychological testing can effectively compensate for normal age- and PD-related visual changes that affect cognitive performance.
Ballesteros, Soledad; Reales, José M; Mayas, Julia
The present study investigated age invariance for naming pictures and whether implicit memory is spared in Alzheimer's disease (AD). During the study phase, young adults, AD patients, and older controls were shown outlines of familiar pictures. After a distracter task, implicit memory was assessed incidentally. The results showed similar visual priming for the three groups, although young adults responded faster than the two older groups. Moreover, the number of errors was smaller for studied than for non-studied pictures. This pattern of results was repeated across the three groups, although AD patients produced more errors than young adults and older controls, and there were no differences between these latter groups. These results confirmed previous visual and haptic findings showing unimpaired perceptual priming in normal aging and AD patients when implicit memory is assessed using identification tasks. These results are interpreted from a cognitive neuroscience perspective.
Full Text Available DNA Damage contributes to cancer development and ageing. Congenital syndromes that affect DNA repair processes are characterized by cancer susceptibility, developmental defects, and accelerated ageing (Schumacher et al., 2008. DNA damage interferes with DNA metabolism by blocking replication and transcription. DNA polymerase blockage leads to replication arrest and can gives rise to genome instability. Transcription, on the other hand, is an essential process for utilizing the information encoded in the genome. DNA damage that interferes with transcription can lead to apoptosis and cellular senescence. Both processes are powerful tumor suppressors (Bartek and Lukas, 2007. Cellular response mechanisms to stalled RNA polymerase (RNAP II complexes have only recently started to be uncovered. Transcription-coupled DNA damage responses might thus play important roles for the adjustments to DNA damage accumulation in the ageing organism (Garinis et al., 2009. Here we review human disorders that are caused by defects in genome stability to explore the role of DNA damage in ageing and disease. We discuss how the nucleotide excision repair (NER system functions at the interface of transcription and repair and conclude with concepts how therapeutic targeting of transcription might be utilized in the treatment of cancer.
Landrum, Timothy J.; McDuffie, Kimberly A.
The concept of learning styles has tremendous logical and intuitive appeal, and educators' desire to focus on learning styles is understandable. Recently, a growing emphasis on differentiated instruction may have further increased teachers' tendency to look at learning styles as an instructionally relevant variable when individualizing instruction…
Bannan, Brenda; Cook, John; Pachler, Norbert
The purpose of this paper is to begin to examine how the intersection of mobile learning and design research prompts the reconceptualization of research and design individually as well as their integration appropriate for current, complex learning environments. To fully conceptualize and reconceptualize design research in mobile learning, the…
Children are thought to learn second languages (L2s) using primarily implicit mechanisms, in contrast to adults, who primarily rely on explicit language learning. This difference is usually attributed to cognitive maturation, but adults also receive more explicit instruction than children, which may influence their learning strategies. This study…
Van Galen, Jane
In October 2011, 200 state school officers and legislators gathered at a hotel in San Francisco to learn how to "revolutionize" learning by "personalizing" instruction. The occasion was former Florida Gov. Jeb Bush's second annual National Summit on Education Reform. The topic was digital learning. The vision of digitally managed curriculum and…
Lei, Baiying; Yang, Peng; Wang, Tianfu; Chen, Siping; Ni, Dong
Accurate identification and understanding informative feature is important for early Alzheimer's disease (AD) prognosis and diagnosis. In this paper, we propose a novel discriminative sparse learning method with relational regularization to jointly predict the clinical score and classify AD disease stages using multimodal features. Specifically, we apply a discriminative learning technique to expand the class-specific difference and include geometric information for effective feature selection. In addition, two kind of relational information are incorporated to explore the intrinsic relationships among features and training subjects in terms of similarity learning. We map the original feature into the target space to identify the informative and predictive features by sparse learning technique. A unique loss function is designed to include both discriminative learning and relational regularization methods. Experimental results based on a total of 805 subjects [including 226 AD patients, 393 mild cognitive impairment (MCI) subjects, and 186 normal controls (NCs)] from AD neuroimaging initiative database show that the proposed method can obtain a classification accuracy of 94.68% for AD versus NC, 80.32% for MCI versus NC, and 74.58% for progressive MCI versus stable MCI, respectively. In addition, we achieve remarkable performance for the clinical scores prediction and classification label identification, which has efficacy for AD disease diagnosis and prognosis. The algorithm comparison demonstrates the effectiveness of the introduced learning techniques and superiority over the state-of-the-arts methods.
Björgvin Steingrímsson 1968
Researchers in second language acquisition have proposed a critical period in language learning for individuals from early age until puberty and argue that if language attainment does not occur within this period it will not be successful. The innateness theory which suggests a critical period for children between age 2 – 6 in learning their first language has also been applied to second language learning. This has been controversial and there is no consensus among scholars. The terms sensiti...
Zhao, Wei; Wang, Han
Nowadays, label distribution learning is among the state-of-the-art methodologies in facial age estimation. It takes the age of each facial image instance as a label distribution with a series of age labels rather than the single chronological age label that is commonly used. However, this methodology is deficient in its simple decision-making criterion: the final predicted age is only selected at the one with maximum description degree. In many cases, different age labels may have very similar description degrees. Consequently, blindly deciding the estimated age by virtue of the highest description degree would miss or neglect other valuable age labels that may contribute a lot to the final predicted age. In this paper, we propose a strategic decision-making label distribution learning algorithm (SDM-LDL) with a series of strategies specialized for different types of age label distribution. Experimental results from the most popular aging face database, FG-NET, show the superiority and validity of all the proposed strategic decision-making learning algorithms over the existing label distribution learning and other single-label learning algorithms for facial age estimation. The inner properties of SDM-LDL are further explored with more advantages.
Full Text Available Nowadays, label distribution learning is among the state-of-the-art methodologies in facial age estimation. It takes the age of each facial image instance as a label distribution with a series of age labels rather than the single chronological age label that is commonly used. However, this methodology is deficient in its simple decision-making criterion: the final predicted age is only selected at the one with maximum description degree. In many cases, different age labels may have very similar description degrees. Consequently, blindly deciding the estimated age by virtue of the highest description degree would miss or neglect other valuable age labels that may contribute a lot to the final predicted age. In this paper, we propose a strategic decision-making label distribution learning algorithm (SDM-LDL with a series of strategies specialized for different types of age label distribution. Experimental results from the most popular aging face database, FG-NET, show the superiority and validity of all the proposed strategic decision-making learning algorithms over the existing label distribution learning and other single-label learning algorithms for facial age estimation. The inner properties of SDM-LDL are further explored with more advantages.
Full Text Available Age is often associated with a decline in cognitive abilities that are important for maintaining functional independence, such as learning new skills. Many forms of motor learning appear to be relatively well preserved with age, while learning tasks that involve associative binding tend to be negatively affected. The current study aimed to determine whether age differences exist on a configural response learning task, which includes aspects of motor learning and associative binding. Young (M = 24 years and older adults (M = 66.5 years completed a modified version of a configural learning task. Given the requirement of associative binding in the configural relationships between responses, we predicted older adults would show significantly less learning than young adults. Older adults demonstrated lower performance (slower reaction time and lower accuracy. However, contrary to our prediction, older adults showed similar rates of learning as indexed by a configural learning score compared to young adults. These results suggest that the ability to acquire knowledge incidentally about configural response relationships is largely unaffected by cognitive aging. The configural response learning task provides insight into the task demands that constrain learning abilities in older adults.
Chader, Gerald J; Taylor, Allen
This volume presents articles based on a workshop held June 14 to 16, 2013 in Rancho Palos Verde, CA sponsored by the Ocular Research Symposia Foundation (ORSF). The mission of the ORSF is to focus attention on unmet needs and current research opportunities in eye research with the objective of accelerating translation of research findings to effective clinical care. In this workshop, the subject of the "The Aging Eye" was addressed, including the prevalence of eye diseases in aging and the economic burden imposed by these diseases. New research work was highlighted on the genetics, biology, biochemistry, neurochemistry, and the impact of nutrition and the environment on function in the older eye. By identifying "low-hanging fruit" (i.e., the best opportunities for successful transition of laboratory research for the prevention of and new treatments and cures for ocular diseases), we seek to spur funding at both the basic research and clinical levels, resulting in sight-saving and sight-restoration measures in the near future.
Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald
Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context.
Circular ribonucleic acids (circRNAs) are non-coding RNAs of approximately 100 nucleotides in length with thousands of members in mammalian cells. The presence of circRNAs is believed to be even greater than that of messenger RNAs. Identification of circRNAs occurred approximately 37 years ago with the subsequent demonstration that covalent bonds are necessary for the unique circular structure of these ribonucleic acids. However, present understanding of the complex biological role of circRNAs remains limited and requires further elucidation. CircRNAs may impact aging, multiple disorders, function as biomarkers, and are able to regulate gene expression by acting as effective microRNA (miRNA) sponges. New work suggests that circRNAs are vital for the modulation of cellular senescence and programmed cell death pathways such as apoptosis. These non-coding RNAs can control cell cycle progression, cellular proliferation, and cellular survival impacting disorders linked to aging, cardiovascular disease, and atherosclerosis through pathways that involve cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase inhibitor 1 (p21), and mammalian forkhead transcription factors. In addition, circRNAs can oversee cellular metabolism and disorders such as diabetes mellitus through the regulation of insulin signaling as well as limit tumor progression through Wnt signaling and β-catenin pathways. Further understanding of the biology of circRNAs offers great promise for the targeting of novel strategies against a wide spectrum of disease entities.
Circular ribonucleic acids (circRNAs) are non-coding RNAs of approximately 100 nucleotides in length with thousands of members in mammalian cells. The presence of circRNAs is believed to be even greater than that of messenger RNAs. Identification of circRNAs occurred approximately 37 years ago with the subsequent demonstration that covalent bonds are necessary for the unique circular structure of these ribonucleic acids. However, present understanding of the complex biological role of circRNAs remains limited and requires further elucidation. CircRNAs may impact aging, multiple disorders, function as biomarkers, and are able to regulate gene expression by acting as effective microRNA (miRNA) sponges. New work suggests that circRNAs are vital for the modulation of cellular senescence and programmed cell death pathways such as apoptosis. These non-coding RNAs can control cell cycle progression, cellular proliferation, and cellular survival impacting disorders linked to aging, cardiovascular disease, and atherosclerosis through pathways that involve cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase inhibitor 1 (p21), and mammalian forkhead transcription factors. In addition, circRNAs can oversee cellular metabolism and disorders such as diabetes mellitus through the regulation of insulin signaling as well as limit tumor progression through Wnt signaling and β-catenin pathways. Further understanding of the biology of circRNAs offers great promise for the targeting of novel strategies against a wide spectrum of disease entities. PMID:27642518
... disease. However, researchers are pursuing several approaches to finding a cure. Scientists are exploring enzyme replacement therapy to provide the ... Online A listing of information and links for finding comprehensive genetics health information ... Last Reviewed: March 17, 2011 See Also: Talking Glossary ...
Duff, Melissa C; Gallegos, Diana R; Cohen, Neal J; Tranel, Daniel
Seminal work in Gary Van Hoesen's laboratory at Iowa in the early 1980s established that the hallmark neuropathology of Alzheimer's disease (AD; neurofibrillary tangles) had its first foothold in specific parts of the hippocampal formation and entorhinal cortex, effectively isolating the hippocampus from much of its input and output and causing the distinctive impairment of new learning that is the leading early characteristic of the disease (Hyman et al., 1984). The boundaries and conditions of the anterograde memory defect in patients with AD have been a topic of intense research interest ever since (e.g., Graham and Hodges, 1977; Nestor et al., 2006). For example, it has been shown that patients with AD may acquire some new semantic information through methods such as errorless learning, but learning under these conditions is typically slow and inefficient. Drawing on a learning paradigm (a collaborative referencing task) that was previously shown to induce robust and enduring learning in patients with hippocampal amnesia, we investigated whether this task would be effective in promoting new learning in patients with AD. We studied five women with early-stage AD and 10 demographically matched healthy comparison participants, each interacting with a familiar communication partner. AD pairs displayed significant and enduring learning across trials, with increased accuracy and decreased time to complete trials, in a manner indistinguishable from healthy comparison pairs, resulting in efficient and economical communication. The observed learning here most likely draws on neural resources outside the medial temporal lobes. These interactive communication sessions provide a potent learning environment with significant implications for memory intervention.
Seligman, Benjamin J.; Cullen, Mark R.; Horwitz, Ralph I.
Background The World Health Organization's Global Burden of Disease (GBD) reports are an important tool for global health policy makers, however the accuracy of estimates for countries undergoing an epidemiologic transition is unclear. We attempted to validate the life table model used to generate estimates for all-cause mortality in developing countries. Methods and Results Data were obtained for males and females from the Human Mortality Database for all countries with available data every ten years from 1900 to 2000. These provided inputs for the GBD life table model and served as comparison observed data. Above age sixty model estimates of survival for both sexes differed substantially from those observed. Prior to the year 1960 for males and 1930 for females, estimated survival tended to be greater than observed; following 1960 for both males and females estimated survival tended to be less than observed. Viewing observed and estimated survival separately, observed survival past sixty increased over the years considered. For males, the increase was from a mean (sd) probability of 0.22 (0.06) to 0.46 (0.1). For females, the increase was from 0.26 (0.06) to 0.65 (0.08). By contrast, estimated survival past sixty decreased over the same period. Among males, estimated survival probability declined from 0.54 (0.2) to 0.09 (0.06). Among females, the decline was from 0.36 (0.12) to 0.15 (0.08). Conclusions These results show that the GBD mortality model did not accurately estimate survival at older ages as developed countries transitioned in the twentieth century and may be similarly flawed in developing countries now undergoing transition. Estimates of the size of older-age populations and their attributable disease burden should be reconsidered. PMID:21629652
Benjamin J Seligman
Full Text Available BACKGROUND: The World Health Organization's Global Burden of Disease (GBD reports are an important tool for global health policy makers, however the accuracy of estimates for countries undergoing an epidemiologic transition is unclear. We attempted to validate the life table model used to generate estimates for all-cause mortality in developing countries. METHODS AND RESULTS: Data were obtained for males and females from the Human Mortality Database for all countries with available data every ten years from 1900 to 2000. These provided inputs for the GBD life table model and served as comparison observed data. Above age sixty model estimates of survival for both sexes differed substantially from those observed. Prior to the year 1960 for males and 1930 for females, estimated survival tended to be greater than observed; following 1960 for both males and females estimated survival tended to be less than observed. Viewing observed and estimated survival separately, observed survival past sixty increased over the years considered. For males, the increase was from a mean (sd probability of 0.22 (0.06 to 0.46 (0.1. For females, the increase was from 0.26 (0.06 to 0.65 (0.08. By contrast, estimated survival past sixty decreased over the same period. Among males, estimated survival probability declined from 0.54 (0.2 to 0.09 (0.06. Among females, the decline was from 0.36 (0.12 to 0.15 (0.08. CONCLUSIONS: These results show that the GBD mortality model did not accurately estimate survival at older ages as developed countries transitioned in the twentieth century and may be similarly flawed in developing countries now undergoing transition. Estimates of the size of older-age populations and their attributable disease burden should be reconsidered.
Marchal, Julia; Pifferi, Fabien; Aujard, Fabienne
Through its antioxidant, anticarcinogenic, and anti-inflammatory properties, resveratrol has become a candidate for drug development in the context of aging studies. Scientific evidence has highlighted its potential as a therapeutic agent for cardiovascular diseases and some cancers but also as an antiaging molecule. Resveratrol is thought to mimic the beneficial effects of chronic and moderate calorie restriction. Nevertheless, no study has demonstrated the prolongation of life span in healthy nonobese mammal models. This review summarizes recent findings on the effects of resveratrol on aging and life span in mammals. In our opinion, more studies should be performed to assess the effects of a chronic dietary intake of resveratrol in long-lived species close to humans, such as nonhuman primates. This will certainly generate more evidence about the ability of resveratrol to achieve the physiological benefits that have been observed in small mammal laboratory models and feature the eventual unwanted secondary effects that may occur under high levels of resveratrol.
Ho, Yuen-Shan; So, Kwok-Fai; Chang, Raymond Chuen-Chung
Aging is a universal biological process that leads to progressive and deleterious changes in organisms. From ancient time, mankind has already interested in preventing and keeping ourselves young. Anti-aging study is certainly not a new research area. Nowadays, the meaning of anti-aging has been changed from simply prolonging lifespan to increasing health span, which emphasizes more on the quality of life. This is the concept of healthy aging and prevention of pathological aging, which is associated with diseases. Keeping our brain functions as in young age is an important task for neuroscientists to prevent aging-associated neurological disorders, such as Alzheimer's diseases (AD) and Parkinson's disease (PD). The causes of these diseases are not fully understood, but it is believed that these diseases are affected by multiple factors. Neurodegenerative diseases can be cross-linked with a number of aging-associated conditions. Based on this, a holistic approach in anti-aging research seems to be more reasonable. Herbal medicine has a long history in Asian countries. It is believed that many of the medicinal herbs have anti-aging properties. Recent studies have shown that some medicinal herbs are effective in intervention or prevention of aging-associated neurological disorders. In this review, we use wolfberry and ginseng as examples to elaborate the properties of anti-aging herbs. The characteristics of medicinal herbs, especially their applications in different disease stages (prevention and intervention) and multi-targets properties, allow them to be potential anti-aging intervention in prevention and treatment of the aging-associated neurological disorders.
Mahapatra, Dwarikanath; Vos, Franciscus M; Buhmann, Joachim M
This paper proposes a novel active learning (AL) framework, and combines it with semi supervised learning (SSL) for segmenting Crohns disease (CD) tissues from abdominal magnetic resonance (MR) images. Robust fully supervised learning (FSL) based classifiers require lots of labeled data of different disease severities. Obtaining such data is time consuming and requires considerable expertise. SSL methods use a few labeled samples, and leverage the information from many unlabeled samples to train an accurate classifier. AL queries labels of most informative samples and maximizes gain from the labeling effort. Our primary contribution is in designing a query strategy that combines novel context information with classification uncertainty and feature similarity. Combining SSL and AL gives a robust segmentation method that: (1) optimally uses few labeled samples and many unlabeled samples; and (2) requires lower training time. Experimental results show our method achieves higher segmentation accuracy than FSL methods with fewer samples and reduced training effort.
Beauchamp, M. H.; Dagher, A.; Panisset, M.; Doyon, J.
While cognitive skill learning is normally acquired implicitly through frontostrial circuitry in healthy individuals, neuroimaging studies suggest that patients with Parkinson's disease (PD) do so by activating alternate, intact brain areas associated with explicit memory processing. To further test this hypothesis, 10 patients with PD and 12…
Full Text Available The present behavioral study readdresses the question of habit learning in Parkinson's disease. Patients were early onset, non-demented, dopa-responsive, candidates for surgical treatment, similar to those we found earlier as suffering greater dopamine depletion in the putamen than in the caudate nucleus. The task was the same conditional associative learning task as that used previously in monkeys and healthy humans to unveil the striatum involvement in habit learning. Sixteen patients and 20 age- and education-matched healthy control subjects learned sets of 3 visuo-motor associations between complex patterns and joystick displacements during two testing sessions separated by a few hours. We distinguished errors preceding versus following the first correct response to compare patients' performance during the earliest phase of learning dominated by goal-directed actions with that observed later on, when responses start to become habitual. The disease significantly retarded both learning phases, especially in patients under sixty years of age. However, only the late phase deficit was disease severity-dependent and persisted on the second testing session. These findings provide the first corroboration in Parkinson patients of two ideas well-established in the animal literature. The first is the idea that associating visual stimuli to motor acts is a form of habit learning that engages the striatum. It is confirmed here by the global impairment in visuo-motor learning induced by Parkinson's disease. The second idea is that goal-directed behaviors are predominantly caudate-dependent whereas habitual responses are primarily putamen-dependent. At the advanced Parkinson's disease stages tested here, dopamine depletion is greater in the putamen than in the caudate nucleus. Accordingly, the late phase of learning corresponding to the emergence of habitual responses was more vulnerable to the disease than the early phase dominated by goal
Yifan He; Jihong Zhu; Fang Huang; Liu Qin; Wenguo Fan; Hongwen He
The tooth belongs to the trigeminal sensory pathway. Dental damage has been associated with impairments in the central nervous system that may be mediated by injury to the trigeminal nerve. In the present study, we investigated the effects of damage to the inferior alveolar nerve, an important peripheral nerve in the trigeminal sensory pathway, on learning and memory be-haviors and structural changes in related brain regions, in a mouse model of Alzheimer’s disease. Inferior alveolar nerve transection or sham surgery was performed in middle-aged (4-month-old) or elderly (7-month-old) senescence-accelerated mouse prone 8 (SAMP8) mice. When the middle-aged mice reached 8 months (middle-aged group 1) or 11 months (middle-aged group 2), and the elderly group reached 11 months, step-down passive avoidance and Y-maze tests of learn-ing and memory were performed, and the cholinergic system was examined in the hippocampus (Nissl staining and acetylcholinesterase histochemistry) and basal forebrain (choline acetyltrans-ferase immunohistochemistry). In the elderly group, animals that underwent nerve transection had fewer pyramidal neurons in the hippocampal CA1 and CA3 regions, fewer cholinergic ifbers in the CA1 and dentate gyrus, and fewer cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band, compared with sham-operated animals, as well as showing impairments in learning and memory. Conversely, no signiifcant differences in histology or be-havior were observed between middle-aged group 1 or group 2 transected mice and age-matched sham-operated mice. The present ifndings suggest that trigeminal nerve damage in old age, but not middle age, can induce degeneration of the septal-hippocampal cholinergic system and loss of hippocampal pyramidal neurons, and ultimately impair learning ability. Our results highlight the importance of active treatment of trigeminal nerve damage in elderly patients and those with Alzheimer’s disease, and
Scheibye-Knudsen, Morten; Scheibye-Alsing, Karsten; Canugovi, Chandrika
to have mitochondrial dysfunction and those diseases showed strong association with mitochondrial disorders. We next evaluated mitochondrial involvement in aging and detected two distinct categories of accelerated aging disorders, one of them being associated with mitochondrial dysfunction. Normal aging...... seemed to associate stronger with the mitochondrial diseases than the non-mitochondrial partially supporting a mitochondrial theory of aging....
Fjell, Anders M; McEvoy, Linda; Holland, Dominic; Dale, Anders M; Walhovd, Kristine B
What can be expected in normal aging, and where does normal aging stop and pathological neurodegeneration begin? With the slow progression of age-related dementias such as Alzheimer's disease (AD), it is difficult to distinguish age-related changes from effects of undetected disease. We review recent research on changes of the cerebral cortex and the hippocampus in aging and the borders between normal aging and AD. We argue that prominent cortical reductions are evident in fronto-temporal regions in elderly even with low probability of AD, including regions overlapping the default mode network. Importantly, these regions show high levels of amyloid deposition in AD, and are both structurally and functionally vulnerable early in the disease. This normalcy-pathology homology is critical to understand, since aging itself is the major risk factor for sporadic AD. Thus, rather than necessarily reflecting early signs of disease, these changes may be part of normal aging, and may inform on why the aging brain is so much more susceptible to AD than is the younger brain. We suggest that regions characterized by a high degree of life-long plasticity are vulnerable to detrimental effects of normal aging, and that this age-vulnerability renders them more susceptible to additional, pathological AD-related changes. We conclude that it will be difficult to understand AD without understanding why it preferably affects older brains, and that we need a model that accounts for age-related changes in AD-vulnerable regions independently of AD-pathology.
Head, Elizabeth; Murphey, Heather L.; Dowling, Amy L.S.; McCarty, Katie L.; Bethel, Samuel R.; Nitz, Jonathan A.; Pleiss, Melanie; Vanrooyen, Jenna; Grossheim, Mike; Smiley, Jeffery R.; Murphy, M. Paul; Beckett, Tina L.; Pagani, Dieter; Bresch, Frederick; Hendrix, Curt
Alzheimer's disease (AD) involves multiple pathological processes in the brain, including increased inflammation and oxidative damage, as well as the accumulation of beta-amyloid (Aβ) plaques. We hypothesized that a combinatorial therapeutic approach to target these multiple pathways may provide cognitive and neuropathological benefits for AD patients. To test this hypothesis, we used a canine model of human aging and AD. Aged dogs naturally develop learning and memory impairments, human-type Aβ deposits and oxidative damage in the brain. Thus, 9 aged beagles (98-115 months) were treated with a medical food cocktail containing (1) an extract of turmeric containing 95% curcuminoids; (2) an extract of green tea containing 50% epigallocatechingallate; (3) N-acetyl cysteine; (4) R-alpha lipoic acid; and (5) an extract of black pepper containing 95% piperine. Nine similarly aged dogs served as placebo-treated controls. After 3 months of treatment, 13 dogs completed a variable distance landmark task used as a measure of spatial attention. As compared to placebo-treated animals, dogs receiving the medical food cocktail had significantly lower error scores (t(11)=4.3, p=0.001) and were more accurate across all distances (F(1,9)=20.7, p=0.001), suggesting an overall improvement in spatial attention. Measures of visual discrimination learning, executive function and spatial memory, and levels of brain and CSF Aβ were unaffected by the cocktail. Our results indicate that this medical food cocktail may be beneficial for improving spatial attention and motivation deficits associated with impaired cognition in aging and AD. PMID:22886019
Alberto Tommasini; Tarcisio Not; Alessandro Ventura
From the time of Gee's landmark writings, the recent history of celiac disease (CD) can be divided into manyages, each driven by a diagnostic advance and a deeperknowledge of disease pathogenesis. At the same time,these advances were paralleled by the identification of new clinical patterns associated with CD and by a continuous redefinition of the prevalence of the diseasein population. In the beginning, CD was considered a chronic indigestion, even if the causative food was notknown; later, the disease was proven to depend on anintolerance to wheat gliadin, leading to typical mucosalchanges in the gut and to a malabsorption syndrome. This knowledge led to curing the disease with a gluten-free diet. After the identification of antibodies to gluten(AGA) in the serum of patients and the identification of gluten-specific lymphocytes in the mucosa, CD was described as an immune disorder, resembling a chronic "gluten infection". The use of serological testing for AGA allowed identification of the higher prevalence of this disorder, revealing atypical patterns of presenta-tion. More recently, the characterization of autoantibod-ies to endomysium and to transglutaminase shifted the attention to a complex autoimmune pathogenesis and to the increased risk of developing autoimmune disor-ders in untreated CD. New diagnostic assays, based on molecular technologies, will introduce new changes, with the promise of better defining the spectrum of gluten reactivity and the real burden of gluten related-disorders in the population. Herein, we describe the different periods of CD experience, and further devel-opments for the next celiac age will be proposed.
This study explores the long-term effects of starting age and the effects of input in an instructed language learning setting. First, with respect to the effects of starting age, the findings suggest that in the long term and after similar amounts of input, starting age is not a predictor of language outcomes. Second, the study examines the…
Cultural services and tourism are among the United Kingdom's fastest growing sectors in terms of employment and consumer demand. Cultural services and tourism bring the following elements to lifelong learning: active rather than passive learning; a means of interpreting the world around us; exposure to cultures other than one's own; confidence and…
Davidson, Cathy N.; Goldberg, David Theo
Over the past two decades, the way we learn has changed dramatically. We have new sources of information and new ways to exchange and to interact with information. But our schools and the way we teach have remained largely the same for years, even centuries. What happens to traditional educational institutions when learning also takes place on a…
Meneses, A; Castillo, C; Ibarra, M; Hong, E
A comparison between behavioral alterations induced by hypertension and aging was made in spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY) of different ages (3-24 months old), trained to perform autoshaping learning and activity tasks. Food-deprived rats received autoshaping training sessions during 6 days; the animals were retrained 1 month later. Two weeks after autoshaping training, the animals were evaluated in the spontaneous activity task during 2 consecutive days. The results show an age-related decrease in learning, memory, and spontaneous activity. Independently of the age group compared, WKY, though showing lower activity, learned and retrieved more than SHR. Accordingly, the reductions in learning and memory were correlated with both aging and hypertension. The combined influence of these two factors had synergistic detrimental effects on cognitive functions.
Geneva Marie Stein
Full Text Available Our understanding of the molecular and genetic regulation of aging and longevity has been greatly augmented through studies using the small model system, C. elegans. It is important to test whether mutations that result in a longer life span also extend the health span of the organism, rather than simply prolonging an aged state. C. elegans can learn and remember both associated and non-associated stimuli, and many of these learning and memory paradigms are subject to regulation by longevity pathways. One of the more distressing results of aging is cognitive decline, and while no gross physical defects in C. elegans sensory neurons have been identified, the organism does lose the ability to perform both simple and complex learned behaviors with age. Here we review what is known about the effects of longevity pathways and the decline of these complex learned behaviors with age, and we highlight outstanding questions in the field.
Jacklin, Susan M.
This study examines the learning of a gross motor coincidence timing task by children with learning difficulties, compared with that by children of average intelligence of an equivalent chronological age and mental age. Results are discussed. (Author/MT)
Full Text Available Using the remarkable overlap between brain circuits affected in Parkinson’s disease (PD and those underlying motor sequence learning, we may improve the effectiveness of motor rehabilitation interventions by identifying motor learning facilitators in PD. For instance, additional sensory stimulation and task cueing enhanced motor learning in people with PD, whereas exercising using musical rhythms or console computer games improved gait and balance, and reduced some motor symptoms, in addition to increasing task enjoyment. Yet, despite these advances, important knowledge gaps remain. Most studies investigating motor learning in PD used laboratory-specific tasks and equipment, with little resemblance to real life situations. Thus, it is unknown whether similar results could be achieved in more ecological setups and whether individual’s task engagement could further improve motor learning capacity. Moreover, the role of social interaction in motor skill learning process has not yet been investigated in PD and the role of mind-set and self-regulatory mechanisms have been sporadically examined. Here we review evidence suggesting that these psychosocial factors may be important modulators of motor learning in PD. We propose their incorporation in future research, given that it could lead to development of improved non-pharmacological interventions aimed to preserve or restore motor function in PD.
Naismith, Sharon L; Mowszowski, Loren; Diamond, Keri; Lewis, Simon J G
This study aimed to evaluate the efficacy of a multifactorial 'healthy brain ageing cognitive training program' for Parkinson's disease. Using a single-blinded waitlist control design, 50 participants with Parkinson's disease were recruited from the Brain & Mind Research Institute, Sydney, Australia. The intervention encompassed both psychoeducation and cognitive training; each component lasted 1-hour. The 2-hour sessions were delivered in a group format, twice-weekly over a 7-week period. Multifactorial psychoeducation was delivered by a range of health professionals. In addition to delivering cognitive strategies, it targeted depression, anxiety, sleep, vascular risk factors, diet, and exercise. Cognitive training was computer-based and was conducted by clinical neuropsychologists. The primary outcome was memory. Secondary outcomes included other aspects of cognition and knowledge pertaining to the psychoeducation material. Results demonstrated that cognitive training was associated with significant improvements in learning and memory corresponding to medium to large effect sizes. Treatment was also associated with medium effect size improvements in knowledge. Although the study was limited by the lack of randomized allocation to treatment and control groups, these findings suggest that a healthy brain ageing cognitive training program may be a viable tool to improve memory and/or slow cognitive decline in people with Parkinson's disease. It also appeared successful for increasing awareness of adaptive and/or compensatory cognitive strategies, as well as modifiable risk factors to optimize brain functioning.
Vermeer, Cees; Theuwissen, Elke
The function of vitamin K is to serve as a co-factor during the post-translational carboxylation of glutamate (Glu) residues into γ-carboxyglutamate (Gla) residues. The vital importance of the Gla-proteins essential for normal haemostasis is well recognized. During recent years, new Gla-containing proteins have been discovered and the vitamin K-dependent carboxylation is also essential for their function. It seems, however, that our dietary vitamin K intake is too low to support the carboxylation of at least some of these Gla-proteins. According to the triage theory, long-term vitamin K inadequacy is an independent, but modifiable risk factor for the development of degenerative diseases of ageing including osteoporosis and atherosclerosis.
Kuntsevich, Viktoriya; Bushell, William C; Theise, Neil D
Mechanisms underlying the modulating effects of yogic cognitive-behavioral practices (eg, meditation, yoga asanas, pranayama breathing, caloric restriction) on human physiology can be classified into 4 transduction pathways: humoral factors, nervous system activity, cell trafficking, and bioelectromagnetism. Here we give examples of these transduction pathways and how, through them, yogic practices might optimize health, delay aging, and ameliorate chronic illness and stress from disability. We also recognize that most studies of these mechanisms remain embedded in a reductionist paradigm, investigating small numbers of elements of only 1 or 2 pathways. Moreover, often, subjects are not long-term practitioners, but recently trained. The models generated from such data are, in turn, often limited, top-down, without the explanatory power to describe beneficial effects of long-term practice or to provide foundations for comparing one practice to another. More flexible and useful models require a systems-biology approach to gathering and analysis of data. Such a paradigm is needed to fully appreciate the deeper mechanisms underlying the ability of yogic practice to optimize health, delay aging, and speed efficient recovery from injury or disease. In this regard, 3 different, not necessarily competing, hypotheses are presented to guide design of future investigations, namely, that yogic practices may: (1) promote restoration of physiologic setpoints to normal after derangements secondary to disease or injury, (2) promote homeostatic negative feedback loops over nonhomeostatic positive feedback loops in molecular and cellular interactions, and (3) quench abnormal "noise" in cellular and molecular signaling networks arising from environmental or internal stresses.
Wilcock, Donna M; Schmitt, Frederick A; Head, Elizabeth
Down syndrome (DS) is a common cause of intellectual disability and is also associated with early age of onset of Alzheimer's disease (AD). Due to an extra copy of chromosome 21, most adults over 40years old with DS have beta-amyloid plaques as a result of overexpression of the amyloid precursor protein. Cerebrovascular pathology may also be a significant contributor to neuropathology observed in the brains of adults with DS. This review describes the features of cardiovascular dysfunction and cerebrovascular pathology in DS that may be modifiable risk factors and thus targets for interventions. We will describe cerebrovascular pathology, the role of co-morbidities, imaging studies indicating vascular pathology and the possible consequences. It is clear that our understanding of aging and AD in people with DS will benefit from further studies to determine the role that cerebrovascular dysfunction contributes to cognitive health. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock.
Full Text Available Abstract The present article examines several lines of converging evidence suggesting that the slow and insidious brain changes that accumulate over the lifespan, resulting in both natural cognitive aging and Alzheimer's disease (AD, represent a metabolism reduction program. A number of such adaptive programs are known to accompany aging and are thought to have decreased energy requirements for ancestral hunter-gatherers in their 30s, 40s and 50s. Foraging ability in modern hunter-gatherers declines rapidly, more than a decade before the average terminal age of 55 years. Given this, the human brain would have been a tremendous metabolic liability that must have been advantageously tempered by the early cellular and molecular changes of AD which begin to accumulate in all humans during early adulthood. Before the recent lengthening of life span, individuals in the ancestral environment died well before this metabolism reduction program resulted in clinical AD, thus there was never any selective pressure to keep adaptive changes from progressing to a maladaptive extent. Aging foragers may not have needed the same cognitive capacities as their younger counterparts because of the benefits of accumulated learning and life experience. It is known that during both childhood and adulthood metabolic rate in the brain decreases linearly with age. This trend is thought to reflect the fact that children have more to learn. AD "pathology" may be a natural continuation of this trend. It is characterized by decreasing cerebral metabolism, selective elimination of synapses and reliance on accumulating knowledge (especially implicit and procedural over raw brain power (working memory. Over decades of subsistence, the behaviors of aging foragers became routinized, their motor movements automated and their expertise ingrained to a point where they no longer necessitated the first-rate working memory they possessed when younger and learning actively. Alzheimer
Background The emergence of the internet, particularly Web 2.0 has provided access to the views and opinions of a wide range of individuals opening up opportunities for new forms of communication and knowledge formation. Previous ways of navigating and filtering available information are likely to prove ineffective in these new contexts. Connectivism is one of the most prominent of the network learning theories which have been developed for e-learning environments. It is beginning to be recog...
Andrew T Kempsell
Full Text Available The physiological and molecular mechanisms of age-related memory loss are complicated by the complexity of vertebrate nervous systems. This study takes advantage of a simple neural model to investigate nervous system aging, focusing on changes in learning and memory in the form of behavioral sensitization in vivo and synaptic facilitation in vitro. The effect of aging on the tail withdrawal reflex (TWR was studied in Aplysia californica at maturity and late in the annual lifecycle. We found that short-term sensitization in TWR was absent in aged Aplysia. This implied that the neuronal machinery governing nonassociative learning was compromised during aging. Synaptic plasticity in the form of short-term facilitation between tail sensory and motor neurons decreased during aging whether the sensitizing stimulus was tail shock or the heterosynaptic modulator serotonin (5-HT. Together, these results suggest that the cellular mechanisms governing behavioral sensitization are compromised during aging, thereby nearly eliminating sensitization in aged Aplysia.
Germine, Laura T.; Duchaine, Bradley; Nakayama, Ken
Research on age-related cognitive change traditionally focuses on either development or aging, where development ends with adulthood and aging begins around 55 years. This approach ignores age-related changes during the 35 years in-between, implying that this period is uninformative. Here we investigated face recognition as an ability that may…
Eskofier, Bjoern M; Lee, Sunghoon I; Daneault, Jean-Francois; Golabchi, Fatemeh N; Ferreira-Carvalho, Gabriela; Vergara-Diaz, Gloria; Sapienza, Stefano; Costante, Gianluca; Klucken, Jochen; Kautz, Thomas; Bonato, Paolo
The development of wearable sensors has opened the door for long-term assessment of movement disorders. However, there is still a need for developing methods suitable to monitor motor symptoms in and outside the clinic. The purpose of this paper was to investigate deep learning as a method for this monitoring. Deep learning recently broke records in speech and image classification, but it has not been fully investigated as a potential approach to analyze wearable sensor data. We collected data from ten patients with idiopathic Parkinson's disease using inertial measurement units. Several motor tasks were expert-labeled and used for classification. We specifically focused on the detection of bradykinesia. For this, we compared standard machine learning pipelines with deep learning based on convolutional neural networks. Our results showed that deep learning outperformed other state-of-the-art machine learning algorithms by at least 4.6 % in terms of classification rate. We contribute a discussion of the advantages and disadvantages of deep learning for sensor-based movement assessment and conclude that deep learning is a promising method for this field.
N. A. Hohlacheva
Full Text Available Goal. Study of the role of risk factors in mechanized gall stone formation depending on sex and age of patients. Material and methods We examined 210 patients with stage I gallstone disease (GSD. In verification of diagnosis used an ultrasound study of the hepatobiliary system, multi-grade duodenal sounding with subsequent macroscopic, microscopic, chemical and physical examination of bile. In the portions “b” and “C” bile was determined the total concentration of bile acids, cholesterol, with the subsequent calculation it consists of cholesterol ratio. Estimation of surface tension of bile viscosity and bile. In the studied blood levels of total cholesterol, lipoproteins of very low density, lowdensity lipoproteins, high density lipoproteins, triglycerides, were determined the coefficient of atherogenicity. To assess the degree of accumulation of body fat was used the Quetelet index. Studied the relative risk of anamnestic risk factors of GSD. Results. The features of biliary lithogenesis based on gender and age of patients. High value PR for the gall stone formation are female gender — 3,16, Mature and elderly age (older than 50 of 3.67. In young women, gall-stone formation is mainly due to the increase of cholesterol level of bile, at the age of 50 years with a decline in zhelchnokamennaja pool, increased viscosity and surface tension of bile. The most important risk factors of cholecystolithiasis are also gender differences: if women is multiple pregnancies and (or childbirth (more than 3 — OR 4,62, overweight (BMI over 26 — OR is 4.57 and the violation of the principles of good nutrition (eating disorders, overeating or starvation, the use of large quantities of animal fats — OR 3,94, for men it’s physical inactivity — OR a 4.25, the increase in KA — PR 3.87 and burdened by GSD genetics — OR of 2.05. Conclusion. The data obtained can be used in the organization of dispensary work with patients with hepatobiliary
This article is about education and learning for the "retired". In using this term, it is recognised that any such definitions and given age bands cover a wide range of situations and learning needs. Such diversity should closely inform the educational agenda for older adults, and as it is a life phase defined by challenge and change…
Fried, Stephen B.; Mehrotra, Chandra M.
Covering 10 topical areas, this annotated bibliography offers a guide to journal articles, book chapters, monographs, and books useful for teaching diversity and aging through active learning. Active learning experiences may help expand students' awareness of elements of their own diversity, broaden their world view, and enhance their culturally…
Voogt, J.; Schols, M.; Bottema, J.; van Bergen, H.; van der Stap, N.; Tomson, A.; Nieweg, M.; Doornenbal, J.W.; Bakker, B.; Smits, A.; Thompson, A.; Searson, M.; Ochoa, M.
The assumption underlying the symposium is that teacher education institutions have a dual challenge. At the one hand they need to prepare pre-service students for teaching and facilitating learning in the digital age, including the use of technology in teaching and learning. At the other hand teach
Tragant, Elsa; Victori, Mia
In studies dealing with language learning strategies in the school context, the variables of proficiency and age are often difficult to isolate since students accumulate more hours of foreign language instruction as they move up from grade to grade. This study aimed to deal with these two variables independently by analysing learning strategy use…
Newberry, Gayle; Martin, Carol; Robbins, Lorna
Background: Not enough is currently known about how people with learning disabilities experience and understand the ageing process. This is particularly important as the population of older people with learning disabilities is growing due to increased life expectancy. This article draws on the first author's doctoral research study, which aimed to…
Horowitz, Beverly P.; Wong, Stephanie Dapice; Dechello, Karen
Americans are living longer, and the meaning of age has changed, particularly for Boomers and seniors. These demographic changes have economic and social ramifications with implications for health care, including rehabilitation services, and health science education. Service learning is an experiential learning pedagogy that integrates traditional…
Lifelong learning programs for older adults are expanding in university communities, given the growing emphasis on successful aging in our society. This dissertation consists of two articles that examine data from ethnographic research in a southeastern lifelong learning institute associated with a state university. Data include observations over…
Yau, Hon Keung; Cheng, Alison Lai Fong
Some past studies find that older students have more confidence in using technology for learning than younger students but some other studies find the opposite result. However, it is found that there are a few researches studying on the age difference in the perception of using technology for learning in Hong Kong. Therefore, the aim of the study…
Gorlick, Marissa A; Giguère, Gyslain; Glass, Brian D; Nix, Brittany N; Mather, Mara; Maddox, W Todd
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.
Olojo Oludare Jethro
Full Text Available E-learning presents an entirely new learning environment for students, thus requiring a different skill set to be successful (Romiszowski, 2004. Critical thinking, research, and evaluation skills are growing in importance as students have increasing volumes of information from a variety of sources to sort through (New Media Consortium, 2007. Also, particularly in courses that are entirely electronic, students are much more independent than in the traditional setting. This requires that they be highly motivated and committed to learning (Huynh et al., 2003, with less social interaction with peers or an instructor. Students in online courses tend to do as well as those in classrooms, but there is higher incidence of withdrawal or incomplete grades (Zhang, Zhou and Briggs, 2006. E-learning can be viewed as computer assisted learning, and as pedagogy for student-centered and collaborative learning. Early developments in e-learning focused on computer assisted learning, where part or all of the learning content is delivered digitally. More recently the pedagogical dimension of e-learning has become prominent. E-learning comprises all forms of electronically supported learning and teaching. The information and communication systems, whether networked learning or not, serve as specific media to implement the learning process.
Berghuis, Kelly M. M.; De Rond, Veerle; Zijdewind, Inge; Koch, Giacomo; Veldman, Menno P.; Hortobagyi, Tibor
There is controversy whether age-related neuroanatomical and neurophysiological changes in the central nervous system affect healthy old adults' abilities to acquire and retain motor skills. We examined the effects of age on motor skill acquisition and retention and potential underlying mechanisms b
Rust, Tiana B.; See, Sheree Kwong
This study assessed professional caregivers of persons with Alzheimer disease (AD) and non-caregivers' knowledge about aging and AD. Participants completed modified versions of the Alzheimer Disease Knowledge Test and the multiple-choice version of the Facts on Aging Quiz #1. Overall, knowledge levels about AD and aging were low. Caregivers were…
Stahl, Sarah T.; Metzger, Aaron
This cross-sectional study examined the associations among perceived vulnerability to disease, aging knowledge, and ageism (positive and negative) in a sample of undergraduate students enrolled in a human development course (N = 649; M age = 19.94 years, SD = 2.84 years). Perceived vulnerability to disease and aging knowledge were associated with…
Nead, Kevin T.; Gaskin, Greg; Chester, Cariad; Swisher-McClure, Samuel; Dudley, Joel T.; Leeper, Nicholas J.; Shah, Nigam H.
We recently found an association between androgen deprivation therapy (ADT) and Alzheimer’s disease. As Alzheimer’s disease is a disease of advanced age, we hypothesize that older individuals on ADT may be at greatest risk. We conducted a retrospective multi-institutional analysis among 16,888 individuals with prostate cancer using an informatics approach. We tested the effect of ADT on Alzheimer’s disease using Kaplan–Meier age stratified analyses in a propensity score matched cohort. We found a lower cumulative probability of remaining Alzheimer’s disease-free between non-ADT users age ≥70 versus those age Alzheimer’s disease was 2.9%, 1.9% and 0.5% among ADT users ≥70, non-ADT users ≥70 and individuals Alzheimer’s disease risk. Future work should investigate the ADT Alzheimer’s disease association in advanced age populations given the greater potential clinical impact.
Nead, Kevin T; Gaskin, Greg; Chester, Cariad; Swisher-McClure, Samuel; Dudley, Joel T; Leeper, Nicholas J; Shah, Nigam H
We recently found an association between androgen deprivation therapy (ADT) and Alzheimer's disease. As Alzheimer's disease is a disease of advanced age, we hypothesize that older individuals on ADT may be at greatest risk. We conducted a retrospective multi-institutional analysis among 16,888 individuals with prostate cancer using an informatics approach. We tested the effect of ADT on Alzheimer's disease using Kaplan-Meier age stratified analyses in a propensity score matched cohort. We found a lower cumulative probability of remaining Alzheimer's disease-free between non-ADT users age ≥70 versus those age Alzheimer's disease was 2.9%, 1.9% and 0.5% among ADT users ≥70, non-ADT users ≥70 and individuals Alzheimer's disease risk. Future work should investigate the ADT Alzheimer's disease association in advanced age populations given the greater potential clinical impact.
Boulton-Lewis, Gillian M.; Tam, M.; Buys, Laurie; Chui, Ernest Wing-tak
This article reports on the findings of qualitative, semistructured interviews conducted with 40 older Australian participants and 39 participants in Hong Kong who either did or did not engage in organized learning in the last 6 months. Phenomenology was used to guide the interviews and analysis to explore the experiences and perspectives of these…
The purpose of this single-case study was to explore the lived experiences of a grade 6 teacher and students who used tablets as part of their classroom instruction. Malone and Lepper's taxonomy of intrinsic motivations for learning is used as a framework for examining whether and how this particular theory of motivation applies equally well for…
What is the future of education when the possibilities that exist for children change and advance so rapidly and are so uncertain? Where learning occurs as naturally in a Web 2.0 environment as in the playground, playing field, front room or street? Where adults may still be playing and experimenting far beyond their childhood in ways we could…
Everyone is living through a period of considerable demographic change, which is predicted to continue and escalate. People are living longer and, generally, healthier lives, and the lifelong learning system in the UK needs to catch-up with this new reality. There is a need for a much more flexible approach that offers choice and opportunities to…
D'Aquila, Patrizia; Bellizzi, Dina; Passarino, Giuseppe
The rate/quality of human aging and the development/progression of diseases depend on a complex interplay among genetics, epigenetics and environment. In this scenario, mitochondrial function (or dysfunction) and mitochondrial DNA have emerged as major players. This is mainly due to their crucial role in energetic balance, in modulating epigenetic programs and in influencing cell stress response. Moreover, it is also emerging the existence of epigenetic changes in mitochondrial DNA and of non coding mitochondrial RNAs which, together with the nuclear ones, play regulatory roles in numerous human phenotypes. In this review we will provide an overview on "mitochondrial epigenetics" state of the art, by summarizing the involvement of mitochondrial function and of mitochondria-nucleus communication in regulating nuclear epigenome, as well as the key aspects of the epigenetic marks related to mitochondrial DNA. Despite the limited data available in the literature to date, mainly due to the novelty of the topic, the intriguing interplay of the mitochondrial epigenetic changes in both physiological and pathological conditions will also be presented.
Amal F Radwan
Full Text Available A 37-year-old hypertensive housewife presented with a sudden onset of left-sided hemiplegia, hemianaesthesia, dysarthria and urinary incontinence. The condition was preceded by recurrent attacks of motor neurological deficits over a 3-year duration. She reported a history of a fall from a height at the age of 10, which was followed by a hearing deficit and a history of two caesarean sections after eclampsia. The blood pressure was 170/100 mmHg. Laboratory investigations revealed hyperglycaemia (fasting glucose 306 mg/dl and normal kidney function tests. The computed tomography scans revealed old multiple bilateral cerebral infarcts with recent intracranial haemorrhage in the right parietal region. The inflammatory markers (ESR and CRP and immune profile (ANA, anti-ds DNA and ANCA were found to be normal. Cerebral angiography revealed a complete occlusion of the intracranial parts of both internal carotid arteries at their supraclinoid segments along with the proximal parts of the anterior cerebral artery and middle cerebral artery, with collaterals from the posterior circulation. Consequently, the diagnosis of moyamoya disease with the collaterals was confirmed. Antihypertensive medications and insulin were administered. Cerebral dehydration measures were undertaken with partial improvement. A superficial temporal artery-middle cerebral artery bypass operation was performed with some postoperative improvement. One month later, she suffered a new stroke with severe impairment of the level of consciousness; the computed tomography scans revealed a large recent cerebral infarct, her condition deteriorated rapidly and she died shortly thereafter.
Galasko, D; Kwo-on-Yuen, P F; Klauber, M R; Thal, L J
To determine the potential value of abnormal neurological findings as markers of Alzheimer's disease (AD) and their relationship to the stage of AD, we compared standardized neurological examinations in 135 community-dwelling patients with AD and 91 nondemented elderly individuals. After correcting for differences in age and education between the two groups, we found that rigidity, stooped posture, graphesthesia, neglect of simultaneous tactile stimuli (face-hand test), and snout, grasp, and glabella reflexes were present significantly more often in patients with AD than in control subjects. These findings increased in prevalence in patients with AD according to the severity of dementia. However, in a multivariate logistic regression model only the grasp reflex, graphesthesia, and the face-hand test were statistically significantly associated with the degree of cognitive impairment. Although abnormal neurological findings occur regularly in AD, they are too infrequent early in the course of AD to serve as diagnostic markers. Prospective studies are needed to determine whether patients with the early onset of extrapyramidal or other findings form a distinct subgroup of AD.
Huang, Debin; Hu, Zehua; Yu, Zhaofen
Eleutheroside B or E, the main component of Acanthopanax, can relieve fatigue, enhance memory, and improve human cognition. Numerous studies have confirmed that high doses of acetylcholine significantly attenuate clinical symptoms and delay the progression of Alzheimer's disease. The present study replicated a rat model of aging induced by injecting quinolinic acid into the hippocampal CA1 region. These rats were intraperitoneally injected with low, medium and high doses of eleutheroside B or E (50, 100, 200 mg/kg), and rats injected with Huperzine A or PBS were used as controls. At 4 weeks after administration, behavioral tests showed that the escape latencies and errors in searching for the platform in a Morris water maze were dose-dependently reduced in rats treated with medium and high-dose eleutheroside B or E. Hematoxylin-eosin staining showed that the number of surviving hippocampal neurons was greater and pathological injury was milder in three eleutheroside B or E groups compared with model group. Hippocampal homogenates showed enhanced cholinesterase activity, and dose-dependent increases in acetylcholine content and decreases in choline content following eleutheroside B or E treatment, similar to those seen in the Huperzine A group. These findings indicate that eleutheroside B or E improves learning and memory in aged rats. These effects of eleutheroside B or E may be mediated by activation of cholinesterase or enhanced reuse of choline to accelerate the synthesis of acetylcholine in hippocampal neurons. PMID:25206404
Huang, Debin; Hu, Zehua; Yu, Zhaofen
Eleutheroside B or E, the main component of Acanthopanax, can relieve fatigue, enhance memory, and improve human cognition. Numerous studies have confirmed that high doses of acetylcholine significantly attenuate clinical symptoms and delay the progression of Alzheimer's disease. The present study replicated a rat model of aging induced by injecting quinolinic acid into the hippocampal CA1 region. These rats were intraperitoneally injected with low, medium and high doses of eleutheroside B or E (50, 100, 200 mg/kg), and rats injected with Huperzine A or PBS were used as controls. At 4 weeks after administration, behavioral tests showed that the escape latencies and errors in searching for the platform in a Morris water maze were dose-dependently reduced in rats treated with medium and high-dose eleutheroside B or E. Hematoxylin-eosin staining showed that the number of surviving hippocampal neurons was greater and pathological injury was milder in three eleutheroside B or E groups compared with model group. Hippocampal homogenates showed enhanced cholinesterase activity, and dose-dependent increases in acetylcholine content and decreases in choline content following eleutheroside B or E treatment, similar to those seen in the Huperzine A group. These findings indicate that eleutheroside B or E improves learning and memory in aged rats. These effects of eleutheroside B or E may be mediated by activation of cholinesterase or enhanced reuse of choline to accelerate the synthesis of acetylcholine in hippocampal neurons.
Debin Huang; Zehua Hu; Zhaofen Yu
Eleutheroside B or E, the main component of Acanthopanax, can relieve fatigue, enhance memory, and improve human cognition. Numerous studies have confirmed that high doses of acetylcholine significantly attenuate clinical symptoms and delay the progression of Alzheimer's disease. The present study replicated a rat model of aging induced by injecting quinolinic acid into the hippocampal CA1 region. These rats were intraperitoneally injected with low, medium and high doses of eleutheroside B or E (50, 100, 200 mg/kg), and rats injected with Huperzine A or PBS were used as controls. At 4 weeks after administration, behavioral tests showed that the escape latencies and errors in searching for the platform in a Morris water maze were dose-dependently reduced in rats treated with medium and high-dose eleutheroside B or E. Hematoxylin-eosin staining showed that the number of surviving hippocampal neurons was greater and pathological injury was milder in three eleutheroside B or E groups compared with model group. Hippocampal homogenates showed enhanced cholinesterase activity, and dose-dependent increases in acetylcholine content and decreases in choline content following eleutheroside B or E treatment, similar to those seen in the Huperzine A group. These findings indicate that eleutheroside B or E improves learning and memory in aged rats. These effects of eleutheroside B or E may be mediated by activation of cholinesterase or enhanced reuse of choline to accelerate the synthesis of acetylcholine in hippocampal neurons.
Lee, Cynthia; Yeung, Alexander Seeshing; Ip, Tiffany
Computer technology provides spaces and locales for language learning. However, learning style preference and demographic variables may affect the effectiveness of technology use for a desired goal. Adapting Reid's pioneering Perceptual Learning Style Preference Questionnaire (PLSPQ), this study investigated the relations of university students'…
Petzold, Anne; Psotta, Laura; Brigadski, Tanja; Endres, Thomas; Lessmann, Volkmar
Brain-derived neurotrophic factor (BDNF) is a crucial mediator of neural plasticity and, consequently, of memory formation. In hippocampus-dependent learning tasks BDNF also seems to play an essential role. However, there are conflicting results concerning the spatial learning ability of aging BDNF(+/-) mice in the Morris water maze paradigm. To evaluate the effect of chronic BDNF deficiency in the hippocampus on spatial learning throughout life, we conducted a comprehensive study to test differently aged BDNF(+/-) mice and their wild type littermates in the Morris water maze and to subsequently quantify their hippocampal BDNF protein levels as well as expression levels of TrkB receptors. We observed an age-dependent learning deficit in BDNF(+/-) animals, starting at seven months of age, despite stable hippocampal BDNF protein expression and continual decline of TrkB receptor expression throughout aging. Furthermore, we detected a positive correlation between hippocampal BDNF protein levels and learning performance during the probe trial in animals that showed a good learning performance during the long-term memory test.
Children attending centre-based early childhood care and education programmes across Australia are most likely to be grouped according to age and development. While multi- or mixed-age grouping has been seen to have positive benefits on young children's learning and pro-social behaviours, this approach is not usually adopted in the organisation of…
Sowerby, Paula; Seal, Simon; Tripp, Gail
Objective: To further define the nature of working memory (WM) impairments in children with combined-type ADHD. Method: A total of 40 Children with ADHD and an age and gender-matched control group (n = 40) completed two measures of visuo-spatial WM and two measures of verbal WM. The effects of age and learning/language difficulties on performance…
Verneau, M.; Kamp, J. van der; Savelsbergh, G,J.; Looze, M.P. de
We assessed the effects of aging in the transfer of motor learning in a sequential manual assembly task that is representative for real working conditions. On two different days, young (18-30years) and middle-aged adults (50-65years) practiced to build two products that consisted of the same six com
Stoter, Arjan J. R.; Scherder, Erik J. A.; Kamsma, Yvo P. T.; Mulder, Theo
Motor imagery and action-based rehearsal were compared during motor sequence-learning by young adults (M = 25 yr., SD = 3) and aged adults (M = 63 yr., SD = 7). General accuracy of aged adults was lower than that of young adults (F-1,F-28 = 7.37, p = .01) even though working-memory capacity was equi
Seddon, G. M.; Shubber, K. E.
Evaluated effectiveness of six instructional programs (each dealing with a different aspect of a spatial task related to diagrams of three-dimensional structures) with Bahraini students (ages 13- to 17-years-old). All brought about a significant degree of learning over all age groups. Implications of these and other findings are discussed.…
Full Text Available Abstract We describe the inflammation pathway from Cholesterol to Aging. Interleukin 6 mediated inflammation is implicated in age-related disorders including Atherosclerosis, Peripheral Vascular Disease, Coronary Artery Disease, Osteoporosis, Type 2 Diabetes, Dementia and Alzheimer's disease and some forms of Arthritis and Cancer. Statins and Bisphosphonates inhibit Interleukin 6 mediated inflammation indirectly through regulation of endogenous cholesterol synthesis and isoprenoid depletion. Polyphenolic compounds found in plants, fruits and vegetables inhibit Interleukin 6 mediated inflammation by direct inhibition of the signal transduction pathway. Therapeutic targets for the control of all the above diseases should include inhibition of Interleukin-6 mediated inflammation.
Shoemark, Deborah K; Allen, Shelley J
This review, gathered from diverse sources, shows how our microbiome influences health and ultimately how well we age. Evidence linking oral bacteria to Alzheimer's disease (AD) is discussed in the context of aging, drawing together data from epidemiological, experimental, genetic, and environmental studies. Immunosenescence results in increased bacterial load as cell-mediated and humoral immune responses wane. The innate immune system gradually takes over; contributing to the rise in circulating proinflammatory cytokines such as TNFα. Maintaining the integrity of the blood-brain barrier (BBB) against a backdrop of increasing bacterial load is important. Aging may favor the proliferation of anaerobes in the mouth eliciting a robust TNFα response from the oral epithelium. Prolonged exposure to high levels of circulating TNFα compromises the integrity of the BBB. Sensitive techniques now detect the "asymptomatic" presence of bacteria in areas previously thought to be sterile, providing new insights into the wider distribution of components of the microbiome. These "immune-tolerated" bacteria may slowly multiply elsewhere until they elicit a chronic inflammatory response; some are now considered causal in instances of atherosclerosis and back pain. Inflammatory processes have long been associated with AD. We propose for a subset of AD patients, aging favors the overgrowth of oral anaerobes established earlier in life provoking a pro-inflammatory innate response that weakens the BBB allowing bacteria to spread and quietly influence the pathogenesis of AD. Finally, we suggest that human polymorphisms considered alongside components of the microbiome may provide new avenues of research for the prevention and treatment of disease.
Dunlosky, John; Baker, Julie M C; Rawson, Katherine A; Hertzog, Christopher
In 2 experiments, the authors investigated whether age-related differences exist in metacomprehension by evaluating predictions based on the ease-of-processing (EOP) hypothesis. According to this hypothesis, judgments of how well a text has been learned are based on how easily each text was processed; easier processing results in higher judgments. Participants read either sentence pairs or longer texts and judged their learning of each immediately afterward. Although an age-related difference in the use of processing ease in judgments was observed with sentence pairs, for longer texts older and younger adults' judgments were similarly related to processing ease. In both experiments, age equivalence was also evident in the accuracy of the judgments at predicting performance on the criterion test. The overall pattern of results suggests that judging text learning remains largely intact with aging.
Rebecca M. C. Spencer
Full Text Available Improvements in motor sequence learning come about via goal-based learning of the sequence of visual stimuli and muscle-based learning of the sequence of movement responses. In young adults, consolidation of goal-based learning is observed after intervals of sleep but not following wake, whereas consolidation of muscle-based learning is greater following intervals with wake compared to sleep. While the benefit of sleep on motor sequence learning has been shown to decline with age, how sleep contributes to consolidation of goal-based versus muscle-based learning in older adults has not been disentangled. We trained young (n=62 and older (n=50 adults on a motor sequence learning task and re-tested learning following 12 hr intervals containing overnight sleep or daytime wake. To probe consolidation of goal-based learning of the sequence, half of the participants were re-tested in a configuration in which the stimulus sequence was the same but, due to a shift in stimulus-response mapping, the movement response sequence differed. To probe consolidation of muscle-based learning, the remaining participants were tested in a configuration in which the stimulus sequence was novel, but now the sequence of movements used for responding was unchanged. In young adults, there was a significant condition (goal-based v. muscle-based learning by interval (sleep v. wake interaction, F(1,58=6.58, p=.013: Goal-based learning tended to be greater following sleep compared to wake, t(29=1.47, p=.072. Conversely, muscle-based learning was greater following wake than sleep, t(29=2.11, p=.021. Unlike young adults, this interaction was not significant in older adults, F(1,46=.04, p=.84, nor was there a main effect of interval, F(1,46=1.14, p=.29. Thus, older adults do not preferentially consolidate sequence learning over wake or sleep.
Wilcken, D E; Wilcken, B
The sulfur-containing amino acid, homocysteine, is formed from the essential amino acid methionine, and a number of B vitamins are involved in methionine metabolism. Pyridoxine, vitamin B6, is a cofactor for cystathionine beta synthase, which mediates the transformation of homocysteine to cystathionine, the initial step in the transsulfuration pathway and the urinary excretion of sulfur. In a normal diet there is conservation of the carbon skeleton, and about 50% of the homocysteine formed is remethylated to methionine via steps that require folic acid and vitamin B12. A deficiency of any of these three vitamins leads to modest homocyst(e)ine elevation, as does diminished renal function, both of which are common in the elderly. It is also established that homocyst(e)ine elevation of this order is associated with increased cardiovascular risk but is also associated with most established risk factors, although it is thought to be an independent contributor. In the inborn error of metabolism homocystinuria due to cystathionine beta synthase deficiency there is greatly increased circulating homocyst(e)ine and a clear association with precocious vascular disease. In about 50% of these patients there is a vascular event before the age of 30 years. The homocysteine-induced adverse vascular changes appear to result from endothelial and smooth muscle cell effects and increased thrombogenesis. We have documented a highly significant reduction in the occurrence of vascular events during 539 patient years of treatment in 32 patients with cystathionine beta synthase deficiency (mean age 30 years, range 9-66 years) by aggressive homocyst(e)ine lowering with pyridoxine, folic acid, and B12 (p = 0.0001). The 15 pyridoxine nonresponsive patients also received oral betaine. Although a cause and effect relationship is postulated for the increased cardiovascular risk associated with mild homocysteine elevation, a common cause of this elevation is the methylenetetrahydrofolate
Glorioso, Christin; Oh, Sunghee; Douillard, Gaelle Guilloux; Sibille, Etienne
Mechanisms determining characteristic age-of-onset for neurological diseases are largely unknown. Normal brain aging associates with robust and progressive transcriptome changes ("molecular aging"), but the intersection with disease pathways is mostly uncharacterized. Here, using cross-cohort microarray analysis of four human brain areas, we show that neurological disease pathways largely overlap with molecular aging and that subjects carrying a newly-characterized low-expressing polymorphism in a putative longevity gene (Sirtuin5; SIRT5(prom2)) have older brain molecular ages. Specifically, molecular aging was remarkably conserved across cohorts and brain areas, and included numerous developmental and transcription-regulator genes. Neurological disease-associated genes were highly overrepresented within age-related genes and changed almost unanimously in pro-disease directions, together suggesting an underlying genetic "program" of aging that progressively promotes disease. To begin testing this putative pathway, we developed and used an age-biosignature to assess five candidate longevity gene polymorphisms' association with molecular aging rates. Most robustly, aging was accelerated in cingulate, but not amygdala, of subjects carrying a SIRT5 promoter polymorphism (+9 years, p=0.004), in concordance with cingulate-specific decreased SIRT5 expression. This effect was driven by a set of core transcripts (+24 years, p=0.0004), many of which were mitochondrial, including Parkinson's disease genes, PINK-1 and DJ-1/PARK7, hence suggesting that SIRT5(prom2) may represent a risk factor for mitochondrial dysfunction-related diseases, including Parkinson's, through accelerated molecular aging of disease-related genes. Based on these results we speculate that a "common mechanism" may underlie age-of-onset across several neurological diseases. Confirming this pathway and its regulation by common genetic variants would provide new strategies for predicting, delaying, and
Full Text Available One of the susceptibility genes in Crohn’s disease (CD is CARD15. Our study examined the relationship between peripheral CARD15 expression and phenotype and duration of CD, treatment methods and inflammatory indices. Sixty patients with CD and 30 healthy volunteers as controls were enrolled in the study. Total RNA was isolated from peripheral blood mononuclear cells (PBMCs with E.Z.N.A. Total RNA Kit (Omega Bio-tek then quantitative real-time PCR was performed on the ABI Prism 7900 HT Real-Time PCR System. CARD15 gene expression in PBMCs in CD was significantly higher than in the control group. The highest level of gene expression was found in CD patients in the fourth decade of life. The mRNA level of the CARD15 gene was higher in patients with disease duration between 12 and 60 months. A positive correlation was found between erythrocyte sedimentation rate (ESR and gene expression level. Gene expression increased with increasing level of C-reactive protein and ESR, but it was not statistically significant. CARD15 expression significantly decreased in CD patients treated with anti-TNFα agents compared to azathioprine or steroid treatment groups. Expression of the CARD15 gene in Crohn›s disease is higher than in healthy individuals. Disease duration and age of patients seem to be the most important factors influencing CARD15 expression.
Lin, Cecilia I. C.; Tang, Wen-hui; Kuo, Feng-Yang
The group of middle-aged and elderly women represents the lowest usage rate of information and communication technology (ICT) in Taiwan. This article reports how a social intervention program, the Taiwan Women Up (TWU) program, has helped such group to successfully learn ICT skills with the support of members of nonprofit organizations. The study…
... COMMISSION Interim Staff Guidance on Changes to the Generic Aging Lessons Learned (GALL) Report Revision 2... Learned (GALL) Report,'' and the NRC staff's aging management review procedure and acceptance criteria... learned and to address emergent issues not covered in license renewal guidance documents. In this way,...
Westendorp Rudi GJ
Full Text Available Abstract Background Is this person ill or just old? This question reflects the pondering mind of a doctor while interpreting the complaints of an elderly person who seeks his help. Many doctors think that ageing is a non-disease. Accordingly, various attempts have been undertaken to separate pathological ageing from normal ageing. However, the existence of a normal ageing process distinct from the pathological processes causing disease later in life can be questioned. Discussion Ageing is the accumulation of damage to somatic cells, leading to cellular dysfunction, and culminates in organ dysfunction and an increased vulnerability to death. Analogously, chronic diseases initiate early in life and their development is slow before they become clinically apparent and culminate in disability or death. The definition of disease is also subject to current opinions and scientific understanding and usually, it is an act of individual creativity when physical changes are recognised as symptoms of a new disease. New diseases, however, are only rarely really new. Most new diseases have gone undiagnosed because their signs and symptoms escaped recognition or were interpreted otherwise. Many physical changes in the elderly that are not yet recognised as a disease are thus ascribed to normal ageing. Therefore, the distinction between normal ageing and disease late in life seems in large part arbitrary. Summary We think that normal ageing cannot be separated from pathological processes causing disease later in life, and we propose that the distinction is avoided.
Full Text Available Abstract Background Systems biological approach of molecular connectivity map has reached to a great interest to understand the gene functional similarities between the diseases. In this study, we developed a computational framework to build molecular connectivity maps by integrating mutated and differentially expressed genes of neurological and psychiatric diseases to determine its relationship with aging. Results The systematic large-scale analyses of 124 human diseases create three classes of molecular connectivity maps. First, molecular interaction of disease protein network generates 3632 proteins with 6172 interactions, which determines the common genes/proteins between diseases. Second, Disease-disease network includes 4845 positively scored disease-disease relationships. The comparison of these disease-disease pairs with Medical Subject Headings (MeSH classification tree suggests 25% of the disease-disease pairs were in same disease area. The remaining can be a novel disease-disease relationship based on gene/protein similarity. Inclusion of aging genes set showed 79 neurological and 20 psychiatric diseases have the strong association with aging. Third and lastly, a curated disease biomarker network was created by relating the proteins/genes in specific disease contexts, such analysis showed 73 markers for 24 diseases. Further, the overall quality of the results was achieved by a series of statistical methods, to avoid insignificant data in biological networks. Conclusions This study improves the understanding of the complex interactions that occur between neurological and psychiatric diseases with aging, which lead to determine the diagnostic markers. Also, the disease-disease association results could be helpful to determine the symptom relationships between neurological and psychiatric diseases. Together, our study presents many research opportunities in post-genomic biomarkers development.
Norris, Cathleen A.; Soloway, Elliot
Speeding past the Steve Jobs Post-PC Era into the Age of Mobilism, the authors foresee how, by 2015, each and every student in America's K-12 classrooms will be using their own mobile computing device, with those devices engendering the most disruptive transformation in education in 150 years. Classrooms will move from today's "I Teach"…
Radulescu, Angela; Daniel, Reka; Niv, Yael
Reinforcement learning (RL) in complex environments relies on selective attention to uncover those aspects of the environment that are most predictive of reward. Whereas previous work has focused on age-related changes in RL, it is not known whether older adults learn differently from younger adults when selective attention is required. In 2 experiments, we examined how aging affects the interaction between RL and selective attention. Younger and older adults performed a learning task in which only 1 stimulus dimension was relevant to predicting reward, and within it, 1 "target" feature was the most rewarding. Participants had to discover this target feature through trial and error. In Experiment 1, stimuli varied on 1 or 3 dimensions and participants received hints that revealed the target feature, the relevant dimension, or gave no information. Group-related differences in accuracy and RTs differed systematically as a function of the number of dimensions and the type of hint available. In Experiment 2 we used trial-by-trial computational modeling of the learning process to test for age-related differences in learning strategies. Behavior of both young and older adults was explained well by a reinforcement-learning model that uses selective attention to constrain learning. However, the model suggested that older adults restricted their learning to fewer features, employing more focused attention than younger adults. Furthermore, this difference in strategy predicted age-related deficits in accuracy. We discuss these results suggesting that a narrower filter of attention may reflect an adaptation to the reduced capabilities of the reinforcement learning system. (PsycINFO Database Record
Kaja, Simon; Sumien, Nathalie; Shah, Vidhi V; Puthawala, Imran; Maynard, Alexandra N; Khullar, Nitasha; Payne, Andrew J; Forster, Michael J; Koulen, Peter
Mutations in presenilin (PS) proteins cause familial Alzheimer's disease. We herein tested the hypothesis that the expression levels of PS proteins are differentially affected during healthy aging, in the absence of pathological mutations. We used a preclinical model for aging to identify associations between PS expression and quantitative behavioral parameters for spatial memory and learning and motor function. We identified significant changes of PS protein expression in both cerebellum and forebrain that correlated with the performance in behavioral paradigms for motor function and memory and learning. Overall, PS1 levels were decreased, while PS2 levels were increased in aged mice compared with young controls. Our study presents novel evidence for the differential expression of PS proteins in a nongenetic model for aging, resulting in an overall increase of the PS2 to PS1 ratio. Our findings provide a novel mechanistic basis for molecular and functional changes during normal aging.
Full Text Available Josef Dolejs,1 Petra Marešová2 1Department of Informatics and Quantitative Methods, 2Department of Economics, Faculty of Informatics and Management, University of Hradec Králové, Hradec Králové, Czech Republic Background: The answer to the question “At what age does aging begin?” is tightly related to the question “Where is the onset of mortality increase with age?” Age affects mortality rates from all diseases differently than it affects mortality rates from nonbiological causes. Mortality increase with age in adult populations has been modeled by many authors, and little attention has been given to mortality decrease with age after birth.Materials and methods: Nonbiological causes are excluded, and the category “all diseases” is studied. It is analyzed in Denmark, Finland, Norway, and Sweden during the period 1994–2011, and all possible models are screened. Age trajectories of mortality are analyzed separately: before the age category where mortality reaches its minimal value and after the age category.Results: Resulting age trajectories from all diseases showed a strong minimum, which was hidden in total mortality. The inverse proportion between mortality and age fitted in 54 of 58 cases before mortality minimum. The Gompertz model with two parameters fitted as mortality increased with age in 17 of 58 cases after mortality minimum, and the Gompertz model with a small positive quadratic term fitted data in the remaining 41 cases. The mean age where mortality reached minimal value was 8 (95% confidence interval 7.05–8.95 years. The figures depict an age where the human population has a minimal risk of death from biological causes.Conclusion: Inverse proportion and the Gompertz model fitted data on both sides of the mortality minimum, and three parameters determined the shape of the age–mortality trajectory. Life expectancy should be determined by the two standard Gompertz parameters and also by the single parameter in
Guo, Guodong; Fu, Yun; Dyer, Charles R; Huang, Thomas S
Estimating human age automatically via facial image analysis has lots of potential real-world applications, such as human computer interaction and multimedia communication. However, it is still a challenging problem for the existing computer vision systems to automatically and effectively estimate human ages. The aging process is determined by not only the person's gene, but also many external factors, such as health, living style, living location, and weather conditions. Males and females may also age differently. The current age estimation performance is still not good enough for practical use and more effort has to be put into this research direction. In this paper, we introduce the age manifold learning scheme for extracting face aging features and design a locally adjusted robust regressor for learning and prediction of human ages. The novel approach improves the age estimation accuracy significantly over all previous methods. The merit of the proposed approaches for image-based age estimation is shown by extensive experiments on a large internal age database and the public available FG-NET database.
Trewartha, Kevin M; Garcia, Angeles; Wolpert, Daniel M; Flanagan, J Randall
Motor learning has been shown to depend on multiple interacting learning processes. For example, learning to adapt when moving grasped objects with novel dynamics involves a fast process that adapts and decays quickly-and that has been linked to explicit memory-and a slower process that adapts and decays more gradually. Each process is characterized by a learning rate that controls how strongly motor memory is updated based on experienced errors and a retention factor determining the movement-to-movement decay in motor memory. Here we examined whether fast and slow motor learning processes involved in learning novel dynamics differ between younger and older adults. In addition, we investigated how age-related decline in explicit memory performance influences learning and retention parameters. Although the groups adapted equally well, they did so with markedly different underlying processes. Whereas the groups had similar fast processes, they had different slow processes. Specifically, the older adults exhibited decreased retention in their slow process compared with younger adults. Within the older group, who exhibited considerable variation in explicit memory performance, we found that poor explicit memory was associated with reduced retention in the fast process, as well as the slow process. These findings suggest that explicit memory resources are a determining factor in impairments in the both the fast and slow processes for motor learning but that aging effects on the slow process are independent of explicit memory declines.
Verneau, Marion; van der Kamp, John; Savelsbergh, Geert J P; de Looze, Michiel P
We assessed the effects of aging in the transfer of motor learning in a sequential manual assembly task that is representative for real working conditions. On two different days, young (18-30 years) and middle-aged adults (50-65 years) practiced to build two products that consisted of the same six components but which had to be assembled in a partly different order. Assembly accuracy and movement time during tests, which were performed before and after the practice sessions, were compared to determine proactive and retroactive transfer. The results showed proactive facilitation (i.e., benefits from having learned the first product on learning the second one) in terms of an overall shortening of movement time in both age-groups. In addition, only the middle-aged adults were found to show sequence-specific proactive facilitation, in which the shortening of movement time was limited to components that had the same the order in the two products. Most likely, however, the sequence-specific transfer was an epiphenomenon of the comparatively low rate of learning among the middle-aged adults. The results, however, did reveal genuine differences between the groups for retroactive transfer (i.e., effects from learning the second product on performance of the first). Middle-aged adults tended to show more pronounced retroactive interference in terms of a general decrease in accuracy, while younger adults showed sequence-specific retroactive facilitation (i.e., shortening of movement times for components that had the same order in the two products), but only when they were fully accurate. Together this suggests that in the learning of sequential motor tasks the effects of age are more marked for retroactive transfer than for proactive transfer.
Jie, Biao; Zhang, Daoqiang; Cheng, Bo; Shen, Dinggang
Multimodality based methods have shown great advantages in classification of Alzheimer's disease (AD) and its prodromal stage, that is, mild cognitive impairment (MCI). Recently, multitask feature selection methods are typically used for joint selection of common features across multiple modalities. However, one disadvantage of existing multimodality based methods is that they ignore the useful data distribution information in each modality, which is essential for subsequent classification. Accordingly, in this paper we propose a manifold regularized multitask feature learning method to preserve both the intrinsic relatedness among multiple modalities of data and the data distribution information in each modality. Specifically, we denote the feature learning on each modality as a single task, and use group-sparsity regularizer to capture the intrinsic relatedness among multiple tasks (i.e., modalities) and jointly select the common features from multiple tasks. Furthermore, we introduce a new manifold-based Laplacian regularizer to preserve the data distribution information from each task. Finally, we use the multikernel support vector machine method to fuse multimodality data for eventual classification. Conversely, we also extend our method to the semisupervised setting, where only partial data are labeled. We evaluate our method using the baseline magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG-PET), and cerebrospinal fluid (CSF) data of subjects from AD neuroimaging initiative database. The experimental results demonstrate that our proposed method can not only achieve improved classification performance, but also help to discover the disease-related brain regions useful for disease diagnosis.
Jaime M. Ross
Full Text Available Mitochondrial dysfunction and impairment of the ubiquitin proteasome system have been described as two hallmarks of the ageing process. Additionally, both systems have been implicated in the etiopathogenesis of many age-related diseases, particularly neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease. Interestingly, these two systems are closely interconnected, with the ubiquitin proteasome system maintaining mitochondrial homeostasis by regulating organelle dynamics, the proteome, and mitophagy, and mitochondrial dysfunction impairing cellular protein homeostasis by oxidative damage. Here, we review the current literature and argue that the interplay of the two systems should be considered in order to better understand the cellular dysfunction observed in ageing and age-related diseases. Such an approach may provide valuable insights into molecular mechanisms underlying the ageing process, and further discovery of treatments to counteract ageing and its associated diseases. Furthermore, we provide a hypothetical model for the heterogeneity described among individuals during ageing.
Chang, Li-Hung; Yotsumoto, Yuko; Salat, David H; Andersen, George J; Watanabe, Takeo; Sasaki, Yuka
Although normal aging is known to reduce cortical structures globally, the effects of aging on local structures and functions of early visual cortex are less understood. Here, using standard retinotopic mapping and magnetic resonance imaging morphologic analyses, we investigated whether aging affects areal size of the early visual cortex, which were retinotopically localized, and whether those morphologic measures were associated with individual performance on visual perceptual learning. First, significant age-associated reduction was found in the areal size of V1, V2, and V3. Second, individual ability of visual perceptual learning was significantly correlated with areal size of V3 in older adults. These results demonstrate that aging changes local structures of the early visual cortex, and the degree of change may be associated with individual visual plasticity.
Full Text Available It has been well documented that aging is associated with declines in a variety of cognitive functions. A growing body of research shows that the age-related cognitive declines are reversible through cognitive training programs, suggesting maintained cognitive plasticity of the aging brain. Retest learning represents a basic form of cognitive plasticity. It has been consistently demonstrated for adults in young-old and old-old ages. Accumulated research indicates that retest learning is effective, robust, endurable and could occur at a more conceptual level beyond item-specific memorization. Recent studies also demonstrate promisingly broader transfer effects from retest practice of activities involving complex executive functioning to other untrained tasks. The results shed light on the development of self-guided mental exercise programs to improve cognitive performance and efficiency of the aging brain. The relevant studies were reviewed, and the findings were discussed in light of their limitations, implications, and future directions.
Amanda L Kauffman
Full Text Available Of all the age-related declines, memory loss is one of the most devastating. While conditions that increase longevity have been identified, the effects of these longevity-promoting factors on learning and memory are unknown. Here we show that the C. elegans Insulin/IGF-1 receptor mutant daf-2 improves memory performance early in adulthood and maintains learning ability better with age but, surprisingly, demonstrates no extension in long-term memory with age. By contrast, eat-2 mutants, a model of Dietary Restriction (DR, exhibit impaired long-term memory in young adulthood but maintain this level of memory longer with age. We find that crh-1, the C. elegans homolog of the CREB transcription factor, is required for long-term associative memory, but not for learning or short-term memory. The expression of crh-1 declines with age and differs in the longevity mutants, and CREB expression and activity correlate with memory performance. Our results suggest that specific longevity treatments have acute and long-term effects on cognitive functions that decline with age through their regulation of rate-limiting genes required for learning and memory.
Moron, I; Ballesteros, M A; Candido, A; Gallo, M
The relationship between hippocampal function and aging was explored in Wistar rats using taste aversion learning by comparing the performance of adult dorsal hippocampal lesioned and fifteen-month-old intact rats with that of adult intact rats. In experiment 1 the conditioned blocking phenomenon was absent in the hippocampal and the aging rats. Unlike the adult intact rats, the hippocampal and aging rats were not impaired in acquiring a learned aversion to a cider vinegar solution (3 %) presented as a serial compound with a previously conditioned saccharin solution (0.1 %). In experiment 2 both the hippocampal and the aging rats developed reduced aversions to a saline solution (0.5 %) followed by an i.p. injection of lithium chloride (0.15 M; 2 % b.w.) if the taste solution was previously preexposed without consequences. This latent inhibition effect was similar to that seen in intact adult rats. In both experiments, the aging rats exhibited enhanced conventional learned taste aversions. It is concluded that aging is not a unitary process but induces both hippocampal dependent and hippocampal independent complex changes in the functioning of the neural circuits, implementing taste aversion learning.
Wallis, Lisa J; Virányi, Zsófia; Müller, Corsin A; Serisier, Samuel; Huber, Ludwig; Range, Friederike
In laboratory dogs, aging leads to a decline in various cognitive domains such as learning, memory and behavioural flexibility. However, much less is known about aging in pet dogs, i.e. dogs that are exposed to different home environments by their caregivers. We used tasks on a touchscreen apparatus to detect differences in various cognitive functions across pet Border Collies aged from 5 months to 13 years. Ninety-five dogs were divided into five age groups and tested in four tasks: (1) underwater photo versus drawing discrimination, (2) clip art picture discrimination, (3) inferential reasoning by exclusion and (4) a memory test with a retention interval of 6 months. The tasks were designed to test three cognitive abilities: visual discrimination learning, logical reasoning and memory. The total number of sessions to reach criterion and the number of correction trials needed in the two discrimination tasks were compared across age groups. The results showed that both measures increased linearly with age, with dogs aged over 13 years displaying slower learning and reduced flexibility in comparison to younger dogs. Inferential reasoning ability increased with age, but less than 10 % of dogs showed patterns of choice consistent with inference by exclusion. No age effect was found in the long-term memory test. In conclusion, the discrimination learning tests used are suitable to detect cognitive aging in pet dogs, which can serve as a basis for comparison to help diagnose cognition-related problems and as a tool to assist with the development of treatments to delay cognitive decline.
Fristrup, Tine; Grut, Sara
In this article, we develop a framework that demonstrates how older adults need to develop diverse capabilities in relation to their educational life course through engagements in Nordic museums, archives and street art activities. We discuss how European museums have taken up UNESCO’s approach...... to lifelong learning as a way to conceptualise activities for older adults’ in museums, as we emphasise an approach to adult education for active ageing articulated as ‘lifelong learning for active ageing’. To illustrate this framing, we outline a number of activities taken from publications, cultural sites...... and conferences in which we have been involved over the last decade in the context of the Nordic Centre of Heritage Learning and Creativity in Östersund, Sweden. We argue that lifelong learning for active ageing in cultural heritage institutions can contribute to the development of older adults’ civic...
Cuddy, Lola L; Sikka, Ritu; Vanstone, Ashley
In striking contrast to the difficulties with new learning and episodic memories in aging and especially in Alzheimer's disease (AD), musical long-term memories appear to be largely preserved. Evidence for spared musical memories in aging and AD is reviewed here. New data involve the development of a Musical Engagement Questionnaire especially designed for use with AD patients. The questionnaire assesses behavioral responses to music and is answered by the care partner. Current results show that, despite cognitive loss, persons with mild to moderate AD preserve musical engagement and music seeking. Familiar music evokes personal autobiographical memories for healthy younger and older adults as well and for those with mild to moderate AD. It is argued that music is a prime candidate for being a stimulus for cognitive stimulation because musical memories and associated emotions may be readily evoked; that is, they are strong and do not need to be repaired. Working with and through music as a resource may enhance social and communication functions.
Kurimoto, Hiroaki; Nishijo, Hisao; Uwano, Teruko; Yamaguchi, Hidetoshi; Zhong, Yong-Mei; Kawanishi, Kazuko; Ono, Taketoshi
Previously we reported that oral application of red ginseng significantly ameliorated learning deficits in aged rats and young rats with hippocampal lesions. In the present study, we investigated the effects of the nonsaponin fraction of red ginseng on learning deficits in aged rats in behavioral studies and those on long-term potentiation (LTP) in the hippocampal CA3 subfield in young rats in electrophysiological studies. In the behavioral studies, three groups of rats [aged rats with and without oral administration of the nonsaponin fraction of red ginseng and young rats] were tested with the three types of spatial-learning task [distance movement task (DMT), random-reward place search task (RRPST), and place-learning task (PLT)] in a circular open field. The results in the DMT and RRPST indicated that motivational and motor activity was not significantly different among the three groups of rats. However, performance of the aged rats without nonsaponin was significantly impaired in the PLT when compared with the young rats. Treatment with nonsaponin significantly ameliorated deficits in place-navigation learning in the aged rats in the PLT. In the electrophysiological studies, effects of nonsaponin on the LTP in the CA3 subfield of the hippocampal slices were investigated in vitro. Pretreatment with nonsaponin significantly augmented the increase in population spike amplitudes in the CA3 subfield after LTP induction. These results suggest that the nonsaponin fraction of red ginseng contains important substances to improve learning and memory in aged rats and that this amelioration by nonsaponin might be attributed partly to augmentation of LTP in the CA3 subfield.
Nancy J. Roizen
Full Text Available We report three cases of asymptomatic celiac disease identified in children with Down syndrome after being screened at around twenty-four months of age. These cases raise the question as to what age is screening for celiac disease indicated in a child with Down syndrome and no symptoms.
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...
Tolstrup, Janne S; Hvidtfeldt, Ulla Arthur; Flachs, Esben Meulengracht;
Objectives. We investigated associations of smoking and coronary heart disease (CHD) by age. Methods. Data came from the Pooling Project on Diet and Coronary Heart Disease (8 prospective studies, 1974-1996; n = 192 067 women and 74 720 men, aged 40-89 years). Results. During follow-up, 4326 cases...
McNealy, Kristin; Mazziotta, John C; Dapretto, Mirella
Very little is known about the neural underpinnings of language learning across the lifespan and how these might be modified by maturational and experiential factors. Building on behavioral research highlighting the importance of early word segmentation (i.e. the detection of word boundaries in continuous speech) for subsequent language learning, here we characterize developmental changes in brain activity as this process occurs online, using data collected in a mixed cross-sectional and longitudinal design. One hundred and fifty-six participants, ranging from age 5 to adulthood, underwent functional magnetic resonance imaging (fMRI) while listening to three novel streams of continuous speech, which contained either strong statistical regularities, strong statistical regularities and speech cues, or weak statistical regularities providing minimal cues to word boundaries. All age groups displayed significant signal increases over time in temporal cortices for the streams with high statistical regularities; however, we observed a significant right-to-left shift in the laterality of these learning-related increases with age. Interestingly, only the 5- to 10-year-old children displayed significant signal increases for the stream with low statistical regularities, suggesting an age-related decrease in sensitivity to more subtle statistical cues. Further, in a sample of 78 10-year-olds, we examined the impact of proficiency in a second language and level of pubertal development on learning-related signal increases, showing that the brain regions involved in language learning are influenced by both experiential and maturational factors.
Christine E. Moran
Full Text Available American students typically attend kindergarten at the chronological age (CA of five and currently with the implementation of Common Core State Standards, there are expectations that children learn how to read in order to meet these academic standards, despite whether or not they are developmentally ready. This mixed methods study examined age and environmental factors that relate to reading with 83 children from the ages of 4–6½ years. The relationship between developmental age (DA via the Gesell Developmental Observation-Revised and early literacy learning via Marie’s Clay observational tool, Concepts About Print (CAP, were explored. The purpose of the study was to highlight the need for better alignment of educational policies and practices as they relate to child development and to promote more effective synthesis between discoveries in the field of neuroscience about how children learn and what is known about child DAs and stages. The findings revealed a statistically significant relationship between a child’s DA and early literacy learning as measured by the CAP. The descriptive statistics revealed that the DA of the children in this study was younger than their CA. Furthermore, a child’s DA was found to be the strongest predictor of early literacy learning.
C. O'Callaghan; A.A. Moustafa; S. de Wit; J.M. Shine; T.W. Robbins; S.J.G. Lewis; M. Hornberger
Discrimination learning deficits in Parkinson's disease (PD) have been well-established. Using both behavioral patient studies and computational approaches, these deficits have typically been attributed to dopamine imbalance across the basal ganglia. However, this explanation of impaired learning in
Shaun K Morris
Full Text Available BACKGROUND: Little is known about the causes of death in children in India after age five years. The objective of this study is to provide the first ever direct national and sub-national estimates of infectious disease mortality in Indian children aged 5 to 14 years. METHODS: A verbal autopsy based assessment of 3 855 deaths is children aged 5 to 14 years from a nationally representative survey of deaths occurring in 2001-03 in 1.1 million homes in India. RESULTS: Infectious diseases accounted for 58% of all deaths among children aged 5 to 14 years. About 18% of deaths were due to diarrheal diseases, 10% due to pneumonia, 8% due to central nervous system infections, 4% due to measles, and 12% due to other infectious diseases. Nationally, in 2005 about 59 000 and 34 000 children aged 5 to 14 years died from diarrheal diseases and pneumonia, corresponding to mortality of 24.1 and 13.9 per 100 000 respectively. Mortality was nearly 50% higher in girls than in boys for both diarrheal diseases and pneumonia. CONCLUSIONS: Approximately 60% of all deaths in this age group are due to infectious diseases and nearly half of these deaths are due to diarrheal diseases and pneumonia. Mortality in this age group from infectious diseases, and diarrhea in particular, is much higher than previously estimated.
Pascual, A C; Martín-Moreno, A M; Giusto, N M; de Ceballos, M L; Pasquaré, S J
Anandamide is an endocannabinoid involved in several physiological functions including neuroprotection. Anandamide is synthesized on demand and its endogenous level is regulated through its degradation, where fatty acid amide hydrolase plays a major role. The aim of this study was to characterize anandamide breakdown in physiological and pathological aging and its regulation by CB1 and CB2 receptor agonists. Fatty acid amide hydrolase activity was analyzed in an independent cohort of human cortical membrane samples from control and Alzheimer's disease patients, and in membrane and synaptosomes from adult and aged rat cerebral cortex. Our results demonstrate that fatty acid amide hydrolase activity decreases in the frontal cortex from human patients with Alzheimer's disease and this effect is mimicked by Aβ(1-40) peptide. This activity increases and decreases in aged rat cerebrocortical membranes and synaptosomes, respectively. Also, while the presence of JWH-133, a CB2 selective agonist, slightly increases anandamide hydrolysis in human controls, it decreases this activity in adults and aged rat cerebrocortical membranes and synaptosomes. In the presence of WIN55,212-2, a mixed CB1/CB2 agonist, anandamide hydrolysis increases in Alzheimer's disease patients but decreases in human controls as well as in adult and aged rat cerebrocortical membranes and synaptosomes. Although a similar profile is observed in fatty acid amide hydrolase activity between aged rat synaptic endings and human Alzheimer's disease brains, it is differently modulated by CB1/CB2 agonists. This modulation leads to a reduced availability of anandamide in Alzheimer's disease and to an increased availability of this endocannabinoid in aging.
Okuniewski Jan E.
Full Text Available The research investigates the German language learning motivations of Polish secondary school students and university students. Questionnaire data were collected from 247 students (126 from secondary school and 121 from university. The aim of this research was to examine the relationships among language attitudes, instrumental, cultural interest, integrative, L2 self and motivated learning. The results show the existence of age and gender difference in variables under consideration. Relationships were found between age and gender to the motivational attitudes: older and female students had a more integrative attitude than younger and mail students and experienced more intensive motivation.
Alexei A Podtelezhnikov
Full Text Available Alzheimer's disease (AD is a complex neurodegenerative disorder that diverges from the process of normal brain aging by unknown mechanisms. We analyzed the global structure of age- and disease-dependent gene expression patterns in three regions from more than 600 brains. Gene expression variation could be almost completely explained by four transcriptional biomarkers that we named BioAge (biological age, Alz (Alzheimer, Inflame (inflammation, and NdStress (neurodegenerative stress. BioAge captures the first principal component of variation and includes genes statistically associated with neuronal loss, glial activation, and lipid metabolism. Normally BioAge increases with chronological age, but in AD it is prematurely expressed as if some of the subjects were 140 years old. A component of BioAge, Lipa, contains the AD risk factor APOE and reflects an apparent early disturbance in lipid metabolism. The rate of biological aging in AD patients, which cannot be explained by BioAge, is associated instead with NdStress, which includes genes related to protein folding and metabolism. Inflame, comprised of inflammatory cytokines and microglial genes, is broadly activated and appears early in the disease process. In contrast, the disease-specific biomarker Alz was selectively present only in the affected areas of the AD brain, appears later in pathogenesis, and is enriched in genes associated with the signaling and cell adhesion changes during the epithelial to mesenchymal (EMT transition. Together these biomarkers provide detailed description of the aging process and its contribution to Alzheimer's disease progression.
Full Text Available Cognitive dysfunction is a feature of Parkinson’s Disease (PD. Some cognitive functions are impaired by dopaminergic medications prescribed to address the movement symptoms that typify PD. Learning appears to be the cognitive function most frequently worsened by dopaminergic therapy. However, this result could reflect either impairments in learning (i.e., acquisition of associations among stimuli, responses, and outcomes or deficits in performance based on learning (e.g., selecting responses. We sought to clarify the specific effects of dopaminergic medication on i stimulus-response association learning from outcome feedback and ii response selection based on learning in PD. We tested 28 PD patients on and/or off dopaminergic medication along with 32 healthy, age- and education-matched controls. In Session 1, participants learned to associate abstract images with specific key-press responses through trial and error via outcome feedback. In Session 2, participants provided specific responses to abstract images learned in Session 1, without feedback, precluding new feedback-based learning. By separating Sessions 1 and 2 by 24 hours, we could distinguish the effect of dopaminergic medication on a feedback-based learning and response selection processes in Session 1 versus on b response selection processes without feedback-based learning in Session 2, when performance accuracy across sessions was comparable. PD patients on medication learned stimulus-response associations more poorly than PD patients off medication and controls. Medication did not influence decision performance in Session 2 in the absence of feedback-based learning. We confirm that dopaminergic therapy impairs feedback-based learning in PD, discounting an alternative explanation that warranted consideration.
Spampinato, C; Palazzo, S; Giordano, D; Aldinucci, M; Leonardi, R
Skeletal bone age assessment is a common clinical practice to investigate endocrinology, genetic and growth disorders in children. It is generally performed by radiological examination of the left hand by using either the Greulich and Pyle (G&P) method or the Tanner-Whitehouse (TW) one. However, both clinical procedures show several limitations, from the examination effort of radiologists to (most importantly) significant intra- and inter-operator variability. To address these problems, several automated approaches (especially relying on the TW method) have been proposed; nevertheless, none of them has been proved able to generalize to different races, age ranges and genders. In this paper, we propose and test several deep learning approaches to assess skeletal bone age automatically; the results showed an average discrepancy between manual and automatic evaluation of about 0.8 years, which is state-of-the-art performance. Furthermore, this is the first automated skeletal bone age assessment work tested on a public dataset and for all age ranges, races and genders, for which the source code is available, thus representing an exhaustive baseline for future research in the field. Beside the specific application scenario, this paper aims at providing answers to more general questions about deep learning on medical images: from the comparison between deep-learned features and manually-crafted ones, to the usage of deep-learning methods trained on general imagery for medical problems, to how to train a CNN with few images.
Koenig, O; Thomas-Antérion, C; Laurent, B
Two experiments were carried out to study procedural learning in Parkinson's disease (PD) patients. In Experiment 1, ten patients and their normal controls participated in a classical mirror reading task and in an inverted reading task where word-stimuli made of non inverted letters had to be processed from right to left (e.g., ygoloruen). In both tasks, reading times for new stimuli were compared to reading times for stimuli that repeated over blocks. Although PD patients and their controls exhibited learning for repeated words in both tasks, PD patients did not respond faster with practice for new words in the inverted reading task. In Experiment 2, PD patients and their controls were presented with an original dot counting task in which participants were asked to process a horizontal series of black and white dots from right to left and to indicate whether a dot that had been designated by a number at the beginning of each trial was black or white. Results showed that PD patients, in contrast to controls, did not exhibit learning in this task. Results are discussed in terms of the cognitive components involved in these tasks. It is suggested that PD patients are impaired in the acquisition of a right-to-left visual scanning skill that could be studied directly in Experiment 2.
Full Text Available Inbred mice provide a unique tool to study aging populations because of the genetic homogeneity within an inbred strain, their short life span, and the tools for analysis which are available. A large-scale longitudinal and cross-sectional aging study was conducted on 30 inbred strains to determine, using histopathology, the type and diversity of diseases mice develop as they age. These data provide tools that when linked with modern in silico genetic mapping tools, can begin to unravel the complex genetics of many of the common chronic diseases associated with aging in humans and other mammals. In addition, novel disease models were discovered in some strains, such as rhabdomyosarcoma in old A/J mice, to diseases affecting many but not all strains including pseudoxanthoma elasticum, pulmonary adenoma, alopecia areata, and many others. This extensive data set is now available online and provides a useful tool to help better understand strain-specific background diseases that can complicate interpretation of genetically engineered mice and other manipulatable mouse studies that utilize these strains.
Díaz-López, M Del Pilar; López-Liria, Remedios; Aguilar-Parra, José M; Padilla-Góngora, David
The purpose of this study is to describe the creation and implementation of an ICT education program for the elderly in various Active Participation Centers in Almería (Spain), assessing its impact on quality of life. From a randomized sample of 200 individuals over the age of 55. Results reveal a high degree of participant satisfaction (76.6 %), as well as improvements in quality of life as compared to the control group after the 3 month program health factor: p = 0.004; leisure and activity factor: p = 0.001; Satisfaction with Life Factor: p higher scores) and gender (the males). This study may serve to facilitate similar works that promotes on-going education in different locations and across the lifespan.
Amedeo Lonardo; Paola Loria; Silvia Lombardini; Federica Scaglioni; Stefano Ballestri; Anna Maria Verrone; Marco Bertolotti; Lucia Carulli; Dorval Ganazzi; Nicola Carulli
AIM: To evaluate carotid intima-media thickening (IMT)and plaques, gallstone disease (GD) and fatty liver (FL)as a function of age.METHODS: In 449 subjects, FL and carotid disease were assessed ultrasonographically. In a subgroup of 65/449 patients with non-alcoholic fatty liver disease (NAFLD), carotid disease, GD and associated factors were determined.RESULTS: FL of unspecified etiology was more common in younger and GD in older individuals. FL subjects had an increased prevalence of IMT and a decreased prevalence of plaques and manifested carotid disease earlier. Plaques were more common in subjects with GD.Age was an independent predictor of carotid disease outcome and FL was a protective factor for plaques. In NAFLD, there was an inverse correlation between body weight and age and the latter independently predicted carotid findings.CONCLUSION: Cardiovascular risk in patients with FL and NAFLD needs to be assessed as a function of age and body weight.
Frank, Steven A.
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.
Accumulating evidence suggests that aging is associated with dysregulated immune and inflammatory responses. Investigation into the cellular and molecular mechanisms underlying this phenomenon suggests that an up-regulated cyclooxygenase (COX)-2 expression, and resulting increase in production of pr...
Rapp, P R; Kansky, M T; Eichenbaum, H
Young and aged rhesus monkeys were tested on 2 versions of a transitive inference task measuring learning and memory for hierarchical relationships. Animals initially acquired 4 object discrimination problems arranged such that the relationship between the stimuli followed the hierarchy A > B > C > D > E. The second version of the task was similar but involved a series of 7 objects. Learning and memory for the hierarchical relationships were evaluated during probe trials in which novel pairs of nonadjacent items (e.g., B and D) were presented for a response. Standard task accuracy measures failed to distinguish young and aged subjects at any point in training. In contrast, response latency effects that are indicative of relational information processing in young monkeys were entirely absent in aged subjects. The findings highlight the value of a relational memory framework for establishing a detailed neuropsychological account of cognitive aging in the monkey.
Lee, J-M; Ramos, E M; Lee, J-H;
Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat. The length of the normal CAG repeat allele has been reported also to influence age at onset, in interaction with the expanded allele. Due to profound...... implications for disease mechanism and modification, we tested whether the normal allele, interaction between the expanded and normal alleles, or presence of a second expanded allele affects age at onset of HD motor signs....
Yang, Zhihong; Ming, Xiu-Fen
The continuing increase in the prevalence of obesity and metabolic disorders such as type-II diabetes and an accelerating aging population globally will remain the major contributors to cardiovascular mortality and morbidity in the 21st century. It is well known that aging is highly associated with metabolic and cardiovascular diseases. Growing evidence also shows that obesity and metabolic diseases accelerate aging process. Studies in experimental animal models demonstrate similarity of meta...
Kallery, Maria; Loupidou, Thomais
The present study examines how the overall cognitive achievements in science of the younger children in a class where the students work in small multi-age groups are influenced by the number of older children in the groups. The context of the study was early-years education. The study has two parts: The first part involved classes attended by…
Full Text Available Age related macular degeneration (AMD is retinal degenerative disorder which starts with the progression of age. Metabolism plays important role in initiation of ageing related diseases. The cholesterol metabolism components and their oxidized products like 7-ketocholesterol have been shown impact on RPE cells degeneration. These molecules can initiate the mitochondrial apoptotic process and also influenced the complements factors and expression of angiogenic proteins like VEGF etc. In this review we have suggested that AMD is ageing disorder not developmental which has been substantiated with disrupted cholesterol metabolism as described in several age related degenerative diseases.
Huber, Jessica E.; Darling, Meghan; Francis, Elaine J.; Zhang, Dabao
Purpose: The present study examines the impact of typical aging and Parkinson's disease (PD) on the relationship among breath pausing, syntax, and punctuation. Method: Thirty young adults, 25 typically aging older adults, and 15 individuals with PD participated. Fifteen participants were age- and sex-matched to the individuals with PD.…
Arciuli, Joanne; Simpson, Ian C
It is possible that statistical learning (SL) plays a role in almost every mental activity. Indeed, research on SL has grown rapidly over recent decades in an effort to better understand perception and cognition. Yet, there remain gaps in our understanding of how SL operates, in particular with regard to its (im)mutability. Here, we investigated whether participant-related variables (such as age) and task-related variables (such as speed of stimulus presentation) affect visual statistical learning (VSL) in typically developing children. We tested 183 participants ranging in age from 5 to 12 years and compared three speeds of presentation (using stimulus durations of 800, 400 and 200 msecs). A multiple regression analysis revealed significant effects of both age and speed of presentation - after attention during familiarization and gender had been taken into consideration. VSL followed a developmental trajectory whereby learning increased with age. The amount of learning increased with longer presentation times (as shown by Turk-Browne, Jungé & Scholl, 2005, in their study of adults). There was no significant interaction between the two variables. These findings assist in elucidating the nature of statistical learning itself. While statistical learning can be observed in very young children and at remarkably fast presentation times, participant- and task-related variables do impact upon this type of learning. The findings reported here may serve to enhance our understanding of individual differences in the cognitive and perceptual processes that are thought to rely, at least in part, on SL (e.g. language processing and object recognition).
Students in every nation of the world learn new and difficult material in ways that are often similar and, at the same time, different from the way other students of the same age, gender, race, religion, culture, and nationality prefer to learn. The purpose of this study was to identify and compare the preferred learning-style characteristics of…
Qiu, Anqi; Lee, Annie; Tan, Mingzhen; Chung, Moo K
We propose a new analysis framework to utilize the full information of brain functional networks for computing the mean of a set of brain functional networks and embedding brain functional networks into a low-dimensional space in which traditional regression and classification analyses can be easily employed. For this, we first represent the brain functional network by a symmetric positive matrix computed using sparse inverse covariance estimation. We then impose a Log-Euclidean Riemannian manifold structure on brain functional networks whose norm gives a convenient and practical way to define a mean. Finally, based on the fact that the computation of linear operations can be done in the tangent space of this Riemannian manifold, we adopt Locally Linear Embedding (LLE) to the Log-Euclidean Riemannian manifold space in order to embed the brain functional networks into a low-dimensional space. We show that the integration of the Log-Euclidean manifold with LLE provides more efficient and succinct representation of the functional network and facilitates regression analysis, such as ridge regression, on the brain functional network to more accurately predict age when compared to that of the Euclidean space of functional networks with LLE. Interestingly, using the Log-Euclidean analysis framework, we demonstrate the integration and segregation of cortical-subcortical networks as well as among the salience, executive, and emotional networks across lifespan.
Cascio, Caterina; Deidda, Irene; Russo, Domenica; Guarneri, Patrizia
These last two decades have seen an explosion of clinical and epidemiological research, and basic research devoted to envisage the influence of gender and hormonal fluctuations in the retina/ocular diseases. Particular attention has been paid to age-related disorders because of the overlap of endocrine and neuronal dysfunction with aging. Hormonal withdrawal has been considered among risk factors for diseases such as glaucoma, diabetic retinopathy and age-related macular disease (AMD), as well as, for Alzheimer's disease, Parkinson's disease, or other neurodegenerative disorders. Sex hormones and aging have been also suggested to drive the incidence of ocular surface diseases such as dry eye and cataract. Hormone therapy has been approached in several clinical trials. The discovery that the retina is another CNS tissue synthesizing neurosteroids, among which neuroactive steroids, has favored these studies. However, the puzzling data emerged from clinical, epidemiological and experimental studies have added several dimensions of complexity; the current landscape is inherently limited to the weak information on the influence and interdependence of endocrine, paracrine and autocrine regulation in the retina, but also in the brain. Focusing on the estrogenic retina, we here review our knowledge on local 17β-oestradiol (E2) synthesis from cholesterol-based neurosteroidogenic path and testosterone aromatization, and presence of estrogen receptors (ERα and ERβ). The first cholesterol-limiting step and the final aromatase-limiting step are discussed as possible check-points of retinal functional/dysfunctional E2. Possible E2 neuroprotection is commented as a group of experimental evidence on excitotoxic and oxidative retinal paradigms, and models of retinal neurodegenerative diseases, such as glaucoma, diabetic retinopathy and AMD. These findings may provide a framework to support clinical studies, although further basic research is needed.
Prenatal undernutrition is associated with increased incidence of obesity, heart disease, diabetes. Effects of pre- and post-natal undernutrition on nervous system function in middle-aged and aging male SD rats were examined. Intrauterine growth retardation (IUGR) was induced by ...
Brookmeyer, R; Gray, S
Projections of the incidence and prevalence of disease are important for public health planning. This paper describes methods for projecting the incidence and prevalence of a chronic disease in ageing populations. The approach uses age-specific disease incidence rates together with assumptions about survival to reconstruct disease prevalence. The methods can be used to evaluate the potential impact of public health interventions that may prevent disease or prolong survival. We used the methods to project the future prevalence of Alzheimer's disease in the United States. We found that the prevalence of Alzheimer's disease will nearly quadruple over the next 50 years. Although projections of the absolute prevalence are sensitive to assumptions about the age-specific incidence rates of disease, the proportionate growth is relatively insensitive. The increase in prevalence results from the ageing of the U.S. population. In order to perform the calculations, we have assembled U.S. Census population projections and U.S. mortality rates into computer software that is available from the authors at www.jhsph.edu/Departments/Biostats/software.h tml.
Poupart, Annick; Trudeau, Natacha; Sutton, Ann
The use of augmentative and alternative communication systems based on graphic symbols requires children to learn to combine symbols to convey utterances. The current study investigated how children without disabilities aged 4 to 6 years (n = 74) performed on a simple sentence (subject-verb and subject-verb-object) transposition task (i.e., spoken…
Montero, Lidia; Serrano, Raquel; Llanes, Àngels
This study examines the effects of foreign language learning context (three-month study-abroad; versus "at-home" instruction) and age (10-11-year-old children versus university students) on the development of effective foreign language communication strategies (CS) in monologue production. Participants (N = 95) were all Spanish/Catalan…
This study analysed the gradual emergence of the teaching/learning process by examining theory of mind (ToM) acquisition and age effects in the preschool period. We observed five dyads performing a jigsaw task drawn from a previous study. Three stages were identified. In the first one, the teacher focuses on the execution of her/his own task…
Presents 30 adult Chinese immigrant women's accounts of their experiences with, and perceptions of, learning English as a Second Language in Canada. Results from interviews with two age groups of adult women reveal the complexity of adult second-language acquisition, which involves factors pertaining both to the learners, and to the social context…
van Dijk, Henk; Mulder, Theo; Hermens, Hermie J.
This study addressed the interaction between age and the informational content of feedback on learning an isometric force-production task. Healthy men and women (30 young adults: 20 to 35 years; 30 older adults: 55 to 70 years) were randomly assigned to a certain type of feedback: knowledge of resul
Alnajar, F.; Shan, C.; Gevers, T.; Geusebroek, J.M.
In this paper we propose to adopt a learning-based encoding method for age estimation under unconstrained imaging conditions. A similar approach [Cao et al., 2010] is applied to face recognition in real-life face images. However, the feature vectors are encoded in hard manner i.e. each feature vecto
Wark, Stuart; Canon-Vanry, Miranda; Ryan, Peta; Hussain, Rafat; Knox, Marie; Edwards, Meaghan; Parmenter, Marie; Parmenter, Trevor; Janicki, Matthew; Leggatt-Cook, Chez
Background: Access to support services in rural areas is known to be problematic both in Australia, and in other countries around the world, but the majority of research on the population of people ageing with learning disability has so far focussed on metropolitan residents. The authors report about select aspects of the lived experience of older…
Stephens, Samuel A.
Summer learning experiences for school-age children can be provided in a variety of ways and settings, including summer school programs (often remedial), community-based programs (often a continuation of afterschool programs), and home-based programs (in which families are provided with information and resources to encourage reading, often run by…
Successful aging and lifelong learning are value-laden concepts that are culturally determined. To this effect, people with different value systems and cultural backgrounds may perceive and understand these two concepts differently, resulting in different definitions and conceptualizations by people in diverse cultural contexts. There have been…
DeKeyser, Robert M.
The effect of age of acquisition on ultimate attainment in second language learning has been a controversial topic for years. After providing a very brief overview of the ideas that are at the core of the controversy, I discuss the two main reasons why these issues are so controversial: conceptual misunderstandings and methodological difficulties.…
Pace-Schott, Edward F; Spencer, Rebecca M C
Improvements in motor sequence learning come about via goal-based learning of the sequence of visual stimuli and muscle-based learning of the sequence of movement responses. In young adults, consolidation of goal-based learning is observed after intervals of sleep but not following wake, whereas consolidation of muscle-based learning is greater following intervals with wake compared to sleep. While the benefit of sleep on motor sequence learning has been shown to decline with age, how sleep contributes to consolidation of goal-based vs. muscle-based learning in older adults (OA) has not been disentangled. We trained young (n = 62) and older (n = 50) adults on a motor sequence learning task and re-tested learning following 12 h intervals containing overnight sleep or daytime wake. To probe consolidation of goal-based learning of the sequence, half of the participants were re-tested in a configuration in which the stimulus sequence was the same but, due to a shift in stimulus-response mapping, the movement response sequence differed. To probe consolidation of muscle-based learning, the remaining participants were tested in a configuration in which the stimulus sequence was novel, but now the sequence of movements used for responding was unchanged. In young adults, there was a significant condition (goal-based vs. muscle-based learning) by interval (sleep vs. wake) interaction, F(1,58) = 6.58, p = 0.013: goal-based learning tended to be greater following sleep compared to wake, t(29) = 1.47, p = 0.072. Conversely, muscle-based learning was greater following wake than sleep, t(29) = 2.11, p = 0.021. Unlike young adults, this interaction was not significant in OA, F(1,46) = 0.04, p = 0.84, nor was there a main effect of interval, F(1,46) = 1.14, p = 0.29. Thus, OA do not preferentially consolidate sequence learning over wake or sleep.
H. Wu (Haiyan)
markdownabstract__Abstract__ Genomic instability is recognized as one of the primary mechanisms that lead to organismal aging, and leads to progeria when developing in an accelerated pace due to defective genomic maintenance systems, such as nucleotide excision repair, in humans and mouse models of
1.Theoretical Background 1.1 Age and second language acquisition Age issue has been one of the most controversial questions in second language acquisition since the birth of Critical Period Hypothesis ( CPH).Actually,the notion of critical period was firstly offered by Penfield & Robert ( 1959 ) by claiming that “for the purposes of learning languages,the human brain becomes progressively stiff and rigid after the age of nine” (Penfield and Roberts 1959,p.236 ) and that ”when languages are taken up for the first time in the second decade of life,it is difficult to achieve a good result because it is unphysiological” ( Penfield and Roberts 1959,p.255).Definitely,they insisted on that it is a causal relationship between age and language proficiency,it is a conceptualization of maturational constraints that is associated with an all - or - nothing - effect and abrupt onsets and offsets of the period,among other things.( Hylstenstam & Ambrahamson,2001 ).Later,Lenneberg( 1967) postulated Critical Period Hypothesis,which states that there is a neurological based critical period,”from roughly two years of age to puberty”,beyond which completely mastery of a language,first or second,is no longer possible.That's because the end of critical period was marked by “ termination of a state of organizational plasticity linked with lateralization of function” (p.176).
Sandhu, Manpreet K; Cohen, Alice
Availability of hydroxyurea (HU) coupled with early therapeutic interventions has increased the life expectancy of patients with sickle cell disease. Hence, the sickle cell community needs to be aware of common diseases of aging that survivors are predisposed to. We chose to investigate the sickle cell disease-related complications as well as non sickle cell disease-related medical problems of aging in 45 sickle cell patients over the age of 40 years. The most frequent chronic complications of sickle cell disease were elevated tricuspid regurgitant jet velocity on echocardiogram, chronic renal disease, iron overload and leg ulcers. Medical co-morbidities in this patient group included hypertension, diabetes mellitus (DM), hypercholesterolemia and symptomatic coronary artery disease (CAD). In our cohort, only 38.0% had a primary care doctor. Only 11.0% over age 50 had a screening colonoscopy, and of the women, 42.0% had a screening mammography. Medical co-morbidities and lack of health maintenance in older sickle cell patients are likely to impact overall health and mortality. Aging patients with sickle cell disease may benefit from a primary medical home for age appropriate comprehensive health care.
Muriel T N Panouillères
Full Text Available Procedural learning is a form of memory where people implicitly acquire a skill through repeated practice. People with Parkinson's disease (PD have been found to acquire motor adaptation, a form of motor procedural learning, similarly to healthy older adults but they have deficits in long-term retention. A similar pattern of normal learning on initial exposure with a deficit in retention seen on subsequent days has also been seen in mirror-reading, a form of non-motor procedural learning. It is a well-studied fact that disrupting sleep will impair the consolidation of procedural memories. Given the prevalence of sleep disturbances in PD, the lack of retention on following days seen in these studies could simply be a side effect of this well-known symptom of PD. Because of this, we wondered whether people with PD would present with deficits in the short-term retention of a non-motor procedural learning task, when the test of retention was done the same day as the initial exposure. The aim of the present study was then to investigate acquisition and retention in the immediate short term of cognitive procedural learning using the mirror-reading task in people with PD. This task involved two conditions: one where triads of mirror-inverted words were always new that allowed assessing the learning of mirror-reading skill and another one where some of the triads were presented repeatedly during the experiment that allowed assessing the word-specific learning. People with PD both ON and OFF their normal medication were compared to healthy older adults and young adults. Participants were re-tested 50 minutes break after initial exposure to probe for short-term retention. The results of this study show that all groups of participants acquired and retained the two skills (mirror-reading and word-specific similarly. These results suggest that neither healthy ageing nor the degeneration within the basal ganglia that occurs in PD does affect the mechanisms
Panouillères, Muriel T N; Tofaris, George K; Brown, Peter; Jenkinson, Ned
Procedural learning is a form of memory where people implicitly acquire a skill through repeated practice. People with Parkinson's disease (PD) have been found to acquire motor adaptation, a form of motor procedural learning, similarly to healthy older adults but they have deficits in long-term retention. A similar pattern of normal learning on initial exposure with a deficit in retention seen on subsequent days has also been seen in mirror-reading, a form of non-motor procedural learning. It is a well-studied fact that disrupting sleep will impair the consolidation of procedural memories. Given the prevalence of sleep disturbances in PD, the lack of retention on following days seen in these studies could simply be a side effect of this well-known symptom of PD. Because of this, we wondered whether people with PD would present with deficits in the short-term retention of a non-motor procedural learning task, when the test of retention was done the same day as the initial exposure. The aim of the present study was then to investigate acquisition and retention in the immediate short term of cognitive procedural learning using the mirror-reading task in people with PD. This task involved two conditions: one where triads of mirror-inverted words were always new that allowed assessing the learning of mirror-reading skill and another one where some of the triads were presented repeatedly during the experiment that allowed assessing the word-specific learning. People with PD both ON and OFF their normal medication were compared to healthy older adults and young adults. Participants were re-tested 50 minutes break after initial exposure to probe for short-term retention. The results of this study show that all groups of participants acquired and retained the two skills (mirror-reading and word-specific) similarly. These results suggest that neither healthy ageing nor the degeneration within the basal ganglia that occurs in PD does affect the mechanisms that underpin the
Meng, Guofeng; Zhong, Xiaoyan; Mei, Hongkang
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.
Squarza, Chiara; Picciolini, Odoardo; Gardon, Laura; Giannì, Maria L; Murru, Alessandra; Gangi, Silvana; Cortinovis, Ivan; Milani, Silvano; Mosca, Fabio
At school age extremely low birth weight (ELBW) and extremely low gestational age (ELGAN) children are more likely to show Learning Disabilities (LDs) and difficulties in emotional regulation. The aim of this study was to investigate the incidence of LDs at school age and to detect neurodevelopmental indicators of risk for LDs at preschool ages in a cohort of ELBW/ELGAN children with broadly average intelligence. All consecutively newborns 2001-2006 admitted to the same Institution entered the study. Inclusion criteria were BW disabilities, genetic abnormalities, and/or a Developmental Quotient below normal limits (learning disabilities at school age was investigated through a parent-report questionnaire at children's age range 9-10 years. Neurodevelopmental profiles were assessed through the Griffiths Mental Development Scales at 1 and 2 years of corrected age and at 3, 4, 5, and 6 years of chronological age and were analyzed comparing two groups of children: those with LDs and those without. At school age 24 on 102 (23.5%) of our ELBW/ELGAN children met criteria for LDs in one or more areas, with 70.8% comorbidity with emotional/attention difficulties. Children with LDs scored significantly lower in the Griffiths Locomotor and Language subscales at 2 years of corrected age and in the Personal-social, Performance and Practical Reasoning subscales at 5 years of chronological age. Our findings suggest that, among the early developmental indicators of adverse school outcome, there is a poor motor experimentation, language delay, and personal-social immaturity. Cognitive rigidity and poor ability to manage practical situations also affect academic attainment. Timely detection of these early indicators of risk is crucial to assist the transition to school.
Taler, Vanessa; Chertkow, Howard; Saumier, Daniel
Alzheimer's disease (AD) subjects, healthy elderly, and young adults interpreted a series of novel noun-noun expressions composed of familiar object words. Subjects interpreted each item by selecting one of three possible definitions: a definition in which the referents of each noun were associated together in a particular context (e.g., rabbit…
Diniz, Daniel G; Foro, César A R; Rego, Carla M D; Gloria, David A; de Oliveira, Fabio R R; Paes, Juliana M P; de Sousa, Aline A; Tokuhashi, Tatyana P; Trindade, Lucas S; Turiel, Maíra C P; Vasconcelos, Erick G R; Torres, João B; Cunnigham, Colm; Perry, Victor H; Vasconcelos, Pedro F da Costa; Diniz, Cristovam W P
Environmental and age-related effects on learning and memory were analysed and compared with changes observed in astrocyte laminar distribution in the dentate gyrus. Aged (20 months) and young (6 months) adult female albino Swiss mice were housed from weaning either in impoverished conditions or in enriched conditions, and tested for episodic-like and water maze spatial memories. After these behavioral tests, brain hippocampal sections were immunolabeled for glial fibrillary acid protein to identify astrocytes. The effects of environmental enrichment on episodic-like memory were not dependent on age, and may protect water maze spatial learning and memory from declines induced by aging or impoverished environment. In the dentate gyrus, the number of astrocytes increased with both aging and enriched environment in the molecular layer, increased only with aging in the polymorphic layer, and was unchanged in the granular layer. We suggest that long-term experience-induced glial plasticity by enriched environment may represent at least part of the circuitry groundwork for improvements in behavioral performance in the aged mice brain.
Krueger, Konstanze; Farmer, Kate; Heinze, Jürgen
Social learning is said to meet the demands of complex environments in which individuals compete over resources and cooperate to share resources. Horses (Equus caballus) were thought to lack social learning skills because they feed on homogenously distributed resources with few reasons for conflict. However, the horse's social environment is complex, which raises the possibility that its capacity for social transfer of feeding behaviour has been underestimated. We conducted a social learning experiment using 30 socially kept horses of different ages. Five horses, one from each group, were chosen as demonstrators, and the remaining 25 horses were designated observers. Observers from each group were allowed to watch their group demonstrator opening a feeding apparatus. We found that young, low-ranking and more exploratory horses learned by observing older members of their own group, and the older the horse, the more slowly it appeared to learn. Social learning may be an adaptive specialisation to the social environment. Older animals may avoid the potential costs of acquiring complex and potentially disadvantageous feeding behaviours from younger group members. We argue that horses show social learning in the context of their social ecology and that research procedures must take such contexts into account. Misconceptions about the horse's sociality may have hampered earlier studies.
Yah-Se K Abada
Full Text Available Chorea and psychiatric symptoms are hallmarks of Huntington disease (HD, a neurodegenerative disorder, genetically characterized by the presence of expanded CAG repeats (>35 in the Huntingtin (HTT gene. HD patients present psychiatric symptoms prior to the onset of motor symptoms and we recently found a similar emergence of non motor and motor deficits in BACHD rats carrying the human full length mutated HTT (97 CAG-CAA repeats. We evaluated cognitive performance in reversal learning and associative memory tests in different age cohorts of BACHD rats. Male wild type (WT and transgenic (TG rats between 2 and 12 months of age were tested. Learning and strategy shifting were assessed in a cross-maze test. Associative memory was evaluated in different fear conditioning paradigms (context, delay and trace. The possible confound of a fear conditioning phenotype by altered sensitivity to a 'painful' stimulus was assessed in a flinch-jump test. In the cross maze, 6 months old TG rats showed a mild impairment in reversal learning. In the fear conditioning tasks, 4, 6 and 12 months old TG rats showed a marked reduction in contextual fear conditioning. In addition, TG rats showed impaired delay conditioning (9 months and trace fear conditioning (3 months. This phenotype was unlikely to be affected by a change in 'pain' sensitivity as WT and TG rats showed no difference in their threshold response in the flinch-jump test. Our results suggest that BACHD rats have a profound associative memory deficit and, possibly, a deficit in reversal learning as assessed in a cross maze task. The time course for the emergence of these symptoms (i.e., before the occurrence of motor symptoms in this rat model for HD appears similar to the time course in patients. These data suggest that BACHD rats may be a useful model for preclinical drug discovery.
Full Text Available A total of 300 patients from first day of life to 17 years of age were analysed for pattern of skin disorders. School going children formed majority (41.3% of cases followed by preschool children (32%. Infections formed the commonest disorder (31 % followed by eczemas (24%, papulosquamous disorders (12%, infestation (8.6% and urticaria (5.3% while vitiligo, acne vulgaris, alopecia areata and genodermatoses were seen in 2.7% cases each.
The recent editorial in this journal by Bull et al. ("Connecting Informal and Formal Learning Experiences in the Age of Participatory Media" Vol 8, Iss 2) discussed the challenges of bridging formal learning practices and informal learning opportunities within the context of today's Web-enhanced world. In this commentary, Christine…
Full Text Available Objective: To evaluate the concomitant systemic diseases with postmenopausal osteoporosis and to investigate the points to be considered in treatment approach of patients with osteoporosis. Materials and Methods: The study included 110 female patients admitted to our clinic and followed up after postmenopausal osteoporosis diagnosis. Besides the demographic data; the concomitant diseases of the patients such as hypertension, hypo-hyperthyroidism, diabetes mellitus, Alzheimer’s disease, malignancy, osteoarthritis, gastrointestinal system diseases, chronic obstructive pulmonary disease (COPD- asthma and depression were also recorded. Results: The mean age of the patients included in our study was 65.9±9.8 years. When the concomitant systemic diseases were examined; 40 patients had hypertension, 32 patients had osteoarthritis, 24 patients had gastrointestinal tract problems, 22 patients had thyroid disease, 21 patients had depression, 15 patients had hyperlipidemia, 12 patients had diabetes mellitus, 10 patients had COPD - asthma, 7 patients had cardiac diseases, 5 patients had malignancy and 2 patients had Alzheimer disease. Conclusion: Osteoporosis is a common disease in the geriatric population. As a chronic disease with an increasing incidence with aging; it can cause many health problems, prevalently pathological bone fractures, in our country and all over the world. Constitutively, prophylaxis of osteoporosis should be the first step. Because systemic diseases with increasing incidence with aging may affect the severity of osteoporosis and impair the treatment; it is important for both clinicians and the society to have sufficient information about osteoporosis.
Romuladus E. Azuine, DrPH, RN
Full Text Available WITH over 4,500 deaths and counting, and new cases identified in two developed countries that are struggling and faltering in their handling of the epidemic, the 2014 Ebola Virus Disease (EVD epidemic is unlike any of its kind ever encountered. The ability of some poor, resource-limited, developing countries in sub-Saharan Africa to efficiently handle the epidemic within their shores provides some lessons learned for the global health community. Among others, the 2014 EVD epidemic teaches us that it is time to put the “P” back in public and population health around the world. The global health community must support a sustainable strategy to mitigate Ebola virus and other epidemics both within and outside their shores, even after the cameras are gone. Ebola virus must not be called the disease of the poor and developing world.
Hammer, Anne Sofie; Andersen, Thomas Holmen; Eriksen, Thomas
bone loss and tooth loss. There was a high prevalence of destructive periodontal disease among blue mink included in this study. Mild to moderate periodontal disease (defined by less than 50% alveolar bone loss related to 1 or more teeth) affected 73.7% of young mink (age = 7 mo) and 67.9% of older...... animals (age &GE; 19 mo). Severe periodontal disease (defined by more than 50% bone loss related to one or more teeth) was not detected in mink aged 7 mo, but affected 15.3% of mink aged 19 mo and 39.6% of mink aged 31 mo. The positive relationship between age and periodontal disease was statistically...... in the mink was related to and possibly caused by destructive periodontal disease. There was no significant difference in the prevalence of periodontal disease between the 2 genotypes and age was found to be the only statistical predictor of poor production results (P < 0.01) in blue mink....
Full Text Available Julia M Sidorova,1,* Raymond J Monnat Jr,1,2,* 1Department of Pathology, 2Department of Genome Sciences, University of Washington, Seattle, WA, USA *The authors contributed equally to this review Abstract: DNA helicases use the energy of ATP hydrolysis to disrupt DNA base pairing and displace proteins from DNA in order to facilitate replication, recombination, transcription, and repair. This article focuses on the human RECQ helicases, five DNA-dependent helicases that play key roles in cellular physiology and disease. Loss of function of three RECQ helicases causes the cancer predisposition syndromes Bloom syndrome, Werner syndrome, and Rothmund–Thomson and related syndromes. We summarize recent work on these syndromes and proteins and discuss disease pathogenesis in light of RECQ helicase biochemical activities and in vivo functions. Keywords: ATP-dependent DNA helicase, Bloom syndrome, Werner syndrome, Rothmund–Thomson syndrome, DNA replication, DNA repair, genetic instability, cancer predisposition syndrome
Knutson, Mitchell D; Leeuwenburgh, Christiaan
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.
Klein, Denise; Mok, Kelvin; Chen, Jen-Kai; Watkins, Kate E
We examined the effects of learning a second language (L2) on brain structure. Cortical thickness was measured in the MRI datasets of 22 monolinguals and 66 bilinguals. Some bilingual subjects had learned both languages simultaneously (0-3 years) while some had learned their L2 after achieving proficiency in their first language during either early (4-7 years) or late childhood (8-13 years). Later acquisition of L2 was associated with significantly thicker cortex in the left inferior frontal gyrus (IFG) and thinner cortex in the right IFG. These effects were seen in the group comparisons of monolinguals, simultaneous bilinguals and early and late bilinguals. Within the bilingual group, significant correlations between age of acquisition of L2 and cortical thickness were seen in the same regions: cortical thickness correlated with age of acquisition positively in the left IFG and negatively in the right IFG. Interestingly, the monolinguals and simultaneous bilinguals did not differ in cortical thickness in any region. Our results show that learning a second language after gaining proficiency in the first language modifies brain structure in an age-dependent manner whereas simultaneous acquisition of two languages has no additional effect on brain development.
Backhaus, W; Kempe, S; Hummel, F C
There is extensive evidence for positive effects of sleep on motor learning in young individuals; however, the effects of sleep on motor learning in people with stroke and in healthy older individuals are not well understood. The aim of this systematic review was to quantify the association between sleep and procedural memory performance - a marker for motor learning - in healthy older people and people with stroke. After searches in PubMed, Medline and Embase fourteen studies, including 44 subjects after stroke and 339 healthy older participants were included. Overall, sleep was found to enhance motor performance in people after stroke in comparison to an equivalent time of wakefulness. In addition, although evidence is limited, sleep only enhanced motor performance in people after stroke and not in age-matched healthy older adults. In older adults the effect of a sleep intervention did - in general - not differ from equivalent periods of wakefulness. Tasks with whole hand or whole body movements could show significant changes. The results suggest a delayed retention effect after longer breaks including sleep, hinting towards a changed learning strategy as a result of aging. Current evidence for sleep dependent learning in people after stroke is promising, however sparse.
Lorenzi, Marco; Pennec, Xavier; Frisoni, Giovanni B; Ayache, Nicholas
The morphology observed in the brains of patients affected by Alzheimer's disease (AD) is a combination of different biological processes, such as normal aging and the pathological matter loss specific to AD. The ability to differentiate between these biological factors is fundamental to reliably evaluate pathological AD-related structural changes, especially in the earliest phase of the disease, at prodromal and preclinical stages. Here we propose a method based on non-linear image registration to estimate and analyze from observed brain morphologies the relative contributions from aging and pathology. In particular, we first define a longitudinal model of the brain's normal aging process from serial T1-weight magnetic resonance imaging scans of 65 healthy participants. The longitudinal model is then used as a reference for the cross-sectional analysis. Given a new brain image, we then estimate its anatomical age relative to the aging model; this is defined as a morphological age shift with respect to the average age of the healthy population at baseline. Finally, we define the specific morphological process as the remainder of the observed anatomy after the removal of the estimated normal aging process. Experimental results from 105 healthy participants, 110 subjects with mild cognitive impairment (MCI), 86 with MCI converted to AD, and 134 AD patients provide a novel description of the anatomical changes observed across the AD time span: normal aging, normal aging at risk, conversion to MCI, and the latest stages of AD. More advanced AD stages are associated with an increased morphological age shift in the brain and with strong disease-specific morphological changes affecting mainly ventricles, temporal poles, the entorhinal cortex, and hippocampi. Our model shows that AD is characterized by localized disease-specific brain changes as well as by an accelerated global aging process. This method may thus represent a more precise instrument to identify potential
Leong, Pou K; Chen, Na; Ko, Kam M
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.
U.S. Department of Health & Human Services — The National Institute on Aging Genetics of Alzheimer's Disease Data Storage Site (NIAGADS) is a national genetics data repository facilitating access to genotypic...
Smith, C D; Walton, A; Loveland, A D; Umberger, G H; Kryscio, R J; Gash, D M
Using an automated test panel, age-associated declines in learning, remembering and performing a novel visuomotor task were assessed in 497 normal adults ranging from 18 to 95 years old. As predicted, task performance times slowed with increasing age in the cross-sectional portion of the study. However in the subsequent longitudinal study, while motor learning was significantly slower in adults over 62 years old, motor memory was pristinely preserved in normal adults from 18 to 95 years old. When tested 2 years after the first training session and without intervening rehearsal, mean performance times were retained and continued to improve by 10% in young adults and 13% in aged adults, reflecting long lasting preservation of motor memories. While the maximum lifetime of an unpracticed, novel motor memory in humans is not known, the present study suggests that new motor memories can be retained for at least 2 years without rehearsal in normal aged adults. This age-resistant component of motor memory stands in contrast to the well-known decrements in other motor and cognitive processes with human aging.
Eppinger, Ben; Hämmerer, Dorothea; Li, Shu-Chen
In this paper, we review the current literature to highlight relations between age-associated declines in dopaminergic and serotonergic neuromodulation and adult age differences in adaptive goal-directed behavior. Specifically, we focus on evidence suggesting that deficits in neuromodulation contribute to older adults' behavioral disadvantages in learning and decision making. These deficits are particularly pronounced when reward information is uncertain or the task context requires flexible adaptations to changing stimulus-reward contingencies. Moreover, emerging evidence points to age-related differences in the sensitivity to rewarding and aversive outcomes during learning and decision making if the acquisition of behavior critically depends on outcome processing. These age-related asymmetries in outcome valuation may be explained by age differences in the interplay of dopaminergic and serotonergic neuromodulation. This hypothesis is based on recent neurocomputational and psychopharmacological approaches, which suggest that dopamine and serotonin serve opponent roles in regulating the balance between approach behavior and inhibitory control. Studying adaptive regulation of behavior across the adult life span may shed new light on how the aging brain changes functionally in response to its diminishing resources.
Chauvel, Guillaume; Maquestiaux, François; Hartley, Alan A; Joubert, Sven; Didierjean, André; Masters, Rich S W
Can motor learning be equivalent in younger and older adults? To address this question, 48 younger (M = 23.5 years) and 48 older (M = 65.0 years) participants learned to perform a golf-putting task in two different motor learning situations: one that resulted in infrequent errors or one that resulted in frequent errors. The results demonstrated that infrequent-error learning predominantly relied on nondeclarative, automatic memory processes whereas frequent-error learning predominantly relied on declarative, effortful memory processes: After learning, infrequent-error learners verbalized fewer strategies than frequent-error learners; at transfer, a concurrent, attention-demanding secondary task (tone counting) left motor performance of infrequent-error learners unaffected but impaired that of frequent-error learners. The results showed age-equivalent motor performance in infrequent-error learning but age deficits in frequent-error learning. Motor performance of frequent-error learners required more attention with age, as evidenced by an age deficit on the attention-demanding secondary task. The disappearance of age effects when nondeclarative, automatic memory processes predominated suggests that these processes are preserved with age and are available even early in motor learning.
van de Vijver, Irene; Ridderinkhof, K Richard; Harsay, Helga; Reneman, Liesbeth; Cavanagh, James F; Buitenweg, Jessika I V; Cohen, Michael X
Reinforcement learning (RL) is supported by a network of striatal and frontal cortical structures that are connected through white-matter fiber bundles. With age, the integrity of these white-matter connections declines. The role of structural frontostriatal connectivity in individual and age-related differences in RL is unclear, although local white-matter density and diffusivity have been linked to individual differences in RL. Here we show that frontostriatal tract counts in young human adults (aged 18-28), as assessed noninvasively with diffusion-weighted magnetic resonance imaging and probabilistic tractography, positively predicted individual differences in RL when learning was difficult (70% valid feedback). In older adults (aged 63-87), in contrast, learning under both easy (90% valid feedback) and difficult conditions was predicted by tract counts in the same frontostriatal network. Furthermore, network-level analyses showed a double dissociation between the task-relevant networks in young and older adults, suggesting that older adults relied on different frontostriatal networks than young adults to obtain the same task performance. These results highlight the importance of successful information integration across striatal and frontal regions during RL, especially with variable outcomes.
O. M. Drapkina
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.
Jakobsen, Marianne Uhre; Overvad, Kim; Dyerberg, Jørn
In a 16-year follow-up study (ending in 1998) of 3,686 Danish men and women aged 30–71 years at recruitment, the association between energy intake from dietary fat and the risk of coronary heart disease was evaluated while assessing the possible modifying role of gender and age. In the models used...... not significantly. In conclusion, the present study suggests that coronary heart disease risk relates to both the quantity and the quality of dietary fats....
Jaime M. Ross; Lars Olson; Giuseppe Coppotelli
Mitochondrial dysfunction and impairment of the ubiquitin proteasome system have been described as two hallmarks of the ageing process. Additionally, both systems have been implicated in the etiopathogenesis of many age-related diseases, particularly neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease. Interestingly, these two systems are closely interconnected, with the ubiquitin proteasome system maintaining mitochondrial homeostasis by regulating organelle dynamics, t...
Dennis, Nancy A; Cabeza, Roberto
Abundant research finds that in young adults explicit learning (EL) is more dependent on the medial temporal lobes (MTL) whereas implicit learning (IL) is more dependent on the striatum. Using fMRI, we investigated age differences in each task and whether this differentiation is preserved in older adults. Results indicated that, while young recruited the MTL for EL and striatum for IL, both activations were significantly reduced in older adults. Additionally, results indicated that older adults recruited the MTL for IL, and this activation was significantly greater in older compared with young adults. A significant Task × Age interaction was found in both regions-with young preferentially recruiting the MTL for EL and striatum for IL, and older adults showing no preferential recruit for either task. Finally, young adults demonstrated significant negative correlations between activity in the striatum and MTL during both the EL and IL tasks. These correlations were attenuated in older adults. Taken together results support dedifferentiation in aging across memory systems.
Dennis, Nancy A.; Cabeza, Roberto
Abundant research finds that in young adults explicit learning (EL) is more dependent on the medial temporal lobes (MTL) whereas implicit learning (IL) is more dependent on the striatum. Using fMRI, we investigated age differences in each task and whether this differentiation is preserved in older adults. Results indicated that, while young recruited the MTL for EL and striatum for IL, both activations were significantly reduced in older adults. Additionally, results indicated that older adults recruited the MTL for IL, and this activation was significantly greater in older compared to young adults. A significant Task × Age interaction was found in both regions– with young preferentially recruiting the MTL for EL and striatum for IL, and older adults showing no preferential recruit for either task. Finally, young adults demonstrated significant negative correlations between activity in the striatum and MTL during both the EL and IL tasks. These correlations were attenuated in older adults. Taken together results support dedifferentiation in aging across memory systems. PMID:20471139
Mohamed Saber Numan
Full Text Available Atmospheric pollution-induced cellular oxidative stress is probably one of the pathogenic mechanisms involved in most of the common autophagy-mediated aging diseases, including neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS, Alzheimer’s, disease, as well as Paget’s disease of bone with or without frontotemporal dementia and inclusion body myopathy. Oxidative stress has serious damaging effects on the cellular contents: DNA, RNA, cellular proteins, and cellular organelles. Autophagy has a pivotal role in recycling these damaged non-functional organelles and misfolded or unfolded proteins. In this paper, we highlight, through a narrative review of the literature, that when autophagy processes are impaired during aging, in presence of cumulative air pollution-induced cellular oxidative stress and due to a direct effect on air pollutant, autophagy-mediated aging diseases may occur.
Full Text Available Background: Research in children with learning difficulties indicates high comorbidity with both behavioral/psycho-emotional disorders. It has been suggested that learning disorders constitute the outcome of a continuum of mental disorders which accompany the individual through life. Aim: The main aim of the current research was to point out and document the clinical profile of children with learning difficulties and co-occuring behavioral/psycho-emotional disorders and to establish a pattern between the two. Methodology: Observational study was conducted on a random group of 54 children with learning disorders of varying ages ranging from 6-11years old. The research was conducted at George Papanikolaou General hospital, mental health care sector of children and adolescents in Thessaloniki. Results: Findings indicated associations between learning difficulties and a wide spectrum of behavioral and psycho-emotional disorders such as hyperactivity, conduct and emotional disorders, childhood emotional disorders, disturbed social functionality. Conclusions: In conclusion, the above findings confirm the degree of comorbidity between learning difficulties and mental disorders in childhood.
Peng, Yan; Huang, Sha; Cheng, Biao; Nie, Xiaohu; Enhe, Jirigala; Feng, Changjiang; Fu, Xiaobing
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.
Reeves, Pauline J. [Radiology Department, Arrowe Park Hospital, Upton, Wirral CH49 5EP (United Kingdom)]. E-mail: firstname.lastname@example.org
This report uses case study methodology to examine the issue of long-term care of the elderly in the United Kingdom, including where that care should take place. The report will examine the difficulties inherent in maintaining independent living for the elderly (in particular the danger and cost of falls). The case study presented is that of an elderly female patient who had suffered from chronic rheumatoid arthritis for over 10 years. She was admitted to hospital several times from December 2003 to January 2004. The discussion of her case is set in the context of the sociology of ageing; long-term care of the elderly and the UK National Service Frameworks, of which standard six relates to falls in the elderly. The report will also consider the problems in deciding whether it is necessary to terminate independent living for an individual.
Full Text Available Down syndrome (DS individuals present increased risk for Alzheimer disease (AD neuropathology and AD-type dementia. Here, we investigated the use of green tea extracts containing (--epigallocatechin-3-gallate (EGCG, as co-adjuvant to enhance the effects of environmental enrichment (EE in Ts65Dn mice, a segmental trisomy model of DS that partially mimics DS/AD pathology, at the age of initiation of cognitive decline. Classical repeated measures ANOVA showed that combined EE-EGCG treatment was more efficient than EE or EGCG alone to improve specific spatial learning related variables. Using principal component analysis (PCA we found that several spatial learning parameters contributed similarly to a first PC and explained a large proportion of the variance among groups, thus representing a composite learning measure. This PC1 revealed that EGCG or EE alone had no significant effect. However, combined EE-EGCG significantly ameliorated learning alterations of middle age Ts65Dn mice. Interestingly, PCA revealed an increased variability along learning sessions with good and poor learners in Ts65Dn, and this stratification did not disappear upon treatments. Our results suggest that combining EE and EGCG represents a viable therapeutic approach for amelioration of age-related cognitive decline in DS, although its efficacy may vary across individuals.
Messinis, Lambros; Nasios, Grigorios; Mougias, Antonios; Politis, Antonis; Zampakis, Petros; Tsiamaki, Eirini; Malefaki, Sonia; Gourzis, Phillipos; Papathanasopoulos, Panagiotis
Rey's Auditory Verbal Learning Test (RAVLT) is a widely used neuropsychological test to assess episodic memory. In the present study we sought to establish normative and discriminative validity data for the RAVLT in the elderly population using previously adapted learning lists for the Greek adult population. We administered the test to 258 cognitively healthy elderly participants, aged 60-89 years, and two patient groups (192 with amnestic mild cognitive impairment, aMCI, and 65 with Alzheimer's disease, AD). From the statistical analyses, we found that age and education contributed significantly to most trials of the RAVLT, whereas the influence of gender was not significant. Younger elderly participants with higher education outperformed the older elderly with lower education levels. Moreover, both clinical groups performed significantly worse on most RAVLT trials and composite measures than matched cognitively healthy controls. Furthermore, the AD group performed more poorly than the aMCI group on most RAVLT variables. Receiver operating characteristic (ROC) analysis was used to examine the utility of the RAVLT trials to discriminate cognitively healthy controls from aMCI and AD patients. Area under the curve (AUC), an index of effect size, showed that most of the RAVLT measures (individual and composite) included in this study adequately differentiated between the performance of healthy elders and aMCI/AD patients. We also provide cutoff scores in discriminating cognitively healthy controls from aMCI and AD patients, based on the sensitivity and specificity of the prescribed scores. Moreover, we present age- and education-specific normative data for individual and composite scores for the Greek adapted RAVLT in elderly subjects aged between 60 and 89 years for use in clinical and research settings.
Hallan, Stein I.; Matsushita, Kunihiro; Sang, Yingying; Mahmoodi, Bakhtawar K.; Black, Corri; Ishani, Areef; Kleefstra, Nanne; Naimark, David; Roderick, Paul; Tonelli, Marcello; Wetzels, Jack F. M.; Astor, Brad C.; Gansevoort, Ron T.; Levin, Adeera; Wen, Chi-Pang; Coresh, Josef
Context Chronic kidney disease (CKD) is prevalent in older individuals, but the risk implications of low estimated glomerular filtration rate (eGFR) and high albuminuria across the full age range are controversial. Objective To evaluate possible effect modification (interaction) by age of the associ
Cuetos, Fernando; Herrera, Elena; Ellis, Andrew W.
Studies of word production in patients with Alzheimer's disease have identified the age of acquisition of words as an important predictor of retention or loss, with early acquired words remaining accessible for longer than later acquired words. If, as proposed by current theories, effects of age of acquisition reflect the involvement of semantic…
Wu, Y.-H.; Swaab, D.F.
Circadian rhythm disturbances, such as sleep disorders, are frequently seen in aging and are even more pronounced in Alzheimer's disease (AD). Alterations in the biological clock, the suprachiasmatic nucleus (SCN), and the pineal gland during aging and AD are considered to be the biological basis fo
Nørremølle, A; Budtz-Jørgensen, E; Fenger, K
Huntington disease (HD) is caused by an expanded CAG repeat sequence in the HD gene. Although the age at onset is correlated to the CAG repeat length, this correlation only explains approximately half of the variation in onset age. Less variation between siblings indicates that the variation is, ...
Bode, C.; Taal, E.; Westerhof, G.J.; Gessel, van L.; Laar, van de M.A.F.J.
Objectives: Self-perceptions of aging have been shown to predict mental and physical health and even longevity. This study examined the aging perceptions of patients with rheumatic disease and compared them with the general Dutch population. Methods: Consecutive patients visiting a rheumatology cl
Shetty, Ashok K.
Comprehending the mechanisms underlying the pathophysiology of aging and Alzheimer’s disease has immense value for developing strategies that promote successful aging and prevent or cure Alzheimer’s disease. The first issue of the new journal, “Aging & Disease” comprises articles that discuss the current knowledge pertaining to changes in reelin signaling in normal & pathological forms of aging, memory and neurogenesis in Aging & Alzheimer’s disease, the efficacy of a non-steroidal anti-infla...
Kaza, K.E.; Diercks, D.R.; Holland, J.W.; Choi, S.U. [and others
The purpose of this generic aging lessons learned (GALL) review is to provide a systematic review of plant aging information in order to assess materials and component aging issues related to continued operation and license renewal of operating reactors. Literature on mechanical, structural, and thermal-hydraulic components and systems reviewed consisted of 97 Nuclear Plant Aging Research (NPAR) reports, 23 NRC Generic Letters, 154 Information Notices, 29 Licensee Event Reports (LERs), 4 Bulletins, and 9 Nuclear Management and Resources Council Industry Reports (NUMARC IRs) and literature on electrical components and systems reviewed consisted of 66 NPAR reports, 8 NRC Generic Letters, 111 Information Notices, 53 LERs, 1 Bulletin, and 1 NUMARC IR. More than 550 documents were reviewed. The results of these reviews were systematized using a standardized GALL tabular format and standardized definitions of aging-related degradation mechanisms and effects. The tables are included in volume s 1 and 2 of this report. A computerized data base has also been developed for all review tables and can be used to expedite the search for desired information on structures, components, and relevant aging effects. A survey of the GALL tables reveals that all ongoing significant component aging issues are currently being addressed by the regulatory process. However, the aging of what are termed passive components has been highlighted for continued scrutiny. This document is Volume 1, consisting of the executive summary, summary and observations, and an appendix listing the GALL literature review tables.
Balistreri, Carmela Rita; Madonna, Rosalinda; Melino, Gerry; Caruso, Calogero
Notch signaling is an evolutionarily conserved pathway, which is fundamental for the development of all tissues, organs and systems of human body. Recently, a considerable and still growing number of studies have highlighted the contribution of Notch signaling in various pathological processes of the adult life, such as age-related diseases. In particular, the Notch pathway has emerged as major player in the maintenance of tissue specific homeostasis, through the control of proliferation, migration, phenotypes and functions of tissue cells, as well as in the cross-talk between inflammatory cells and the innate immune system, and in onset of inflammatory age-related diseases. However, until now there is a confounding evidence about the related mechanisms. Here, we discuss mechanisms through which Notch signaling acts in a very complex network of pathways, where it seems to have the crucial role of hub. Thus, we stress the possibility to use Notch pathway, the related molecules and pathways constituting this network, both as innovative (predictive, diagnostic and prognostic) biomarkers and targets for personalised treatments for age-related diseases.
Baker, Rodney R.
Examined preferences of 275 health care providers for working with elderly patients exhibiting symptoms of normal aging or diseases. In comparing descriptions of two hospitalized patients, physicians, nurses and social workers expressed a preference for working with patients with disease symptoms, raising concerns about geriatric care. (JAC)
Full Text Available Few studies have examined the risk factors of serious psychological distress (SPD and behavioral factors for heart disease separately stratified as young (18–44 years, middle aged (45–64 years, and elderly (65 years or older. A total of 3,540 adults with heart disease and 37,703 controls were selected from the 2005 California Health Interview Survey. Data were weighted to be representative and adjusted for potential undercoverage and nonresponse biases. Multiple logistic regression models were used to estimate the associations of the factors with heart disease at different ages. The prevalence of SPD was 8% in cases and 4% in controls, respectively. For young adults, SPD and higher federal poverty level (FPL were associated with an increased risk of heart disease while for middle-aged adults, SPD, past smoking, lack of physical activity, obesity, male, and unemployment were associated with an increased risk of heart disease. In addition, SPD, past smoking, lack of physical activity, obesity, male, unemployment, White, and lower FPL were associated with an increased risk of heart disease in elderly. Our findings indicate that risk factors for heart disease vary across all ages. Intervention strategies that target risk reduction of heart disease may be tailored accordingly.
R. van Leeuwen (Redmer)
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
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.
James, Lori E; Fogler, Kethera A; Tauber, Sarah K
No previous research has tested whether the specific age-related deficit in learning face-name associations that has been identified using recall tasks also occurs for recognition memory measures. Young and older participants saw pictures of unfamiliar people with a name and an occupation for each person, and were tested on a matching (in Experiment 1) or multiple-choice (in Experiment 2) recognition memory test. For both recognition measures, the pattern of effects was the same as that obtained using a recall measure: More face-occupation associations were remembered than face-name associations, young adults remembered more associated information than older adults overall, and older adults had disproportionately poorer memory for face-name associations. Findings implicate age-related difficulty in forming and retrieving the association between the face and the name as the primary cause of obtained deficits in previous name learning studies.
Carrasco, Carmen; Vicens, Paloma; Redolat, Rosa
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.
Tsui, David; van der Kooy, Derek
We utilized olfactory-mediated chemotaxis in Caenorhabditis elegans to examine the effect of aging on information processing and animal behavior. Wild-type (N2) young adults (day 4) initially approach and eventually avoid a point source of benzaldehyde. Aged adult animals (day 7) showed a stronger initial approach and a delayed avoidance to benzaldehyde compared with young adults. This delayed avoidance is due to an increased attraction rather than a decreased avoidance to benzaldehyde because (1) aged odr-3 mutants that are defective in odor attraction showed no delayed benzaldehyde avoidance, and (2) the delay in avoidance was also observed with another attractant diacetyl, but not the repellent octanol. Interestingly, the stronger expression of attractive behavior was only observed at benzaldehyde concentrations of 1% or higher. When worms were grown on nonbacterial growth media instead of Escherichia coli, thus removing the contingency between odors released from the food and the food itself, the increase in attraction to benzaldehyde disappeared. The increased attraction recovered after reinitiating the odor-food contingency by returning animals to E. coli food or supplementing axenic media with benzaldehyde. Moreover, serotonin-deficient mutants showed a deficit in the age-enhanced attraction. These results suggest that the increased attraction to benzaldehyde in aged worms is (1) serotonin mediated, (2) specific to high concentration of odorants, and (3) dependent on a learned association of odor metabolites with the presence of food. We propose that associative learning may selectively modify pathways at or downstream from a low-affinity olfactory receptor.
Bates, Anthony William
The book examines the underlying principles that guide effective teaching in an age when all of us, and in particular the students we are teaching, are using technology. A framework for making decisions about your teaching is provided, while understanding that every subject is different, and every instructor has something unique and special to bring to their teaching.The book enables teachers and instructors to help students develop the knowledge and skills they will need in a digital age: not so much the IT skills, but the thinking and attitudes to learning that will bring them success.
Takashi eTarumi; Rong eZhang
Alzheimer disease (AD) and cerebrovascular disease often coexist with advanced age. Mounting evidence indicates that the presence of vascular disease and its risk factors increase the risk of AD, suggesting a potential overlap of the underlying pathophysiological mechanisms. In particular, atherosclerosis, endothelial dysfunction, and stiffening of central elastic arteries have been shown to associate with AD. Currently, there are no effective treatments for the cure and prevention of AD. Vas...
Barbur, John L; Konstantakopoulou, Evgenia
The purpose of this study was to obtain additional information about the health of the retina (HR) by measuring the rate of loss of chromatic sensitivity with decreasing light level. The HR(index) is introduced to separate the effects of normal aging from early stage disease. For normal subjects the HR(index is largely independent of age (r(2)~0.1), but ~11% of clinically normal, asymptomatic, older subjects exhibit values below the 2σ limit. The HR(index provides a single number that captures how light level affects chromatic sensitivity irrespective of age and can be used to screen for preclinical signs of retinal disease.
markdownabstractThe studies presented in this dissertation aimed to investigate whether observing or producing deictic gestures (i.e., pointing and tracing gestures to index a referent in space or a movement pathway), could facilitate memory and learning in children, young adults, and older adults. More specifically, regarding memory it was investigated whether the use of deictic gestures would improve performance on tasks targeting cognitive functions that are found to change with age (worki...
Cassandra A Adduri
Full Text Available BACKGROUND: Previous research has shown that individuals with Alzheimer's disease (AD develop visuospatial difficulties that affect their ability to mentally rotate objects. Surprisingly, the existing literature has generally ignored the impact of this mental rotation deficit on the ability of AD patients to recognize faces from different angles. Instead, the devastating loss of the ability to recognize friends and family members in AD has primarily been attributed to memory loss and agnosia in later stages of the disorder. The impact of AD on areas of the brain important for mental rotation should not be overlooked by face processing investigations -- even in early stages of the disorder. METHODOLOGY/PRINCIPAL FINDINGS: This study investigated the sensitivity of face processing in AD, young controls and older non-neurological controls to two changes of the stimuli -- a rotation in depth and an inversion. The control groups showed a systematic effect of depth rotation, with errors increasing with the angle of rotation, and with inversion. The majority of the AD group was not impaired when faces were presented upright and no transformation in depth was required, and were most accurate when all faces were presented in frontal views, but accuracy was severely impaired with any rotation or inversion. CONCLUSIONS/SIGNIFICANCE: These results suggest that with the onset of AD, mental rotation difficulties arise that affect the ability to recognize faces presented at different angles. The finding that a frontal view is "preferred" by these patients provides a valuable communication strategy for health care workers.
Full Text Available The ability to update associative memory is an important aspect of episodic memory and a critical skill for social adaptation. Previous research with younger adults suggests that emotional arousal alters brain mechanisms underlying memory updating; however, it is unclear whether this applies to older adults. Given that the ability to update associative information declines with age, it is important to understand how emotion modulates the brain processes underlying memory updating in older adults. The current study investigated this question using reversal learning tasks, where younger and older participants (age ranges 19-35 and 61-78 respectively learn a stimulus–outcome association and then update their response when contingencies change. We found that younger and older adults showed similar patterns of activation in the frontopolar OFC and the amygdala during emotional reversal learning. In contrast, when reversal learning did not involve emotion, older adults showed greater parietal cortex activity than did younger adults. Thus, younger and older adults show more similarities in brain activity during memory updating involving emotional stimuli than during memory updating not involving emotional stimuli.
Rostami, Hamid Reza; Ashayeri, Hassan
One of the prominent disturbances in Parkinson's disease (PD) is bradykinesia. We studied performance of hand-to-mouth reach reaction time (RT) in right-handed PD patients and nine age and sex matched healthy control subjects. Participants practiced hand-to-mouth reach skill in response to a visual stimulus, 120 times a day for a period of one week. Using Kinemetrix 3D Motion Analysis system, the effects of motor skill practice and learning retention were investigated. Pretest performance was compared with performances on the second and seventh day of the study, and also performance on fourteenth day with no further practice for one week. There was a significant reduction in the mean RT in the control group after one week of practice. In PD patients the reduction in the mean RT was significant between pretest and first test sessions (P lasting.
Fidelus, R K; Tsan, M F
A decline in tissue and serum of glutathione (GSH) content and GSH-metabolizing enzymes with age has been implicated in the increasing susceptibility to carcinogens, disease and drugs which occurs with advanced age. Immunological senescence has been directly associated with increased incidence of cancer and infection with age. The auto-immune diseases of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) demonstrate depressed T-cell function together with B-cell hyperactivity. In addition, RA and SLE are chronic inflammatory conditions which have been associated with low serum and erythrocyte GSH concentrations when compared to normal. We hypothesized that augmentation of intracellular GSH concentrations in lymphocytes may enhance immune function in depressed immune states. Our data, using murine animal models for ageing (C57BL/6J) and the RA/SLE-like auto-immune diseases of the MRL/lpr mouse, indicate that intracellular glutathione of splenic lymphocytes does not decline with age or with a chronic inflammatory auto-immune disease. In contrast, immune responsiveness in splenic lymphocytes does decline. We can, however, augment both intracellular GSH concentrations and the immune response of splenic lymphocytes from animals of all ages as well as in those animals with the SLE-like auto-immune disease.
Carnahan, H; Vandervoort, A A; Swanson, L R
This study examined whether older adults (mean age = 75.0 years) use summary knowledge of results (KR) to facilitate learning in a manner similar to that of young adults (mean age = 22.5 years). All subjects were required to learn a computer-key-pressing task in a specified goal time. During acquisition, subjects received either KR after every trial, or summary KR. All subjects then performed no-KR retention trials. In acquisition, KR after every trial facilitated timing accuracy for both the younger and older groups in comparison to the summary KR groups. The young subjects were equally variable in both KR practice groups. For older subjects summary KR facilitated more consistent performance. In retention, the summary groups were more accurate than those subjects who received KR after every trial. There were no accuracy or variability differences between the two age groups during retention. These results suggest that older adults are able to use summary KR to facilitate learning in a manner similar to that of young adults.
Langbehn, D R; Brinkman, R R; Falush, D; Paulsen, J S; Hayden, M R
Huntington's disease (HD) is a neurodegenerative disorder caused by an unstable CAG repeat. For patients at risk, participating in predictive testing and learning of having CAG expansion, a major unanswered question shifts from "Will I get HD?" to "When will it manifest?" Using the largest cohort of HD patients analyzed to date (2913 individuals from 40 centers worldwide), we developed a parametric survival model based on CAG repeat length to predict the probability of neurological disease onset (based on motor neurological symptoms rather than psychiatric onset) at different ages for individual patients. We provide estimated probabilities of onset associated with CAG repeats between 36 and 56 for individuals of any age with narrow confidence intervals. For example, our model predicts a 91% chance that a 40-year-old individual with 42 repeats will have onset by the age of 65, with a 95% confidence interval from 90 to 93%. This model also defines the variability in HD onset that is not attributable to CAG length and provides information concerning CAG-related penetrance rates.
Blackburn, Elizabeth H; Epel, Elissa S; Lin, Jue
Telomeres are the protective end-complexes at the termini of eukaryotic chromosomes. Telomere attrition can lead to potentially maladaptive cellular changes, block cell division, and interfere with tissue replenishment. Recent advances in the understanding of human disease processes have clarified the roles of telomere biology, especially in diseases of human aging and in some aging-related processes. Greater overall telomere attrition predicts mortality and aging-related diseases in inherited telomere syndrome patients, and also in general human cohorts. However, genetically caused variations in telomere maintenance either raise or lower risks and progression of cancers, in a highly cancer type-specific fashion. Telomere maintenance is determined by genetic factors and is also cumulatively shaped by nongenetic influences throughout human life; both can interact. These and other recent findings highlight both causal and potentiating roles for telomere attrition in human diseases.
Verwey, W.B.; Abrahamse, E.L.; Ruitenberg, M.F.L.; Jiménez, L.; Kleine, de E.
The present study examined whether middle-aged participants, like young adults, learn movement patterns by preparing and executing integrated sequence representations (i.e., motor chunks) that eliminate the need for external guidance of individual movements. Twenty-four middle-aged participants (age
Danese, Andrea; Moffitt, Terrie E.; Harrington, HonaLee; Milne, Barry J.; Polanczyk, Guilherme; Pariante, Carmine M.; Poulton, Richie; Caspi, Avshalom
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
Archibald, Lisa M D; Oram Cardy, Janis; Joanisse, Marc F; Ansari, Daniel
Dyscalculia, dyslexia, and specific language impairment (SLI) are relatively specific developmental learning disabilities in math, reading, and oral language, respectively, that occur in the context of average intellectual capacity and adequate environmental opportunities. Past research has been dominated by studies focused on single impairments despite the widespread recognition that overlapping and comorbid deficits are common. The present study took an epidemiological approach to study the learning profiles of a large school age sample in language, reading, and math. Both general learning profiles reflecting good or poor performance across measures and specific learning profiles involving either weak language, weak reading, weak math, or weak math and reading were observed. These latter four profiles characterized 70% of children with some evidence of a learning disability. Low scores in phonological short-term memory characterized clusters with a language-based weakness whereas low or variable phonological awareness was associated with the reading (but not language-based) weaknesses. The low math only group did not show these phonological deficits. These findings may suggest different etiologies for language-based deficits in language, reading, and math, reading-related impairments in reading and math, and isolated math disabilities.
Lisa M D Archibald
Full Text Available Dyscalculia, dyslexia, and specific language impairment (SLI are relatively specific developmental learning disabilities in math, reading, and oral language, respectively, that occur in the context of average intellectual capacity and adequate environmental opportunities. Past research has been dominated by studies focused on single impairments despite the widespread recognition that overlapping and comorbid deficits are common. The present study took an epidemiological approach to study the learning profiles of a large school age sample in language, reading, and math. Both general learning profiles reflecting good or poor performance across measures and specific learning profiles involving either weak language, weak reading, weak math, or weak math and reading were observed. These latter four profiles characterized 70% of children with some evidence of a learning disability. Low scores in phonological short-term memory characterized clusters with a language-based weakness whereas low or variable phonological awareness was associated with the reading (but not language-based weaknesses. The low math only group did not show these phonological deficits. These findings may suggest different etiologies for language-based deficits in language, reading, and math, reading-related impairments in reading and math, and isolated math disabilities.
Skolimowska, Justyna; Wesierska, Malgorzata; Lewandowska, Monika; Szymaszek, Aneta; Szelag, Elzbieta
This study focuses on age-related differences concerning two kinds of spatial memory assessed by: (1) Paired Associates Learning (PAL) test from the CANTAB and (2) a test of Real Idiothetic Memory (RIM) using real-life settings. Despite a clear age-related drop in PAL that is reported in existing studies, age-related differences in idiothetic navigation still remain unclear. In our study we tested 80 healthy volunteers classified according to their age into two groups, i.e. young (aged from 20 to 29 years of life; n=40; 20M/20F) and elderly (from 64 to 77 years; n=40; 20M/20F) healthy volunteers. They were asked in the PAL test to remember the spatial location of visual patterns presented on a computer screen, and in the RIM test to walk on the arena in darkness in order to find a cue place and then to return to the start/exit point. A white noise was switched on at entering the cue place and switched off at leaving this place. Elderly subjects indicated poorer performance than their younger counterparts on the PAL test, as evidenced by all tested outcome measures. In contrast, for the RIM test no clear age effect was evidenced. In both tests no gender effect was observed. A dissociation in age-related changes for these two tests indicates that visuo-spatial associative learning and idiothetic navigation may have different cognitive control which is probably rooted in an interplay of different brain structures.
Lassen, Aske Juul
Active ageing has increasingly become the ideal of how to live later life. Concepts of activity, participation and independence are central to how elderly see themselves and practice aging (Katz 2000). The elderly are encouraged and expected to stay active and independent. This is believed...... to be good for their quality of life, health, functionality and the economy (Sundhedsstyrelsen 2008, EC 2006, WHO 2002). At the same time active aging is inscribed into a general health care focus, which individualizes the responsibility for health and disease. This requires subjects ready to self......-care, by paying attention to the signals of the body and leading healthy lives (Rose 2001). However, active aging seems to contain an ambiguity in this aspect, as the practice of active aging is often a way for elderly to keep diseases at arm’s length, and not a way to sense the possible abnormalities in the body...
Reddy, P Hemachandra; Blackmon, Joan; Molinar-Lopez, Veronica; Ament, Clay; Manczak, Maria; Kandimalla, Ramesh; Yin, Xianglin; Pandey, Akhilesh; Kuruva, Chandra Sekhar; Wang, Rui; Fry, David; Osborn, Carrah; Stonum, Kathleen; Quesada, Kandi; Gonzales, Ruben; Boles, Annette
The Garrison Institute on Aging (GIA) is an established institute within Texas Tech University Health Sciences Center, whose mission is to promote healthy aging through cutting-edge research on Alzheimer's disease (AD) and other diseases of aging through innovative educational opportunities for students, clinicians, researchers, health care professionals, and the public. The GIA has multiple programs, including both research and education on healthy aging and AD, community outreach, caregiving, the Retired Senior Volunteer Program, Healthy Lubbock, the GIA Brain Bank, healthy aging seminars, research seminars, and collaborations and scholarships. The GIA programs connect basic and clinical researchers and health care professionals, and provide a unique environment to help our growing elderly population and patients with AD and their families.
Simon L Conti
Full Text Available As couples are increasingly delaying parenthood, the effect of the aging men and women on reproductive outcomes has been an area of increased interest. Advanced paternal age has been shown to independently affect the entire spectrum of male fertility as assessed by reductions in sperm quality and fertilization (both assisted and unassisted. Moreover, epidemiological data suggest that paternal age can lead to higher rates of adverse birth outcomes and congenital anomalies. Mounting evidence also suggests increased risk of specific pediatric and adult disease states ranging from cancer to behavioral traits. While disease states associated with advancing paternal age have been well described, consensus recommendations for neonatal screening have not been as widely implemented as have been with advanced maternal age.
Douaud, Gwenaëlle; Groves, Adrian R; Tamnes, Christian K; Westlye, Lars Tjelta; Duff, Eugene P; Engvig, Andreas; Walhovd, Kristine B; James, Anthony; Gass, Achim; Monsch, Andreas U; Matthews, Paul M; Fjell, Anders M; Smith, Stephen M; Johansen-Berg, Heidi
Several theories link processes of development and aging in humans. In neuroscience, one model posits for instance that healthy age-related brain degeneration mirrors development, with the areas of the brain thought to develop later also degenerating earlier. However, intrinsic evidence for such a link between healthy aging and development in brain structure remains elusive. Here, we show that a data-driven analysis of brain structural variation across 484 healthy participants (8-85 y) reveals a largely--but not only--transmodal network whose lifespan pattern of age-related change intrinsically supports this model of mirroring development and aging. We further demonstrate that this network of brain regions, which develops relatively late during adolescence and shows accelerated degeneration in old age compared with the rest of the brain, characterizes areas of heightened vulnerability to unhealthy developmental and aging processes, as exemplified by schizophrenia and Alzheimer's disease, respectively. Specifically, this network, while derived solely from healthy subjects, spatially recapitulates the pattern of brain abnormalities observed in both schizophrenia and Alzheimer's disease. This network is further associated in our large-scale healthy population with intellectual ability and episodic memory, whose impairment contributes to key symptoms of schizophrenia and Alzheimer's disease. Taken together, our results suggest that the common spatial pattern of abnormalities observed in these two disorders, which emerge at opposite ends of the life spectrum, might be influenced by the timing of their separate and distinct pathological processes in disrupting healthy cerebral development and aging, respectively.
Deak, Ferenc; Freeman, Willard M; Ungvari, Zoltan; Csiszar, Anna; Sonntag, William E
As the population of the Western world is aging, there is increasing awareness of age-related impairments in cognitive function and a rising interest in finding novel approaches to preserve cerebral health. A special collection of articles in The Journals of Gerontology: Biological Sciences and Medical Sciences brings together information of different aspects of brain aging, from latest developments in the field of neurodegenerative disorders to cerebral microvascular mechanisms of cognitive decline. It is emphasized that although the cellular changes that occur within aging neurons have been widely studied, more research is required as new signaling pathways are discovered that can potentially protect cells. New avenues for research targeting cellular senescence, epigenetics, and endocrine mechanisms of brain aging are also discussed. Based on the current literature it is clear that understanding brain aging and reducing risk for neurological disease with age requires searching for mechanisms and treatment options beyond the age-related changes in neuronal function. Thus, comprehensive approaches need to be developed that address the multiple, interrelated mechanisms of brain aging. Attention is brought to the importance of maintenance of cerebromicrovascular health, restoring neuroendocrine balance, and the pressing need for funding more innovative research into the interactions of neuronal, neuroendocrine, inflammatory and microvascular mechanisms of cognitive impairment, and Alzheimer's disease.
Matheson, Melanie C; Haydn Walters, E; Burgess, John A; Jenkins, Mark A; Giles, Graham G; Hopper, John L; Abramson, Michael J; Dharmage, Shyamali C
The association between childhood immunizations and risk of atopic diseases is unclear. No study has examined possible associations between childhood immunizations and such diseases in middle age. The Tasmanian Longitudinal Health Study (TAHS) is a population based cohort study of respiratory disease. The TAHS participants were followed from 7 to 44 yrs of age. Immunizations during childhood were examined for any association with asthma and atopic disease at age 44 yrs. Multivariable regression models were used to estimate relative risks while adjusting for confounders. Cox regression was used to estimate the association between childhood immunizations and asthma developing after the age of 7 yrs. We found no association between any childhood immunization (Diphtheria, Tetanus, Pertussis, Polio, Smallpox) and asthma (ORs ranged from 0.87 to 1.17 p > 0.05), eczema (ORs ranged from 0.99 to 1.07 p > 0.05), food allergy (ORs ranged from 0.97 to 1.11 p > 0.05), or hay fever (ORs ranged from 1.02 to 1.05 p > 0.05) at age 44. Nor did we find any association between childhood immunizations and an increased risk of incident asthma after the age of 7 yrs (Diphtheria HR = 1.06, 95% CI 0.82, 1.36; Tetanus HR = 1.13, 95% CI 0.88, 1.44; Pertussis HR = 1.03, 95% CI 0.81, 1.30; Polio HR = 1.15, 95% CI 0.86, 1.54; Smallpox HR = 1.21, 95% CI 0.99, 1.48; DTP HR = 1.05, 95% CI 0.85, 1.30). Our analysis does not support any association between common childhood immunizations and risk of asthma and atopic disease in middle-age. Our findings should provide reassurance that in terms of life time risk of asthma and atopic disease, childhood immunization is safe.
Tsujimoto, Ritsu; Maeda, Junichiro; Abe, Yasuyo; Arima, Kazuhiko; Tomita, Masato; Koseki, Hironobu; Kaida, Eiji; Aoyagi, Kiyoshi; Osaki, Makoto
Little research has been done on the prevalence of Kienböck's disease, and there is no consensus on the relationship between Kienböck's disease and negative ulnar variance. The goal of this cross-sectional study was to determine the prevalence of Kienböck's disease in middle-aged and elderly Japanese women and to clarify the relationship between Kienböck's disease and negative ulnar variance. The authors analyzed plain radiographs of both hands in women 40 years and older residing in the community to investigate the prevalence of Kienböck's disease and the relationship between Kienböck's disease and negative ulnar variance. Kienböck's disease was seen in 7 of the 572 participants. In the group with Kienböck's disease, ulnar variance did not differ significantly between affected (0.3 mm; SD, 1.5) and unaffected (0.3 mm; SD, 1.0; P=.285) sides. No significant difference was seen in ulnar variance values between the affected side in the group with Kienböck's disease and the normal group (P=.118). The number or proportion of participants with negative ulnar variance did not differ significantly between the affected side in the group with Kienböck's disease (3 of 7) and the unaffected side in the group with Kienböck's disease (1 of 7; P=.237) and between the affected side in the group with Kienböck's disease and the normal group (111 of 504; P=.189) by chi-square test. The prevalence of Kienböck's disease was 1.2% in middle-aged and elderly Japanese women. Negative ulnar variance is not a contributing factor to Kienböck's disease.
Black, Eric M; Blazar, Philip E
Dupuytren disease, a clinical entity originally described more than 400 years ago, is a progressive disease of genetic origin. Excessive myofibroblast proliferation and altered collagen matrix composition lead to thickened and contracted palmar fascia; the resultant digital flexion contractures may severely limit function. The pathophysiology is multifactorial and remains a topic of research and debate. Genetic predisposition, trauma, inflammatory response, ischemia, and environment, as well as variable expression of proteins and growth factors within the local tissue, all play a role in the disease process. Common treatments of severe disease include open fasciectomy or fasciotomy. These procedures may be complicated by the complex anatomic relationships between cords (pathologic contracted fascia) and adjacent neurovascular structures. Recent advances in the management of Dupuytren disease involve less invasive treatments, such as percutaneous needle fasciotomy and injectable collagenase Clostridium histolyticum. Postoperative management focuses on minimizing the cellular response of cord disruption and maximizing range of motion through static or dynamic extension splinting.
Ahlskog, J Eric; Geda, Yonas E; Graff-Radford, Neill R; Petersen, Ronald C
A rapidly growing literature strongly suggests that exercise, specifically aerobic exercise, may attenuate cognitive impairment and reduce dementia risk. We used PubMed (keywords exercise and cognition) and manuscript bibliographies to examine the published evidence of a cognitive neuroprotective effect of exercise. Meta-analyses of prospective studies documented a significantly reduced risk of dementia associated with midlife exercise; similarly, midlife exercise significantly reduced later risks of mild cognitive impairment in several studies. Among patients with dementia or mild cognitive impairment, randomized controlled trials (RCTs) documented better cognitive scores after 6 to 12 months of exercise compared with sedentary controls. Meta-analyses of RCTs of aerobic exercise in healthy adults were also associated with significantly improved cognitive scores. One year of aerobic exercise in a large RCT of seniors was associated with significantly larger hippocampal volumes and better spatial memory; other RCTs in seniors documented attenuation of age-related gray matter volume loss with aerobic exercise. Cross-sectional studies similarly reported significantly larger hippocampal or gray matter volumes among physically fit seniors compared with unfit seniors. Brain cognitive networks studied with functional magnetic resonance imaging display improved connectivity after 6 to 12 months of exercise. Animal studies indicate that exercise facilitates neuroplasticity via a variety of biomechanisms, with improved learning outcomes. Induction of brain neurotrophic factors by exercise has been confirmed in multiple animal studies, with indirect evidence for this process in humans. Besides a brain neuroprotective effect, physical exercise may also attenuate cognitive decline via mitigation of cerebrovascular risk, including the contribution of small vessel disease to dementia. Exercise should not be overlooked as an important therapeutic strategy.
Igor L. Shlykov, PhD¹, ScD¹
Full Text Available Background: Aging is associated with an increased hypercoagulable state. Degenerative diseases of the large joints are also accompanied by increased coagulation activity. We investigated the effect of age on the hemostatic function in patients with osteoarthritis. Material and Methods: The study included 192 patients with osteoarthritis admitted to the clinic for primary hip or knee arthroplasty. The patients were categorized into 5 age groups: the age group under 40 years, the 41–to-50 -year age group, the 51–to-60-year age group, the 61-to-70- year age group, and the age group over 70 years. The general blood clotting tests, platelet number, fibrinogen, antithrombin, protein C, TAT, D-dimer, vonWillebrand factor (vWF, PAI-1, ß-thromboglobulin were determined. Results: Among patients with osteoarthritis, the antithrombin III level significantly decreased by the age of 50; however, above the age of 60 there was a distinct decrease in platelet count, and over the age of 70 the activity of the extrinsic coagulation pathway and the plasminogen level dropped significantly. TAT and D-dimer levels were elevated in most of the patients. Conclusion: The decrease in platelet count coupled with the activity of the extrinsic coagulation pathway in elderly osteoarthritic patients may increase blood loss during total arthroplasty; also, the drop in the anticoagulant and fibrinolytic potential may play a negative role in strengthening the prothrombotic state during the postoperative period.
Low, Gail; Ross, Carolyn; Stickland, Michael; Wilson, Donna; Wong, Eric
Among pulmonary rehabilitation attendees, we explored their tendency to downplay versus acknowledge physical and psychosocial health limitations, and the subsequent impact either strategy had on how they perceive their own aging process. Participants (N = 87) were 44 to 82 years of age, and diagnosed with chronic obstructive pulmonary disease (COPD). The St. George's Respiratory Questionnaire measured their health limitations. The Attitudes to Aging Questionnaire captured their perspectives of aging. Participants downplayed their symptoms and psychosocial impact, and remained most positive about psychosocial loss and carefully reserved about psychological growth. Acknowledged activity impairment had negative consequences, however, for their perspectives of physical change. These findings signify a balanced identity and perspective of aging that supports the Identity Process Theory. We encourage nurses and other practitioners, and researchers in pulmonary rehabilitation setting, to use this theory to better understand how people with COPD adapt to aging.
Nayana A Shah
Full Text Available Introduction: Among endocrine disorders commonly encountered in pediatric age group, thyroid diseases are more frequent. Congenital hypothyroidism is one of the major problems in this age with worldwide incidence of 1:3000-4000 live birth and in India it is 1:2500-2800. Objectives: The aim of this study is to know the prevalence of thyroid diseases in newborn and children by hormonal evaluation. Methodology: We have studied 50 children suspected of having signs and symptoms of thyroid diseases. Hormonal evaluation was done by the estimation of serum TSH, T3 and T4. Results: Out of total 50 children, 16 were detected with abnormal hormone level and diagnosed having thyroid diseases. Out of 16 affected children, 4 had congenital hypothyroidism (25%, 6 had subclinical or acquired hypothyroidism (37.5%, 3 had autoimmune thyroiditis (18.75% and 3 had goiter with graves disease (18.75%. Conclusion: Congenital hypothyroidism is one of the major preventable thyroid disease if diagnosed early. Other thyroid diseases commonly seen in pediatric age are subclinical hypothyroidism, autoimmune thyroiditis, goiter and rarely hyperthyroidism. [Natl J Med Res 2013; 3(4.000: 367-370
Manuel J. Amador-Patarroyo
Full Text Available The age at onset refers to the time period at which an individual experiences the first symptoms of a disease. In autoimmune diseases (ADs, these symptoms can be subtle but are very relevant for diagnosis. They can appear during childhood, adulthood or late in life and may vary depending on the age at onset. Variables like mortality and morbidity and the role of genes will be reviewed with a focus on the major autoimmune disorders, namely, systemic lupus erythematosus (SLE, rheumatoid arthritis (RA, multiple sclerosis (MS, type 1 diabetes mellitus (T1D, Sjögren's syndrome, and autoimmune thyroiditis (AITD. Early age at onset is a worst prognostic factor for some ADs (i.e., SLE and T1D, while for others it does not have a significant influence on the course of disease (i.e., SS or no unanimous consensus exists (i.e., RA and MS.
Full Text Available The use of wearable devices to study gait and postural control is a growing field on neurodegenerative disorders such as Alzheimer’s disease (AD. In this paper, we investigate if machine-learning classifiers offer the discriminative power for the diagnosis of AD based on postural control kinematics. We compared Support Vector Machines (SVMs, Multiple Layer Perceptrons (MLPs, Radial Basis Function Neural Networks (RBNs, and Deep Belief Networks (DBNs on 72 participants (36 AD patients and 36 healthy subjects exposed to seven increasingly difficult postural tasks. The decisional space was composed of 18 kinematic variables (adjusted for age, education, height, and weight, with or without neuropsychological evaluation (Montreal cognitive assessment (MoCA score, top ranked in an error incremental analysis. Classification results were based on threefold cross validation of 50 independent and randomized runs sets: training (50%, test (40%, and validation (10%. Having a decisional space relying solely on postural kinematics, accuracy of AD diagnosis ranged from 71.7 to 86.1%. Adding the MoCA variable, the accuracy ranged between 91 and 96.6%. MLP classifier achieved top performance in both decisional spaces. Having comprehended the interdynamic interaction between postural stability and cognitive performance, our results endorse machine-learning models as a useful tool for computer-aided diagnosis of AD based on postural control kinematics.
Yelshyna, Darya; Bicho, Estela
The use of wearable devices to study gait and postural control is a growing field on neurodegenerative disorders such as Alzheimer's disease (AD). In this paper, we investigate if machine-learning classifiers offer the discriminative power for the diagnosis of AD based on postural control kinematics. We compared Support Vector Machines (SVMs), Multiple Layer Perceptrons (MLPs), Radial Basis Function Neural Networks (RBNs), and Deep Belief Networks (DBNs) on 72 participants (36 AD patients and 36 healthy subjects) exposed to seven increasingly difficult postural tasks. The decisional space was composed of 18 kinematic variables (adjusted for age, education, height, and weight), with or without neuropsychological evaluation (Montreal cognitive assessment (MoCA) score), top ranked in an error incremental analysis. Classification results were based on threefold cross validation of 50 independent and randomized runs sets: training (50%), test (40%), and validation (10%). Having a decisional space relying solely on postural kinematics, accuracy of AD diagnosis ranged from 71.7 to 86.1%. Adding the MoCA variable, the accuracy ranged between 91 and 96.6%. MLP classifier achieved top performance in both decisional spaces. Having comprehended the interdynamic interaction between postural stability and cognitive performance, our results endorse machine-learning models as a useful tool for computer-aided diagnosis of AD based on postural control kinematics. PMID:28074090
Glassock, Richard J; Rule, Andrew D
The varied functions of the kidneys are influenced by the complex process of aging. The glomerular filtration rate (GFR) steadily declines with normal aging, and the progress of this process can be influenced by superimposed diseases. Microscopically, nephron numbers decrease as global glomerulosclerosis becomes more evident. The precise mechanisms underlying nephron loss with aging are not well understood, but derangements in podocyte biology appear to be involved. Classifications of chronic kidney disease (CKD) incorporate GFR values and attendant risk of adverse events. Arbitrary and fixed thresholds of GFR for defining CKD have led to an overdiagnosis of CKD in the elderly. An age-sensitive definition of CKD could offer a solution to this problem and more meaningfully capture the prognostic implications of CKD.
Ljubisavljevic, M R; Ismail, F Y; Filipovic, S
Although the brain's ability to change constantly in response to external and internal inputs is now well recognized the mechanisms behind it in normal aging and neurodegeneration are less well understood. To gain a better understanding, transcranial magnetic stimulation (TMS) has been used extensively to characterize non-invasively the cortical neurophysiology of the aging and degenerating brain. Furthermore, there has been a surge of studies examining whether repetitive TMS (rTMS) can be used to improve functional deficits in various conditions including normal aging, Alzheimer's and Parkinson's disease. The results of these studies in normal aging and neurodegeneration have emerged reasonably coherent in delineating the main pathology in spite of considerable technical limitations, omnipresent methodological variability, and extraordinary patient heterogeneity. Nevertheless, comparing and integrating what is known about TMS measurements of cortical excitability and plasticity in disorders that predominantly affect cortical brain structures with disorders that predominantly affect subcortical brain structures may provide better understanding of normal and abnormal brain aging fostering new. The present review provides a TMS perspective of changes in cortical neurophysiology and neurochemistry in normal aging and neurodegeneration by integrating what is revealed in individual TMS measurements of cortical excitability and plasticity in physiological aging, Alzheimer's, Parkinson's, and Huntington's, disease. The paper also reflects on current developments in utilizing TMS as a physiologic biomarker to discriminate physiologic aging from neurodegeneration and its potential as a method of therapeutic intervention.
Tones, Megan; Pillay, Hitendra; Kelly, Kathy
More recently, lifespan development psychology models of adaptive development have been applied to the workforce to investigate ageing worker and lifespan issues. The current study uses the Learning and Development Survey (LDS) to investigate employee selection and engagement of learning and development goals and opportunities and constraints for…
Hayashi, Christine A.; Fisher-Adams, Grace
This study surveys graduates of a west-coast university regarding their perception of how well their graduate degree programs prepared them to meet the challenge of leading for learning in the digital age, particularly in the areas of visionary leadership, student learning, organizational management, working with diverse families, ethics, and the…
Speer, Paula; Wersching, Heike; Bruchmann, Sabine; Bracht, Dorothea; Stehling, Christoph; Thielsch, Meinald; Knecht, Stefan; Lohmann, Hubertus
Rey's Auditory Verbal Learning Test (AVLT) is widely used to evaluate dysfunctional episodic memory. The current study aimed to provide extended age- and gender-specific norms for the German AVLT for individuals older than 50 years. In 690 subjects, a comprehensive medical examination including a structural 3.0-tesla magnetic resonance imaging scan was administered, as well as extensive neuropsychological tests. After controlling for exclusion criteria, 407 subjects were included in the analysis. AVLT performance decreased with age, and women outperformed men. We present age- and gender-specific normative data for the German AVLT from subjects aged between 50 and 70 years.
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.
Singh, Gitanjali M; Danaei, Goodarz; Farzadfar, Farshad;
The effects of systolic blood pressure (SBP), serum total cholesterol (TC), fasting plasma glucose (FPG), and body mass index (BMI) on the risk of cardiovascular diseases (CVD) have been established in epidemiological studies, but consistent estimates of effect sizes by age and sex are not availa......The effects of systolic blood pressure (SBP), serum total cholesterol (TC), fasting plasma glucose (FPG), and body mass index (BMI) on the risk of cardiovascular diseases (CVD) have been established in epidemiological studies, but consistent estimates of effect sizes by age and sex...
Full Text Available Alzheimer's disease (AD, the most common form of dementia, shares many aspects of abnormal brain aging. We present a novel magnetic resonance imaging (MRI-based biomarker that predicts the individual progression of mild cognitive impairment (MCI to AD on the basis of pathological brain aging patterns. By employing kernel regression methods, the expression of normal brain-aging patterns forms the basis to estimate the brain age of a given new subject. If the estimated age is higher than the chronological age, a positive brain age gap estimation (BrainAGE score indicates accelerated atrophy and is considered a risk factor for conversion to AD. Here, the BrainAGE framework was applied to predict the individual brain ages of 195 subjects with MCI at baseline, of which a total of 133 developed AD during 36 months of follow-up (corresponding to a pre-test probability of 68%. The ability of the BrainAGE framework to correctly identify MCI-converters was compared with the performance of commonly used cognitive scales, hippocampus volume, and state-of-the-art biomarkers derived from cerebrospinal fluid (CSF. With accuracy rates of up to 81%, BrainAGE outperformed all cognitive scales and CSF biomarkers in predicting conversion of MCI to AD within 3 years of follow-up. Each additional year in the BrainAGE score was associated with a 10% greater risk of developing AD (hazard rate: 1.10 [CI: 1.07-1.13]. Furthermore, the post-test probability was increased to 90% when using baseline BrainAGE scores to predict conversion to AD. The presented framework allows an accurate prediction even with multicenter data. Its fast and fully automated nature facilitates the integration into the clinical workflow. It can be exploited as a tool for screening as well as for monitoring treatment options.
Klosinski, Lauren P; Yao, Jia; Yin, Fei; Fonteh, Alfred N; Harrington, Michael G; Christensen, Trace A; Trushina, Eugenia; Brinton, Roberta Diaz
White matter degeneration is a pathological hallmark of neurodegenerative diseases including Alzheimer's. Age remains the greatest risk factor for Alzheimer's and the prevalence of age-related late onset Alzheimer's is greatest in females. We investigated mechanisms underlying white matter degeneration in an animal model consistent with the sex at greatest Alzheimer's risk. Results of these analyses demonstrated decline in mitochondrial respiration, increased mitochondrial hydrogen peroxide production and cytosolic-phospholipase-A2 sphingomyelinase pathway activation during female brain aging. Electron microscopic and lipidomic analyses confirmed myelin degeneration. An increase in fatty acids and mitochondrial fatty acid metabolism machinery was coincident with a rise in brain ketone bodies and decline in plasma ketone bodies. This mechanistic pathway and its chronologically phased activation, links mitochondrial dysfunction early in aging with later age development of white matter degeneration. The catabolism of myelin lipids to generate ketone bodies can be viewed as a systems level adaptive response to address brain fuel and energy demand. Elucidation of the initiating factors and the mechanistic pathway leading to white matter catabolism in the aging female brain provides potential therapeutic targets to prevent and treat demyelinating diseases such as Alzheimer's and multiple sclerosis. Targeting stages of disease and associated mechanisms will be critical.
Santiago; Vivas; Luis; Vaquero; Laura; Rodríguez-Martín; Alberto; Caminero
Celiac disease may appear both in early childhood andin elderly subjects. Current knowledge of the disease has revealed some differences associated to the age of presentation. Furthermore, monitoring and prognosis of celiac subjects can vary depending on the pediatric or adult stage. The main objective of this review is to provide guidance for the adult diagnostic and follow-up processes, which must be tailored specifically for adults and be different from pediatric patients.
Holly, Deirdre; Sharp, John
People with learning disabilities are at increased risk of coronary heart disease (CHD). Research suggests this may be due to inequalities in health status and inequities in the way health services respond to need. Little is known about the most effective way to improve health outcomes for people with learning disabilities. A previously developed…
Li, Ruijie; Liu, Karen P. Y.
The aim of this article was to review the evidence of errorless learning on learning outcomes in patients with early-stage Alzheimer's disease. A computer-aided literature search from 1999 to 2011 was carried out using MEDLINE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO and PsycArticles. Keywords included…
Suksuphew, Sarawut; Noisa, Parinya
Progressively loss of neural and glial cells is the key event that leads to nervous system dysfunctions and diseases. Several neurodegenerative diseases, for instance Alzheimer's disease, Parkinson's disease, and Huntington's disease, are associated to aging and suggested to be a consequence of deficiency of neural stem cell pool in the affected brain regions. Endogenous neural stem cells exist throughout life and are found in specific niches of human brain. These neural stem cells are responsible for the regeneration of new neurons to restore, in the normal circumstance, the functions of the brain. Endogenous neural stem cells can be isolated, propagated, and, notably, differentiated to most cell types of the brain. On the other hand, other types of stem cells, such as mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells can also serve as a source for neural stem cell production, that hold a great promise for regeneration of the brain. The replacement of neural stem cells, either endogenous or stem cell-derived neural stem cells, into impaired brain is highly expected as a possible therapeutic mean for neurodegenerative diseases. In this review, clinical features and current routinely treatments of age-related neurodegenerative diseases are documented. Noteworthy, we presented the promising evidence of neural stem cells and their derivatives in curing such diseases, together with the remaining challenges to achieve the best outcome for patients.
Flora Filho Rowilson
Full Text Available The purpose of this study was to explore the relationship between the intensity of acid reflux and severity of esophageal tissue damage in a cross-sectional study of patients with gastroesophageal reflux disease (GERD. Seventy-eight patients with were selected in accordance with the strict 24-hour ambulatory esophageal pHmetry (24h-pHM criteria and distributed into three age groups: Group A: 14 - 24 years of age. Group B: 25 - 54; and Group C: 55 - 64. The 24h-pHM was carried out in accordance with DeMeester standardization, and the Savary-Miller classification for the diagnosis of reflux esophagitis was used. The groups were similar in 24h-pHM parameters (p > 0.05, having above normal values. For the study group as a whole, there was no correlation between age group and intensity of acid reflux, and there was no correlation between intensity of acid reflux and severity of esophageal tissue damage. However, when the same patients were sub-grouped in accordance with the depth of their epithelial injury and then distributed into age groups, there was a significant difference in esophagitis without epithelial discontinuity. Younger patients had less epithelial damage than older patients. Additionally, although there was a significant progression from the least severe to the moderate stages of epithelial damage among the age groups, there was no apparent difference among the age groups in the distribution between the moderate stages and most severe stages. The findings support the conclusion that the protective response of individuals to acid reflux varies widely. Continued aggression by acid reflux appears to lead to the exhaustion of individual mechanisms of epithelial protection in some patients, but not others, regardless of age or duration of the disease. Therefore, the diagnosis and follow-up of GERD should include both measurements of the quantity of refluxed acid and an assessment of the damage to the esophageal epithelium.
Eriksen, Nina; Stark, Anette Kirstine; Pakkenberg, Bente
During aging, decline in memory and cognitive abilities as well as motor weakening is of great concern. The dopaminergic system mediates some aspects of manual dexterity, in addition to cognition and emotion, and may be especially vulnerable to aging. A common neurodegenerative disorder...... of this system, Parkinson's disease, is characterized by a selective, progressive loss of dopaminergic neurons in the substantia nigra pars compacta. This review includes studies quantifying age and Parkinson's-related changes of the substantia nigra, with emphasis on stereological studies performed...
Eriksen, Nina; Stark, Anette Kirstine; Pakkenberg, Bente
of this system, Parkinson's disease, is characterized by a selective, progressive loss of dopaminergic neurons in the substantia nigra pars compacta. This review includes studies quantifying age and Parkinson's-related changes of the substantia nigra, with emphasis on stereological studies performed......During aging, decline in memory and cognitive abilities as well as motor weakening is of great concern. The dopaminergic system mediates some aspects of manual dexterity, in addition to cognition and emotion, and may be especially vulnerable to aging. A common neurodegenerative disorder...
Full Text Available Contemporary teaching and learning implies that pupils encounter curricular content in the form of multimodal representations such as film, museum visits, PowerPoint presentations, roleplay and digital games. Spoken language is no longer the only mode for knowledge representation and meaning-making. This means a new demand for teaching (and assessment, since the school tradition is heavily based on verbal language and assessments of verbal representations. In this article, we will present an analysis of the use of resources and different media in classroom work about the Middle Ages, and discuss the need for the development of assessment tools.
Cornelis Kees Mulder
Full Text Available Introduction: with time-place learning (TPL, animals link an event with the spatial location and the time of day. The what-where-when TPL components make the task putatively episodic-like in nature. Animals use an internal sense of time to master TPL, which is circadian system based. Finding indications for a role of the hippocampus and (early aging-sensitivity in TPL would strengthen the episodic-like memory nature of the paradigm. Methods: previously, we used C57Bl/6 mice for our TPL research. Here, we used CD1 mice which are less hippocampal-driven and age faster compared to C57Bl/6 mice. To demonstrate the low degree of hippocampal-driven performance in CD1 mice, a cross maze was used. The spontaneous alternation test was used to score spatial working memory in CD1 mice at four different age categories (young (3-6 months, middle-aged (7-11 months, aged (12-18 months and old (>19 months. TPL performance of middle-aged and aged CD1 mice was tested in a setup with either two or three time points per day (2-arm or 3-arm TPL task. Immunostainings was applied on brains of young and middle-aged C57Bl/6 mice that had successfully mastered the 3-arm TPL task. Results: in contrast to C57Bl/6 mice, middle-aged and aged CD1 mice were less hippocampus-driven and failed to master the 3-arm TPL task. They could, however, master the 2-arm TPL task primarily via an ordinal (non-circadian timing system. c-Fos, CRY2, vasopressin (AVP, and pCREB were investigated. We found no differences at the level of the suprachiasmatic nucleus (SCN; circadian master clock, whereas CRY2 expression was increased in the hippocampal dentate gyrus. The most pronounced difference between TPL trained and control mice was found in c-Fos expression in the paraventricular thalamic nucleus, a circadian system relay station. Conclusions: These results further indicate a key role of CRY proteins in TPL and confirm the limited role of the SCN in TPL. Based on the poor TPL performance of
Brown, Karen L; Mabbott, Neil A
The occurrence of variant Creutzfeldt-Jakob (vCJD) disease in humans was almost certainly the result of consumption of food contaminated with bovine spongiform encephalopathy (BSE) prions. Despite probable widespread exposure of the UK population to BSE-contaminated food in the 1980s, vCJD has been identified predominantly in young individuals, and there have been fewer cases of clinical disease than anticipated. The reasons for this are uncertain. Following peripheral exposure, many prions replicate within the lymphoid tissues before infecting the central nervous system. We have shown that the effects of host age on the microarchitecture of the spleen significantly impair susceptibility to mouse-adapted prions after peripheral exposure. The transmission of prions between different mammalian species is considered to be limited by the 'species barrier', which is dependent on several factors, including an intact immune system. Thus, cross-species prion transmission may be much less efficient in aged individuals. To test this hypothesis, we compared prion pathogenesis in groups of young (6-8 weeks old) and aged (600 days old) mice injected with primary BSE brain homogenate. We showed that prion pathogenesis was impaired dramatically in aged mice when compared with young animals. Whereas most young mice succumbed to clinical prion disease, all aged mice failed to develop clinical disease during their lifespans. However, the demonstration that prion accumulation was detected in the lymphoid tissues of some aged mice after injection with primary BSE brain homogenate, in the absence of clinical signs of prion disease, has important implications for human health.
Hayes, Scott M; Alosco, Michael L; Forman, Daniel E
Aging is characterized by a decline in cognitive functions, particularly in the domains of executive function, processing speed and episodic memory. These age-related declines are exacerbated by cardiovascular disease (CVD) and cardiovascular risk factors (hypertension, diabetes, obesity, elevated total cholesterol). Structural and functional alterations in brain regions, including the fronto-parietal and medial temporal lobes, have been linked to age- and CVD-related cognitive decline. Multiple recent studies indicate that aerobic exercise programs may slow the progression of age-related neural changes and reduce the risk for mild cognitive impairment as well as dementia. We review age- and CVD-related decline in cognition and the underlying changes in brain morphology and function, and then clarify the impact of aerobic exercise on moderating these patterns.
Erdozain, Jose-Gabriel; Villar, Irama; Nieto, Javier; Ruiz-Arruza, Ioana
Objective To analyse the differential influence of risk factors of peripheral artery disease (PAD) according to age in patients with SLE. Methods 216 patients from the Lupus-Cruces cohort were divided in three age groups: ≤34 years, 35–49 years and ≥50 years. A low ankle–brachial index defined PAD. Significant variables were identified by univariant and multivariant analysis in each age group. Results Different factors were identified in different age groups: antiphospholipid antibodies/antiphospholipid syndrome and glucocorticoids in patients ≤34 years; in patients 35–49 years old, hypertension was the only statistically significant predictor, although a trend was observed for fibrinogen levels; a trend was observed for hypercholesterolaemia in those ≥50 years. Conclusions Age may modulate the influence of risk factors for PAD in patients with SLE. PMID:28123770
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
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.
Kumar, Hemant; Lim, Hyung-Woo; More, Sandeep Vasant; Kim, Byung-Wook; Koppula, Sushruta; Kim, In Su; Choi, Dong-Kug
Free radical production and their targeted action on biomolecules have roles in aging and age-related disorders such as Parkinson's disease (PD). There is an age-associated increase in oxidative damage to the brain, and aging is considered a risk factor for PD. Dopaminergic neurons show linear fallout of 5-10% per decade with aging; however, the rate and intensity of neuronal loss in patients with PD is more marked than that of aging. Here, we enumerate the common link between aging and PD at the cellular level with special reference to oxidative damage caused by free radicals. Oxidative damage includes mitochondrial dysfunction, dopamine auto-oxidation, α-synuclein aggregation, glial cell activation, alterations in calcium signaling, and excess free iron. Moreover, neurons encounter more oxidative stress as a counteracting mechanism with advancing age does not function properly. Alterations in transcriptional activity of various pathways, including nuclear factor erythroid 2-related factor 2, glycogen synthase kinase 3β, mitogen activated protein kinase, nuclear factor kappa B, and reduced activity of superoxide dismutase, catalase and glutathione with aging might be correlated with the increased incidence of PD.
Van Houcke, Jessie; De Groef, Lies; Dekeyster, Eline; Moons, Lieve
Considering the increasing number of elderly in the world's population today, developing effective treatments for age-related pathologies is one of the biggest challenges in modern medical research. Age-related neurodegeneration, in particular, significantly impacts important sensory, motor, and cognitive functions, seriously constraining life quality of many patients. Although our understanding of the causal mechanisms of aging has greatly improved in recent years, animal model systems still have much to tell us about this complex process. Zebrafish (Danio rerio) have gained enormous popularity for this research topic over the past decade, since their life span is relatively short but, like humans, they are still subject to gradual aging. In addition, the extensive characterization of its well-conserved molecular and cellular physiology makes the zebrafish an excellent model to unravel the underlying mechanisms of aging, disease, and repair. This review provides a comprehensive overview of the progress made in zebrafish gerontology, with special emphasis on nervous system aging. We review the evidence that classic hallmarks of aging can also be recognized within this small vertebrate, both at the molecular and cellular level. Moreover, we illustrate the high level of similarity with age-associated human pathologies through a survey of the functional deficits that arise as zebrafish age.
Lu, Shen; Xia, Yong; Cai, Tom Weidong; Feng, David Dagan
Dementia, Alzheimer's disease (AD) in particular is a global problem and big threat to the aging population. An image based computer-aided dementia diagnosis method is needed to providing doctors help during medical image examination. Many machine learning based dementia classification methods using medical imaging have been proposed and most of them achieve accurate results. However, most of these methods make use of supervised learning requiring fully labeled image dataset, which usually is not practical in real clinical environment. Using large amount of unlabeled images can improve the dementia classification performance. In this study we propose a new semi-supervised dementia classification method based on random manifold learning with affinity regularization. Three groups of spatial features are extracted from positron emission tomography (PET) images to construct an unsupervised random forest which is then used to regularize the manifold learning objective function. The proposed method, stat-of-the-art Laplacian support vector machine (LapSVM) and supervised SVM are applied to classify AD and normal controls (NC). The experiment results show that learning with unlabeled images indeed improves the classification performance. And our method outperforms LapSVM on the same dataset.
Brewer, Alyssa A; Barton, Brian
Although several studies have suggested that cortical alterations underlie such age-related visual deficits as decreased acuity, little is known about what changes actually occur in visual cortex during healthy aging. Two recent studies showed changes in primary visual cortex (V1) during normal aging; however, no studies have characterized the effects of aging on visual cortex beyond V1, important measurements both for understanding the aging process and for comparison to changes in age-related diseases. Similarly, there is almost no information about changes in visual cortex in Alzheimer's disease (AD), the most common form of dementia. Because visual deficits are often reported as one of the first symptoms of AD, measurements of such changes in the visual cortex of AD patients might improve our understanding of how the visual system is affected by neurodegeneration as well as aid early detection, accurate diagnosis and timely treatment of AD. Here we use fMRI to first compare the visual field map (VFM) organization and population receptive fields (pRFs) between young adults and healthy aging subjects for occipital VFMs V1, V2, V3, and hV4. Healthy aging subjects do not show major VFM organizational deficits, but do have reduced surface area and increased pRF sizes in the foveal representations of V1, V2, and hV4 relative to healthy young control subjects. These measurements are consistent with behavioral deficits seen in healthy aging. We then demonstrate the feasibility and first characterization of these measurements in two patients with mild AD, which reveal potential changes in visual cortex as part of the pathophysiology of AD. Our data aid in our understanding of the changes in the visual processing pathways in normal aging and provide the foundation for future research into earlier and more definitive detection of AD.
Huang, Debin; Hu, Zehua; Yu, Zhaofen
Eleutheroside B or E, the main component of Acanthopanax, can relieve fatigue, enhance memory, and improve human cognition. Numerous studies have confirmed that high doses of acetylcholine significantly attenuate clinical symptoms and delay the progression of Alzheimer's disease. The present study replicated a rat model of aging induced by injecting quinolinic acid into the hippocampal CA1 region. These rats were intraperitoneally injected with low, medium and high doses of eleutheroside B or...
David C Geary
Full Text Available Traits that facilitate competition for reproductive resources or that influence mate choice have evolved to signal resilience to infectious disease and other stressors. As a result, the dynamics of competition and choice can, in theory, be used to generate predictions about sex-, age-, and trait-specific vulnerabilities for any sexually reproducing species, including humans. These dynamics and associated vulnerabilities are reviewed for nonhuman species, focusing on traits that are compromised by exposure to parasites. Using the same approach, sex-, age-, and trait-specific vulnerabilities to parasitic disease are illustrated for children's and adolescent's physical growth and fitness. Suggestions are then provided for widening the assessment of human vulnerabilities to include age-appropriate measures of behavioral (e.g., children's play and cognitive (e.g., language fluency traits. These are traits that are likely to be compromised by infection in age- and sex-specific ways. Inclusion of these types of measures in studies of neglected tropic diseases has the potential to provide a more nuanced understanding of how these diseases undermine human wellbeing and may provide a useful means to study the efficacy of associated treatments.
Vittori, Angelica; Orth, Michael; Roos, Raymund A C; Outeiro, Tiago F; Giorgini, Flaviano; Hollox, Edward J; Kremer, Berry
BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by the abnormal expansion of a CAG triplet repeat tract in the huntingtin gene. While the length of this CAG expansion is the major determinant of the age of onset (AO), other genetic factors have also b
Wardlaw, J.M.; Smith, E.E.; Biessels, G.J.; Cordonnier, C.; Fazekas, F.; Frayne, R.; Lindley, R.I.; O'Brien, J.T.; Barkhof, F.; Benavente, O.R.; Black, S.E.; Brayne, C.; Breteler, M.; Chabriat, H.; DeCarli, C.; Leeuw, F.E. de; Doubal, F.; Duering, M.; Fox, N.C.; Greenberg, S.; Hachinski, V.; Kilimann, I.; Mok, V.; Oostenbrugge, R.; Pantoni, L.; Speck, O.; Stephan, B.C.; Teipel, S.; Viswanathan, A.; Werring, D.; Chen, C.; Smith, C.; Buchem, M. van; Norrving, B.; Gorelick, P.B.; Dichgans, M.; nEuroimaging, S.T.f.R.V.c.o.
Cerebral small vessel disease (SVD) is a common accompaniment of ageing. Features seen on neuroimaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. SVD can present as a stroke or cognitive decline, or can have
J. Barnes (John); F. Dickerson (Faith); C. Frost (Chris); L.C. Jiskoot (Lize); D. Wolk (David); W.M. van der Flier (Wiesje)
textabstractIntroduction Determining the relationship between age and Alzheimer's disease (AD) presentation is important to improve understanding and provide better patient services. Methods We used AD patient data (N = 7815) from the National Alzheimer Coordinating Center database and multinomial l
Jiang, Hong; Schiffer, Eric; Song, Zhangfa; Wang, Jianwei; Zürbig, Petra; Thedieck, Kathrin; Moes, Suzette; Bantel, Heike; Saal, Nadja; Jantos, Justyna; Brecht, Meiken; Jenö, Paul; Hall, Michael N; Hager, Klaus; Manns, Michael P; Hecker, Hartmut; Ganser, Arnold; Döhner, Konstanze; Bartke, Andrzej; Meissner, Christoph; Mischak, Harald; Ju, Zhenyu; Rudolph, K Lenhard
Telomere dysfunction limits the proliferative capacity of human cells by activation of DNA damage responses, inducing senescence or apoptosis. In humans, telomere shortening occurs in the vast majority of tissues during aging, and telomere shortening is accelerated in chronic diseases that increase
... 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) ...
Wu, Y.H.; Zhou, J.N.; Heerikhuize, J. van; Jockers, R.; Swaab, D.F.
The pineal hormone melatonin is involved in the regulation of circadian rhythms and feeds back to the central biological clock, the hypothalamic suprachiasmatic nucleus (SCN) via melatonin receptors. Supplementary melatonin is considered to be a potential treatment for aging and Alzheimer's disease
Koopman, Carla; Bots, Michiel L.; Van Dis, Ineke; Vaartjes, Ilonca
Background Shifts in the burden of coronary heart disease (CHD) from an acute to chronic illness have important public health consequences. Objective To assess age-sex-specific time trends in rates and characteristics of acute and chronic forms of CHD hospital admissions in the Netherlands. Methods
Ramezani Tehrani, F.; Montazeri, S. A.; Khalili, D.; Cheraghi, L.; Broekmans, F. J.; Momenan, A. A.; de Kat, A. C.; Azizi, F.
Objective: To explore the relationship between age-specific anti-Müllerian hormone level, as a predictor of ovarian reserve status, and electrocardiographic silent coronary artery disease in a population-based, prospective cohort, the Tehran Lipid and Glucose Study. Methods: For the present study, 1
Social participation is an important strategy in promoting successful aging. Although participating in volunteering has been proven to benefit older adults' health and well-being, we often ignore its role as a process of learning while helping others. The purpose of this study was to use the self-defined successful aging concept of seniors to…
Jones, Cindy; Moyle, Wendy
Expression of sexuality by older people, particularly those with dementia, can be challenging and confronting for aged-care staff. Education on this topic is often a low priority area for aged-care organizations, and there appears to be limited training programs available. Results from our study highlighted the value of an eLearning education…
Strøm, Marin; Halldorsson, Thorhallur I; Mortensen, Erik L;
Previous studies have indicated a protective effect of long-chain n-3 polyunsaturated fatty acids (LCn3FAs) against cardiovascular disease; however, women are underrepresented in cardiovascular research. The aim of this study was to explore the association between intake of LCn3FAs and the risk......, and ischemic heart disease used to define a combined measure of cardiovascular diseases. Intake of fish and LCn3FAs was assessed by a food-frequency questionnaire and telephone interviews. During follow-up (1996-2008; median: 8 years), 577 events of cardiovascular disease were identified. Low LCn3FA intake...... of cardiovascular disease in a large prospective cohort of young women (mean age at baseline: 29.9 years [range: 15.7-46.9]). Exposure information on 48 627 women from the Danish National Birth Cohort was linked to the Danish National Patients Registry for information on events of hypertensive, cerebrovascular...
Full Text Available BACKGROUND: Graves' disease (GD is a complex disease in which genetic predisposition is modified by environmental factors. The aim of the study was to examine the association between genetic variants in genes encoding proteins involved in immune response and the age at diagnosis of GD. METHODS: 735 GD patients and 1216 healthy controls from Poland were included into the study. Eight genetic variants in the HLA-DRB1, TNF, CTLA4, CD40, NFKb, PTPN22, IL4 and IL10 genes were genotyped. Patients were stratified by the age at diagnosis of GD and the association with genotype was analysed. RESULTS: Polymorphism in the HLA-DRB1, TNF and CTLA4 genes were associated with GD. The carriers of the HLA DRB1*03 allele were more frequent in patients with age at GD diagnosis ≤30 years than in patients with older age at GD diagnosis. CONCLUSIONS: HLADRB1*03 allele is associated with young age at diagnosis of Graves' disease in Polish population.
Sato, Shigeru; Sasaki, Yoshihiro; Adachi, Akiko; Ghazizadeh, Mohammad
Measurement of the normal range of glomerular basement membrane (GBM) thickness by electron microscopy is required for the diagnosis of thin basement membrane disease or diabetic nephropathy; however, this measurement is influenced by aging. The aim of this study was to introduce a simple histogram plotting method for the validation of the results of the GBM thickness measurements by the accepted arithmetic mean ± SD method. We examined renal biopsy specimens obtained from 19 patients (10 males and 9 females) with minimal change disease, ranging in age from 3 to 70 years. Renal tissue samples obtained at autopsy from a male baby (3 months old) with no renal disease were also examined. For each case, GBM thicknesses at 10-15 evenly distributed points per glomerular loop were directly measured and the arithmetic mean ± SD was calculated. Subsequently, the arithmetic mean ± SD for each group of cases classified by age into 4 groups, i.e. babyhood (3 months old), childhood (3-11 years old), adulthood (12-57 years old), and old age (60-70 years old), was determined. On the other hand, a histogram of the frequency of GBM points measured against thickness was plotted to determine the distribution pattern and the range of measurements in each age group. The histogram plot showed 4 clearly divided modes for GBM thickness. Comparison of the results obtained by the 2 methods revealed a significant correlation indicating the feasibility of the histogram plotting method as a useful adjunct to validate GBM thickness measurements.
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
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.
Swami, Meera; Hendricks, Audrey E; Gillis, Tammy; Massood, Tiffany; Mysore, Jayalakshmi; Myers, Richard H; Wheeler, Vanessa C
The age of onset of Huntington's disease (HD) is determined primarily by the length of the HD CAG repeat mutation, but is also influenced by other modifying factors. Delineating these modifiers is a critical step towards developing validated therapeutic targets in HD patients. The HD CAG repeat is somatically unstable, undergoing progressive length increases over time, particularly in brain regions that are the targets of neurodegeneration. Here, we have explored the hypothesis that somatic instability of the HD CAG repeat is itself a modifier of disease. Using small-pool PCR, we quantified somatic instability in the cortex region of the brain from a cohort of HD individuals exhibiting phenotypic extremes of young and old disease onset as predicted by the length of their constitutive HD CAG repeat lengths. After accounting for constitutive repeat length, somatic instability was found to be a significant predictor of onset age, with larger repeat length gains associated with earlier disease onset. These data are consistent with the hypothesis that somatic HD CAG repeat length expansions in target tissues contribute to the HD pathogenic process, and support pursuing factors that modify somatic instability as viable therapeutic targets.
Ruban, T N; Jacob, B; Pope, J E; Keystone, E C; Bombardier, C; Kuriya, B
This study aims to compare characteristics between late-onset rheumatoid arthritis (RA) and young-onset RA and determine the association between age at disease onset and disease severity. We cross-sectionally studied 971 patients at the time of entry into the Ontario Best Practices Research Initiative, a registry of RA patients followed up in routine care. We restricted patients to ≤5 years of disease duration. Late-onset RA was defined as an onset ≥60 years of age and young-onset RA <60 years. Group differences were compared, and multivariate linear regression models were used to test the influence of age at onset on Disease Activity Score in 28 Joints with erythrocyte sedimentation rate (DAS28-ESR), Clinical Disease Activity Index (CDAI), and Health Assessment Questionnaire (HAQ) scores. The swollen joint count (6.2 vs. 5.3), acute phase reactants (C-reactive protein (CRP) 17.4 vs. 11.8 mg/L, ESR 30.6 vs. 21.5 mm/h), and comorbidity burden were higher in late-onset RA compared to young-onset RA (p < 0.01). Mean DAS28-ESR (4.6 vs. 4.3) and HAQ (1.2 vs. 1.1) scores were higher in late-onset RA patients (p < 0.05). Late-onset RA patients received more initial disease-modifying antirheumatic drug (DMARD) monotherapy and corticosteroids in comparison to greater DMARD/biologic combination therapy in young-onset RA patients (p < 0.05). Adjusted multivariate analyses showed that late-onset RA was independently associated with higher mean DAS28-ESR and HAQ scores, but not CDAI. Late-onset RA patients have greater disease activity that may contribute to disability early in the disease course. Despite this, initial treatment consists of less combination DMARD and biologic use in late-onset RA patients. This may have implications for future response to therapy and development of joint damage, disability, and comorbidities in this group.
Examination of British government rhetoric about lifelong learning and access indicates they are actually promoting education as an economic policy. This is evident in the exclusion of older adults. Genuine lifelong learning should be a philosophy and practice that embraces a wide range of learning, enhancing quality of life. (Contains 32…
Saji, Genn [Ex-Secretariat of Nuclear Safety Commission (Japan)], E-mail: email@example.com; Timofeev, Boris [CRISM Prometey, Shpalernaja 49, St. Petersburg 193015 (Russian Federation)
The study of the effects behind the degradation of components and materials is becoming increasingly important for the safe operation of aged plants especially when it comes to life extension. Since the Russian nuclear community began to examine life extension issues nearly 15 years ago, there is much to learn from these pioneering studies. At the Ninth International Conference entitled 'Material Issues in Design, Manufacturing and Operation of Nuclear Power Plants Equipment' held in St. Petersburg, 2006, recent data were introduced regarding the ageing effects of mechanical properties of various kinds of steel and welding joints of Russian NPP components. The meeting was organized by the Central Research Institute of Structural Materials (CRISM) 'Prometey' in cooperation with the IAEA and JRC-EU. In reviewing the recent data presented at the Ninth Conference, the authors believe that the paradigms of structural integrity issues in aged plants are now reasonably well established in (1) fracture mechanics and irradiation hardening of reactor vessels and core internals and (2) thermal ageing and annealing effects. However, the first author, G. Saji, believes that the current approach of low-cycle fatigue is still unable to prevent and predict environmentally assisted cracks such as demonstrated in the IGSCC issues in the down-comer pipes of RBMK plants and various steam generator corrosion issues. This fundamental flaw stems from design codes, which do not incorporate the basic knowledge of electrochemical corrosion mechanisms as represented by the corrosion current.
Brianne Alyssia Kent
Full Text Available Alzheimer’s disease (AD is a global epidemic. Unfortunately, we are still without effective treatments or a cure for this disease, which is having devastating consequences for patients, their families, and societies around the world. Until effective treatments are developed, promoting overall health may hold potential for delaying the onset or preventing neurodegenerative diseases such as AD. In particular, chronobiological concepts may provide a useful framework for identifying the earliest signs of age-related disease as well as inexpensive and noninvasive methods for promoting health. It is well reported that AD is associated with disrupted circadian functioning to a greater extent than normal aging. However, it is unclear if the central circadian clock (i.e., the suprachiasmatic nucleus is dysfunctioning, or whether the synchrony between the central and peripheral clocks that control behaviour and metabolic processes are becoming uncoupled. Desynchrony of rhythms can negatively affect health, increasing morbidity and mortality in both animal models and humans. If the uncoupling of rhythms is contributing to AD progression or exacerbating symptoms, then it may be possible to draw from the food-entrainment literature to identify mechanisms for re-synchronizing rhythms to improve overall health and reduce the severity of symptoms. The following review will briefly summarize the circadian system, its potential role in AD, and propose using a feeding-related neuropeptide, such as ghrelin, to synchronize uncoupled rhythms. Synchronizing rhythms may be an inexpensive way to promote healthy aging and delay the onset of neurodegenerative disease such as AD.
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Attali, Eve; Dalla Barba, Gianfranco
Normal aging is characterized by deficits that cross multiple cognitive domains including episodic memory and attention. Compared to young adults (YA), older adults (OA) not only show reduction in true memories, but also an increase in false memories. In this study we aim to elucidate how the production of confabulation is influenced by encoding and retrieval processes. We hypothesized that in OA, compared to YA, over-learned information interferes with the recall of specific, unique past episodes and this interference should be more prominent when a concurrent task perturbs the encoding of the episodes to be recalled. We tested this hypothesis using an experimental paradigm in which a group of OA and a group of YA had to recall three different types of story: a previously unknown story, a well-known fairy tale (Snow White), and a modified well-known fairy tale (Little Red Riding Hood is not eaten by the wolf), in three different experimental conditions: (1) free encoding and free retrieval; (2) Divided attention (DA) at encoding and free retrieval; and (3) free encoding and DA at retrieval. Results showed that OA produced significantly more confabulations than YA, particularly, in the recall of the modified fairy tale. Moreover, DA at encoding markedly increased the number of confabulations, whereas DA at retrieval had no effect on confabulation. Our findings reveal the implications of two phenomena in the production of confabulation in normal aging: the effect of poor encoding and the interference of strongly represented, over-learned information in episodic memory recall.
Full Text Available Animal models are necessary tools for solving the most serious challenges facing medical research. In aging and neurodegenerative disease studies, rodents occupy a place of choice. However, the most challenging questions about longevity, the complexity and functioning of brain networks or social intelligence can almost only be investigated in nonhuman primates. Beside the fact that their brain structure is much closer to that of humans, they develop highly complex cognitive strategies and they are visually-oriented like humans. For these reasons, they deserve consideration, although their management and care are more complicated and the related costs much higher. Despite these caveats, considerable scientific advances have been possible using nonhuman primates. This review concisely summarizes their role in the study of aging and of the mechanisms involved in neurodegenerative disorders associated mainly with cognitive dysfunctions (Alzheimer’s and prion diseases or motor deficits (Parkinson’s and related diseases.
Dorra Hmida-Ben Brahim
Full Text Available Huntington’s disease (HD is an autosomal dominant neurodegenerative disorder. The causative mutation is an expansion of more than 36 CAG repeats in the first exon of IT15 gene. Many studies have shown that the IT15 interacts with several modifier genes to regulate the age at onset (AO of HD. Our study aims to investigate the implication of CAG expansion and 9 modifiers in the age at onset variance of 15 HD Tunisian patients and to establish the correlation between these modifiers genes and the AO of this disease. Despite the small number of studied patients, this report consists of the first North African study in Huntington disease patients. Our results approve a specific effect of modifiers genes in each population.
Zhuang Jian-Jun; Ning Xin-Bao; Yang Xiao-Dong; Hou Feng-Zhen; Huo Cheng-Yu
In this paper the decrease in the Hurst exponent of human gait with aging and neurodegenerative diseases was observed by using an improved rescaled range (R/S) analysis method. It indicates that the long-range correlations of gait rhythm from young healthy people are stronger than those from the healthy elderly and the diseased.The result further implies that fractal dynamics in human gait will be altered due to weakening or impairment of neural control on locomotion resulting from aging and neurodegenerative diseases. Due to analysing short-term data sequences rather than long datasets required by most nonlinear methods, the algorithm has the characteristics of simplicity and sensitivity, most importantly, fast calculation as well as powerful anti-noise capacities. These findings have implications for modelling locomotor control and also for quantifying gait dynamics in varying physiologic and pathologic states.
Zhuang, Jian-Jun; Ning, Xin-Bao; Yang, Xiao-Dong; Hou, Feng-Zhen; Huo, Cheng-Yu
In this paper the decrease in the Hurst exponent of human gait with aging and neurodegenerative diseases was observed by using an improved rescaled range (R/S) analysis method. It indicates that the long-range correlations of gait rhythm from young healthy people are stronger than those from the healthy elderly and the diseased. The result further implies that fractal dynamics in human gait will be altered due to weakening or impairment of neural control on locomotion resulting from aging and neurodegenerative diseases. Due to analysing short-term data sequences rather than long datasets required by most nonlinear methods, the algorithm has the characteristics of simplicity and sensitivity, most importantly, fast calculation as well as powerful anti-noise capacities. These findings have implications for modelling locomotor control and also for quantifying gait dynamics in varying physiologic and pathologic states.
Full Text Available Introduction: Speech recognition in adverse listening conditions becomes more difficult as we age, particularly for individuals with age-related hearing loss (ARHL. Whether these difficulties can be eased with training remains debated, because it is not clear whether the outcomes are sufficiently general to be of use outside of the training context. The aim of the current study was to compare training-induced learning and generalization between normal-hearing older adults and those with ARHL.Methods: 56 listeners (60-72 y/o, 35 participants with ARHL and 21 normal hearing adults participated in the study. The study design was a cross over design with three groups (immediate-training, delayed-training and no-training group. Trained participants received 13 sessions of home-based auditory training over the course of 4 weeks. Three adverse listening conditions were targeted: (1 Speech-in-noise (2 time compressed speech and (3 competing speakers, and the outcomes of training were compared between normal and ARHL groups. Pre- and post-test sessions were completed by all participants. Outcome measures included tests on all of the trained conditions as well as on a series of untrained conditions designed to assess the transfer of learning to other speech and non-speech conditions. Results: Significant improvements on all trained conditions were observed in both ARHL and normal-hearing groups over the course of training. Normal hearing participants learned more than participants with ARHL in the speech-in-noise condition, but showed similar patterns of learning in the other conditions. Greater pre- to post-test changes were observed in trained than in untrained listeners on all trained conditions. In addition, the ability of trained listeners from the ARHL group to discriminate minimally different pseudowords in noise also improved with training. Conclusions: ARHL did not preclude auditory perceptual learning but there was little generalization to
Karawani, Hanin; Bitan, Tali; Attias, Joseph; Banai, Karen
Introduction : Speech recognition in adverse listening conditions becomes more difficult as we age, particularly for individuals with age-related hearing loss (ARHL). Whether these difficulties can be eased with training remains debated, because it is not clear whether the outcomes are sufficiently general to be of use outside of the training context. The aim of the current study was to compare training-induced learning and generalization between normal-hearing older adults and those with ARHL. Methods : Fifty-six listeners (60–72 y/o), 35 participants with ARHL, and 21 normal hearing adults participated in the study. The study design was a cross over design with three groups (immediate-training, delayed-training, and no-training group). Trained participants received 13 sessions of home-based auditory training over the course of 4 weeks. Three adverse listening conditions were targeted: (1) Speech-in-noise, (2) time compressed speech, and (3) competing speakers, and the outcomes of training were compared between normal and ARHL groups. Pre- and post-test sessions were completed by all participants. Outcome measures included tests on all of the trained conditions as well as on a series of untrained conditions designed to assess the transfer of learning to other speech and non-speech conditions. Results : Significant improvements on all trained conditions were observed in both ARHL and normal-hearing groups over the course of training. Normal hearing participants learned more than participants with ARHL in the speech-in-noise condition, but showed similar patterns of learning in the other conditions. Greater pre- to post-test changes were observed in trained than in untrained listeners on all trained conditions. In addition, the ability of trained listeners from the ARHL group to discriminate minimally different pseudowords in noise also improved with training. Conclusions : ARHL did not preclude auditory perceptual learning but there was little generalization to
Wei, Min; Brandhorst, Sebastian; Shelehchi, Mahshid; Mirzaei, Hamed; Cheng, Chia Wei; Budniak, Julia; Groshen, Susan; Mack, Wendy J; Guen, Esra; Di Biase, Stefano; Cohen, Pinchas; Morgan, Todd E; Dorff, Tanya; Hong, Kurt; Michalsen, Andreas; Laviano, Alessandro; Longo, Valter D
Calorie restriction or changes in dietary composition can enhance healthy aging, but the inability of most subjects to adhere to chronic and extreme diets, as well as potentially adverse effects, limits their application. We randomized 100 generally healthy participants from the United States into two study arms and tested the effects of a fasting-mimicking diet (FMD)-low in calories, sugars, and protein but high in unsaturated fats-on markers/risk factors associated with aging and age-related diseases. We compared subjects who followed 3 months of an unrestricted diet to subjects who consumed the FMD for 5 consecutive days per month for 3 months. Three FMD cycles reduced body weight, trunk, and total body fat; lowered blood pressure; and decreased insulin-like growth factor 1 (IGF-1). No serious adverse effects were reported. After 3 months, control diet subjects were crossed over to the FMD program, resulting in a total of 71 subjects completing three FMD cycles. A post hoc analysis of subjects from both FMD arms showed that body mass index, blood pressure, fasting glucose, IGF-1, triglycerides, total and low-density lipoprotein cholesterol, and C-reactive protein were more beneficially affected in participants at risk for disease than in subjects who were not at risk. Thus, cycles of a 5-day FMD are safe, feasible, and effective in reducing markers/risk factors for aging and age-related diseases. Larger studies in patients with diagnosed diseases or selected on the basis of risk factors are warranted to confirm the effect of the FMD on disease prevention and treatment.
Bruce N. Ames
Full Text Available I review three of our research efforts which suggest that optimizing micronutrient intake will in turn optimize metabolism, resulting in decreased DNA damage and less cancer as well as other degenerative diseases of aging. (1 Research on delay of the mitochondrial decay of aging, including release of mutagenic oxidants, by supplementing rats with lipoic acid and acetyl carnitine. (2 The triage theory, which posits that modest micronutrient deficiencies (common in much of the population accelerate molecular aging, including DNA damage, mitochondrial decay, and supportive evidence for the theory, including an in-depth analysis of vitamin K that suggests the importance of achieving optimal micronutrient intake for longevity. (3 The finding that decreased enzyme binding constants (increased Km for coenzymes (or substrates can result from protein deformation and loss of function due to an age-related decline in membrane fluidity, or to polymorphisms or mutation. The loss of enzyme function can be compensated by a high dietary intake of any of the B vitamins, which increases the level of the vitamin-derived coenzyme. This dietary remediation illustrates the importance of understanding the effects of age and polymorphisms on optimal micronutrient requirements. Optimizing micronutrient intake could have a major effect on the prevention of cancer and other degenerative diseases of aging.
Tamás, Andrea; Lubics, Andrea; Lengvári, István; Reglodi, Dóra
The effects of aging and gender on the neurochemistry of the dopaminergic system have been studied extensively; however, data on comparative behavioral consequences of lesions of the dopaminergic system in aging and in female animals are limited. This study presents experimental results on the behavioral and morphological outcome in young, aging, and gonadectomized male and female rats in the 6-OHDA model of Parkinson's disease. Both young and aging male animals were more susceptible to 6-OHDA than females: female rats had significantly less dopaminergic cell loss and showed a higher degree of behavioral recovery. Although the dopaminergic cell loss was only slightly more in the aging rats of the same sex, they showed more severe behavioral deficits in both gender groups. Ovariectomy did not significantly influence the dopaminergic cell loss, but behavioral recovery was worse when compared to non-ovariectomized females. In contrast, castrated males had significantly less dopaminergic cell loss than non-castrated males, but the behavioral recovery was not significantly better. The obtained results are discussed in light of the available literature on the age and gender differences in animals models of Parkinson's disease.
Chang, Jie; Li, Boyang; Li, Jingjing; Sun, Yang
In contrast with most developed countries, mortality due to ischemic heart disease (IHD) continues to rise in China. We examined the effects of age, period, and cohort on IHD mortality in urban and rural populations from 1987 to 2013 to identify the drivers of this trend. Region-specific data on annual IHD mortality among adults aged 20 to 84 years and corresponding population statistics were collected. We then tested for age, period, and cohort effects using the Intrinsic Estimator approach. Our results indicated that IHD mortality in China increased significantly over the three decades studied. There was a log-linear increase in the age effect on IHD mortality as those aged 80–84 showed 277 and 161 times greater IHD mortality risk than those aged 20–24 in urban and rural populations, respectively. While there was an upward trend in the period effect in both populations, the influence of the cohort effect on mortality decreased over time for those born from 1904 to 1993. The age, period, and cohort effects on mortality in China were generally comparable between urban and rural populations. The results suggest that population aging is a major driver behind the rapid rise in IHD mortality. Increased exposure to air pollution may also have played a role in driving the period effect
孙云; 邓杨梅; 王德俊; 沈春锋; 刘晓梅; 张洪泉
To observe the effects of Cistanche desertica polysaccharides (CDP) on the learning and memory functions and cerebral ultrastructure in experimental aging mice. Methods: CDP was administrated intragastrically 50 or 100 mg/kg per day for 64 successive days to experimental aging model mice induced by D-galactose, then the learning and memory functions of mice were estimated by step-down test and Y-maze test; organelles of brain tissue and cerebral ultrastructure were observed by transmission electron microscope and physical strength was determined by swimming test. Results: CDP could obviously enhance the learning and memory functions (P＜0.01) and prolong the swimming time (P＜0.05), decrease the number of lipofuscin and slow down the degeneration of mitochondria in neurons(P＜0.05), and improve the degeneration of cerebral ultra-structure in aging mice. Conclusion: CDP could improve the impaired physiological function and alleviate cerebral morphological change in experimental aging mice.