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Sample records for age-related cognitive change

  1. Shared and Unique Genetic and Environmental Influences on Aging-Related Changes in Multiple Cognitive Abilities

    ERIC Educational Resources Information Center

    Tucker-Drob, Elliot M.; Reynolds, Chandra A.; Finkel, Deborah; Pedersen, Nancy L.

    2014-01-01

    Aging-related declines occur in many different domains of cognitive function during middle and late adulthood. However, whether a global dimension underlies individual differences in changes in different domains of cognition and whether global genetic influences on cognitive changes exist is less clear. We addressed these issues by applying…

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

    ERIC Educational Resources Information Center

    Zelanti, Pierre S.; Droit-Volet, Sylvie

    2011-01-01

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

  3. Sleep Duration and Age-Related Changes in Brain Structure and Cognitive Performance

    PubMed Central

    Lo, June C.; Loh, Kep Kee; Zheng, Hui; Sim, Sam K.Y.; Chee, Michael W.L.

    2014-01-01

    Study Objectives: To investigate the contribution of sleep duration and quality to age-related changes in brain structure and cognitive performance in relatively healthy older adults. Design: Community-based longitudinal brain and cognitive aging study using a convenience sample. Setting: Participants were studied in a research laboratory. Participants: Relatively healthy adults aged 55 y and older at study commencement. Interventions: N/A. Measurements and Results: Participants underwent magnetic resonance imaging and neuropsychological assessment every 2 y. Subjective assessments of sleep duration and quality and blood samples were obtained. Each hour of reduced sleep duration at baseline augmented the annual expansion rate of the ventricles by 0.59% (P = 0.007) and the annual decline rate in global cognitive performance by 0.67% (P = 0.050) in the subsequent 2 y after controlling for the effects of age, sex, education, and body mass index. In contrast, global sleep quality at baseline did not modulate either brain or cognitive aging. High-sensitivity C-reactive protein, a marker of systemic inflammation, showed no correlation with baseline sleep duration, brain structure, or cognitive performance. Conclusions: In healthy older adults, short sleep duration is associated with greater age-related brain atrophy and cognitive decline. These associations are not associated with elevated inflammatory responses among short sleepers. Citation: Lo JC, Loh KK, Zheng H, Sim SK, Chee MW. Sleep duration and age-related changes in brain structure and cognitive performance. SLEEP 2014;37(7):1171-1178. PMID:25061245

  4. Contribution of changes in ubiquitin and myelin basic protein to age-related cognitive decline.

    PubMed

    Wang, Deng-Shun; Bennett, David A; Mufson, Elliott J; Mattila, Petri; Cochran, Elizabeth; Dickson, Dennis W

    2004-01-01

    The structural substrates for age-associated cognitive and motor slowing are not known, but age-related white matter changes, such as ubiquitin (UBQ)-immunoreactive granular degeneration of myelin, might contribute to this slowing. To address this hypothesis we measured immunoreactivity for UBQ and myelin basic protein (MBP) in frontal white matter of age-, sex- and postmortem interval-matched cases with no cognitive impairment (NCI; N=12), mild cognitive impairment (MCI; N=14) and Alzheimer disease (AD; N=12). There were no significant correlations between UBQ in white matter and cognitive measures, but MBP was significantly lower in AD compared with NCI and MCI. MBP correlated with overall cognition as assessed by neuropsychological summary scores, as well as with timed cognitive tests and those that reflect frontal functions. An age-related decrease in MBP immunoreactivity was detected in NCI cases (r=0.71). These results support the hypothesis that white matter pathology may contribute to age-associated decline in cognition. PMID:14687885

  5. Shared and unique genetic and environmental influences on aging-related changes in multiple cognitive abilities.

    PubMed

    Tucker-Drob, Elliot M; Reynolds, Chandra A; Finkel, Deborah; Pedersen, Nancy L

    2014-01-01

    Aging-related declines occur in many different domains of cognitive function during middle and late adulthood. However, whether a global dimension underlies individual differences in changes in different domains of cognition and whether global genetic influences on cognitive changes exist is less clear. We addressed these issues by applying multivariate growth curve models to longitudinal data from 857 individuals from the Swedish Adoption/Twin Study of Aging, who had been measured on 11 cognitive variables representative of verbal, spatial, memory, and processing speed abilities up to 5 times over up to 16 years between ages 50 and 96 years. Between ages 50 and 65 years scores on different tests changed relatively independently of one another, and there was little evidence for strong underlying dimensions of change. In contrast, over the period between 65 and 96 years of age, there were strong interrelations among rates of change both within and across domains. During this age period, variability in rates of change were, on average, 52% domain-general, 8% domain-specific, and 39% test-specific. Quantitative genetic decomposition indicated that 29% of individual differences in a global domain-general dimension of cognitive changes during this age period were attributable to genetic influences, but some domain-specific genetic influences were also evident, even after accounting for domain-general contributions. These findings are consistent with a balanced global and domain-specific account of the genetics of cognitive aging. PMID:23586942

  6. Like cognitive function, decision making across the life span shows profound age-related changes

    PubMed Central

    Tymula, Agnieszka; Rosenberg Belmaker, Lior A.; Ruderman, Lital; Glimcher, Paul W.; Levy, Ifat

    2013-01-01

    It has long been known that human cognitive function improves through young adulthood and then declines across the later life span. Here we examined how decision-making function changes across the life span by measuring risk and ambiguity attitudes in the gain and loss domains, as well as choice consistency, in an urban cohort ranging in age from 12 to 90 y. We identified several important age-related patterns in decision making under uncertainty: First, we found that healthy elders between the ages of 65 and 90 were strikingly inconsistent in their choices compared with younger subjects. Just as elders show profound declines in cognitive function, they also show profound declines in choice rationality compared with their younger peers. Second, we found that the widely documented phenomenon of ambiguity aversion is specific to the gain domain and does not occur in the loss domain, except for a slight effect in older adults. Finally, extending an earlier report by our group, we found that risk attitudes across the life span show an inverted U-shaped function; both elders and adolescents are more risk-averse than their midlife counterparts. Taken together, these characterizations of decision-making function across the life span in this urban cohort strengthen the conclusions of previous reports suggesting a profound impact of aging on cognitive function in this domain. PMID:24082105

  7. Microstructural white matter changes mediate age-related cognitive decline on the Montreal Cognitive Assessment (MoCA).

    PubMed

    Jolly, Todd A D; Cooper, Patrick S; Badwi, Syarifah Azizah Wan Ahmadul; Phillips, Natalie A; Rennie, Jaime L; Levi, Christopher R; Drysdale, Karen A; Parsons, Mark W; Michie, Patricia T; Karayanidis, Frini

    2016-02-01

    Although the relationship between aging and cognitive decline is well established, there is substantial individual variability in the degree of cognitive decline in older adults. The present study investigates whether variability in cognitive performance in community-dwelling older adults is related to the presence of whole brain or tract-specific changes in white matter microstructure. Specifically, we examine whether age-related decline in performance on the Montreal Cognitive Assessment (MoCA), a cognitive screening tool, is mediated by the white matter microstructural decline. We also examine if this relationship is driven by the presence of cardiovascular risk factors or variability in cerebral arterial pulsatility, an index of cardiovascular risk. Sixty-nine participants (aged 43-87) completed behavioral and MRI testing including T1 structural, T2-weighted FLAIR, and diffusion-weighted imaging (DWI) sequences. Measures of white matter microstructure were calculated using diffusion tensor imaging analyses on the DWI sequence. Multiple linear regression revealed that MoCA scores were predicted by radial diffusivity (RaD) of white matter beyond age or other cerebral measures. While increasing age and arterial pulsatility were associated with increasing RaD, these factors did not mediate the relationship between total white matter RaD and MoCA. Further, the relationship between MoCA and RaD was specific to participants who reported at least one cardiovascular risk factor. These findings highlight the importance of cardiovascular risk factors in the presentation of cognitive decline in old age. Further work is needed to establish whether medical or lifestyle management of these risk factors can prevent or reverse cognitive decline in old age. PMID:26511789

  8. Age-related changes in dentate gyrus cell numbers, neurogenesis, and associations with cognitive impairments in the rhesus monkey.

    PubMed

    Ngwenya, Laura B; Heyworth, Nadine C; Shwe, Yamin; Moore, Tara L; Rosene, Douglas L

    2015-01-01

    The generation of new neurons in the adult mammalian brain is well-established for the hippocampal dentate gyrus (DG). However, the role of neurogenesis in hippocampal function and cognition, how it changes in aging, and the mechanisms underlying this are yet to be elucidated in the monkey brain. To address this, we investigated adult neurogenesis in the DG of 42 rhesus monkeys (39 cognitively tested) ranging in age from young adult to the elderly. We report here that there is an age-related decline in proliferation and a delayed development of adult neuronal phenotype. Additionally, we show that many of the new neurons survive throughout the lifetime of the animal and may contribute to a modest increase in total neuron number in the granule cell layer of the DG over the adult life span. Lastly, we find that measures of decreased adult neurogenesis are only modestly predictive of age-related cognitive impairment. PMID:26236203

  9. Age-related changes in dentate gyrus cell numbers, neurogenesis, and associations with cognitive impairments in the rhesus monkey

    PubMed Central

    Ngwenya, Laura B.; Heyworth, Nadine C.; Shwe, Yamin; Moore, Tara L.; Rosene, Douglas L.

    2015-01-01

    The generation of new neurons in the adult mammalian brain is well-established for the hippocampal dentate gyrus (DG). However, the role of neurogenesis in hippocampal function and cognition, how it changes in aging, and the mechanisms underlying this are yet to be elucidated in the monkey brain. To address this, we investigated adult neurogenesis in the DG of 42 rhesus monkeys (39 cognitively tested) ranging in age from young adult to the elderly. We report here that there is an age-related decline in proliferation and a delayed development of adult neuronal phenotype. Additionally, we show that many of the new neurons survive throughout the lifetime of the animal and may contribute to a modest increase in total neuron number in the granule cell layer of the DG over the adult life span. Lastly, we find that measures of decreased adult neurogenesis are only modestly predictive of age-related cognitive impairment. PMID:26236203

  10. APOE and aging-related cognitive change in a longitudinal cohort of men.

    PubMed

    Rantalainen, Ville; Lahti, Jari; Henriksson, Markus; Kajantie, Eero; Tienari, Pentti; Eriksson, Johan G; Raikkonen, Katri

    2016-08-01

    We examined associations between APOE major isoforms, rs405509 promoter and rs440446 intron-1 polymorphisms, and nonpathologic cognitive aging. Men from the Helsinki Birth Cohort Study took the Finnish Defence Forces Basic Intellectual Ability Test twice, at age 20.1 (n = 404) and 67.6 years (n = 247). APOE major isoforms did not associate with cognitive ability. In the APOE major isoform-adjusted analyses, the number of rs405509 minor alleles was associated with a higher cognitive ability total and verbal, arithmetic, and visuospatial subtest scores at 67.6 years (p-values < 0.004). In the analyses of cognitive change, the visuospatial subtest score increased across time in rs440446 minor allele carriers but decreased in noncarriers (p = 0.007). Associations in the APOE major isoform-stratified analyses were significant in the APOE ε3/3 homozygotes only. The APOE locus harbors additional modifying alleles, independent of APOE major isoforms that are associated with better preserved general cognitive ability in nondemented elderly men and change in visuospatial ability across 5 decades. These results suggest that at least 2 distinct mechanisms link the APOE locus with cognitive ability. PMID:27318143

  11. Age-Related Changes in Sleep and Circadian Rhythms: Impact on Cognitive Performance and Underlying Neuroanatomical Networks

    PubMed Central

    Schmidt, Christina; Peigneux, Philippe; Cajochen, Christian

    2012-01-01

    Circadian and homeostatic sleep-wake regulatory processes interact in a fine tuned manner to modulate human cognitive performance. Dampening of the circadian alertness signal and attenuated deterioration of psychomotor vigilance in response to elevated sleep pressure with aging change this interaction pattern. As evidenced by neuroimaging studies, both homeostatic sleep pressure and circadian sleep-wake promotion impact on cognition-related cortical and arousal-promoting subcortical brain regions including the thalamus, the anterior hypothalamus, and the brainstem locus coeruleus (LC). However, how age-related changes in circadian and homeostatic processes impact on the cerebral activity subtending waking performance remains largely unexplored. Post-mortem studies point to neuronal degeneration in the SCN and age-related modifications in the arousal-promoting LC. Alongside, cortical frontal brain areas are particularly susceptible both to aging and misalignment between circadian and homeostatic processes. In this perspective, we summarize and discuss here the potential neuroanatomical networks underlying age-related changes in circadian and homeostatic modulation of waking performance, ranging from basic arousal to higher order cognitive behaviors. PMID:22855682

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

    ERIC Educational Resources Information Center

    American Psychologist, 2012

    2012-01-01

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

  13. Inspection Time and Cognitive Abilities in Twins Aged 7 to 17 Years: Age-Related Changes, Heritability and Genetic Covariance

    ERIC Educational Resources Information Center

    Edmonds, Caroline J.; Isaacs, Elizabeth B.; Visscher, Peter M.; Rogers, Mary; Lanigan, Julie; Singhal, Atul; Lucas, Alan; Gringras, Paul; Denton, Jane; Deary, Ian J.

    2008-01-01

    We studied the age-related differences in inspection time and multiple cognitive domains in a group of monozygotic (MZ) and dizygotic (DZ) twins aged 7 to 17 years. Data from 111 twin pairs and 19 singleton siblings were included. We found clear age-related trends towards more efficient visual information processing in older participants. There…

  14. Age-related changes in the cerebral substrates of cognitive procedural learning.

    PubMed

    Hubert, Valérie; Beaunieux, Hélène; Chételat, Gaël; Platel, Hervé; Landeau, Brigitte; Viader, Fausto; Desgranges, Béatrice; Eustache, Francis

    2009-04-01

    Cognitive procedural learning occurs in three qualitatively different phases (cognitive, associative, and autonomous). At the beginning of this process, numerous cognitive functions are involved, subtended by distinct brain structures such as the prefrontal and parietal cortex and the cerebellum. As the learning progresses, these cognitive components are gradually replaced by psychomotor abilities, reflected by the increasing involvement of the cerebellum, thalamus, and occipital regions. In elderly subjects, although cognitive studies have revealed a learning effect, performance levels differ during the acquisition of a procedure. The effects of age on the learning of a cognitive procedure have not yet been examined using functional imaging. The aim of this study was therefore to characterize the cerebral substrates involved in the learning of a cognitive procedure, comparing a group of older subjects with young controls. For this purpose, we performed a positron emission tomography activation study using the Tower of Toronto task. A direct comparison of the two groups revealed the involvement of a similar network of brain regions at the beginning of learning (cognitive phase). However, the engagement of frontal and cingulate regions persisted in the older group as learning continued, whereas it ceased in the younger controls. We assume that this additional activation in the older group during the associative and autonomous phases reflected compensatory processes and the fact that some older subjects failed to fully automate the procedure. PMID:18537110

  15. Age-related changes in the cerebral substrates of cognitive procedural learning

    PubMed Central

    Hubert, Valérie; Beaunieux, Hélène; Chételat, Gaël; Platel, Hervé; Landeau, Brigitte; Viader, Fausto; Desgranges, Béatrice; Eustache, Francis

    2009-01-01

    Cognitive procedural learning occurs in three qualitatively different phases (cognitive, associative and autonomous). At the beginning of this process, numerous cognitive functions are involved, subtended by distinct brain structures such as the prefrontal and parietal cortex and the cerebellum. As the learning progresses, these cognitive components are gradually replaced by psychomotor abilities, reflected by the increasing involvement of the cerebellum, thalamus and occipital regions. In elderly subjects, although cognitive studies have revealed a learning effect, performance levels differ during the acquisition of a procedure. The effects of age on the learning of a cognitive procedure have not yet been examined using functional imaging. The aim of this study was therefore to characterize the cerebral substrates involved in the learning of a cognitive procedure, comparing a group of older subjects with young controls. For this purpose, we performed a positron emission tomography activation study using the Tower of Toronto task. A direct comparison of the two groups revealed the involvement of a similar network of brain regions at the beginning of learning (cognitive phase). However, whereas the engagement of frontal and cingulate regions persisted in the older group as learning continued, it ceased in the younger controls. We assume that this additional activation in the older group during the associative and autonomous phases reflected compensatory processes and the fact that some older subjects failed to fully automate the procedure. PMID:18537110

  16. Age-Related Changes in Cognitive Processing of Moral and Social Conventional Violations

    ERIC Educational Resources Information Center

    Lahat, Ayelet; Helwig, Charles C.; Zelazo, Philip David

    2012-01-01

    Moral and conventional violations are usually judged differently: Only moral violations are treated as independent of social rules. To investigate the cognitive processing involved in the development of this distinction, undergraduates (N = 34), adolescents (N = 34), and children (N = 14) read scenarios presented on a computer that had 1 of 3…

  17. Age-Related White Matter Changes

    PubMed Central

    Xiong, Yun Yun; Mok, Vincent

    2011-01-01

    Age-related white matter changes (WMC) are considered manifestation of arteriolosclerotic small vessel disease and are related to age and vascular risk factors. Most recent studies have shown that WMC are associated with a host of poor outcomes, including cognitive impairment, dementia, urinary incontinence, gait disturbances, depression, and increased risk of stroke and death. Although the clinical relevance of WMC has been extensively studied, to date, only very few clinical trials have evaluated potential symptomatic or preventive treatments for WMC. In this paper, we reviewed the current understanding in the pathophysiology, epidemiology, clinical importance, chemical biomarkers, and treatments of age-related WMC. PMID:21876810

  18. Consequences of Age-Related Cognitive Declines

    PubMed Central

    Salthouse, Timothy

    2013-01-01

    Adult age differences in a variety of cognitive abilities are well documented, and many of those abilities have been found to be related to success in the workplace and in everyday life. However, increased age is seldom associated with lower levels of real-world functioning, and the reasons for this lab-life discrepancy are not well understood. This article briefly reviews research concerned with relations of age to cognition, relations of cognition to successful functioning outside the laboratory, and relations of age to measures of work performance and achievement. The final section discusses several possible explanations for why there are often little or no consequences of age-related cognitive declines in everyday functioning. PMID:21740223

  19. Intrinsic Hippocampal Excitability Changes of Opposite Signs and Different Origins in CA1 and CA3 Pyramidal Neurons Underlie Aging-Related Cognitive Deficits

    PubMed Central

    Oh, M. Matthew; Simkin, Dina; Disterhoft, John F.

    2016-01-01

    Aging-related cognitive deficits have been attributed to dysfunction of neurons due to failures at synaptic or intrinsic loci, or both. Given the importance of the hippocampus for successful encoding of memory and that the main output of the hippocampus is via the CA1 pyramidal neurons, much of the research has been focused on identifying the aging-related changes of these CA1 pyramidal neurons. We and others have discovered that the postburst afterhyperpolarization (AHP) following a train of action potentials is greatly enlarged in CA1 pyramidal neurons of aged animals. This enlarged postburst AHP is a significant factor in reducing the intrinsic excitability of these neurons, and thus limiting their activity in the neural network during learning. Based on these data, it has largely been thought that aging-related cognitive deficits are attributable to reduced activity of pyramidal neurons. However, recent in vivo and ex vivo studies provide compelling evidence that aging-related deficits could also be due to a converse change in CA3 pyramidal neurons, which show increased activity with aging. In this review, we will incorporate these recent findings and posit that an interdependent dynamic dysfunctional change occurs within the hippocampal network, largely due to altered intrinsic excitability in CA1 and CA3 hippocampal pyramidal neurons, which ultimately leads to the aging-related cognitive deficits. PMID:27375440

  20. Neuroanatomical Substrates of Age-Related Cognitive Decline

    ERIC Educational Resources Information Center

    Salthouse, Timothy A.

    2011-01-01

    There are many reports of relations between age and cognitive variables and of relations between age and variables representing different aspects of brain structure and a few reports of relations between brain structure variables and cognitive variables. These findings have sometimes led to inferences that the age-related brain changes cause the…

  1. Age-Related Changes in Creative Thinking

    ERIC Educational Resources Information Center

    Roskos-Ewoldsen, Beverly; Black, Sheila R.; Mccown, Steven M.

    2008-01-01

    Age-related differences in cognitive processes were used to understand age-related declines in creativity. According to the Geneplore model (Finke, Ward, & Smith, 1992), there are two phases of creativity--generating an idea and exploring the implications of the idea--each with different underlying cognitive processes. These two phases are…

  2. Age-related changes in brain activity are specific for high order cognitive processes during successful encoding of information in working memory

    PubMed Central

    Pinal, Diego; Zurrón, Montserrat; Díaz, Fernando

    2015-01-01

    Memory capacity suffers an age-related decline, which is supposed to be due to a generalized slowing of processing speed and to a reduced availability of processing resources. Information encoding in memory has been demonstrated to be very sensitive to age-related changes, especially when carried out through self-initiated strategies or under high cognitive demands. However, most event-related potentials (ERP) research on age-related changes in working memory (WM) has used tasks that preclude distinction between age-related changes in encoding and retrieval processes. Here, we used ERP recording and a delayed match to sample (DMS) task with two levels of memory load to assess age-related changes in electrical brain activity in young and old adults during successful information encoding in WM. Age-related decline was reflected in lower accuracy rates and longer reaction times in the DMS task. Beside, only old adults presented lower accuracy rates under high than low memory load conditions. However, effects of memory load on brain activity were independent of age and may indicate an increased need of processing after stimulus classification as reflected in larger mean voltages in high than low load conditions between 550 and 1000 ms post-stimulus for young and old adults. Regarding age-related effects on brain activity, results also revealed smaller P2 and P300 amplitudes that may signal the existence of an age dependent reduction in the processing resources available for stimulus evaluation and categorization. Additionally, P2 and N2 latencies were longer in old than in young participants. Furthermore, longer N2 latencies were related to greater accuracy rates on the DMS task, especially in old adults. These results suggest that age-related slowing of processing speed may be specific for target stimulus analysis and evaluation processes. Thus, old adults seem to improve their performance the longer they take to evaluate the stimulus they encode in visual WM. PMID

  3. Age-related changes in brain activity are specific for high order cognitive processes during successful encoding of information in working memory.

    PubMed

    Pinal, Diego; Zurrón, Montserrat; Díaz, Fernando

    2015-01-01

    Memory capacity suffers an age-related decline, which is supposed to be due to a generalized slowing of processing speed and to a reduced availability of processing resources. Information encoding in memory has been demonstrated to be very sensitive to age-related changes, especially when carried out through self-initiated strategies or under high cognitive demands. However, most event-related potentials (ERP) research on age-related changes in working memory (WM) has used tasks that preclude distinction between age-related changes in encoding and retrieval processes. Here, we used ERP recording and a delayed match to sample (DMS) task with two levels of memory load to assess age-related changes in electrical brain activity in young and old adults during successful information encoding in WM. Age-related decline was reflected in lower accuracy rates and longer reaction times in the DMS task. Beside, only old adults presented lower accuracy rates under high than low memory load conditions. However, effects of memory load on brain activity were independent of age and may indicate an increased need of processing after stimulus classification as reflected in larger mean voltages in high than low load conditions between 550 and 1000 ms post-stimulus for young and old adults. Regarding age-related effects on brain activity, results also revealed smaller P2 and P300 amplitudes that may signal the existence of an age dependent reduction in the processing resources available for stimulus evaluation and categorization. Additionally, P2 and N2 latencies were longer in old than in young participants. Furthermore, longer N2 latencies were related to greater accuracy rates on the DMS task, especially in old adults. These results suggest that age-related slowing of processing speed may be specific for target stimulus analysis and evaluation processes. Thus, old adults seem to improve their performance the longer they take to evaluate the stimulus they encode in visual WM. PMID

  4. Age-related Changes in Respiratory Function and Daily Living. A Tentative Model Including Psychosocial Variables, Respiratory Diseases and Cognition.

    PubMed

    Facal, David; González-Barcala, Francisco-Javier

    2016-01-01

    Changes in respiratory function are common in older populations and affect quality of life, social relationships, cognitive function and functional capacity. This paper reviews evidence reported in medical and psychological journals between 2000 and 2014 concerning the impact of changes in respiratory function on daily living in older adults. A tentative model establishes relationships involving respiratory function, cognitive function and functional capacities. The conclusion stresses the need for both longitudinal studies, to establish causal pathways between respiratory function and psychosocial aspects in aging, and intervention studies. PMID:26593253

  5. Age-Related Changes in Electrophysiological and Neuropsychological Indices of Working Memory, Attention Control, and Cognitive Flexibility

    PubMed Central

    Peltz, Carrie Brumback; Gratton, Gabriele; Fabiani, Monica

    2011-01-01

    Older adults exhibit great variability in their cognitive abilities, with some maintaining high levels of performance on executive control tasks and others showing significant deficits. Previous event-related potential (ERP) work has shown that some of these performance differences are correlated with persistence of the novelty/frontal P3 in older adults elicited by task-relevant events, presumably reflecting variability in the capacity to suppress orienting to unexpected but no longer novel events. In recent ERP work in young adults, we showed that the operation-span (OSPAN) task (a measure of attention control) is predictive of the ability of individuals to keep track of stimulus sequencing and to maintain running mental representations of task stimuli, as indexed by the parietally distributed P300 (or P3b). Both of these phenomena reflect aspects of frontal function (cognitive flexibility and attention control, respectively). To investigate these phenomena we sorted both younger and older adults into low- and high-working memory spans and low- and high-cognitive flexibility subgroups, and examined ERPs during an equal-probability choice reaction time task. For both age groups (a) participants with high OSPAN scores were better able to keep track of stimulus sequencing, as indicated by their smaller P3b to sequential changes; and (b) participants with lower cognitive flexibility had larger P3a than their high-scoring counterparts. However, these two phenomena did not interact suggesting that they manifest dissociable control mechanisms. Further, the fact that both effects are already visible in younger adults suggests that at least some of the brain mechanisms underlying individual differences in cognitive aging may already operate early in life. PMID:21887150

  6. Age-related changes in brain metabolites and cognitive function in APP/PS1 transgenic mice.

    PubMed

    Chen, Shuang-qing; Cai, Qing; Shen, Yu-ying; Wang, Pei-jun; Teng, Gao-jun; Zhang, Wei; Zang, Feng-chao

    2012-11-01

    Proton magnetic resonance spectroscopy ((1)H-MRS) and the Morris water maze (MWM) have played an important role in Alzheimer's disease (AD) research. The aim of this study was to determine whether (1)H-MRS and the MWM can detect for early AD in APP/PS1 transgenic (tg) mice. (1)H-MRS was performed in 20 tg mice and 15 wild-type mice at 3, 5 and 8 months of age. The concentration of N-acetylaspartate (NAA), glutamate (Glu), myo-inositol (mI), choline (Cho) and creatine (Cr) in the hippocampus were measured, and the NAA/Cr, Glu/Cr, mI/Cr and Cho/Cr ratios were quantified. Additionally, the spatial learning and memory of the mice were evaluated by MWM. The (1)H-MRS revealed that mI levels in tg mice were significantly higher at 3 months of age compared to wt mice, while the NAA and Glu levels in 5- and 8-month-old tg mice were significantly decreased (p<0.05). Additionally, significant cognitive changes only occurred at 8 months of age in APP/PS1 tg mice. These results indicated that metabolic changes preceded overt cognitive dysfunctions in early-stage AD, suggesting that (1)H-MRS is a more sensitive biomarker for assessing early AD. PMID:22828014

  7. Veterans have less age-related cognitive decline.

    PubMed

    McLay, R N; Lyketsos, C G

    2000-08-01

    Military service involves exposure to a number of stresses, both psychological and physical. On the other hand, military personnel generally maintain excellent fitness, and veterans have increased access to education and health care. The overall effect on age-related cognitive decline, whether for good or ill, of having served in the armed forces has not been investigated previously. In this study, we examined a diverse population of 208 veterans and 1,216 civilians followed as part of the Epidemiologic Catchment Area Study in 1981, 1982, and 1993 to 1996. We examined change in Mini-Mental State Examination (MMSE) score after a median of 11.5 years. Veterans were found to have significantly less decrease in MMSE scores at follow-up even after sex, race, and education were taken into account. These results suggest an overall positive effect of military service on the rate of age-related cognitive decline. PMID:10957857

  8. Age-related difference in relationships between cognitive processing speed and general cognitive status.

    PubMed

    Tam, Helena M K; Lam, Charlene L M; Huang, Haixia; Wang, Baolan; Lee, Tatia M C

    2015-01-01

    General cognitive status (GCS) is a composite of cognitive abilities reflecting full function. The literature suggests a relationship between cognitive processing speed and GCS, as well as age-related changes of processing speed on cognitive performance. Therefore, this study recruited 34 younger and 39 older adults to verify age-related differences in relationships between cognitive processing speed and GCS. We measured cognitive processing speed with the Processing Speed Index of the Wechsler Adult Intelligence Scale. Findings indicated that cognitive processing speed predicted GCS in older but not younger adults. Future research may be needed to verify the training effect of processing speed on GCS. This study also further examined cognitive factors related to processing speed in aging and the relationships between cognitive processing speed and verbal fluency, cognitive inhibition, and divided attention. A stepwise regression analysis indicated that only verbal fluency contributed significantly to cognitive processing speed in older adults, accounting for 21% of the variance. These observations suggest that age-related changes of prefrontal regions may not fully explain age-related decline in cognitive processing speed. PMID:24927241

  9. Epigenetic modification of PKMζ rescues aging-related cognitive impairment

    PubMed Central

    Chen, Chen; Meng, Shi-Qiu; Xue, Yan-Xue; Han, Ying; Sun, Cheng-Yu; Deng, Jia-Hui; Chen, Na; Bao, Yan-Ping; Zhang, Fei-Long; Cao, Lin-Lin; Zhu, Wei-Guo; Shi, Jie; Song, Wei-Hong; Lu, Lin

    2016-01-01

    Cognition is impacted by aging. However, the mechanisms that underlie aging-associated cognitive impairment are unclear. Here we showed that cognitive decline in aged rats was associated with changes in DNA methylation of protein kinase Mζ (PKMζ) in the prelimbic cortex (PrL). PKMζ is a crucial molecule involved in the maintenance of long-term memory. Using different behavioral models, we confirmed that aged rats exhibited cognitive impairment in memory retention test 24 h after training, and overexpression of PKMζ in the PrL rescued cognitive impairment in aged rats. After fear conditioning, the protein levels of PKMζ and the membrane expression of GluR2 increased in the PrL in young and adult rats but not in aged rats, and the levels of methylated PKMζ DNA in the PrL decreased in all age groups, whereas the levels of unmethylated PKMζ DNA increased only in young and adult rats. We also found that environmentally enriched housing reversed the hypermethylation of PKMζ and restored cognitive performance in aged rats. Inactivation of PKMζ prevented the potentiating effects of environmental enrichment on memory retention in aged rats. These results indicated that PKMζ might be a potential target for the treatment of aging-related cognitive impairment, suggesting a potential therapeutic avenue. PMID:26926225

  10. [Age-related changes of sensory system].

    PubMed

    Iwamoto, Toshihiko; Hanyu, Haruo; Umahara, Takahiko

    2013-10-01

    Pathological processes usually superimpose on physiological aging even in the sensory system including visual, hearing, olfactory, taste and somatosensory functions. Representative changes of age-related changes are presbyopia, cataracts, and presbyacusis. Reduced sense of smell is seen in normal aging, but the prominent reduction detected by the odor stick identification test is noticed especially in early stage of Alzheimer or Parkinson disease. Reduced sense of taste is well-known especially in salty sense, while the changes of sweet, bitter, and sour tastes are different among individuals. Finally, deep sensation of vibration and proprioception is decreased with age as well as superficial sensation (touch, temperature, pain). As a result, impaired sensory system could induce deterioration of the activities of daily living and quality of life in the elderly. PMID:24261198

  11. Age Related Changes in Preventive Health Behavior.

    ERIC Educational Resources Information Center

    Leventhal, Elaine A.; And Others

    Health behavior may be influenced by age, beliefs, and symptomatology. To examine age-related health beliefs and behaviors with respect to six diseases (the common cold, colon-rectal cancer, lung cancer, heart attack, high blood pressure, and senility), 396 adults (196 males, 200 females) divided into three age groups completed a questionnaire…

  12. Age-Related Changes in the Misinformation Effect.

    ERIC Educational Resources Information Center

    Sutherland, Rachel; Hayne, Harlene

    2001-01-01

    Two experiments examined relation between age-related changes in retention and age-related changes in the misinformation effect. Found large age-related retention differences when participants were interviewed immediately and after 1 day, but after 6 weeks, differences were minimal. Exposure to misleading information increased commission errors.…

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

    NASA Astrophysics Data System (ADS)

    Barnes, Daniel R.

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

  14. Divergent Thinking and Age-Related Changes

    ERIC Educational Resources Information Center

    Palmiero, Massimiliano; Di Giacomo, Dina; Passafiume, Domenico

    2014-01-01

    Aging can affect cognition in different ways. The extent to which aging affects divergent thinking is unclear. In this study, younger and older adults were compared at the performance on the Torrance Test of Creative Thinking in visual and verbal form. Results showed that older adults can think divergently as younger participants, although they…

  15. A Method for Investigating Age-related Differences in the Functional Connectivity of Cognitive Control Networks Associated with Dimensional Change Card Sort Performance

    PubMed Central

    DeBenedictis, Bianca; Morton, J. Bruce

    2014-01-01

    The ability to adjust behavior to sudden changes in the environment develops gradually in childhood and adolescence. For example, in the Dimensional Change Card Sort task, participants switch from sorting cards one way, such as shape, to sorting them a different way, such as color. Adjusting behavior in this way exacts a small performance cost, or switch cost, such that responses are typically slower and more error-prone on switch trials in which the sorting rule changes as compared to repeat trials in which the sorting rule remains the same. The ability to flexibly adjust behavior is often said to develop gradually, in part because behavioral costs such as switch costs typically decrease with increasing age. Why aspects of higher-order cognition, such as behavioral flexibility, develop so gradually remains an open question. One hypothesis is that these changes occur in association with functional changes in broad-scale cognitive control networks. On this view, complex mental operations, such as switching, involve rapid interactions between several distributed brain regions, including those that update and maintain task rules, re-orient attention, and select behaviors. With development, functional connections between these regions strengthen, leading to faster and more efficient switching operations. The current video describes a method of testing this hypothesis through the collection and multivariate analysis of fMRI data from participants of different ages. PMID:24837515

  16. Hippocampal dysregulation of synaptic plasticity-associated proteins with age-related cognitive decline

    PubMed Central

    VanGuilder, Heather D.; Farley, Julie A.; Yan, Han; Van Kirk, Colleen A.; Mitschelen, Matthew; Sonntag, William E.; Freeman, Willard M.

    2011-01-01

    Age-related cognitive decline occurs without frank neurodegeneration and is the most common cause of memory impairment in aging individuals. With increasing longevity, cognitive deficits, especially in hippocampus-dependent memory processes, are increasing in prevalence. Nevertheless, the neurobiological basis of age-related cognitive decline remains unknown. While concerted efforts have led to the identification of neurobiological changes with aging, few age-related alterations have been definitively correlated to behavioral measures of cognitive decline. In this work, adult (12 Months) and aged (28 months) rats were categorized by Morris water maze performance as Adult cognitively Intact, Aged cognitively Intact or Aged cognitively Impaired, and protein expression was examined in hippocampal synaptosome preparations. Previously described differences in synaptic expression of neurotransmission-associated proteins (Dnm1, Hpca, Stx1, Syn1, Syn2, Syp, SNAP25, VAMP2 and 14-3-3 eta, gamma, and zeta) were confirmed between Adult and Aged rats, with no further dysregulation associated with cognitive impairment. Proteins related to synaptic structural stability (MAP2, drebrin, Nogo-A) and activity-dependent signaling (PSD-95, 14-3-3θ, CaMKIIα) were up- and down-regulated, respectively, with cognitive impairment but were not altered with increasing age. Localization of MAP2, PSD-95, and CaMKIIα demonstrated protein expression alterations throughout the hippocampus. The altered expression of activity- and structural stability-associated proteins suggests that impaired synaptic plasticity is a distinct phenomenon that occurs with age-related cognitive decline, and demonstrates that cognitive decline is not simply an exacerbation of the aging phenotype. PMID:21440628

  17. Age-related changes in prefrontal norepinephrine transporter density: The basis for improved cognitive flexibility after low doses of atomoxetine in adolescent rats.

    PubMed

    Bradshaw, Sarah E; Agster, Kara L; Waterhouse, Barry D; McGaughy, Jill A

    2016-06-15

    Adolescence is a period of major behavioral and brain reorganization. As diagnoses and treatment of disorders like attention deficit hyperactivity disorder (ADHD) often occur during adolescence, it is important to understand how the prefrontal cortices change and how these changes may influence the response to drugs during development. The current study uses an adolescent rat model to study the effect of standard ADHD treatments, atomoxetine and methylphenidate on attentional set shifting and reversal learning. While both of these drugs act as norepinephrine reuptake inhibitors, higher doses of atomoxetine and all doses of methylphenidate also block dopamine transporters (DAT). Low doses of atomoxetine, were effective at remediating cognitive rigidity found in adolescents. In contrast, methylphenidate improved performance in rats unable to form an attentional set due to distractibility but was without effect in normal subjects. We also assessed the effects of GBR 12909, a selective DAT inhibitor, but found no effect of any dose on behavior. A second study in adolescent rats investigated changes in norepinephrine transporter (NET) and dopamine beta hydroxylase (DBH) density in five functionally distinct sub-regions of the prefrontal cortex: infralimbic, prelimbic, anterior cingulate, medial and lateral orbitofrontal cortices. These regions are implicated in impulsivity and distractibility. We found that NET, but not DBH, changed across adolescence in a regionally selective manner. The prelimbic cortex, which is critical to cognitive rigidity, and the lateral orbitofrontal cortex, critical to reversal learning and some forms of response inhibition, showed higher levels of NET at early than mid- to late adolescence. This article is part of a Special Issue entitled SI: Noradrenergic System. PMID:26774596

  18. 8 Areas of Age-Related Change

    MedlinePlus

    ... PROSTATE GLAND surrounds the tube (URETHRA) that passes urine. This can be a source of problems as ... changes, or an infection, can cause problems passing urine. Sometimes men in their 30s and 40s may ...

  19. Glutamatergic regulation prevents hippocampal-dependent age-related cognitive decline through dendritic spine clustering

    PubMed Central

    Pereira, Ana C.; Lambert, Hilary K.; Grossman, Yael S.; Dumitriu, Dani; Waldman, Rachel; Jannetty, Sophia K.; Calakos, Katina; Janssen, William G.; McEwen, Bruce S.; Morrison, John H.

    2014-01-01

    The dementia of Alzheimer’s disease (AD) results primarily from degeneration of neurons that furnish glutamatergic corticocortical connections that subserve cognition. Although neuron death is minimal in the absence of AD, age-related cognitive decline does occur in animals as well as humans, and it decreases quality of life for elderly people. Age-related cognitive decline has been linked to synapse loss and/or alterations of synaptic proteins that impair function in regions such as the hippocampus and prefrontal cortex. These synaptic alterations are likely reversible, such that maintenance of synaptic health in the face of aging is a critically important therapeutic goal. Here, we show that riluzole can protect against some of the synaptic alterations in hippocampus that are linked to age-related memory loss in rats. Riluzole increases glutamate uptake through glial transporters and is thought to decrease glutamate spillover to extrasynaptic NMDA receptors while increasing synaptic glutamatergic activity. Treated aged rats were protected against age-related cognitive decline displayed in nontreated aged animals. Memory performance correlated with density of thin spines on apical dendrites in CA1, although not with mushroom spines. Furthermore, riluzole-treated rats had an increase in clustering of thin spines that correlated with memory performance and was specific to the apical, but not the basilar, dendrites of CA1. Clustering of synaptic inputs is thought to allow nonlinear summation of synaptic strength. These findings further elucidate neuroplastic changes in glutamatergic circuits with aging and advance therapeutic development to prevent and treat age-related cognitive decline. PMID:25512503

  20. Glutamatergic regulation prevents hippocampal-dependent age-related cognitive decline through dendritic spine clustering.

    PubMed

    Pereira, Ana C; Lambert, Hilary K; Grossman, Yael S; Dumitriu, Dani; Waldman, Rachel; Jannetty, Sophia K; Calakos, Katina; Janssen, William G; McEwen, Bruce S; Morrison, John H

    2014-12-30

    The dementia of Alzheimer's disease (AD) results primarily from degeneration of neurons that furnish glutamatergic corticocortical connections that subserve cognition. Although neuron death is minimal in the absence of AD, age-related cognitive decline does occur in animals as well as humans, and it decreases quality of life for elderly people. Age-related cognitive decline has been linked to synapse loss and/or alterations of synaptic proteins that impair function in regions such as the hippocampus and prefrontal cortex. These synaptic alterations are likely reversible, such that maintenance of synaptic health in the face of aging is a critically important therapeutic goal. Here, we show that riluzole can protect against some of the synaptic alterations in hippocampus that are linked to age-related memory loss in rats. Riluzole increases glutamate uptake through glial transporters and is thought to decrease glutamate spillover to extrasynaptic NMDA receptors while increasing synaptic glutamatergic activity. Treated aged rats were protected against age-related cognitive decline displayed in nontreated aged animals. Memory performance correlated with density of thin spines on apical dendrites in CA1, although not with mushroom spines. Furthermore, riluzole-treated rats had an increase in clustering of thin spines that correlated with memory performance and was specific to the apical, but not the basilar, dendrites of CA1. Clustering of synaptic inputs is thought to allow nonlinear summation of synaptic strength. These findings further elucidate neuroplastic changes in glutamatergic circuits with aging and advance therapeutic development to prevent and treat age-related cognitive decline. PMID:25512503

  1. Age-Related Changes in 1/f Neural Electrophysiological Noise

    PubMed Central

    Kramer, Mark A.; Case, John; Lepage, Kyle Q.; Tempesta, Zechari R.; Knight, Robert T.; Gazzaley, Adam

    2015-01-01

    Aging is associated with performance decrements across multiple cognitive domains. The neural noise hypothesis, a dominant view of the basis of this decline, posits that aging is accompanied by an increase in spontaneous, noisy baseline neural activity. Here we analyze data from two different groups of human subjects: intracranial electrocorticography from 15 participants over a 38 year age range (15–53 years) and scalp EEG data from healthy younger (20–30 years) and older (60–70 years) adults to test the neural noise hypothesis from a 1/f noise perspective. Many natural phenomena, including electrophysiology, are characterized by 1/f noise. The defining characteristic of 1/f is that the power of the signal frequency content decreases rapidly as a function of the frequency (f) itself. The slope of this decay, the noise exponent (χ), is often <−1 for electrophysiological data and has been shown to approach white noise (defined as χ = 0) with increasing task difficulty. We observed, in both electrophysiological datasets, that aging is associated with a flatter (more noisy) 1/f power spectral density, even at rest, and that visual cortical 1/f noise statistically mediates age-related impairments in visual working memory. These results provide electrophysiological support for the neural noise hypothesis of aging. SIGNIFICANCE STATEMENT Understanding the neurobiological origins of age-related cognitive decline is of critical scientific, medical, and public health importance, especially considering the rapid aging of the world's population. We find, in two separate human studies, that 1/f electrophysiological noise increases with aging. In addition, we observe that this age-related 1/f noise statistically mediates age-related working memory decline. These results significantly add to this understanding and contextualize a long-standing problem in cognition by encapsulating age-related cognitive decline within a neurocomputational model of 1/f noise

  2. Age-related changes in the misinformation effect.

    PubMed

    Sutherland, R; Hayne, H

    2001-08-01

    In these experiments, we examined the relation between age-related changes in retention and age-related changes in the misinformation effect. Children (5- and 6- and 11- and 12-year-olds) and adults viewed a video, and their memory was assessed immediately, 1 day, or 6 weeks later (Experiment 1). There were large age-related differences in retention when participants were interviewed immediately and after 1 day, but after the 6-week delay, age-related differences in retention were minimal. In Experiment 2, 11- and 12-year-olds and adults were exposed to neutral, leading, and misleading postevent information 1 day or 6 weeks after they viewed the video. Exposure to misleading information increased the number of commission errors, particularly when participants were asked about peripheral aspects of the video. At both retention intervals, children were more likely than adults to incorporate the misleading postevent information into their subsequent verbal accounts. These findings indicate that age-related changes in the misinformation effect are not predicted by age-related changes in retention. PMID:11511130

  3. Correlations among central serotonergic parameters and age-related emotional and cognitive changes assessed through the elevated T-maze and the Morris water maze

    PubMed Central

    Oliveira, Luciana; Graeff, Frederico G.; Pereira, Silvia R. C.; Oliveira-Silva, Ieda F.; Franco, Glaura C.

    2010-01-01

    Emotion and spatial cognitive aspects were assessed in adult and middle-aged rats using the elevated T-maze (ETM) and the Morris water maze (MWM) tasks. Both adult and middle-aged rats were able to acquire inhibitory avoidance behaviour, though the middle-aged subjects showed larger latencies along the trials, including the baseline, which was significantly longer than that showed by adult rats. Further, compared to adult rats, middle-aged rats had longer escape latency. In spite of the worse performance in the second session of the spatial cognitive task, the middle-aged rats were able to learn the task and remember the information along the whole probe trial test. Both thalamic serotonin (5-HT) concentration and amygdala serotonergic activity (5-HIAA/5-HT) are significantly correlated, respectively, to escape latency and behavioural extinction in the MWM only for middle-aged rats. A significant correlation between the 5-HIAA/5-HT ratio in the amygdala and behavioural extinction for middle-aged, but not for adult, rats was observed. This result suggests that serotonergic activity in the amygdala may regulate behavioural flexibility in aged animals. In addition, a significant negative correlation was found between hippocampal 5-HIAA/5-HT ratio and the path length at the second training session of the MWM task, although only for adult subjects. This was the only session where a significant difference between the performance of middle-aged and adult rats has occurred. Although the involvement of the hippocampus in learning and memory is well established, the present work shows, for the first time, a correlation between a serotonergic hippocampal parameter and performance of a spatial task, which is lost with ageing. PMID:20431986

  4. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice.

    PubMed

    Villeda, Saul A; Plambeck, Kristopher E; Middeldorp, Jinte; Castellano, Joseph M; Mosher, Kira I; Luo, Jian; Smith, Lucas K; Bieri, Gregor; Lin, Karin; Berdnik, Daniela; Wabl, Rafael; Udeochu, Joe; Wheatley, Elizabeth G; Zou, Bende; Simmons, Danielle A; Xie, Xinmin S; Longo, Frank M; Wyss-Coray, Tony

    2014-06-01

    As human lifespan increases, a greater fraction of the population is suffering from age-related cognitive impairments, making it important to elucidate a means to combat the effects of aging. Here we report that exposure of an aged animal to young blood can counteract and reverse pre-existing effects of brain aging at the molecular, structural, functional and cognitive level. Genome-wide microarray analysis of heterochronic parabionts--in which circulatory systems of young and aged animals are connected--identified synaptic plasticity-related transcriptional changes in the hippocampus of aged mice. Dendritic spine density of mature neurons increased and synaptic plasticity improved in the hippocampus of aged heterochronic parabionts. At the cognitive level, systemic administration of young blood plasma into aged mice improved age-related cognitive impairments in both contextual fear conditioning and spatial learning and memory. Structural and cognitive enhancements elicited by exposure to young blood are mediated, in part, by activation of the cyclic AMP response element binding protein (Creb) in the aged hippocampus. Our data indicate that exposure of aged mice to young blood late in life is capable of rejuvenating synaptic plasticity and improving cognitive function. PMID:24793238

  5. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice

    PubMed Central

    Villeda, Saul A; Plambeck, Kristopher E; Middeldorp, Jinte; Castellano, Joseph M; Mosher, Kira I; Luo, Jian; Smith, Lucas K; Bieri, Gregor; Lin, Karin; Berdnik, Daniela; Wabl, Rafael; Udeochu, Joe; Wheatley, Elizabeth G; Zou, Bende; Simmons, Danielle A; Xie, Xinmin S; Longo, Frank M; Wyss-Coray, Tony

    2014-01-01

    As human lifespan increases, a greater fraction of the population is suffering from age-related cognitive impairments, making it important to elucidate a means to combat the effects of aging1,2. Here we report that exposure of an aged animal to young blood can counteract and reverse pre-existing effects of brain aging at the molecular, structural, functional and cognitive level. Genome-wide microarray analysis of heterochronic parabionts—in which circulatory systems of young and aged animals are connected—identified synaptic plasticity–related transcriptional changes in the hippocampus of aged mice. Dendritic spine density of mature neurons increased and synaptic plasticity improved in the hippocampus of aged heterochronic parabionts. At the cognitive level, systemic administration of young blood plasma into aged mice improved age-related cognitive impairments in both contextual fear conditioning and spatial learning and memory. Structural and cognitive enhancements elicited by exposure to young blood are mediated, in part, by activation of the cyclic AMP response element binding protein (Creb) in the aged hippocampus. Our data indicate that exposure of aged mice to young blood late in life is capable of rejuvenating synaptic plasticity and improving cognitive function. PMID:24793238

  6. Prospective study of Dietary Approaches to Stop Hypertension– and Mediterranean-style dietary patterns and age-related cognitive change: the Cache County Study on Memory, Health and Aging123

    PubMed Central

    Munger, Ronald G; Cutler, Adele; Quach, Anna; Bowles, Austin; Corcoran, Christopher; Tschanz, JoAnn T; Norton, Maria C; Welsh-Bohmer, Kathleen A

    2013-01-01

    Background: Healthy dietary patterns may protect against age-related cognitive decline, but results of studies have been inconsistent. Objective: We examined associations between Dietary Approaches to Stop Hypertension (DASH)– and Mediterranean-style dietary patterns and age-related cognitive change in a prospective, population-based study. Design: Participants included 3831 men and women ≥65 y of age who were residents of Cache County, UT, in 1995. Cognitive function was assessed by using the Modified Mini-Mental State Examination (3MS) ≤4 times over 11 y. Diet-adherence scores were computed by summing across the energy-adjusted rank-order of individual food and nutrient components and categorizing participants into quintiles of the distribution of the diet accordance score. Mixed-effects repeated-measures models were used to examine 3MS scores over time across increasing quintiles of dietary accordance scores and individual food components that comprised each score. Results: The range of rank-order DASH and Mediterranean diet scores was 1661–25,596 and 2407–26,947, respectively. Higher DASH and Mediterranean diet scores were associated with higher average 3MS scores. People in quintile 5 of DASH averaged 0.97 points higher than those in quintile 1 (P = 0.001). The corresponding difference for Mediterranean quintiles was 0.94 (P = 0.001). These differences were consistent over 11 y. Higher intakes of whole grains and nuts and legumes were also associated with higher average 3MS scores [mean quintile 5 compared with 1 differences: 1.19 (P < 0.001), 1.22 (P < 0.001), respectively]. Conclusions: Higher levels of accordance with both the DASH and Mediterranean dietary patterns were associated with consistently higher levels of cognitive function in elderly men and women over an 11-y period. Whole grains and nuts and legumes were positively associated with higher cognitive functions and may be core neuroprotective foods common to various healthy plant

  7. Can psychosocial work conditions protect against age-related cognitive decline? Results from a systematic review

    PubMed Central

    Nexø, Mette Andersen; Meng, Annette; Borg, Vilhelm

    2016-01-01

    According to the use it or lose it hypothesis, intellectually stimulating activities postpone age-related cognitive decline. A previous systematic review concluded that a high level of mental work demands and job control protected against cognitive decline. However, it did not distinguish between outcomes that were measured as cognitive function at one point in time or as cognitive decline. Our study aimed to systematically review which psychosocial working conditions were prospectively associated with high levels of cognitive function and/or changes in cognitive function over time. Articles were identified by a systematic literature search (MEDLINE, Web of Science (WOS), PsycNET, Occupational Safety and Health (OSH)). We included only studies with longitudinal designs examining the impact of psychosocial work conditions on outcomes defined as cognitive function or changes in cognitive function. Two independent reviewers compared title-abstract screenings, full-text screenings and quality assessment ratings. Eleven studies were included in the final synthesis and showed that high levels of mental work demands, occupational complexity or job control at one point in time were prospectively associated with higher levels of cognitive function in midlife or late life. However, the evidence to clarify whether these psychosocial factors also affected cognitive decline was insufficient, conflicting or weak. It remains speculative whether job control, job demands or occupational complexity can protect against cognitive decline. Future studies using methodological advancements can reveal whether workers gain more cognitive reserve in midlife and late life than the available evidence currently suggests. The public health implications of a previous review should thereby be redefined accordingly. PMID:27178844

  8. Can psychosocial work conditions protect against age-related cognitive decline? Results from a systematic review.

    PubMed

    Nexø, Mette Andersen; Meng, Annette; Borg, Vilhelm

    2016-07-01

    According to the use it or lose it hypothesis, intellectually stimulating activities postpone age-related cognitive decline. A previous systematic review concluded that a high level of mental work demands and job control protected against cognitive decline. However, it did not distinguish between outcomes that were measured as cognitive function at one point in time or as cognitive decline. Our study aimed to systematically review which psychosocial working conditions were prospectively associated with high levels of cognitive function and/or changes in cognitive function over time. Articles were identified by a systematic literature search (MEDLINE, Web of Science (WOS), PsycNET, Occupational Safety and Health (OSH)). We included only studies with longitudinal designs examining the impact of psychosocial work conditions on outcomes defined as cognitive function or changes in cognitive function. Two independent reviewers compared title-abstract screenings, full-text screenings and quality assessment ratings. Eleven studies were included in the final synthesis and showed that high levels of mental work demands, occupational complexity or job control at one point in time were prospectively associated with higher levels of cognitive function in midlife or late life. However, the evidence to clarify whether these psychosocial factors also affected cognitive decline was insufficient, conflicting or weak. It remains speculative whether job control, job demands or occupational complexity can protect against cognitive decline. Future studies using methodological advancements can reveal whether workers gain more cognitive reserve in midlife and late life than the available evidence currently suggests. The public health implications of a previous review should thereby be redefined accordingly. PMID:27178844

  9. Prevention of Age-Related Cognitive Decline: Which Strategies, When, and for Whom?

    PubMed

    Shatenstein, Bryna; Barberger-Gateau, Pascale; Mecocci, Patrizia

    2015-01-01

    Brain aging is characterized by the progressive and gradual accumulation of detrimental changes in structure and function, which increase risk of age-related cognitive decline and dementia. This devastating chronic condition generates a huge social and economic burden and accounts for 11.2% of years of disability. The increase in lifespan has contributed to the increase in dementia prevalence; however, there is currently no curative treatment for most causes of dementias. This paper reviews evidence-based strategies to build, enhance, and preserve cognition over the lifespan by examining approaches that work best, proposing when in the life course they should be implemented, and in which population group(s). Recent work shows a tendency to decreased age-specific prevalence and incidence of cognitive problems and dementia among people born later in the first half of the 20th century, citing higher educational levels, improvements in lifestyle, and better handling of vascular risk factors. This implies that we can target modifiable environmental, lifestyle, and health risk factors to modify the trajectory of cognitive decline before the onset of irreversible dementia. Because building cognitive reserve and prevention of cognitive decline are of critical importance, interventions are needed at every stage of the life course to foster cognitive stimulation, and enable healthy eating habits and physical activity throughout the lifespan. Preventive interventions to decrease and delay cognitive decline and its consequences in old age will also require collaboration and action on the part of policy-makers at the political and social level. PMID:26401926

  10. The role of cognition in age-related hearing loss.

    PubMed

    Craik, Fergus I M

    2007-01-01

    The article presents a commentary on the accompanying six papers from the perspective of a cognitive psychologist. Treisman's (1964, 1969) levels of analysis model of selective attention is suggested as a framework within which the interactions between 'bottom-up' auditory factors and 'top-down' cognitive factors may be understood. The complementary roles of auditory and cognitive aspects of hearing are explored, and their mutually compensatory properties discussed. The findings and ideas reported in the six accompanying papers fit well into such a 'levels of processing' framework, which may therefore be proposed as a model for understanding the effects of aging on speech processing and comprehension. PMID:18236642

  11. Glycosaminoglycans in the Human Cornea: Age-Related Changes

    PubMed Central

    Pacella, Elena; Pacella, Fernanda; De Paolis, Giulio; Parisella, Francesca Romana; Turchetti, Paolo; Anello, Giulia; Cavallotti, Carlo

    2015-01-01

    AIM To investigate possible age-related changes in glycosaminoglycans (GAGs) in the human cornea. The substances today called GAGs were previously referred to as mucopolysaccharides. METHODS Samples of human cornea were taken from 12 younger (age 21 ± 1.2) and 12 older (age 72 ± 1.6) male subjects. Samples were weighed, homogenized, and used for biochemical and molecular analyses. All the quantitative results were statistically analyzed. RESULTS The human cornea appears to undergo age-related changes, as evidenced by our biochemical and molecular results. The total GAG and hyaluronic acid counts were significantly higher in the younger subjects than in the older subjects. The sulfated heavy GAGs, such as chondroitin, dermatan, keratan, and heparan sulfate, were lower in the younger subjects than in the older subjects. DISCUSSION GAGs of the human cornea undergo numerous age-related changes. Their quantity is significantly altered in the elderly in comparison with younger subjects. GAGs play an important role in age-related diseases of the human cornea. PMID:25674020

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

    PubMed

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

    2016-04-01

    Age-related alterations in brain structure and function have been challenging to link to cognition due to potential overlapping influences of multiple neurobiological cascades. We examined multiple brain markers associated with age-related variation in cognition. Clinically normal older humans aged 65-90 from the Harvard Aging Brain Study (N = 186) were characterized on a priori magnetic resonance imaging markers of gray matter thickness and volume, white matter hyperintensities, fractional anisotropy (FA), resting-state functional connectivity, positron emission tomography markers of glucose metabolism and amyloid burden, and cognitive factors of processing speed, executive function, and episodic memory. Partial correlation and mediation analyses estimated age-related variance in cognition shared with individual brain markers and unique to each marker. The largest relationships linked FA and striatum volume to processing speed and executive function, and hippocampal volume to episodic memory. Of the age-related variance in cognition, 70-80% was accounted for by combining all brain markers (but only ∼20% of total variance). Age had significant indirect effects on cognition via brain markers, with significant markers varying across cognitive domains. These results suggest that most age-related variation in cognition is shared among multiple brain markers, but potential specificity between some brain markers and cognitive domains motivates additional study of age-related markers of neural health. PMID:25316342

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

    PubMed

    Maillet, David; Schacter, Daniel L

    2016-01-01

    The majority of studies that have investigated the effects of healthy aging on cognition have focused on age-related differences in voluntary and deliberately engaged cognitive processes. Yet many forms of cognition occur spontaneously, without any deliberate attempt at engaging them. In this article we review studies that have assessed age-related differences in four such types of spontaneous thought processes: mind-wandering, involuntary autobiographical memory, intrusive thoughts, and spontaneous prospective memory retrieval. These studies suggest that older adults exhibit a reduction in frequency of both mind-wandering and involuntary autobiographical memory, whereas findings regarding intrusive thoughts have been more mixed. Additionally, there is some preliminary evidence that spontaneous prospective memory retrieval may be relatively preserved in aging. We consider the roles of age-related differences in cognitive resources, motivation, current concerns and emotional regulation in accounting for these findings. We also consider age-related differences in the neural correlates of spontaneous cognitive processes. PMID:26617263

  14. Topography of age-related changes in sleep spindles.

    PubMed

    Martin, Nicolas; Lafortune, Marjolaine; Godbout, Jonathan; Barakat, Marc; Robillard, Rebecca; Poirier, Gaétan; Bastien, Célyne; Carrier, Julie

    2013-02-01

    Aging induces multiple changes to sleep spindles, which may hinder their alleged functional role in memory and sleep protection mechanisms. Brain aging in specific cortical regions could affect the neural networks underlying spindle generation, yet the topography of these age-related changes is currently unknown. In the present study, we analyzed spindle characteristics in 114 healthy volunteers aged between 20 and 73 years over 5 anteroposterior electroencephalography scalp derivations. Spindle density, amplitude, and duration were higher in young subjects than in middle-aged and elderly subjects in all derivations, but the topography of age effects differed drastically. Age-related decline in density and amplitude was more prominent in anterior derivations, whereas duration showed a posterior prominence. Age groups did not differ in all-night spindle frequency for any derivation. These results show that age-related changes in sleep spindles follow distinct topographical patterns that are specific to each spindle characteristic. This topographical specificity may provide a useful biomarker to localize age-sensitive changes in underlying neural systems during normal and pathological aging. PMID:22809452

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

    PubMed Central

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

    2015-01-01

    The effects of aging on rehabilitation of aging-related diseases are rarely a design consideration in rehabilitation research. In this brief review we present strong coincidental evidence from these two fields suggesting that deficits in aging-related disease or injury are compounded by the interaction between aging-related brain changes and disease-related brain changes. Specifically, we hypothesize that some aphasia, motor, and neglect treatments using repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) in stroke patients may address the aging side of this interaction. The importance of testing this hypothesis and addressing the larger aging by aging-related disease interaction is discussed. Underlying mechanisms in aging that most likely are relevant to rehabilitation of aging-related diseases also are covered. PMID:26074807

  16. Closed-Loop Rehabilitation of Age-Related Cognitive Disorders

    PubMed Central

    Mishra, Jyoti; Gazzaley, Adam

    2015-01-01

    Cognitive deficits are common in older adults, as a result of both the natural aging process and neurodegenerative disease. Although medical advancements have successfully prolonged the human lifespan, the challenge of remediating cognitive aging remains. The authors discuss the current state of cognitive therapeutic interventions and then present the need for development and validation of more powerful neurocognitive therapeutics. They propose that the next generation of interventions be implemented as closed-loop systems that target specific neural processing deficits, incorporate quantitative feedback to the individual and clinician, and are personalized to the individual’s neurocognitive capacities using real-time performance-adaptive algorithms. This approach should be multimodal and seamlessly integrate other treatment approaches, including neurofeedback and transcranial electrical stimulation. This novel approach will involve the generation of software that engages the individual in an immersive and enjoyable game-based interface, integrated with advanced biosensing hardware, to maximally harness plasticity and assure adherence. Introducing such next-generation closed-loop neurocognitive therapeutics into the mainstream of our mental health care system will require the combined efforts of clinicians, neuroscientists, bioengineers, software game developers, and industry and policy makers working together to meet the challenges and opportunities of translational neuroscience in the 21st century. PMID:25520029

  17. Closed-loop rehabilitation of age-related cognitive disorders.

    PubMed

    Mishra, Jyoti; Gazzaley, Adam

    2014-11-01

    Cognitive deficits are common in older adults, as a result of both the natural aging process and neurodegenerative disease. Although medical advancements have successfully prolonged the human lifespan, the challenge of remediating cognitive aging remains. The authors discuss the current state of cognitive therapeutic interventions and then present the need for development and validation of more powerful neurocognitive therapeutics. They propose that the next generation of interventions be implemented as closed-loop systems that target specific neural processing deficits, incorporate quantitative feedback to the individual and clinician, and are personalized to the individual's neurocognitive capacities using real-time performance-adaptive algorithms. This approach should be multimodal and seamlessly integrate other treatment approaches, including neurofeedback and transcranial electrical stimulation. This novel approach will involve the generation of software that engages the individual in an immersive and enjoyable game-based interface, integrated with advanced biosensing hardware, to maximally harness plasticity and assure adherence. Introducing such next-generation closed-loop neurocognitive therapeutics into the mainstream of our mental health care system will require the combined efforts of clinicians, neuroscientists, bioengineers, software game developers, and industry and policy makers working together to meet the challenges and opportunities of translational neuroscience in the 21st century. PMID:25520029

  18. Age-related changes in the adaptability of neuromuscular output.

    PubMed

    Morrison, Steven; Sosnoff, Jacob J

    2009-05-01

    The aging process is associated with a general decline in biological function. One characteristic that researchers believe represents this diminished functioning of the aging neuromuscular system is increased physiological tremor. The present study is constructed to assess what age-related differences exist in the dynamics of tremor and forearm muscle activity under postural conditions in which the number of arm segments involved in the task was altered. The authors predicted that any alteration in the tremor or electromyographic (EMG) output of these two groups would provide a clearer understanding of the differential effects of aging or task dynamics on physiological function. Results reveal no age-related differences in finger tremor or forearm extensor muscle EMG activity under conditions in which participants were only required to extend their index finger against gravity. However, when participants had to hold their entire upper limb steady against gravity, the authors observed significant increases in forearm EMG activity, finger-tremor amplitude, power in the 8-12-Hz range, and signal regularity between the 2 age groups. The selective changes in signal regularity, EMG activity, and 8-12-Hz tremor amplitude under more challenging postural demands support the view that the age-related changes in neuromuscular dynamics are not fully elucidated when single task demands are utilized. PMID:19366659

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

    PubMed Central

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

    2014-01-01

    With a rapidly aging society it becomes increasingly important to counter normal age-related decline in cognitive functioning. Growing evidence suggests that cognitive training programs may have the potential to counteract this decline. On the basis of a growing body of research that shows that meditation has positive effects on cognition in younger and middle-aged adults, meditation may be able to offset normal age-related cognitive decline or even enhance cognitive function in older adults. In this paper, we review studies investigating the effects of meditation on age-related cognitive decline. We searched the Web of Science (1900 to present), PsycINFO (1597 to present), MEDLINE (1950 to present), and CABI (1910 to present) to identify original studies investigating the effects of meditation on cognition and cognitive decline in the context of aging. Twelve studies were included in the review, six of which were randomized controlled trials. Studies involved a wide variety of meditation techniques and reported preliminary positive effects on attention, memory, executive function, processing speed, and general cognition. However, most studies had a high risk of bias and small sample sizes. Reported dropout rates were low and compliance rates high. We conclude that meditation interventions for older adults are feasible, and preliminary evidence suggests that meditation can offset age-related cognitive decline. PMID:24571182

  20. Age-related changes in mouse bone permeability.

    PubMed

    Rodriguez-Florez, Naiara; Oyen, Michelle L; Shefelbine, Sandra J

    2014-03-21

    The determination of lacunar-canalicular permeability is essential for understanding local fluid flow in bone, which may indicate how bone senses changes in the mechanical environment to regulate mechano-adaptation. The estimates of lacunar-canalicular permeability found in the literature vary by up to eight orders of magnitude, and age-related permeability changes have not been measured in non-osteonal mouse bone. The objective of this study is to use a poroelastic approach based on nanoindentation data to characterize lacunar-canalicular permeability in murine bone as a function of age. Nine wild type C57BL/6 mice of different ages (2, 7 and 12 months) were used. Three tibiae from each age group were embedded in epoxy resin, cut in half and indented in the longitudinal direction in the mid-cortex using two spherical fluid indenter tips (R=238 μm and 500 μm). Results suggest that the lacunar-canalicular intrinsic permeability of mouse bone decreases from 2 to 7 months, with no significant changes from 7 to 12 months. The large indenter tip imposed larger contact sizes and sampled larger ranges of permeabilities, particularly for the old bone. This age-related difference in the distribution was not seen for indents with the smaller radius tip. We conclude that the small tip effectively measured lacunar-canalicular permeability, while larger tip indents were influenced by vascular permeability. Exploring the age-related changes in permeability of bone measured by nanoindentation will lead to a better understanding of the role of fluid flow in mechano-transduction. This understanding may help indicate alterations in bone adaptation and remodeling. PMID:24433671

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

    PubMed

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

    2016-01-01

    The default mode network (DMN) is a set of regions that is tonically engaged during the resting state and exhibits task-related deactivation that is readily reproducible across a wide range of paradigms and modalities. The DMN has been implicated in numerous disorders of cognition and, in particular, in disorders exhibiting age-related cognitive decline. Despite these observations, investigations of the DMN in normal aging are scant. Here, we used blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) acquired during rest to investigate age-related changes in functional connectivity of the DMN in 120 healthy normal volunteers comprising six, 20-subject, decade cohorts (from 20-29 to 70-79). Structural equation modeling (SEM) was used to assess age-related changes in inter-regional connectivity within the DMN. SEM was applied both using a previously published, meta-analytically derived, node-and-edge model, and using exploratory modeling searching for connections that optimized model fit improvement. Although the two models were highly similar (only 3 of 13 paths differed), the sample demonstrated significantly better fit with the exploratory model. For this reason, the exploratory model was used to assess age-related changes across the decade cohorts. Progressive, highly significant changes in path weights were found in 8 (of 13) paths: four rising, and four falling (most changes were significant by the third or fourth decade). In all cases, rising paths and falling paths projected in pairs onto the same nodes, suggesting compensatory increases associated with age-related decreases. This study demonstrates that age-related changes in DMN physiology (inter-regional connectivity) are bidirectional, progressive, of early onset and part of normal aging. PMID:27378909

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

    PubMed Central

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

    2016-01-01

    The default mode network (DMN) is a set of regions that is tonically engaged during the resting state and exhibits task-related deactivation that is readily reproducible across a wide range of paradigms and modalities. The DMN has been implicated in numerous disorders of cognition and, in particular, in disorders exhibiting age-related cognitive decline. Despite these observations, investigations of the DMN in normal aging are scant. Here, we used blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) acquired during rest to investigate age-related changes in functional connectivity of the DMN in 120 healthy normal volunteers comprising six, 20-subject, decade cohorts (from 20–29 to 70–79). Structural equation modeling (SEM) was used to assess age-related changes in inter-regional connectivity within the DMN. SEM was applied both using a previously published, meta-analytically derived, node-and-edge model, and using exploratory modeling searching for connections that optimized model fit improvement. Although the two models were highly similar (only 3 of 13 paths differed), the sample demonstrated significantly better fit with the exploratory model. For this reason, the exploratory model was used to assess age-related changes across the decade cohorts. Progressive, highly significant changes in path weights were found in 8 (of 13) paths: four rising, and four falling (most changes were significant by the third or fourth decade). In all cases, rising paths and falling paths projected in pairs onto the same nodes, suggesting compensatory increases associated with age-related decreases. This study demonstrates that age-related changes in DMN physiology (inter-regional connectivity) are bidirectional, progressive, of early onset and part of normal aging. PMID:27378909

  3. Epigenetic alterations in the suprachiasmatic nucleus and hippocampus contribute to age-related cognitive decline

    PubMed Central

    Deibel, Scott H.; Zelinski, Erin L.; Keeley, Robin J.; Kovalchuk, Olga; McDonald, Robert J.

    2015-01-01

    Circadian rhythm dysfunction and cognitive decline, specifically memory loss, frequently accompany natural aging. Circadian rhythms and memory are intertwined, as circadian rhythms influence memory formation and recall in young and old rodents. Although, the precise relationship between circadian rhythms and memory is still largely unknown, it is hypothesized that circadian rhythm disruption, which occurs during aging, contributes to age-associated cognitive decline, specifically memory loss. While there are a variety of mechanisms that could mediate this effect, changes in the epigenome that occur during aging has been proposed as a potential candidate. Interestingly, epigenetic mechanisms, such as DNA methylation and sirtuin1 (SIRT1) are necessary for both circadian rhythms and memory. During aging, similar alterations of epigenetic mechanisms occur in the suprachiasmatic nucleus (SCN) and hippocampus, which are necessary for circadian rhythm generation and memory, respectively. Recently, circadian rhythms have been linked to epigenetic function in the hippocampus, as some of these epigenetic mechanisms oscillate in the hippocampus and are disrupted by clock gene deletion. The current paper will review how circadian rhythms and memory change with age, and will suggest how epigenetic changes in these processes might contribute to age-related cognitive decline. PMID:26252151

  4. Age-related cognitive decline during normal aging: the complex effect of education.

    PubMed

    Ardila, A; Ostrosky-Solis, F; Rosselli, M; Gómez, C

    2000-08-01

    The purpose of this study was to further analyze the effects of education on cognitive decline during normal aging. An 806-subject sample was taken from five different Mexican regions. Participants ranged in age from 16 to 85 years. Subjects were grouped into four educational levels: illiterate, 1-4, 5-9, and 10 or more years of education, and four age ranges: 16-30, 31-50, 51-65, and 66-85 years. A brief neuropsychological test battery (NEUROPSI), standardized and normalized in Spanish, was administered. The NEUROPSI test battery includes assessment of orientation, attention, memory, language, visuoperceptual abilities, motor skills, and executive functions. In general, test scores were strongly associated with level of educational, and differences among age groups were smaller than differences among education groups. However, there was an interaction between age and education such as that among illiterate individuals scores of participants 31-50 years old were higher than scores of participants 16-30 years old for over 50% of the tests. Different patterns of interaction among educational groups were distinguished. It was concluded that: (a) The course of life-span changes in cognition are affected by education. Among individuals with a low level of education, best neuropsychological test performance is observed at an older age than among higher-educated subjects; and (b) there is not a single relationship between age-related cognitive decline and education, but different patterns may be found, depending upon the specific cognitive domain. PMID:14590204

  5. Age-Related Neurochemical Changes in the Vestibular Nuclei

    PubMed Central

    Smith, Paul F.

    2016-01-01

    There is evidence that the normal aging process is associated with impaired vestibulo-ocular reflexes (VOR) and vestibulo-spinal reflexes, causing reduced visual acuity and postural instability. Nonetheless, the available evidence is not entirely consistent, especially with respect to the VOR. Some recent studies have reported that VOR gain can be intact even above 80 years of age. Similarly, although there is evidence for age-related hair cell loss and neuronal loss in Scarpa’s ganglion and the vestibular nucleus complex (VNC), it is not entirely consistent. Whatever structural and functional changes occur in the VNC as a result of aging, either to cause vestibular impairment or to compensate for it, neurochemical changes must underlie them. However, the neurochemical changes that occur in the VNC with aging are poorly understood because the available literature is very limited. This review summarizes and critically evaluates the available evidence relating to the noradrenaline, serotonin, dopamine, glutamate, GABA, glycine, and nitric oxide neurotransmitter systems in the aging VNC. It is concluded that, at present, it is difficult, if not impossible, to relate the neurochemical changes observed to the function of specific VNC neurons and whether the observed changes are the cause of a functional deficit in the VNC or an effect of it. A better understanding of the neurochemical changes that occur during aging may be important for the development of potential drug treatments for age-related vestibular disorders. However, this will require the use of more sophisticated methodology such as in vivo microdialysis with single neuron recording and perhaps new technologies such as optogenetics. PMID:26973593

  6. Age-Related Neurochemical Changes in the Vestibular Nuclei.

    PubMed

    Smith, Paul F

    2016-01-01

    There is evidence that the normal aging process is associated with impaired vestibulo-ocular reflexes (VOR) and vestibulo-spinal reflexes, causing reduced visual acuity and postural instability. Nonetheless, the available evidence is not entirely consistent, especially with respect to the VOR. Some recent studies have reported that VOR gain can be intact even above 80 years of age. Similarly, although there is evidence for age-related hair cell loss and neuronal loss in Scarpa's ganglion and the vestibular nucleus complex (VNC), it is not entirely consistent. Whatever structural and functional changes occur in the VNC as a result of aging, either to cause vestibular impairment or to compensate for it, neurochemical changes must underlie them. However, the neurochemical changes that occur in the VNC with aging are poorly understood because the available literature is very limited. This review summarizes and critically evaluates the available evidence relating to the noradrenaline, serotonin, dopamine, glutamate, GABA, glycine, and nitric oxide neurotransmitter systems in the aging VNC. It is concluded that, at present, it is difficult, if not impossible, to relate the neurochemical changes observed to the function of specific VNC neurons and whether the observed changes are the cause of a functional deficit in the VNC or an effect of it. A better understanding of the neurochemical changes that occur during aging may be important for the development of potential drug treatments for age-related vestibular disorders. However, this will require the use of more sophisticated methodology such as in vivo microdialysis with single neuron recording and perhaps new technologies such as optogenetics. PMID:26973593

  7. Age-Related Changes in Skeletal Muscle of Cattle.

    PubMed

    Costagliola, A; Wojcik, S; Pagano, T B; De Biase, D; Russo, V; Iovane, V; Grieco, E; Papparella, S; Paciello, O

    2016-03-01

    Sarcopenia, the age-related loss of muscle mass and strength, is a multifactorial condition that represents a major healthcare concern for the elderly population. Although its morphologic features have been extensively studied in humans, animal models, and domestic and wild animals, only a few reports about spontaneous sarcopenia exist in other long-lived animals. In this work, muscle samples from 60 healthy Podolica-breed old cows (aged 15-23 years) were examined and compared with muscle samples from 10 young cows (3-6 years old). Frozen sections were studied through standard histologic and histoenzymatic procedures, as well as by immunohistochemistry, immunofluorescence, and Western blot analysis. The most prominent age-related myopathic features seen in the studied material included angular fiber atrophy (90% of cases), mitochondrial alterations (ragged red fibers, 70%; COX-negative fibers, 60%), presence of vacuolated fibers (75%), lymphocytic (predominantly CD8+) inflammation (40%), and type II selective fiber atrophy (40%). Immunohistochemistry revealed increased expression of major histocompatibility complex I in 36 cases (60%) and sarcoplasmic accumulations of β-amyloid precursor protein-positive material in 18 cases (30%). In aged cows, muscle atrophy was associated with accumulation of myostatin. Western blot analysis indicated increased amount of both proteins-myostatin and β-amyloid precursor protein-in muscles of aged animals compared with controls. These findings confirm the presence of age-related morphologic changes in cows similar to human sarcopenia and underline the possible role of amyloid deposition and subsequent inflammation in muscle senescence. PMID:26869152

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

    PubMed

    Lever, Anne G; Geurts, Hilde M

    2016-06-01

    It is largely unknown how age impacts cognition in autism spectrum disorder (ASD). We investigated whether age-related cognitive differences are similar, reduced or increased across the adult lifespan, examined cognitive strengths and weaknesses, and explored whether objective test performance is related to subjective cognitive challenges. Neuropsychological tests assessing visual and verbal memory, generativity, and theory of mind (ToM), and a self-report measure assessing cognitive failures were administered to 236 matched participants with and without ASD, aged 20-79 years (IQ > 80). Group comparisons revealed that individuals with ASD had higher scores on visual memory, lower scores on generativity and ToM, and similar performance on verbal memory. However, ToM impairments were no longer present in older (50+ years) adults with ASD. Across adulthood, individuals with ASD demonstrated similar age-related effects on verbal memory, generativity, and ToM, while age-related differences were reduced on visual memory. Although adults with ASD reported many cognitive failures, those were not associated with neuropsychological test performance. Hence, while some cognitive abilities (visual and verbal memory) and difficulties (generativity and semantic memory) persist across adulthood in ASD, others become less apparent in old age (ToM). Age-related differences characteristic of typical aging are reduced or parallel, but not increased in individuals with ASD, suggesting that ASD may partially protect against an age-related decrease in cognitive functioning. Despite these findings, adults with ASD experience many cognitive daily challenges, which highlights the need for adequate social support and the importance of further research into this topic, including longitudinal studies. Autism Res 2016, 9: 666-676. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. PMID:26333004

  9. Age-related changes in the tiger salamander retina.

    PubMed

    Townes-Anderson, E; Colantonio, A; St Jules, R S

    1998-05-01

    Tiger salamanders have been used in visual science because of the large size of their cells and the ease of preparation and maintenance of in vitro retinal preparations. We have found that salamanders over 27 cm in length show a variety of visual abnormalities. Compared to smaller animals (15-23 cm), large animals exhibited a decrease in visual responses determined by tests of the optomotor reflex. Small animals responded correctly an average of 84.5% of the time in visual testing at three light levels compared to an average of 68.4% for the large animals with the poorest visual performance at the lowest level of illumination. In addition, large animals contained (i) histological degeneration of the outer retina, in particular, loss and disruption of outer segments and abnormalities of the retinal pigmented epithelium, (ii) loss of cells, including photoreceptors, by apoptosis as evaluated with the TUNEL technique, and (iii) an increase in the number of macrophages and lymphocytes within the retina as determined by morphological examination. These histological changes were present in all large animals and all quadrants of their retinas. In contrast, small animals showed virtually no retinal degeneration, no TUNEL-positive cells, and few immune-like cells in the retina. Since large animals are also older animals. the visual changes are age-related. Loss of visual function and histological degeneration in the outer retina also typify aged human eyes. Thus, we propose that large salamanders serve as an animal model for age-related retinal degeneration. In addition to providing a source of aging retina that is readily accessible to experimental manipulation, the salamander provides a pigmented retina with a mixed (2:1, rod:cone) population of photoreceptors, similar to the degeneration-prone parafoveal region of the human eye. PMID:9631666

  10. Age related changes in steroid receptors on cultured lung fibroblasts

    SciTech Connect

    Barile, F.A.; Bienkowski, R.S.

    1986-03-05

    The number of high affinity glucocorticoid receptors (Ro) on human fetal lung fibroblasts decreases as the cells age in vitro, and it has been suggested that these cell systems may be useful models of age-related changes in vivo. They examined the relation between change in Ro with in vitro aging and donor age. Confluent monolayers of lung fibroblasts at various population doubling levels (PDL), were incubated with (/sup 3/H)-dexamethasone ((/sup 3/H)Dex) either alone or with excess (.01 mM) Dex. Specific binding was calculated as the difference between radioactivity in cells incubated with and without unlabeled Dex; Scatchard plots were used to analyze the data. Ro, measured as fmol (/sup 3/H)Dex/10/sup 6/ cells, for two lines of human fetal cells (HFL-1 and MRC-5) decreased with increasing age in vitro. However, human newborn (CRL-1485) and adult (CCL-201) cells and fetal rabbit cells (FAB-290), showed increases in Ro with continuous passage. For each cell line, the affinity constant (K/sub d/) did not change significantly with passage. They conclude that the direction of changes in steroid receptor levels on cells aging in vitro is influenced by donor age and species. Caution should be used in applying results obtained from model systems to aging organisms.

  11. Age-related decline in cognitive control: the role of fluid intelligence and processing speed

    PubMed Central

    2014-01-01

    Background Research on cognitive control suggests an age-related decline in proactive control abilities whereas reactive control seems to remain intact. However, the reason of the differential age effect on cognitive control efficiency is still unclear. This study investigated the potential influence of fluid intelligence and processing speed on the selective age-related decline in proactive control. Eighty young and 80 healthy older adults were included in this study. The participants were submitted to a working memory recognition paradigm, assessing proactive and reactive cognitive control by manipulating the interference level across items. Results Repeated measures ANOVAs and hierarchical linear regressions indicated that the ability to appropriately use cognitive control processes during aging seems to be at least partially affected by the amount of available cognitive resources (assessed by fluid intelligence and processing speed abilities). Conclusions This study highlights the potential role of cognitive resources on the selective age-related decline in proactive control, suggesting the importance of a more exhaustive approach considering the confounding variables during cognitive control assessment. PMID:24401034

  12. Cognitive Load and Listening Effort: Concepts and Age-Related Considerations.

    PubMed

    Lemke, Ulrike; Besser, Jana

    2016-01-01

    Listening effort has been recognized as an important dimension of everyday listening, especially with regard to the comprehension of spoken language. At constant levels of comprehension performance, the level of effort exerted and perceived during listening can differ considerably across listeners and situations. In this article, listening effort is used as an umbrella term for two different types of effort that can arise during listening. One of these types is processing effort, which is used to denote the utilization of "extra" mental processing resources in listening conditions that are adverse for an individual. A conceptual description is introduced how processing effort could be defined in terms of situational influences, the listener's auditory and cognitive resources, and the listener's personal state. Also, the proposed relationship between processing effort and subjectively perceived listening effort is discussed. Notably, previous research has shown that the availability of mental resources, as well as the ability to use them efficiently, changes over the course of adult aging. These common age-related changes in cognitive abilities and their neurocognitive organization are discussed in the context of the presented concept, especially regarding situations in which listening effort may be increased for older people. PMID:27355774

  13. Disconnected aging: cerebral white matter integrity and age-related differences in cognition.

    PubMed

    Bennett, I J; Madden, D J

    2014-09-12

    Cognition arises as a result of coordinated processing among distributed brain regions and disruptions to communication within these neural networks can result in cognitive dysfunction. Cortical disconnection may thus contribute to the declines in some aspects of cognitive functioning observed in healthy aging. Diffusion tensor imaging (DTI) is ideally suited for the study of cortical disconnection as it provides indices of structural integrity within interconnected neural networks. The current review summarizes results of previous DTI aging research with the aim of identifying consistent patterns of age-related differences in white matter integrity, and of relationships between measures of white matter integrity and behavioral performance as a function of adult age. We outline a number of future directions that will broaden our current understanding of these brain-behavior relationships in aging. Specifically, future research should aim to (1) investigate multiple models of age-brain-behavior relationships; (2) determine the tract-specificity versus global effect of aging on white matter integrity; (3) assess the relative contribution of normal variation in white matter integrity versus white matter lesions to age-related differences in cognition; (4) improve the definition of specific aspects of cognitive functioning related to age-related differences in white matter integrity using information processing tasks; and (5) combine multiple imaging modalities (e.g., resting-state and task-related functional magnetic resonance imaging; fMRI) with DTI to clarify the role of cerebral white matter integrity in cognitive aging. PMID:24280637

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

    ERIC Educational Resources Information Center

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

    2013-01-01

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

  15. Recent Advances in Berry Supplementation and Age-Related Cognitive Decline

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To summarize recent findings and current concepts in the beneficial effects of berry consumption on brain function during aging. Berryfruit supplementation has continued to demonstrate efficacy in reversing age-related cognitive decline in animal studies. In terms of the mechanisms behind the effe...

  16. Mathematical morphologic analysis of aging-related epidermal changes.

    PubMed

    Moragas, A; Castells, C; Sans, M

    1993-04-01

    Fractographic techniques based on mathematical morphology were used to study aging-related epidermal changes in abdominal skin samples obtained from 96 autopsy cases. Three linear roughness indices were evaluated for the rete peg profile and the shrinkage effect on the basal layer and interface between the granular and horny layers. Elderly subjects had a 36.3% decrease in rete peg-related roughness index when compared with younger subjects. This roughness index has been corrected, with shrinkage due to skin elasticity taken into account. For females, fitting of a logistic decay function yielded a curve with right and left asymptotes and a steeper descent between 40 and 60 years. Half value time--i.e., the time when half rete peg profile flattening occurred--was 46.8 years. In contrast, males showed almost monotonical decay. Epidermal thickness measured between rete pegs showed the same exponential decline for both sexes, with values from 22.6 to 11.4 microns. Skin shrinkage in elderly subjects decreased 22% in superficial layers and only 6% in the lower epidermis. In both cases shrinkage had a linear relation with age, and no sex differences were found. PMID:8318130

  17. Age-Related Changes in Demand-Withdraw Communication Behaviors.

    PubMed

    Holley, Sarah R; Haase, Claudia M; Levenson, Robert W

    2013-08-01

    Demand-withdraw communication is a set of conflict-related behaviors in which one partner blames or pressures while the other partner withdraws or avoids. The present study examined age-related changes in these behaviors longitudinally over the course of later life stages. One hundred twenty-seven middle-aged and older long-term married couples were observed at 3 time points across 13 years as they engaged in a conversation about an area of relationship conflict. Husbands' and wives' demand-withdraw behaviors (i.e., blame, pressure, withdrawal, avoidance) were objectively rated by trained coders at each time point. Data were analyzed using dyad-level latent growth curve models in a structural equation modeling framework. For both husbands and wives, the results showed a longitudinal pattern of increasing avoidance behavior over time and stability in all other demand and withdraw behaviors. This study supports the notion that there is an important developmental shift in the way that conflict is handled in later life. PMID:23913982

  18. Age-Related Changes in Demand–Withdraw Communication Behaviors

    PubMed Central

    Holley, Sarah R.; Haase, Claudia M.; Levenson, Robert W.

    2013-01-01

    Demand–withdraw communication is a set of conflict-related behaviors in which one partner blames or pressures while the other partner withdraws or avoids. The present study examined age-related changes in these behaviors longitudinally over the course of later life stages. One hundred twenty-seven middle-aged and older long-term married couples were observed at 3 time points across 13 years as they engaged in a conversation about an area of relationship conflict. Husbands’ and wives’ demand–withdraw behaviors (i.e., blame, pressure, withdrawal, avoidance) were objectively rated by trained coders at each time point. Data were analyzed using dyad-level latent growth curve models in a structural equation modeling framework. For both husbands and wives, the results showed a longitudinal pattern of increasing avoidance behavior over time and stability in all other demand and withdraw behaviors. This study supports the notion that there is an important developmental shift in the way that conflict is handled in later life. PMID:23913982

  19. Age-related changes in serological susceptibility patterns to measles

    PubMed Central

    Xiong, Yongzhen; Wang, Dong; Lin, Weiyan; Tang, Hao; Chen, Shaoli; Ni, Jindong

    2014-01-01

    The present study was performed to determine the seroprevalence of IgG measles antibodies in Dongguan residents (irrespective of vaccination status), to analyze the changes in age-related serological susceptibility patterns. A total of 1960 residents aged 0–60 years and 315 mother–infant pairs were studied. Serum IgG antibodies against measles virus were measured by ELISA. The overall seroprevalence was 93.4% in the general population in Dongguan, China. In subgroups aged 1–29 years who were likely vaccinated, there was a declining trend of seropositivity with age from 98.6% at 1–4 years to 85.7% at 20–29 years (P < 0.0001). Seroprevalence were near or >95% in the older population (30–39 years and ≥40 years) who had not been immunized against measles. Age and sex were independent factors associated with seropositivity. Seroprevalence in pregnant women and their newborns was 87.0% and 84.1%, respectively. Our results suggest that the waning vaccine-induced immunity may be the main cause of increased serological susceptibility in young adults and young infants. An additional vaccination strategy that targets young adults is important for elimination of measles. PMID:24448194

  20. The Age-Related Orientational Changes of Human Semicircular Canals

    PubMed Central

    Lyu, Hui-Ying; Chen, Ke-Guang; Yin, Dong-Ming; Hong, Juan; Yang, Lin; Zhang, Tian-Yu; Dai, Pei-Dong

    2016-01-01

    Objectives Some changes are found in the labyrinth anatomy during postnatal development. Although the spatial orientation of semicircular canals was thought to be stable after birth, we investigated the age-related orientational changes of human semicircular canals during development. Methods We retrospectively studied the computed tomography (CT) images of both ears of 76 subjects ranged from 1 to 70 years old. They were divided into 4 groups: group A (1–6 years), group B (7–12 years), group C (13–18 years), and group D (>18 years). The anatomical landmarks of the inner ear structures were determined from CT images. Their coordinates were imported into MATLAB software for calculating the semicircular canals orientation, angles between semicircular canal planes and the jugular bulb (JB) position. Differences between age groups were analyzed using multivariate statistics. Relationships between variables were analyzed using Pearson analysis. Results The angle between the anterior semicircular canal plane and the coronal plane, and the angle between the horizontal semicircular canal plane and the coronal plane were smaller in group D than those in group A (P<0.05). The JB position, especially the anteroposterior position of right JB, correlated to the semicircular canals orientation (P<0.05). However, no statistically significant differences in the angles between ipsilateral canal planes among different age groups were found. Conclusion The semicircular canals had tendencies to tilt anteriorly simultaneously as a whole with age. The JB position correlated to the spatial arrangement of semicircular canals, especially the right JB. Our calculation method helps detect developmental and pathological changes in vestibular anatomy. PMID:27090280

  1. Age-related changes in intrinsic function of the superior temporal sulcus in autism spectrum disorders.

    PubMed

    Alaerts, Kaat; Nayar, Kritika; Kelly, Clare; Raithel, Jessica; Milham, Michael P; Di Martino, Adriana

    2015-10-01

    Currently, the developmental trajectories of neural circuits implicated in autism spectrum disorders (ASD) are largely unknown. Here, we specifically focused on age-related changes in the functional circuitry of the posterior superior temporal sulcus (pSTS), a key hub underlying social-cognitive processes known to be impaired in ASD. Using a cross-sectional approach, we analysed resting-state functional magnetic resonance imaging (fMRI) data collected from children, adolescents and adults available through the autism brain imaging data exchange repository [n = 106 with ASD and n = 109 typical controls (TC), ages 7-30 years]. The observed age-related changes of pSTS intrinsic functional connectivity (iFC) suggest that no single developmental pattern characterizes ASD. Instead, pSTS circuitry displayed a complex developmental picture, with some functional circuits showing patterns consistent with atypical development in ASD relative to TC (pSTS-iFC with fusiform gyrus and angular gyrus) and others showing delayed maturation (pSTS-iFC with regions of the action perception network). Distinct developmental trajectories in different functional circuits in ASD likely reflect differential age-related changes in the socio-cognitive processes they underlie. Increasing insight on these mechanisms is a critical step in the development of age-specific interventions in ASD. PMID:25809403

  2. Molecular aspects of age-related cognitive decline: the role of GABA signaling

    PubMed Central

    McQuail, Joseph A.; Frazier, Charles J.; Bizon, Jennifer L.

    2015-01-01

    Alterations in inhibitory interneurons contribute to cognitive deficits associated with several psychiatric and neurological diseases. Phasic and tonic inhibition imparted by γ-amino-butyric acid (GABA) receptors regulates neural activity and helps to establish the appropriate network dynamics in cortical circuits that support normal cognition. This review highlights basic science demonstrating that inhibitory signaling is altered in aging, and discusses the impact of age-related shifts in inhibition on different forms of memory function, including hippocampus-dependent spatial reference memory and prefrontal cortex (PFU)-dependent working memory. The clinical appropriateness and tractability of select therapeutic candidates for cognitive aging that target receptors mediating inhibition are also discussed. PMID:26070271

  3. Age-Related Changes to the Neural Correlates of Social Evaluation

    PubMed Central

    Cassidy, Brittany S.; Shih, Joanne Y.; Gutchess, Angela H.

    2012-01-01

    Recent work suggests the existence of a specialized neural system underlying social processing that may be relatively spared with age, unlike pervasive aging-related decline occurring in many cognitive domains. We investigated how neural mechanisms underlying social evaluation are engaged with age, and how age-related changes to socioemotional goals affect recruitment of regions within this network. In a functional MRI study, fifteen young and fifteen older adults formed behavior-based impressions of individuals. They also responded to a prompt that was interpersonally meaningful, social but interpersonally irrelevant, or non-social. Both age groups engaged regions implicated in mentalizing and impression formation when making social relative to non-social evaluations, including dorsal and ventral medial prefrontal cortices, precuneus, and temporoparietal junction. Older adults had increased activation over young in right temporal pole when making social relative to non-social evaluations, suggesting reliance on past experiences when evaluating others. Young had greater activation than old in posterior cingulate gyrus when making interpersonally irrelevant, compared to interpersonally meaningful, evaluations, potentially reflecting enhanced valuation of this information. The findings demonstrate the age-related preservation of the neural correlates underlying social evaluation, and suggest that functioning in these regions might be mediated by age-related changes in socioemotional goals. PMID:22439896

  4. Age-related changes in the Brazilian woman's smile.

    PubMed

    Correia, Luiza Nayara Almeida Lyra; Reis, Silvia Augusta Braga; Conti, Ana Claudia de Castro Ferreira; Capelozza Filho, Leopoldino; Almeida-Pedrin, Renata Rodrigues

    2016-01-01

    The aim of this research was to evaluate age-related changes in the smile of Brazilian women. The sample consisted of 249 Brazilian women who had not undergone previous orthodontic treatment or facial surgery. They were divided into four groups, according to age: G1 (20-29), G2 (30-39), G3 (40-49) and G4 (50 or older). Standardized front view photographs were taken while smiling and at rest. Measurements were evaluated by ANOVA and post-hoc Tukey. The Chi-square test was applied for qualitative variables. Upper lip thickness at rest and exposure of upper incisors on smiling decreased with age. Most individuals (60.9%) exhibited a medium smile. High smiles were more often seen in G1 (45%) and less frequently in G4 (18.8%), whereas the opposite occurred with the low smile, i.e., G4 (21.9%) and G1 (6.7%). Variations among the groups were observed in the transverse exposure of the teeth on smiling. In G1 and G3, there was a balance between tooth exposures, so that the teeth were exposed as far as the premolars and/or molars. Most of the women (56.3%) in G2 exposed their teeth as far as the first molars on smiling, whereas most of those (40.6%) in G4 exposed their teeth only as far as the first premolars on smiling. As age increased, there was decreased exposure of the upper incisors, decreased upper lip thickness and lower exposure of teeth vertically and transversely. PMID:27119585

  5. Foreign language training as cognitive therapy for age-related cognitive decline: A hypothesis for future research

    PubMed Central

    Antoniou, Mark; Gunasekera, Geshri; Wong, Patrick C. M.

    2014-01-01

    Over the next fifty years, the number of older adults is set to reach record levels. Protecting older adults from the age-related effects of cognitive decline is one of the greatest challenges of the next few decades as it places increasing pressure on families, health systems, and economies on a global scale. The disease-state of age-related cognitive decline—Alzheimer's disease and other dementias—hijacks our consciousness and intellectual autonomy. However, there is evidence that cognitively stimulating activities protect against the adverse effects of cognitive decline. Similarly, bilingualism is also considered to be a safeguard. We propose that foreign language learning programs aimed at older populations are an optimal solution for building cognitive reserve because language learning engages an extensive brain network that is known to overlap with the regions negatively affected by the aging process. It is recommended that future research should test this potentially fruitful hypothesis. PMID:24051310

  6. Effects of a computer-based cognitive exercise program on age-related cognitive decline.

    PubMed

    Bozoki, Andrea; Radovanovic, Mirjana; Winn, Brian; Heeter, Carrie; Anthony, James C

    2013-01-01

    We developed a 'senior friendly' suite of online 'games for learning' with interactive calibration for increasing difficulty, and evaluated the feasibility of a randomized clinical trial to test the hypothesis that seniors aged 60-80 can improve key aspects of cognitive ability with the aid of such games. Sixty community-dwelling senior volunteers were randomized to either an online game suite designed to train multiple cognitive abilities, or to a control arm with online activities that simulated the look and feel of the games but with low level interactivity and no calibration of difficulty. Study assessment included measures of recruitment, retention and play-time. Cognitive change was measured with a computerized assessment battery administered just before and within two weeks after completion of the six-week intervention. Impediments to feasibility included: limited access to in-home high-speed internet, large variations in the amount of time devoted to game play, and a reluctance to pursue more challenging levels. Overall analysis was negative for assessed performance (transference effects) even though subjects improved on the games themselves. Post hoc analyses suggest that some types of games may have more value than others, but these effects would need to be replicated in a study designed for that purpose. We conclude that a six-week, moderate-intensity computer game-based cognitive intervention can be implemented with high-functioning seniors, but the effect size is relatively small. Our findings are consistent with Owen et al. (2010), but there are open questions about whether more structured, longer duration or more intensive 'games for learning' interventions might yield more substantial cognitive improvement in seniors. PMID:23542053

  7. Vagal Recovery From Cognitive Challenge Moderates Age-Related Deficits in Executive Functioning.

    PubMed

    Crowley, Olga V; Kimhy, David; McKinley, Paula S; Burg, Matthew M; Schwartz, Joseph E; Lachman, Margie E; Tun, Patricia A; Ryff, Carol D; Seeman, Teresa E; Sloan, Richard P

    2016-05-01

    Decline in executive functioning (EF) is a hallmark of cognitive aging. We have previously reported that faster vagal recovery from cognitive challenge is associated with better EF. This study examined the association between vagal recovery from cognitive challenge and age-related differences in EF among 817 participants in the Midlife in the U.S. study (aged 35-86). Cardiac vagal control was measured as high-frequency heart rate variability. Vagal recovery moderated the association between age and EF (β = .811, p = .004). Secondary analyses revealed that older participants (aged 65-86) with faster vagal recovery had superior EF compared to their peers who had slower vagal recovery. In contrast, among younger (aged 35-54) and middle-aged (aged 55-64) participants, vagal recovery was not associated with EF. We conclude that faster vagal recovery from cognitive challenge is associated with reduced deficits in EF among older, but not younger individuals. PMID:26303063

  8. Vagal Recovery From Cognitive Challenge Moderates Age-Related Deficits in Executive Functioning

    PubMed Central

    Crowley, Olga V.; Kimhy, David; McKinley, Paula S.; Burg, Matthew M.; Schwartz, Joseph E.; Lachman, Margie E.; Tun, Patricia A.; Ryff, Carol D.; Seeman, Teresa E.; Sloan, Richard P.

    2015-01-01

    Decline in executive functioning (EF) is a hallmark of cognitive aging. We have previously reported that faster vagal recovery from cognitive challenge is associated with better EF. This study examined the association between vagal recovery from cognitive challenge and age-related differences in EF among 817 participants in the Midlife in the U.S. study (aged 35–86). Cardiac vagal control was measured as high-frequency heart rate variability. Vagal recovery moderated the association between age and EF (β = .811, p = .004). Secondary analyses revealed that older participants (aged 65–86) with faster vagal recovery had superior EF compared to their peers who had slower vagal recovery. In contrast, among younger (aged 35–54) and middle-aged (aged 55–64) participants, vagal recovery was not associated with EF. We conclude that faster vagal recovery from cognitive challenge is associated with reduced deficits in EF among older, but not younger individuals. PMID:26303063

  9. Age-related changes in Egr1 transcription and DNA methylation within the hippocampus.

    PubMed

    Penner, M R; Parrish, R R; Hoang, L T; Roth, T L; Lubin, F D; Barnes, C A

    2016-08-01

    Aged animals show functional alterations in hippocampal neurons that lead to deficits in synaptic plasticity and changes in cognitive function. Transcription of immediate-early genes (IEGs), including Egr1, is necessary for processes such as long-term potentiation and memory consolidation. Here, we show an age-related reduction in the transcription of Egr1 in the dentate gyrus following spatial behavior, whereas in the area CA1, Egr1 is reduced at rest, but its transcription can be effectively driven by spatial behavior to levels equivalent to those observed in adult animals. One mechanism possibly contributing to these aging-related changes is an age-associated, CpG site-specific change in methylation in DNA associated with the promoter region of the Egr1 gene. Our results add to a growing body of work demonstrating that complex transcriptional and epigenetic changes in the hippocampus significantly contribute to brain and cognitive aging. © 2016 Wiley Periodicals, Inc. PMID:26972614

  10. Progressive Age-Related Changes Similar to Age-Related Macular Degeneration in a Transgenic Mouse Model

    PubMed Central

    Rakoczy, Piroska Elizabeth; Zhang, Dan; Robertson, Terry; Barnett, Nigel L.; Papadimitriou, John; Constable, Ian Jeffrey; Lai, Chooi-May

    2002-01-01

    Age-related macular degeneration (AMD) is the major cause of blindness in the developed world. Its pathomechanism is unknown and its late onset, complex genetics and strong environmental components have all hampered investigations. Here we demonstrate the development of an animal model for AMD that reproduces features associated with geographic atrophy; a transgenic mouse line (mcd/mcd) expressing a mutated form of cathepsin D that is enzymatically inactive thus impairing processing of phagocytosed photoreceptor outer segments in the retinal pigment epithelial (RPE) cells. Pigmentary changes indicating RPE cell atrophy and a decreased response to flash electroretinograms were observed in 11- to 12-month-old mcd/mcd mice. Histological studies showed RPE cell proliferation, photoreceptor degeneration, shortening of photoreceptor outer segments, and accumulation of immunoreactive photoreceptor breakdown products in the RPE cells. An accelerated photoreceptor cell death was detected in 12-month-old mcd/mcd mice. Transmission electron microscopy demonstrated presence of basal laminar and linear deposits that are considered to be the hallmarks of AMD. Small hard drusen associated with human age-related maculopathy were absent in the mcd/mcd mouse model at the ages analyzed. In summary, this model presents several features of AMD, thus providing a valuable tool for investigating the underlying biological processes and pathomechanism of AMD. PMID:12368224

  11. Computer Simulations of Loss of Organization of Neurons as a Model for Age-related Cognitive Decline

    NASA Astrophysics Data System (ADS)

    Cruz, Luis; Fengometidis, Elene; Jones, Frank; Jampani, Srinivas

    2011-03-01

    In normal aging, brains suffer from progressive cognitive decline not linked with loss of neurons common in neurodegenerative disorders such as Alzheimer's disease. However, in some brain areas neurons have lost positional organization specifically within microcolumns: arrays of interconnected neurons which may constitute fundamental computational units in the brain. This age-related loss of organization, likely a result of micron-sized random displacements in neuronal positions, is hypothesized to be a by-product of the loss of support from the surrounding medium, including dendrites. Using a dynamical model applied to virtual 3D representation of neuronal arrangements, that previously showed loss of organization in brains of cognitively tested rhesus monkeys, the relationship between these displacements and changes to the surrounding dendrite network are presented. The consequences of these displacements on the structure of the dendritic network, with possible disruptions in signal synchrony important to cognitive function, are discussed. NIH R01AG021133.

  12. Age-related changes in angiogenesis in human dermis.

    PubMed

    Gunin, Andrei G; Petrov, Vadim V; Golubtzova, Natalia N; Vasilieva, Olga V; Kornilova, Natalia K

    2014-07-01

    Present research is aimed to examine the number of dermal blood vessels, vascular endothelial growth factor (VEGF), delta-like ligand 4(Dll4) and Jagged-1 (Jag-1) in dermal blood vessels of human from 20weeks of pregnancy to 85years old. Numbers and proliferative activity of dermal fibroblast-like cells were also examined. Blood vessels were viewed with immunohistochemical staining for von Willebrand factor or CD31. VEGF, Dll4, Jag-1, and proliferating cell nuclear antigen (PCNA) were detected immunohistochemically. Results showed that the numbers of fibroblast-like cells, PCNA positive fibroblast-like cells, von Willebrand factor positive or CD31 positive blood vessels in dermis are dramatically decreased with age. The intensity of immunohistochemical staining for VEGF or Jag-1 in blood vessels of dermis is increased from antenatal to deep old period. The degree of immunohistochemical staining of dermal blood vessels for Dll4 has gone up from 20-40weeks of pregnancy to early life period (0-20years), and further decreased below antenatal values. Age-related decrease in the number of dermal blood vessels is suggested to be due to an impairment of VEGF signaling and to be mediated by Dll4 and Jag-1. It may be supposed that diminishing in blood supply of dermis occurring with age is a cause of a decrease in the number and proliferative pool of dermal fibroblasts. PMID:24768823

  13. High cognitive reserve is associated with a reduced age-related deficit in spatial conflict resolution

    PubMed Central

    Puccioni, Olga; Vallesi, Antonino

    2012-01-01

    Several studies support the existence of a specific age-related difficulty in suppressing potentially distracting information. The aim of the present study is to investigate whether spatial conflict resolution is selectively affected by aging. The way aging affects individuals could be modulated by many factors determined by the socieconomic status: we investigated whether factors such as cognitive reserve (CR) and years of education may play a compensatory role against age-related deficits in the spatial domain. A spatial Stroop task with no feature repetitions was administered to a sample of 17 non-demented older adults (69–79 years-old) and 18 younger controls (18–34 years-old) matched for gender and years of education. The two age groups were also administered with measures of intelligence and CR. The overall spatial Stroop effect did not differ according to age, neither for speed nor for accuracy. The two age groups equally showed sequential effects for congruent trials: reduced response times (RTs) if another congruent trial preceded them, and accuracy at ceiling. For incongruent trials, older adults, but not younger controls, were influenced by congruency of trialn−1, since RTs increased with preceding congruent trials. Interestingly, such an age-related modulation negatively correlated with CR. These findings suggest that spatial conflict resolution in aging is predominantly affected by general slowing, rather than by a more specific deficit. However, a high level of CR seems to play a compensatory role for both factors. PMID:23248595

  14. Age-related differences in gap detection: Effects of task difficulty and cognitive ability

    PubMed Central

    Harris, Kelly C.; Eckert, Mark A.; Ahlstrom, Jayne B.; Dubno, Judy R.

    2009-01-01

    Differences in gap detection for younger and older adults have been shown to vary with the complexity of the task or stimuli, but the factors that contribute to these differences remain unknown. To address this question, we examined the extent to which age-related differences in processing speed and workload predicted age-related differences in gap detection. Gap detection thresholds were measured for 10 younger and 11 older adults in two conditions that varied in task complexity but used identical stimuli: (1) gap location fixed at the beginning, middle, or end of a noise burst and (2) gap location varied randomly from trial to trial from the beginning, middle, or end of the noise. We hypothesized that gap location uncertainty would place increased demands on cognitive and attentional resources and result in significantly higher gap detection thresholds for older but not younger adults. Overall, gap detection thresholds were lower for the middle location as compared to beginning and end locations and were lower for the fixed than the random condition. In general, larger age-related differences in gap detection were observed for more challenging conditions. That is, gap detection thresholds for older adults were significantly larger for the random condition than for the fixed condition when the gap was at the beginning and end locations but not the middle. In contrast, gap detection thresholds for younger adults were not significantly different for the random and fixed condition at any location. Subjective ratings of workload indicated that older adults found the gap-detection task more mentally demanding than younger adults. Consistent with these findings, results of the Purdue Pegboard and Connections tests revealed age-related slowing of processing speed. Moreover, age group differences in workload and processing speed predicted gap detection in younger and older adults when gap location varied from trial to trial; these associations were not observed when gap

  15. Who Moved My Cheese? Adjusting to Age-Related Changes

    ERIC Educational Resources Information Center

    Langer, Nieli

    2012-01-01

    The popular book, Who Moved My Cheese? (Johnson, 1998) is a metaphor for change. This parable-like story has particular resonance with older adults who face many potential life-altering changes. The four characters in the book are looking for their cheese in a maze. Cheese represents whatever makes people happy. How each character adjusts to the…

  16. AGE-RELATED CHANGES IN SENSITIVITY TO ENVIRONMENTAL CHEMICALS

    EPA Science Inventory

    The processes of aging result in many physiological changes which can lead to alterations in both pharmacokinetic and pharmacodynamic properties. uch changes can result in altered sensitivity to chemicals, whether drugs or environmental agents, in the elderly. t is extremely diff...

  17. Age-related differences in white matter integrity and cognitive function are related to APOE status

    PubMed Central

    Ryan, Lee; Walther, Katrin; Bendlin, Barbara B.; Lue, Lih-Fen; Walker, Douglas G.; Glisky, Elizabeth L.

    2010-01-01

    While an extensive literature is now available on age-related differences in white matter integrity measured by diffusion MRI, relatively little is known about the relationships between diffusion and cognitive functions in older adults. Even less is known about whether these relationships are influenced by the apolipoprotein (APOE) ε4 allele, despite growing evidence that ε4 increases cognitive impairment in older adults. The purpose of the present study was to examine these relationships in a group of community-dwelling cognitively normal older adults. Data were obtained from a sample of 126 individuals (ages 52–92) that included 32 ε4 heterozygotes, 6 ε4 homozygotes, and 88 non-carriers. Two measures of diffusion, the apparent diffusion coefficient (ADC) and fractional anisotropy (FA), were obtained from six brain regions – frontal white matter, lateral parietal white matter, the centrum semiovale, the genu and splenium of the corpus callosum, and the temporal stem white matter – and were used to predict composite scores of cognitive function in two domains, executive function and memory function. Results indicated that ADC and FA differed with increasing age in all six brain regions, and these differences were significantly greater for ε4 carriers compared to noncarriers. Importantly, after controlling for age, diffusion measures predicted cognitive function in a region-specific way that was also influenced by ε4 status. Regardless of APOE status, frontal ADC and FA independently predicted executive function scores for all participants, while temporal lobe ADC additionally predicted executive function for ε4 carriers, but not noncarriers. Memory scores were predicted by temporal lobe ADC but not frontal diffusion for all participants, and this relationship was significantly stronger in ε4 carriers compared to noncarriers. Taken together, age and temporal lobe ADC accounted for a striking 53% of the variance in memory scores within the ε4 carrier

  18. Age-Related Changes in Electroencephalographic Signal Complexity

    PubMed Central

    Zappasodi, Filippo; Marzetti, Laura; Olejarczyk, Elzbieta; Tecchio, Franca; Pizzella, Vittorio

    2015-01-01

    The study of active and healthy aging is a primary focus for social and neuroscientific communities. Here, we move a step forward in assessing electrophysiological neuronal activity changes in the brain with healthy aging. To this end, electroencephalographic (EEG) resting state activity was acquired in 40 healthy subjects (age 16–85). We evaluated Fractal Dimension (FD) according to the Higuchi algorithm, a measure which quantifies the presence of statistical similarity at different scales in temporal fluctuations of EEG signals. Our results showed that FD increases from age twenty to age fifty and then decreases. The curve that best fits the changes in FD values across age over the whole sample is a parabola, with the vertex located around age fifty. Moreover, FD changes are site specific, with interhemispheric FD asymmetry being pronounced in elderly individuals in the frontal and central regions. The present results indicate that fractal dimension well describes the modulations of brain activity with age. Since fractal dimension has been proposed to be related to the complexity of the signal dynamics, our data demonstrate that the complexity of neuronal electric activity changes across the life span of an individual, with a steady increase during young adulthood and a decrease in the elderly population. PMID:26536036

  19. Perspective: A Critical Look at the Ancillary Age-Related Eye Disease Study 2: Nutrition and Cognitive Function Results in Older Individuals with Age-Related Macular Degeneration.

    PubMed

    Hammond, Billy R; Renzi-Hammond, Lisa M

    2016-05-01

    A large body of literature suggests that the dietary carotenoids lutein and zeaxanthin and long-chain polyunsaturated fatty acids such as docosahexaenoic acid are related to improved cognitive function across the life span. A recent report by the Age-Related Eye Disease Study (AREDS) group appears to contradict the general findings of others in the field. In this review, we look critically at the methods, study designs, and analysis techniques used in the larger body of literature and compare them with the recent AREDS reports. PMID:27184270

  20. Age-related changes in genomic stability of horses.

    PubMed

    Wnuk, Maciej; Bugno-Poniewierska, Monika; Lewinska, Anna; Oklejewicz, Bernadetta; Zabek, Tomasz; Bartosz, Grzegorz; Słota, Ewa

    2011-05-01

    Recently, the old horse has been proposed as a model to study telomere-dependent senescence, immunosenescence and inflamm-aging. In the present paper, we used 80 Hucul and Anglo-Arabian horses divided into 3 age groups (juvenile, adult, old) to evaluate age-dependent changes at the genomic and DNA level and in cell proliferative potential. The level of positive TUNEL cells (both apoptotic and with DNA fragmentation), oxidative DNA damage (8-oxoG immunostaining), sister chromatid exchange and bleomycin-induced chromatid breaks were significantly increased in the combined old group compared to the combined adult group. We observed a negative correlation between micronuclei formation and age, which may be associated with damaged cells undergoing apoptosis, rather than expressing micronuclei. We were unable to show any significant changes in the nuclear division index value, which reflects the proliferative status of the viable cell fraction during aging. Here, we show that breed-independent and age-associated changes in genomic stability may contribute, at least in part, to the aging process in the horse. PMID:21557962

  1. Age-related changes in chest geometry during cardiopulmonary resuscitation.

    PubMed

    Dean, J M; Koehler, R C; Schleien, C L; Michael, J R; Chantarojanasiri, T; Rogers, M C; Traystman, R J

    1987-06-01

    We studied alterations of chest geometry during conventional cardiopulmonary resuscitation in anesthetized immature swine. Pulsatile force was applied to the sternum in increments to determine the effects of increasing compression on chest geometry and intrathoracic vascular pressures. In 2-wk- and 1-mo-old piglets, permanent changes in chest shape developed due to incomplete recoil of the chest along the anteroposterior axis, and large intrathoracic vascular pressures were generated. In 3-mo-old animals, permanent chest deformity did not develop, and large intrathoracic vascular pressures were not produced. We propose a theoretical model of the chest as an elliptic cylinder. Pulsatile displacement along the minor axis of an ellipse produces a greater decrease in cross-sectional area than displacement of a circular cross section. As thoracic cross section became less circular due to deformity, greater changes in thoracic volume, and hence pressure, were produced. With extreme deformity at high force, pulsatile displacement became limited, diminishing pressure generation. We conclude that changes in chest geometry are important in producing intrathoracic intravascular pressure during conventional cardiopulmonary resuscitation in piglets. PMID:3610916

  2. Longitudinal Attentional Engagement Rescues Mice from Age-Related Cognitive Declines and Cognitive Inflexibility

    ERIC Educational Resources Information Center

    Matzel, Louis D.; Light, Kenneth R.; Wass, Christopher; Colas-Zelin, Danielle; Denman-Brice, Alexander; Waddel, Adam C.; Kolata, Stefan

    2011-01-01

    Learning, attentional, and perseverative deficits are characteristic of cognitive aging. In this study, genetically diverse CD-1 mice underwent longitudinal training in a task asserted to tax working memory capacity and its dependence on selective attention. Beginning at 3 mo of age, animals were trained for 12 d to perform in a dual radial-arm…

  3. Dosimetric implications of age related glandular changes in screening mammography

    NASA Astrophysics Data System (ADS)

    Beckett, J. R.; Kotre, C. J.

    2000-03-01

    The UK National Health Service Breast Screening Programme is currently organized to routinely screen women between the ages of 50 and 64, with screening for older women available on request. The lower end of this age range closely matches the median age for the menopause (51 years), during which significant changes in the composition of the breast are known to occur. In order to quantify the dosimetric effect of these changes, radiographic factors and compressed breast thickness data for a cohort of 1258 women aged between 35 and 79 undergoing breast screening mammography have been used to derive estimates of breast glandularity and mean glandular dose (MGD), and examine their variation with age. The variation of mean radiographic exposure factors with age is also investigated. The presence of a significant number of age trial women within the cohort allowed an extended age range to be studied. Estimates of MGD including corrections for breast glandularity based on compressed breast thickness only, compressed breast thickness and age and for each individual woman are compared with the MGD based on the conventional assumption of a 50:50 adipose/glandular composition. It has been found that the use of the conventional 50:50 assumption leads to overestimates of MGD of up to 13% over the age range considered. By using compressed breast thickness to estimate breast glandularity, this error range can be reduced to 8%, whilst age and compressed breast thickness based glandularity estimates result in an error range of 1%.

  4. Age related changes in age of starting to smoke.

    PubMed

    Weinkam, J J; Sterling, T D

    1990-01-01

    The Average Age of Starting to Smoke (AASS) has been reported to decline for younger birth cohorts. That apparent decline has been used to support a conclusion of an increase in smoking among younger individuals. However, in some cases the apparent decline is an artifact of the method of computation which arises when the quantity being averaged is related to a quantity used to classify subjects for comparison. In one other case, a second type of error arises because the distribution of smoking initiation with age changed in such a way that the proportion of individuals taking up smoking at older ages declined more rapidly than the proportion starting at younger ages. In fact, comparison of the 1970 National Health Interview Survey (NHIS) to the 1979/80 NHIS shows a uniform decrease in starting to smoke among teens and preteens. Examples are discussed which show that estimates of possible disease related factors actually experienced by a cohort are possible only if other suitable data are available for comparable representative sections of the population at different time periods and for different ages. PMID:2303843

  5. Age-related changes in matching novel objects across viewpoints

    PubMed Central

    Konar, Yaroslav; Vuong, Quoc C.; Bennett, Patrick J.; Sekuler, Allison B.

    2016-01-01

    Object recognition is an important visual process. We are not only required to recognize objects across a variety of lighting conditions and variations in size, but also across changes in viewpoint. It has been shown that reaction times in object matching increase as a function of increasing angular disparity between two views of the same object, and it is thought that this is related to the time it takes to mentally rotate an object. Recent studies have shown that object rotations for familiar objects affect older subjects differently than younger subjects. To investigate the general normalization effects for recognizing objects across different viewpoints regardless of visual experience with an object, in the current study we used novel 3D stimuli. Older and younger subjects matched objects across a variety of viewpoints along both in-depth and picture-plane rotations. Response times (RTs) for in-depth rotations were generally slower than for picture plane rotations and older subjects, overall, responded slower than younger subjects. However, a male RT advantage was only found for objects that differed by large, in-depth rotations. Compared to younger subjects, older subjects were not only slower but also less accurate at matching objects across both rotation axes. The age effect was primarily due to older male subjects performing worse than younger male subjects, whereas there was no significant age difference for female subjects. In addition, older males performed even worse than older females, which argues against a general male advantage in mental rotations tasks. PMID:21784094

  6. Over the hill at 24: persistent age-related cognitive-motor decline in reaction times in an ecologically valid video game task begins in early adulthood.

    PubMed

    Thompson, Joseph J; Blair, Mark R; Henrey, Andrew J

    2014-01-01

    Typically studies of the effects of aging on cognitive-motor performance emphasize changes in elderly populations. Although some research is directly concerned with when age-related decline actually begins, studies are often based on relatively simple reaction time tasks, making it impossible to gauge the impact of experience in compensating for this decline in a real world task. The present study investigates age-related changes in cognitive motor performance through adolescence and adulthood in a complex real world task, the real-time strategy video game StarCraft 2. In this paper we analyze the influence of age on performance using a dataset of 3,305 players, aged 16-44, collected by Thompson, Blair, Chen & Henrey [1]. Using a piecewise regression analysis, we find that age-related slowing of within-game, self-initiated response times begins at 24 years of age. We find no evidence for the common belief expertise should attenuate domain-specific cognitive decline. Domain-specific response time declines appear to persist regardless of skill level. A second analysis of dual-task performance finds no evidence of a corresponding age-related decline. Finally, an exploratory analyses of other age-related differences suggests that older participants may have been compensating for a loss in response speed through the use of game mechanics that reduce cognitive load. PMID:24718593

  7. Over the Hill at 24: Persistent Age-Related Cognitive-Motor Decline in Reaction Times in an Ecologically Valid Video Game Task Begins in Early Adulthood

    PubMed Central

    Thompson, Joseph J.; Blair, Mark R.; Henrey, Andrew J.

    2014-01-01

    Typically studies of the effects of aging on cognitive-motor performance emphasize changes in elderly populations. Although some research is directly concerned with when age-related decline actually begins, studies are often based on relatively simple reaction time tasks, making it impossible to gauge the impact of experience in compensating for this decline in a real world task. The present study investigates age-related changes in cognitive motor performance through adolescence and adulthood in a complex real world task, the real-time strategy video game StarCraft 2. In this paper we analyze the influence of age on performance using a dataset of 3,305 players, aged 16-44, collected by Thompson, Blair, Chen & Henrey [1]. Using a piecewise regression analysis, we find that age-related slowing of within-game, self-initiated response times begins at 24 years of age. We find no evidence for the common belief expertise should attenuate domain-specific cognitive decline. Domain-specific response time declines appear to persist regardless of skill level. A second analysis of dual-task performance finds no evidence of a corresponding age-related decline. Finally, an exploratory analyses of other age-related differences suggests that older participants may have been compensating for a loss in response speed through the use of game mechanics that reduce cognitive load. PMID:24718593

  8. Jumping Stand Apparatus Reveals Rapidly Specific Age-Related Cognitive Impairments in Mouse Lemur Primates

    PubMed Central

    Picq, Jean-Luc; Villain, Nicolas; Gary, Charlotte; Pifferi, Fabien; Dhenain, Marc

    2015-01-01

    The mouse lemur (Microcebus murinus) is a promising primate model for investigating normal and pathological cerebral aging. The locomotor behavior of this arboreal primate is characterized by jumps to and from trunks and branches. Many reports indicate insufficient adaptation of the mouse lemur to experimental devices used to evaluate its cognition, which is an impediment to the efficient use of this animal in research. In order to develop cognitive testing methods appropriate to the behavioral and biological traits of this species, we adapted the Lashley jumping stand apparatus, initially designed for rats, to the mouse lemur. We used this jumping stand apparatus to compare performances of young (n = 12) and aged (n = 8) adults in acquisition and long-term retention of visual discriminations. All mouse lemurs completed the tasks and only 25 trials, on average, were needed to master the first discrimination problem with no age-related differences. A month later, all mouse lemurs made progress for acquiring the second discrimination problem but only the young group reached immediately the criterion in the retention test of the first discrimination problem. This study shows that the jumping stand apparatus allows rapid and efficient evaluation of cognition in mouse lemurs and demonstrates that about half of the old mouse lemurs display a specific deficit in long-term retention but not in acquisition of visual discrimination. PMID:26716699

  9. Jumping Stand Apparatus Reveals Rapidly Specific Age-Related Cognitive Impairments in Mouse Lemur Primates.

    PubMed

    Picq, Jean-Luc; Villain, Nicolas; Gary, Charlotte; Pifferi, Fabien; Dhenain, Marc

    2015-01-01

    The mouse lemur (Microcebus murinus) is a promising primate model for investigating normal and pathological cerebral aging. The locomotor behavior of this arboreal primate is characterized by jumps to and from trunks and branches. Many reports indicate insufficient adaptation of the mouse lemur to experimental devices used to evaluate its cognition, which is an impediment to the efficient use of this animal in research. In order to develop cognitive testing methods appropriate to the behavioral and biological traits of this species, we adapted the Lashley jumping stand apparatus, initially designed for rats, to the mouse lemur. We used this jumping stand apparatus to compare performances of young (n = 12) and aged (n = 8) adults in acquisition and long-term retention of visual discriminations. All mouse lemurs completed the tasks and only 25 trials, on average, were needed to master the first discrimination problem with no age-related differences. A month later, all mouse lemurs made progress for acquiring the second discrimination problem but only the young group reached immediately the criterion in the retention test of the first discrimination problem. This study shows that the jumping stand apparatus allows rapid and efficient evaluation of cognition in mouse lemurs and demonstrates that about half of the old mouse lemurs display a specific deficit in long-term retention but not in acquisition of visual discrimination. PMID:26716699

  10. Changes in pattern completion – a key mechanism to explain age-related recognition memory deficits?

    PubMed Central

    Vieweg, Paula; Stangl, Matthias; Howard, Lorelei R.; Wolbers, Thomas

    2016-01-01

    Accurate memory retrieval from partial or degraded input requires the reactivation of memory traces, a hippocampal mechanism termed pattern completion. Age-related changes in hippocampal integrity have been hypothesized to shift the balance of memory processes in favor of the retrieval of already stored information (pattern completion), to the detriment of encoding new events (pattern separation). Using a novel behavioral paradigm, we investigated the impact of cognitive aging (1) on recognition performance across different levels of stimulus completeness, and (2) on potential response biases. Participants were required to identify previously learned scenes among new ones. Additionally, all stimuli were presented in gradually masked versions to alter stimulus completeness. Both young and older adults performed increasingly poorly as the scenes became less complete, and this decline in performance was more pronounced in elderly participants indicative of a pattern completion deficit. Intriguingly, when novel scenes were shown, only the older adults showed an increased tendency to identify these as familiar scenes. In line with theoretical models, we argue that this reflects an age-related bias towards pattern completion. PMID:25597525

  11. Age-related changes in the performance of forward reach.

    PubMed

    Lin, S I; Liao, C F

    2011-01-01

    Aging is widely considered to be associated with limited balance capacity. It is not clear if forward reach ability is also affected by aging. The purpose of this study was to determine if aging was associated with reduced ability of forward reach or changes in movement patterns. Thirty-three young and 31 older adults were instructed to reach forward as far as possible without losing balance. A motion analysis system was used to record the body kinematics to calculate the joint angle and estimate the motion of center of mass (COM) using a five-segment model. Reach distance (measured from the finger marker), COM displacement, and the distance that the COM exceeded the 2nd toe marker (COM-toe) were used to represent reach performance. The movement patterns were classified as hip, ankle or mixed strategies based upon joint kinematics. It was found that the initial location of the COM was significantly more anterior in the older adults. Older adults were found to have significantly smaller COM displacement and greater hip flexion, but did not differ from young adults in reach distance or COM-toe. Older adults overwhelmingly adopted a hip strategy, but none adopted an ankle strategy. The distribution of the different strategies also differed significantly between groups. These findings suggest that aging appears to be associated with modifications in movement patterns, but not necessarily with a reduction in the ability to approach the boundary of stability. Clinically, balance training for older adults may include the exploration and instruction of atypical movement patterns. PMID:20951591

  12. Age-related changes in dynamic moduli of ovine vitreous.

    PubMed

    Colter, Jourdan; Williams, Alex; Moran, Patrick; Coats, Brittany

    2015-01-01

    Multiple rheological studies have characterized the dynamic material properties of adult vitreous, but no studies have investigated vitreous properties in the immature eye. In this study, premature, infant and adult ovine vitreous specimens were tested in shear to identify differences in dynamic moduli with age. Significant inertial artifact and rapid degradation of the vitreous ex vivo hindered the ability to accurately collect dynamic data through standard oscillation protocols. Therefore, dynamic moduli were calculated by converting relaxation spectrum data to the retardation spectrum, resulting in the calculation of the storage (G') and loss (G") moduli from the first few milliseconds of creep testing when tissue degradation and inertia is minimal. The technique was validated against two synthetic materials that span the viscoelastic spectrum. G' and G" of the primarily viscous synthetic material (polystyrene, tanδ=0.61) and G' of the primarily elastic material (agar, tanδ=0.06) were not significantly different than those calculated from dynamic oscillatory testing (p<0.05). G" of agar was overestimated (4-39%) with the interconversion technique due to creep ringing. Ovine vitreous was primarily viscous (tanδ=1.31), so this technique was used to evaluate changes in dynamic moduli with age. G' and G" for adult vitreous was 2-4 times and 1.5-2 times lower, respectively, than infant vitreous, corresponding to the structural breakdown of the vitreous with age. The dynamic moduli of premature vitreous was lower than infant and adult, likely due to premature development of the vitreal structure. These data suggest that significant differences exist between the viscoelastic response of infant and adult vitreous, and computational models of the pediatric eye will require appropriate age and rate material properties of vitreous. PMID:25266808

  13. Causes and consequences of age-related steroid hormone changes: insights gained from nonhuman primates.

    PubMed

    Sorwell, K G; Urbanski, H F

    2013-11-01

    Similar to humans, rhesus macaques (Macaca mulatta) are large, long-lived diurnal primates, and show similar age-related changes in the secretion of many steroid hormones, including oestradiol, testosterone, cortisol and dehydroepiandrosterone (DHEA). Consequently, they represent a pragmatic animal model in which to examine the mechanisms by which these steroidal changes contribute to perturbed sleep-wake cycles and cognitive decline in the elderly. Using remote serial blood sampling, we have found the circulating levels of DHEA sulphate, as well as oestradiol and testosterone, decline markedly in old monkeys. Furthermore, using the real-time polymerase chain reaction, we have shown that the genes for the enzymes associated with the conversion of DHEA to oestradiol and testosterone (3β-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase, and aromatase) are highly expressed in brain areas associated with cognition and behaviour, including the hippocampus, prefrontal cortex and amygdala. Taken together, these findings suggest that the administration of supplementary DHEA in the elderly may have therapeutic potential for cognitive and behavioural disorders, although with fewer negative side effects outside of the central nervous system. To test this, we have developed a novel steroid supplementation paradigm for use in old animals; this involves the oral administration of DHEA and testosterone at physiologically relevant times of the day to mimic the circadian hormone patterns observed in young adults. We are currently evaluating the efficacy of this steroid supplementation paradigm with respect to reversing age-associated disorders, including perturbed sleep-wake cycles and cognitive decline, as well as an impaired immune response. PMID:23796387

  14. College Students' Attitudes towards Age-Related Changes in Physical Appearance.

    ERIC Educational Resources Information Center

    Kanter, Allison; Agliata, Daniel; Tantleff-Dunn, Stacey

    The aim of this study was to identify factors associated with young adults' concerns about age related changes in body image and their anticipated impact on psychosocial functioning. One hundred and sixty-seven college students completed the Body Image and Aging Survey, designed to assess age related issues in body image, the Peer Dieting Survey,…

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

    NASA Astrophysics Data System (ADS)

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

    2002-11-01

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

  16. Lower cognitive function in patients with age-related macular degeneration: a meta-analysis

    PubMed Central

    Zhou, Li-Xiao; Sun, Cheng-Lin; Wei, Li-Juan; Gu, Zhi-Min; Lv, Liang; Dang, Yalong

    2016-01-01

    Objective To investigate the cognitive impairment in patients with age-related macular degeneration (AMD). Methods Relevant articles were identified through a search of the following electronic databases through October 2015, without language restriction: 1) PubMed; 2) the Cochrane Library; 3) EMBASE; 4) ScienceDirect. Meta-analysis was conducted using STATA 12.0 software. Standardized mean differences with corresponding 95% confidence intervals were calculated. All of the included studies met the following four criteria: 1) the study design was a case–control or randomized controlled trial (RCT) study; 2) the study investigated cognitive function in the patient with AMD; 3) the diagnoses of AMD must be provided; 4) there were sufficient scores data to extract for evaluating cognitive function between cases and controls. The Newcastle–Ottawa Scale criteria were used to assess the methodological quality of the studies. Results Of the initial 278 literatures, only six case–control and one RCT studies met all of the inclusion criteria. A total of 794 AMD patients and 1,227 controls were included in this study. Five studies were performed with mini-mental state examination (MMSE), two studies with animal fluency, two studies with trail making test (TMT)-A and -B, one study with Mini-Cog. Results of the meta-analysis revealed lower cognitive function test scores in patients with AMD, especially with MMSE and Mini-Cog test (P≤0.001 for all). The results also showed that differences in the TMT-A (except AMD [total] vs controls) and TMT-B test had no statistical significance (P>0.01). The Newcastle–Ottawa Scale score was ≥5 for all of the included studies. Based on the sensitivity analysis, no single study influenced the overall pooled estimates. Conclusion This meta-analysis suggests lower cognitive function test scores in patients with AMD, especially with MMSE and Mini-Cog test. The other cognitive impairment screening tests, such as animal fluency test and

  17. ROLE OF SOLUBLE EPOXIDE HYDROLASE IN AGE-RELATED VASCULAR COGNITIVE DECLINE

    PubMed Central

    Nelson, Jonathan W.; Young, Jennifer M.; Borkar, Rohan; Woltjer, Randy L.; Quinn, Joseph F.; Silbert, Lisa C.; Grafe, Marjorie R.; Alkayed, Nabil J.

    2014-01-01

    P450 eicosanoids are important regulators of the cerebral microcirculation, but their role in cerebral small vessel disease is unclear. We tested the hypothesis that vascular cognitive impairment (VCI) is linked to reduced cerebral microvascular eicosanoid signaling. We analyzed human brain tissue from individuals formerly enrolled in the Oregon Brain Aging Study, who had a history of cognitive impairment histopathological evidence of microvascular disease. VCI subjects had significantly higher lesion burden both on premortem MRI and postmortem histopathology compared to age- and sex-matched controls. Mass spectrometry-based eicosanoid analysis revealed that 14,15-dihydroxyeicosatrienoic acid (DHET) was elevated in cortical brain tissue from VCI subjects. Immunoreactivity of soluble epoxide hydrolase (sEH), the enzyme responsible for 14,15-DHET formation, was localized to cerebral microvascular endothelium, and was enhanced in microvessels of affected tissue. Finally, we evaluated the genotype frequency of two functional single nucleotide polymorphisms of sEH gene EPHX2 in VCI and control groups. Our findings support a role for sEH and a potential benefit from sEH inhibitors in age-related VCI. PMID:25277097

  18. Age-related differences in the course of cognitive skill acquisition: the role of regional cortical shrinkage and cognitive resources.

    PubMed

    Head, Denise; Raz, Naftali; Gunning-Dixon, Faith; Williamson, Adrienne; Acker, James D

    2002-03-01

    This study examined the impact of age-related differences in regional cerebral volumes and cognitive resources on acquisition of a cognitive skill. Volumes of brain regions were measured on magnetic resonance images of healthy adults (aged 22-80). At the early stage of learning to solve the Tower of Hanoi puzzle, speed and efficiency were associated with age, prefrontal cortex volume, and working memory. A similar pattern of brain-behavior associations was observed with perseveration measured on the Wisconsin Card Sorting Test. None of the examined structural brain variables were important at the later stages of skill acquisition. When hypertensive participants were excluded, the effect of prefrontal shrinkage on executive aspects of performance was no longer significant, but the effect of working memory remained. PMID:11931289

  19. The Relation between canine cognitive dysfunction and age-related brain lesions

    PubMed Central

    OZAWA, Makiko; CHAMBERS, James K.; UCHIDA, Kazuyuki; NAKAYAMA, Hiroyuki

    2016-01-01

    Canine cognitive dysfunction (CCD) is a syndrome that manifests itself in abnormal behaviors, such as disorientation and wandering. β-amyloid deposition in the brain, including the senile plaque (SP) and cerebral amyloid angiopathy (CAA), has been suggested as a major cause of the syndrome. However, the pathological significance of β-amyloid deposition in CCD dogs remains unclear. The present study was conducted using 16 dogs aged 10 years or older to clarify the relationship between the age-related histopathological lesions, such as β-amyloid deposition, in the brain and the clinical symptoms of CCD as evaluated in a questionnaire previously established in a large survey. In addition, age-related brain lesions were assessed in 37 dogs. The pathological lesions were evaluated by the severity of β-amyloid deposition (SP and CAA), the amount of ubiquitin-positive granules (UBQ), GFAP-positive astrocytes, Iba-1-positive microglia and Nissle stain-positive nerve cells. The results revealed that there was no significant correlation between the severities of canine SP and CCD. The SP increased until 14 years old, but decreased thereafter, although the incidence of CCD is high at these ages. The CAA consistently increased with age, but did not correlate greatly with the CCD score. In contrast, the increases of UBQ, astrocytes and microglia were significantly correlated with CCD. Thus, the impairment in the synapse and/or myelin suggested by increased UBQ and glial activation might be involved in CCD pathogenesis, but β-amyloid deposition, especially SP, is not a direct pathogenic factor of CCD. PMID:26922972

  20. AGE-RELATED GENE EXPRESSION CHANGES IN HUMAN SKIN FIBROBLASTS INDUCED BY MMS

    EPA Science Inventory

    Age-Related Gene Expression Changes In Human Skin Fibroblasts Induced By methyl methanesulfonate. Geremy W. Knapp, Alan H. Tennant, and Russell D. Owen. Environmental Carcinogenesis Division, National Health and Environmental Effects Research Laboratory, U. S. Environmental Prote...

  1. The Digital Ageing Atlas: integrating the diversity of age-related changes into a unified resource

    PubMed Central

    Craig, Thomas; Smelick, Chris; Tacutu, Robi; Wuttke, Daniel; Wood, Shona H.; Stanley, Henry; Janssens, Georges; Savitskaya, Ekaterina; Moskalev, Alexey; Arking, Robert; de Magalhães, João Pedro

    2015-01-01

    Multiple studies characterizing the human ageing phenotype have been conducted for decades. However, there is no centralized resource in which data on multiple age-related changes are collated. Currently, researchers must consult several sources, including primary publications, in order to obtain age-related data at various levels. To address this and facilitate integrative, system-level studies of ageing we developed the Digital Ageing Atlas (DAA). The DAA is a one-stop collection of human age-related data covering different biological levels (molecular, cellular, physiological, psychological and pathological) that is freely available online (http://ageing-map.org/). Each of the >3000 age-related changes is associated with a specific tissue and has its own page displaying a variety of information, including at least one reference. Age-related changes can also be linked to each other in hierarchical trees to represent different types of relationships. In addition, we developed an intuitive and user-friendly interface that allows searching, browsing and retrieving information in an integrated and interactive fashion. Overall, the DAA offers a new approach to systemizing ageing resources, providing a manually-curated and readily accessible source of age-related changes. PMID:25232097

  2. Age-related changes in the functional neuroanatomy of overt speech production

    PubMed Central

    Sörös, Peter; Bose, Arpita; Sokoloff, Lisa Guttman; Graham, Simon J.; Stuss, Donald T.

    2016-01-01

    Alterations of existing neural networks during healthy aging, resulting in behavioral deficits and changes in brain activity, have been described for cognitive, motor, and sensory functions. To investigate age-related changes in the neural circuitry underlying overt non-lexical speech production, functional MRI was performed in 14 healthy younger (21–32 years) and 14 healthy older individuals (62–84 years). The experimental task involved the acoustically cued overt production of the vowel /a/ and the polysyllabic utterance /pataka/. In younger and older individuals, overt speech production was associated with the activation of a widespread articulo-phonological network, including the primary motor cortex, the supplementary motor area, the cingulate motor areas, and the posterior superior temporal cortex, similar in the /a/ and /pataka/ condition. An analysis of variance with the factors age and condition revealed a significant main effect of age. Irrespective of the experimental condition, significantly greater activation was found in the bilateral posterior superior temporal cortex, the posterior temporal plane, and the transverse temporal gyri in younger compared to older individuals. Significantly greater activation was found in the bilateral middle temporal gyri, medial frontal gyri, middle frontal gyri, and inferior frontal gyri in older vs. younger individuals. The analysis of variance did not reveal a significant main effect of condition and no significant interaction of age and condition. These results suggest a complex reorganization of neural networks dedicated to the production of speech during healthy aging. PMID:19782435

  3. Dietary Vitamin D Deficiency in Rats from Middle- to Old-age Leads to Elevated Tyrosine Nitration and Proteomics Changes in Levels of Key Proteins in Brain: Implications for Low Vitamin D-dependent Age-Related Cognitive Decline

    PubMed Central

    Keeney, Jeriel T. R.; Förster, Sarah; Sultana, Rukhsana; Brewer, Lawrence D.; Latimer, Caitlin S.; Cai, Jian; Klein, Jon B.; Porter, Nada M.; Butterfield, D. Allan

    2013-01-01

    status. Together, these results suggest that dietary VitD deficiency contributes to significant nitrosative stress in brain and may promote cognitive decline in middle-aged and elderly adults. PMID:23872023

  4. Dietary vitamin D deficiency in rats from middle to old age leads to elevated tyrosine nitration and proteomics changes in levels of key proteins in brain: implications for low vitamin D-dependent age-related cognitive decline.

    PubMed

    Keeney, Jeriel T R; Förster, Sarah; Sultana, Rukhsana; Brewer, Lawrence D; Latimer, Caitlin S; Cai, Jian; Klein, Jon B; Porter, Nada M; Butterfield, D Allan

    2013-12-01

    results suggest that dietary VitD deficiency contributes to significant nitrosative stress in brain and may promote cognitive decline in middle-aged and elderly adults. PMID:23872023

  5. Stimulus and listener factors affecting age-related changes in competing speech perception.

    PubMed

    Helfer, Karen S; Freyman, Richard L

    2014-08-01

    The purpose of this study was to examine associations among hearing thresholds, cognitive ability, and speech understanding in adverse listening conditions within and between groups of younger, middle-aged, and older adults. Participants repeated back sentences played in the presence of several types of maskers (syntactically similar and syntactically different competing speech from one or two other talkers, and steady-state speech-shaped noise). They also completed tests of auditory short-term/working memory, processing speed, and inhibitory ability. Results showed that group differences in accuracy of word identification and in error patterns differed depending upon the number of masking voices; specifically, older and middle-aged individuals had particular difficulty, relative to younger subjects, in the presence of a single competing message. However, the effect of syntactic similarity was consistent across subject groups. Hearing loss, short-term memory, processing speed, and inhibitory ability were each related to some aspects of performance by the middle-aged and older participants. Notably, substantial age-related changes in speech recognition were apparent within the group of middle-aged listeners. PMID:25096109

  6. Age-related changes in learning across early childhood: a new imitation task.

    PubMed

    Dickerson, Kelly; Gerhardstein, Peter; Zack, Elizabeth; Barr, Rachel

    2013-11-01

    Imitation plays a critical role in social and cognitive development, but the social learning mechanisms contributing to the development of imitation are not well understood. We developed a new imitation task designed to examine social learning mechanisms across the early childhood period. The new task involves assembly of abstract-shaped puzzle pieces in an arbitrary sequence on a magnet board. Additionally, we introduce a new scoring system that extends traditional goal-directed imitation scoring to include measures of both children's success at copying gestures (sliding the puzzle pieces) and goals (connecting the puzzle pieces). In Experiment 1, we demonstrated an age-invariant baseline from 1.5 to 3.5 years of age, accompanied by age-related changes in success at copying goals and gestures from a live demonstrator. In Experiment 2, we applied our new task to learning following a video demonstration. Imitation performance in the video demonstration group lagged behind that of the live demonstration group, showing a protracted video deficit effect. Across both experiments, children were more likely to copy gestures at earlier ages, suggesting mimicry, and only later copy both goals and gestures, suggesting imitation. Taken together, the findings suggest that different social learning strategies may predominate in imitation learning dependent upon the degree of object affordance, task novelty, and task complexity. PMID:22786801

  7. Processing Speed, Inhibitory Control, and Working Memory: Three Important Factors to Account for Age-Related Cognitive Decline

    ERIC Educational Resources Information Center

    Pereiro Rozas, Arturo X.; Juncos-Rabadan, Onesimo; Gonzalez, Maria Soledad Rodriguez

    2008-01-01

    Processing speed, inhibitory control and working memory have been identified as the main possible culprits of age-related cognitive decline. This article describes a study of their interrelationships and dependence on age, including exploration of whether any of them mediates between age and the others. We carried out a LISREL analysis of the…

  8. Recovery of functional and structural age-related changes in the rat primary auditory cortex with operant training

    PubMed Central

    de Villers-Sidani, Etienne; Alzghoul, Loai; Zhou, Xiaoming; Simpson, Kimberly L.; Lin, Rick C. S.; Merzenich, Michael M.

    2010-01-01

    Cognitive decline is a virtually universal aspect of the aging process. However, its neurophysiological basis remains poorly understood. We describe here more than 20 age-related cortical processing deficits in the primary auditory cortex of aging versus young rats that appear to be strongly contributed to by altered cortical inhibition. Consistent with these changes, we recorded in old rats a decrease in parvalbumin-labeled inhibitory cortical neurons. Furthermore, old rats were slower to master a simple behavior, with learning progressions marked by more false-positive responses. We then examined the effect of intensive auditory training on the primary auditory cortex in these aged rats by using an oddball discrimination task. Following training, we found a nearly complete reversal of the majority of previously observed functional and structural cortical impairments. These findings suggest that age-related cognitive decline is a tightly regulated plastic process, and demonstrate that most of these age-related changes are, by their fundamental nature, reversible. PMID:20643928

  9. A genome-wide scan for common variants affecting the rate of age-related cognitive decline

    PubMed Central

    De Jager, Philip L.; Shulman, Joshua M.; Chibnik, Lori B.; Keenan, Brendan T.; Raj, Towfique; Wilson, Robert S.; Yu, Lei; Leurgans, Sue E.; Tran, Dong; Aubin, Cristin; Anderson, Christopher D.; Biffi, Alessandro; Corneveaux, Jason J.; Huentelman, Matthew J.; Rosand, Jonathan; Daly, Mark J.; Myers, Amanda J.; Reiman, Eric M.; Bennett, David A.; Evans, Denis A.

    2011-01-01

    Age-related cognitive decline is likely promoted by accumulated brain injury due to chronic conditions of aging, including neurodegenerative and vascular disease. Since common neuronal mechanisms may mediate the adaptation to diverse cerebral insults, we hypothesized that susceptibility for age-related cognitive decline may be due in part to a shared genetic network. We have therefore performed a genome-wide association study using a quantitative measure of global cognitive decline slope, based on repeated measures of 17 cognitive tests in 749 subjects from the Religious Orders Study. Top results were evaluated in three independent replication cohorts, consisting of 2,279 additional subjects with repeated cognitive testing. As expected, we find that the Alzheimer’s disease (AD) susceptibility locus, APOE, is strongly associated with rate of cognitive decline (PDISC=5.6×10−9; PJOINT=3.7×10−27). We additionally discover a variant, rs10808746, which shows consistent effects in the replication cohorts and modestly improved evidence of association in the joint analysis (PDISC=6.7×10−5; PREP=9.4×10−3; PJOINT=2.3×10−5). This variant influences the expression of two adjacent genes, PDE7A and MTFR1, which are potential regulators of inflammation and oxidative injury, respectively. Using aggregate measures of genetic risk, we find that known susceptibility loci for cardiovascular disease, type II diabetes, and inflammatory diseases are not significantly associated with cognitive decline in our cohort. Our results suggest that intermediate phenotypes, when coupled with larger sample sizes, may be a useful tool to dissect susceptibility loci for age-related cognitive decline and uncover shared molecular pathways with a role in neuronal injury. PMID:22054870

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  11. Muscle-specificity of age-related changes in markers of autophagy and sphingolipid metabolism.

    PubMed

    Russ, David W; Boyd, Iva M; McCoy, Katherine M; McCorkle, Katherine W

    2015-12-01

    Our previous findings indicate that the gastrocnemius muscle of aging rats exhibits impairments of muscle quality (force/unit muscle tissue) and autophagy and increased sarcoplasmic reticulum stress. The purpose of this study was to examine age-related changes in soleus muscle contractility and in markers of autophagy in the soleus and gastrocnemius muscles. We assessed in situ muscle force and size in the soleus muscle of adult (7-8 months) and aged (24-26 months) male, F344/BN rats. We used immunoblotting to compare abundance of markers of autophagy, sarcoplasmic reticulum (SR) stress and sphingolipid metabolism in the soleus and medial gastrocnemius (MG) muscles of these animals. Relative to adults, aged rats maintained soleus muscle quality and increased muscle size, resulting in increased tetanic force production. Immunoblotting revealed a general pattern of an age-related reduction of basal autophagy, despite increases in indicators of SR stress and upstream autophagic pathway activation in the MG. The MG also exhibited changes in markers of sphingolipid metabolism suggestive of increased muscle ceramide. Minimal age-related changes were observed in the soleus. The soleus maintains muscle mass and quality with age, and exhibits fewer age-related changes in markers of stress and autophagy than the MG. Based on these data, we suggest that maintenance of autophagy may preserve muscle quality by preventing excessive SR stress. PMID:26296420

  12. Age-Related Changes in Duration Reproduction: Involvement of Working Memory Processes

    ERIC Educational Resources Information Center

    Baudouin, Alexia; Vanneste, Sandrine; Pouthas, Viviane; Isingrini, Michel

    2006-01-01

    The aim of the present research was to study age-related changes in duration reproduction by differentiating the working memory processes underlying this time estimation task. We compared performances of young and elderly adults in a duration reproduction task performed in simple and concurrent task conditions. Participants were also administered…

  13. Age-related changes in visual exploratory behavior in a natural scene setting

    PubMed Central

    Hamel, Johanna; De Beukelaer, Sophie; Kraft, Antje; Ohl, Sven; Audebert, Heinrich J.; Brandt, Stephan A.

    2013-01-01

    Diverse cognitive functions decline with increasing age, including the ability to process central and peripheral visual information in a laboratory testing situation (useful visual field of view). To investigate whether and how this influences activities of daily life, we studied age-related changes in visual exploratory behavior in a natural scene setting: a driving simulator paradigm of variable complexity was tested in subjects of varying ages with simultaneous eye- and head-movement recordings via a head-mounted camera. Detection and reaction times were also measured by visual fixation and manual reaction. We considered video computer game experience as a possible influence on performance. Data of 73 participants of varying ages were analyzed, driving two different courses. We analyzed the influence of route difficulty level, age, and eccentricity of test stimuli on oculomotor and driving behavior parameters. No significant age effects were found regarding saccadic parameters. In the older subjects head-movements increasingly contributed to gaze amplitude. More demanding courses and more peripheral stimuli locations induced longer reaction times in all age groups. Deterioration of the functionally useful visual field of view with increasing age was not suggested in our study group. However, video game-experienced subjects revealed larger saccade amplitudes and a broader distribution of fixations on the screen. They reacted faster to peripheral objects suggesting the notion of a general detection task rather than perceiving driving as a central task. As the video game-experienced population consisted of younger subjects, our study indicates that effects due to video game experience can easily be misinterpreted as age effects if not accounted for. We therefore view it as essential to consider video game experience in all testing methods using virtual media. PMID:23801970

  14. Inflammatory insult during pregnancy accelerates age-related behavioral and neurobiochemical changes in CD-1 mice.

    PubMed

    Li, Xue-Yan; Wang, Fang; Chen, Gui-Hai; Li, Xue-Wei; Yang, Qi-Gang; Cao, Lei; Yan, Wen-Wen

    2016-06-01

    Data shows that inflammation during pregnancy significantly exerts a long-term influence on offspring, such as increasing the risk of adult cognition decline in animals. However, it is unclear whether gestational inflammation affects the neurobehavioral and neurobiochemical outcomes in the mother-self during aging. In this study, pregnant CD-1 mice intraperitoneally received lipopolysaccharide (LPS) in two doses (25 and 50 g/kg, respectively) or normal saline daily during gestational days 15-17. At the age of 15 months, a battery of behavioral tasks was employed to evaluate their species-typical behaviors, sensorimotor ability, anxiety levels, and spatial learning and memory abilities. An immunohistochemical method was utilized preliminarily to detect neurobiochemical indicators consisting of amyloid-β, phosphorylated tau, presynaptic proteins synaptotagmin-1 and syntaxin-1, glial fibrillary acidic protein (GFAP), and histone-4 acetylation on the K8 site (H4K8ac). The behavioral results showed that LPS exposure during pregnancy exacerbated a decline in 15-month-old CD-1 mice's abilities to nest, their sensorimotor and spatial learning and memory capabilities, and increased their anxiety levels. The neurobiochemical results indicated that gestational LPS exposure also intensified age-related hippocampal changes, including increased amyloid-β42, phosphorylated tau, synaptotagmin-1 and GFAP, and decreased syntaxin-1 and H4K8ac. Our results suggested that the inflammatory insult during pregnancy could be an important risk factor for the development of Alzheimer's disease, and the H4K8 acetylation might play an important role in the underlying mechanism. This study offers a perspective for improving strategies that support healthy development and successful aging. PMID:27194408

  15. Age-related change of technetium-99m-HMDP distribution in the skeleton

    SciTech Connect

    Kigami, Yusuke; Yamamoto, Itsuo; Ohnishi, Hideo

    1996-05-01

    To understand age-related changes of whole-body and regional skeletal metabolism, it is important to investigate the mechanisms of age-related bone loss and to develop suitable treatments for it. Bone biopsies show metabolism of the particular site examined while biochemical markers for bone metabolism reflect total skeletal metabolis. Bone scintigraphy is a convenient and simple way to analyze whole-body and regional skeletal metabolism. We attempted to study and understand age-related changes in bone metabolism by quantifying the bone scan and correlating it with biochemical bone metabolic markers. The whole-body skeletal uptake (WBSU) and whole-body skeletal tracer distribution pattern were studied in men and women by bone scintigraphy using {sup 99m}Tc-hydroxy-methane-diphosphonate (HMDP). Bone scans were performed using a standard protocol and quantified by setting regions of interest (ROIs) on selected regions. WBSU and the skeletal distribution pattern were compared with simultaneously obtained serum biochemical markers. WBSU showed an increase with age in both sexes, but in women, uptake in the head and legs increased more relatively than in the thoracic region, while in men no such tendency was observed. Increase of WBSU and relative increase of uptakes in the head demonstrated a weak correlation with the serum levels of alkaline phosphatase and type 1 collagen metabolites. These results show an age-related increase of skeletal turnover and sex-dependent regional skeletal metabolism. The age-related changes seen in bone scintigrams might be a sign of progressive bone loss, reflecting changes in local bone matabolism. 23 refs., 3 figs., 1 tab.

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

    PubMed

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

    2014-06-01

    Aging is a progressive process that results in the accumulation of intra- and extracellular alterations that in turn contribute to a reduction in health. Age-related changes in DNA methylation have been reported before and may be responsible for aging-induced changes in gene expression, although a causal relationship has yet to be shown. Using genome-wide assays, we analyzed age-induced changes in DNA methylation and their effect on gene expression with and without transient induction with the synthetic transcription modulating agent WY14,643. To demonstrate feasibility of the approach, we isolated peripheral blood mononucleated cells (PBMCs) from five young and five old healthy male volunteers and cultured them with or without WY14,643. Infinium 450K BeadChip and Affymetrix Human Gene 1.1 ST expression array analysis revealed significant differential methylation of at least 5 % (ΔYO > 5 %) at 10,625 CpG sites between young and old subjects, but only a subset of the associated genes were also differentially expressed. Age-related differential methylation of previously reported epigenetic biomarkers of aging including ELOVL2, FHL2, PENK, and KLF14 was confirmed in our study, but these genes did not display an age-related change in gene expression in PBMCs. Bioinformatic analysis revealed that differentially methylated genes that lack an age-related expression change predominantly represent genes involved in carcinogenesis and developmental processes, and expression of most of these genes were silenced in PBMCs. No changes in DNA methylation were found in genes displaying transiently induced changes in gene expression. In conclusion, aging-induced differential methylation often targets developmental genes and occurs mostly without change in gene expression. PMID:24789080

  17. Age-Related Changes in Predictive Capacity Versus Internal Model Adaptability: Electrophysiological Evidence that Individual Differences Outweigh Effects of Age.

    PubMed

    Bornkessel-Schlesewsky, Ina; Philipp, Markus; Alday, Phillip M; Kretzschmar, Franziska; Grewe, Tanja; Gumpert, Maike; Schumacher, Petra B; Schlesewsky, Matthias

    2015-01-01

    Hierarchical predictive coding has been identified as a possible unifying principle of brain function, and recent work in cognitive neuroscience has examined how it may be affected by age-related changes. Using language comprehension as a test case, the present study aimed to dissociate age-related changes in prediction generation versus internal model adaptation following a prediction error. Event-related brain potentials (ERPs) were measured in a group of older adults (60-81 years; n = 40) as they read sentences of the form "The opposite of black is white/yellow/nice." Replicating previous work in young adults, results showed a target-related P300 for the expected antonym ("white"; an effect assumed to reflect a prediction match), and a graded N400 effect for the two incongruous conditions (i.e. a larger N400 amplitude for the incongruous continuation not related to the expected antonym, "nice," versus the incongruous associated condition, "yellow"). These effects were followed by a late positivity, again with a larger amplitude in the incongruous non-associated versus incongruous associated condition. Analyses using linear mixed-effects models showed that the target-related P300 effect and the N400 effect for the incongruous non-associated condition were both modulated by age, thus suggesting that age-related changes affect both prediction generation and model adaptation. However, effects of age were outweighed by the interindividual variability of ERP responses, as reflected in the high proportion of variance captured by the inclusion of by-condition random slopes for participants and items. We thus argue that - at both a neurophysiological and a functional level - the notion of general differences between language processing in young and older adults may only be of limited use, and that future research should seek to better understand the causes of interindividual variability in the ERP responses of older adults and its relation to cognitive performance. PMID

  18. Beneficial effects of multisensory and cognitive stimulation on age-related cognitive decline in long-term-care institutions

    PubMed Central

    De Oliveira, Thaís Cristina Galdino; Soares, Fernanda Cabral; De Macedo, Liliane Dias E Dias; Diniz, Domingos Luiz Wanderley Picanço; Bento-Torres, Natáli Valim Oliver; Picanço-Diniz, Cristovam Wanderley

    2014-01-01

    The aim of the present report was to evaluate the effectiveness and impact of multisensory and cognitive stimulation on improving cognition in elderly persons living in long-term-care institutions (institutionalized [I]) or in communities with their families (noninstitutionalized [NI]). We compared neuropsychological performance using language and Mini-Mental State Examination (MMSE) test scores before and after 24 and 48 stimulation sessions. The two groups were matched by age and years of schooling. Small groups of ten or fewer volunteers underwent the stimulation program, twice a week, over 6 months (48 sessions in total). Sessions were based on language and memory exercises, as well as visual, olfactory, auditory, and ludic stimulation, including music, singing, and dance. Both groups were assessed at the beginning (before stimulation), in the middle (after 24 sessions), and at the end (after 48 sessions) of the stimulation program. Although the NI group showed higher performance in all tasks in all time windows compared with I subjects, both groups improved their performance after stimulation. In addition, the improvement was significantly higher in the I group than the NI group. Language tests seem to be more efficient than the MMSE to detect early changes in cognitive status. The results suggest the impoverished environment of long-term-care institutions may contribute to lower cognitive scores before stimulation and the higher improvement rate of this group after stimulation. In conclusion, language tests should be routinely adopted in the neuropsychological assessment of elderly subjects, and long-term-care institutions need to include regular sensorimotor, social, and cognitive stimulation as a public health policy for elderly persons. PMID:24600211

  19. Beneficial effects of multisensory and cognitive stimulation on age-related cognitive decline in long-term-care institutions.

    PubMed

    De Oliveira, Thaís Cristina Galdino; Soares, Fernanda Cabral; De Macedo, Liliane Dias E Dias; Diniz, Domingos Luiz Wanderley Picanço; Bento-Torres, Natáli Valim Oliver; Picanço-Diniz, Cristovam Wanderley

    2014-01-01

    The aim of the present report was to evaluate the effectiveness and impact of multisensory and cognitive stimulation on improving cognition in elderly persons living in long-term-care institutions (institutionalized [I]) or in communities with their families (noninstitutionalized [NI]). We compared neuropsychological performance using language and Mini-Mental State Examination (MMSE) test scores before and after 24 and 48 stimulation sessions. The two groups were matched by age and years of schooling. Small groups of ten or fewer volunteers underwent the stimulation program, twice a week, over 6 months (48 sessions in total). Sessions were based on language and memory exercises, as well as visual, olfactory, auditory, and ludic stimulation, including music, singing, and dance. Both groups were assessed at the beginning (before stimulation), in the middle (after 24 sessions), and at the end (after 48 sessions) of the stimulation program. Although the NI group showed higher performance in all tasks in all time windows compared with I subjects, both groups improved their performance after stimulation. In addition, the improvement was significantly higher in the I group than the NI group. Language tests seem to be more efficient than the MMSE to detect early changes in cognitive status. The results suggest the impoverished environment of long-term-care institutions may contribute to lower cognitive scores before stimulation and the higher improvement rate of this group after stimulation. In conclusion, language tests should be routinely adopted in the neuropsychological assessment of elderly subjects, and long-term-care institutions need to include regular sensorimotor, social, and cognitive stimulation as a public health policy for elderly persons. PMID:24600211

  20. Long-term moderate alcohol consumption does not exacerbate age-related cognitive decline in healthy, community-dwelling older adults

    PubMed Central

    Moussa, Malaak N.; Simpson, Sean L.; Mayhugh, Rhiannon E.; Grata, Michelle E.; Burdette, Jonathan H.; Porrino, Linda J.; Laurienti, Paul J.

    2015-01-01

    Recent census data has found that roughly 40% of adults 65 years and older not only consume alcohol but also drink more of it than previous generations. Older drinkers are more vulnerable than younger counterparts to the psychoactive effects of alcohol due to natural biological changes that occur with aging. This study was specifically designed to measure the effect of long-term moderate alcohol consumption on cognitive health in older adult drinkers. An extensive battery of validated tests commonly used in aging and substance use literature was used to measure performance in specific cognitive domains, including working memory and attention. An age (young, old) * alcohol consumption (light, moderate) factorial study design was used to evaluate the main effects of age and alcohol consumption on cognitive performance. The focus of the study was then limited to light and moderate older drinkers, and whether or not long-term moderate alcohol consumption exacerbated age-related cognitive decline. No evidence was found to support the idea that long-term moderate alcohol consumption in older adults exacerbates age-related cognitive decline. Findings were specific to healthy community dwelling social drinkers in older age and they should not be generalized to individuals with other consumption patterns, like heavy drinkers, binge drinkers or ex-drinkers. PMID:25601835

  1. Age-related changes in rostral basal forebrain cholinergic and GABAergic projection neurons: Relationship with spatial impairment

    PubMed Central

    Bañuelos, C.; LaSarge, C. L.; McQuail, J. A.; Hartman, J. J.; Gilbert, R. J.; Ormerod, B. K.; Bizon, J. L.

    2013-01-01

    Both cholinergic and GABAergic projections from the rostral basal forebrain have been implicated in hippocampal function and mnemonic abilities. While dysfunction of cholinergic neurons has been heavily implicated in age-related memory decline, significantly less is known regarding how age-related changes in co-distributed GABAergic projection neurons contribute to a decline in hippocampal-dependent spatial learning. In the current study, confocal stereology was used to quantify cholinergic (choline acetyltransferase (ChAT) immunopositive) neurons, GABAergic projection (glutamic decarboxylase 67 (GAD67) immunopositive) neurons, and total (NeuN immunopositive) neurons in the rostral basal forebrain of young and aged rats that were first characterized on a spatial learning task. ChAT immunopositive neurons were significantly but modestly reduced in aged rats. Although ChAT immunopositive neuron number was strongly correlated with spatial learning abilities among young rats, the reduction of ChAT immunopositive neurons was not associated with impaired spatial learning in aged rats. In contrast, the number of GAD67 immunopositive neurons was robustly and selectively elevated in aged rats that exhibited impaired spatial learning. Interestingly, the total number of rostral basal forebrain neurons was comparable in young and aged rats, regardless of their cognitive status. These data demonstrate differential effects of age on phenotypically distinct rostral basal forebrain projection neurons, and implicate dysregulated cholinergic and GABAergic septohippocampal circuitry in age-related mnemonic decline. PMID:22817834

  2. Oxidative changes and signalling pathways are pivotal in initiating age-related changes in articular cartilage

    PubMed Central

    Hui, Wang; Young, David A; Rowan, Andrew D; Xu, Xin; Cawston, Tim E; Proctor, Carole J

    2016-01-01

    Objective To use a computational approach to investigate the cellular and extracellular matrix changes that occur with age in the knee joints of mice. Methods Knee joints from an inbred C57/BL1/6 (ICRFa) mouse colony were harvested at 3–30 months of age. Sections were stained with H&E, Safranin-O, Picro-sirius red and antibodies to matrix metalloproteinase-13 (MMP-13), nitrotyrosine, LC-3B, Bcl-2, and cleaved type II collagen used for immunohistochemistry. Based on this and other data from the literature, a computer simulation model was built using the Systems Biology Markup Language using an iterative approach of data analysis and modelling. Individual parameters were subsequently altered to assess their effect on the model. Results A progressive loss of cartilage matrix occurred with age. Nitrotyrosine, MMP-13 and activin receptor-like kinase-1 (ALK1) staining in cartilage increased with age with a concomitant decrease in LC-3B and Bcl-2. Stochastic simulations from the computational model showed a good agreement with these data, once transforming growth factor-β signalling via ALK1/ALK5 receptors was included. Oxidative stress and the interleukin 1 pathway were identified as key factors in driving the cartilage breakdown associated with ageing. Conclusions A progressive loss of cartilage matrix and cellularity occurs with age. This is accompanied with increased levels of oxidative stress, apoptosis and MMP-13 and a decrease in chondrocyte autophagy. These changes explain the marked predisposition of joints to develop osteoarthritis with age. Computational modelling provides useful insights into the underlying mechanisms involved in age-related changes in musculoskeletal tissues. PMID:25475114

  3. Age-related changes in reservoir and excess components of central aortic pressure in asymptomatic adults.

    PubMed

    Bia, Daniel; Cymberknop, Leandro; Zócalo, Yanina; Farro, Ignacio; Torrado, Juan; Farro, Federico; Pessana, Franco; Armentano, Ricardo L

    2011-01-01

    Study of humans aging has presented difficulties in separating the aging process from concomitant disease and/or in defining normality and abnormality during its development. In accordance with this, aging associates structural and functional changes evidenced in variations in vascular parameters witch suffer alterations during atherosclerosis and have been proposed as early markers of the disease. The absence of adequate tools to differentiate the expected (normal) vascular changes due to aging from those related with a vascular disease is not a minor issue. For an individual, an early diagnosis of a vascular disease should be as important as the diagnosis of a healthy vascular aging. Recent studies have proposed that the capacitive or reservoir function of the aorta and large elastic arteries plays a major role in determining the pulse wave morphology. The arterial pressure waveform can be explained in terms of a reservoir pressure, related to the arterial system compliance, and an "excess" or wave-related pressure, associated with the traveling waves. The aim of this study was to evaluate, by means of a mathematical approach, age-related changes in measured, reservoir and excess central aortic pressure in order to determine if age-related changes are concentrated in particular decades of life. Central aortic pressure waveform was non-invasively obtained in healthy subjects (age range: 20-69 years old). Age-related profiles in measured, reservoir and excess pressure were calculated. PMID:22255816

  4. Age-related changes of mitochondrial transcription factor a expression in rotator cuff degeneration

    PubMed Central

    Ichiseki, Toru; Ueda, Shusuke; Ueda, Yoshimichi; Kaneuji, Ayumi; Kawahara, Norio; Matsumoto, Tadami

    2015-01-01

    One cause of rotator cuff tears is thought to be age-related degenerative changes occurring in the rotator cuff. Using Rat rotator cuff we determined age-related changes in mitochondrial transcription factor A (TFAM) expression in rotator cuff degeneration to clarify the presence/absence of mitochondrial stress. The materials used were rotator cuffs (supraspinatus) of 5-, 24-, 48-, and 100-week-old Wistar Rats (five animals each). Histopathological study revealed a 4-layer structure consisting of a bone layer, calcified cartilage layer, non-calcified cartilage layer, and tendinous component), with age-related narrowing of the non-calcified cartilage layer confirmed to be present. In an immunohistochemical TFAM study positive findings of the non-calcified cartilage layer were less prominent in the 100-week-old group. In an Enzyme-Linked Immunosorbent Assay (ELISA) study, these were more prominent in the 5-week-old to 24-week-old groups, and slightly less so in the 48-week-old group as compared to the 24-week-old one. In the 100-week-old group as compared to the 24-week-old one they were significantly less prominent (p<0.05). The non-calcified cartilage layer is a major site for the dispersion of mechanical energy, and the change in TFAM expression noted at the same site in the present study and the results of ELISA suggest that age-related changes in mitochondrial stress may be one cause of rotator cuff degeneration. PMID:26692954

  5. Are delta-aminolevulinate dehydratase inhibition and metal concentrations additional factors for the age-related cognitive decline?

    PubMed

    Baierle, Marília; Charão, Mariele F; Göethel, Gabriela; Barth, Anelise; Fracasso, Rafael; Bubols, Guilherme; Sauer, Elisa; Campanharo, Sarah C; Rocha, Rafael C C; Saint'Pierre, Tatiana D; Bordignon, Suelen; Zibetti, Murilo; Trentini, Clarissa M; Avila, Daiana S; Gioda, Adriana; Garcia, Solange C

    2014-01-01

    Aging is often accompanied by cognitive impairments and influenced by oxidative status and chemical imbalances. Thus, this study was conducted to examine whether age-related cognitive deficit is associated with oxidative damage, especially with inhibition of the enzyme delta-aminolevulinate dehydratase (ALA-D), as well as to verify the influence of some metals in the enzyme activity and cognitive performance. Blood ALA-D activity, essential (Fe, Zn, Cu, Se) and non-essential metals (Pb, Cd, Hg, As, Cr, Ni, V) were measured in 50 elderly and 20 healthy young subjects. Cognitive function was assessed by tests from Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery and other. The elderly group presented decreased ALA-D activity compared to the young group. The index of ALA-D reactivation was similar to both study groups, but negatively associated with metals. The mean levels of essential metals were within the reference values, while the most toxic metals were above them in both groups. Cognitive function impairments were observed in elderly group and were associated with decreased ALA-D activity, with lower levels of Se and higher levels of toxic metals (Hg and V). Results suggest that the reduced ALA-D activity in elderly can be an additional factor involved in cognitive decline, since its inhibition throughout life could lead to accumulation of the neurotoxic compound ALA. Toxic metals were found to contribute to cognitive decline and also to influence ALA-D reactivation. PMID:25329536

  6. Video Games as a Means to Reduce Age-Related Cognitive Decline: Attitudes, Compliance, and Effectiveness

    PubMed Central

    Boot, Walter R.; Champion, Michael; Blakely, Daniel P.; Wright, Timothy; Souders, Dustin J.; Charness, Neil

    2013-01-01

    Recent research has demonstrated broad benefits of video game play to perceptual and cognitive abilities. These broad improvements suggest that video game-based cognitive interventions may be ideal to combat the many perceptual and cognitive declines associated with advancing age. Furthermore, game interventions have the potential to induce higher rates of intervention compliance compared to other cognitive interventions as they are assumed to be inherently enjoyable and motivating. We explored these issues in an intervention that tested the ability of an action game and a “brain fitness” game to improve a variety of abilities. Cognitive abilities did not significantly improve, suggesting caution when recommending video game interventions as a means to reduce the effects of cognitive aging. However, the game expected to produce the largest benefit based on previous literature (an action game) induced the lowest intervention compliance. We explain this low compliance by participants’ ratings of the action game as less enjoyable and by their prediction that training would have few meaningful benefits. Despite null cognitive results, data provide valuable insights into the types of video games older adults are willing to play and why. PMID:23378841

  7. Video games as a means to reduce age-related cognitive decline: attitudes, compliance, and effectiveness.

    PubMed

    Boot, Walter R; Champion, Michael; Blakely, Daniel P; Wright, Timothy; Souders, Dustin J; Charness, Neil

    2013-01-01

    Recent research has demonstrated broad benefits of video game play to perceptual and cognitive abilities. These broad improvements suggest that video game-based cognitive interventions may be ideal to combat the many perceptual and cognitive declines associated with advancing age. Furthermore, game interventions have the potential to induce higher rates of intervention compliance compared to other cognitive interventions as they are assumed to be inherently enjoyable and motivating. We explored these issues in an intervention that tested the ability of an action game and a "brain fitness" game to improve a variety of abilities. Cognitive abilities did not significantly improve, suggesting caution when recommending video game interventions as a means to reduce the effects of cognitive aging. However, the game expected to produce the largest benefit based on previous literature (an action game) induced the lowest intervention compliance. We explain this low compliance by participants' ratings of the action game as less enjoyable and by their prediction that training would have few meaningful benefits. Despite null cognitive results, data provide valuable insights into the types of video games older adults are willing to play and why. PMID:23378841

  8. One of the most well-established age-related changes in neural activity disappears after controlling for visual acuity.

    PubMed

    Porto, Fábio H G; Tusch, Erich S; Fox, Anne M; Alperin, Brittany R; Holcomb, Phillip J; Daffner, Kirk R

    2016-04-15

    Numerous studies using a variety of imaging techniques have reported age-related differences in neural activity while subjects carry out cognitive tasks. Surprisingly little attention has been paid to the potential impact of age-associated changes in sensory acuity on these findings. Studies in the visual modality frequently report that their subjects had "normal or corrected- to-normal vision." However, in most cases, there is no indication that visual acuity was actually measured, and it is likely that the investigators relied largely on self-reported visual status of subjects, which is often inaccurate. We investigated whether differences in visual acuity influence one of the most commonly observed findings in the event-related potentials literature on cognitive aging, a reduction in posterior P3b amplitude, which is an index of cognitive decision-making/updating. Well-matched young (n=26) and old adults (n=29) participated in a visual oddball task. Measured visual acuity with corrective lenses was worse in old than young adults. Results demonstrated that the robust age-related decline in P3b amplitude to visual targets disappeared after controlling for visual acuity, but was unaffected by accounting for auditory acuity. Path analysis confirmed that the relationship between age and diminished P3b to visual targets was mediated by visual acuity, suggesting that conveyance of suboptimal sensory data due to peripheral, rather than central, deficits may undermine subsequent neural processing. We conclude that until the relationship between age-associated differences in visual acuity and neural activity during experimental tasks is clearly established, investigators should exercise caution attributing results to differences in cognitive processing. PMID:26825439

  9. Age-related changes in glial cells of dopamine midbrain subregions in rhesus monkeys

    PubMed Central

    Kanaan, Nicholas M.; Kordower, Jeffrey H.; Collier, Timothy J.

    2010-01-01

    Aging remains the strongest risk factor for developing Parkinson’s disease (PD), and there is selective vulnerability in midbrain DA neuron degeneration in PD. By tracking normal aging-related changes with an emphasis on regional specificity, factors involved in selective vulnerability and resistance to degeneration can be studied. Towards this end, we sought to determine whether age-related changes in microglia and astrocytes in rhesus monkeys are region-specific, suggestive of involvement in regional differences in vulnerability to degeneration that may be relevant to PD pathogenesis. Gliosis in midbrain DA subregions was measured by estimating glia number using unbiased stereology, assessing fluorescence intensity for proteins upregulated during activation, and rating morphology. With normal aging, microglia exhibited increased staining intensity and a shift to more activated morphologies preferentially in the vulnerable substantia nigra-ventral tier (vtSN). Astrocytes did not exhibit age-related changes consistent with an involvement in regional vulnerability in any measure. Our results suggest advancing age is associated with chronic mild inflammation in the vtSN, which may render these DA neurons more vulnerable to degeneration. PMID:18715678

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

    PubMed

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

    2016-07-01

    Previous work investigating respiratory system mechanics in mice has reported an aging-related increase in compliance and mean linear intercept (Lm). However, these changes were assessed using only a young (2-mo-old) and old (20- and 26-mo-old) group yet were interpreted to reflect a linear evolution across the life span. Therefore, to investigate respiratory system mechanics and lung morphometry across a more complete spectrum of ages, we utilized 2 (100% survival, n = 6)-, 6 (100% survival, n = 12)-, 18 (90% survival, n = 12)-, 24 (75% survival, n = 12)-, and 30 (25% survival, n = 12)-mo-old C57BL/6 mice. We found a nonlinear aging-related decrease in respiratory system resistance and increase in dynamic compliance and hysteresis between 2- and 24-mo-old mice. However, in 30-mo-old mice, respiratory system resistance increased, and dynamic compliance and hysteresis decreased relative to 24-mo-old mice. Respiratory system impedance spectra were measured between 1-20.5 Hz at positive end-expiratory pressures (PEEP) of 1, 3, 5, and 7 cmH2O. Respiratory system resistance and reactance at each level of PEEP were increased and decreased, respectively, only in 2-mo-old animals. No differences in the respiratory system impedance spectra were observed in 6-, 18-, 24-, and 30-mo-old mice. Additionally, lungs were fixed following tracheal instillation of 4% paraformaldehyde at 25 cmH2O and processed for Lm and airway collagen deposition. There was an aging-related increase in Lm consistent with emphysematous-like changes and no evidence of increased airway collagen deposition. Accordingly, we demonstrate nonlinear aging-related changes in lung mechanics and morphometry in C57BL/6 mice. PMID:27288490

  11. Age-related changes of adaptive and neuropsychological features in persons with Down Syndrome.

    PubMed

    Ghezzo, Alessandro; Salvioli, Stefano; Solimando, Maria Caterina; Palmieri, Alice; Chiostergi, Chiara; Scurti, Maria; Lomartire, Laura; Bedetti, Federica; Cocchi, Guido; Follo, Daniela; Pipitone, Emanuela; Rovatti, Paolo; Zamberletti, Jessica; Gomiero, Tiziano; Castellani, Gastone; Franceschi, Claudio

    2014-01-01

    Down Syndrome (DS) is characterised by premature aging and an accelerated decline of cognitive functions in the vast majority of cases. As the life expectancy of DS persons is rapidly increasing, this decline is becoming a dramatic health problem. The aim of this study was to thoroughly evaluate a group of 67 non-demented persons with DS of different ages (11 to 66 years), from a neuropsychological, neuropsychiatric and psychomotor point of view in order to evaluate in a cross-sectional study the age-related adaptive and neuropsychological features, and to possibly identify early signs predictive of cognitive decline. The main finding of this study is that both neuropsychological functions and adaptive skills are lower in adult DS persons over 40 years old, compared to younger ones. In particular, language and short memory skills, frontal lobe functions, visuo-spatial abilities and adaptive behaviour appear to be the more affected domains. A growing deficit in verbal comprehension, along with social isolation, loss of interest and greater fatigue in daily tasks, are the main features found in older, non demented DS persons evaluated in our study. It is proposed that these signs can be alarm bells for incipient dementia, and that neuro-cognitive rehabilitation and psycho-pharmacological interventions must start as soon as the fourth decade (or even earlier) in DS persons, i.e. at an age where interventions can have the greatest efficacy. PMID:25419980

  12. Age-Related Changes of Adaptive and Neuropsychological Features in Persons with Down Syndrome

    PubMed Central

    Ghezzo, Alessandro; Salvioli, Stefano; Solimando, Maria Caterina; Palmieri, Alice; Chiostergi, Chiara; Scurti, Maria; Lomartire, Laura; Bedetti, Federica; Cocchi, Guido; Follo, Daniela; Pipitone, Emanuela; Rovatti, Paolo; Zamberletti, Jessica; Gomiero, Tiziano; Castellani, Gastone; Franceschi, Claudio

    2014-01-01

    Down Syndrome (DS) is characterised by premature aging and an accelerated decline of cognitive functions in the vast majority of cases. As the life expectancy of DS persons is rapidly increasing, this decline is becoming a dramatic health problem. The aim of this study was to thoroughly evaluate a group of 67 non-demented persons with DS of different ages (11 to 66 years), from a neuropsychological, neuropsychiatric and psychomotor point of view in order to evaluate in a cross-sectional study the age-related adaptive and neuropsychological features, and to possibly identify early signs predictive of cognitive decline. The main finding of this study is that both neuropsychological functions and adaptive skills are lower in adult DS persons over 40 years old, compared to younger ones. In particular, language and short memory skills, frontal lobe functions, visuo-spatial abilities and adaptive behaviour appear to be the more affected domains. A growing deficit in verbal comprehension, along with social isolation, loss of interest and greater fatigue in daily tasks, are the main features found in older, non demented DS persons evaluated in our study. It is proposed that these signs can be alarm bells for incipient dementia, and that neuro-cognitive rehabilitation and psycho-pharmacological interventions must start as soon as the fourth decade (or even earlier) in DS persons, i.e. at an age where interventions can have the greatest efficacy. PMID:25419980

  13. Investigating age-related changes in anterior and posterior neural activity throughout the information processing stream.

    PubMed

    Alperin, Brittany R; Tusch, Erich S; Mott, Katherine K; Holcomb, Phillip J; Daffner, Kirk R

    2015-10-01

    Event-related potential (ERP) and other functional imaging studies often demonstrate age-related increases in anterior neural activity and decreases in posterior activity while subjects carry out task demands. It remains unclear whether this "anterior shift" is limited to late cognitive operations like those indexed by the P3 component, or is evident during other stages of information processing. The temporal resolution of ERPs provided an opportunity to address this issue. Temporospatial principal component analysis (PCA) was used to identify underlying components that may be obscured by overlapping ERP waveforms. ERPs were measured during a visual oddball task in 26 young, 26 middle-aged, and 29 old subjects who were well-matched for IQ, executive function, education, and task performance. PCA identified six anterior factors peaking between ∼140 ms and 810 ms, and four posterior factors peaking between ∼300 ms and 810 ms. There was an age-related increase in the amplitude of anterior factors between ∼200 and 500 ms, and an age-associated decrease in amplitude of posterior factors after ∼500 ms. The increase in anterior processing began as early as middle-age, was sustained throughout old age, and appeared to be linear in nature. These results suggest that age-associated increases in anterior activity occur after early sensory processing has taken place, and are most prominent during a period in which attention is being marshaled to evaluate a stimulus. In contrast, age-related decreases in posterior activity manifest during operations involved in stimulus categorization, post-decision monitoring, and preparation for an upcoming event. PMID:26295684

  14. Primary and secondary control over age-related changes in physical appearance.

    PubMed

    Thompson, S C; Thomas, C; Rickabaugh, C A; Tantamjarik, P; Otsuki, T; Pan, D; Garcia, B F; Sinar, E

    1998-08-01

    Beliefs about appearance-related changes due to aging were used to test the effects of perceived control and secondary control (acceptance) in a sample of 412 young, early-middle-age, and late-middle-age college-educated adults. Mean difference in aging-related appearance control and hypotheses regarding the adaptiveness of primary and secondary control were examined. Primary control over aging-related appearance was lower in older adults and secondary control was higher. In addition, the results indicated support for the Primacy/Back-Up Model that primary perceived control is important at all levels of actual control. Those with stronger beliefs in their primary control were less distressed. Secondary control served a back-up function in that it was related to less distress only for those who had medium or lower beliefs in primary control. The implications of these findings, that primary control may be advantageous even in low-control circumstances, are discussed. PMID:9728417

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

    PubMed Central

    2014-01-01

    Aging is characterized by increased oxidative stress, chronic inflammation, and organ dysfunction, which occur in a progressive and irreversible manner. Superoxide dismutase (SOD) serves as a major antioxidant and neutralizes superoxide radicals throughout the body. In vivo studies have demonstrated that copper/zinc superoxide dismutase-deficient (Sod1−/−) mice show various aging-like pathologies, accompanied by augmentation of oxidative damage in organs. We found that antioxidant treatment significantly attenuated the age-related tissue changes and oxidative damage-associated p53 upregulation in Sod1−/− mice. This review will focus on various age-related pathologies caused by the loss of Sod1 and will discuss the molecular mechanisms underlying the pathogenesis in Sod1−/− mice. PMID:25276767

  16. [Age-related changes of the hypothalamic-pituitary-adrenal axis: experimental studies in primates].

    PubMed

    Goncharova, N D

    2014-01-01

    The article presents a review of the results of the author's works that examine the character of age-related changes of the hypothalamic-pituitary-adrenal (HPA) axis in primates during aging in basal conditions, including disturbances of its circadian rhythms and in conditions of its inhibition and activation by specific stimuli. In addition, the original data are presented on the peculiarities of the HPA axis functioning under acute psycho-emotional stress taking into account the time of day and individual features of the adaptive behavior of animals, severe chronic stress caused by hemoblastosis process and repeated mild psycho-emotional stress impact. Age disturbances in the HPA axis functioning are of pathophysiological significance for the development of stress- and age-related pathologies and progression of the aging process. Individuals with depression adaptive behavior are most vulnerable to stress and pathological aging. PMID:25306658

  17. Thymus: reexamination of age-related changes in size and shape

    SciTech Connect

    Francis, I.R.; Glazer, G.M.; Bookstein, F.L.; Gross, B.H.

    1985-08-01

    The computed tomographic appearance of the normal and abnormal thymus and its age-related changes have been described. However, there is little quantitative data regarding thymic morphology at the extremes of age and the value of thymic measurements in particular thickness, to recognize thymic abnormality. Using computed tomography the thymic morphology in 309 normal patients was analyzed retrospectively, examining its appearance at the extremes of age and measuring its dimensions for comparison with similar data in 23 patients with clinically or surgically proven thymic abnormality. The study confirmed the previously reported age-related growth and subsequent involution of the normal thymus. Comparison of normal and abnormal glands suggests that thymic shape reliably separates normal from abnormal glands. While thymic thickness and the logarithm of the product of transverse dimension and thickness were sensitive indicators of thymic abnormality, these were not necessary for accurate recognition of abnormality.

  18. Age-related changes in conventional road versus off-road triathlon performance.

    PubMed

    Lepers, Romuald; Stapley, Paul J

    2011-08-01

    The aims of this study were: (i) to analyze age-related declines in swimming, cycling, and running performances for road-based and off-road triathlons, and (ii) to compare age-related changes in these three disciplines between road-based and off-road triathlons. Swimming, cycling, running and total time performances of the top five males between 20 and 70 years of age (in 5-year intervals) were analyzed for short distance road-based (1.5 km swim, 40 km cycle, and 10 km run) and off-road (1.5 km swim, 30 km mountain bike, and 11 km trail run) triathlons at the 2009 World Championships. Independently of age, there was a lesser age-related decline in cycling performance (P < 0.01) compared to running and swimming for road-based triathlon. In contrast, age-related decline did not differ between the three locomotion modes for off-road triathlon. With advancing age, the performance decline was less pronounced (P < 0.01) for road-based than for off-road triathlon in swimming (≥65 years), cycling (≥50 years), running (≥60 years), and total event (≥55 years) times, respectively. These results suggest that the rate of the decline in performance for off-road triathlon is greater than for road-based triathlon, indicating that the type of discipline (road vs. mountain bike cycling and road vs. trail running) exerts an important influence on the magnitude of the age-associated changes in triathlon performance. PMID:21210278

  19. Formaldehyde as a trigger for protein aggregation and potential target for mitigation of age-related, progressive cognitive impairment.

    PubMed

    Su, Tao; Monte, Woodrow C; Hu, Xintian; He, Yingge; He, Rongqiao

    2016-01-01

    Recently, formaldehyde (FA), existing in a number of different cells including neural cells, was found to affect age-related cognitive impairment. Oral administration of methanol (the metabolic precursor of FA) triggers formation of senile plaques (SPs) and Tau hyperphosphorylation in the brains of monkeys with memory decline. Intraperitoneal injection of FA leads to hyperphosphorylation of Tau in wild-type mouse brains and N2a cells through activation of glycogen synthase kinase-3β (GSK-3β). Furthermore, formaldehyde at low concentrations can directly induce Tau aggregation and amyloid β (Aβ) peptide deposits in vitro. Formaldehyde-induced Tau aggregation is implicated in cytotoxicity and neural cell apoptosis. Clarifying how FA triggers Aβ deposits and Tau hyperphosphorlyation will not only improve our understanding of the molecular and cellular mechanisms of age-related cognitive impairment but will also contribute to the ongoing investigation of alternate targets for new drugs. Here, we review the role of FA, particularly that of endogenous origin, in protein aggregation and as a potential drug intervention in the development of agerelated cognitive impairment. PMID:26268337

  20. Age-related decline in verbal learning is moderated by demographic factors, working memory capacity, and presence of amnestic mild cognitive impairment.

    PubMed

    Constantinidou, Fofi; Zaganas, Ioannis; Papastefanakis, Emmanouil; Kasselimis, Dimitrios; Nidos, Andreas; Simos, Panagiotis G

    2014-09-01

    Age-related memory changes are highly varied and heterogeneous. The study examined the rate of decline in verbal episodic memory as a function of education level, auditory attention span and verbal working memory capacity, and diagnosis of amnestic mild cognitive impairment (a-MCI). Data were available on a community sample of 653 adults aged 17-86 years and 70 patients with a-MCI recruited from eight broad geographic areas in Greece and Cyprus. Measures of auditory attention span and working memory capacity (digits forward and backward) and verbal episodic memory (Auditory Verbal Learning Test [AVLT]) were used. Moderated mediation regressions on data from the community sample did not reveal significant effects of education level on the rate of age-related decline in AVLT indices. The presence of a-MCI was a significant moderator of the direct effect of Age on both immediate and delayed episodic memory indices. The rate of age-related decline in verbal episodic memory is normally mediated by working memory capacity. Moreover, in persons who display poor episodic memory capacity (a-MCI group), age-related memory decline is expected to advance more rapidly for those who also display relatively poor verbal working memory capacity. PMID:25156204

  1. ERBB4 Polymorphism and Family History of Psychiatric Disorders on Age-Related Cortical Changes in Healthy Children

    PubMed Central

    Douet, Vanessa; Chang, Linda; Lee, Kristin; Ernst, Thomas

    2015-01-01

    Background Genetic variations in ERBB4 were associated with increased susceptibility for schizophrenia (SCZ) and bipolar disorders (BPD). Structural imaging studies showed cortical abnormalities in adolescents and adults with SCZ or BPD. However, less is known about subclinical cortical changes or the influence of ERBB4 on cortical development. Methods 971 healthy children (ages 3–20 years old; 462 girls and 509 boys) were genotyped for the ERBB4-rs7598440 variants, had structural MRI, and cognitive evaluation (NIH Toolbox ®). We investigated the effects of ERBB4 variants and family history of SCZ and/or BPD (FH) on cortical measures and cognitive performances across ages 3–20 years using a general additive model. Results Variations in ERBB4 and FH impact differentially the age-related cortical changes in regions often affected by SCZ and BPD. The ERBB4-TT-risk genotype children with no FH had subtle cortical changes across the age span, primarily located in the left temporal lobe and superior parietal cortex. In contrast, the TT-risk genotype children with FH had more pronounced age-related changes, mainly in the frontal lobes compared to the non-risk genotype children. Interactive effects of age, FH and ERBB4 variations were also found on episodic memory and working memory, which are often impaired in SCZ and BPD. Conclusions Healthy children carrying the risk-genotype in ERBB4 and/or with FH had cortical measures resembling those reported in SCZ or BPD. These subclinical cortical variations may provide early indicators for increased risk of psychiatric disorders and improve our understanding of the effect of the NRG1–ERBB4 pathway on brain development. PMID:25744101

  2. Age-related changes in the thickness of cortical zones in humans.

    PubMed

    McGinnis, Scott M; Brickhouse, Michael; Pascual, Belen; Dickerson, Bradford C

    2011-10-01

    Structural neuroimaging studies have demonstrated that all regions of the cortex are not affected equally by aging, with frontal regions appearing especially susceptible to atrophy. The "last in, first out" hypothesis posits that aging is, in a sense, the inverse of development: late-maturing regions of the brain are preferentially vulnerable to age-related loss of structural integrity. We tested this hypothesis by analyzing age-related changes in regional cortical thickness via three methods: (1) an exploratory linear regression of cortical thickness and age across the entire cortical mantle (2) an analysis of age-related differences in the thickness of zones of cortex defined by functional/cytoarchitectural affiliation (including primary sensory/motor, unimodal association, heteromodal association, and paralimbic zones), and (3) an analysis of age-related differences in the thickness of regions of cortex defined by surface area expansion in the period between birth and early adulthood. Subjects were grouped as young (aged 18-29, n = 138), middle-aged (aged 30-59, n = 80), young-old (aged 60-79, n = 60), and old-old (aged 80+, n = 38). Thinning of the cortex between young and middle-aged adults was greatest in heteromodal association cortex and regions of high postnatal surface area expansion. In contrast, thinning in old-old age was greatest in primary sensory/motor cortices and regions of low postnatal surface area expansion. In sum, these results lead us to propose a sequential "developmental-sensory" model of aging, in which developmental factors influence cortical vulnerability relatively early in the aging process, whereas later-in more advanced stages of aging-factors specific to primary sensory and motor cortices confer vulnerability. This model offers explicitly testable hypotheses and suggests the possibility that normal aging may potentially allow for multiple opportunities for intervention to promote the structural integrity of the cerebral

  3. Age-related changes in the rate of esterification of plasma cholesterol in Fischer-344 rats.

    PubMed

    Carlile, S I; Kudchodkar, B J; Wang, C S; Lacko, A G

    1986-01-01

    Plasma cholesterol and triglyceride levels and selected molecular species of plasma cholesteryl esters and triglycerides were determined in 6-, 12-, 15-, 18-, 21-, and 24-month-old Fischer-344 rats. Lecithin:cholesterol acyltransferase (LCAT) activity was also determined using two independent methods utilizing endogenous and exogenous substrates. Plasma cholesterol levels increased up to 18 months of age and then plateaued. Of the plasma triglyceride molecular species investigated (C50, C52, C54 and C56), only the levels of C52 increased linearly with age. The concentration of other triglyceride molecular species did not change with age. The fractional rate of plasma cholesterol esterification showed a decreasing trend with age, whereas, the net cholesterol esterification rate showed a gradual age related increase. However, this latter parameter remained unchanged with age when the data were normalized for body weight. The cholesterol esterification rates measured using an exogenous substrate (estimating LCAT enzyme levels) showed essentially no change with age. These data indicate that changes in the levels and/or composition of lipoprotein substrate(s) for LCAT are likely causes of the observed age-related changes in the fractional rate of plasma cholesterol esterification. The net esterification rate of plasma cholesterol was significantly correlated with the plasma triglyceride levels when the animals for all age groups were treated as one experimental group. PMID:3959602

  4. Intranasal Insulin Improves Age-Related Cognitive Deficits and Reverses Electrophysiological Correlates of Brain Aging.

    PubMed

    Maimaiti, Shaniya; Anderson, Katie L; DeMoll, Chris; Brewer, Lawrence D; Rauh, Benjamin A; Gant, John C; Blalock, Eric M; Porter, Nada M; Thibault, Olivier

    2016-01-01

    Peripheral insulin resistance is a key component of metabolic syndrome associated with obesity, dyslipidemia, hypertension, and type 2 diabetes. While the impact of insulin resistance is well recognized in the periphery, it is also becoming apparent in the brain. Recent studies suggest that insulin resistance may be a factor in brain aging and Alzheimer's disease (AD) whereby intranasal insulin therapy, which delivers insulin to the brain, improves cognition and memory in AD patients. Here, we tested a clinically relevant delivery method to determine the impact of two forms of insulin, short-acting insulin lispro (Humalog) or long-acting insulin detemir (Levemir), on cognitive functions in aged F344 rats. We also explored insulin effects on the Ca(2+)-dependent hippocampal afterhyperpolarization (AHP), a well-characterized neurophysiological marker of aging which is increased in the aged, memory impaired animal. Low-dose intranasal insulin improved memory recall in aged animals such that their performance was similar to that seen in younger animals. Further, because ex vivo insulin also reduced the AHP, our results suggest that the AHP may be a novel cellular target of insulin in the brain, and improved cognitive performance following intranasal insulin therapy may be the result of insulin actions on the AHP. PMID:25659889

  5. Age-Related Changes in CD8 T Cell Homeostasis and Immunity to Infection

    PubMed Central

    Nikolich-Zugich, Janko; Li, Gang; Uhrlaub, Jennifer L.; Renkema, Kristin R.; Smithey, Megan J.

    2012-01-01

    Studies of CD8 T cell responses to vaccination or infection with various pathogens in both animal models and human subjects have revealed a markedly consistent array of age-related defects. In general, recent work shows that aged CD8 T cell responses are decreased in magnitude, and show poor differentiation into effector cells, with a reduced arsenal of effector functions. Here we review potential mechanisms underlying these defects. We specifically address phenotypic and numeric changes to the naïve CD8 T cell precursor pool, the impact of persistent viral infection(s) and inflammation, and contributions of the aging environment in which these cells are activated. PMID:22554418

  6. Age-related changes in the transcriptome of antibody-secreting cells

    PubMed Central

    Kurupati, Raj; Showe, Louise C.; Ertl, Hildegund C.J.

    2016-01-01

    We analyzed age-related defects in B cell populations from young and aged mice. Microarray analysis of bone marrow resident antibody secreting cells (ASCs) showed significant changes upon aging, affecting multiple genes, pathways and functions including those that play a role in immune regulation, humoral immune responses, chromatin structure and assembly, cell metabolism and the endoplasmic reticulum (ER) stress response. Further analysis showed upon aging defects in energy production through glucose catabolism with reduced oxidative phosphorylation. In addition aged B cells had increased levels of reactive oxygen-species (ROS), which was linked to enhanced expression of the co-inhibitor programmed cell death (PD)-1. PMID:26967249

  7. Sex-specific age-related changes of information processing rate indicators during childhood and adolescence.

    PubMed

    Zebec, Mislav S; Budimir, Sanja; Merkas, Marina; Szirovicza, Lajos; Zivicnjak, Miroslav

    2014-06-01

    Despite the relevant findings on non-average information processing rate (IPR) indicators-intelligence relation, and on age-related changes of some of these indicators during aging, the research on sex-specific age-related changes of these indicators during childhood and adolescence are lacking. In a transversal study, 1197 school children (598 girls) aged 8-18 have been individually measured on 5 IPR indicators--two averages (mean_t, median_t) and three non-averages (min_t, max_t, sd_t). The results corroborated the expected non-linear changes of average IPR indicators in the observed developmental period, whereby the sex difference in related developmental patterns was detected: marked age-related decrement in girls ceased at the age of 12, and in boys around the age of 13-14, after which progress in both sexes gradually ceased by the age of 18 and was less pronounced in girls. Generally similar non-linear age-related decrements of non-average indicators were registered, but they showed mutual intensity differences at specific ages and sex difference in developmental patterns was detected, analogously to average indicators. Systematic sex differences in the whole observed period were obtained only in two non-average indicators: girls showed minor sd_t and boys showed minor min_t. In specific age groups, a number of sex differences were obtained that are explainable by two possible mechanisms: earlier maturation in girls and sex bias of the IPR task content. The justifiability of separate, average and non-average, IPR indicators application was corroborated by their distribution form differences, by mutual, predominantly low and medium correlations, by the different intensity of their developmental changes and by their different ability to detect sex differences. For all registered phenomena, the theoretical and/or empirical explanations were offered from the domain of sex specific intellectual, motor and neural development, and it has been shown that non

  8. Changes in Age-Related Reproductive Tactics in the Female of the Butterfly, Eurema hecabe

    NASA Astrophysics Data System (ADS)

    Hiroki, Masato; Obara, Yoshiaki; Kato, Yoshiomi

    The occurrence of mate solicitation by virgin females was investigated in the butterfly Euremahecabe. Young (1-day-old) virgin females rarely showed mate solicitation to male model, however, old (at least 6-day-old) virgin females frequently showed such flight. The duration of solicitation was significantly longer in older females than in younger ones. The age-related behavioral change occurs with female oogenesis (Hiroki and Kato 1996), and such behavior may thus be a result of female adaptation to maximize their fecundity.

  9. Mitochondrial haplogroups modify the effect of black carbon on age-related cognitive impairment

    PubMed Central

    2014-01-01

    Background Traffic-related air pollution has been linked with impaired cognition in older adults, possibly due to effects of oxidative stress on the brain. Mitochondria are the main source of cellular oxidation. Haplogroups in mitochondrial DNA (mtDNA) mark individual differences in oxidative potential and are possible determinants of neurodegeneration. The aim of this study was to investigate whether mtDNA haplogroups determined differential susceptibility to cognitive effects of long-term exposure to black carbon (BC), a marker of traffic-related air pollution. Methods We investigated 582 older men (72 ± 7 years) in the VA Normative Aging Study cohort with ≤4 visits per participant (1.8 in average) between 1995–2007. Low (≤25) Mini Mental State Examination (MMSE) was used to assess impaired cognition in multiple domains. We fitted repeated-measure logistic regression using validated-LUR BC estimated in the year before their first visit at the participant’s address. Results Mitochondrial haplotyping identified nine haplogroups phylogenetically categorized in four clusters. BC showed larger effect on MMSE in Cluster 4 carriers, including I, W and X haplogroups, [OR = 2.7; 95% CI (1.3-5.6)], moderate effect in Cluster 1, including J and T haplogroups [OR = 1.6; 95% CI: (0.9-2.9)], and no effect in Cluster 2 (H and V haplogroups) [OR = 1.1; 95% CI: (0.8-1.5)] or Cluster 3 (K and U haplogroups) [OR = 1.0; 95% CI: (0.6-1.6)]. BC effect varied only moderately across the I, X, and W haplogroups or across the J and T haplogroups. Conclusions The association of BC with impaired cognition was worsened in carriers of phylogenetically-related mtDNA haplogroups in Cluster 4. No BC effects were detected in Cluster 2 and 3 carriers. MtDNA haplotypes may modify individual susceptibility to the particle cognitive effects. PMID:24884505

  10. Age-Related Decline in Cognitive Pain Modulation Induced by Distraction: Evidence From Event-Related Potentials.

    PubMed

    Zhou, Shu; Després, Olivier; Pebayle, Thierry; Dufour, André

    2015-09-01

    Distraction is known to reduce perceived pain but not always efficiently. Overlapping cognitive resources play a role in both pain processing and executive functions. We hypothesized that with aging, the analgesic effects of cognitive modulation induced by distraction would be reduced as a result of functional decline of frontal networks. Twenty-eight elderly and 28 young participants performed a tonic heat pain test with and without distraction (P + D vs P condition), and 2 executive tasks involving the frontal network (1-back [working memory] and go/no-go [response inhibition]), during which event-related potentials were recorded. A significant age-related difference in modulatory effect was observed during the pain-distraction test, with the older group reporting higher pain perception than the younger group during the P + D than during the P condition. Greater brain activity of early processes (P2 component) in both go/no-go and 1-back tasks correlated with less perceived pain during distraction in younger participants. For later processes, more cognitive control and attentional resources (increased N2 and P3 amplitude) needed for working memory processes were associated with greater pain perception in the older group. Inhibition processes were related to conscious distraction estimation in both groups. These findings indicate that cognitive processes subtended by resources in the frontal network, particularly working memory processes, are elicited more in elderly than in younger individuals for pain tolerance when an irrelevant task is performed simultaneously. Perspective: This study suggests that age-related declines in pain modulation are caused by functional degeneration of frontal cerebral networks, which may contribute to a higher prevalence of chronic pain. Analyzing the impact of frontal network function on pain modulation may assist in the development of more effective targeted treatment plans. PMID:26080043

  11. Examining age-related shared variance between face cognition, vision, and self-reported physical health: a test of the common cause hypothesis for social cognition

    PubMed Central

    Olderbak, Sally; Hildebrandt, Andrea; Wilhelm, Oliver

    2015-01-01

    The shared decline in cognitive abilities, sensory functions (e.g., vision and hearing), and physical health with increasing age is well documented with some research attributing this shared age-related decline to a single common cause (e.g., aging brain). We evaluate the extent to which the common cause hypothesis predicts associations between vision and physical health with social cognition abilities specifically face perception and face memory. Based on a sample of 443 adults (17–88 years old), we test a series of structural equation models, including Multiple Indicator Multiple Cause (MIMIC) models, and estimate the extent to which vision and self-reported physical health are related to face perception and face memory through a common factor, before and after controlling for their fluid cognitive component and the linear effects of age. Results suggest significant shared variance amongst these constructs, with a common factor explaining some, but not all, of the shared age-related variance. Also, we found that the relations of face perception, but not face memory, with vision and physical health could be completely explained by fluid cognition. Overall, results suggest that a single common cause explains most, but not all age-related shared variance with domain specific aging mechanisms evident. PMID:26321998

  12. Examining age-related shared variance between face cognition, vision, and self-reported physical health: a test of the common cause hypothesis for social cognition.

    PubMed

    Olderbak, Sally; Hildebrandt, Andrea; Wilhelm, Oliver

    2015-01-01

    The shared decline in cognitive abilities, sensory functions (e.g., vision and hearing), and physical health with increasing age is well documented with some research attributing this shared age-related decline to a single common cause (e.g., aging brain). We evaluate the extent to which the common cause hypothesis predicts associations between vision and physical health with social cognition abilities specifically face perception and face memory. Based on a sample of 443 adults (17-88 years old), we test a series of structural equation models, including Multiple Indicator Multiple Cause (MIMIC) models, and estimate the extent to which vision and self-reported physical health are related to face perception and face memory through a common factor, before and after controlling for their fluid cognitive component and the linear effects of age. Results suggest significant shared variance amongst these constructs, with a common factor explaining some, but not all, of the shared age-related variance. Also, we found that the relations of face perception, but not face memory, with vision and physical health could be completely explained by fluid cognition. Overall, results suggest that a single common cause explains most, but not all age-related shared variance with domain specific aging mechanisms evident. PMID:26321998

  13. Age-Related Neurochemical Changes in the Rhesus Macaque Superior Olivary Complex

    PubMed Central

    Gray, Daniel T.; Engle, James R.; Recanzone, Gregg H.

    2014-01-01

    Positive immunoreactivity to the calcium-binding protein parvalbumin (PV) and nitric oxide synthase NADPH-diaphorase (NADPHd) is well documented within neurons of the central auditory system of both rodents and primates. These proteins are thought to play roles in the regulation of auditory processing. Studies examining the age-related changes in expression of these proteins have been conducted primarily in rodents but are sparse in primate models. In the brainstem, the superior olivary complex (SOC) is crucial for the computation of sound source localization in azimuth, and one hallmark of age-related hearing deficits is a reduced ability to localize sounds. To investigate how these histochemical markers change as a function of age and hearing loss, we studied eight rhesus macaques ranging in age from 12 to 35 years. Auditory brainstem responses (ABRs) were obtained in anesthetized animals for click and tone stimuli. The brainstems of these same animals were then stained for PV and NADPHd reactivity. Reactive neurons in the three nuclei of the SOC were counted, and the densities of each cell type were calculated. We found that PV and NADPHd expression increased with both age and ABR thresholds in the medial superior olive but not in either the medial nucleus of the trapezoid body or the lateral superior olive. Together these results suggest that the changes in protein expression employed by the SOC may compensate for the loss of efficacy of auditory sensitivity in the aged primate. PMID:25232570

  14. Optimizing the assessment of age-related changes in trabecular bone

    NASA Astrophysics Data System (ADS)

    Kubik, T.; Pasowicz, M.; Tabor, Z.; Rokita, E.

    2002-05-01

    The goal of this study was to develop an optimal procedure to determine age-related changes in trabecular bone. The investigations were based on two-dimensional images of the human vertebral trabecular bone specimens. The following indices of trabecular structure were considered: bone volume/total volume, star volume of the marrow cavity, Euler number and the probability of disconnection (straightforwardly connected with the number of separated parts of the network). To follow precisely the changes in the trabecular structure with age, a computer simulation model was used. Up to 35 years of physiological remodelling were simulated. The validation of the model calculations was based on a quantitative comparison with the data measured for older individuals. The simulations confirmed that the description of the age-related changes in the trabecular bone by means of the architectural parameter (star volume) constitutes a promising tool for subjects older than ~50 years. For individuals younger than ~50 years bone mineral density (bone volume/total volume) seems to be the best suited descriptor. The results suggest that the optimal diagnostic procedure is age-dependent and should not be limited to the bone mineral density measurement. The clinical usefulness of the procedure has been validated by examination of the CT images.

  15. Age-related changes in processing faces from detection to identification: ERP evidence

    PubMed Central

    Daniel, Sharon; Bentin, Shlomo

    2010-01-01

    We examined the ability of people 70 to 90 years old to apply global, configural and featural face-processing strategies. In addition we investigated age-related changes in the ability to categorize faces at basic, subordinate and individual levels. Using the N170 potential as index of early face processing and the P300 component as index of categorical decision making and effort, we found significant age-related perceptual changes which slowed and somewhat impaired face processing. Specifically, older participants had problems integrating face features into global structures, demonstrating enhanced dependence on distal global information. They did not apply configural computations by default while processing faces which suggests that, unless identification is required, they process faces only at a basic level. These perceptual changes could be the cause for slower and less accurate subordinate categorization, particularly when it is based on details. At the neural levels face processing was not right-lateralized, reflecting excessive involvement of the left hemisphere in perception leading to a more general reduction of inter-hemispheric asymmetry. In addition we found excessive but nonselective activation of frontal regions adding support to the view that executive control and particularly inhibition of irrelevant input are reduced in the elderly. PMID:20961658

  16. Age-Related Changes in Hepatic Function: An Update on Implications for Drug Therapy.

    PubMed

    Tan, Joseph L; Eastment, Jacques G; Poudel, Arjun; Hubbard, Ruth E

    2015-12-01

    The accumulation of deficits with increasing age results in a decline in the functional capacity of multiple organs and systems. These changes can have a significant influence on the pharmacokinetics and pharmacodynamics of prescribed drugs. Although alterations in body composition and worsening renal clearance are important considerations, for most drugs the liver has the greatest effect on metabolism. Age-related change in hepatic function thereby causes much of the variability in older people's responses to medication. In this review, we propose that a decline in the ability of the liver to inactivate toxins may contribute to a proinflammatory state in which frailty can develop. Since inflammation also downregulates drug metabolism, medication prescribed to frail older people in accordance with disease-specific guidelines may undergo reduced systemic clearance, leading to adverse drug reactions, further functional decline and increasing polypharmacy, exacerbating rather than ameliorating frailty status. We also describe how increasing chronological age and frailty status impact liver size, blood flow and protein binding and enzymes of drug metabolism. This is used to contextualise our discussion of appropriate prescribing practices. For example, while the general axiom of 'start low, go slow' should underpin the initiation of medication (titrating to a defined therapeutic goal), it is important to consider whether drug clearance is flow or capacity-limited. By summarising the effect of age-related changes in hepatic function on medications commonly used in older people, we aim to provide a guide that will have high clinical utility for practising geriatricians. PMID:26547855

  17. Experimental evidence of age-related adaptive changes in human acinar airways.

    PubMed

    Quirk, James D; Sukstanskii, Alexander L; Woods, Jason C; Lutey, Barbara A; Conradi, Mark S; Gierada, David S; Yusen, Roger D; Castro, Mario; Yablonskiy, Dmitriy A

    2016-01-15

    The progressive decline of lung function with aging is associated with changes in lung structure at all levels, from conducting airways to acinar airways (alveolar ducts and sacs). While information on conducting airways is becoming available from computed tomography, in vivo information on the acinar airways is not conventionally available, even though acini occupy 95% of lung volume and serve as major gas exchange units of the lung. The objectives of this study are to measure morphometric parameters of lung acinar airways in living adult humans over a broad range of ages by using an innovative MRI-based technique, in vivo lung morphometry with hyperpolarized (3)He gas, and to determine the influence of age-related differences in acinar airway morphometry on lung function. Pulmonary function tests and MRI with hyperpolarized (3)He gas were performed on 24 healthy nonsmokers aged 19-71 years. The most significant age-related difference across this population was a 27% loss of alveolar depth, h, leading to a 46% increased acinar airway lumen radius, hence, decreased resistance to acinar air transport. Importantly, the data show a negative correlation between h and the pulmonary function measures forced expiratory volume in 1 s and forced vital capacity. In vivo lung morphometry provides unique information on age-related changes in lung microstructure and their influence on lung function. We hypothesize that the observed reduction of alveolar depth in subjects with advanced aging represents a remodeling process that might be a compensatory mechanism, without which the pulmonary functional decline due to other biological factors with advancing age would be significantly larger. PMID:26542518

  18. Age related-changes in the neural basis of self-generation in verbal paired associate learning.

    PubMed

    Vannest, Jennifer; Maloney, Thomas; Kay, Benjamin; Siegel, Miriam; Allendorfer, Jane B; Banks, Christi; Altaye, Mekibib; Szaflarski, Jerzy P

    2015-01-01

    Verbal information is better retained when it is self-generated rather than when it is received passively. The application of self-generation procedures has been found to improve memory in healthy elderly and in individuals with impaired cognition. Overall, the available studies support the notion that active participation in verbal encoding engages memory mechanisms that supplement those used during passive observation. Thus, the objective of this study was to investigate the age-related changes in the neural mechanisms involved in the encoding of paired-associates using a self-generation method that has been shown to improve memory performance across the lifespan. Subjects were 113 healthy right-handed adults (Edinburgh Handedness Inventory >50; 67 females) ages 18-76, native speakers of English with no history of neurological or psychiatric disorders. Subjects underwent fMRI at 3 T while performing didactic learning ("read") or self-generation learning ("generate") of 30 word pairs per condition. After fMRI, recognition memory for the second word in each pair was evaluated outside of the scanner. On the post-fMRI testing more "generate" words were correctly recognized than "read" words (p < 0.001) with older adults recognizing the "generated" words less accurately (p < 0.05). Independent component analysis of fMRI data identified task-related brain networks. Several components were positively correlated with the task reflecting multiple cognitive processes involved in self-generated encoding; other components correlated negatively with the task, including components of the default-mode network. Overall, memory performance on generated words decreased with age, but the benefit from self-generation remained consistently significant across ages. Independent component analysis of the neuroimaging data revealed an extensive set of components engaged in self-generation learning compared with didactic learning, and identified areas that were associated with age-related

  19. Age-related hair changes in men: mechanisms and management of alopecia and graying.

    PubMed

    Mirmirani, Paradi

    2015-01-01

    The appearance of human scalp hair is often tied to perceptions of youth and virility, especially in men. Hair loss, or alopecia and hair graying are commonly associated with advancing age and are frequently a source for emotional distress and anxiety. Our understanding of the complex molecular signals and mechanisms that regulate and influence the hair follicle has expanded in recent years. By harnessing this understanding we are poised to address the esthetic concerns of aging hair. Additionally, changes in the hair follicle may be a reflection of systemic senescent signals, thus because of its accessibility, the hair follicle may serve as an important research tool in gerontology. In this review, the most current knowledge and research regarding mechanisms of androgenetic alopecia, senescent alopecia, and graying are discussed, as are extrinsic factors that may contribute to hair changes with age. Evidence based management strategies for treatment of age-related hair changes are also reviewed. PMID:25466305

  20. Age-related changes in human posture control: Motor coordination tests

    NASA Technical Reports Server (NTRS)

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

    1989-01-01

    Postural responses to support surface displacements were measured in 214 normal human subjects ranging in age from 7 to 81 years. Motor tests measured leg muscle Electromyography (EMG) latencies, body sway, and the amplitude and timing of changes in center of pressure displacements in response to sudden forward and backward horizontal translations of the support surface upon which the subjects stood. There were small increases in both EMG latencies and the time to reach the peak amplitude of center of pressure responses with increasing age. The amplitude of center of pressure responses showed little change with age if the amplitude measures were normalized by a factor related to subject height. In general, postural responses to sudden translations showed minimal changes with age, and all age related trends which were identified were small relative to the variability within the population.

  1. Age-related changes in neural gap detection thresholds in the rat auditory cortex.

    PubMed

    Zhao, Yin; Xu, Xiaoxiao; He, Juan; Xu, Jinghong; Zhang, Jiping

    2015-02-01

    The ability of the auditory system to resolve sound temporal information is crucial for the understanding of human speech and other species-specific communications. Gap detection threshold, i.e. the ability to detect the shortest duration of a silent interval in a sound, is commonly used to study the auditory temporal resolution. Behavioral studies in humans and rats have shown that normal developing infants have higher gap detection thresholds than adults; however, the underlying neural mechanism is not fully understood. In the present study, we determined and compared the neural gap detection thresholds in the primary auditory cortex of three age groups of rats: the juvenile group (postnatal day 20-30), adult group I (8-10 weeks), and adult group II (28-30 weeks). We found age-related changes in auditory temporal acuity in the auditory cortex, i.e. the proportion of cortical units with short neural gap detection thresholds (< 5 ms) was much lower in juvenile groups compared with that in both adult groups at a constant sound level, and no significant differences in neural gap detection thresholds were found between the two adult groups. In addition, units in the auditory cortex of each group generally showed better gap detection thresholds at higher sound levels than at lower sound levels, exhibiting a level-dependent temporal acuity. These results provided evidence for neural correlates of age-related changes in behavioral gap detection ability during postnatal hearing development. PMID:25388865

  2. Age-Related Changes in Hepatic Activity and Expression of Detoxification Enzymes in Male Rats

    PubMed Central

    Vyskočilová, Erika; Szotáková, Barbora; Skálová, Lenka; Bártíková, Hana; Hlaváčová, Jitka

    2013-01-01

    Process of aging is accompanied by changes in the biotransformation of xenobiotics and impairment of normal cellular functions by free radicals. Therefore, this study was designed to determine age-related differences in the activities and/or expressions of selected drug-metabolizing and antioxidant enzymes in young and old rats. Specific activities of 8 drug-metabolizing enzymes and 4 antioxidant enzymes were assessed in hepatic subcellular fractions of 6-week-old and 21-month-old male Wistar rats. Protein expressions of carbonyl reductase 1 (CBR1) and glutathione S-transferase (GST) were determined using immunoblotting. Remarkable age-related decrease in specific activities of CYP2B, CYP3A, and UDP-glucuronosyl transferase was observed, whereas no changes in activities of CYP1A2, flavine monooxygenase, aldo-keto reductase 1C, and antioxidant enzymes with advancing age were found. On the other hand, specific activity of CBR1 and GST was 2.4 folds and 5.6 folds higher in the senescent rats compared with the young ones, respectively. Interindividual variability in CBR1 activity increased significantly with rising age. We suppose that elevated activities of GST and CBR1 may protect senescent rats against xenobiotic as well as eobiotic electrophiles and reactive carbonyls, but they may alter metabolism of drugs, which are CBR1 and especially GSTs substrates. PMID:23971034

  3. Age-related changes of auditory brainstem responses in nonhuman primates.

    PubMed

    Ng, Chi-Wing; Navarro, Xochi; Engle, James R; Recanzone, Gregg H

    2015-07-01

    Nonhuman primates, compared with humans and rodents, have historically been far less used for studies of age-related hearing loss, primarily because of their long life span and high cost of maintenance. Strong similarities in genetics, anatomy, and neurophysiology of the auditory nervous system between humans and monkeys, however, could provide fruitful opportunities to enhance our understanding of hearing loss. The present study used a common, noninvasive technique for testing hearing sensitivity in humans, the auditory brainstem response (ABR), to assess the hearing of 48 rhesus macaques from 6 to 35 yr of age to clicks and tone stimuli between 0.5 and 16.0 kHz. Old monkeys, particularly those above 21.5 yr of age, had missing ABR waveforms at high frequencies. Regression analyses revealed that ABR threshold increased as a function of age at peaks II and IV simultaneously. In the suprathreshold hearing condition (70 dB peak sound pressure level), ABR-based audiograms similarly varied as a function of age such that old monkeys had smaller peak amplitudes and delayed latencies at low, middle, and high frequencies. Peripheral hearing differences remained a major influence associated with age-related changes in audiometric functions of old monkeys at a comparable sensation level across animals. The present findings suggest that hearing loss occurs in old monkeys across a wide range of frequencies and that these deficits increase in severity with age. Parallel to prior studies in monkeys, we found weak effects of sex on hearing, and future investigations are necessary to clarify its role in age-related hearing loss. PMID:25972589

  4. Age-related changes of auditory brainstem responses in nonhuman primates

    PubMed Central

    Ng, Chi-Wing; Navarro, Xochi; Engle, James R.

    2015-01-01

    Nonhuman primates, compared with humans and rodents, have historically been far less used for studies of age-related hearing loss, primarily because of their long life span and high cost of maintenance. Strong similarities in genetics, anatomy, and neurophysiology of the auditory nervous system between humans and monkeys, however, could provide fruitful opportunities to enhance our understanding of hearing loss. The present study used a common, noninvasive technique for testing hearing sensitivity in humans, the auditory brainstem response (ABR), to assess the hearing of 48 rhesus macaques from 6 to 35 yr of age to clicks and tone stimuli between 0.5 and 16.0 kHz. Old monkeys, particularly those above 21.5 yr of age, had missing ABR waveforms at high frequencies. Regression analyses revealed that ABR threshold increased as a function of age at peaks II and IV simultaneously. In the suprathreshold hearing condition (70 dB peak sound pressure level), ABR-based audiograms similarly varied as a function of age such that old monkeys had smaller peak amplitudes and delayed latencies at low, middle, and high frequencies. Peripheral hearing differences remained a major influence associated with age-related changes in audiometric functions of old monkeys at a comparable sensation level across animals. The present findings suggest that hearing loss occurs in old monkeys across a wide range of frequencies and that these deficits increase in severity with age. Parallel to prior studies in monkeys, we found weak effects of sex on hearing, and future investigations are necessary to clarify its role in age-related hearing loss. PMID:25972589

  5. Age-Related Changes in Transient and Oscillatory Brain Responses to Auditory Stimulation during Early Adolescence

    ERIC Educational Resources Information Center

    Poulsen, Catherine; Picton, Terence W.; Paus, Tomas

    2009-01-01

    Maturational changes in the capacity to process quickly the temporal envelope of sound have been linked to language abilities in typically developing individuals. As part of a longitudinal study of brain maturation and cognitive development during adolescence, we employed dense-array EEG and spatiotemporal source analysis to characterize…

  6. Age-Related Changes in Corneal Deformation Dynamics Utilizing Scheimpflug Imaging

    PubMed Central

    Rogowska, Marta E.; Iskander, D. Robert

    2015-01-01

    Purpose To study age-related changes in corneal deformation response to air-puff applanation tonometry. Methods Fifty healthy subjects were recruited for a prospective study and divided into two equal age groups (≤ 28 and ≥ 50 years old). Up to three measurements by a corneal deformation analyser based on the Scheimpflug principle were performed on the left eye of each subject. Raw Scheimpflug images were used to extract changes in anterior and posterior corneal profiles, which were further modelled by an orthogonal series of Chebyshev polynomial functions. Time series of the polynomial coefficients of even order exhibited a dynamic behavior in which three distinct stages were recognized. A bilinear function was used to model the first and the third stage of corneal dynamics. Slope parameters of the bilinear fit were then tested between the two age groups using Wilcoxon rank sum test and two-way non-parametric ANOVA (Friedman) test. Results Statistically significant changes (Wilcoxon test, P<0.05) between the age groups were observed in the phase of the second applanation dynamics for the posterior corneal profile. In a two-way comparison, in which the corneal profile was used as a dependent variable, statistically significant changes (ANOVA/Friedman test, P = 0.017) between the groups were also observed for that phase. Conclusion Corneal biomechanics depend on age. The changes in corneal deformation dynamics, which correspond to mostly free return of the cornea to its original shape after the air pulse, indicate that the age related differences in corneal biomechanics are subtle but observable with high speed imaging. PMID:26460972

  7. Age-related changes of myocardial ATP supply and demand mechanisms

    PubMed Central

    Yaniv, Yael; Juhaszova, Magdalena; Sollott, Steven J.

    2013-01-01

    In advanced age, the resting myocardial oxygen consumption (M V̇O2) and cardiac work (CW) in the rat remain intact. However, M V̇O2, CW and cardiac efficiency achieved at high demand are decreased with age, compared to maximal values in the young. Whether this deterioration is due to decrease in myocardial ATP demand, ATP supply, or the control mechanisms that match them, remains controversial. Here we discuss evolving perspectives of age-related changes of myocardial ATP supply and demand mechanisms, and critique experimental models used to investigate aging. Specifically, we evaluate experimental data collected at the level of isolated mitochondria, tissue, or organism, and discuss how mitochondrial energetic mechanisms change in advanced age, both at basal and high energy demand levels. PMID:23845538

  8. Support vector machines for detecting age-related changes in running kinematics.

    PubMed

    Fukuchi, Reginaldo K; Eskofier, Bjoern M; Duarte, Marcos; Ferber, Reed

    2011-02-01

    Age-related changes in running kinematics have been reported in the literature using classical inferential statistics. However, this approach has been hampered by the increased number of biomechanical gait variables reported and subsequently the lack of differences presented in these studies. Data mining techniques have been applied in recent biomedical studies to solve this problem using a more general approach. In the present work, we re-analyzed lower extremity running kinematic data of 17 young and 17 elderly male runners using the Support Vector Machine (SVM) classification approach. In total, 31 kinematic variables were extracted to train the classification algorithm and test the generalized performance. The results revealed different accuracy rates across three different kernel methods adopted in the classifier, with the linear kernel performing the best. A subsequent forward feature selection algorithm demonstrated that with only six features, the linear kernel SVM achieved 100% classification performance rate, showing that these features provided powerful combined information to distinguish age groups. The results of the present work demonstrate potential in applying this approach to improve knowledge about the age-related differences in running gait biomechanics and encourages the use of the SVM in other clinical contexts. PMID:20980005

  9. Age-related changes in the visual pathways: blame it on the axon.

    PubMed

    Calkins, David J

    2013-12-01

    The aging visual system is marked by a decline in some, but not all, key functions. Some of this decline is attributed to changes in the optics of the eye, but other aspects must have a neural basis. Across mammals, with aging there is remarkable persistence of central structures to which retinal ganglion cell (RGC) axons project with little or no loss of neurons. Similarly, RGC bodies in the retina are subject to variable age-related loss, with most mammals showing none over time. In contrast, the RGC axon itself is highly vulnerable. Across species, the rate of axon loss in the optic nerve is related inversely to the total number of axons at maturity and lifespan. The result of this scaling is approximately a 40% total decline in axon number. Evidence suggests that the consistent vulnerability of RGC axons to aging arises from their high metabolic demand combined with diminishing resources. Thus, therapeutic interventions that conserve bioenergetics may have potential to abate age-related decline in visual function. PMID:24335066

  10. Neurophysiological correlates of age-related changes in working memory capacity.

    PubMed

    Mattay, Venkata S; Fera, Francesco; Tessitore, Alessandro; Hariri, Ahmad R; Berman, Karen F; Das, Saumitra; Meyer-Lindenberg, Andreas; Goldberg, Terry E; Callicott, Joseph H; Weinberger, Daniel R

    2006-01-01

    Cognitive abilities such as working memory (WM) capacity decrease with age. To determine the neurophysiological correlates of age-related reduction in working memory capacity, we studied 10 young subjects (<35 years of age; mean age=29) and twelve older subjects (>55 years of age; mean age=59) with whole brain blood oxygenation-level dependent (BOLD) fMRI on a 1.5 T GE MR scanner using a SPIRAL FLASH pulse sequence (TE=24 ms, TR=56 ms, FA=60 degrees , voxel dimensions=3.75 mm(3)). Subjects performed a modified version of the "n" back working memory task at different levels of increasing working memory load (1-Back, 2-Back and 3-Back). Older subjects performed as well as the younger subjects at 1-Back (p=0.4), but performed worse than the younger subjects at 2-Back (p<0.01) and 3-Back (p=0.06). Older subjects had significantly longer reaction time (RT) than younger subjects (p<0.04) at all levels of task difficulty. Image analysis using SPM 99 revealed a similar distribution of cortical activity between younger and older subjects at all task levels. However, an analysis of variance revealed a significant group x task interaction in the prefrontal cortex bilaterally; within working memory capacity, as in 1-Back when the older subjects performed as well as the younger subjects, they showed greater prefrontal cortical (BA 9) activity bilaterally. At higher working memory loads, however, when they performed worse then the younger subjects, the older subjects showed relatively reduced activity in these prefrontal regions. These data suggest that, within capacity, compensatory mechanisms such as additional prefrontal cortical activity are called upon to maintain proficiency in task performance. As cognitive demand increases, however, they are pushed past a threshold beyond which physiological compensation cannot be made and, a decline in performance occurs. PMID:16213083

  11. Age-Related Changes in Immunological Factors and Their Relevance in Allergic Disease Development During Childhood

    PubMed Central

    Chang, Woo-Sung; Kim, Eun-Jin; Lim, Yeon-Mi; Yoon, Dankyu; Son, Jo-Young; Park, Jung-Won; Hong, Soo-Jong; Cho, Sang-Heon

    2016-01-01

    Purpose Allergic diseases are triggered by Th2-mediated immune reactions to allergens and orchestrated by various immunological factors, including immune cells and cytokines. Although many reports have suggested that childhood is the critical period in the onset of allergic diseases and aging leads to alter the susceptibility of an individual to allergic diseases, age-related changes in various immunological factors in healthy individuals as well as their difference between healthy and allergic children have not yet been established. Methods We investigated the ratio of Th1/Th2 cells and the levels of 22 allergy-related cytokines across all age groups in individuals who were classified as clinically non-atopic and healthy. We also examined their differences between healthy and allergic children to evaluate immunological changes induced by the development of allergic diseases during childhood. Results The Th1/Th2 ratio rose gradually during the growth period including childhood, reaching peak values in the twenties-thirties age group. Th1/Th2 ratios were significantly lower in allergic children than in healthy controls, whereas 14 of 22 cytokines were significantly higher in allergic children than in healthy controls. On the other hand, there were no differences in Th1/Th2 ratios and cytokines between healthy and allergic adolescents. Conclusions In this study, age-related changes in Th1/Th2 ratios were found in normal controls across all age groups, and decreases in Th1/Th2 ratio were observed with increasing of 14 cytokines in allergic children. The results of this study may be helpful as reference values for both monitoring immunological changes according to aging in healthy individuals and distinguishing between normal and allergic subjects in terms of immune cells and soluble factors. PMID:27126727

  12. Combined effects of physical exercise and education on age-related cortical thinning in cognitively normal individuals

    PubMed Central

    Lee, Jin San; Shin, Hee Young; Kim, Hee Jin; Jang, Young Kyoung; Jung, Na-Yeon; Lee, Juyoun; Kim, Yeo Jin; Chun, Phillip; Yang, Jin-Ju; Lee, Jong-Min; Kang, Mira; Park, Key-Chung; Na, Duk L.; Seo, Sang Won

    2016-01-01

    We investigated the association between self-reported physical exercise and cortical thickness in a large sample of cognitively normal individuals. We also determined whether a combination of physical exercise and education had more protective effects on age-related cortical thinning than either parameter alone. A total of 1,842 participants were included in this analysis. Physical exercise was assessed using a questionnaire regarding intensity, frequency, and duration. Cortical thickness was measured using a surface-based method. Longer duration of exercise (≥1 hr/day), but not intensity or frequency, was associated with increased mean cortical thickness globally (P-value = 0.013) and in the frontal regions (P-value = 0.007). In particular, the association of exercise with cortical thinning had regional specificity in the bilateral dorsolateral prefrontal, precuneus, left postcentral, and inferior parietal regions. The combination of higher exercise level and higher education level showed greater global and frontal mean thickness than either parameter alone. Testing for a trend with the combination of high exercise level and high education level confirmed this finding (P-value = 0.001–0.003). Our findings suggest that combined exercise and education have important implications for brain health, especially considering the paucity of known protective factors for age-related cortical thinning. PMID:27063336

  13. Age-related changes in spleen of Dark Agouti rats immunized for experimental autoimmune encephalomyelitis.

    PubMed

    Djikić, Jasmina; Nacka-Aleksić, Mirjana; Pilipović, Ivan; Kosec, Duško; Arsenović-Ranin, Nevena; Stojić-Vukanić, Zorica; Dimitrijević, Mirjana; Leposavić, Gordana

    2015-01-15

    The study was undertaken considering age-related changes in susceptibility to experimental autoimmune encephalomyelitis (EAE) and a putative role of spleen in pathogenesis of this disease. The phenotypic and functional characteristics of T splenocytes were examined in young (3-month-old), middle-aged (8-month-old) and aged (26-month-old) Dark Agouti rats immunized for EAE with rat spinal cord in complete Freund's adjuvant. The rat susceptibility to EAE induction, as well as the number of activated CD4+CD134+ lymphocytes retrieved from their spinal cords progressively decreased with aging. To the contrary, in rats immunized for EAE the number of activated CD4+ splenocytes, i.e., CD4+CD134+, CD4+CD25+FoxP3- and CD4+CD40L+ cells, progressively increased with aging. This was associated with age-related increase in (i) CD4+ splenocyte surface expression of CD44, the molecule suggested to be involved in limiting emigration of encephalitogenic CD4+ cells from spleen into blood and (ii) frequency of regulatory T cells, including CD4+CD25+FoxP3+ cells, which are also shown to control encephalitogenic cell migration from spleen into the central nervous system. In favor of expansion of T-regulatory cell pool in aged rats was the greater concentration of IL-10 in unstimulated, Concanavalin A (ConA)- and myelin basic protein (MBP)-stimulated splenocyte cultures from aged rats compared with the corresponding cultures from young ones. Consistent with the age-related increase in the expression of CD44, which is shown to favor Th1 effector cell survival by interfering with CD95-mediated signaling, the frequency of apoptotic cells among CD4+ splenocytes, despite the greater frequency of CD95+ cells, was diminished in splenocyte cultures from aged compared with young rats. In addition, in control, as well as in ConA- and MBP-stimulated splenocyte cultures from aged rats, despite of impaired CD4+ cell proliferation, IFN-γ concentrations were greater than in corresponding cultures

  14. Serum osteocalcin in dairy cows: age-related changes and periparturient variation.

    PubMed

    Sato, Reiichiro; Onda, Ken; Ochiai, Hideharu; Iriki, Tsunenori; Yamazaki, Yukio; Wada, Yasunori

    2011-10-01

    We evaluated age-related changes in serum osteocalcin concentrations in non-periparturient cows and variations in serum osteocalcin concentration in periparturient primiparous and multiparous cows. The serum osteocalcin levels were evaluated in 144 non-periparturient Holstein dairy cows aged 11 days to 10 years; these levels were the highest in the youngest cows, appeared to steadily decrease with age until the time of the first calving, and were subsequently maintained at low levels. Between 14 days before calving and 21 days after calving, the serum osteocalcin levels were significantly higher in the primiparous cows than in the multiparous cows. A comparison between age-matched non-periparturient and periparturient cows showed that serum osteocalcin levels were significantly lowered during late gestation in both primiparous and multiparous cows. These results suggest that serum osteocalcin measurement might be useful for the detection of mineral imbalances at the time of parturition in cows. PMID:21300389

  15. Age-related changes in the thymus gland: CT-pathologic correlation

    SciTech Connect

    Moore, A.V.; Korobkin, M.; Olanow, W.; Heaston, D.K.; Ram, P.C.; Dunnick, N.R.; Silverman, P.M.

    1983-08-01

    Recent reports suggest that computed tomography (CT) is useful for thymoma detection in patients with myasthenia gravis. However, that usefulness may be conditioned by the state of the normal thymus. To examine this concept, the CT findings in 64 consecutive patients with histologic confirmation of thymic status after thymectomy or thymic biopsy during mediastinal exploration were reviewed. The normal thymus has a bilobed, arrowhead-shaped cross section at all ages, with gradual focal or diffuse fatty infiltration of the parenchyma usually occurring between 20 and 40 years of age. A thymoma is usually a spherical or oval mass, often producing a focal, distinct bulge in the adjacent pleural reflection. The differentiation of thymoma from normal thymus should be possible in most patients if age-related changes in the normal gland are appreciated.

  16. Spermidine feeding decreases age-related locomotor activity loss and induces changes in lipid composition.

    PubMed

    Minois, Nadège; Rockenfeller, Patrick; Smith, Terry K; Carmona-Gutierrez, Didac

    2014-01-01

    Spermidine is a natural polyamine involved in many important cellular functions, whose supplementation in food or water increases life span and stress resistance in several model organisms. In this work, we expand spermidine's range of age-related beneficial effects by demonstrating that it is also able to improve locomotor performance in aged flies. Spermidine's mechanism of action on aging has been primarily related to general protein hypoacetylation that subsequently induces autophagy. Here, we suggest that the molecular targets of spermidine also include lipid metabolism: Spermidine-fed flies contain more triglycerides and show altered fatty acid and phospholipid profiles. We further determine that most of these metabolic changes are regulated through autophagy. Collectively, our data suggests an additional and novel lipid-mediated mechanism of action for spermidine-induced autophagy. PMID:25010732

  17. Age-related changes in the function and structure of the peripheral sensory pathway in mice.

    PubMed

    Canta, Annalisa; Chiorazzi, Alessia; Carozzi, Valentina Alda; Meregalli, Cristina; Oggioni, Norberto; Bossi, Mario; Rodriguez-Menendez, Virginia; Avezza, Federica; Crippa, Luca; Lombardi, Raffaella; de Vito, Giuseppe; Piazza, Vincenzo; Cavaletti, Guido; Marmiroli, Paola

    2016-09-01

    This study is aimed at describing the changes occurring in the entire peripheral nervous system sensory pathway along a 2-year observation period in a cohort of C57BL/6 mice. The neurophysiological studies evidenced significant differences in the selected time points corresponding to childhood, young adulthood, adulthood, and aging (i.e., 1, 7, 15, and 25 months of age), with a parabolic course as function of time. The pathological assessment allowed to demonstrate signs of age-related changes since the age of 7 months, with a remarkable increase in both peripheral nerves and dorsal root ganglia at the subsequent time points. These changes were mainly in the myelin sheaths, as also confirmed by the Rotating-Polarization Coherent-Anti-stokes-Raman-scattering microscopy analysis. Evident changes were also present at the morphometric analysis performed on the peripheral nerves, dorsal root ganglia neurons, and skin biopsies. This extensive, multimodal characterization of the peripheral nervous system changes in aging provides the background for future mechanistic studies allowing the selection of the most appropriate time points and readouts according to the investigation aims. PMID:27459934

  18. Spatiotemporal Dependency of Age-Related Changes in Brain Signal Variability

    PubMed Central

    McIntosh, A. R.; Vakorin, V.; Kovacevic, N.; Wang, H.; Diaconescu, A.; Protzner, A. B.

    2014-01-01

    Recent theoretical and empirical work has focused on the variability of network dynamics in maturation. Such variability seems to reflect the spontaneous formation and dissolution of different functional networks. We sought to extend these observations into healthy aging. Two different data sets, one EEG (total n = 48, ages 18–72) and one magnetoencephalography (n = 31, ages 20–75) were analyzed for such spatiotemporal dependency using multiscale entropy (MSE) from regional brain sources. In both data sets, the changes in MSE were timescale dependent, with higher entropy at fine scales and lower at more coarse scales with greater age. The signals were parsed further into local entropy, related to information processed within a regional source, and distributed entropy (information shared between two sources, i.e., functional connectivity). Local entropy increased for most regions, whereas the dominant change in distributed entropy was age-related reductions across hemispheres. These data further the understanding of changes in brain signal variability across the lifespan, suggesting an inverted U-shaped curve, but with an important qualifier. Unlike earlier in maturation, where the changes are more widespread, changes in adulthood show strong spatiotemporal dependence. PMID:23395850

  19. Common cell biologic and biochemical changes in aging and age-related diseases of the eye: Toward new therapeutic approaches to age-related ocular diseases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reviews of information about age related macular degeneration (AMD), cataract, and glaucoma make it apparent that while each eye tissue has its own characteristic metabolism, structure and function, there are common perturbations to homeostasis that are associated with age-related dysfunction. The c...

  20. Age-Related Changes in the Anterior Segment Biometry During Accommodation

    PubMed Central

    Shao, Yilei; Tao, Aizhu; Jiang, Hong; Mao, Xinjie; Zhong, Jianguang; Shen, Meixiao; Lu, Fan; Xu, Zhe; Karp, Carol L.; Wang, Jianhua

    2015-01-01

    Purpose. We investigated the dynamic response of human accommodative elements as a function of age during accommodation using synchronized spectral domain optical coherence tomography devices (SD-OCT). Methods. We enrolled 33 left eyes from 33 healthy subjects (age range, 20–39 years, 17 males and 16 females). Two SD-OCT devices were synchronized to simultaneously image the anterior segment through pupil and the ciliary muscle during 6.00 diopter (D) accommodation for approximately 3.7 seconds in two repeated measurements. The anterior segment parameters included the lens thickness (LT), radius of curvature of the lens anterior surface (LAC), maximum thickness of ciliary muscle (CMTMAX), and anterior length of the ciliary muscle (CMAL). A first-order exponential equation was used to fit the dynamic changes during accommodation. The age-related changes in the dynamic response and their relationship were calculated and compared. Results. The amplitude (r = −0.40 and 0.53 for LT and LAC, respectively) and peak velocity (r = −0.65 and 0.71 for LT and LAC, respectively) of the changes in LT and LAC significantly decreased with age (P < 0.05), whereas the parameters of the ciliary muscle remained unchanged (P > 0.05), except for the peak velocity of the CMAL (r = 0.44, P = 0.01). The difference in the time constant between the lens reshaping (LT and LAC) and CMTMAX increased with age (r = 0.46 and 0.57 for LT and LAC, respectively, P < 0.01). The changes in LT and LAC per millimeter of CMTMAX change decreased with age (r = −0.52 and −0.34, respectively, P < 0.05). The ciliary muscle forward movement correlated with the lens deformation (r = −0.35 and 0.40 for amplitude, while r = 0.36 and 0.58 for time constant, respectively, P < 0.05). Conclusions. Age-related changes in the lens reshaping and ciliary muscle forward movement were found. Lens reshaping was much slower than the contraction of the ciliary muscle, especially in aging eyes, and this process

  1. Low-Dose, Ionizing Radiation and Age-Related Changes in Skeletal Microarchitecture

    PubMed Central

    Alwood, Joshua S.; Kumar, Akhilesh; Tran, Luan H.; Wang, Angela; Limoli, Charles L.; Globus, Ruth K.

    2012-01-01

    Osteoporosis can profoundly affect the aged as a consequence of progressive bone loss; high-dose ionizing radiation can cause similar changes, although less is known about lower doses (≤100 cGy). We hypothesized that exposure to relatively low doses of gamma radiation accelerates structural changes characteristic of skeletal aging. Mice (C57BL/6J-10 wk old, male) were irradiated (total body; 0-sham, 1, 10 or 100 cGy 137Cs) and tissues harvested on the day of irradiation, 1 or 4 months later. Microcomputed tomography was used to quantify microarchitecture of high turnover, cancellous bone. Irradiation at 100 cGy caused transient microarchitectural changes over one month that were only evident at longer times in controls (4 months). Ex vivo bone cell differentiation from the marrow was unaffected by gamma radiation. In conclusion, acute ionizing gamma irradiation at 100 cGy (but not at 1 cGy or 10 cGy) exacerbated microarchitectural changes normally found during progressive, postpubertal aging prior to the onset of age-related osteoporosis. PMID:22570786

  2. Age-related changes in thyroid hormone levels of bonobos and chimpanzees indicate heterochrony in development.

    PubMed

    Behringer, Verena; Deschner, Tobias; Murtagh, Róisín; Stevens, Jeroen M G; Hohmann, Gottfried

    2014-01-01

    We present information on age related changes of thyroid hormone levels in bonobos (N = 96) and chimpanzees (N = 100) ranging between one and 56 years of age. Fresh urine samples were used for hormone measurements with a commercial competitive total triiodothyronine (T3) ELISA. In both species, immature individuals had higher TT3 levels than adults and there was a marked decrease in TT3 levels between age classes. The two species differed in terms of the timing of TT3 level changes, with chimpanzees experiencing a significant decline in TT3 levels after 10 years of age and bonobos after 20 years of age. The decline of TT3 in chimpanzees appears to coincide with the time when somatic growth terminates while TT3 values in bonobos decrease much later. This temporal asymmetry in urinary thyroid hormone levels indicates heterochrony in the ontogenetic changes of the two sister species and developmental delay in bonobos. The prolongation of high TT3 levels in bonobos, which is characteristic of immatures of both Pan species may affect the behavior of bonobos; namely, the low intensity of aggression they display. Given that developmental studies are often based on post-mortem analyses of skeletons, measures of urinary thyroid hormones offer a non-invasive tool for exploring ontogenetic changes in living wild and captive hominoids. PMID:24275194

  3. Low-Dose, Ionizing Radiation and Age-Related Changes in Skeletal Microarchitecture

    DOE PAGESBeta

    Alwood, Joshua S.; Kumar, Akhilesh; Tran, Luan H.; Wang, Angela; Limoli, Charles L.; Globus, Ruth K.

    2012-01-01

    Osteoporosis can profoundly affect the aged as a consequence of progressive bone loss; high-dose ionizing radiation can cause similar changes, although less is known about lower doses (≤100 cGy). We hypothesized that exposure to relatively low doses of gamma radiation accelerates structural changes characteristic of skeletal aging. Mice (C57BL/6J-10 wk old, male) were irradiated (total body; 0-sham, 1, 10 or 100 cGy 137 Cs) and tissues harvested on the day of irradiation, 1 or 4 months later. Microcomputed tomography was used to quantify microarchitecture of high turnover, cancellous bone. Irradiation at 100 cGy caused transient microarchitectural changes over one month that were only evidentmore » at longer times in controls (4 months). Ex vivo bone cell differentiation from the marrow was unaffected by gamma radiation. In conclusion, acute ionizing gamma irradiation at 100 cGy (but not at 1 cGy or 10 cGy) exacerbated microarchitectural changes normally found during progressive, postpubertal aging prior to the onset of age-related osteoporosis.« less

  4. Age-Related Declines in General Cognitive Abilities of Balb/C Mice and General Activity Are Associated with Disparities in Working Memory, Body Weight, and General Activity

    ERIC Educational Resources Information Center

    Matzel, Louis D.; Grossman, Henya; Light, Kenneth; Townsend, David; Kolata, Stefan

    2008-01-01

    A defining characteristic of age-related cognitive decline is a deficit in general cognitive performance. Here we use a testing and analysis regimen that allows us to characterize the general learning abilities of young (3-5 mo old) and aged (19-21 mo old) male and female Balb/C mice. Animals' performance was assessed on a battery of seven diverse…

  5. Computer-Based Cognitive Programs for Improvement of Memory, Processing Speed and Executive Function during Age-Related Cognitive Decline: A Meta-Analysis

    PubMed Central

    Shao, Yan-kun; Mang, Jing; Li, Pei-lan; Wang, Jie; Deng, Ting; Xu, Zhong-xin

    2015-01-01

    Background Several studies have assessed the effects of computer-based cognitive programs (CCP) in the management of age-related cognitive decline, but the role of CCP remains controversial. Therefore, this systematic review evaluated the evidence on the efficacy of CCP for age-related cognitive decline in healthy older adults. Methods Six electronic databases (through October 2014) were searched. The risk of bias was assessed using the Cochrane Collaboration tool. The standardized mean difference (SMD) and 95% confidence intervals (CI) of a random-effects model were calculated. The heterogeneity was assessed using the Cochran Q statistic and quantified with the I2 index. Results Twelve studies were included in the current review and were considered as moderate to high methodological quality. The aggregated results indicate that CCP improves memory performance (SMD, 0.31; 95% CI 0.16 to 0.45; p < 0.0001) and processing speed (SMD, 0.50; 95% CI 0.14 to 0.87; p = 0.007) but not executive function (SMD, -0.12; 95% CI -0.33 to 0.09; p = 0.27). Furthermore, there were long-term gains in memory performance (SMD, 0.59; 95% CI 0.13 to 1.05; p = 0.01). Conclusion CCP may be a valid complementary and alternative therapy for age-related cognitive decline, especially for memory performance and processing speed. However, more studies with longer follow-ups are warranted to confirm the current findings. PMID:26098943

  6. A four-component model of age-related memory change.

    PubMed

    Healey, M Karl; Kahana, Michael J

    2016-01-01

    We develop a novel, computationally explicit, theory of age-related memory change within the framework of the context maintenance and retrieval (CMR2) model of memory search. We introduce a set of benchmark findings from the free recall and recognition tasks that include aspects of memory performance that show both age-related stability and decline. We test aging theories by lesioning the corresponding mechanisms in a model fit to younger adult free recall data. When effects are considered in isolation, many theories provide an adequate account, but when all effects are considered simultaneously, the existing theories fail. We develop a novel theory by fitting the full model (i.e., allowing all parameters to vary) to individual participants and comparing the distributions of parameter values for older and younger adults. This theory implicates 4 components: (a) the ability to sustain attention across an encoding episode, (b) the ability to retrieve contextual representations for use as retrieval cues, (c) the ability to monitor retrievals and reject intrusions, and (d) the level of noise in retrieval competitions. We extend CMR2 to simulate a recognition memory task using the same mechanisms the free recall model uses to reject intrusions. Without fitting any additional parameters, the 4-component theory that accounts for age differences in free recall predicts the magnitude of age differences in recognition memory accuracy. Confirming a prediction of the model, free recall intrusion rates correlate positively with recognition false alarm rates. Thus, we provide a 4-component theory of a complex pattern of age differences across 2 key laboratory tasks. PMID:26501233

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

    PubMed

    Liu, Mu-En; Huang, Chu-Chung; Yang, Albert C; Tu, Pei-Chi; Yeh, Heng-Liang; Hong, Chen-Jee; Chen, Jin-Fan; Liou, Ying-Jay; Lin, Ching-Po; Tsai, Shih-Jen

    2013-01-01

    The anti-apoptotic protein B-cell CLL/lymphoma 2 (Bcl-2) gene is a major regulator of neural plasticity and cellular resilience. Recently, the Bcl-2 rs956572 single nucleotide polymorphism was proposed to be a functional allelic variant that modulates cellular vulnerability to apoptosis. Our cross-sectional study investigated the genetic effect of this Bcl-2 polymorphism on age-related decreases in gray matter (GM) volume across the adult lifespan. Our sample comprised 330 healthy volunteers (191 male, 139 female) with a mean age of 56.2±22.0 years (range: 21-92). Magnetic resonance imaging and genotyping of the Bcl-2 rs956572 were performed for each participant. The differences in regional GM volumes between G homozygotes and A-allele carriers were tested using optimized voxel-based morphometry. The association between the Bcl-2 rs956572 polymorphism and age was a predictor of regional GM volumes in the right cerebellum, bilateral lingual gyrus, right middle temporal gyrus, and right parahippocampal gyrus. We found that the volume of these five regions decreased with increasing age (all P<.001). Moreover, the downward slope was steeper among the Bcl-2 rs956572 A-allele carriers than in the G-homozygous participants. Our data provide convergent evidence for the genetic effect of the Bcl-2 functional allelic variant in brain aging. The rs956572 G-allele, which is associated with significantly higher Bcl-2 protein expression and diminished cellular sensitivity to stress-induced apoptosis, conferred a protective effect against age-related changes in brain GM volume, particularly in the cerebellum. PMID:23437205

  8. Age-related changes in dynamic compressive properties of trochanteric soft tissues over the hip.

    PubMed

    Choi, W J; Russell, C M; Tsai, C M; Arzanpour, S; Robinovitch, S N

    2015-02-26

    Hip fracture risk increases dramatically with age, and 90% of fractures are due to falls. During a fall on the hip, the soft tissues overlying the hip region (skin, fat, and muscle) act as shock absorbers to absorb energy and reduce the peak force applied to the underlying bone. We conducted dynamic indentation experiments with young women (aged 19-30; n=17) and older women (aged 65-81; n=17) to test the hypothesis that changes occur with age in the stiffness and damping properties of these tissues. Tissue stiffness and damping were derived from experiments where subjects lay sideways on a bed with the greater trochanter contacting a 3.8cm diameter indenter, which applied sinusoidal compression between 5 to 30Hz with a peak-to-peak amplitude of 1mm. Soft tissue thickness was measured using ultrasound. On average, stiffness was 2.9-fold smaller in older than young women (5.7 versus 16.8kN/m, p=0.0005) and damping was 3.5-fold smaller in older than young women (81 versus 282Ns/m, p=0.001). Neither parameter associated with soft tissue thickness. Our results indicate substantial age-related reductions in the stiffness and damping of soft tissues over the hip region, which likely reduce their capacity to absorb and dissipate energy (before "bottoming out") during a fall. Strategies such as wearable hip protectors or compliant flooringmay compensate for age-related reductions in the shock-absorbing properties of soft tissues and decrease the injury potential of falls. PMID:25596629

  9. Corpus callosum atrophy as a predictor of age-related cognitive and motor impairment: a 3-year follow-up of the LADIS study cohort.

    PubMed

    Ryberg, C; Rostrup, E; Paulson, O B; Barkhof, F; Scheltens, P; van Straaten, E C W; van der Flier, W M; Fazekas, F; Schmidt, R; Ferro, J M; Baezner, H; Erkinjuntti, T; Jokinen, H; Wahlund, L-O; Poggesi, A; Pantoni, L; Inzitari, D; Waldemar, G

    2011-08-15

    The aim of this 3-year follow-up study was to investigate whether corpus callosum (CC) atrophy may predict future motor and cognitive impairment in an elderly population. On baseline MRI from 563 subjects with age-related white matter changes (ARWMC) from the Leukoaraiosis And DISability (LADIS) study, the CC was segmented and subdivided into five anterior-posterior regions (CC1-CC5). Associations between the CC areas and decline in motor performance and cognitive functions over a 3-year period were analyzed. CC atrophy at baseline was significantly associated with impaired cognitive performance (p<0.01 for CC1, p<0.05 for CC5), motor function (p<0.05 for CC2 and CC5), and walking speed (p<0.01 for CC2 and CC5, p<0.05 for CC3 and total CC), and with development of dementia at 3 years (p<0.05 for CC1) after correction for appropriate confounders (ARWMC volume, atrophy, age, gender and handedness). In conclusion, CC atrophy, an indicator of reduced functional connectivity between cortical areas, seems to contribute, independently of ARWMC load, to future cognitive and motor decline in the elderly. PMID:21621224

  10. Age-related changes in hypocretin (orexin) immunoreactivity in the cat brainstem.

    PubMed

    Zhang, Jian Hua; Sampogna, Sharon; Morales, Francisco R; Chase, Michael H

    2002-03-15

    Terminals of hypothalamic hypocretin-containing neurons are observed within brainstem nuclei involved in the control of sleep and wakefulness. Because aged humans, cats and other species exhibit changes in sleep and wakefulness in old age, we were interested in examining age-related changes in hypocretin/orexin projections to the following brainstem regions which are associated with the regulation of sleep and wakefulness: the dorsal raphe nucleus, the laterodorsal tegmental nucleus, the pedunculo-pontine tegmental nucleus and the locus coeruleus. Based upon the results of immunohistochemical determinations, in all the regions examined, round or oval "spot-like" structures were observed in aged cats. Many of these "spot-like" structures resembled enlarged varicosities of a nature that would be expected to disrupt hypocretin neurotransmission. In addition, a site-specific decrease in immunostaining was observed in the locus coeruleus in old cats compared with adult controls; this result likely reflects a decrease in the number of labeled fibers, which indicates that there occurs a degeneration of hypocretinergic function in conjunction with old age. The proceeding changes may account for some of sleep-wake disturbance which are observed in aged animals as well as elderly humans. PMID:11879811

  11. Age-related changes in functional network connectivity associated with high levels of verbal fluency performance.

    PubMed

    Marsolais, Yannick; Perlbarg, Vincent; Benali, Habib; Joanette, Yves

    2014-09-01

    The relative preservation of receptive language abilities in older adults has been associated with adaptive changes in cerebral activation patterns, which have been suggested to be task-load dependent. However, the effects of aging and task demands on the functional integration of neural networks contributing to speech production abilities remain largely unexplored. In the present functional neuroimaging study, data-driven spatial independent component analysis and hierarchical measures of integration were used to explore age-related changes in functional connectivity among cortical areas contributing to semantic, orthographic, and automated word fluency tasks in healthy young and older adults, as well as to assess the effect of age and task demands on the functional integration of a verbal fluency network. The results showed that the functional integration of speech production networks decreases with age, while at the same time this has a marginal effect on behavioral outcomes in high-performing older adults. Moreover, a significant task demand/age interaction was found in functional connectivity within the anterior and posterior subnetworks of the verbal fluency network. These results suggest that local changes in functional integration among cortical areas supporting lexical speech production are modulated by age and task demands. PMID:25014614

  12. Age-Related Differences in Plasma Proteins: How Plasma Proteins Change from Neonates to Adults

    PubMed Central

    Ignjatovic, Vera; Lai, Cera; Summerhayes, Robyn; Mathesius, Ulrike; Tawfilis, Sherif; Perugini, Matthew A.; Monagle, Paul

    2011-01-01

    The incidence of major diseases such as cardiovascular disease, thrombosis and cancer increases with age and is the major cause of mortality world-wide, with neonates and children somehow protected from such diseases of ageing. We hypothesized that there are major developmental differences in plasma proteins and that these contribute to age-related changes in the incidence of major diseases. We evaluated the human plasma proteome in healthy neonates, children and adults using the 2D-DIGE approach. We demonstrate significant changes in number and abundance of up to 100 protein spots that have marked differences in during the transition of the plasma proteome from neonate and child through to adult. These proteins are known to be involved in numerous physiological processes such as iron transport and homeostasis, immune response, haemostasis and apoptosis, amongst others. Importantly, we determined that the proteins that are differentially expressed with age are not the same proteins that are differentially expressed with gender and that the degree of phosphorylation of plasma proteins also changes with age. Given the multi-functionality of these proteins in human physiology, understanding the differences in the plasma proteome in neonates and children compared to adults will make a major contribution to our understanding of developmental biology in humans. PMID:21365000

  13. Age-related changes in retinoic, docosahexaenoic and arachidonic acid modulation in nuclear lipid metabolism.

    PubMed

    Gaveglio, Virginia L; Pascual, Ana C; Giusto, Norma M; Pasquaré, Susana J

    2016-08-15

    The aim of this work was to study how age-related changes could modify several enzymatic activities that regulate lipid mediator levels in nuclei from rat cerebellum and how these changes are modulated by all-trans retinoic acid (RA), docosahexaenoic acid (DHA) and arachidonic acid (AA). The higher phosphatidate phosphohydrolase activity and lower diacylglycerol lipase (DAGL) activity observed in aged animals compared with adults could augment diacylglycerol (DAG) availability in the former. Additionally, monoacylglycerol (MAG) availability could be high due to an increase in lysophosphatidate phosphohydrolase (LPAPase) activity and a decrease in monocylglycerol lipase activity. Interestingly, RA, DHA and AA were observed to modulate these enzymatic activities and this modulation was found to change in aged rats. In adult nuclei, whereas RA led to high DAG and MAG production through inhibition of their hydrolytic enzymes, DHA and AA promoted high MAG production by LPAPase and DAGL stimulation. In contrast, in aged nuclei RA caused high MAG generation whereas DHA and AA diminished it through LPAPase activity modulation. These results demonstrate that aging promotes a different nuclear lipid metabolism as well as a different type of non-genomic regulation by RA, DHA and AA, which could be involved in nuclear signaling events. PMID:27355428

  14. The functional consequences of age-related changes in microRNA expression in skeletal muscle.

    PubMed

    Soriano-Arroquia, Ana; House, Louise; Tregilgas, Luke; Canty-Laird, Elizabeth; Goljanek-Whysall, Katarzyna

    2016-06-01

    A common characteristic of ageing is disrupted homeostasis between growth and atrophy of skeletal muscle resulting in loss of muscle mass and function, which is associated with sarcopenia. Sarcopenia is related to impaired balance, increased falls and decline in quality of life of older people. Ageing-related transcriptome and proteome changes in skeletal muscle have been characterised, however the molecular mechanisms underlying sarcopenia are still not fully understood. microRNAs are novel regulators of gene expression known to modulate skeletal muscle development and homeostasis. Expression of numerous microRNAs is disrupted in skeletal muscle with age however, the functional consequences of this are not yet understood. Given that a single microRNA can simultaneously affect multiple signalling pathways, microRNAs are potent modulators of pathophysiological changes occurring during ageing. Here we use microRNA and transcript expression profiling together with microRNA functional assays to show that disrupted microRNA:target interactions play an important role in maintaining muscle homeostasis. We identified miR-181a as a regulator of the sirtuin1 (Sirt1) gene expression in skeletal muscle and show that the expression of miR-181a and its target gene is disrupted in skeletal muscle from old mice. Moreover, we show that miR-181a:Sirt1 interactions regulate myotube size. Our results demonstrate that disrupted microRNA:target interactions are likely related to the pathophysiological changes occurring in skeletal muscle during ageing. PMID:26922183

  15. Age related changes and osteochondrosis in swine articular and epiphyseal cartilage: light ane electron microscopy.

    PubMed

    Bhatnagar, R; Christian, R G; Nakano, T; Aherne, F X; Thompson, J R

    1981-04-01

    Age related changes and osteochondrosis in swine were studied using light microscopy and electron microscopy in articular cartilage and light microscopy and epiphyseal cartilage of swine from three days to 30 weeks of age. Thickness, cellularity and vascularity of both the epiphyseal and articular cartilage, decreased as the swine aged. Osteochondrotic changes included formation of "plugs" of cartilage indicating localized failure of ossification and separation and space formation in epiphyseal cartilage. Eosinophilic streaks and space formation in epiphyseal cartilage was observed in relation to epiphyseal separation. Electron microscopy showed a continuous fibrillar layer on the surface of the cartilage corresponding to the lamina splendens of light microscopy. This layer increased in the thickness and showed accumulation of amorphous material between the fibrils with aging. In the matrix, the orientation and distribution of the collagen fibers changed with growth and thicker fibers with clear sub banding were more common in older age groups. Also, necrotic cells, glycogen containing bodies and cellular debris were noticed in the matrix of normal cartilage in old animals. Chondrocytes in the younger cartilage showed accumulation of organelles responsible for protein synthesis; while Golgi bodies, vesicles, lysosomes, well developed foot processes and other inclusions were noticed in older cartilage. Cartilage erosions had a clumped and disrupted lamina splendens on the surface and electron lucent patches in the ground substances of the matrix and chondrocyte cytoplasm. PMID:7260732

  16. The effectiveness of unitization in mitigating age-related relational learning impairments depends on existing cognitive status.

    PubMed

    D'Angelo, Maria C; Smith, Victoria M; Kacollja, Arber; Zhang, Felicia; Binns, Malcolm A; Barense, Morgan D; Ryan, Jennifer D

    2016-11-01

    Binding relations among items in the transverse patterning (TP) task is dependent on the integrity of the hippocampus and its extended network. Older adults have impaired TP learning, corresponding to age-related reductions in hippocampal volumes. Unitization is a training strategy that can mitigate TP impairments in amnesia by reducing reliance on hippocampal-dependent relational binding and increasing reliance on fused representations. Here we examined whether healthy older adults and those showing early signs of cognitive decline would also benefit from unitization. Although both groups of older adults had neuropsychological performance within the healthy range, their TP learning differed both under standard and unitized training conditions. Healthy older adults with impaired TP learning under standard training benefited from unitized training. Older adults who failed the Montreal Cognitive Assessment (MoCA) showed greater impairments under standard conditions, and showed no evidence of improvement with unitization. These individuals' failures to benefit from unitization may be a consequence of early deficits not seen in older adults who pass the MoCA. PMID:27049878

  17. The effectiveness of unitization in mitigating age-related relational learning impairments depends on existing cognitive status

    PubMed Central

    D’Angelo, Maria C.; Smith, Victoria M.; Kacollja, Arber; Zhang, Felicia; Binns, Malcolm A.; Barense, Morgan D.; Ryan, Jennifer D.

    2016-01-01

    ABSTRACT Binding relations among items in the transverse patterning (TP) task is dependent on the integrity of the hippocampus and its extended network. Older adults have impaired TP learning, corresponding to age-related reductions in hippocampal volumes. Unitization is a training strategy that can mitigate TP impairments in amnesia by reducing reliance on hippocampal-dependent relational binding and increasing reliance on fused representations. Here we examined whether healthy older adults and those showing early signs of cognitive decline would also benefit from unitization. Although both groups of older adults had neuropsychological performance within the healthy range, their TP learning differed both under standard and unitized training conditions. Healthy older adults with impaired TP learning under standard training benefited from unitized training. Older adults who failed the Montreal Cognitive Assessment (MoCA) showed greater impairments under standard conditions, and showed no evidence of improvement with unitization. These individuals’ failures to benefit from unitization may be a consequence of early deficits not seen in older adults who pass the MoCA. PMID:27049878

  18. Age-Related Changes in Predictive Capacity Versus Internal Model Adaptability: Electrophysiological Evidence that Individual Differences Outweigh Effects of Age

    PubMed Central

    Bornkessel-Schlesewsky, Ina; Philipp, Markus; Alday, Phillip M.; Kretzschmar, Franziska; Grewe, Tanja; Gumpert, Maike; Schumacher, Petra B.; Schlesewsky, Matthias

    2015-01-01

    Hierarchical predictive coding has been identified as a possible unifying principle of brain function, and recent work in cognitive neuroscience has examined how it may be affected by age–related changes. Using language comprehension as a test case, the present study aimed to dissociate age-related changes in prediction generation versus internal model adaptation following a prediction error. Event-related brain potentials (ERPs) were measured in a group of older adults (60–81 years; n = 40) as they read sentences of the form “The opposite of black is white/yellow/nice.” Replicating previous work in young adults, results showed a target-related P300 for the expected antonym (“white”; an effect assumed to reflect a prediction match), and a graded N400 effect for the two incongruous conditions (i.e. a larger N400 amplitude for the incongruous continuation not related to the expected antonym, “nice,” versus the incongruous associated condition, “yellow”). These effects were followed by a late positivity, again with a larger amplitude in the incongruous non-associated versus incongruous associated condition. Analyses using linear mixed-effects models showed that the target-related P300 effect and the N400 effect for the incongruous non-associated condition were both modulated by age, thus suggesting that age-related changes affect both prediction generation and model adaptation. However, effects of age were outweighed by the interindividual variability of ERP responses, as reflected in the high proportion of variance captured by the inclusion of by-condition random slopes for participants and items. We thus argue that – at both a neurophysiological and a functional level – the notion of general differences between language processing in young and older adults may only be of limited use, and that future research should seek to better understand the causes of interindividual variability in the ERP responses of older adults and its relation to

  19. Age-related cortical thinning in cognitively healthy individuals in their 60s: the PATH Through Life study.

    PubMed

    Shaw, Marnie E; Sachdev, Perminder S; Anstey, Kaarin J; Cherbuin, Nicolas

    2016-03-01

    Although it is recognized that the human cortex thins with age, longitudinal estimates of thinning patterns specific to healthy young-old age (<75 years) individuals are lacking. Importantly, many neurodegenerative disorders first manifest between midlife and old age, and normative estimates may provide a reference for differential change associated with such disorders. Here, we provide longitudinal estimates of cortical thinning observed over 12 years in a large group (n = 396) of healthy individuals, aged 60-66 years at baseline scan, who were scanned with magnetic resonance imaging (1.5T) on 4 occasions. Longitudinal age-related thinning was observed across most of the cortices, with a mean change of -0.3% per year. We measured significant thinning in heteromodal association cortex, with less thinning in regions expected to atrophy later in life (e.g., primary sensory cortex). Men showed more extensive thinning than women. Our comparison of cross-sectional and longitudinal estimates adds to growing evidence that cross-sectional designs may underestimate age-related changes in cortical thickness. PMID:26923417

  20. Age-Related Changes in the Cellular Composition and Epithelial Organization of the Mouse Trachea

    PubMed Central

    Wansleeben, Carolien; Bowie, Emily; Hotten, Danielle F.; Yu, Yen-Rei A.; Hogan, Brigid L. M.

    2014-01-01

    We report here senescent changes in the structure and organization of the mucociliary pseudostratified epithelium of the mouse trachea and main stem bronchi. We confirm previous reports of the gradual appearance of age-related, gland-like structures (ARGLS) in the submucosa, especially in the intercartilage regions and carina. Immunohistochemistry shows these structures contain ciliated and secretory cells and Krt5+ basal cells, but not the myoepithelial cells or ciliated ducts typical of normal submucosal glands. Data suggest they arise de novo by budding from the surface epithelium rather than by delayed growth of rudimentary or cryptic submucosal glands. In old mice the surface epithelium contains fewer cells per unit length than in young mice and the proportion of Krt5+, p63+ basal cells is reduced in both males and females. However, there appears to be no significant difference in the ability of basal stem cells isolated from individual young and old mice to form clonal tracheospheres in culture or in the ability of the epithelium to repair after damage by inhaled sulfur dioxide. Gene expression analysis by Affymetrix microarray and quantitative PCR, as well as immunohistochemistry and flow sorting studies, are consistent with low-grade chronic inflammation in the tracheas of old versus young mice and an increase in the number of immune cells. The significance of these changes for ARGL formation are not clear since several treatments that induce acute inflammation in young mice did not result in budding of the surface epithelium. PMID:24675804

  1. Age-related changes in human vestibulo-ocular reflexes: Sinusoidal rotation and caloric tests

    NASA Technical Reports Server (NTRS)

    Peterka, R. J.; Black, F. O.; Schoenhoff, M. B.

    1989-01-01

    The dynamic response properties of horizontal vestibulo-ocular reflex (VOR) were characterized in 216 human subjects ranging in age from 7 to 81 years. The object of this cross-sectional study was to determine the effects of aging on VOR dynamics, and to identify the distributions of parameters which describe VOR responses to caloric and to sinusoidal rotational stimuli in a putatively normal population. Caloric test parameters showed no consistent trend with age. Rotation test parameters showed declining response amplitude and slightly less compensatory response phase with increasing age. The magnitudes of these changes were not large relative to the variability within the population. The age-related trends in VOR were not consistent with the anatomic changes in the periphery reported by others which showed an increasing rate of peripheral hair cell and nerve fiber loss in subjects over 55 years. The poor correlation between physiological and anatomical data suggest that adaptive mechanisms in the central nervous system are important in maintaining the VOR.

  2. Age-related changes of dental pulp tissue after experimental tooth movement in rats.

    PubMed

    Von Böhl, Martina; Ren, Yijin; Kuijpers-Jagtman, Anne M; Fudalej, Piotr S; Maltha, Jaap C

    2016-01-01

    It is generally accepted that the effect of orthodontic tooth movement on the dental pulp in adolescents is reversible and that it has no long-lasting effect on pulpal physiology. However, it is not clear yet if the same conclusion is also valid for adult subjects. Thus, in two groups of rats, aged 6 and 40 weeks respectively, 3 molars at one side of the maxilla were moved together in a mesial direction with a standardized orthodontic appliance delivering a force of 10 cN. The contralateral side served as a control. Parasagittal histological sections were prepared after tooth movement for 1, 2, 4, 8, and 12 weeks. The pulp tissue was characterized for the different groups, with special emphasis on cell density, inflammatory cells, vascularity, and odontoblasts. Dimensions of dentin and the pulpal horns was determined and related with the duration of orthodontic force application and age ware evaluated. We found that neither in young nor in adult rats, force application led to long-lasting or irreversible changes in pulpal tissues. Dimensional variables showed significant age-related changes. In conclusion, orthodontic tooth movement per se has no long-lasting or irreversible effect on pulpal tissues, neither in the young nor in the adult animals. PMID:26855867

  3. Age-related changes of dental pulp tissue after experimental tooth movement in rats

    PubMed Central

    Von Böhl, Martina; Ren, Yijin; Kuijpers-Jagtman, Anne M.; Maltha, Jaap C.

    2016-01-01

    It is generally accepted that the effect of orthodontic tooth movement on the dental pulp in adolescents is reversible and that it has no long-lasting effect on pulpal physiology. However, it is not clear yet if the same conclusion is also valid for adult subjects. Thus, in two groups of rats, aged 6 and 40 weeks respectively, 3 molars at one side of the maxilla were moved together in a mesial direction with a standardized orthodontic appliance delivering a force of 10 cN. The contralateral side served as a control. Parasagittal histological sections were prepared after tooth movement for 1, 2, 4, 8, and 12 weeks. The pulp tissue was characterized for the different groups, with special emphasis on cell density, inflammatory cells, vascularity, and odontoblasts. Dimensions of dentin and the pulpal horns was determined and related with the duration of orthodontic force application and age ware evaluated. We found that neither in young nor in adult rats, force application led to long-lasting or irreversible changes in pulpal tissues. Dimensional variables showed significant age-related changes. In conclusion, orthodontic tooth movement per se has no long-lasting or irreversible effect on pulpal tissues, neither in the young nor in the adult animals. PMID:26855867

  4. Change in contrast sensitivity functions with Corning CPF filters in patients with age related macular degeneration

    NASA Astrophysics Data System (ADS)

    Rimbergas, Sylvia; Raghuram, Aparna; Boothroyd, Gané; Vatianou, Angelo; Lakshminarayanan, Vasudevan; Stelmack, Joan; Stelmack, Thomas

    2005-09-01

    Do Corning CPF filters change contrast sensitivity in patients with age related macular degeneration (AMD)? A retrospective review was conducted of 54 charts of veterans with AMD receiving comprehensive low vision services at VICTORS (VA Chicago West Side). CSF measurements with the VISTECH 6500 test system were compared before and after introduction of Corning CPF filters. Veterans were asked if filters made a noticeable change in contrast. Pre/post-filter CSF data was obtained for 63 trials at 1?m test distance and 60 trials at the 3?m test distance. To evaluate the data we used an analytic function to fit the contrast sensitivity data previously described by Lakshminarayanan [Optom. Vis. Sci. 72 511 (1995)]. An index was used to compare pre- and post-filter information. Veterans were prescribed filters if improvement in contrast was noted, or a subjective improvement was made. Patients were then contacted post-filter during this retrospective study to determine if the filters still enhanced daily activities. Mean improvement in the contrast sensitivity for each spatial frequency ranged from +0.344 to +0.422 patches with the filters at 1?m and +0.183 to +0.548 patches at 3?m. 87.5% of patients reported improvement in contrast while performing activities of daily living with Corning filters. Paired t test are t = -3.8298 (p?=?0.003) at 1?m and t = -4.957 (p = 0.000 01) at 3?m test distance. While the changes in the CSF with filters are statistically significant and consistent with report of self-improvement by patients, the change in the number of patches on the VISTECH 6500 chart is not clinically significant. Clinical implications are that the chart in its current format is not useful for the prescription of filters leaving patient perception of change as a better guideline.

  5. Age related-changes in the neural basis of self-generation in verbal paired associate learning

    PubMed Central

    Vannest, Jennifer; Maloney, Thomas; Kay, Benjamin; Siegel, Miriam; Allendorfer, Jane B.; Banks, Christi; Altaye, Mekibib; Szaflarski, Jerzy P.

    2015-01-01

    Verbal information is better retained when it is self-generated rather than when it is received passively. The application of self-generation procedures has been found to improve memory in healthy elderly and in individuals with impaired cognition. Overall, the available studies support the notion that active participation in verbal encoding engages memory mechanisms that supplement those used during passive observation. Thus, the objective of this study was to investigate the age-related changes in the neural mechanisms involved in the encoding of paired-associates using a self-generation method that has been shown to improve memory performance across the lifespan. Subjects were 113 healthy right-handed adults (Edinburgh Handedness Inventory >50; 67 females) ages 18–76, native speakers of English with no history of neurological or psychiatric disorders. Subjects underwent fMRI at 3 T while performing didactic learning (“read”) or self-generation learning (“generate”) of 30 word pairs per condition. After fMRI, recognition memory for the second word in each pair was evaluated outside of the scanner. On the post-fMRI testing more “generate” words were correctly recognized than “read” words (p < 0.001) with older adults recognizing the “generated” words less accurately (p < 0.05). Independent component analysis of fMRI data identified task-related brain networks. Several components were positively correlated with the task reflecting multiple cognitive processes involved in self-generated encoding; other components correlated negatively with the task, including components of the default-mode network. Overall, memory performance on generated words decreased with age, but the benefit from self-generation remained consistently significant across ages. Independent component analysis of the neuroimaging data revealed an extensive set of components engaged in self-generation learning compared with didactic learning, and identified areas that were

  6. NMR based biomarkers to study age-related changes in the human quadriceps.

    PubMed

    Azzabou, Noura; Hogrel, Jean-Yves; Carlier, Pierre G

    2015-10-01

    Age-related sarcopenia is a major health issue. To improve elderly person quality of life, it is important to characterize age-associated structural changes within the skeletal muscle. NMR imaging offers quantitative tools to monitor these changes. We scanned 93 subjects: 33 young adults aged between 19 and 27 years old and 60 older adults between 69 and 80 years old. Their physical activity was assessed using a tri-axial accelerometer and they were classified either as active or sedentary. A standard multi-slice multi-echo (MSME) sequence was run and water T2 maps were extracted using a tri-exponential fit. Fat fraction was quantified using three-point Dixon technique. Each quadriceps muscle was characterized by: water T2 mean value, water T2 heterogeneity and the mean fat fraction. Statistical analysis (ANOVA) showed that water T2 mean values and its heterogeneity indices as well as fat fraction were significantly higher in the elderly group (p<0.05). Only fat fraction was significantly lower in the active group compared to the sedentary one (p<0.05). Linear regression confirmed the significant impact of age on these NMR parameters whereas physical activity impact was not systematic. NMR imaging provided a comprehensive assessment of the aging process impact on skeletal muscle composition. Water T2 increase might be related to changes in fiber typology while increased T2 heterogeneities might correlate with some degree of tissue disorganization, like the development of interstitial fibrosis. Fat fraction and water T2 heterogeneity increase was partly slowed down by physical activity. These changes were not gender dependent. PMID:26122131

  7. Age-related changes in urinary testosterone levels suggest differences in puberty onset and divergent life history strategies in bonobos and chimpanzees.

    PubMed

    Behringer, V; Deschner, T; Deimel, C; Stevens, J M G; Hohmann, G

    2014-08-01

    Research on age-related changes in morphology, social behavior, and cognition suggests that the development of bonobos (Pan paniscus) is delayed in comparison to chimpanzees (Pan troglodytes). However, there is also evidence for earlier reproductive maturation in bonobos. Since developmental changes such as reproductive maturation are induced by a number of endocrine processes, changes in hormone levels are indicators of different developmental stages. Age-related changes in testosterone excretion are an indirect marker for the onset of puberty in human and non-human primates. In this study we investigated patterns of urinary testosterone levels in male and female bonobos and chimpanzees to determine the onset of puberty. In contrast to other studies, we found that both species experience age-related changes in urinary testosterone levels. Older individuals of both sexes had significantly higher urinary testosterone levels than younger individuals, indicating that bonobos and chimpanzees experience juvenile pause. The males of both species showed a similar pattern of age-related changes in urinary testosterone levels, with a sharp increase in levels around the age of eight years. This suggests that species-differences in aggression and male mate competition evolved independently of developmental changes in testosterone levels. Females showed a similar pattern of age-related urinary testosterone increase. However, in female bonobos the onset was about three years earlier than in female chimpanzees. The earlier rise of urinary testosterone levels in female bonobos is in line with reports of their younger age of dispersal, and suggests that female bonobos experience puberty at a younger age than female chimpanzees. PMID:25086337

  8. Microperimetric changes in neovascular age-related macular degeneration treated with ranibizumab

    PubMed Central

    Alexander, P; Mushtaq, F; Osmond, C; Amoaku, W

    2012-01-01

    Purpose To assess the value of microperimetry in eyes with neovascular age-related macular degeneration previously treated with ranibizumab and now in the maintenance phase of therapy. Methods A total of 21 eyes (14 patients) were included. Microperimetry was performed using the Macular Integrity Assessment Device on at least three occasions for each eye. Intravitreal ranibizumab was administered if visual acuity (VA) or optical coherence tomography (OCT) showed signs of active disease. Results Five eyes showed no change in VA or OCT findings, and required no intravitreal injections. In these eyes, mean threshold sensitivity (TS) decreased by 13% (paired t-test, P=0.05) during the study period, but fixation stability (FS) was unchanged. In all, 16 eyes showed signs of disease activity, and therefore required ranibizumab injections during the study. In these eyes, VA, central retinal thickness (CRT), FS, and TS remained unchanged during follow-up. Peak TS was noted when CRT was 210 μm; above or below 210 μm, there was a gradual reduction in TS. Conclusion This study has provided novel information on the relationship between macular sensitivity, CRT, and VA in the maintenance phase of ranibizumab therapy. Patients with stable VA and CRT may still have deteriorating retinal sensitivity. This is usually a late manifestation and may indicate subclinical CNV activity. PMID:22322998

  9. Age-related changes in p2 odorant receptor mapping in the olfactory bulb.

    PubMed

    Costanzo, Richard M; Kobayashi, Masayoshi

    2010-06-01

    The ability to identify odors is dependent on the spatial mapping of odorant receptors onto fixed positions within the olfactory bulb. In elderly adults, odor identification and discrimination is often impaired. The objective of this study was to determine if there are age-related changes in odorant receptor mapping. We studied 8 groups of mice ranging in age from 2 weeks to 2.5 years and mapped the projection of P2 odorant receptors onto targeted glomeruli within medial and lateral domains of the olfactory bulb. A total of 60 mice were used to measure the number of P2 glomeruli, bulb length, the position of each glomerulus, and the amount of P2 axons targeting each glomerulus. We found that over 70% of olfactory bulbs contained multiple P2 glomeruli, bulb length increased 42% between the ages of 2 and 13 weeks, and the position of P2 glomeruli shifted with bulb growth. In most cases, targeted glomeruli were either completely or partially filled with P2 axons. In some cases, targeting was diffuse, with glomeruli receiving only a few stray P2-labeled axons. The frequency of diffuse targeting was rare (<4%) in adult mice 3-6 months in age. However, significant increases in diffuse targeting were observed in older mice, reaching 10% at 1 year and 22% at 2 years of age. These findings suggest that odorant receptor mapping becomes more disrupted in old age and could account for impaired olfactory function in elderly adults. PMID:20231263

  10. Age-related changes in red blood cell complement regulatory proteins and susceptibility to severe malaria.

    PubMed

    Waitumbi, John N; Donvito, Béatrice; Kisserli, Aymric; Cohen, Jacques H M; Stoute, José A

    2004-09-15

    Severe malaria-associated anemia and cerebral malaria are life-threatening complications of Plasmodium falciparum infection. Red blood cell (RBC) complement regulatory proteins (CRPs) have been implicated in the pathogenesis of both. We sought to determine whether there are age-related changes in the expression of CRPs that could explain the susceptibility to severe malaria-associated anemia in young children and the susceptibility to cerebral malaria in older children and adults. In cross-sectional surveys in malaria-endemic and -nonendemic areas of Kenya and in Reims, France, the level of RBC CRPs was lowest in young children and increased into adulthood. In case-control studies, patients with cerebral malaria and matched control subjects had higher levels of RBC CRPs than did patients with severe anemia and matched control subjects, especially during convalescence. We conclude that RBC CRP levels vary with age and that the lower levels of these proteins in young children in areas of high transmission, such as western Kenya, may place these children at greater risk of severe malaria-associated anemia than cerebral malaria. PMID:15319870

  11. Use of an Income-Equivalence Scale to Understand Age-Related Changes in Financial Strain

    PubMed Central

    FRANCOEUR, RICHARD BENOIT

    2007-01-01

    Income-equivalence scales (IES) provide distinct advantages over poverty indices to adjust family income for differences in family size, including improved specification of hypothesized causal relationships involving objective measures of economic well-being. In a novel IES application, cancer patients' out-of-pocket health costs are adjusted for differences in family income and size and, along with five other subindices, contribute to an overall index of “objective family financial stress.” Age-related changes are modeled simultaneously within relationships between overall objective family financial stress and subjective patient perceptions about financial strain. Among the findings, the impact of age on one area of subjective financial strain, “difficulty paying bills,” is negative and curvilinear. Regardless of adjusted out-of-pocket costs, as age advances, patients appear increasingly likely to accommodate to financial stress by reporting less difficulty paying bills. This phenomenon could serve to mask and isolate older adults who are foregoing needed yet unaffordable medical care and prescriptions. PMID:18443643

  12. Children's recognition of fairness and others' welfare in a resource allocation task: Age related changes.

    PubMed

    Rizzo, Michael T; Elenbaas, Laura; Cooley, Shelby; Killen, Melanie

    2016-08-01

    The present study investigated age-related changes regarding children's (N = 136) conceptions of fairness and others' welfare in a merit-based resource allocation paradigm. To test whether children at 3- to 5-years-old and 6- to 8-years-old took others' welfare into account when dividing resources, in addition to merit and equality concerns, children were asked to allocate, judge, and reason about allocations of necessary (needed to avoid harm) and luxury (enjoyable to have) resources to a hardworking and a lazy character. While 3- to 5-year-olds did not differentiate between distributing luxury and necessary resources, 6- to 8-year-olds allocated luxury resources more meritoriously than necessary resources. Further, children based their allocations of necessary resources on concerns for others' welfare, rather than merit, even when one character was described as working harder. The findings revealed that, with age, children incorporated the concerns for others' welfare and merit into their conceptions of fairness in a resource allocation context, and prioritized these concerns differently depending on whether they were allocating luxury or necessary resources. Further, with age, children weighed multiple moral concerns including equality, merit, and others' welfare, when determining the fair allocation of resources. (PsycINFO Database Record PMID:27455189

  13. Age-related changes in total protein and collagen metabolism in rat liver.

    PubMed

    Mays, P K; McAnulty, R; Laurent, G J

    1991-12-01

    Liver collagen levels are determined by a balance between synthesis and degradation, processes known to have rapid rates in growing animals. We report age-related changes in liver collagen synthesis and degradation rates, as well as protein synthesis rates, in rats at five ages from 1 to 24 mo. Fractional collagen synthesis rates were determined after injection of [14C]proline with a flooding dose of unlabeled proline and its incorporation as hydroxy-[14C]proline into proteins. Fractional protein synthesis rates were based on the uptake of [14C]proline into proteins. Fractional collagen degradation rates were calculated from the difference between collagen fractional synthesis and deposition rates. Fractional rates of collagen synthesis were similar between 1 mo (23.0% +/- 4.6%/day) and 24 mo (19.6% +/- 3.4%/day) of age. Collagen deposition into the extracellular matrix was extremely low at every age studied; therefore degradation pathways accounted for the bulk of the collagen synthesized. The mean fractional synthesis rate for the total protein pool was unaltered between 1 mo (105.0% +/- 7.2%/day) and 15 mo (89.9% +/- 6.0%/day) of age, after which it increased to 234.9% +/- 33.0%/day (p less than 0.05) by 24 mo of age. These results indicate that liver collagen and total protein synthesis rates were maintained at relatively high levels during development and maturity but that protein synthesis rates were highest in senescent animals. PMID:1959872

  14. Age-related changes in reappraisal of appetitive cravings during adolescence.

    PubMed

    Giuliani, Nicole R; Pfeifer, Jennifer H

    2015-03-01

    The ability to regulate temptation and manage appetitive cravings is an important aspect of healthy adolescent development, but the neural systems underlying this process are understudied. In the present study, 60 healthy females evenly distributed from 10 to 23years of age used reappraisal to regulate the desire to consume personally-craved and not craved unhealthy foods. Reappraisal elicited activity in common self-regulation regions including the dorsal and ventral lateral prefrontal cortex (specifically superior and inferior frontal gyri), dorsal anterior cingulate cortex, and inferior parietal lobule. Viewing personally-craved foods (versus not craved foods) elicited activity in regions including the ventral striatum, as well as more rostral and ventral anterior cingulate cortex extending into the orbitofrontal cortex. Age positively correlated with regulation-related activity in the right inferior frontal gyrus, and negatively correlated with reactivity-related activity in the right superior and dorsolateral prefrontal cortices. Age-adjusted BMI negatively correlated with regulation-related activity in the predominantly left lateralized frontal and parietal regions. These results suggest that the age-related changes seen in the reappraisal of negative emotion may not be as pronounced in the reappraisal of food craving. Therefore, reappraisal of food craving in particular may be an effective way to teach teenagers to manage cravings for other temptations encountered in adolescence, including alcohol, drugs, and unhealthy food. PMID:25536500

  15. Hearing, Cognition, and Healthy Aging: Social and Public Health Implications of the Links between Age-Related Declines in Hearing and Cognition.

    PubMed

    Pichora-Fuller, M Kathleen; Mick, Paul; Reed, Marilyn

    2015-08-01

    Sensory input provides the signals used by the brain when listeners understand speech and participate in social activities with other people in a range of everyday situations. When sensory inputs are diminished, there can be short-term consequences to brain functioning, and long-term deprivation can affect brain neuroplasticity. Indeed, the association between hearing loss and cognitive declines in older adults is supported by experimental and epidemiologic evidence, although the causal mechanisms remain unknown. These interactions of auditory and cognitive aging play out in the challenges confronted by people with age-related hearing problems when understanding speech and engaging in social interactions. In the present article, we use the World Health Organization's International Classification of Functioning, Disability and Health and the Selective Optimization with Compensation models to highlight the importance of adopting a healthy aging perspective that focuses on facilitating active social participation by older adults. First, we examine epidemiologic evidence linking ARHL to cognitive declines and other health issues. Next, we examine how social factors influence and are influenced by auditory and cognitive aging and if they may provide a possible explanation for the association between ARHL and cognitive decline. Finally, we outline how audiologists could reposition hearing health care within the broader context of healthy aging. PMID:27516713

  16. Hearing, Cognition, and Healthy Aging: Social and Public Health Implications of the Links between Age-Related Declines in Hearing and Cognition

    PubMed Central

    Pichora-Fuller, M. Kathleen; Mick, Paul; Reed, Marilyn

    2015-01-01

    Sensory input provides the signals used by the brain when listeners understand speech and participate in social activities with other people in a range of everyday situations. When sensory inputs are diminished, there can be short-term consequences to brain functioning, and long-term deprivation can affect brain neuroplasticity. Indeed, the association between hearing loss and cognitive declines in older adults is supported by experimental and epidemiologic evidence, although the causal mechanisms remain unknown. These interactions of auditory and cognitive aging play out in the challenges confronted by people with age-related hearing problems when understanding speech and engaging in social interactions. In the present article, we use the World Health Organization's International Classification of Functioning, Disability and Health and the Selective Optimization with Compensation models to highlight the importance of adopting a healthy aging perspective that focuses on facilitating active social participation by older adults. First, we examine epidemiologic evidence linking ARHL to cognitive declines and other health issues. Next, we examine how social factors influence and are influenced by auditory and cognitive aging and if they may provide a possible explanation for the association between ARHL and cognitive decline. Finally, we outline how audiologists could reposition hearing health care within the broader context of healthy aging. PMID:27516713

  17. High Resolution Topography of Age-Related Changes in Non-Rapid Eye Movement Sleep Electroencephalography

    PubMed Central

    Sprecher, Kate E.; Riedner, Brady A.; Smith, Richard F.; Tononi, Giulio; Davidson, Richard J.; Benca, Ruth M.

    2016-01-01

    Sleeping brain activity reflects brain anatomy and physiology. The aim of this study was to use high density (256 channel) electroencephalography (EEG) during sleep to characterize topographic changes in sleep EEG power across normal aging, with high spatial resolution. Sleep was evaluated in 92 healthy adults aged 18–65 years old using full polysomnography and high density EEG. After artifact removal, spectral power density was calculated for standard frequency bands for all channels, averaged across the NREM periods of the first 3 sleep cycles. To quantify topographic changes with age, maps were generated of the Pearson’s coefficient of the correlation between power and age at each electrode. Significant correlations were determined by statistical non-parametric mapping. Absolute slow wave power declined significantly with increasing age across the entire scalp, whereas declines in theta and sigma power were significant only in frontal regions. Power in fast spindle frequencies declined significantly with increasing age frontally, whereas absolute power of slow spindle frequencies showed no significant change with age. When EEG power was normalized across the scalp, a left centro-parietal region showed significantly less age-related decline in power than the rest of the scalp. This partial preservation was particularly significant in the slow wave and sigma bands. The effect of age on sleep EEG varies substantially by region and frequency band. This non-uniformity should inform the design of future investigations of aging and sleep. This study provides normative data on the effect of age on sleep EEG topography, and provides a basis from which to explore the mechanisms of normal aging as well as neurodegenerative disorders for which age is a risk factor. PMID:26901503

  18. Decorin expression is important for age-related changes in tendon structure and mechanical properties.

    PubMed

    Dunkman, Andrew A; Buckley, Mark R; Mienaltowski, Michael J; Adams, Sheila M; Thomas, Stephen J; Satchell, Lauren; Kumar, Akash; Pathmanathan, Lydia; Beason, David P; Iozzo, Renato V; Birk, David E; Soslowsky, Louis J

    2013-01-01

    The aging population is at an increased risk of tendon injury and tendinopathy. Elucidating the molecular basis of tendon aging is crucial to understanding the age-related changes in structure and function in this vulnerable tissue. In this study, the structural and functional features of tendon aging are investigated. In addition, the roles of decorin and biglycan in the aging process were analyzed using transgenic mice at both mature and aged time points. Our hypothesis is that the increase in tendon injuries in the aging population is the result of altered structural properties that reduce the biomechanical function of the tendon and consequently increase susceptibility to injury. Decorin and biglycan are important regulators of tendon structure and therefore, we further hypothesized that decreased function in aged tendons is partly the result of altered decorin and biglycan expression. Biomechanical analyses of mature (day 150) and aged (day 570) patellar tendons revealed deteriorating viscoelastic properties with age. Histology and polarized light microscopy demonstrated decreased cellularity, alterations in tenocyte shape, and reduced collagen fiber alignment in the aged tendons. Ultrastructural analysis of fibril diameter distributions indicated an altered distribution in aged tendons with an increase of large diameter fibrils. Aged wild type tendons maintained expression of decorin which was associated with the structural and functional changes seen in aged tendons. Aged patellar tendons exhibited altered and generally inferior properties across multiple assays. However, decorin-null tendons exhibited significantly decreased effects of aging compared to the other genotypes. The amelioration of the functional deficits seen in the absence of decorin in aged tendons was associated with altered tendon fibril structure. Fibril diameter distributions in the decorin-null aged tendons were comparable to those observed in the mature wild type tendon with the absence

  19. Decorin expression is important for age-related changes in tendon structure and mechanical properties

    PubMed Central

    Dunkman, Andrew A.; Buckley, Mark R.; Mienaltowski, Michael J.; Adams, Sheila M.; Thomas, Stephen J.; Satchell, Lauren; Kumar, Akash; Pathmanathan, Lydia; Beason, David P.; Iozzo, Renato V.; Birk, David E.; Soslowsky, Louis J.

    2013-01-01

    The aging population is at an increased risk of tendon injury and tendinopathy. Elucidating the molecular basis of tendon aging is crucial to understanding the age-related changes in structure and function in this vulnerable tissue. In this study, the structural and functional features of tendon aging are investigated. In addition, the roles of decorin and biglycan in the aging process were analyzed using transgenic mice at both mature and aged time points. Our hypothesis is that the increase in tendon injuries in the aging population is the result of altered structural properties that reduce the biomechanical function of the tendon and consequently increase susceptibility to injury. Decorin and biglycan are important regulators of tendon structure and therefore, we further hypothesized that decreased function in aged tendons is partly the result of altered decorin and biglycan expression. Biomechanical analyses of mature (day 150) and aged (day 570) patellar tendons revealed deteriorating viscoelastic properties with age. Histology and polarized light microscopy demonstrated decreased cellularity, alterations in tenocyte shape, and reduced collagen fiber alignment in the aged tendons. Ultrastructural analysis of fibril diameter distributions indicated an altered distribution in aged tendons with an increase of large diameter fibrils. Aged wild type tendons maintained expression of decorin which was associated with the structural and functional changes seen in aged tendons. Aged patellar tendons exhibited altered and generally inferior properties across multiple assays. However, decorin-null tendons exhibited significantly decreased effects of aging compared to the other genotypes. The amelioration of the functional deficits seen in the absence of decorin in aged tendons was associated with altered tendon fibril structure. Fibril diameter distributions in the decorin-null aged tendons were comparable to those observed in the mature wild type tendon with the absence

  20. Age-related gene expression change of GABAergic system in visual cortex of rhesus macaque.

    PubMed

    Liao, Chenghong; Han, Qian; Ma, Yuanye; Su, Bing

    2016-09-30

    Degradation of visual function is a common phenomenon during aging and likely mediated by change in the impaired central visual pathway. Treatment with GABA or its agonist could recover the ability of visual neurons in the primary visual cortex of senescent macaques. However, little is known about how GABAergic system change is related to the aged degradation of visual function in nonhuman primate. With the use of quantitative PCR method, we measured the expression change of 24 GABA related genes in the primary visual cortex (Brodmann's 17) of different age groups. In this study, both of mRNA and protein of glutamic acid decarboxylase (GAD65) were measured by real-time RT-PCR and Western blot, respectively. Results revealed that the level of GAD65 message was not significantly altered, but the proteins were significantly decreased in the aged monkey. As GAD65 plays an important role in GABA synthesis, the down-regulation of GAD65 protein was likely the key factor leading to the observed GABA reduction in the primary visual cortex of the aged macaques. In addition, 7 of 14 GABA receptor genes were up-regulated and one GABA receptor gene was significantly reduced during aging process even after Banjamini correction for multiple comparisons (P<0.05). These results suggested that the dysregulation of GAD65 protein might contribute to some age-related neural visual dysfunctions and most of GABA receptor genes induce a clear indication of compensatory effect for the reduced GABA release in the healthy aged monkey cortex. PMID:27196061

  1. Age related changes and osteochondrosis in swine articular and epiphyseal cartilage: light ane electron microscopy.

    PubMed Central

    Bhatnagar, R; Christian, R G; Nakano, T; Aherne, F X; Thompson, J R

    1981-01-01

    Age related changes and osteochondrosis in swine were studied using light microscopy and electron microscopy in articular cartilage and light microscopy and epiphyseal cartilage of swine from three days to 30 weeks of age. Thickness, cellularity and vascularity of both the epiphyseal and articular cartilage, decreased as the swine aged. Osteochondrotic changes included formation of "plugs" of cartilage indicating localized failure of ossification and separation and space formation in epiphyseal cartilage. Eosinophilic streaks and space formation in epiphyseal cartilage was observed in relation to epiphyseal separation. Electron microscopy showed a continuous fibrillar layer on the surface of the cartilage corresponding to the lamina splendens of light microscopy. This layer increased in the thickness and showed accumulation of amorphous material between the fibrils with aging. In the matrix, the orientation and distribution of the collagen fibers changed with growth and thicker fibers with clear sub banding were more common in older age groups. Also, necrotic cells, glycogen containing bodies and cellular debris were noticed in the matrix of normal cartilage in old animals. Chondrocytes in the younger cartilage showed accumulation of organelles responsible for protein synthesis; while Golgi bodies, vesicles, lysosomes, well developed foot processes and other inclusions were noticed in older cartilage. Cartilage erosions had a clumped and disrupted lamina splendens on the surface and electron lucent patches in the ground substances of the matrix and chondrocyte cytoplasm. Images Fig. 1. Fig. 2 and 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. Fig. 9. Fig. 10 and 11. Fig. 12. Fig. 13. Fig. 14. Fig. 15. Fig. 16. Fig. 17. Fig. 18. PMID:7260732

  2. Age-related changes in intraventricular kinetic energy: a physiological or pathological adaptation?

    PubMed Central

    Wong, James; Chabiniok, Radomir; deVecchi, Adelaide; Dedieu, Nathalie; Sammut, Eva; Schaeffter, Tobias

    2016-01-01

    Aging has important deleterious effects on the cardiovascular system. We sought to compare intraventricular kinetic energy (KE) in healthy subjects of varying ages with subjects with ventricular dysfunction to understand if changes in energetic momentum may predispose individuals to heart failure. Four-dimensional flow MRI was acquired in 35 healthy subjects (age: 1–67 yr) and 10 patients with left ventricular (LV) dysfunction (age: 28–79 yr). Healthy subjects were divided into age quartiles (1st quartile: <16 yr, 2nd quartile: 17–32 yr, 3rd quartile: 33–48 yr, and 4th quartile: 49–64 yr). KE was measured in the LV throughout the cardiac cycle and indexed to ventricular volume. In healthy subjects, two large peaks corresponding to systole and early diastole occurred during the cardiac cycle. A third smaller peak was seen during late diastole in eight adults. Systolic KE (P = 0.182) and ejection fraction (P = 0.921) were preserved through all age groups. Older adults showed a lower early peak diastolic KE compared with children (P < 0.0001) and young adults (P = 0.025). Subjects with LV dysfunction had reduced ejection fraction (P < 0.001) and compared with older healthy adults exhibited a similar early peak diastolic KE (P = 0.142) but with the addition of an elevated KE in diastasis (P = 0.029). In healthy individuals, peak diastolic KE progressively decreases with age, whereas systolic peaks remain constant. Peak diastolic KE in the oldest subjects is comparable to those with LV dysfunction. Unique age-related changes in ventricular diastolic energetics might be physiological or herald subclinical pathology. PMID:26747496

  3. Age-Related Changes in Children’s Associations of Economic Resources and Race

    PubMed Central

    Elenbaas, Laura; Killen, Melanie

    2016-01-01

    Age-related changes in children’s associations of economic resources and race were investigated. The sample (N = 308) included 5–6 year-olds (n = 153, M = 6.01 years, SD = 0.33 years) and 10–11 year-olds (n = 155, M = 11.12 years, SD = 0.59 years) of African–American (n = 93), European–American (n = 92), Latino (n = 62), Asian–American (n = 23), and multi-racial or multi-ethnic (n = 26) background. Participants matched pairs of target children (African–American and European–American) with visual indicators of low, middle, and high economic status. Children’s associations of economic resources with racial groups changed with age, and reflected different associations at high, middle, and low levels of the economic spectrum. Specifically, children associated targets of both races with middle economic status at a comparable rate, and with age, increasingly associated targets of both races with indicators of middle economic status. By contrast, both younger and older children associated African–American targets with indicators of low economic status more frequently than European–American targets. Finally, children associated African–American targets with indicators of high economic status less frequently with age, resulting in a perceived disparity in favor of European–American targets at high economic status among older children that was not present among younger children. No differences were found by participants’ own racial or ethnic background. These results highlight the need to move beyond a dichotomized view (rich or poor) to include middle economic status when examining children’s associations of economic resources and race. PMID:27378981

  4. Age-related changes in the relationship between auditory brainstem responses and envelope-following responses.

    PubMed

    Parthasarathy, Aravindakshan; Datta, Jyotishka; Torres, Julie Ann Luna; Hopkins, Charneka; Bartlett, Edward L

    2014-08-01

    Hearing thresholds and wave amplitudes measured using auditory brainstem responses (ABRs) to brief sounds are the predominantly used clinical measures to objectively assess auditory function. However, frequency-following responses (FFRs) to tonal carriers and to the modulation envelope (envelope-following responses or EFRs) to longer and spectro-temporally modulated stimuli are rapidly gaining prominence as a measure of complex sound processing in the brainstem and midbrain. In spite of numerous studies reporting changes in hearing thresholds, ABR wave amplitudes, and the FFRs and EFRs under neurodegenerative conditions, including aging, the relationships between these metrics are not clearly understood. In this study, the relationships between ABR thresholds, ABR wave amplitudes, and EFRs are explored in a rodent model of aging. ABRs to broadband click stimuli and EFRs to sinusoidally amplitude-modulated noise carriers were measured in young (3-6 months) and aged (22-25 months) Fischer-344 rats. ABR thresholds and amplitudes of the different waves as well as phase-locking amplitudes of EFRs were calculated. Age-related differences were observed in all these measures, primarily as increases in ABR thresholds and decreases in ABR wave amplitudes and EFR phase-locking capacity. There were no observed correlations between the ABR thresholds and the ABR wave amplitudes. Significant correlations between the EFR amplitudes and ABR wave amplitudes were observed across a range of modulation frequencies in the young. However, no such significant correlations were found in the aged. The aged click ABR amplitudes were found to be lower than would be predicted using a linear regression model of the young, suggesting altered gain mechanisms in the relationship between ABRs and FFRs with age. These results suggest that ABR thresholds, ABR wave amplitudes, and EFRs measure complementary aspects of overlapping neurophysiological processes and the relationships between these

  5. Age-Related Changes in Children's Associations of Economic Resources and Race.

    PubMed

    Elenbaas, Laura; Killen, Melanie

    2016-01-01

    Age-related changes in children's associations of economic resources and race were investigated. The sample (N = 308) included 5-6 year-olds (n = 153, M = 6.01 years, SD = 0.33 years) and 10-11 year-olds (n = 155, M = 11.12 years, SD = 0.59 years) of African-American (n = 93), European-American (n = 92), Latino (n = 62), Asian-American (n = 23), and multi-racial or multi-ethnic (n = 26) background. Participants matched pairs of target children (African-American and European-American) with visual indicators of low, middle, and high economic status. Children's associations of economic resources with racial groups changed with age, and reflected different associations at high, middle, and low levels of the economic spectrum. Specifically, children associated targets of both races with middle economic status at a comparable rate, and with age, increasingly associated targets of both races with indicators of middle economic status. By contrast, both younger and older children associated African-American targets with indicators of low economic status more frequently than European-American targets. Finally, children associated African-American targets with indicators of high economic status less frequently with age, resulting in a perceived disparity in favor of European-American targets at high economic status among older children that was not present among younger children. No differences were found by participants' own racial or ethnic background. These results highlight the need to move beyond a dichotomized view (rich or poor) to include middle economic status when examining children's associations of economic resources and race. PMID:27378981

  6. Age-related changes in intraventricular kinetic energy: a physiological or pathological adaptation?

    PubMed

    Wong, James; Chabiniok, Radomir; deVecchi, Adelaide; Dedieu, Nathalie; Sammut, Eva; Schaeffter, Tobias; Razavi, Reza

    2016-03-15

    Aging has important deleterious effects on the cardiovascular system. We sought to compare intraventricular kinetic energy (KE) in healthy subjects of varying ages with subjects with ventricular dysfunction to understand if changes in energetic momentum may predispose individuals to heart failure. Four-dimensional flow MRI was acquired in 35 healthy subjects (age: 1-67 yr) and 10 patients with left ventricular (LV) dysfunction (age: 28-79 yr). Healthy subjects were divided into age quartiles (1st quartile: <16 yr, 2nd quartile: 17-32 yr, 3rd quartile: 33-48 yr, and 4th quartile: 49-64 yr). KE was measured in the LV throughout the cardiac cycle and indexed to ventricular volume. In healthy subjects, two large peaks corresponding to systole and early diastole occurred during the cardiac cycle. A third smaller peak was seen during late diastole in eight adults. Systolic KE (P = 0.182) and ejection fraction (P = 0.921) were preserved through all age groups. Older adults showed a lower early peak diastolic KE compared with children (P < 0.0001) and young adults (P = 0.025). Subjects with LV dysfunction had reduced ejection fraction (P < 0.001) and compared with older healthy adults exhibited a similar early peak diastolic KE (P = 0.142) but with the addition of an elevated KE in diastasis (P = 0.029). In healthy individuals, peak diastolic KE progressively decreases with age, whereas systolic peaks remain constant. Peak diastolic KE in the oldest subjects is comparable to those with LV dysfunction. Unique age-related changes in ventricular diastolic energetics might be physiological or herald subclinical pathology. PMID:26747496

  7. Age-Related Changes in Processing Simultaneous Amplitude Modulated Sounds Assessed Using Envelope Following Responses.

    PubMed

    Parthasarathy, Aravindakshan; Lai, Jesyin; Bartlett, Edward L

    2016-04-01

    Listening conditions in the real world involve segregating the stimuli of interest from competing auditory stimuli that differ in their sound level and spectral content. It is in these conditions of complex spectro-temporal processing that listeners with age-related hearing loss experience the most difficulties. Envelope following responses (EFRs) provide objective neurophysiological measures of auditory processing. EFRs were obtained to two simultaneous sinusoidally amplitude modulated (sAM) tones from young and aged Fischer-344 rats. One was held at a fixed suprathreshold sound level (sAM1FL) while the second varied in sound level (sAM2VL) and carrier frequency. EFR amplitudes to sAM1FL in the young decreased with signal-to-noise ratio (SNR), and this reduction was more pronounced when the sAM2VL carrier frequency was spectrally separated from sAM1FL. Aged animals showed similar trends, while having decreased overall response amplitudes compared to the young. These results were replicated using an established computational model of the auditory nerve. The trends observed in the EFRs were shown to be due to the contributions of the low-frequency tails of high-frequency neurons, rather than neurons tuned to the sAM1FL carrier frequency. Modeling changes in threshold and neural loss reproduced some of the changes seen with age, but accuracy improved when combined with an additional decrease representing synaptic loss of auditory nerve neurons. Sound segregation in this case derives primarily from peripheral processing, regardless of age. Contributions by more central neural mechanisms are likely to occur only at low SNRs. PMID:26905273

  8. Glaucomatous and Age-Related Changes in Corneal Pulsation Shape. The Ocular Dicrotism

    PubMed Central

    Danielewska, Monika E.; Krzyżanowska-Berkowska, Patrycja; Iskander, D. Robert

    2014-01-01

    Purpose To ascertain whether the incidence of ocular dicrotic pulse (ODP) increases with age, it is more pronounced in glaucomatous than in normal eyes and whether it is related to cardiovascular activity. Methods 261 subjects aged 47 to 78 years were included in the study and classified into four groups: primary open angle glaucoma (POAG), primary angle-closure glaucoma (PACG), glaucoma suspects with glaucomatous optic disc appearance (GODA) and the controls (CG). Additionally, in each group, subjects with ODP were divided into two age subgroups around the median age. A non-contact ultrasonic method was used to measure corneal indentation pulse (CIP) synchronically with the acquisition of electrocardiography (ECG) and blood pulse signals. ODP was assessed from the acquired signals that were numerically processed in a custom written program. Results ODP incidence was about 78%, 66%, 66% and 84% for CG, GODA, POAG, and PACG group, respectively. With advancing age, the ODP incidence increased for all subjects (Δ = 12%), the highest being for the PACG and POAG groups (Δ = 30%). GODA group did not show an age-related increase in the incidence of ODP. Conclusions The ocular dicrotism, measured with non-contact ultrasonic method, was found to be a common phenomenon in elderly subjects. The increased ODP incidence in PACG and POAG group may correspond to either higher stiffness of glaucoma eyes, biochemical abnormalities in eye tissues, changes in ocular hemodynamics, may reflect the effect of medications or be a combination of all those factors. The results of GODA group suggest different mechanisms governing their ocular pulse that makes them less susceptible to generating ODP and having decreased predisposition to glaucoma. PMID:25032962

  9. A Study on the Age-Related Changes in Hepatitis B and C Virus Serology

    PubMed Central

    Guclu, Ertugrul; Ogutlu, Aziz; Karabay, Oguz

    2016-01-01

    Objective: There are a limited number of studies on the seroprevalence of Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infection in Turkey. This study aimed to compare HBV and HCV seroprevalence rates before and after the implementation of national hepatitis B vaccination program (NHPVP) and to explore age-related changes in the seroprevalences. Materials and Methods: Results of Hepatitis B surface antigen (HBsAg), Hepatitis B virus surface antibody (antiHBs) and anti-HCV tests performed during 2009 and 2010 in a state hospital laboratory were reviewed retrospectively. As NHPVP was started in 1998, 12 years of age and younger children were considered post- NHPVP period subjects. Results: A total of 3280 HBsAg, 2444 antiHBs and 3188 anti-HCV test results were reviewed, representing approximately 3% of the population of the city where the study was conducted. HBsAg, antiHBs and anti-HCV positivity were 3.2%, 36.12% and 0.97%, respectively. HBsAg and antiHBs positivity were higher among males (p<0.001). When assessed by age groups, HBsAg positivity was found to be the lowest in the age group 0–12 and highest in the age group 51–60. HBsAg positivity was lower in the post-NHPVP period versus pre-NHPVP period (p=0.01). Anti-HCV positivity was similar for pre- and post- NHPVP periods (p>0.05). Conclusion: Owing to the use of NHPVP, HBsAg seropositivity has decreased, and it is expected to decrease further in the next years with a wider implementation of the program. Efforts should be continued to increase the level of awareness in the community for HBV and the importance of immunization. PMID:27026763

  10. UV-induced retinal proteome changes in the rat model of age-related macular degeneration.

    PubMed

    Kraljević Pavelić, Sandra; Klobučar, Marko; Sedić, Mirela; Micek, Vedran; Gehrig, Peter; Grossman, Jonas; Pavelić, Krešimir; Vojniković, Božidar

    2015-09-01

    Age-related macular degeneration (AMD) is characterized by irreversible damage of photoreceptors in the central posterior part of the retina, called the macula and is the most common cause of vision loss in those aged over 50. A growing body of evidence shows that cumulative long-term exposure to UV radiation may be harmful to the retina and possibly leads to AMD irrespective of age. In spite of many research efforts, cellular and molecular mechanisms leading to UV-induced retinal damage and possibly retinal diseases such as AMD are not completely understood. In the present study we explored damage mechanisms accounting for UV-induced retinal phototoxicity in the rats exposed to UVA and UVB irradiation using a proteomics approach. Our study showed that UV irradiation induces profound changes in the retinal proteomes of the rats associated with the disruption of energy homeostasis, oxidative stress, DNA damage response and structural and functional impairments of the interphotoreceptor matrix components and their cell surface receptors such as galectins. Two small leucine-rich proteoglycans, biglycan and lumican, were identified as phototoxicity biomarkers associated with UV-induced disruption of interphotoreceptor matrix (IPM). In addition, UVB induced activation of Src kinase, which could account for cytoskeletal rearrangements in the retina was observed at the proteomics level. Pharmacological intervention either to target Src kinase with the aim of preventing cytoskeletal rearrangements in the retinal pigment epithelium (RPE) and neuronal retina or to help rebuild damaged IPM may provide fresh avenues of treatment for patients suffering from AMD. PMID:26071645

  11. Investigating Age-Related Changes in Fine Motor Control Across Different Effectors and the Impact of White Matter Integrity

    PubMed Central

    Holtrop, Joseph L.; Loucks, Torrey M; Sosnoff, Jacob J; Sutton, Bradley P

    2014-01-01

    Changes in fine motor control that eventually compromise dexterity accompany advanced age; however there is evidence that age-related decline in motor control may not be uniform across effectors. Particularly, the role of central mechanisms in effector-specific decline has not been examined but is relevant for placing age-related motor declines into the growing literature of age-related changes in brain function. We examined sub-maximal force control across three different effectors (fingers, lips, and tongue) in 18 young and 14 older adults. In parallel with the force variability measures we examined changes in white matter structural integrity in effector-specific pathways in the brain with diffusion tensor imaging (DTI). Motor pathways for each effector were identified by using an fMRI localizer task followed by tractography to identify the fiber tracts propagating to the midbrain. Increases in force control variability were found with age in all three effectors but the effectors showed different degrees of age-related variability. Motor control changes were accompanied by a decline in white matter structural integrity with age shown by measures of fractional anisotropy and radial diffusivity. The DTI metrics appear to mediate some of the age-related declines in motor control. Our findings indicate that the structural integrity of descending motor systems may play a significant role in age-related increases in motor performance variability, but that differential age-related declines in oral and manual effectors are not likely due to structural integrity of descending motor pathways in the brain. PMID:24657352

  12. Hippocampal expression of myelin-associated inhibitors is induced with age-related cognitive decline and correlates with deficits of spatial learning and memory

    PubMed Central

    VanGuilder, Heather D.; Bixler, Georgina V.; Sonntag, William E.; Freeman, Willard M.

    2012-01-01

    Impairment of cognitive functions including hippocampus-dependent spatial learning and memory affects nearly half of the aged population. Age-related cognitive decline is associated with synaptic dysfunction that occurs in the absence of neuronal cell loss, suggesting that impaired neuronal signaling and plasticity may underlie age-related deficits of cognitive function. Expression of myelin-associated inhibitors (MAIs) of synaptic plasticity, including the ligands MAG, Nogo-A, and OMgp, and their common receptor, NgR1, was examined in hippocampal synaptosomes and CA1, CA3 and DG subregions derived from adult (12–13 months) and aged (26–28 months) Fischer 344 × Brown Norway rats. Rats were behaviorally phenotyped by Morris water maze testing and classified as aged cognitively intact (n=7–8) or aged cognitively impaired (n=7–10) relative to adults (n=5–7). MAI protein expression was induced in cognitively impaired, but not cognitively intact, aged rats and correlated with cognitive performance in individual rats. Immunohistochemical experiments demonstrated that upregulation of MAIs occurs, in part, in hippocampal neuronal axons and somata. While a number of pathways and processes are altered with brain aging, we report a coordinated induction of myelin-associated inhibitors of functional and structural plasticity only in cognitively impaired aged rats. Induction of MAIs may decrease stimulus-induced synaptic strengthening and structural remodeling, ultimately impairing synaptic mechanisms of spatial learning and memory and resulting in cognitive decline. PMID:22269040

  13. Age-related striatal BOLD changes without changes in behavioral loss aversion

    PubMed Central

    Viswanathan, Vijay; Lee, Sang; Gilman, Jodi M.; Kim, Byoung Woo; Lee, Nick; Chamberlain, Laura; Livengood, Sherri L.; Raman, Kalyan; Lee, Myung Joo; Kuster, Jake; Stern, Daniel B.; Calder, Bobby; Mulhern, Frank J.; Blood, Anne J.; Breiter, Hans C.

    2015-01-01

    Loss aversion (LA), the idea that negative valuations have a higher psychological impact than positive ones, is considered an important variable in consumer research. The literature on aging and behavior suggests older individuals may show more LA, although it is not clear if this is an effect of aging in general (as in the continuum from age 20 and 50 years), or of the state of older age (e.g., past age 65 years). We also have not yet identified the potential biological effects of aging on the neural processing of LA. In the current study we used a cohort of subjects with a 30 year range of ages, and performed whole brain functional MRI (fMRI) to examine the ventral striatum/nucleus accumbens (VS/NAc) response during a passive viewing of affective faces with model-based fMRI analysis incorporating behavioral data from a validated approach/avoidance task with the same stimuli. Our a priori focus on the VS/NAc was based on (1) the VS/NAc being a central region for reward/aversion processing; (2) its activation to both positive and negative stimuli; (3) its reported involvement with tracking LA. LA from approach/avoidance to affective faces showed excellent fidelity to published measures of LA. Imaging results were then compared to the behavioral measure of LA using the same affective faces. Although there was no relationship between age and LA, we observed increasing neural differential sensitivity (NDS) of the VS/NAc to avoidance responses (negative valuations) relative to approach responses (positive valuations) with increasing age. These findings suggest that a central region for reward/aversion processing changes with age, and may require more activation to produce the same LA behavior as in younger individuals, consistent with the idea of neural efficiency observed with high IQ individuals showing less brain activation to complete the same task. PMID:25983682

  14. Age-related striatal BOLD changes without changes in behavioral loss aversion.

    PubMed

    Viswanathan, Vijay; Lee, Sang; Gilman, Jodi M; Kim, Byoung Woo; Lee, Nick; Chamberlain, Laura; Livengood, Sherri L; Raman, Kalyan; Lee, Myung Joo; Kuster, Jake; Stern, Daniel B; Calder, Bobby; Mulhern, Frank J; Blood, Anne J; Breiter, Hans C

    2015-01-01

    Loss aversion (LA), the idea that negative valuations have a higher psychological impact than positive ones, is considered an important variable in consumer research. The literature on aging and behavior suggests older individuals may show more LA, although it is not clear if this is an effect of aging in general (as in the continuum from age 20 and 50 years), or of the state of older age (e.g., past age 65 years). We also have not yet identified the potential biological effects of aging on the neural processing of LA. In the current study we used a cohort of subjects with a 30 year range of ages, and performed whole brain functional MRI (fMRI) to examine the ventral striatum/nucleus accumbens (VS/NAc) response during a passive viewing of affective faces with model-based fMRI analysis incorporating behavioral data from a validated approach/avoidance task with the same stimuli. Our a priori focus on the VS/NAc was based on (1) the VS/NAc being a central region for reward/aversion processing; (2) its activation to both positive and negative stimuli; (3) its reported involvement with tracking LA. LA from approach/avoidance to affective faces showed excellent fidelity to published measures of LA. Imaging results were then compared to the behavioral measure of LA using the same affective faces. Although there was no relationship between age and LA, we observed increasing neural differential sensitivity (NDS) of the VS/NAc to avoidance responses (negative valuations) relative to approach responses (positive valuations) with increasing age. These findings suggest that a central region for reward/aversion processing changes with age, and may require more activation to produce the same LA behavior as in younger individuals, consistent with the idea of neural efficiency observed with high IQ individuals showing less brain activation to complete the same task. PMID:25983682

  15. Age-Related Changes in Inter-Network Connectivity by Component Analysis

    PubMed Central

    La, Christian; Mossahebi, Pouria; Nair, Veena A.; Bendlin, Barbara B.; Birn, Rasmus; Meyerand, Mary E.; Prabhakaran, Vivek

    2015-01-01

    Healthy aging is associated with brain changes that reflect an alteration to a functional unit in response to the available resources and architecture. Even before the onset of noticeable cognitive decline, the neural scaffolds underlying cognitive function undergo considerable change. Prior studies have suggested a disruption of the connectivity pattern within the “default-mode” network (DMN), and more specifically a disruption of the anterio-posterior connectivity. In this study, we explored the effects of aging on within-network connectivity of three DMN subnetworks: a posterior DMN (pDMN), an anterior DMN (aDMN), and a ventral DMN (vDMN); as well as between-network connectivity during resting-state. Using groupICA on 43 young and 43 older healthy adults, we showed a reduction of network co-activation in two of the DMN subnetworks (pDMN and aDMN) and demonstrated a difference in between-component connectivity levels. The older group exhibited more numerous high-correlation pairs (Pearson's rho > 0.3, Number of comp-pairs = 46) in comparison to the young group (Number of comp-pairs = 34), suggesting a more connected/less segregated cortical system. Moreover, three component-pairs exhibited statistically significant differences between the two populations. Visual areas V2–V1 and V2–V4 were more correlated in the older adults, while aDMN–pDMN correlation decreased with aging. The increase in the number of high-correlation component-pairs and the elevated correlation in the visual areas are consistent with the prior hypothesis that aging is associated with a reduction of functional segregation. However, the aDMN-pDMN dis-connectivity may be occurring under a different mechanism, a mechanism more related to a breakdown of structural integrity along the anterio-posterior axis. PMID:26733864

  16. Role of DHA in aging-related changes in mouse brain synaptic plasma membrane proteome.

    PubMed

    Sidhu, Vishaldeep K; Huang, Bill X; Desai, Abhishek; Kevala, Karl; Kim, Hee-Yong

    2016-05-01

    Aging has been related to diminished cognitive function, which could be a result of ineffective synaptic function. We have previously shown that synaptic plasma membrane proteins supporting synaptic integrity and neurotransmission were downregulated in docosahexaenoic acid (DHA)-deprived brains, suggesting an important role of DHA in synaptic function. In this study, we demonstrate aging-induced synaptic proteome changes and DHA-dependent mitigation of such changes using mass spectrometry-based protein quantitation combined with western blot or messenger RNA analysis. We found significant reduction of 15 synaptic plasma membrane proteins in aging brains including fodrin-α, synaptopodin, postsynaptic density protein 95, synaptic vesicle glycoprotein 2B, synaptosomal-associated protein 25, synaptosomal-associated protein-α, N-methyl-D-aspartate receptor subunit epsilon-2 precursor, AMPA2, AP2, VGluT1, munc18-1, dynamin-1, vesicle-associated membrane protein 2, rab3A, and EAAT1, most of which are involved in synaptic transmission. Notably, the first 9 proteins were further reduced when brain DHA was depleted by diet, indicating that DHA plays an important role in sustaining these synaptic proteins downregulated during aging. Reduction of 2 of these proteins was reversed by raising the brain DHA level by supplementing aged animals with an omega-3 fatty acid sufficient diet for 2 months. The recognition memory compromised in DHA-depleted animals was also improved. Our results suggest a potential role of DHA in alleviating aging-associated cognitive decline by offsetting the loss of neurotransmission-regulating synaptic proteins involved in synaptic function. PMID:27103520

  17. Projected changes in age-related macular degeneration and driving license holders in Finland

    PubMed Central

    Viitanen, Olli; Arjamaa, Olli

    2014-01-01

    Purpose The aim of the study was to approximate the occurrence of all forms of age-related macular degeneration (AMD) of the retina among the driving license holders aged 80 or more, and to project the changes to 2030 in Finland. AMD, destroying the visual cells in the central part of the retina, is a common disease of older age: one out of three individuals aged 70 or older shows early signs of AMD progressing later to relentless loss of vision. This eye disease can be detected only by an ophthalmologist. In general, little is known about the prevalence of AMD among driving license holders aged 80 or older. Methods At first the prevalence of individuals with either drusen or AMD in Finland among those 80 or older was approximated. Then the number of license holders in this age group was extracted from the statistics of the Finnish Transport Safety Agency and Eurostat provided us with the demographical data. The changes were projected to 2030. Results In Finland, with a population of 5.35 million, the number of those aged 80 or over will increase by 175,000 by 2030. The total number of individuals with either drusen or AMD will increase from 118,000 to 193,000 by the year 2030 and an increasing proportion of them will have a driving license. The proportion of women in 2012 having a driving license in the groups 60 or younger is about 45%, while in those aged 80 or older it is only 20%. Conclusion The number of people aged 80 years or older will increase in Finland by 2030. The number of those in this age group having a driving license will increase more rapidly as the population ages because the proportion of women with a driving license will increase in this age group. As the prevalence of drusen and AMD among women aged 80 or over is higher than among men at comparable age, this means that AMD will increase even more rapidly among drivers in this age group. PMID:25284977

  18. Age-related effects on spatial memory across viewpoint changes relative to different reference frames.

    PubMed

    Montefinese, Maria; Sulpizio, Valentina; Galati, Gaspare; Committeri, Giorgia

    2015-07-01

    Remembering object positions across different views is a fundamental competence for acting and moving appropriately in a large-scale space. Behavioural and neurological changes in elderly subjects suggest that the spatial representations of the environment might decline compared to young participants. However, no data are available on the use of different reference frames within topographical space in aging. Here we investigated the use of allocentric and egocentric frames in aging, by asking young and older participants to encode the location of a target in a virtual room relative either to stable features of the room (allocentric environment-based frame), or to an unstable objects set (allocentric objects-based frame), or to the viewer's viewpoint (egocentric frame). After a viewpoint change of 0° (absent), 45° (small) or 135° (large), participants judged whether the target was in the same spatial position as before relative to one of the three frames. Results revealed a different susceptibility to viewpoint changes in older than young participants. Importantly, we detected a worst performance, in terms of reaction times, for older than young participants in the allocentric frames. The deficit was more marked for the environment-based frame, for which a lower sensitivity was revealed as well as a worst performance even when no viewpoint change occurred. Our data provide new evidence of a greater vulnerability of the allocentric, in particular environment-based, spatial coding with aging, in line with the retrogenesis theory according to which cognitive changes in aging reverse the sequence of acquisition in mental development. PMID:25037856

  19. Multispectral MRI segmentation of age related white matter changes using a cascade of support vector machines.

    PubMed

    Damangir, Soheil; Manzouri, Amirhossein; Oppedal, Ketil; Carlsson, Stefan; Firbank, Michael J; Sonnesyn, Hogne; Tysnes, Ole-Bjørn; O'Brien, John T; Beyer, Mona K; Westman, Eric; Aarsland, Dag; Wahlund, Lars-Olof; Spulber, Gabriela

    2012-11-15

    White matter changes (WMC) are the focus of intensive research and have been linked to cognitive impairment and depression in the elderly. Cumbersome manual outlining procedures make research on WMC labor intensive and prone to subjective bias. We present a fast, fully automated method for WMC segmentation using a cascade of reduced support vector machines (SVMs) with active learning. Data of 102 subjects was used in this study. Two MRI sequences (T1-weighted and FLAIR) and masks of manually outlined WMC from each subject were used for the image analysis. The segmentation framework comprises pre-processing, classification (training and core segmentation) and post-processing. After pre-processing, the model was trained on two subjects and tested on the remaining 100 subjects. The effectiveness and robustness of the classification was assessed using the receiver operating curve technique. The cascade of SVMs segmentation framework outputted accurate results with high sensitivity (90%) and specificity (99.5%) values, with the manually outlined WMC as reference. An algorithm for the segmentation of WMC is proposed. This is a completely competitive and fast automatic segmentation framework, capable of using different input sequences, without changes or restrictions of the image analysis algorithm. PMID:22921728

  20. A BOLD Perspective on Age-Related Neurometabolic-Flow Coupling and Neural Efficiency Changes in Human Visual Cortex.

    PubMed

    Hutchison, Joanna Lynn; Shokri-Kojori, Ehsan; Lu, Hanzhang; Rypma, Bart

    2013-01-01

    Age-related performance declines in visual tasks have been attributed to reductions in processing efficiency. The neural basis of these declines has been explored by comparing the blood-oxygen-level-dependent (BOLD) index of neural activity in older and younger adults during visual task performance. However, neural activity is one of many factors that change with age and lead to BOLD signal differences. We investigated the origin of age-related BOLD changes by comparing blood flow and oxygen metabolic constituents of BOLD signal. Subjects periodically viewed flickering annuli and pressed a button when detecting luminance changes in a central fixation cross. Using magnetic resonance dual-echo arterial spin labeling and CO2 ingestion, we observed age-equivalent (i.e., similar in older and younger groups) fractional cerebral blood flow (ΔCBF) in the presence of age-related increases in fractional cerebral metabolic rate of oxygen (ΔCMRO2). Reductions in ΔCBF responsiveness to increased ΔCMRO2 in elderly led to paradoxical age-related BOLD decreases. Age-related ΔCBF/ΔCMRO2 ratio decreases were associated with reaction times, suggesting that age-related slowing resulted from less efficient neural activity. We hypothesized that reduced vascular responsiveness to neural metabolic demand would lead to a reduction in ΔCBF/ΔCMRO2. A simulation of BOLD relative to ΔCMRO2 for lower and higher neurometabolic-flow coupling ratios (approximating those for old and young, respectively) indicated less BOLD signal change in old than young in relatively lower CMRO2 ranges, as well as greater BOLD signal change in young compared to old in relatively higher CMRO2 ranges. These results suggest that age-comparative studies relying on BOLD signal might be misinterpreted, as age-related BOLD changes do not merely reflect neural activity changes. Age-related declines in neurometabolic-flow coupling might lead to neural efficiency reductions that can adversely affect visual task

  1. Hope for the best, prepare for the worst? Future self-views and preparation for age-related changes.

    PubMed

    Kornadt, Anna E; Voss, Peggy; Rothermund, Klaus

    2015-12-01

    Extending research on the impact of views on aging and developmental regulation across the life span, we tested the hypothesis that more positive views of oneself as an older person predict more preparation for age-related changes. Drawing on recent evidence regarding the domain specificity of aging-related developmental processes, we assumed this relationship to be moderated by the relevance of preparation in different life domains for different age groups. We investigated these research questions in a longitudinal study that assessed future self-views and preparation for different life domains in a sample covering a large part of the adult life span. Findings supported our hypotheses: More positive/negative personal views of one's own aging at T1 predicted subsequent increases/decreases in preparation, with influences being strongest for those domains in which relevant age-related changes are expected to occur for the respective age groups. Our study provides additional evidence for the idea that views on aging shape development, identifying age-related provision making as an important mediating process. Furthermore, our findings highlight the added value of a domain-specific approach that takes the differential relevance of life domains and age-related developmental tasks into account. PMID:26302028

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

    NASA Technical Reports Server (NTRS)

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

    1989-01-01

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

  3. Brain site-specific proteome changes in aging-related dementia

    PubMed Central

    Manavalan, Arulmani; Mishra, Manisha; Feng, Lin; Sze, Siu Kwan; Akatsu, Hiroyasu; Heese, Klaus

    2013-01-01

    This study is aimed at gaining insights into the brain site-specific proteomic senescence signature while comparing physiologically aged brains with aging-related dementia brains (for example, Alzheimer's disease (AD)). Our study of proteomic differences within the hippocampus (Hp), parietal cortex (pCx) and cerebellum (Cb) could provide conceptual insights into the molecular mechanisms involved in aging-related neurodegeneration. Using an isobaric tag for relative and absolute quantitation (iTRAQ)-based two-dimensional liquid chromatography coupled with tandem mass spectrometry (2D-LC-MS/MS) brain site-specific proteomic strategy, we identified 950 proteins in the Hp, pCx and Cb of AD brains. Of these proteins, 31 were significantly altered. Most of the differentially regulated proteins are involved in molecular transport, nervous system development, synaptic plasticity and apoptosis. Particularly, proteins such as Gelsolin (GSN), Tenascin-R (TNR) and AHNAK could potentially act as novel biomarkers of aging-related neurodegeneration. Importantly, our Ingenuity Pathway Analysis (IPA)-based network analysis further revealed ubiquitin C (UBC) as a pivotal protein to interact with diverse AD-associated pathophysiological molecular factors and suggests the reduced ubiquitin proteasome degradation system (UPS) as one of the causative factors of AD. PMID:24008896

  4. Age-related changes in the intrinsic functional connectivity of the human ventral vs. dorsal striatum from childhood to middle age.

    PubMed

    Porter, James N; Roy, Amy K; Benson, Brenda; Carlisi, Christina; Collins, Paul F; Leibenluft, Ellen; Pine, Daniel S; Luciana, Monica; Ernst, Monique

    2015-02-01

    The striatum codes motivated behavior. Delineating age-related differences within striatal circuitry can provide insights into neural mechanisms underlying ontogenic behavioral changes and vulnerabilities to mental disorders. To this end, a dual ventral/dorsal model of striatal function was examined using resting state intrinsic functional connectivity (iFC) imaging in 106 healthy individuals, ages 9-44. Broadly, the dorsal striatum (DS) is connected to prefrontal and parietal cortices and contributes to cognitive processes; the ventral striatum (VS) is connected to medial orbitofrontal and anterior cingulate cortices, and contributes to affective valuation and motivation. Findings revealed patterns of age-related changes that differed between VS and DS iFCs. We found an age-related increase in DS iFC with posterior cingulate cortex (pCC) that stabilized after the mid-twenties, but a decrease in VS iFC with anterior insula (aIns) and dorsal anterior cingulate cortex (dACC) that persisted into mid-adulthood. These distinct developmental trajectories of VS vs. DS iFC might underlie adolescents' unique behavioral patterns and vulnerabilities to psychopathology, and also speaks to changes in motivational networks that extend well past 25 years old. PMID:25257972

  5. Normal age-related brain morphometric changes: nonuniformity across cortical thickness, surface area and gray matter volume?

    PubMed

    Lemaitre, Herve; Goldman, Aaron L; Sambataro, Fabio; Verchinski, Beth A; Meyer-Lindenberg, Andreas; Weinberger, Daniel R; Mattay, Venkata S

    2012-03-01

    Normal aging is accompanied by global as well as regional structural changes. While these age-related changes in gray matter volume have been extensively studied, less has been done using newer morphological indexes, such as cortical thickness and surface area. To this end, we analyzed structural images of 216 healthy volunteers, ranging from 18 to 87 years of age, using a surface-based automated parcellation approach. Linear regressions of age revealed a concomitant global age-related reduction in cortical thickness, surface area and volume. Cortical thickness and volume collectively confirmed the vulnerability of the prefrontal cortex, whereas in other cortical regions, such as in the parietal cortex, thickness was the only measure sensitive to the pronounced age-related atrophy. No cortical regions showed more surface area reduction than the global average. The distinction between these morphological measures may provide valuable information to dissect age-related structural changes of the brain, with each of these indexes probably reflecting specific histological changes occurring during aging. PMID:20739099

  6. Autism Spectrum Disorder in Children and Adolescents with Fragile X Syndrome: Within-Syndrome Differences and Age-Related Changes

    ERIC Educational Resources Information Center

    McDuffie, Andrea; Abbeduto, Leonard; Lewis, Pamela; Kover, Sara; Kim, Jee-Seon; Weber, Ann; Brown, W. Ted

    2010-01-01

    The Autism Diagnostic Interview-Revised (ADI-R) was used to examine diagnostic profiles and age-related changes in autism symptoms for a group of verbal children and adolescents who had fragile X syndrome, with and without autism. After controlling for nonverbal IQ, we found statistically significant between-group differences for lifetime and…

  7. Age-Related Changes in Segmental Body Composition by Ethnicity and History of Weight Change across the Adult Lifespan.

    PubMed

    Tian, Simiao; Morio, Béatrice; Denis, Jean-Baptiste; Mioche, Laurence

    2016-01-01

    This study assessed age-related changes in body composition (specifically in trunk fat and appendicular lean masses), with consideration of body mass index (BMI) at age 20 years (BMI reference age, "BMIref"), ethnicity and lifetime weight change history. A cross-sectional dual-energy X-ray absorptiometry-based dataset was extracted from the U.S. National Health and Nutrition Examination Survey (NHANES) 1999-2004. Only European-American and African-American subjects were used (2705 men, 2527 women). For each gender and ethnicity, 6 analytic cases were considered, based on three BMIref categories (normal, overweight and obese, being 22, 27 and 30 kg/m², respectively) and two weight contexts (stable weight or weight gain across the lifespan). A nonparametric model was developed to investigate age-related changes in body composition. Then, parametric modelling was developed for assessing BMIref- and ethnicity-specific effects during aging. In the stable weight, both genders' and ethnicities' trunk fat (TF) increased gradually; body fat (BF) remained stable until 40 years and increased thereafter; trunk lean (TL) remained stable, but appendicular lean (APL) and body lean (BL) declined from 20 years. In the weight gain context, TF and BF increased at a constant rate, while APL, TL and BL increased until 40-50 years, and then declined slightly. Compared with European-American subjects of both genders, African-American subjects had lower TF and BF masses. Ethnic differences in body composition were quantified and found to remain constant across the lifespan. PMID:27529269

  8. Age-Related Changes in Segmental Body Composition by Ethnicity and History of Weight Change across the Adult Lifespan

    PubMed Central

    Tian, Simiao; Morio, Béatrice; Denis, Jean-Baptiste; Mioche, Laurence

    2016-01-01

    This study assessed age-related changes in body composition (specifically in trunk fat and appendicular lean masses), with consideration of body mass index (BMI) at age 20 years (BMI reference age, “BMIref”), ethnicity and lifetime weight change history. A cross-sectional dual-energy X-ray absorptiometry-based dataset was extracted from the U.S. National Health and Nutrition Examination Survey (NHANES) 1999–2004. Only European-American and African-American subjects were used (2705 men, 2527 women). For each gender and ethnicity, 6 analytic cases were considered, based on three BMIref categories (normal, overweight and obese, being 22, 27 and 30 kg/m2, respectively) and two weight contexts (stable weight or weight gain across the lifespan). A nonparametric model was developed to investigate age-related changes in body composition. Then, parametric modelling was developed for assessing BMIref- and ethnicity-specific effects during aging. In the stable weight, both genders’ and ethnicities’ trunk fat (TF) increased gradually; body fat (BF) remained stable until 40 years and increased thereafter; trunk lean (TL) remained stable, but appendicular lean (APL) and body lean (BL) declined from 20 years. In the weight gain context, TF and BF increased at a constant rate, while APL, TL and BL increased until 40–50 years, and then declined slightly. Compared with European-American subjects of both genders, African-American subjects had lower TF and BF masses. Ethnic differences in body composition were quantified and found to remain constant across the lifespan. PMID:27529269

  9. Age-related changes in hypertensive brain damage in the hippocampi of spontaneously hypertensive rats

    PubMed Central

    LI, YALI; LIU, JIAN; GAO, DENGFENG; WEI, JIN; YUAN, HAIFENG; NIU, XIAOLIN; ZHANG, QIAOJUN

    2016-01-01

    The aim of the present study was to investigate the age-related alterations in hypertensive brain damage in the hippocampi of spontaneously hypertensive rats (SHR) and the underlying mechanisms. Aging resulted in a significant increase in the number of activated astrocytes and apoptotic cells in the SHR group, which was accompanied by increased expression of oxidative stress markers (iNOS and gp47phox) and apoptotic regulatory proteins (Bax and caspase-3). In addition, the expression of PPAR-γ and Bcl-2 were progressively reduced with increasing age in the SHR group. The 32 and 64-week-old SHRs exhibited significantly increased numbers of apoptotic cells, oxidative stress markers and pro-apoptotic proteins compared with age-matched WKY rats, which was accompanied by reduced expression of PPAR-γ. Compared with the 16 and 32-week-old WKY group, the 64-week-old WKY rats exhibited increased oxidative stress and pro-apoptotic markers, and increased levels apoptotic cells. In conclusion, the present study indicated that both aging and hypertension enhanced brain damage and oxidative stress injury in the hippocampi of SHRs, indicated by an increased presence of apoptotic cells and astrocytes. In addition, reduced expression of PPAR-γ may contribute to the age-related brain damage in SHRs. PMID:26846626

  10. Age-related changes in neurochemical components and retinal projections of rat intergeniculate leaflet.

    PubMed

    Fiuza, Felipe P; Silva, Kayo D A; Pessoa, Renata A; Pontes, André L B; Cavalcanti, Rodolfo L P; Pires, Raquel S; Soares, Joacil G; Nascimento Júnior, Expedito S; Costa, Miriam S M O; Engelberth, Rovena C G J; Cavalcante, Jeferson S

    2016-02-01

    Aging leads to several anatomical and functional deficits in circadian timing system. In previous works, we observed morphological alterations with age in hypothalamic suprachiasmatic nuclei, one central component of this system. However, there are few data regarding aging effects on other central components of this system, such as thalamic intergeniculate leaflet (IGL). In this context, we studied possible age-related alterations in neurochemical components and retinal projections of rat IGL. For this goal, young (3 months), adult (13 months), and aged (23 months) Wistar rats were submitted to an intraocular injection of neural tracer, cholera toxin subunit b (CTb), 5 days before a tissue fixation process by paraformaldehyde perfusion. Optical density measurements and cell count were performed at digital pictures of brain tissue slices processed by immunostaining for glutamic acid decarboxylase (GAD), enkephalin (ENK), neuropeptide Y (NPY) and CTb, characteristic markers of IGL and its retinal terminals. We found a significant age-related loss in NPY immunoreactive neurons, but not in immunoreactivity to GAD and ENK. We also found a decline of retinal projections to IGL with age. We conclude aging impairs both a photic environmental clue afferent to IGL and a neurochemical expression which has an important modulatory circadian function, providing strong anatomical correlates to functional deficits of the aged biological clock. PMID:26718202

  11. Temperature affects longevity and age-related locomotor and cognitive decay in the short-lived fish Nothobranchius furzeri.

    PubMed

    Valenzano, Dario R; Terzibasi, Eva; Cattaneo, Antonino; Domenici, Luciano; Cellerino, Alessandro

    2006-06-01

    Temperature variations are known to modulate aging and life-history traits in poikilotherms as different as worms, flies and fish. In invertebrates, temperature affects lifespan by modulating the slope of age-dependent acceleration in death rate, which is thought to reflect the rate of age-related damage accumulation. Here, we studied the effects of temperature on aging kinetics, aging-related behavioural deficits, and age-associated histological markers of senescence in the short-lived fish Nothobranchius furzeri. This species shows a maximum captive lifespan of only 3 months, which is tied with acceleration in growth and expression of aging biomarkers. These biological peculiarities make it a very convenient animal model for testing the effects of experimental manipulations on life-history traits in vertebrates. Here, we show that (i) lowering temperature from 25 degrees C to 22 degrees C increases both median and maximum lifespan; (ii) life extension is due to reduction in the slope of the age-dependent acceleration in death rate; (iii) lowering temperature from 25 degrees C to 22 degrees C retards the onset of age-related locomotor and learning deficits; and (iv) lowering temperature from 25 degrees C to 22 degrees C reduces the accumulation of the age-related marker lipofuscin. We conclude that lowering water temperature is a simple experimental manipulation which retards the rate of age-related damage accumulation in this short-lived species. PMID:16842500

  12. Age-Related Physical Changes Interfere With Judgments of Male Sexual Orientation From Faces.

    PubMed

    Tskhay, Konstantin O; Krendl, Anne C; Rule, Nicholas O

    2016-09-01

    Although studies have shown that sexual orientation can be judged from faces, this research has not considered how age-related differences in perceivers or targets affect such judgments. In the current work, we evaluated whether accuracy differed among young adults (YA) and older adults (OA) for young and old men's faces by recruiting a sample of YA and OA in the lab, a community sample of sexual minority men, and a sample of online participants. We found that OA and YA judged sexual orientation with similar accuracy. Perceptions of gender atypicality mediated the difference in judging older and younger targets' sexual orientation. Although participants used positive affect to correctly discern sexual orientation regardless of target age, perceptions of masculinity were valid only for judgments of YA. PMID:27340151

  13. Age-related changes in monocytes exacerbate neointimal hyperplasia after vascular injury

    PubMed Central

    Martinez, Laisel; Gomez, Camilo; Vazquez-Padron, Roberto I.

    2015-01-01

    Neointimal hyperplasia is the leading cause of restenosis after endovascular interventions. It is characterized by the accumulation of myofibroblast-like cells and extracellular matrix in the innermost layer of the wall and is exacerbated by inflammation. Monocytes from either young or aged rats were applied perivascularly to injured vascular walls of young recipient animals. Monocytes from aged rats, but not young donors, increased neointima thickness. Accordingly, the gene expression profiles of CD11b+ monocytes from aged rats showed significant up-regulation of genes involved in cellular adhesion, lipid degradation, cytotoxicity, differentiation, and inflammation. These included cadherin 13 (Cdh13), colony stimulating factor 1 (Csf1), chemokine C-X-C motif ligand 1 (Cxcl1), endothelial cell-selective adhesion molecule (Esam), and interferon gamma (Ifng). In conclusion, our results suggest that the increased inflammatory and adhesive profile of monocytes contributes to pathological wall remodeling in aged-related vascular diseases. PMID:25965835

  14. Age-related changes in monocytes exacerbate neointimal hyperplasia after vascular injury.

    PubMed

    Martinez, Laisel; Gomez, Camilo; Vazquez-Padron, Roberto I

    2015-07-10

    Neointimal hyperplasia is the leading cause of restenosis after endovascular interventions. It is characterized by the accumulation of myofibroblast-like cells and extracellular matrix in the innermost layer of the wall and is exacerbated by inflammation. Monocytes from either young or aged rats were applied perivascularly to injured vascular walls of young recipient animals. Monocytes from aged rats, but not young donors, increased neointima thickness. Accordingly, the gene expression profiles of CD11b+ monocytes from aged rats showed significant up-regulation of genes involved in cellular adhesion, lipid degradation, cytotoxicity, differentiation, and inflammation. These included cadherin 13 (Cdh13), colony stimulating factor 1 (Csf1), chemokine C-X-C motif ligand 1 (Cxcl1), endothelial cell-selective adhesion molecule (Esam), and interferon gamma (Ifng). In conclusion, our results suggest that the increased inflammatory and adhesive profile of monocytes contributes to pathological wall remodeling in aged-related vascular diseases. PMID:25965835

  15. Age-related changes and diseases of the ocular surface and cornea.

    PubMed

    Gipson, Ilene K

    2013-12-01

    Aging of the ocular surface and corneal tissues, major components of the visual system, causes major eye disease and results in substantial cost in medical and social terms. These diseases include the highly prevalent dry eye disease that affects the ocular surface and its glands, leading to tear film alterations, discomfort, and decreased vision. Studies show that 14.4% of the population in the United States older than 50 years have dry eye disease and demonstrate that it is particularly prevalent among women. Annual medical costs per patient with dry eye in the United States are estimated at $783 per year, with an overall medical cost adjusted to prevalence of $3.84 billion per year. Societal costs, which include loss of productivity, are estimated per patient at $11,302 per year, with overall costs adjusted to prevalence of $55.4 billion per year. Because there are few effective treatments for the disease, more research on its etiology and mechanisms is warranted and needed. Increased public education about risk factors for the disease is also required. Another major age-related eye disease of the cornea that leads to vision impairment and potentially blindness if left untreated is Fuchs' endothelial corneal dystrophy. This disease leads to loss of the endothelial cells on the internal side of the cornea that are responsible for keeping the cornea in the proper hydration state to ensure its transparency to light. The mechanism of cell loss is unknown, and the only treatment available to date is surgical transplantation of the cornea or inner part of the cornea. These medically costly procedures require donor corneas, eye banking, and medical follow-up, with accrued costs. Fuchs' endothelial corneal dystrophy is a major cause of corneal transplantation in the United States; therefore, research support is needed to determine the mechanism of this age-related disease, to develop medical, nonsurgical methods for treatment. PMID:24335068

  16. Understanding age-related reductions in visual working memory capacity: Examining the stages of change detection

    PubMed Central

    Duda, Bryant; Hussey, Erin; Mason, Emily; Molitor, Robert J.; Woodman, Geoffrey F.; Ally, Brandon A.

    2014-01-01

    Visual working memory (VWM) capacity is reduced in older adults. Research has shown age-related impairments to VWM encoding, but aging is likely to affect multiple stages of VWM. In the present study, we recorded the event-related potentials (ERPs) of younger and older adults during VWM maintenance and retrieval. We measured encoding-stage processing with the P1 component, maintenance-stage processing with the contralateral delay activity (CDA), and retrieval-stage processing by comparing the activity for old and new items (old–new effect). Older adults showed lower behavioral capacity estimates (K) than did younger adults, but surprisingly, their P1 components and CDAs were comparable to those of younger adults. This remarkable dissociation between neural activity and behavior in the older adults indicated that the P1 and CDA did not accurately assess their VWM capacity. However, the neural activity evoked during VWM retrieval yielded results that helped clarify the age-related differences. During retrieval, younger adults showed early old–new effects in frontal and occipital areas and a late central–parietal old–new effect, whereas older adults showed a late right-lateralized parietal old–new effect. The younger adults’ early old–new effects strongly resembled an index of perceptual fluency, suggesting that perceptual implicit memory was activated. The activation of implicit memory could have facilitated the younger adults’ behavior, and the lack of these early effects in older adults may suggest that they have much lower-resolution memory than do younger adults. From these data, we speculated that younger and older adults store the same number of items in VWM, but that younger adults store a higher-resolution representation than do older adults. PMID:24420648

  17. Developing Connections for Affective Regulation: Age-Related Changes in Emotional Brain Connectivity

    ERIC Educational Resources Information Center

    Perlman, Susan B.; Pelphrey, Kevin A.

    2011-01-01

    The regulation of affective arousal is a critical aspect of children's social and cognitive development. However, few studies have examined the brain mechanisms involved in the development of this aspect of "hot" executive functioning. This process has been conceptualized as involving prefrontal control of the amygdala. Here, using functional…

  18. Description and Prediction of Age-Related Change in Everyday Task Performance.

    ERIC Educational Resources Information Center

    Marsiske, Michael; Willis, Sherry L.

    Traditionally, assessment of the cognitive competencies of older adults has focused on abstract laboratory tests, which have often seemed quite unlike the demands of tasks encountered in everyday activities. Consequently, external validity of these laboratory tasks has been questioned, and their utility for assessing real-world competence has been…

  19. A "concrete view" of aging: event related potentials reveal age-related changes in basic integrative processes in language.

    PubMed

    Huang, Hsu-Wen; Meyer, Aaron M; Federmeier, Kara D

    2012-01-01

    Normal aging is accompanied by changes in both structural and functional cerebral organization. Although verbal knowledge seems to be relatively stable across the lifespan, there are age-related changes in the rapid use of that knowledge during on-line language processing. In particular, aging has been linked to reduce effectiveness in preparing for upcoming words and building an integrated sentence-level representation. The current study assessed whether such age-related changes extend even to much simpler language units, such as modification relations between a centrally presented adjective and a lateralized noun. Adjectives were used to elicit concrete and abstract meanings of the same, polysemous lexical items (e.g., "green book" vs. "interesting book"). Consistent with findings that lexical information is preserved with age, older adults, like younger adults, exhibited concreteness effects at the adjectives, with more negative responses to concrete adjectives over posterior (300-500 ms; N400) and frontal (300-900 ms) channels. However, at the noun, younger adults exhibited concreteness-based predictability effects linked to left hemisphere processing and imagery effects linked to right hemisphere processing, contingent on whether the adjectives and nouns formed a cohesive conceptual unit. In contrast, older adults showed neither effect, suggesting that they were less able to rapidly link the adjective-noun meaning to form an integrated conceptual representation. Age-related changes in language processing may thus be more pervasive than previously realized. PMID:22044648

  20. Age related changes in the lipoprotein substrates for the esterification of plasma cholesterol in rats.

    PubMed

    Lee, S M; Kudchodkar, B J; Lacko, A G

    1991-11-15

    The activity of the enzyme lecithin:cholesterol acyltransferase (LCAT) and the properties of its lipoprotein substrates have been investigated in 6- and 19-month-old Fischer-344 rats. These studies were carried out to determine the nature of the relationship between the observed hypercholesterolemia and the age-related decrease in the fractional rate of lipoprotein cholesterol esterification. The distribution of LCAT activity of plasma fractions was determined following gel chromatography and ultracentrifugation respectively. LCAT activity was found to be associated with the high density lipoprotein (HDL) fraction when rat plasma was passed through a Bio-Gel A-5 M column. Upon density gradient ultracentrifugation for 24 h it was found associated with HDL fraction; d = 1.125-1.21 g/ml. However, following prolonged ultracentrifugation (40 h), the majority of the LCAT activity was displaced into the lipoprotein-free infranatant (d greater than 1.225 g/ml). The dissociation of LCAT from its complex with HDL occurred to a smaller extent in aged rat plasma than in young rat plasma. Substrate specificity studies indicated that HDL was a considerably better substrate for LCAT than very low density lipoproteins (VLDL) in both young and aged rats. In addition, HDL from young rats was a better substrate for LCAT than the HDL from aged rats. Incubation experiments followed by the isolation of lipoproteins and the subsequent analyses of their cholesterol contents revealed that the age-related hypercholesterolemia was mainly due to an increase in the cholesterol carried by lipoprotein fractions d = 1.025 -1.07 g/ml (LDL + HDL1). These and other low density lipoproteins (d less than 1.025 g/ml) were poor substrates for LCAT. However, these lipoproteins could provide free cholesterol for esterification by first transferring it to HDL (d = 1.07-1.21). The HDL isolated from the plasma of aged rats was enriched with apolipoprotein (apo) E and these lipoprotein particles were found to

  1. Age-related changes in emotional face processing across childhood and into young adulthood: Evidence from event-related potentials.

    PubMed

    MacNamara, Annmarie; Vergés, Alvaro; Kujawa, Autumn; Fitzgerald, Kate D; Monk, Christopher S; Phan, K Luan

    2016-01-01

    Socio-emotional processing is an essential part of development, and age-related changes in its neural correlates can be observed. The late positive potential (LPP) is a measure of motivated attention that can be used to assess emotional processing; however, changes in the LPP elicited by emotional faces have not been assessed across a wide age range in childhood and young adulthood. We used an emotional face matching task to examine behavior and event-related potentials (ERPs) in 33 youth aged 7-19 years old. Younger children were slower when performing the matching task. The LPP elicited by emotional faces but not control stimuli (geometric shapes) decreased with age; by contrast, an earlier ERP (the P1) decreased with age for both faces and shapes, suggesting increased efficiency of early visual processing. Results indicate age-related attenuation in emotional processing that may stem from greater efficiency and regulatory control when performing a socio-emotional task. PMID:26220144

  2. Age-related pathophysiological changes in rats with unilateral renal agenesis.

    PubMed

    Amakasu, Kohei; Suzuki, Katsushi; Katayama, Kentaro; Suzuki, Hiroetsu

    2011-06-01

    Affected rats of the unilateral urogenital anomalies (UUA) strain show renal agenesis restricted to the left side. To determine whether unilateral renal agenesis is a risk factor for the progression of renal insufficiency, we studied age-related pathophysiological alterations in affected rats. Although body growth and food intake were normal, polydipsia and polyuria with low specific gravity were present at 10 weeks and deteriorated further with age. Blood hemoglobin concentrations were normal, though there was slight erythropenia with increased MCV and MCH. Although hypoalbuminemia, hypercholesterolemia, azotemia, and hypermagnesemia were manifested after age 20 weeks, neither hyperphosphatemia nor hypocalcemia was observed. Plasma Cre and UN concentrations gradually increased with age. Cre clearance was almost normal, whereas fractional UN excretion was consistently lower than normal. Proteinuria increased with age, and albumin was the major leakage protein. In addition to cortical lesions, dilated tubules, cast formation, and interstitial fibrosis were observed in the renal medulla of 50 week-old affected rats. Renal weight was increased 1.7-fold and glomerular number 1.2-fold compared with normal rats. These findings show that the remaining kidney in UUA rats is involved not only in compensatory reactions but experiences pathophysiological alterations associated with progressive renal insufficiency. PMID:21307619

  3. Age-related changes in auditory and visual interactions in temporal rate perception

    PubMed Central

    Brooks, Cassandra J.; Anderson, Andrew J.; Roach, Neil W.; McGraw, Paul V.; McKendrick, Allison M.

    2015-01-01

    We investigated how aging affects the integration of temporal rate for auditory flutter (amplitude modulation) presented with visual flicker. Since older adults were poorer at detecting auditory amplitude modulation, modulation depth was individually adjusted so that temporal rate was equally discriminable for 10 Hz flutter and flicker, thereby balancing the reliability of rate information available to each sensory modality. With age-related sensory differences normalized in this way, rate asynchrony skewed both auditory and visual rate judgments to the same extent in younger and older adults. Therefore, reliability-based weighting of temporal rate is preserved in older adults. Concurrent presentation of synchronous 10 Hz flicker and flutter improved temporal rate discrimination consistent with statistically optimal integration in younger but not older adults. In a control experiment, younger adults were presented with the same physical auditory stimulus as older adults. This time, rate asynchrony skewed perceived rate with greater auditory weighting rather than balanced integration. Taken together, our results indicate that integration of discrepant auditory and visual rates is not altered due to the healthy aging process once sensory deficits are accounted for, but that aging does abolish the minor improvement in discrimination performance seen in younger observers when concordant rates are integrated. PMID:26624937

  4. Aging Related Changes of Retina and Optic Nerve of Uromastyx aegyptia and Falco tinnunculus

    PubMed Central

    2013-01-01

    Aging is a biological phenomenon that involves gradual degradation of the structure and function of the retina and optic nerve. To our knowledge, little is known about the aging-related ocular cell loss in avian (Falco tinnunculus) and reptilian species (Uromastyx aegyptia). A selected 90 animals of pup, middle, and old age U. aegyptia (reptilian) and F. tinnunculus (avian) were used. The retinae and optic nerves were investigated by light and transmission electron microscopy (TEM) and assessments of neurotransmitters, antioxidant enzymes (catalase, superoxide dismustase and glutathione s transferase), caspase-3 and -7, malonadialdhyde, and DNA fragmentation. Light and TEM observations of the senile specimens revealed apparent deterioration of retinal cell layers, especially the pigmented epithelium and photoreceptor outer segments. Their inclusions of melanin were replaced by lipofuscins. Also, vacuolar degeneration and demyelination of the optic nerve axons were detected. Concomitantly, there was a marked increase of oxidative stress involved reduction of neurotransmitters and antioxidant enzymes and an increase of lipid peroxidation, caspase-3 and -7, subG0/G1 apoptosis, and P53. We conclude that aging showed an inverse relationship with the neurotransmitters and antioxidant enzymes and a linear relationship of caspases, malondialdhyde, DNA apoptosis, and P53 markers of cell death. These markers reflected the retinal cytological alterations and lipofuscin accumulation within inner segments. PMID:24215233

  5. Age-related changes in multifinger synergies in accurate moment of force production tasks

    PubMed Central

    Olafsdottir, Halla; Zhang, Wei; Zatsiorsky, Vladimir M.; Latash, Mark L.

    2010-01-01

    The purpose of this investigation was to document and quantify age-related differences in the coordination of fingers during a task that required production of an accurate time profile of the total moment of force by the four fingers of a hand. We hypothesized that elderly subjects would show a decreased ability to stabilize a time profile of the total moment of force, leading to larger indexes of moment variability compared with young subjects. The subjects followed a trapezoidal template on a computer screen by producing a time profile of the total moment of force while pressing down on force sensors with the four fingers of the right (dominant) hand. To quantify synergies, we used the framework of the uncontrolled manifold hypothesis. The elderly subjects produced larger total force, larger variance of both total force and total moment of force, and larger involvement of fingers that produced moment of force against the required moment direction (antagonist moment). This was particularly prominent during supination efforts. Young subjects showed covariation of commands to fingers across trials that stabilized the moment of total force (moment-stabilizing synergy), while elderly subjects failed to do so. Both subject groups showed similar indexes of covariation of commands to the fingers that stabilized the time profile of the total force. The lack of moment-stabilizing synergies may be causally related to the documented impairment of hand function with age. PMID:17204576

  6. Age-related pharmacokinetic changes of acetaminophen, antipyrine, diazepam, diphenhydramine, and ofloxacin in male cynomolgus monkeys and beagle dogs.

    PubMed

    Koyanagi, Takashi; Yamaura, Yoshiyuki; Yano, Koji; Kim, Soonih; Yamazaki, Hiroshi

    2014-10-01

    1. The pharmacokinetics of acetaminophen (marker of gastric emptying), antipyrine (marker of hepatic metabolic activity and total body water), diazepam (lipophilic and highly distributed), diphenhydramine (hepatic blood flow-limited and alpha-1 acid glycoprotein bound) and ofloxacin (renally eliminated) were evaluated in cynomolgus monkeys (3-18 years old) and beagle dogs (2-11 years old) as models in elderly persons. 2. Gastric pH fluctuated with aging in monkeys and dogs. The concentration of alpha-1 acid glycoprotein appeared to be increased by aging. There were no age-related differences in the absorption rates of the drugs under the conditions used in the study. Total body fat increased and water decreased in monkeys, but these parameters did not change in dogs. 3. Hepatic blood flow decreased in both species, but a significant decrease of hepatic clearance was only seen in monkeys. Renal clearance decreased significantly with age in monkeys and showed a tendency to decrease in dogs. 4. Age-related alterations of physiological parameters in monkeys are in agreement with clinical observations in humans, except for the lack of a change in the plasma albumin concentration. Therefore, this study suggests that monkey might be a suitable animal model for prediction of age-related changes in pharmacokinetics in humans. PMID:24650193

  7. Raman spectroscopy of oral buccal mucosa: a study on age-related physiological changes and tobacco-related pathological changes.

    PubMed

    Sahu, Aditi; Deshmukh, Atul; Ghanate, A D; Singh, S P; Chaturvedi, Pankaj; Krishna, C Murali

    2012-12-01

    Biophysical techniques play an important role in detecting physiological alterations during pathogenesis. Raman spectroscopy has shown immense potential in identifying several diseased conditions, including oral cancers. Classification of normal, inflammatory, premalignant and malignant conditions has been demonstrated using ex vivo Raman spectroscopy. Feasibility of recording in vivo spectra in clinically implementable time has also been shown. Translation of this technology to clinics requires extensive validation of methodologies, building of robust models and testing the same under stringent conditions as well as on diverse populations. In this context, the ability of Raman spectroscopy in identifying subtle changes in oral mucosa with increasing age, and the influence of these aging related changes on classification with tobacco-related pathological changes was evaluated. A total of 451 spectra from 62 subjects were recorded from buccal mucosa of healthy subjects of 4 different age groups (aged 20-60 years). Also, 478 spectra from 85 subjects belonging to 4 different categories, tobacco exposed mucosa, contralateral normal (opposite side of tumor), premalignant patches and tumors on buccal mucosa were recorded using fiber optic probe-coupled commercial Raman spectrometer. Differences in spectra were explored by unsupervised Principal Component Analysis (PCA) and supervised Linear Discriminant Analysis (LDA), followed by Leave one out cross validation. Results indicate feasibility of classifying early and late age groups. Also, clear classification is observed between healthy and pathological groups, thus inherent heterogeneity in healthy groups seems to have no bearing on classification of normal with abnormal conditions. Findings of the study indicate high sensitivity of Raman spectroscopy in detecting subtle mucosal changes, further supporting efficacy of Raman spectroscopic approaches in oral cancer applications. Prospectively, more vigorous validation

  8. Age-related hearing loss: GABA, nicotinic acetylcholine and NMDA receptor expression changes in spiral ganglion neurons of the mouse.

    PubMed

    Tang, X; Zhu, X; Ding, B; Walton, J P; Frisina, R D; Su, J

    2014-02-14

    Age-related hearing loss - presbycusis - is the number one communication disorder and most prevalent neurodegenerative condition of our aged population. Although speech understanding in background noise is quite difficult for those with presbycusis, there are currently no biomedical treatments to prevent, delay or reverse this condition. A better understanding of the cochlear mechanisms underlying presbycusis will help lead to future treatments. Objectives of the present study were to investigate GABAA receptor subunit α1, nicotinic acetylcholine (nACh) receptor subunit β2, and N-methyl-d-aspartate (NMDA) receptor subunit NR1 mRNA and protein expression changes in spiral ganglion neurons (SGN) of the CBA/CaJ mouse cochlea, that occur in age-related hearing loss, utilizing quantitative immunohistochemistry and semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) techniques. We found that auditory brainstem response (ABR) thresholds shifted over 40dB from 3 to 48kHz in old mice compared to young adults. DPOAE thresholds also shifted over 40dB from 6 to 49kHz in old mice, and their amplitudes were significantly decreased or absent in the same frequency range. SGN density decreased with age in basal, middle and apical turns, and SGN density of the basal turn declined the most. A positive correlation was observed between SGN density and ABR wave 1amplitude. mRNA and protein expression of GABAAR α1 and AChR β2 decreased with age in SGNs in the old mouse cochlea. mRNA and protein expression of NMDAR NR1 increased with age in SGNs of the old mice. These findings demonstrate that there are functionally-relevant age-related changes of GABAAR, nAChR, NMDAR expression in CBA mouse SGNs reflecting their degeneration, which may be related to functional changes in cochlear synaptic transmission with age, suggesting biological mechanisms for peripheral age-related hearing loss. PMID:24316061

  9. Age-related changes to TNF receptors affect neuron survival in the presence of beta-amyloid

    PubMed Central

    Patel, Jigisha R.; Brewer, Gregory J.

    2007-01-01

    Inflammation including local accumulations of tumor necrosis factor alpha (TNFα) is a part of Alzheimer’s disease (AD) pathology and may exacerbate age-related neurodegeneration. Most studies on TNFα and TNF neuronal receptors are conducted using embryonic neurons. Few studies consider age-related deficits that may occur in neurons. Age-related changes in susceptibility to TNFα through TNF receptor 1 (TNFR1) and receptor 2 (TNFR2) expression could increase susceptibility to β-amyloid (1-42, Abeta42). Evidence is conflicting about which receptor mediates survival and/or apoptosis. We determined how aging affects receptor expression in cultured adult rat cortical neurons. Old neurons were more susceptible to Abeta42 toxicity than middle-age neurons and the addition of TNFα was neuroprotective in middle-age, but exacerbated the toxicity from Abeta42 in old neurons. These pathologic and protective responses in old and middle-age neurons respectively correlated with higher starting TNFR1 and TNFR2 mRNA levels in old versus middle-age neurons. Middle-age neurons treated with TNFα plus Abeta42 did not show an increase in either TNFR1 or TNFR2 mRNA but old neurons showed an upregulation in TNFR2 mRNA and not TNFR1 mRNA. Despite these mRNA changes, surface immunoreactivity of both TNFR1 and TNFR2 increased with dose of TNFα in middle-age neurons. However, middle-age neurons treated with TNFα plus Abeta42 showed an upregulation in both TNFR1 and TNFR2 surface expression, whereas old neurons failed to upregulate surface expression of either receptor. These findings support the hypothesis that age-related changes in TNFα surface receptor expression contribute to the neuronal loss associated with inflammation in AD. PMID:18418902

  10. Hearing and age-related changes in the gray mouse lemur.

    PubMed

    Schopf, Christian; Zimmermann, Elke; Tünsmeyer, Julia; Kästner, Sabine B R; Hubka, Peter; Kral, Andrej

    2014-12-01

    In order to examine auditory thresholds and hearing sensitivity during aging in the gray mouse lemur (Microcebus murinus), suggested to represent a model for early primate evolution and Alzheimer research, we applied brainstem-evoked response audiometry (BERA), traditionally used for screening hearing sensitivity in human babies. To assess the effect of age, we determined auditory thresholds in two age groups of adult mouse lemurs (young adults, 1-5 years; old adults, ≥7 years) using clicks and tone pips. Auditory thresholds indicated frequency sensitivity from 800 Hz to almost 50 kHz, covering the species tonal communication range with fundamentals from about 8 to 40 kHz. The frequency of best hearing at 7.9 kHz was slightly lower than that and coincided with the dominant frequencies of communication signals of a predator. Aging shifted auditory thresholds in the range between 2 and 50.4 kHz significantly by 12-27 dB. This mild presbyacusis, expressed in a drop of amplitudes of BERA signals, but not discernible in latencies of responses, suggests a metabolic age-related decrease potentially combined with an accompanying degeneration of the cochlear nerve. Our findings on hearing range of this species support the hypothesis that predation was a driving factor for the evolution of hearing in small ancestral primates. Likewise, results provide the empirical basis for future approaches trying to differentiate peripheral from central factors when studying Alzheimer's disease-like pathologies in the aging brain. PMID:25112886

  11. Quantitative investigations on the human entorhinal area: left-right asymmetry and age-related changes.

    PubMed

    Heinsen, H; Henn, R; Eisenmenger, W; Götz, M; Bohl, J; Bethke, B; Lockemann, U; Püschel, K

    1994-08-01

    The total nerve cell numbers in the right and in the left human entorhinal areas have been calculated by volume estimations with the Cavalieri principle and by cell density determinations with the optical disector. Thick gallocyanin-stained serial frozen sections through the parahippocampal gyrus of 22 human subjects (10 female, 12 male) ranging from 18 to 86 years were analysed. The laminar composition of gallocyanin (Nissl)-stained sections could easily be compared with Braak's (1972, 1980) pigmentoarchitectonic study, and Braak's nomenclature of the entorhinal laminas was adopted. Cell-sparse laminae dissecantes can more clearly be distinguished in Nissl than in aldehydefuchsin preparations. These cell-poor dissecantes, lamina dissecans externa (dis-ext), lamina dissecans 1 (dis-1) and lamina dissecans 2 (dis-2), were excluded from nerve cell number determinations. An exact delineation of the entorhinal area is indispensable for any kind of quantitative investigation. We have defined the entorhinal area by the presence of pre-alpha cell clusters and the deeper layers of lamina principalis externa (pre-beta and gamma) separated from lamina principalis interna (pri) by lamina dissecans 1 (dis-1). The human entorhinal area is quantitatively characterized by a left-sided (asymmetric) higher pre-alpha cell number and an age-related nerve cell loss in pre as well as pri layers. At variance with other CNS cortical and subcortical structures, the neuronal number of the entorhinal area appears to decrease continuously from the earliest stages analysed, although a secular trend has to be considered. The asymmetry in pre-alpha cell number is discussed in the context of higher human mental capabilities, especially language. PMID:7818090

  12. Age-related changes in human oestrogen receptor alpha function and levels in osteoblasts.

    PubMed Central

    Ankrom, M A; Patterson, J A; d'Avis, P Y; Vetter, U K; Blackman, M R; Sponseller, P D; Tayback, M; Robey, P G; Shapiro, J R; Fedarko, N S

    1998-01-01

    Oestrogen receptors (ERs) are present in human osteoblasts and mediate anti-resorptive effects on bone. Human osteoblast-like cells derived from different aged healthy female donors not on hormone replacement therapy were utilized under well-defined conditions in vitro to investigate ER function and levels. Treatment with 0.1 nM oestradiol-17beta of cell strains derived from eight young women (less than 50 years of age) increased hydroxyproline levels significantly [an average (2.2+/-0.1 S.E.M.)-fold increase], whereas cells derived from nine older women (more than 50 years of age) were not significantly affected. Similarly, cell strains, derived from younger women, transfected with a consensus oestrogen-responsive element linked to chloramphenicol acetyltransferase exhibited a greater response to oestrogen than strains derived from older women. When basal ERalpha levels were measured by enzyme immunoassay and normalized on a per cell basis, osteoblast-like strains derived from younger women (n=24) had a mean value of 2.54+/-0.16 fmol of ERalpha per 10(6) cells. In contrast, strains derived from older women (n=20) had a mean value of 5.44+/-0.48 fmol of ERalpha per 10(6) cells. An age-related increase in ERalpha number was also observed in human skin-derived fibroblasts and directly in dermal biopsies from women not on hormone replacement therapy. The results demonstrate ligand concentration-dependent ERalpha induction and indicate a loss of receptor regulation and diminution of ligand-receptor signal transduction with increasing donor age. PMID:9677341

  13. Age-related macular degeneration and changes in the extracellular matrix

    PubMed Central

    Nita, Małgorzata; Strzałka-Mrozik, Barbara; Grzybowski, Andrzej; Mazurek, Urszula; Romaniuk, Wanda

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of permanent, irreversible, central blindness (scotoma in the central visual field that makes reading and writing impossible, stereoscopic vision, recognition of colors and details) in patients over the age of 50 years in European and North America countries, and an important role is attributed to disorders in the regulation of the extracellular matrix (ECM). The main aim of this article is to present the crucial processes that occur on the level of Bruch’s membrane, with special consideration of the metalloproteinase substrates, metalloproteinase, and tissue inhibitor of metalloproteinase (TIMP). A comprehensive review of the literature was performed through MEDLINE and PubMed searches, covering the years 2005–2012, using the following keywords: AMD, extracellular matrix, metalloproteinases, tissue inhibitors of metalloproteinases, Bruch’s membrane, collagen, elastin. In the pathogenesis of AMD, a significant role is played by collagen type I and type IV; elastin; fibulin-3, -5, and -6; matrix metalloproteinase (MMP)-2, MMP-9, MMP-14, and MMP-1; and TIMP-3. Other important mechanisms include: ARMS2 and HTR1 proteins, the complement system, the urokinase plasminogen activator system, and pro-renin receptor activation. Continuous rebuilding of the extracellular matrix occurs in both early and advanced AMD, simultaneously with the dysfunction of retinal pigment epithelium (RPE) cells and endothelial cells. The pathological degradation or accumulation of ECM structural components are caused by impairment or hyperactivity of specific MMPs/TIMPs complexes, and is also endangered by the influence of other mechanisms connected with both genetic and environmental factors. PMID:24938626

  14. Age-related differences in the P3 amplitude in change blindness.

    PubMed

    Bergmann, Katharina; Schubert, Anna-Lena; Hagemann, Dirk; Schankin, Andrea

    2016-07-01

    Observers often miss visual changes in the environment when they co-occur with other visual disruptions. This phenomenon is called change blindness. Previous research has shown that change blindness increases with age. The aim of the current study was to explore the role of post-perceptual stimulus processing in age differences. Therefore, the P3 component of the event-related potential was measured while younger, middle-aged, and older participants performed a change detection task under different task demands. Older adults detected fewer changes than younger adults, even when the task was very easy. Detected changes elicited greater P3 amplitudes than undetected changes in younger adults. This effect was reduced or even absent for middle-aged and older participants, irrespective of task demands. Because this P3 effect is supposed to reflect participants' confidence in change detection, less confidence in own responses may explain the decline of change detection performance in normal aging. PMID:25957278

  15. Age-Related Cognitive Impairments in Mice with a Conditional Ablation of the Neural Cell Adhesion Molecule

    ERIC Educational Resources Information Center

    Bisaz, Reto; Boadas-Vaello, Pere; Genoux, David; Sandi, Carmen

    2013-01-01

    Most of the mechanisms involved in neural plasticity support cognition, and aging has a considerable effect on some of these processes. The neural cell adhesion molecule (NCAM) of the immunoglobulin superfamily plays a pivotal role in structural and functional plasticity and is required to modulate cognitive and emotional behaviors. However,…

  16. Preliminary Study on Electrophysiological Changes After Cellular Autograft in Age-Related Macular Degeneration

    PubMed Central

    Limoli, Paolo Giuseppe; Vingolo, Enzo Maria; Morales, Marco Ulisses; Nebbioso, Marcella; Limoli, Celeste

    2014-01-01

    Abstract Evolving atrophic macular degeneration represents at least 80% of all macular degenerations and is currently without a standardized care. Autologous fat transplantation efficacy was demonstrated by several studies, as these cells are able to produce growth factors. The aim of the work was to demonstrate possible therapeutic effect of the joined suprachoroidal graft of adipocytes, adipose-derived stem cells (ADSCs) in stromal vascular fractions (SVFs) of adipose tissue, and platelet-rich plasma (PRP). Twelve eyes in 12 dry age-related macular degeneration (AMD) patients, aged 71.25 (SD ± 6.8) between 62 and 80 years, were analyzed. A complete ocular evaluation was performed using best corrected visual acuity (BCVA), retinographic analysis, spectral-domain optical coherence tomography, microperimetry, computerized visual field, and standard electroretinogram (ERG). Each eye received a cell in graft between choroid and sclera of mature fat cells and ADSCs in SVF enriched with PRP by means of the variant second Limoli (Limoli retinal restoration technique [LRRT]). In order to test if the differences pre- and post-treatment were significant, the Wilcoxon signed-rank test has been performed. Adverse effects were not reported in the patients. After surgery with LRRT, the most significant increase in the ERG values was recorded by scotopic rod-ERG (answer coming from the rods), from 41.26 to 60.83 μV with an average increase of 47.44% highly significant (P < 0.05). Moderately significant was the one recorded by scotopic maximal ERG (answer coming from the rods and cones), from 112.22 to 129.68 μV with an average increase of 15.56% (P < 0.1). Cell-mediated therapy based on growth factors used appears interesting because it can improve the retinal functionality responses in the short term. The ERG could, therefore, be used to monitor the effect of cell-mediated regenerative therapies. PMID:25546695

  17. Touchscreen-Based Cognitive Tasks Reveal Age-Related Impairment in a Primate Aging Model, the Grey Mouse Lemur (Microcebus murinus)

    PubMed Central

    2014-01-01

    Mouse lemurs are suggested to represent promising novel non-human primate models for aging research. However, standardized and cross-taxa cognitive testing methods are still lacking. Touchscreen-based testing procedures have proven high stimulus control and reliability in humans and rodents. The aim of this study was to adapt these procedures to mouse lemurs, thereby exploring the effect of age. We measured appetitive learning and cognitive flexibility of two age groups by applying pairwise visual discrimination (PD) and reversal learning (PDR) tasks. On average, mouse lemurs needed 24 days of training before starting with the PD task. Individual performances in PD and PDR tasks correlate significantly, suggesting that individual learning performance is unrelated to the respective task. Compared to the young, aged mouse lemurs showed impairments in both PD and PDR tasks. They needed significantly more trials to reach the task criteria. A much higher inter-individual variation in old than in young adults was revealed. Furthermore, in the PDR task, we found a significantly higher perseverance in aged compared to young adults, indicating an age-related deficit in cognitive flexibility. This study presents the first touchscreen-based data on the cognitive skills and age-related dysfunction in mouse lemurs and provides a unique basis to study mechanisms of inter-individual variation. It furthermore opens exciting perspectives for comparative approaches in aging, personality, and evolutionary research. PMID:25299046

  18. Age-Related Visual Changes and Their Impications for the Motor Skill Performance of Older Adults.

    ERIC Educational Resources Information Center

    Haywood, Kathleen M.; Trick, Linda R.

    Physical changes in and conditions of the eye associated with the normal aging process are discussed with reference to their impact on performance in physical and recreational activities. Descriptions are given of characteristic changes in visual acuity in the areas of: (1) presbyopia (inability to clearly focus near images); (2) sensitivity to…

  19. Age-related changes in the motricity of the inbred mice strains 129/sv and C57BL/6j.

    PubMed

    Serradj, Najet; Jamon, Marc

    2007-02-12

    The development of motor skills was studied at different stages in the life of the mouse, focusing on three key aspects of motor development: early rhythmic motor activities prior to the acquisition of quadruped locomotion, motor skills in young adults, and the effect of aging on motor skills. The age-related development pattern was analysed and compared in two strains of major importance for genomic studies (C57Bl6/j and 129/sv). Early rhythmic air-stepping activities by l-dopa injected mice showed similar overall development in both strains; differences were observed with greater beating frequency and less inter-limb coordination in 129/sv, suggesting that 129/sv had a different maturation process. Performance on the rotarod by young adult C57Bl6/j gradually improved between 1 and 3 months, but then declined with age; performance on the treadmill also declined with an age-related increase in fatigability. Overall performance by 129/sv mice was lower than C57Bl6/j, and the age-related pattern of change was different, with 129/sv having relatively stable performance over time. Inter-strain differences and their possible causes, in particular the role of dopaminergic pathways, are discussed together with repercussions affecting mutant phenotyping procedures. PMID:17126421

  20. Age-related changes in the central nervous system in selected domestic mammals and primates.

    PubMed

    Firląg, Maciej; Kamaszewski, Maciej; Gaca, Katarzyna; Bałasińska, Bożena

    2013-01-01

    Aging is a process which operates at many levels of physiological, genetic and molecular organization and leads inevitably to death. Brain macroscopic changes by MRI investigation during aging were observed in humans and dogs but chimpanzees did not display significant changes. This suggestion led to the statement that brain aging is different in various species. Although human brain changes, e.g. β-amyloid storage, neurofibrillary tangle formation, lipofuscin, are relatively well known, we are still looking for a suitable animal model to study the mechanisms of aging and neurodegenerative diseases. Therefore, this paper presents a comparative analysis of the changes described in the brains of senile dog, horse and gorilla. In addition we present the latest, non-invasive methods that can be applied in the diagnosis of old age in mammals. Our considerations have shown that the best animal model for further studies and observations on aging is the dog. PMID:23619226

  1. Early age-related changes in episodic memory retrieval as revealed by event-related potentials.

    PubMed

    Guillaume, Cécile; Clochon, Patrice; Denise, Pierre; Rauchs, Géraldine; Guillery-Girard, Bérengère; Eustache, Francis; Desgranges, Béatrice

    2009-01-28

    Familiarity is better preserved than recollection in ageing. The age at which changes first occur and the slope of the subsequent decline, however, remain unclear. In this study, we investigated changes in episodic memory, by using event-related potentials (ERPs) in young (m=24), middle-aged (m=58) and older (m=70) adults. Although behavioural performance did not change before the age of 65 years, changes in ERP correlates were already present in the middle-aged adults. The ERP correlates of recollection and monitoring processes were the first to be affected by ageing, with a linear decrease as age increased. Conversely, the ERP correlate of familiarity remained unchanged, at least up to the age of 65 years. These results suggest a differential time course for the age effects on episodic retrieval. PMID:19104457

  2. Age-related changes in the attentional control of visual cortex: A selective problem in the left visual hemifield

    PubMed Central

    Nagamatsu, Lindsay S.; Carolan, Patrick; Liu-Ambrose, Teresa Y.L.; Handy, Todd C.

    2012-01-01

    To what extent does our visual-spatial attention change with age? In this regard, it has been previously reported that relative to young controls, seniors show delays in attention-related sensory facilitation. Given this finding, our study was designed to examine two key questions regarding age-related changes in the effect of spatial attention on sensory-evoked responses in visual cortex –– are there visual field differences in the age-related impairments in sensory processing, and do these impairments co-occur with changes in the executive control signals associated with visual spatial orienting? Therefore, our study examined both attentional control and attentional facilitation in seniors (aged 66 to 74 years) and young adults (aged 18 to 25 years) using a canonical spatial orienting task. Participants responded to attended and unattended peripheral targets while we recorded event-related potentials (ERPs) to both targets and attention-directing spatial cues. We found that not only were sensory-evoked responses delayed in seniors specifically for unattended events in the left visual field as measured via latency shifts in the lateral occipital P1 elicited by visual targets, but seniors also showed amplitude reductions in the anterior directing attentional negativity (ADAN) component elicited by cues directing attention to the left visual field. At the same time, seniors also had significantly higher error rates for targets presented in the left vs. right visual field. Taken together, our data thus converge on the conclusion that age-related changes in visual spatial attention involve both sensory-level and executive attentional control processes, and that these effects appear to be strongly associated with the left visual field. PMID:21356222

  3. Age-Related Degenerative Functional, Radiographic, and Histological Changes of the Shoulder in Non-Human Primates

    PubMed Central

    Plate, Johannes F.; Bates, Christopher M.; Mannava, Sandeep; Smith, Thomas L.; Jorgensen, Matthew J.; Register, Thomas C.; Stehle, John R.; High, Kevin P.; Shively, Carol A.; Kaplan, Jay R.; Saul, Katherine R.; Tuohy, Christopher J.

    2013-01-01

    Background Non-human primates have similar shoulder anatomy and physiology compared to humans and may represent a previously underutilized model for shoulder research. This study sought to identify naturally occurring bony and muscular degeneration in the shoulder of non-human primates and to assess relationships between structural and functional aspects of the shoulder and measures of physical function of the animals. We hypothesized that age-related degenerative changes in the shoulders of non-human primates would resemble those observed in aging humans. Methods Middle-aged (n=5, ages 9.4 to 11.8 years) and elderly (n=6, ages 19.8 to 26.4 years) female vervet monkeys were studied for changes in mobility and shoulder function, and radiographic and histologic signs of age-related degeneration. Results Four out of six (4/6) elderly animals had degenerative changes of the glenoid compared to 0/5 of the middle-aged animals (p=0.005). Elderly animals had glenoid retroversion, decreased joint space, walked slower and spent less time climbing and hanging than middle-aged vervets (p<0.05). Physical mobility and shoulder function correlated with glenoid version angle (p<0.05). Supraspinatus muscles of elderly animals were less dense (p=0.001), had decreased fiber cross-sectional area (p<0.001), but similar amounts of nuclear material (p=0.085). Degenerative rotator cuff tears were not observed in any of the eleven animals. Discussion and Conclusion The vervet monkey naturally undergoes age-related functional, radiographic and histological changes of the shoulder and may qualify as an animal model for selected translational research of shoulder osteoarthritis. Level of evidence Basic Science Study, in-vivo Animal Model PMID:23352182

  4. Age-related changes in the innervation of the prostate gland

    PubMed Central

    White, Carl W; Xie, Jin Han; Ventura, Sabatino

    2013-01-01

    The adult prostate gland grows and develops under hormonal control while its physiological functions are controlled by the autonomic nervous system. The prostate gland receives sympathetic input via the hypogastric nerve and parasympathetic input via the pelvic nerve. In addition, the hypogastric and pelvic nerves also provide sensory inputs to the gland. This review provides a summary of the innervation of the adult prostate gland and describes the changes which occur with age and disease. Growth and development of the prostate gland is age dependent as is the occurrence of both benign prostate disease and prostate cancer. In parallel, the activity and influence of both the sympathetic and parasympathetic nervous system changes with age. The influence of the sympathetic nervous system on benign prostatic hyperplasia is well documented and this review considers the possibility of a link between changes in autonomic innervation and prostate cancer progression. PMID:23872639

  5. Age-Related Changes in Strength, Joint Laxity, and Walking Patterns: Are They Related to Knee Osteoarthritis?

    PubMed Central

    Rudolph, Katherine S; Schmitt, Laura C; Lewek, Michael D

    2008-01-01

    Background and Purpose Aging is associated with musculoskeletal changes and altered walking patterns. These changes are common in people with knee osteoarthritis (OA) and may precipitate the development of OA. We examined age-related changes in musculoskeletal structures and walking patterns to better understand the relationship between aging and knee OA. Methods Forty-four individuals without OA (15 younger, 15 middle-aged, 14 older adults) and 15 individuals with medial knee OA participated. Knee laxity, quadriceps femoris muscle strength (force-generating capacity), and gait were assessed. Results Medial laxity was greater in the OA group, but there were no differences between the middle-aged and older control groups. Quadriceps femoris strength was less in the older control group and in the OA group. During the stance phase of walking, the OA group demonstrated less knee flexion and greater knee adduction, but there were no differences in knee motion among the control groups. During walking, the older control group exhibited greater quadriceps femoris muscle activity and the OA group used greater muscle co-contraction. Discussion and Conclusion Although weaker, the older control group did not use truncated motion or higher co-contraction. The maintenance of movement patterns that were similar to the subjects in the young control group may have helped to prevent development of knee OA. Further investigation is warranted regarding age-related musculoskeletal changes and their influence on the development of knee OA. PMID:17785376

  6. Age-related changes in rat intrinsic laryngeal muscles: analysis of muscle fibers, muscle fiber proteins, and subneural apparatuses.

    PubMed

    Nishida, Naoya; Taguchi, Aki; Motoyoshi, Kazumi; Hyodo, Masamitsu; Gyo, Kiyofumi; Desaki, Junzo

    2013-03-01

    We compared age-related changes in the intrinsic laryngeal muscles of aged and young adult rats by determining the number and diameter of muscle fibers, contractile muscle protein (myosin heavy chain isoforms, MHC) composition, and the morphology of the subneural apparatuses. In aged rats, both the numbers and the diameters of muscle fibers decreased in the cricothyroid (CT) muscle. The number of fibers, but not diameter, decreased in the thyroarytenoid (TA) muscle. In the posterior cricoarytenoid (PCA) muscle, neither the number nor the diameter of fibers changed significantly. Aging was associated with a decrease in type IIB and an increase in type IIA MHC isoform levels in CT muscle, but no such changes were observed in the TA or PCA muscles. Morphological examination of primary synaptic clefts of the subneural apparatus revealed that aging resulted in decreased labyrinthine and increased depression types in only the CT muscle. In the aged group, morphologically immature subneural apparatuses were found infrequently in the CT muscle, indicating continued tissue remodeling. We suggest, therefore, that age-related changes in the intrinsic laryngeal muscles primarily involve the CT muscle, whereas the structures of the TA and PCA muscles may better resist aging processes and therefore are less vulnerable to functional impairment. This may reflect differences in their roles; the CT muscle controls the tone of the vocal folds, while the TA and PCA muscles play an essential role in vital activities such as respiration and swallowing. PMID:23100084

  7. Age-Related Differences in Profiles of Mood-Change Trajectories

    ERIC Educational Resources Information Center

    Stanley, Jennifer Tehan; Isaacowitz, Derek M.

    2011-01-01

    As a group, older adults report positive affective lives. The extent to which there are subgroups of older adults whose moods are less positive, however, is unclear. Our aim in the present study was to identify and characterize different subgroups of adults who exhibit distinct trajectories of mood change across a relatively short time period.…

  8. Age-related changes in body composition in laboratory rats: Strain and gender comparisons

    EPA Science Inventory

    Long Evans (LE), Sprague Dawley (SD), Fischer 344 (F344), and Brown Norway (BN) rats are all commonly used as laboratory research subjects. These strains have been studied under many conditions, but few studies have measured changes in body composition as the animals age. Underst...

  9. Age-related changes in microRNA expression and pharmacogenes in human liver

    PubMed Central

    Burgess, Kimberly S.; Philips, Santosh; Benson, Eric A.; Desta, Zeruesenay; Gaedigk, Andrea; Gaedigk, Roger; Segar, Matthew W.; Liu, Yunlong; Skaar, Todd C.

    2015-01-01

    Developmental changes in the liver can significantly impact drug disposition. Due to the emergence of microRNAs (miRNAs) as important regulators of drug disposition gene expression, we studied age-dependent changes in miRNA expression. Expression of 533 miRNAs was measured in 90 human liver tissues (fetal, pediatric (1-17 years), and adult (28-80 years); n=30 each). 114 miRNAs were upregulated and 72 were downregulated from fetal to pediatric, and 2 and 3, respectively, from pediatric to adult. Among the developmentally changing miRNAs, 99 miRNA-mRNA interactions were predicted or experimentally validated (e.g. hsamiR-125b-5p-CYP1A1; hsa-miR-34a-5p-HNF4A). In human liver samples (n=10 each), analyzed by RNA-sequencing, significant negative correlations were observed between the expression of >1000 miRNAs and mRNAs of drug disposition and regulatory genes. Our data suggest a mechanism for the marked changes in hepatic gene expression between the fetal and pediatric developmental periods, and support a role for these age-dependent miRNAs in regulating drug disposition. PMID:25968989

  10. Age-related changes in the plasticity and toughness of human cortical bone at multiple length-scales

    SciTech Connect

    Zimmermann, Elizabeth A.; Schaible, Eric; Bale, Hrishikesh; Barth, Holly D.; Tang, Simon Y.; Reichert, Peter; Busse, Bjoern; Alliston, Tamara; Ager III, Joel W.; Ritchie, Robert O.

    2011-08-10

    The structure of human cortical bone evolves over multiple length-scales from its basic constituents of collagen and hydroxyapatite at the nanoscale to osteonal structures at nearmillimeter dimensions, which all provide the basis for its mechanical properties. To resist fracture, bone’s toughness is derived intrinsically through plasticity (e.g., fibrillar sliding) at structural-scales typically below a micron and extrinsically (i.e., during crack growth) through mechanisms (e.g., crack deflection/bridging) generated at larger structural-scales. Biological factors such as aging lead to a markedly increased fracture risk, which is often associated with an age-related loss in bone mass (bone quantity). However, we find that age-related structural changes can significantly degrade the fracture resistance (bone quality) over multiple lengthscales. Using in situ small-/wide-angle x-ray scattering/diffraction to characterize sub-micron structural changes and synchrotron x-ray computed tomography and in situ fracture-toughness measurements in the scanning electron microscope to characterize effects at micron-scales, we show how these age-related structural changes at differing size-scales degrade both the intrinsic and extrinsic toughness of bone. Specifically, we attribute the loss in toughness to increased non-enzymatic collagen cross-linking which suppresses plasticity at nanoscale dimensions and to an increased osteonal density which limits the potency of crack-bridging mechanisms at micron-scales. The link between these processes is that the increased stiffness of the cross-linked collagen requires energy to be absorbed by “plastic” deformation at higher structural levels, which occurs by the process of microcracking.

  11. Age-related changes in the plasticity and toughness of human cortical bone at multiple length scales.

    PubMed

    Zimmermann, Elizabeth A; Schaible, Eric; Bale, Hrishikesh; Barth, Holly D; Tang, Simon Y; Reichert, Peter; Busse, Bjoern; Alliston, Tamara; Ager, Joel W; Ritchie, Robert O

    2011-08-30

    The structure of human cortical bone evolves over multiple length scales from its basic constituents of collagen and hydroxyapatite at the nanoscale to osteonal structures at near-millimeter dimensions, which all provide the basis for its mechanical properties. To resist fracture, bone's toughness is derived intrinsically through plasticity (e.g., fibrillar sliding) at structural scales typically below a micrometer and extrinsically (i.e., during crack growth) through mechanisms (e.g., crack deflection/bridging) generated at larger structural scales. Biological factors such as aging lead to a markedly increased fracture risk, which is often associated with an age-related loss in bone mass (bone quantity). However, we find that age-related structural changes can significantly degrade the fracture resistance (bone quality) over multiple length scales. Using in situ small-angle X-ray scattering and wide-angle X-ray diffraction to characterize submicrometer structural changes and synchrotron X-ray computed tomography and in situ fracture-toughness measurements in the scanning electron microscope to characterize effects at micrometer scales, we show how these age-related structural changes at differing size scales degrade both the intrinsic and extrinsic toughness of bone. Specifically, we attribute the loss in toughness to increased nonenzymatic collagen cross-linking, which suppresses plasticity at nanoscale dimensions, and to an increased osteonal density, which limits the potency of crack-bridging mechanisms at micrometer scales. The link between these processes is that the increased stiffness of the cross-linked collagen requires energy to be absorbed by "plastic" deformation at higher structural levels, which occurs by the process of microcracking. PMID:21873221

  12. Sex-dependent modulation of age-related cognitive decline by the L-type calcium channel gene Cacna1c (Cav 1.2).

    PubMed

    Zanos, Panos; Bhat, Shambhu; Terrillion, Chantelle E; Smith, Robert J; Tonelli, Leonardo H; Gould, Todd D

    2015-10-01

    Increased calcium influx through L-type voltage-gated calcium channels has been implicated in the neuronal dysfunction underlying age-related memory declines. The present study aimed to test the specific role of Cacna1c (which encodes Cav 1.2) in modulating age-related memory dysfunction. Short-term, spatial and contextual/emotional memory was evaluated in young and aged, wild-type as well as mice with one functional copy of Cacna1c (haploinsufficient), using the novel object recognition, Y-maze and passive avoidance tasks, respectively. Hippocampal expression of Cacna1c mRNA was measured by quantitative polymerase chain reaction. Ageing was associated with object recognition and contextual/emotional memory deficits, and a significant increase in hippocampal Cacna1c mRNA expression. Cacna1c haploinsufficiency was associated with decreased Cacna1c mRNA expression in both young and old animals. However, haploinsufficient mice did not manifest an age-related increase in expression of this gene. Behaviourally, Cacna1c haploinsufficiency prevented object recognition deficits during ageing in both male and female mice. A significant correlation between higher Cacna1c levels and decreased object recognition performance was observed in both sexes. Also, a sex-dependent protective role of decreased Cacna1c levels in contextual/emotional memory loss has been observed, specifically in male mice. These data provide evidence for an association between increased hippocampal Cacna1c expression and age-related cognitive decline. Additionally, they indicate an interaction between the Cacna1c gene and sex in the modulation of age-related contextual memory declines. PMID:25989111

  13. Age-related changes in tissue macrophages precede cardiac functional impairment.

    PubMed

    Pinto, Alexander R; Godwin, James W; Chandran, Anjana; Hersey, Lucy; Ilinykh, Alexei; Debuque, Ryan; Wang, Lina; Rosenthal, Nadia A

    2014-05-01

    Cardiac tissue macrophages (cTMs) are abundant in the murine heart but the extent to which the cTM phenotype changes with age is unknown. This study characterizes aging-dependent phenotypic changes in cTM subsets. Using theCx3cr1(GFP/+) mouse reporter line where GFP marks cTMs, and the tissue macrophage marker Mrc1, we show that two major cardiac tissue macrophage subsets, Mrc1-GFP(hi) and Mrc1+GFP(hi) cTMs, are present in the young (<10 week old) mouse heart, and a third subset, Mrc1+GFP(lo), comprises ~50% of total Mrc1+ cTMs from 30 weeks of age. Immunostaining and functional assays show that Mrc1+ cTMs are the principal myeloid sentinels in the mouse heart and that they retain proliferative capacity throughout life. Gene expression profiles of the two Mrc1+ subsets also reveal that Mrc1+GFP(lo) cTMs have a decreased number of immune response genes (Cx3cr1, Lpar6, CD9, Cxcr4, Itga6 and Tgfβr1), and an increased number of fibrogenic genes (Ltc4s, Retnla, Fgfr1, Mmp9 and Ccl24), consistent with a potential role for cTMs in cardiac fibrosis. These findings identify early age-dependent gene expression changes in cTMs, with significant implications for cardiac tissue injury responses and aging-associated cardiac fibrosis. PMID:24861132

  14. Full circle: 3D femoral mapping demonstrates age-related changes that influence femoral implant positioning.

    PubMed

    Tucker, Damien; Surup, Timm; Petersik, Andreas; Kelly, Michael

    2016-02-01

    The geometry of the femur is important in the final position of an intramedullary implant; we hypothesised that the femoral geometry changes with age and this may predispose the elderly to anterior mal-positioning of these implants. We used CT DICOM data of 919 intact left femora and specialist software that allowed us to defined landmarks for measurement reference - such as the linea aspera - on a template bone that could be mapped automatically to the entire database. We found that older (>80 years) cortical bone is up to 1.5 mm thinner anteriorly and 2 mm thinner posteriorly than younger (<40 years) bone but the rate of change of posterior to anterior cortex thickness is greater in the older bone. We also found the isthmus in the elderly to be more distal and less substantial than in the younger bone. This study has demonstrated femoral geometry changes with age that may explain our perception that the elderly are at increased risk for anterior mal-positioning of intramedullary implants. PMID:26686594

  15. Endopolyploidy Changes with Age-Related Polyethism in the Honey Bee, Apis mellifera

    PubMed Central

    Rangel, Juliana; Strauss, Kim; Seedorf, Kaileah; Hjelmen, Carl E.; Johnston, J. Spencer

    2015-01-01

    Honey bees (Apis mellifera) exhibit age polyethism, whereby female workers assume increasingly complex colony tasks as they age. While changes in DNA methylation accompany age polyethism, other DNA modifications accompanying age polyethism are less known. Changes in endopolyploidy (DNA amplification in the absence of cell division) with increased larval age are typical in many insect cells and are essential in adults for creating larger cells, more copies of essential loci, or greater storage capacity in secretory cells. However, changes in endopolyploidy with increased adult worker age and polyethism are unstudied. In this study, we examined endopolyploidy in honey bee workers ranging in age from newly emerged up to 55 days old. We found a nonsignificant increase in ploidy levels with age (P < 0.1) in the most highly endopolyploid secretory cells, the Malpighian tubules. All other cell types decreased ploidy levels with age. Endopolyploidy decreased the least amount (nonsignificant) in neural (brain) cells and the stinger (P < 0.1). There was a significant reduction of endopolyploidy with age in leg (P < 0.05) and thoracic (P < 0.001) muscles. Ploidy in thoracic muscle dropped from an average of 0.5 rounds of replication in newly emerged workers to essentially no rounds of replication (0.125) in the oldest workers. Ploidy reduction in flight muscle cells is likely due to the production of G1 (2C) nuclei by amitotic division in the multinucleate striated flight muscles that are essential to foragers, the oldest workers. We suggest that ploidy is constrained by the shape, size and makeup of the multinucleate striated muscle cells. Furthermore, the presence of multiple 2C nuclei might be optimal for cell function, while higher ploidy levels might be a dead-end strategy of some aging adult tissues, likely used to increase cell size and storage capacity in secretory cells. PMID:25881205

  16. Age-related changes to cardiac systolic and diastolic function during whole-body passive hyperthermia

    PubMed Central

    Lucas, Rebekah A. I.; Sarma, Satyam; Schlader, Zachary J.; Pearson, James; Crandall, Craig G.

    2016-01-01

    The effect of ageing on hyperthermia-induced changes in cardiac function is unknown. This study tested the hypothesis that hyperthermia-induced changes in left ventricular systolic and diastolic function are attenuated in older adults when compared with young adults. Eight older (71 ± 5 years old) and eight young adults (29 ± 5 years old), matched for sex, physical activity and body mass index, underwent whole-body passive hyperthermia. Mean arterial pressure (Finometer Pro), heart rate, forearm vascular conductance (venous occlusion plethysmography) and echocardiographic indices of diastolic and systolic function were measured during a normothermic supine period and again after an increase in internal temperature of ~1.0 °C. Hyperthermia decreased mean arterial pressure and left ventricular end-diastolic volumes and increased heart rate to a similar extent in both groups (P > 0.05). Ageing did not alter the magnitude of hyperthermia-induced changes in indices of systolic (lateral mitral annular S′ velocity) or diastolic function (lateral mitral annular E′ velocity, peak early diastolic filling and isovolumic relaxation time; P > 0.05). However, with hyperthermia the global longitudinal systolic strain increased in the older group, but was unchanged in the young group (P = 0.03). Also, older adults were unable to augment late diastolic ventricular filling [i.e. E/A ratio and A/(A + E) ratio] during hyperthermia, unlike the young (P <0.05). These findings indicate that older adults depend on a greater systolic contribution (global longitudinal systolic strain) to meet hyperthermic demand and that the atrial contribution to diastolic filling was not further augmented in older adults when compared with young adults. PMID:25641368

  17. Investigation of age-related changes in LMNA splicing and expression of progerin in human skeletal muscles.

    PubMed

    Luo, Yue-Bei; Mitrpant, Chalermchai; Johnsen, Russell D; Fabian, Victoria A; Fletcher, Sue; Mastaglia, Frank L; Wilton, Steve D

    2013-01-01

    Age-related changes in splice-forms of LMNA, which encodes the nuclear lamina proteins lamin A/C, have not been investigated in skeletal muscle. In the rare premature ageing disease, Hutchinson-Gilford progeria syndrome (HGPS), de novo point mutations in LMNA activate a cryptic splice site in exon 11, resulting in a 150 base deletion in LMNA mRNA and accumulation of a truncated protein isoform, progerin. The LMNA Δ150 progerin transcript has also been found in trace quantities in tissues of healthy people and its implication in 'natural' ageing has been proposed. We therefore investigated the expression of progerin and lamin A/C in normal human and mouse skeletal muscles of different ages. LMNA Δ150 was detected in most muscle samples from healthy individuals aged 16-71 years, but was not present in any mouse muscle samples up to the age of 18 months. Real time qPCR of human muscle samples showed that there was an age-related increase in both the full length lamin A and LMNA Δ150 transcripts, whereas their protein levels did not change significantly with age. These findings indicate that there is a basal level of mis-splicing during LMNA expression that does not change with ageing in human muscle, but at levels that do not result in increased aberrant protein. The significance of these findings in the pathophysiology of muscle ageing is uncertain and warrants further investigation. PMID:24294364

  18. Investigation of age-related changes in LMNA splicing and expression of progerin in human skeletal muscles

    PubMed Central

    Luo, Yue-Bei; Mitrpant, Chalermchai; Johnsen, Russell D; Fabian, Victoria A; Fletcher, Sue; Mastaglia, Frank L; Wilton, Steve D

    2013-01-01

    Age-related changes in splice-forms of LMNA, which encodes the nuclear lamina proteins lamin A/C, have not been investigated in skeletal muscle. In the rare premature ageing disease, Hutchinson-Gilford progeria syndrome (HGPS), de novo point mutations in LMNA activate a cryptic splice site in exon 11, resulting in a 150 base deletion in LMNA mRNA and accumulation of a truncated protein isoform, progerin. The LMNA Δ150 progerin transcript has also been found in trace quantities in tissues of healthy people and its implication in ‘natural’ ageing has been proposed. We therefore investigated the expression of progerin and lamin A/C in normal human and mouse skeletal muscles of different ages. LMNA Δ150 was detected in most muscle samples from healthy individuals aged 16-71 years, but was not present in any mouse muscle samples up to the age of 18 months. Real time qPCR of human muscle samples showed that there was an age-related increase in both the full length lamin A and LMNA Δ150 transcripts, whereas their protein levels did not change significantly with age. These findings indicate that there is a basal level of mis-splicing during LMNA expression that does not change with ageing in human muscle, but at levels that do not result in increased aberrant protein. The significance of these findings in the pathophysiology of muscle ageing is uncertain and warrants further investigation. PMID:24294364

  19. Age-Related Change in Mobility: Perspectives From Life Course Epidemiology and Geroscience.

    PubMed

    Ferrucci, Luigi; Cooper, Rachel; Shardell, Michelle; Simonsick, Eleanor M; Schrack, Jennifer A; Kuh, Diana

    2016-09-01

    Mobility is the most studied and most relevant physical ability affecting quality of life with strong prognostic value for disability and survival. Natural selection has built the "engine" of mobility with great robustness, redundancy, and functional reserve. Efficient patterns of mobility can be acquired during development even by children affected by severe impairments. Analogously, age-associated impairments in mobility-related physiological systems are compensated and overt limitations of mobility only occur when the severity can no longer be compensated. Mobility loss in older persons usually results from multiple impairments in the central nervous system, muscles, joints, and energetic and sensory physiological systems. Early preclinical changes in these physiological systems that precede mobility loss have been poorly studied. Peak performance, rate of decline, compensatory behaviors, or subclinical deterioration of physiological resources may cumulatively influence both timing of mobility loss and chances of recovery, but their role as risk factors has not been adequately characterized. Understanding the natural history of these early changes and intervening on them would likely be the most effective strategy to reduce the burden of disability in the population. For example, young women with low bone peak mass could be counseled to start strength resistance exercise to reduce their high risk of developing osteoporosis and fracture later in life. Expanding this approach to other physiological domains requires collecting and interpreting data from life course epidemiological studies, establishing normative measures of mobility, physical function, and physical activity, and connecting them with life course trajectories of the mobility-relevant physiological domains. PMID:26975983

  20. Age-related changes in executive control and their relationships with activity performance in handwriting.

    PubMed

    Rosenblum, Sara; Engel-Yeger, Batya; Fogel, Yael

    2013-04-01

    Deterioration in the frontal and prefrontal cortex associated with executive functions (EF) occurs with age and may be associated with changes in daily performance. The aim of the present study was to describe changes occurring with age in Executive Functions (EF) and handwriting activity, as well as to analyze relationships between age, EF and handwriting performance. The study population included 80 healthy participants (aged 31 to 76+) living in the community. After answering five questions about their writing habits, the participants completed the Behavioral Assessment of the Dysexecutive Syndrome (BADS). In addition, they performed a handwriting task on a digitizer included in the Computerized Penmanship Evaluation Tool (ComPET), which provides kinematic measures of the handwriting process. Significant differences were found between the four age groups for both EF and temporal and spatial handwriting measures. A series of regressions indicated that age predicted 35% of the variance of the BADS profile score (EF control) and 32% of the variance of in-air time while writing. The results of this study indicated age effect on both EF control and handwriting performance. Possible implications for further research and clinical evaluation and intervention are discussed. PMID:23558056

  1. Age-related Changes in Error Processing in Young Children: A School-based Investigation

    PubMed Central

    Grammer, Jennie K.; Carrasco, Melisa; Gehring, William J.; Morrison, Frederick J.

    2014-01-01

    Growth in executive functioning skills (EF) play a role children’s academic success, and the transition to elementary school is an important time for the development of these abilities. Despite this, evidence concerning the development of the ERP components linked to EF, including the error-related negativity (ERN) and the error positivity (Pe), over this period is inconclusive. Data were recorded in a school setting from 3–7 year-old children (N=96, mean age=5 years 11 months) as they performed a Go/No-Go task. Results revealed the presence of the ERN and Pe on error relative to correct trials at all age levels. Older children showed increased response inhibition as evidenced by faster, more accurate responses. Although developmental changes in the ERN were not identified, the Pe increased with age. In addition, girls made fewer mistakes and showed elevated Pe amplitudes relative to boys. Based on a representative school-based sample, findings indicate that the ERN is present in children as young as 3, and that development can be seen in the Pe between ages 3–7. Results varied as a function of gender, providing insight into the range of factors associated with developmental changes in the complex relations between behavioral and electrophysiological measures of error processing. PMID:24631799

  2. [Dynamic age-related changes in the human physique at stages in postnatal development].

    PubMed

    Shaparenko, P F

    1989-12-01

    In 926 children (7 age groups) combined group differences of the signs have been studied by means of a unified standardized method, using the hand length as a linear measure; the conformity index to definitive size has been applied. For newborns proportional discrepancy to the definitive sizes is specific. They have a relatively long, thick and round body, short extremities, large dimensions of the head and abundant adipose subcutaneous deposits. According to the constitutional peculiarities the newborns resemble the children of the digestive type in mature persons--pycnotic or endomorphic. Beginning from birth, including children of early and first childhood (4-7 years of age), age changes of complexion go in two directions: a) dolichomorphy of complexion is realized; for it decreasing diameters of the chest and dimensions of the neck, chest, abdomen, pelvis (in boys), shoulder, arm, hand, foot and decrease in the subcutaneous adipose tissue are specific; b) longitudinal proportions of body and extremity segments change under influence of biomechanical adaptations to physical loads in connection with adaptation to the vertical position. PMID:2631652

  3. Effects of Aerobic Fitness on Aging-Related Changes of Interhemispheric Inhibition and Motor Performance

    PubMed Central

    McGregor, Keith M.; Nocera, Joe R.; Sudhyadhom, Atchar; Patten, Carolynn; Manini, Todd M.; Kleim, Jeffrey A.; Crosson, Bruce; Butler, Andrew J.

    2013-01-01

    Physical fitness has been long associated with maintenance and improvement of motor performance as we age. In particular, measures of psychomotor speed and motor dexterity tend to be higher in physically fit aging adults as compared to their sedentary counterparts. Using functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS), we explored the patterns of neural activity that may, in part, account for differences between individuals of varying physical fitness levels. In this study, we enrolled both sedentary and physically fit middle age (40–60) and younger (18–30) adults and measured upper extremity motor performance during behavioral testing. In a follow-up session, we employed TMS and fMRI to assess levels of interhemispheric communication during unimanual tasks. Results show that increased physical fitness is associated with better upper extremity motor performance on distal dexterity assessments and increased levels of interhemispheric inhibition in middle age adults. Further, the functional correlates of changes of ipsilateral activity appears to be restricted to the aging process as younger adults of varying fitness levels do not differ in hemispheric patterns of activity or motor performance. We conclude that sedentary aging confers a loss of interhemispheric inhibition that is deleterious to some aspects of motor function, as early as midlife, but these changes can be mediated by chronic engagement in aerobic exercise. PMID:24198784

  4. Maternal inflammation linearly exacerbates offspring age-related changes of spatial learning and memory, and neurobiology until senectitude.

    PubMed

    Li, Xue-Wei; Cao, Lei; Wang, Fang; Yang, Qi-Gang; Tong, Jing-Jing; Li, Xue-Yan; Chen, Gui-Hai

    2016-06-01

    Maternal inflammation during pregnancy can elevate the risk of neurodegenerative disorders in offspring. However, how it affects age-related impairments of spatial learning and memory and changes in the neurobiological indictors in the offspring in later adulthood is still elusive. In this study, the CD-1 mice with maternal gestational inflammation due to receiving lipopolysaccharide (LPS, i.p. 50 or 25μg/kg) were divided into 3-, 12-, 18-, and 22-month-old groups. The spatial learning and memory were evaluated using a six-radial arm water maze and the levels of presynaptic proteins (synaptotagmin-1 and syntaxin-1) and histone acetylation (H3K9ac and H4K8ac) in the dorsal hippocampus were detected using the immunohistochemical method. The results indicated that there were significant age-related impairments of spatial learning and memory, decreased levels of H4K8ac, H3K9ac, and syntaxin-1, and increased levels of synaptotagmin-1 in the offspring mice from 12 months old to 22 months old compared to the same-age controls. Maternal LPS treatment significantly exacerbated the offspring impairments of spatial learning and memory, the reduction of H3K9ac, H4K8ac, and syntaxin-1, and the increment of synaptotagmin-1 from 12 months old to 22 months old compared to the same-age control groups. The changes in the neurobiological indicators significantly correlated with the impairments of spatial learning and memory. Furthermore, this correlation, besides the age and LPS-treatment effects, also showed a dose-dependent effect. Our results suggest that maternal inflammation during pregnancy could exacerbate age-related impairments of spatial learning and memory, and neurobiochemical indicators in the offspring CD-1 mice from midlife to senectitude. PMID:26992827

  5. Reduction in white matter connectivity, revealed by diffusion tensor imaging, may account for age-related changes in face perception.

    PubMed

    Thomas, Cibu; Moya, Linda; Avidan, Galia; Humphreys, Kate; Jung, Kwan Jin; Peterson, Mary A; Behrmann, Marlene

    2008-02-01

    An age-related decline in face processing, even under conditions in which learning and memory are not implicated, has been well documented, but the mechanism underlying this perceptual alteration remains unknown. Here, we examine whether this behavioral change may be accounted for by a reduction in white matter connectivity with age. To this end, we acquired diffusion tensor imaging data from 28 individuals aged 18 to 86 years and quantified the number of fibers, voxels, and fractional anisotropy of the two major tracts that pass through the fusiform gyrus, the pre-eminent face processing region in the ventral temporal cortex. We also measured the ability of a subset of these individuals to make fine-grained discriminations between pairs of faces and between pairs of cars. There was a significant reduction in the structural integrity of the inferior fronto-occipital fasciculus (IFOF) in the right hemisphere as a function of age on all dependent measures and there were also some changes in the left hemisphere, albeit to a lesser extent. There was also a clear age-related decrement in accuracy of perceptual discrimination, especially for more challenging perceptual discriminations, and this held to a greater degree for faces than for cars. Of greatest relevance, there was a robust association between the reduction of IFOF integrity in the right hemisphere and the decline in face perception, suggesting that the alteration in structural connectivity between the right ventral temporal and frontal cortices may account for the age-related difficulties in face processing. PMID:18275334

  6. Age-related changes in human vestibulo-ocular and optokinetic reflexes: Pseudorandom rotation tests

    NASA Technical Reports Server (NTRS)

    Peterka, R. J.; Black, F. O.; Schoenhoff, M. B.

    1989-01-01

    The dynamic response properties of horizontal vestibulo-ocular reflex (VOR) and optokinetic reflex (OKR) were characterized in 216 human subjects ranging in age from 7 to 81 years. The object of this cross-sectional study was to determine the effects of aging on VOR and OKR reflex dynamics, and to identify the distributions of parameters which describe VOR and OKR responses to pseudorandom stimuli in a putatively normal population. In general, VOR and OKR response parameters changed in a manner consistent with declining function with increasing age. For the VOR this was reflected in declining response amplitudes, although the magnitude of the decline was small relative to the variability of the data. For the OKR the lag time of the response, probably associated with the time required for visual information processing, increased linearly with age at a rate of about 1 ms per year.

  7. Age related changes in the bone tissue under conditions of hypokinesia

    NASA Technical Reports Server (NTRS)

    Podrushnyak, E. P.; Suslov, E. I.

    1980-01-01

    Microroentgenography of nine young people, aged 24-29, before and after hypokinesia (16-37 days strict bed rest), showed that the heel bone density of those with initially high bone density generally decreased and that of those with initially low bone density generally increased. X-ray structural analysis of the femurs of 25 corpses of accidentally killed healthy people, aged 18-70, data are presented and discussed, with the conclusion that the bone hydroxyapatite crystal structure stabilizes by ages 20 to 25, is stable from ages 25 to 60 and decreases in density after age 60. It is concluded that bone tissue structure changes, both with age, and in a comparatively short time in hypokinesia.

  8. The age-related quantitative ultrastructural changes in pinealocytes of gerbils.

    PubMed

    Swietoslawski, Jacek

    1999-01-01

    OBJECTIVES. Relatively few ultrastructural studies of the pineal gland of aging animals have been published. The pineal gland of the gerbil is especially interesting in respect to aging because of its progressive calcification with age, and this species has been considered as an excellent model for research on aging. Therefore, the aim of the present study was to examine the quantitative ultrastructure of pinealocytes of the gerbil in three different age groups. METHODS. Three groups of animals were included in the study: 1-month-old, 3-month-old, and 14-month-old. Cross-sectional areas of the pinealocyte and its nucleus and relative volumes of the following cell organelles: mitochondria, lysosomes, Golgi apparatus, granular endoplasmic reticulum and calcareous concretions as well as the number of dense-core vesicles and "synaptic" ribbons were analyzed. RESULTS. No age-dependent changes were observed in the size of pinealocytes and their nuclei. The relative volume of mitochondria and the number of dense-core vesicles increased progressively with age, and that of lysosomes was lowest in the 1-month-old animals and increased at age of 3 and 14 months, whereas a decrease in the relative volume of granular endoplasmic reticulum was observed in 3- and 14-month-old gerbils in comparison with 1-month-old animals. No difference was observed in relative volume of Golgi apparatus and in the number of "synaptic" ribbons. The most striking change was observed in the formation of calcareous concretion within the pineal with age. The pineal gland of 1-month-old gerbils was essentially devoid of these structures, their number and size in 3-month-old animals were moderate, and increased dramatically in 14-month-old animals. CONCLUSION. The ultrastructural features of the gerbil pinealocyte in all examined age groups point to high metabolic activity of these cells. PMID:11458204

  9. Age-related changes in renal AQP3 and AQP4 expression in Sprague Dawley rats.

    PubMed

    Jing, X H; Liu, J; Hou, W Y; Gao, Y

    2016-01-01

    Aquaporin (AQP) 3 and AQP4 are important in urine concentrating mechanisms and in other physiological functions such as brain water balance, cell migration, cell proliferation, fat metabolism, and epidermal hydration. The results of studies investigating AQP3 and AQP4 expression in the kidneys are inconsistent, and systematic research is rare. This study aimed to obtain a better understanding of the changes in renal AQP3 and AQP4 mRNA expression that take place with age. The expression of AQP3 and AQP4 mRNA, during prenatal and postnatal development, and during aging, was investigated in kidneys from Sprague-Dawley rats. The pattern of AQP3 expression was similar to that of AQP4 expression during development, and both were detected at gestational day 19 in the rat kidney where they maintained a stable level to postnatal day 14. Subsequently, a significant increase in expression was observed from day 21 to day 35, with peak expression occurring at day 35. No significant change in AQP3 or AQP4 mRNA expression was observed after day 35, apart from AQP4, which increased at day 540. Moreover, the expression of both AQP3 and AQP4 on day 850 was higher than on day -2, and lower than on days 28 and 35. The expression of AQP3 and AQP4 was similar on days 1, 7, 14, and 21. These findings indicate that mRNA expression of AQP3 and AQP4 varies with age, which should be considered when treating kidney disease in pediatric and elderly patients. PMID:27525904

  10. Henle Fiber Layer Phase Retardation Changes Associated With Age-Related Macular Degeneration

    PubMed Central

    VanNasdale, Dean A.; Elsner, Ann E.; Peabody, Todd D.; Kohne, Kimberly D.; Malinovsky, Victor E.; Haggerty, Bryan P.; Weber, Anke; Clark, Christopher A.; Burns, Stephen A.

    2015-01-01

    Purpose. To quantify and compare phase retardation amplitude and regularity associated with the Henle fiber layer (HFL) between nonexudative AMD patients and age-matched controls using scanning laser polarimetry (SLP) imaging. Methods. A scanning laser polarimeter was used to collect 15 × 15° macular-centered images in 25 patients with nonexudative AMD and 25 age-matched controls. Raw image data were used to compute macular phase retardation maps associated with the HFL. Consecutive, annular regions of interest from 0.5 to 3.0° eccentricity, centered on the fovea, were used to generate intensity profiles from phase retardation data and analyzed with two complementary techniques: a normalized second harmonic frequency (2f) of the fast Fourier Transform (FFT) analysis and a curve fitting analysis using a 2f sine function. Paired t-tests were used to compare the normalized 2f FFT magnitude at each eccentricity between the two groups, the eccentricity that yielded the maximum normalized 2f FFT between paired individuals across the two groups, and curve fitting RMS error at each eccentricity between the two groups. Results. Normalized 2f FFT components were lower in the AMD group at each eccentricity, with no difference between the two groups in the maximum normalized 2f FFT component eccentricity. The root-mean-square (RMS) error from curve fitting was significantly higher in the AMD group. Conclusions. Phase retardation changes in the central macula indicate loss and/or structural alterations to central cone photoreceptors in nonexudative AMD patients. Scanning laser polarimetry imaging is a noninvasive method for quantifying cone photoreceptor changes associated with central macular disease. PMID:25525166

  11. Age-related cognitive decline and electroencephalogram slowing in Down's syndrome as a model of Alzheimer's disease.

    PubMed

    Soininen, H; Partanen, J; Jousmäki, V; Helkala, E L; Vanhanen, M; Majuri, S; Kaski, M; Hartikainen, P; Riekkinen, P

    1993-03-01

    We studied quantitative electroencephalogram and neuropsychological performance in an aging series of 31 patients with Down's syndrome and compared the findings with those of 36 patients with probable Alzheimer's disease and age-matched controls. We found an age-related decline of cortical functions and slowing of the electroencephalogram in Down's syndrome patients aged from 20 to 60 years. Slowing of the electroencephalogram, i.e. the decrease of the peak frequency, was significantly related to Mini-Mental status scores, and visual, praxic and speech functions, as well as memory in the Down patients, similar to the Alzheimer patients. Similar correlations were not demonstrated for young or elderly controls. This study provides neuropsychological and electrophysiological data to suggest that studying Down's syndrome patients of different ages can serve as a model for progression of Alzheimer's disease. PMID:8469312

  12. Age-related changes in the control of finger force vectors.

    PubMed

    Kapur, Shweta; Zatsiorsky, Vladimir M; Latash, Mark L

    2010-12-01

    We explored changes in finger interaction in the process of healthy aging as a window into neural control strategies of natural movements. In particular, we quantified the amount of force produced by noninstructed fingers in different directions, the amount of force produced by the instructed finger orthogonally to the task direction, and the strength of multifinger synergies stabilizing the total force magnitude and direction during accurate force production. Healthy elderly participants performed accurate isometric force production tasks in five directions by individual fingers and by all four fingers acting together. Their data were compared with a dataset obtained in a similar earlier study of young subjects. Finger force vectors were measured using six-component force/torque sensors. Multifinger synergies were quantified using the framework of the uncontrolled manifold hypothesis. The elderly participants produced lower force magnitudes by noninstructed fingers and higher force magnitudes by instructed fingers in nontask directions. They showed strong synergies stabilizing the magnitude and direction of the total force vector. However, the synergy indexes were significantly lower than those observed in the earlier study of young subjects. The results are consistent with an earlier hypothesis of preferential weakening of intrinsic hand muscles with age. We interpret the findings as a shift in motor control from synergic to element-based, which may be causally linked to the documented progressive neuronal death at different levels of the neural axis. PMID:20829494

  13. Age-related Changes in the Sleep-dependent Reorganization of Declarative Memories.

    PubMed

    Baran, Bengi; Mantua, Janna; Spencer, Rebecca M C

    2016-06-01

    Consolidation of declarative memories has been associated with slow wave sleep in young adults. Previous work suggests that, in spite of changes in sleep, sleep-dependent consolidation of declarative memories may be preserved with aging, although reduced relative to young adults. Previous work on young adults shows that, with consolidation, retrieval of declarative memories gradually becomes independent of the hippocampus. To investigate whether memories are similarly reorganized over sleep at the neural level, we compared functional brain activation associated with word pair recall following a nap and equivalent wake in young and older adults. SWS during the nap predicted better subsequent memory recall and was negatively associated with retrieval-related hippocampal activation in young adults. In contrast, in older adults there was no relationship between sleep and memory performance or with retrieval-related hippocampal activation. Furthermore, compared with young adults, postnap memory retrieval in older adults required strong functional connectivity of the hippocampus with the PFC, whereas there were no differences between young and older adults in the functional connectivity of the hippocampus following wakefulness. These results suggest that, although neural reorganization takes place over sleep in older adults, the shift is unique from that seen in young adults, perhaps reflecting memories at an earlier stage of stabilization. PMID:26918588

  14. Age-related changes in modular organization of human brain functional networks.

    PubMed

    Meunier, David; Achard, Sophie; Morcom, Alexa; Bullmore, Ed

    2009-02-01

    Graph theory allows us to quantify any complex system, e.g., in social sciences, biology or technology, that can be abstractly described as a set of nodes and links. Here we derived human brain functional networks from fMRI measurements of endogenous, low frequency, correlated oscillations in 90 cortical and subcortical regions for two groups of healthy (young and older) participants. We investigated the modular structure of these networks and tested the hypothesis that normal brain aging might be associated with changes in modularity of sparse networks. Newman's modularity metric was maximised and topological roles were assigned to brain regions depending on their specific contributions to intra- and inter-modular connectivity. Both young and older brain networks demonstrated significantly non-random modularity. The young brain network was decomposed into 3 major modules: central and posterior modules, which comprised mainly nodes with few inter-modular connections, and a dorsal fronto-cingulo-parietal module, which comprised mainly nodes with extensive inter-modular connections. The mean network in the older group also included posterior, superior central and dorsal fronto-striato-thalamic modules but the number of intermodular connections to frontal modular regions was significantly reduced, whereas the number of connector nodes in posterior and central modules was increased. PMID:19027073

  15. Age-related changes in adaptation to severe anemia in childhood in developing countries

    PubMed Central

    O'Donnell, Angela; Premawardhena, A.; Arambepola, M.; Allen, S. J.; Peto, T. E. A.; Fisher, C. A.; Rees, D. C.; Olivieri, Nancy F.; Weatherall, D. J.

    2007-01-01

    Severe forms of anemia in children in the developing countries may be characterized by different clinical manifestations at particular stages of development. Whether this reflects developmental changes in adaptation to anemia or other mechanisms is not clear. The pattern of adaptation to anemia has been assessed in 110 individuals with hemoglobin (Hb) E β-thalassemia, one of the commonest forms of inherited anemia in Asia. It has been found that age and Hb levels are independent variables with respect to erythropoietin response and that there is a decline in the latter at a similar degree of anemia during development. To determine whether this finding is applicable to anemia due to other causes, a similar study has been carried out on 279 children with severe anemia due to Plasmodium falciparum malaria; the results were similar to those in the patients with thalassemia. These observations may have important implications both for the better understanding of the pathophysiology of profound anemia in early life and for its more logical and cost-effective management. PMID:17517643

  16. Age-Related Changes in Population of Stromal Precursor Cells in Hematopoietic and Lymphoid Organs.

    PubMed

    Gorskaya, Yulia F.; Latzinik, Natalia V.; Shuklina, Ekaterina U.; Nesterenko, Vladimir G.

    2000-07-01

    It is shown that the content of precursor cells of stromal tissue (CFC-F) in the hemopoietic and lymphoid organs of SAMP (rapidly-ageing mice) and SAMR mice (mice with a normal ageing rate) decreases as the animals grow older. However the decrease in the content of CFC-F in SAMP mice begins substantially earlier - in the age group of 9-11 months, while in the SAMR mice - only in the age group of 16-19 months. It was found that the age reduction of the number to an equal degree relates to the whole population of CFC-F, in particular both the fraction of weakly-linked CFC-F, which is isolated by means of mechanical disaggregation of the tissue, and the fraction which may only be isolated using trypsin. It is shown that the concentration of inducible osteogenic precursor cells (IOPC) in the spleen of guinea pigs does not change with age, but their content in that organ in old animals (2-3 years old) drops by two times. It was found that in elderly animals the mass of the ectopic osseous tissue, formed by the implantation of an osteoinductor (autologous epithelium of the urinary bladder) in a system open for entrance of cells, decreases by two times. After curettage of the medullary cavity of guinea pig tibia (i.e. under conditions of an increased demand for osteogenic cells) the mass of induced ectopic osseous tissue decreases by 4 times, which indicates to the possible functional relationship between the pool of determined and inducible osteogenic precursor cells. On the whole, the obtained data show that during ageing there is a reduction in the number of stromal precursor cells (CFC-F and IOPC), which form a specific microenvironment for hemopoietic and lymphoid organs, which is important to understand the role of these cells in the development of age pathologies, in particular senile osteoporosis. PMID:12687170

  17. Age-related changes of serum mitochondrial uncoupling 1, rumen and rectal temperature in goats.

    PubMed

    Arfuso, Francesca; Rizzo, Maria; Giannetto, Claudia; Giudice, Elisabetta; Fazio, Francesco; Piccione, Giuseppe

    2016-07-01

    Thermoregulatory processes are induced not only by exposure to cold or heat but also by a variety of physiological situations including age, fasting and food intake that result in changes in body temperature. The aim of the present study was to evaluate the differences in serum mitochondrial uncoupling protein 1 (UCP1), rumen temperature (TRUMEN) and rectal temperature (TRECTAL) values between adult and kids goats. Ten adult male Maltese goats aged 3-5 years old (Group A) and 30 male kids, raised for meat, were enrolled in this study. The kids were equally divided into 3 groups according to their age: Group B included kids aged 3 months, Group C included kids aged 4 months and Group D included kids aged 5 months. Blood samples and measurements of TRUMEN and TRECTAL were obtained from each animal. One-way repeated measures analysis of variance (ANOVA) was applied to evaluate the effect of age on the studied parameters. Statistically significant higher serum UCP1 levels (P<0.001) were found in Group A as compared to Groups B, C and D. Higher TRUMEN values (P<0.001) were found in Group A than in Groups B, C and D, and in Group B than in Groups C and D. Group A showed lower TRECTAL values (P<0.001) than Groups B, C and D. The Pearson's Correlation test was applied to assess significant relationship among studied parameters showing a statistically significant negative correlation between the values of TRECTAL and serum UCP1 in all studied Groups (P<0.001). These results indicate that goats have good control of body temperature suggesting that further details about the thermogenic capacity and the function of UCP1 in kids and adult goats are worth exploring. PMID:27264887

  18. Age Related Changes in Craniofacial Morphology in GDF-8 (Myostatin) Deficient Mice

    PubMed Central

    Vecchione, Lisa; Miller, Jeffrey; Byron, Craig; Cooper, Gregory M.; Barbano, Timothy; Cray, James; Losee, Joseph E.; Hamrick, Mark W.; Sciote, James J.; Mooney, Mark P.

    2011-01-01

    It is well recognized that masticatory muscle function helps determine morphology, although the extent of function on final form is still debated. GDF-8 (myostatin), a transcription factor is a negative regulator of skeletal muscle growth. A recent study has shown that mice homozygous for the myostatin mutation had increased muscle mass and craniofacial dysmorphology in adulthood. However, it is unclear whether such dysmorphology is present at birth. This study examines the onset and relationship between hypermuscularity and craniofacial morphology in neonatal and adult mice with GDF-8 deficiency. Fifteen (8 wild-type and 7 GDF-8 −/−), 1 day old and 16 (9 wt and 7 GDF-8 −/−), 180 day old male CD-1 mice were used. Standardized radiographs were taken of each head, scanned, traced, and cephalometric landmarks identified. Significant mean differences were assessed using a group × age, two-way ANOVA. Myostatin-deficient mice had significantly (p<0.01) smaller body and masseter muscle weights and craniofacial skeletons at 1 day of age and significantly greater body and masseter muscle weights at 180 days of age compared to controls. Myostatin-deficient mice showed significantly (p<0.001) longer and “rocker-shaped” mandibles and shorter and wider crania compared to controls at 180 days. Significant correlations were noted between masseter muscle weight and all cephalometric measurements in 180 day old Myostatin-deficient mice. Results suggest in this mouse model, there may be both early systemic skeletal growth deficiencies and later compensatory changes from hypermuscularity. These findings reiterate the role that masticatory muscle function plays on the ontogeny of the cranial vault, base, and most notably the mandible. PMID:19899116

  19. Using the gradient of human cortical bone properties to determine age-related bone changes via ultrasonic guided waves.

    PubMed

    Baron, Cécile

    2012-06-01

    Bone fragility depends not only on bone mass but also on bone quality (structure and material). To accurately evaluate fracture risk or propose therapeutic treatment, clinicians need a criterion, which reflects the determinants of bone strength: geometry, structure and material. In human long bone, the changes due to aging, accentuated by osteoporosis are often revealed through the trabecularization of cortical bone, i.e., increased porosity of endosteal bone inducing a thinning of the cortex. Consequently, the intracortical porosity gradient corresponding to the spatial variation in porosity across the cortical thickness is representative of loss of mass, changes in geometry (thinning) and variations in structure (porosity). This article examines the gradient of material properties and its age-related evolution as a relevant parameter to assess bone geometry, structure and material. By applying a homogenization process, cortical bone can be considered as an anisotropic functionally graded material with variations in material properties. A semi-analytical method based on the sextic Stroh formalism is proposed to solve the wave equation in an anisotropic functionally graded waveguide for two geometries, a plate and a tube, without using a multilayered model to represent the structure. This method provides an analytical solution called the matricant and explicitly expressed under the Peano series expansion form. Our findings indicate that ultrasonic guided waves are sensitive to the age-related evolution of realistic gradients in human bone properties across the cortical thickness and have their place in a multimodal clinical protocol. PMID:22502890

  20. Age-Related Changes following In Vitro Stimulation with Rhodococcus equi of Peripheral Blood Leukocytes from Neonatal Foals

    PubMed Central

    Kachroo, Priyanka; Ivanov, Ivan; Seabury, Ashley G.; Liu, Mei; Chowdhary, Bhanu P.; Cohen, Noah D.

    2013-01-01

    Rhodococcus equi is an intracellular bacterium primarily known as an equine pathogen that infects young foals causing a pyogranulomatuous pneumonia. The molecular mechanisms mediating the immune response of foals to R. equi are not fully elucidated. Hence, global genomic high-throughput tools like gene expression microarrays might identify age-related gene expression signatures and molecular pathways that contribute to the immune mechanisms underlying the inherent susceptibility of foals to disease caused by R. equi. The objectives of this study were 2-fold: 1) to compare the expression profiles at specific ages of blood leukocytes from foals stimulated with virulent R. equi with those of unstimulated leukocytes; and, 2) to characterize the age-related changes in the gene expression profile associated with blood leukocytes in response to stimulation with virulent R. equi. Peripheral blood leukocytes were obtained from 6 foals within 24 hours (h) of birth (day 1) and 2, 4, and 8 weeks after birth. The samples were split, such that half were stimulated with live virulent R. equi, and the other half served as unstimulated control. RNA was extracted and the generated cDNA was labeled with fluorescent dyes for microarray hybridizations using an equine microarray. Our findings suggest that there is age-related differential expression of genes involved in host immune response and immunity. We found induction of genes critical for host immunity against pathogens (MHC class II) only at the later time-points (compared to birth). While it appears that foals up to 8-weeks of age are able to initiate a protective inflammatory response against the bacteria, relatively decreased expression of various other immune-related genes points toward inherent diminished immune responses closer to birth. These genes and pathways may contribute to disease susceptibility in foals if infected early in life, and might thus be targeted for developing preventative or therapeutic strategies. PMID

  1. The aging of elite male athletes: age-related changes in performance and skeletal muscle structure and function

    PubMed Central

    Faulkner, John A.; Davis, Carol S.; Mendias, Christopher L.; Brooks, Susan V.

    2009-01-01

    Objective The paper addresses the degree to which the attainment of the status as an elite athlete in different sports ameliorates the known age-related losses in skeletal muscle structure and function. Design The retrospective design, based on comparisons of published data on former elite and masters athletes and data on control subjects, assessed the degree to which the attainment of ‘elite and masters athlete status’ ameliorated the known age-related changes in skeletal muscle structure and function. Setting Institutional. Participants Elite male athletes. Interventions Participation in selected individual and team sports. Main Outcome Measurements Strength, power, VO2 max and performance. Results For elite athletes in all sports, as for the general population, age-related muscle atrophy begins at about 50 years of age. Despite the loss of muscle mass, elite athletes who maintain an active life style age gracefully with few health problems. Conversely, those who lapse into inactivity regress toward general population norms for fitness, weight control, and health problems. Elite athletes in the dual and team sports have careers that rarely extend into the thirties. Conclusions Life long physical activity does not appear to have any impact on the loss in fiber number. The loss of fibers can be buffered to some degree by hypertrophy of fibers that remain. Surprisingly, the performance of elite athletes in all sports appears to be impaired before the onset of the fiber loss. Even with major losses in physical capacity and muscle mass, the performance of elite and masters athletes is remarkable. PMID:19001883

  2. Age-Related Cognitive Impairment as a Sign of Geriatric Neurocardiovascular Interactions: May Polyphenols Play a Protective Role?

    PubMed Central

    Jagla, Fedor; Pechanova, Olga

    2015-01-01

    It is known that endothelial dysfunction plays an important role in the development and progression of cardiovascular diseases implicated also in cognitive decline. Experimental studies pointed to the fact that the modification of NO levels via NOS activity may affect the blood pressure level as well as several higher nervous functions—for example, learning and memory. There are emerging evidences from in vitro and animal studies suggesting that polyphenols may potentially have a protective effect on the development of neurodegenerative diseases and may improve cognitive function as well as positively affecting the blood pressure regulatory mechanisms. This review accentuates the need for precisely defined clinically controlled studies as well as for use of adequate experimental procedures discriminating between the human higher brain functions and the only overall activation of the brain cortex. The physiological neurocardiovascular interactions are implicated in the increased healthy life span as well. PMID:26180593

  3. Operationalizing diagnostic criteria for Alzheimer’s disease and other age-related cognitive impairment—Part 2*

    PubMed Central

    Seshadri, Sudha; Beiser, Alexa; Au, Rhoda; Wolf, Philip A.; Evans, Denis A.; Wilson, Robert S.; Petersen, Ronald C.; Knopman, David S.; Rocca, Walter A.; Kawas, Claudia H.; Corrada, Maria M.; Plassman, Brenda L.; Langa, Kenneth M.; Chui, Helena C.

    2011-01-01

    This article focuses on the effects of operational differences in case ascertainment on estimates of prevalence and incidence of cognitive impairment/dementia of the Alzheimer type. Experience and insights are discussed by investigators from the Framingham Heart Study, the East Boston Senior Health Project, the Chicago Health and Aging Project, the Mayo Clinic Study of Aging, the Baltimore Longitudinal Study of Aging, and the Aging, Demographics, and Memory Study. There is a general consensus that the single most important factor regulating prevalence estimates of Alzheimer’s disease (AD) is the severity of cognitive impairment used for case ascertainment. Studies that require a level of cognitive impairment in which persons are unable to provide self-care will have much lower estimates than studies aimed at identifying persons in the earliest stages of AD. There is limited autopsy data from the above-mentioned epidemiologic studies to address accuracy in the diagnosis of etiologic subtype, namely the specification of AD alone or in combination with other types of pathology. However, other community-based cohort studies show that many persons with mild cognitive impairment (MCI) meet pathologic criteria for AD, and a large minority of persons without dementia or MCI also meets pathologic criteria for AD, thereby suggesting that the number of persons who would benefit from an effective secondary prevention intervention is probably higher than the highest published prevalence estimates. Improved accuracy in the clinical diagnosis of AD is anticipated with the addition of molecular and structural biomarkers in the next generation of epidemiologic studies. PMID:21255742

  4. Characteristics of age-related behavioral changes in senescence-accelerated mouse SAMP8 and SAMP10.

    PubMed

    Miyamoto, M

    1997-01-01

    Senescence-Accelerated Mouse (SAM), a murine model of accelerated senescence, has been established by Takeda et al. (1981). SAM consists of senescence-accelerated-prone mouse (SAMP) and senescence-accelerated-resistant mouse (SAMR), the latter of which shows normal aging characteristics. In 1991 there were eight different substrains in the P-series, which commonly exhibited accelerated aging with a shortened life span (Takeda et al., 1991). Among the P-series, we have found that SAMP8 mice show significant impairments in a variety of learning tasks when compared with SAMR1 mice (Miyamoto et al., 1986). Further studies suggest that SAMP8 exhibits an age-related emotional disorder characterized by reduced anxiety-like behavior (Miyamoto et al., 1992). On the other hand, it has been shown that SAMP10 exhibits brain atrophy and learning impairments in an avoidance task (Shimada et al., 1992, 1993). Here, characteristics of age-related deficits in learning and memory, changes in emotional behavior, and abnormality of circadian rhythms in SAMP8 and SAMP10 mice are described. In the experiments, SAMP8/Ta (SAMP8), SAMP10/(/)Ta (SAMP10) and SAMR1TA (SAMR1) reared under specific pathogen-free conditions at Takeda Chemical Industries were used. PMID:9088911

  5. Age-related changes in the brain antioxidant status: modulation by dietary supplementation of Decalepis hamiltonii and physical exercise.

    PubMed

    Ravikiran, Tekupalli; Sowbhagya, Ramachandregowda; Anupama, Sindhghatta Kariyappa; Anand, Santosh; Bhagyalakshmi, Dundaiah

    2016-08-01

    The synergistic effects of physical exercise and diet have profound benefits on brain function. The present study was aimed to determine the effects of exercise and Decalepis hamiltonii (Dh) on age-related responses on the antioxidant status in discrete regions of rat brain. Male Wistar albino rats of 4 and 18 months old were orally supplemented with Dh extract and swim trained at 3 % intensity for 30 min/day, 5 days/week, for a period of 30 days. Supplementation of 100 mg Dh aqueous extract/kg body weight and its combination with exercise significantly elevated the antioxidant enzyme activities irrespective of age. Age-related and region-specific changes were observed in superoxide levels, and protein carbonyl and malondialdehyde contents, and were found to be decreased in both trained and supplemented groups. Levels of total thiols, protein, and nonprotein thiols decreased with age and significantly increased in the SW-T(+100 mg) groups. Our results demonstrated that the interactive effects of two treatments enhanced the antioxidant status and decreased the risk of protein and lipid oxidation in the rat brain. PMID:27379504

  6. Age-related differences in neural recruitment during the use of cognitive reappraisal and selective attention as emotion regulation strategies

    PubMed Central

    Allard, Eric S.; Kensinger, Elizabeth A.

    2014-01-01

    The present study examined age differences in the timing and neural recruitment within lateral and medial PFC while younger and older adults hedonically regulated their responses to unpleasant film clips. When analyses focused on activity during the emotional peak of the film clip (the most emotionally salient portion of the film), several age differences emerged. When comparing regulation to passive viewing (combined effects of selective attention and reappraisal) younger adults showed greater regulation related activity in lateral PFC (DLPFC, VLPFC, OFC) and medial PFC (ACC) while older adults showed greater activation within a region DLPFC. When assessing distinct effects of the regulation conditions, an ANOVA revealed a significant Age × Regulation Condition interaction within bilateral DLPFC and ACC; older adults but not young adults showed greater recruitment within these regions for reappraisal than selective attention. When examining activity at the onset of the film clip and at its emotional peak, the timing of reappraisal-related activity within VLPFC differed between age groups: younger adults showed greater activity at film onset while older adults showed heightened activity during the peak. Our results suggest that older adults rely more heavily on PFC recruitment when engaging cognitively demanding reappraisal strategies while PFC-mediated regulation might not be as task-specific for younger adults. Older adults' greater reliance on cognitive control processing during emotion regulation may also be reflected in the time needed to implement these strategies. PMID:24782800

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

    NASA Astrophysics Data System (ADS)

    VanNasdale, Dean Allan, Jr.

    2011-12-01

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

  8. Age-related changes in the content of the C-terminal region of aggrecan in human articular cartilage.

    PubMed Central

    Dudhia, J; Davidson, C M; Wells, T M; Vynios, D H; Hardingham, T E; Bayliss, M T

    1996-01-01

    The content of the C-terminal region of aggrecan was investigated in samples of articular cartilage from individuals ranging in age from newborn to 65 years. This region contains the globular G3 domain which is known to be removed from aggrecan in mature cartilage, probably by proteolytic cleavage, but the age-related changes in its abundance in human cartilage have not been described previously. The analysis was performed by immunosorbant assay using an antiserum (JD5) against recombinant amino acid residues of human aggrecan, on crude extracts of cartilage without further purification of aggrecan. The results showed that the content of the C-terminal region decreased with age relative to the G1 domain content (correlation coefficient = 0.463). This represented a 92% fall in the content of this region of the molecule from newborn to 65 years of age. furthermore, when the G1 content of the cartilage extracts was corrected to only include the G1 attached to aggrecan and to exclude the G1 fragments which accumulate as a by-product of normal aggrecan turnover (free G1), the age-related decrease in the C-terminal region remained very pronounced. Analysis by composite agarose/PAGE showed that the number of subpopulations of aggrecan resolved increased from one in newborn to three in adult cartilage. All of these reacted with an antiserum to the human G1 domain, but only the slowest migrating species reacted with the C-terminal region antiserum (JD5). Similar analysis by SDS/PAGE confirmed the presence of high-molecular-mass (200 kDa) proteins reactive with JD5, but no reactive fragments of lower electrophoretic mobility were detected. In contrast, when probed with the antiserum to the human G1 domain, the immunoblots showed protein species corresponding to the free G1 and G1-G2 fragments, which were present at high concentrations in adult cartilage. The results suggest that the loss of the C-terminal region is not directly part of the process of aggrecan turnover, but

  9. Autism Spectrum Disorder in Children and Adolescents with Fragile X Syndrome: Within-Syndrome Differences and Age-Related Changes

    PubMed Central

    McDuffie, Andrea; Abbeduto, Leonard; Lewis, Pamela; Kim, Jee-Seon; Kover, Sara T.; Weber, Ann; Brown, W. Ted

    2010-01-01

    The Autism Diagnostic Interview-Revised was used to examine diagnostic profiles and age-related changes in autism symptoms for a group of verbal children and adolescents with FXS, with and without autism. After controlling for nonverbal IQ, statistically significant between-group differences for lifetime and current autism symptoms were found for the Communication and Restricted Interests/Repetitive Behaviors domains, but not the Reciprocal Social Interaction domain. Effect sizes for differences in Reciprocal Social Interaction also were smaller than effect sizes for the other domains with one exception. Overall, severity of autism symptoms improved with age for all participants, with the least improvement noted for Restricted Interests and Repetitive Behaviors. FMRP did not account for unique variance in autism symptoms over and above nonverbal IQ. PMID:20567604

  10. Evidence for age-related changes to temporal attention and memory from the choice time production task

    PubMed Central

    Gooch, Cynthia M.; Stern, Yaakov; Rakitin, Brian C.

    2009-01-01

    The effect of aging on interval timing was examined using a choice time production task, which required participants to choose a key response based on the location of the stimulus, but to delay responding until after a learned time interval. Experiment 1 varied attentional demands of the response choice portion of the task by varying difficulty of stimulus-response mapping. Choice difficulty affected temporal accuracy equally in both age groups, but older participants’ response latencies were more variable under more difficult response choice conditions. Experiment 2 tested the contribution of long-term memory to differences in choice time production between age groups over 3 days of testing. Direction of errors in time production between the two age groups diverged over the 3 sessions, but variability did not differ. Results from each experiment separately show age-related changes to attention and memory in temporal processing using different measures and manipulations in the same task. PMID:19132578

  11. Morphological analysis of age-related iridocorneal angle changes in normal and glaucomatous cases using anterior segment optical coherence tomography

    PubMed Central

    Maruyama, Yuko; Mori, Kazuhiko; Ikeda, Yoko; Ueno, Morio; Kinoshita, Shigeru

    2014-01-01

    Purpose To analyze age-related morphological changes of the iridocorneal angle in normal subjects and glaucomatous cases, using anterior segment optical coherence tomography (AS-OCT). Methods This study involved 58 eyes of 58 open-angle glaucoma cases and 72 eyes of 72 age-matched normal-open-angle control subjects. Iridocorneal angle structures in nasal and temporal regions and anterior chamber depth (ACD) were measured using AS-OCT. Axial length and refractive error were measured by use of an ocular biometer and auto refractor keratometer. Angle opening distance (AOD), angle recess area (ARA), and trabecular-iris space area (TISA), measured at 500 μm (TISA500) and 750 μm (TISA750) distant from the scleral spur, were calculated, in the nasal and temporal regions. A new index, the peripheral angle frame index (PAFI), which represents the peripheral angle structure, was proposed, and was defined as (TISA750-TISA500)/TISA500. Results Refractive power in the glaucoma cases was less than in control cases (P<0.0001). Axial length (P<0.0001) and ACD (P=0.0004) were longer and deeper, respectively, in the glaucoma cases, compared with the control cases. In both control and glaucoma groups, ACD, AOD, ARA, and TISA decreased linearly in an age-dependent manner, while PAFI stayed at relatively constant values throughout the age distribution. AOD in the glaucoma group was longer than in the control group, in both the temporal and nasal regions; ARA and TISA were larger in the glaucoma than in the control group. However, no significant differences in nasal or temporal PAFI were found between the glaucoma and control groups. Conclusion The findings of this study show that AS-OCT is useful for the quantitative evaluation of age-related changes in peripheral angle structure in glaucoma and control cases. PMID:24379654

  12. Age-related changes in the morphology and protein expression of the thymus of healthy yaks (Bos grunniens).

    PubMed

    Zhang, Qian; Yang, Kun; Yangyang, Pan; He, Junfeng; Yu, Sijiu; Cui, Yan

    2016-06-01

    OBJECTIVE To evaluate age-related changes in the morphology and expression of cluster of differentiation 3 (CD3), S100 β, and caspase-3 of the thymus of healthy yaks (Bos grunniens). ANIMALS 15 healthy male yaks of various ages from highland plateaus. PROCEDURES Yaks were allocated to 3 groups on the basis of age (newborn [1 to 7 days old; n = 5], juvenile [5 to 7 months old, 5], and adult [3 to 4 years old; 5]) and euthanized. The thymus was harvested from each yak within 10 minutes after euthanasia. Morphological characteristics were assessed by histologic examination and transmission electron microscopy. Expression of CD3, S100 β, and caspase-3 mRNA and protein was measured by quantitative real-time PCR assay, Western blot analysis, and immunohistochemical staining. RESULTS As age increased, functional thymic tissue was replaced with adipose and connective tissues and the thymic capsule thickened. Expression of CD3 and S100 β mRNA and protein decreased with age, whereas expression of caspase-3 mRNA and protein increased with age. Immunohistochemical staining revealed that CD3-positive thymocytes were located within both the thymic cortex and medulla, S100 β-positive thymic dendritic cells were located in the corticomedullary junction and medulla, and caspase-3-positive thymocytes were diffusely scattered throughout the cortex and medulla. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that age-related thymic changes in yaks that live on highland plateaus were similar to those observed in humans and other mammals. Thus, yaks might serve as a model to study thymic immune system adaptations to high elevations. PMID:27227493

  13. Age-Related Changes in Antioxidant and Glutathione S-Transferase Enzyme Activities in the Asian Clam.

    PubMed

    Vranković, J

    2016-03-01

    Aging is accompanied by increased production of free oxygen radicals and impairment of normal cellular functions. The aim of this work was to provide preliminary data on age-related differences in the activities of antioxidant enzymes and phase II biotransformation enzyme glutathione S-transferase (GST) in a wild population of the Asian clam Corbicula fluminea. The antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR), and GST were assessed in visceral mass of four age classes (0+-, 1+-, 2+-, and 3+-year-old) of C. fluminea clams. Age-related changes were seen in antioxidant enzyme status: levels of total SOD (totSOD) (P < 0.05), MnSOD, and CuZnSOD (P < 0.05) activities increased progressively during aging from younger to older clams. Changes in CAT and GR activities with advancing age were found, the levels being the highest in age class II, then being lower in age classes III and IV (P < 0.05). Activities of GPX and GST were lower in the senescent individuals (2+- and 3+-year-old clams) compared with young individuals (0+- and 1+-year-old clams). Overall, the decline of glutathione-dependent enzyme activities, coupled with higher and lower activities of totSOD and CAT, respectively, as the individual grows older, may render the older animals more susceptible to oxidative stress. Data reported here are not intended to be exhaustive since they concern only age/size structure of the population at one locality, so more detailed studies on both the developmental stages and levels of antioxidant enzymes of this new alien species in Serbian rivers are required. PMID:27262191

  14. Age-related changes in the effects of stress in pregnancy on infant motor development by maternal report: The Queensland Flood Study.

    PubMed

    Simcock, Gabrielle; Kildea, Sue; Elgbeili, Guillaume; Laplante, David P; Stapleton, Helen; Cobham, Vanessa; King, Suzanne

    2016-07-01

    The current study examined the effects of a natural disaster (a sudden onset flood) as a stressor in pregnancy on infant fine and gross motor development at 2, 6, and 16 months of age. Whether the timing of the stressor in pregnancy or sex of the infant moderated the impact of the prenatal maternal stress on motor development was also explored. Mothers' objective experiences of the flood, emotional reactions and distress, and their cognitive appraisal of the event were assessed retrospectively. Infants' fine and gross motor skills were assessed with the Ages and Stages Questionnaire, and results showed age-related changes in the effects of prenatal maternal stress on these domains. At 2 months, higher levels of prenatal maternal stress was positively related to infant motor development, yet at 6 and 16 months of age there was a negative association, particularly if flood exposure occurred later in pregnancy and if mothers had negative cognitive appraisals of the event. Results also showed differential effects of the maternal stress responses to the floods on infants' fine and gross motor development at each age and that infant sex did not buffer these effects. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58: 640-659, 2016. PMID:27004939

  15. Circadian regulation of human sleep and age-related changes in its timing, consolidation and EEG characteristics

    NASA Technical Reports Server (NTRS)

    Dijk, D. J.; Duffy, J. F.

    1999-01-01

    The light-entrainable circadian pacemaker located in the suprachiasmatic nucleus of the hypothalamus regulates the timing and consolidation of sleep by generating a paradoxical rhythm of sleep propensity; the circadian drive for wakefulness peaks at the end of the day spent awake, ie close to the onset of melatonin secretion at 21.00-22.00 h and the circadian drive for sleep crests shortly before habitual waking-up time. With advancing age, ie after early adulthood, sleep consolidation declines, and time of awakening and the rhythms of body temperature, plasma melatonin and cortisol shift to an earlier clock hour. The variability of the phase relationship between the sleep-wake cycle and circadian rhythms increases, and in old age sleep is more susceptible to internal arousing stimuli associated with circadian misalignment. The propensity to awaken from sleep advances relative to the body temperature nadir in older people, a change that is opposite to the phase delay of awakening relative to internal circadian rhythms associated with morningness in young people. Age-related changes do not appear to be associated with a shortening of the circadian period or a reduction of the circadian drive for wake maintenance. These changes may be related to changes in the sleep process itself, such as reductions in slow-wave sleep and sleep spindles as well as a reduced strength of the circadian signal promoting sleep in the early morning hours. Putative mediators and modulators of circadian sleep regulation are discussed.

  16. Circadian regulation of human sleep and age-related changes in its timing, consolidation and EEG characteristics.

    PubMed

    Dijk, D J; Duffy, J F

    1999-04-01

    The light-entrainable circadian pacemaker located in the suprachiasmatic nucleus of the hypothalamus regulates the timing and consolidation of sleep by generating a paradoxical rhythm of sleep propensity; the circadian drive for wakefulness peaks at the end of the day spent awake, ie close to the onset of melatonin secretion at 21.00-22.00 h and the circadian drive for sleep crests shortly before habitual waking-up time. With advancing age, ie after early adulthood, sleep consolidation declines, and time of awakening and the rhythms of body temperature, plasma melatonin and cortisol shift to an earlier clock hour. The variability of the phase relationship between the sleep-wake cycle and circadian rhythms increases, and in old age sleep is more susceptible to internal arousing stimuli associated with circadian misalignment. The propensity to awaken from sleep advances relative to the body temperature nadir in older people, a change that is opposite to the phase delay of awakening relative to internal circadian rhythms associated with morningness in young people. Age-related changes do not appear to be associated with a shortening of the circadian period or a reduction of the circadian drive for wake maintenance. These changes may be related to changes in the sleep process itself, such as reductions in slow-wave sleep and sleep spindles as well as a reduced strength of the circadian signal promoting sleep in the early morning hours. Putative mediators and modulators of circadian sleep regulation are discussed. PMID:10344586

  17. Age-related changes in motor unit firing pattern of vastus lateralis muscle during low-moderate contraction.

    PubMed

    Watanabe, Kohei; Holobar, Aleš; Kouzaki, Motoki; Ogawa, Madoka; Akima, Hiroshi; Moritani, Toshio

    2016-06-01

    Age-related changes in motor unit activation properties remain unclear for locomotor muscles such as quadriceps muscles, although these muscles are preferentially atrophied with aging and play important roles in daily living movements. The present study investigated and compared detailed motor unit firing characteristics for the vastus lateralis muscle during isometric contraction at low to moderate force levels in the elderly and young. Fourteen healthy elderly men and 15 healthy young men performed isometric ramp-up contraction to 70 % of the maximal voluntary contractions (MVC) during knee extension. Multichannel surface electromyograms were recorded from the vastus lateralis muscle using a two-dimensional grid of 64 electrodes and decomposed with the convolution kernel compensation technique to extract individual motor units. Motor unit firing rates in the young were significantly higher (~+29.7 %) than in the elderly (p < 0.05). There were significant differences in firing rates among motor units with different recruitment thresholds at each force level in the young (p < 0.05) but not in the elderly (p > 0.05). Firing rates at 60 % of the MVC force level for the motor units recruited at <20 % of MVC were significantly correlated with MVC force in the elderly (r = 0.885, p < 0.0001) but not in the young (r = 0.127, p > 0.05). These results suggest that the motor unit firing rate in the vastus lateralis muscle is affected by aging and muscle strength in the elderly and/or age-related strength loss is related to motor unit firing/recruitment properties. PMID:27084115

  18. Pairing Cholinergic Enhancement with Perceptual Training Promotes Recovery of Age-Related Changes in Rat Primary Auditory Cortex

    PubMed Central

    Voss, Patrice; Thomas, Maryse; Chou, You Chien; Cisneros-Franco, José Miguel; Ouellet, Lydia; de Villers-Sidani, Etienne

    2016-01-01

    We used the rat primary auditory cortex (A1) as a model to probe the effects of cholinergic enhancement on perceptual learning and auditory processing mechanisms in both young and old animals. Rats learned to perform a two-tone frequency discrimination task over the course of two weeks, combined with either the administration of a cholinesterase inhibitor or saline. We found that while both age groups learned the task more quickly through cholinergic enhancement, the young did so by improving target detection, whereas the old did so by inhibiting erroneous responses to nontarget stimuli. We also found that cholinergic enhancement led to marked functional and structural changes within A1 in both young and old rats. Importantly, we found that several functional changes observed in the old rats, particularly those relating to the processing and inhibition of nontargets, produced cortical processing features that resembled those of young untrained rats more so than those of older adult rats. Overall, these findings demonstrate that combining auditory training with neuromodulation of the cholinergic system can restore many of the auditory cortical functional deficits observed as a result of normal aging and add to the growing body of evidence demonstrating that many age-related perceptual and neuroplastic changes are reversible. PMID:27057359

  19. Prevalence of Age-Related Changes in Ovine Lumbar Intervertebral Discs during Computed Tomography and Magnetic Resonance Imaging.

    PubMed

    Nisolle, Jean-François; Bihin, Benoît; Kirschvink, Nathalie; Neveu, Fabienne; Clegg, Peter; Dugdale, Alexandra; Wang, Xiaoqing; Vandeweerd, Jean-Michel

    2016-01-01

    Ovine models are used to study intervertebral disc (IVD) degeneration. The objective of the current study was to assess the naturally occurring age-related changes of the IVD that can be diagnosed by CT and MRI in the lumbar spine of sheep. We used CT and T2-weighted MR images to score the IVD (L6S1 to L1L2) in 41 sheep (age, 6 mo to 11 y) that were euthanized for reasons not related to musculoskeletal disease. T2 mapping and measurement of T2 time of L6S1 to L2L3 were performed in 22 of the sheep. Degenerative changes manifested as early as 2 y of age and occurred at every IVD level. Discs were more severely damaged in older sheep. The age effect of the L6S1 IVD was larger than the average age effect for the other IVD. The current study provides evidence that lesions similar to those encountered in humans can be identified by CT and MRI in lumbar spine of sheep. Ideally, research animals should be assessed at the initiation of preclinical trials to determine the extent of prevalent degenerative changes. The ovine lumbosacral disc seems particularly prone to degeneration and might be a favorable anatomic site for studying IVD degeneration. PMID:27538861

  20. Pairing Cholinergic Enhancement with Perceptual Training Promotes Recovery of Age-Related Changes in Rat Primary Auditory Cortex.

    PubMed

    Voss, Patrice; Thomas, Maryse; Chou, You Chien; Cisneros-Franco, José Miguel; Ouellet, Lydia; de Villers-Sidani, Etienne

    2016-01-01

    We used the rat primary auditory cortex (A1) as a model to probe the effects of cholinergic enhancement on perceptual learning and auditory processing mechanisms in both young and old animals. Rats learned to perform a two-tone frequency discrimination task over the course of two weeks, combined with either the administration of a cholinesterase inhibitor or saline. We found that while both age groups learned the task more quickly through cholinergic enhancement, the young did so by improving target detection, whereas the old did so by inhibiting erroneous responses to nontarget stimuli. We also found that cholinergic enhancement led to marked functional and structural changes within A1 in both young and old rats. Importantly, we found that several functional changes observed in the old rats, particularly those relating to the processing and inhibition of nontargets, produced cortical processing features that resembled those of young untrained rats more so than those of older adult rats. Overall, these findings demonstrate that combining auditory training with neuromodulation of the cholinergic system can restore many of the auditory cortical functional deficits observed as a result of normal aging and add to the growing body of evidence demonstrating that many age-related perceptual and neuroplastic changes are reversible. PMID:27057359

  1. Age-related changes in the ``complexity'' of cardiovascular dynamics: A potential marker of vulnerability to disease

    NASA Astrophysics Data System (ADS)

    Lewis, D. A. Lipsitz M.

    1995-03-01

    Healthy physiologic control of cardiovascular function is a result of complex interactions between multiple regulatory processes that operate over different time scales. These include the sympathetic and parasympathetic nervous systems which regulate beat-to-beat heart rate (HR) and blood pressure (BP), as well as extravascular volume, body temperature, and sleep which influence HR and BP over the longer term. Interactions between these control systems generate highly variable fluctuations in continuous HR and BP signals. Techniques derived from nonlinear dynamics and chaos theory are now being adapted to quantify the dynamic behavior of physiologic time series and study their changes with age or disease. We have shown significant age-related changes in the 1/fx relationship between the log amplitude and log frequency of the heart rate power spectrum, as well as declines in approximate dimension and approximate entropy of both heart rate and blood pressure time series. These changes in the ``complexity'' of cardiovascular dynamics reflect the breakdown and decoupling of integrated physiologic regulatory systems with aging, and may signal an impairment in cardiovascular ability to adapt to external and internal perturbations. Studies are currently underway to determine whether the complexity of HR or BP time series can distinguish patients with fainting spells due to benign vasovagal reactions from those due to life-threatening cardiac arrhythmias. Thus, measures of the complexity of physiologic variability may provide novel methods to monitor cardiovascular aging and test the efficacy of specific interventions to improve adaptive capacity in old age.

  2. Age related increase in mTOR activity contributes to the pathological changes in ovarian surface epithelium

    PubMed Central

    Bajwa, Preety; Nagendra, Prathima B.; Nielsen, Sarah; Sahoo, Subhransu S.; Bielanowicz, Amanda; Lombard, Janine M.; Wilkinson, Erby J.; Miller, Richard A.; Tanwar, Pradeep S.

    2016-01-01

    Ovarian cancer is a disease of older women. However, the molecular mechanisms of ovarian aging and their contribution to the pathogenesis of ovarian cancer are currently unclear. mTOR signalling is a major regulator of aging as suppression of this pathway extends lifespan in model organisms. Overactive mTOR signalling is present in up to 80% of ovarian cancer samples and is associated with poor prognosis. This study examined the role of mTOR signalling in age-associated changes in ovarian surface epithelium (OSE). Histological examination of ovaries from both aged mice and women revealed OSE cell hyperplasia, papillary growth and inclusion cysts. These pathological lesions expressed bonafide markers of ovarian cancer precursor lesions, Pax8 and Stathmin 1, and were presented with elevated mTOR signalling. To understand whether overactive mTOR signalling is responsible for the development of these pathological changes, we analysed ovaries of the Pten trangenic mice and found significant reduction in OSE lesions compared to controls. Furthermore, pharmacological suppression of mTOR signalling significantly decreased OSE hyperplasia in aged mice. Treatment with mTOR inhibitors reduced human ovarian cancer cell viability, proliferation and colony forming ability. Collectively, we have established the role of mTOR signalling in age-related OSE pathologies and initiation of ovarian cancer. PMID:27036037

  3. Age-Related Differences and Cognitive Correlates of Self-Reported and Direct Navigation Performance: The Effect of Real and Virtual Test Conditions Manipulation

    PubMed Central

    Taillade, Mathieu; N'Kaoua, Bernard; Sauzéon, Hélène

    2016-01-01

    The present study investigated the effect of aging on direct navigation measures and self-reported ones according to the real-virtual test manipulation. Navigation (wayfinding tasks) and spatial memory (paper-pencil tasks) performances, obtained either in real-world or in virtual-laboratory test conditions, were compared between young (n = 32) and older (n = 32) adults who had self-rated their everyday navigation behavior (SBSOD scale). Real age-related differences were observed in navigation tasks as well as in paper-pencil tasks, which investigated spatial learning relative to the distinction between survey-route knowledge. The manipulation of test conditions (real vs. virtual) did not change these age-related differences, which are mostly explained by age-related decline in both spatial abilities and executive functioning (measured with neuropsychological tests). In contrast, elderly adults did not differ from young adults in their self-reporting relative to everyday navigation, suggesting some underestimation of navigation difficulties by elderly adults. Also, spatial abilities in young participants had a mediating effect on the relations between actual and self-reported navigation performance, but not for older participants. So, it is assumed that the older adults carried out the navigation task with fewer available spatial abilities compared to young adults, resulting in inaccurate self-estimates. PMID:26834666

  4. Age-Related Changes in BOLD Activation Pattern in Phonemic Fluency Paradigm: An Investigation of Activation, Functional Connectivity and Psychophysiological Interactions.

    PubMed

    La, Christian; Garcia-Ramos, Camille; Nair, Veena A; Meier, Timothy B; Farrar-Edwards, Dorothy; Birn, Rasmus; Meyerand, Mary E; Prabhakaran, Vivek

    2016-01-01

    Healthy aging is associated with decline of cognitive functions. However, even before those declines become noticeable, the neural architecture underlying those mechanisms has undergone considerable restructuring and reorganization. During performance of a cognitive task, not only have the task-relevant networks demonstrated reorganization with aging, which occurs primarily by recruitment of additional areas to preserve performance, but the task-irrelevant network of the "default-mode" network (DMN), which is normally deactivated during task performance, has also consistently shown reduction of this deactivation with aging. Here, we revisited those age-related changes in task-relevant (i.e., language system) and task-irrelevant (i.e., DMN) systems with a language production paradigm in terms of task-induced activation/deactivation, functional connectivity, and context-dependent correlations between the two systems. Our task fMRI data demonstrated a late increase in cortical recruitment in terms of extent of activation, only observable in our older healthy adult group, when compared to the younger healthy adult group, with recruitment of the contralateral hemisphere, but also other regions from the network previously underutilized. Our middle-aged individuals, when compared to the younger healthy adult group, presented lower levels of activation intensity and connectivity strength, with no recruitment of additional regions, possibly reflecting an initial, uncompensated, network decline. In contrast, the DMN presented a gradual decrease in deactivation intensity and deactivation extent (i.e., low in the middle-aged, and lower in the old) and similar gradual reduction of functional connectivity within the network, with no compensation. The patterns of age-related changes in the task-relevant system and DMN are incongruent with the previously suggested notion of anti-correlation of the two systems. The context-dependent correlation by psycho-physiological interaction

  5. Age-Related Changes in BOLD Activation Pattern in Phonemic Fluency Paradigm: An Investigation of Activation, Functional Connectivity and Psychophysiological Interactions

    PubMed Central

    La, Christian; Garcia-Ramos, Camille; Nair, Veena A.; Meier, Timothy B.; Farrar-Edwards, Dorothy; Birn, Rasmus; Meyerand, Mary E.; Prabhakaran, Vivek

    2016-01-01

    Healthy aging is associated with decline of cognitive functions. However, even before those declines become noticeable, the neural architecture underlying those mechanisms has undergone considerable restructuring and reorganization. During performance of a cognitive task, not only have the task-relevant networks demonstrated reorganization with aging, which occurs primarily by recruitment of additional areas to preserve performance, but the task-irrelevant network of the “default-mode” network (DMN), which is normally deactivated during task performance, has also consistently shown reduction of this deactivation with aging. Here, we revisited those age-related changes in task-relevant (i.e., language system) and task-irrelevant (i.e., DMN) systems with a language production paradigm in terms of task-induced activation/deactivation, functional connectivity, and context-dependent correlations between the two systems. Our task fMRI data demonstrated a late increase in cortical recruitment in terms of extent of activation, only observable in our older healthy adult group, when compared to the younger healthy adult group, with recruitment of the contralateral hemisphere, but also other regions from the network previously underutilized. Our middle-aged individuals, when compared to the younger healthy adult group, presented lower levels of activation intensity and connectivity strength, with no recruitment of additional regions, possibly reflecting an initial, uncompensated, network decline. In contrast, the DMN presented a gradual decrease in deactivation intensity and deactivation extent (i.e., low in the middle-aged, and lower in the old) and similar gradual reduction of functional connectivity within the network, with no compensation. The patterns of age-related changes in the task-relevant system and DMN are incongruent with the previously suggested notion of anti-correlation of the two systems. The context-dependent correlation by psycho

  6. Age-related changes to spectral voice characteristics affect judgments of prosodic, segmental, and talker attributes for child and adult speech

    PubMed Central

    Dilley, Laura C.; Wieland, Elizabeth A.; Gamache, Jessica L.; McAuley, J. Devin; Redford, Melissa A.

    2013-01-01

    Purpose As children mature, changes in voice spectral characteristics covary with changes in speech, language, and behavior. Spectral characteristics were manipulated to alter the perceived ages of talkers’ voices while leaving critical acoustic-prosodic correlates intact, to determine whether perceived age differences were associated with differences in judgments of prosodic, segmental, and talker attributes. Method Speech was modified by lowering formants and fundamental frequency, for 5-year-old children’s utterances, or raising them, for adult caregivers’ utterances. Next, participants differing in awareness of the manipulation (Exp. 1a) or amount of speech-language training (Exp. 1b) made judgments of prosodic, segmental, and talker attributes. Exp. 2 investigated the effects of spectral modification on intelligibility. Finally, in Exp. 3 trained analysts used formal prosody coding to assess prosodic characteristics of spectrally-modified and unmodified speech. Results Differences in perceived age were associated with differences in ratings of speech rate, fluency, intelligibility, likeability, anxiety, cognitive impairment, and speech-language disorder/delay; effects of training and awareness of the manipulation on ratings were limited. There were no significant effects of the manipulation on intelligibility or formally coded prosody judgments. Conclusions Age-related voice characteristics can greatly affect judgments of speech and talker characteristics, raising cautionary notes for developmental research and clinical work. PMID:23275414

  7. Aging-related anatomical and biochemical changes in lymphatic collectors impair lymph transport, fluid homeostasis, and pathogen clearance.

    PubMed

    Zolla, Valerio; Nizamutdinova, Irina Tsoy; Scharf, Brian; Clement, Cristina C; Maejima, Daisuke; Akl, Tony; Nagai, Takashi; Luciani, Paola; Leroux, Jean-Christophe; Halin, Cornelia; Stukes, Sabriya; Tiwari, Sangeeta; Casadevall, Arturo; Jacobs, William R; Entenberg, David; Zawieja, David C; Condeelis, John; Fooksman, David R; Gashev, Anatoliy A; Santambrogio, Laura

    2015-08-01

    The role of lymphatic vessels is to transport fluid, soluble molecules, and immune cells to the draining lymph nodes. Here, we analyze how the aging process affects the functionality of the lymphatic collectors and the dynamics of lymph flow. Ultrastructural, biochemical, and proteomic analysis indicates a loss of matrix proteins, and smooth muscle cells in aged collectors resulting in a decrease in contraction frequency, systolic lymph flow velocity, and pumping activity, as measured in vivo in lymphatic collectors. Functionally, this impairment also translated into a reduced ability for in vivo bacterial transport as determined by time-lapse microscopy. Ultrastructural and proteomic analysis also indicates a decrease in the thickness of the endothelial cell glycocalyx and loss of gap junction proteins in aged lymph collectors. Redox proteomic analysis mapped an aging-related increase in the glycation and carboxylation of lymphatic's endothelial cell and matrix proteins. Functionally, these modifications translate into apparent hyperpermeability of the lymphatics with pathogen escaping from the collectors into the surrounding tissue and a decreased ability to control tissue fluid homeostasis. Altogether, our data provide a mechanistic analysis of how the anatomical and biochemical changes, occurring in aged lymphatic vessels, compromise lymph flow, tissue fluid homeostasis, and pathogen transport. PMID:25982749

  8. Age-related changes in natural killer cell repertoires: impact on NK cell function and immune surveillance.

    PubMed

    Manser, Angela R; Uhrberg, Markus

    2016-04-01

    A key feature of human natural killer (NK) cells, which enables efficient recognition of infected and malignant target cells, is the expression of HLA class I-specific receptors of the KIR and NKG2 gene families. Cell-to-cell variability in receptor expression leads to the formation of complex NK cell repertoires. As outlined here, NK cells go through major changes from newborns to adults characterized by downregulation of the inhibitory NKG2A receptor and concomitant upregulation of KIR family members. This process is completed in young adults, and in the majority of individuals, KIR/NKG2A repertoires remain remarkably stable until old age. Nonetheless, age-related factors have the potential to majorly influence the complexity of NK cell repertoires: Firstly infection with HCMV is associated with major clonal expansions of terminally differentiated NKG2C- and KIR-expressing NK cells in certain individuals. Secondly, ineffective hematopoiesis can lead to immature and less diversified NK cell repertoires as observed in myelodysplastic syndrome (MDS), a malignant disease of the elderly. Thus, whereas in the majority of elderly the NK cell compartment appears to be highly stable in terms of function and phenotype, in a minority of subjects a breakdown of NK cell repertoire diversity is observed that might influence immune surveillance and healthy aging. PMID:26288343

  9. Morphological study of the human hyoid bone with three-dimensional CT images -Gender difference and age-related changes.

    PubMed

    Ito, Kyoichi; Ando, Satoshi; Akiba, Norihiko; Watanabe, Yuichi; Okuyama, Yasuo; Moriguchi, Hisamoto; Yoshikawa, Kohki; Takahashi, Tsuneo; Shimada, Morio

    2012-01-01

    The human hyoid bone supports the base of the tongue and is involved in breathing, chewing, and swallowing as well as in the muscle movements associated with articulation. Accordingly it plays an important bone for a human to live. It is a very interesting organ also in multiple special area, including anatomy, mastication, swallowing, articulation, and also forensic medicine. In the morphological study of the human hyoid bone, there is a comparative anthropological research early in 1900, whereas the metrological research has been little reported later. We first used MDCT, and recorded each organic hyoid locus with a three-dimensional image for three-dimensional morphometry of gender differences, age-related changes, and the morphologic characters of the hyoid bone, and compared them with the results of our predecessors. By measuring the volume of the human hyoid bone, we identified gender difference at high rates, and estimated a certain level of ages based on the ossification at the junction area of the hyoid body and greater horns observed. Our results can be applied in the forensic medicine. By examining 600 cases, atypical horseshoes-shapes were found and the existence of the hyoid bone protrusion was demonstrated at high rates. PMID:23429053

  10. Aging-related anatomical and biochemical changes in lymphatic collectors impair lymph transport, fluid homeostasis, and pathogen clearance

    PubMed Central

    Zolla, Valerio; Nizamutdinova, Irina Tsoy; Scharf, Brian; Clement, Cristina C; Maejima, Daisuke; Akl, Tony; Nagai, Takashi; Luciani, Paola; Leroux, Jean-Christophe; Halin, Cornelia; Stukes, Sabriya; Tiwari, Sangeeta; Casadevall, Arturo; Jacobs, William R; Entenberg, David; Zawieja, David C; Condeelis, John; Fooksman, David R; Gashev, Anatoliy A; Santambrogio, Laura

    2015-01-01

    The role of lymphatic vessels is to transport fluid, soluble molecules, and immune cells to the draining lymph nodes. Here, we analyze how the aging process affects the functionality of the lymphatic collectors and the dynamics of lymph flow. Ultrastructural, biochemical, and proteomic analysis indicates a loss of matrix proteins, and smooth muscle cells in aged collectors resulting in a decrease in contraction frequency, systolic lymph flow velocity, and pumping activity, as measured in vivo in lymphatic collectors. Functionally, this impairment also translated into a reduced ability for in vivo bacterial transport as determined by time-lapse microscopy. Ultrastructural and proteomic analysis also indicates a decrease in the thickness of the endothelial cell glycocalyx and loss of gap junction proteins in aged lymph collectors. Redox proteomic analysis mapped an aging-related increase in the glycation and carboxylation of lymphatic’s endothelial cell and matrix proteins. Functionally, these modifications translate into apparent hyperpermeability of the lymphatics with pathogen escaping from the collectors into the surrounding tissue and a decreased ability to control tissue fluid homeostasis. Altogether, our data provide a mechanistic analysis of how the anatomical and biochemical changes, occurring in aged lymphatic vessels, compromise lymph flow, tissue fluid homeostasis, and pathogen transport. PMID:25982749

  11. Age-related changes in involuntary and voluntary attention as reflected in components of the event-related potential (ERP).

    PubMed

    Kok, A

    2000-10-01

    The present paper provides an overview of age-related changes in both involuntary and voluntary attention in adult subjects as manifested in scalp-recorded ERPs. A decline in orienting with old age was inferred from a substantial reduction with age in the magnitude of deviance-related ERP components like MMN, target as well as nontarget P3s, novelty P3 and N400. A review of focused attention studies further suggested that old and young subjects do not differ substantially in the quality of attentional operations. In old subjects early selection processes, as reflected in their selection potentials, have a somewhat slower onset than in young subjects, especially in conditions in which selection is based upon complex discrimination of stimulus features. Furthermore, the global pattern emerging from visual and memory search studies is that search-related negativities in the ERPs are smaller and of longer duration in old than in young subjects over the central and anterior scalp sites. These effects could indicate that controlled search is less intense or takes more time per search operation in old than in young subjects. At more posterior scalp sites there was tendency towards an enhanced search-related negativity that could reflect a specific difficulty (or compensatory increase in mental effort) of old subjects in spatially locating targets in complex visual fields. PMID:11035221

  12. Age-related and depot-specific changes in white adipose tissue of growth hormone receptor-null mice.

    PubMed

    Sackmann-Sala, Lucila; Berryman, Darlene E; Lubbers, Ellen R; Zhang, Han; Vesel, Clare B; Troike, Katie M; Gosney, Elahu S; List, Edward O; Kopchick, John J

    2014-01-01

    Growth hormone receptor-null (GHR(-/-)) mice are dwarf, insulin sensitive, and long-lived in spite of increased adiposity. However, their adiposity is not uniform, with select white adipose tissue (WAT) depots enlarged. To study WAT depot-specific effects on insulin sensitivity and life span, we analyzed individual WAT depots of 12- and 24-month-old GHR(-) (/-) and wild-type (WT) mice, as well as their plasma levels of selected hormones. Adipocyte sizes and plasma insulin, leptin, and adiponectin levels decreased with age in both GHR(-) (/-) and WT mice. Two-dimensional gel electrophoresis proteomes of WAT depots were similar among groups, but several proteins involved in endocytosis and/or cytoskeletal organization (Ehd2, S100A10, actin), anticoagulation (S100A10, annexin A5), and age-related conditions (alpha2-macroglobulin, apolipoprotein A-I, transthyretin) showed significant differences between genotypes. Because Ehd2 may regulate endocytosis of Glut4, we measured Glut4 levels in the WAT depots of GHR(-) (/-) and WT mice. Inguinal WAT of 12-month-old GHR(-) (/-) mice displayed lower levels of Glut4 than WT. Overall, the protein changes detected in this study offer new insights into possible mechanisms contributing to enhanced insulin sensitivity and extended life span in GHR(-) (/-) mice. PMID:23873966

  13. Beat-induced fluctuations in auditory cortical beta-band activity: using EEG to measure age-related changes.

    PubMed

    Cirelli, Laura K; Bosnyak, Dan; Manning, Fiona C; Spinelli, Christina; Marie, Céline; Fujioka, Takako; Ghahremani, Ayda; Trainor, Laurel J

    2014-01-01

    People readily extract regularity in rhythmic auditory patterns, enabling prediction of the onset of the next beat. Recent magnetoencephalography (MEG) research suggests that such prediction is reflected by the entrainment of oscillatory networks in the brain to the tempo of the sequence. In particular, induced beta-band oscillatory activity from auditory cortex decreases after each beat onset and rebounds prior to the onset of the next beat across tempi in a predictive manner. The objective of the present study was to examine the development of such oscillatory activity by comparing electroencephalography (EEG) measures of beta-band fluctuations in 7-year-old children to adults. EEG was recorded while participants listened passively to isochronous tone sequences at three tempi (390, 585, and 780 ms for onset-to-onset interval). In adults, induced power in the high beta-band (20-25 Hz) decreased after each tone onset and rebounded prior to the onset of the next tone across tempo conditions, consistent with MEG findings. In children, a similar pattern was measured in the two slower tempo conditions, but was weaker in the fastest condition. The results indicate that the beta-band timing network works similarly in children, although there are age-related changes in consistency and the tempo range over which it operates. PMID:25071691

  14. Age-Related and Depot-Specific Changes in White Adipose Tissue of Growth Hormone Receptor-Null Mice

    PubMed Central

    2014-01-01

    Growth hormone receptor-null (GHR−/−) mice are dwarf, insulin sensitive, and long-lived in spite of increased adiposity. However, their adiposity is not uniform, with select white adipose tissue (WAT) depots enlarged. To study WAT depot–specific effects on insulin sensitivity and life span, we analyzed individual WAT depots of 12- and 24-month-old GHR− /− and wild-type (WT) mice, as well as their plasma levels of selected hormones. Adipocyte sizes and plasma insulin, leptin, and adiponectin levels decreased with age in both GHR− /− and WT mice. Two-dimensional gel electrophoresis proteomes of WAT depots were similar among groups, but several proteins involved in endocytosis and/or cytoskeletal organization (Ehd2, S100A10, actin), anticoagulation (S100A10, annexin A5), and age-related conditions (alpha2-macroglobulin, apolipoprotein A-I, transthyretin) showed significant differences between genotypes. Because Ehd2 may regulate endocytosis of Glut4, we measured Glut4 levels in the WAT depots of GHR− /− and WT mice. Inguinal WAT of 12-month-old GHR− /− mice displayed lower levels of Glut4 than WT. Overall, the protein changes detected in this study offer new insights into possible mechanisms contributing to enhanced insulin sensitivity and extended life span in GHR− /− mice. PMID:23873966

  15. Age-related changes in AMPK activation: Role for AMPK phosphatases and inhibitory phosphorylation by upstream signaling pathways.

    PubMed

    Salminen, Antero; Kaarniranta, Kai; Kauppinen, Anu

    2016-07-01

    AMP-activated protein kinase (AMPK) is a fundamental regulator of energy metabolism, stress resistance, and cellular proteostasis. AMPK signaling controls an integrated signaling network which is involved in the regulation of healthspan and lifespan e.g. via FoxO, mTOR/ULK1, CRCT-1/CREB, and SIRT1 signaling pathways. Several studies have demonstrated that the activation capacity of AMPK signaling declines with aging, which impairs the maintenance of efficient cellular homeostasis and enhances the aging process. However, it seems that the aging process affects AMPK activation in a context-dependent manner since occasionally, it can also augment AMPK activation, possibly attributable to the type of insult and tissue homeostasis. Three protein phosphatases, PP1, PP2A, and PP2C, inhibit AMPK activation by dephosphorylating the Thr172 residue of AMPKα, required for AMPK activation. In addition, several upstream signaling pathways can phosphorylate Ser/Thr residues in the β/γ interaction domain of the AMPKα subunit that subsequently blocks the activation of AMPK. These inhibitory pathways include the insulin/AKT, cyclic AMP/PKA, and RAS/MEK/ERK pathways. We will examine the evidence whether the efficiency of AMPK responsiveness declines during the aging process. Next, we will review the mechanisms involved in curtailing the activation of AMPK. Finally, we will elucidate the potential age-related changes in the inhibitory regulation of AMPK signaling that might be a part of the aging process. PMID:27060201

  16. Global and domain-specific changes in cognition throughout adulthood.

    PubMed

    Tucker-Drob, Elliot M

    2011-03-01

    Normative adult age-related decrements are well documented for many diverse forms of effortful cognitive processing. However, it is currently unclear whether each of these decrements reflects a distinct and independent developmental phenomenon, or, in part, a more global phenomenon. A number of studies have recently been published that show moderate to large magnitudes of positive relations among individual differences in rates of changes in different cognitive variables during adulthood. This suggests that a small number of common dimensions or even a single common dimension may underlie substantial proportions of individual differences in aging-related cognitive declines. This possibility was directly examined using data from 1,281 adults 18-95 years of age who were followed longitudinally over up to 7 years on 12 different measures of effortful processing. Multivariate growth curve models were applied to examine the dimensionality of individual differences in longitudinal changes. Results supported a hierarchical structure of aging-related changes, with an average of 39% of individual differences in change in a given variable attributable to global (domain-general) developmental processes, 33% attributable to domain-specific developmental processes (abstract reasoning, spatial visualization, episodic memory, and processing speed), and 28% attributable to test-specific developmental processes. Although it is often assumed that systematic and pervasive sources of cognitive decline only emerge in later adulthood, domain-general influences on change were apparent for younger (18-49 years), middle aged (50-69 years), and older (70-95 years) adults. PMID:21244145

  17. Age-related changes in oxidative capacity differ between locomotory muscles and are associated with physical activity behavior

    PubMed Central

    Larsen, Ryan G.; Callahan, Damien M.; Foulis, Stephen A.; Kent-Braun, Jane A.

    2013-01-01

    There is discrepancy in the literature regarding the degree to which old age affects muscle bioenergetics. These discrepancies are likely influenced by several factors, including variations in physical activity (PA) and differences in the muscle group investigated. To test the hypothesis that age may affect muscles differently, we quantified oxidative capacity of tibialis anterior (TA) and vastus lateralis (VL) muscles in healthy, relatively sedentary younger (8 YW, 8 YM; 21–35 years) and older (8 OW, 8 OM; 65–80 years) adults. To investigate the effect of physical activity on muscle oxidative capacity in older adults, we compared older sedentary women to older women with mild-to-moderate mobility impairment and lower physical activity (OIW, n = 7), and older sedentary men with older active male runners (OAM, n = 6). Oxidative capacity was measured in vivo as the rate constant, kPCr, of postcontraction phosphocreatine recovery, obtained by 31P magnetic resonance spectroscopy following maximal isometric contractions. While kPCr was higher in TA of older than activity-matched younger adults (28%; p = 0.03), older adults had lower kPCr in VL (23%; p = 0.04). In OIW compared with OW, kPCr was lower in VL (~45%; p = 0.01), but not different in TA. In contrast, OAM had higher kPCr than OM (p = 0.03) in both TA (41%) and VL (54%). In older adults, moderate-to-vigorous PA was positively associated with kPCr in VL (r = 0.65, p < 0.001) and TA (r = 0.41, p = 0.03). Collectively, these results indicate that age-related changes in oxidative capacity vary markedly between locomotory muscles, and that altered PA behavior may play a role in these changes. PMID:22236246

  18. Age-related changes in the tooth-bone interface area of acrodont dentition in the chameleon.

    PubMed

    Dosedělová, Hana; Štěpánková, Kateřina; Zikmund, Tomáš; Lesot, Herve; Kaiser, Jozef; Novotný, Karel; Štembírek, Jan; Knotek, Zdeněk; Zahradníček, Oldřich; Buchtová, Marcela

    2016-09-01

    Chameleon teeth develop as individual structures at a distance from the developing jaw bone during the pre-hatching period and also partially during the post-hatching period. However, in the adult, all teeth are fused together and tightly attached to the jaw bone by mineralized attachment tissue to form one functional unit. Tooth to bone as well as tooth to tooth attachments are so firm that if injury to the oral cavity occurs, several neighbouring teeth and pieces of jaw can be broken off. We analysed age-related changes in chameleon acrodont dentition, where ankylosis represents a physiological condition, whereas in mammals, ankylosis only occurs in a pathological context. The changes in hard-tissue morphology and mineral composition leading to this fusion were analysed. For this purpose, the lower jaws of chameleons were investigated using X-ray micro-computed tomography, laser-induced breakdown spectroscopy and microprobe analysis. For a long time, the dental pulp cavity remained connected with neighbouring teeth and also to the underlying bone marrow cavity. Then, a progressive filling of the dental pulp cavity by a mineralized matrix occurred, and a complex network of non-mineralized channels remained. The size of these unmineralized channels progressively decreased until they completely disappeared, and the dental pulp cavity was filled by a mineralized matrix over time. Moreover, the distribution of calcium, phosphorus and magnesium showed distinct patterns in the different regions of the tooth-bone interface, with a significant progression of mineralization in dentin as well as in the supporting bone. In conclusion, tooth-bone fusion in chameleons results from an enhanced production of mineralized tissue during post-hatching development. Uncovering the developmental processes underlying these outcomes and performing comparative studies is necessary to better understand physiological ankylosis; for that purpose, the chameleon can serve as a useful model

  19. Age-related changes in the rate of disease transmission: implications for the design of vaccination programmes.

    PubMed Central

    Anderson, R. M.; May, R. M.

    1985-01-01

    Mathematical models are developed to aid in the investigation of the implications of heterogeneity in contact with infection within a community, on the design of mass vaccination programmes for the control of childhood viral and bacterial infections in developed countries. Analyses are focused on age-dependency in the rate at which individuals acquire infection, the question of 'who acquires infection from whom', and the implications of genetic variability in susceptibility to infection. Throughout, theoretical predictions are based on parameter estimates obtained from epidemiological studies and are compared with observed temporal trends in disease incidence and age-stratified serological profiles. Analysis of case notification records and serological data suggest that the rate at which individuals acquire many common infections changes from medium to high and then to low levels in the infant, child and teenage plus adult age groups respectively. Such apparent age-dependency in attack rate acts to reduce slightly the predicted levels of herd immunity required for the eradication of infections such as measles, when compared with the predictions of models based on age-independent transmission. The action of maternally derived immunity in prohibiting vaccination in infants, and the broad span of age classes over which vaccination currently takes place in the U.K., however, argue that levels of herd immunity of between 90 and 94% would be required to eliminate measles. Problems surrounding the interpretation of apparent age-related trends in the acquisition of infection and their relevance to the design of vaccination programmes, are discussed in relation to the possible role of genetically based variation in susceptibility to infection and observations on epidemics in 'virgin' populations. Heterogeneous mixing models provide predictions of changes in serology and disease incidence under the impact of mass vaccination which well mirror observed trends in England and

  20. Age-Related Changes in Dynamic Postural Control and Attentional Demands are Minimally Affected by Local Muscle Fatigue

    PubMed Central

    Remaud, Anthony; Thuong-Cong, Cécile; Bilodeau, Martin

    2016-01-01

    Normal aging results in alterations in the visual, vestibular and somtaosensory systems, which in turn modify the control of balance. Muscle fatigue may exacerbate these age-related changes in sensory and motor functions, and also increase the attentional demands associated with dynamic postural control. The purpose of this study was to investigate the effect of aging on dynamic postural control and posture-related attentional demands before and after a plantar flexor fatigue protocol. Participants (young adults: n = 15; healthy seniors: n = 13) performed a dynamic postural task along the antero-posterior (AP) and the medio-lateral (ML) axes, with and without the addition of a simple reaction time (RT) task. The dynamic postural task consisted in following a moving circle on a computer screen with the representation of the center of pressure (COP). This protocol was repeated before and after a fatigue task where ankle plantar flexor muscles were targeted. The mean COP-target distance and the mean COP velocity were calculated for each trial. Cross-correlation analyses between the COP and target displacements were also performed. RTs were recorded during dual-task trials. Results showed that while young adults adopted an anticipatory control mode to move their COP as close as possible to the target center, seniors adopted a reactive control mode, lagging behind the target center. This resulted in longer COP-target distance and higher COP velocity in the latter group. Concurrently, RT increased more in seniors when switching from static stance to dynamic postural conditions, suggesting potential alterations in the central nervous system (CNS) functions. Finally, plantar flexor muscle fatigue and dual-tasking had only minor effects on dynamic postural control of both young adults and seniors. Future studies should investigate why the fatigue-induced changes in quiet standing postural control do not seem to transfer to dynamic balance tasks. PMID:26834626

  1. Functional consequences of age-related morphologic changes to pyramidal neurons of the rhesus monkey prefrontal cortex

    PubMed Central

    Coskren, Patrick J.; Luebke, Jennifer I.; Kabaso, Doron; Wearne, Susan L.; Yadav, Aniruddha; Rumbell, Timothy; Hof, Patrick R.; Weaver, Christina M.

    2014-01-01

    Layer 3 (L3) pyramidal neurons in the lateral prefrontal cortex (LPFC) of rhesus monkeys exhibit dendritic regression, spine loss and increased action potential (AP) firing rates during normal aging. The relationship between these structural and functional alterations, if any, is unknown. To address this issue, morphological and electrophysiological properties of L3 LPFC pyramidal neurons from young and aged rhesus monkeys were characterized using in vitro whole-cell patch-clamp recordings and high-resolution digital reconstruction of neurons. Consistent with our previous studies, aged neurons exhibited significantly reduced dendritic arbor length and spine density, as well as increased input resistance and firing rates. Computational models using the digital reconstructions with Hodgkin-Huxley and AMPA channels allowed us to assess relationships between demonstrated age-related changes and to predict physiological changes that have not yet been tested empirically. For example, the models predict that in both backpropagating APs and excitatory postsynaptic currents (EPSCs), attenuation is lower in aged versus young neurons. Importantly, when identical densities of passive parameters and voltage- and calcium-gated conductances were used in young and aged model neurons, neither input resistance nor firing rates differed between the two age groups. Tuning passive parameters for each model predicted significantly higher membrane resistance (Rm) in aged versus young neurons. This Rm increase alone did not account for increased firing rates in aged models, but coupling these Rm values with subtle differences in morphology and membrane capacitance did. The predicted differences in passive parameters (or parameters with similar effects) are mathematically plausible, but must be tested empirically. PMID:25527184

  2. Age-Related Changes of Intraocular Pressure in Elderly People in Southern China: Lingtou Eye Cohort Study

    PubMed Central

    Han, Xiaotong; Niu, Yong; Guo, Xinxing; Hu, Yin; Yan, William; He, Mingguang

    2016-01-01

    Purpose To study age-related changes of intraocular pressure (IOP) and assess the cohort effect in both cross-sectional and longitudinal settings among elderly Chinese adults. Methods Participants were enrolled from the Lingtou Eye Cohort Study with Chinese government officials aged 40 years and older at baseline and received physical check-up and ocular examinations from 2010 to 2012. IOP was measured using a non-contact tonometer according to standardized protocols, as well as systolic blood pressure (SBP), diastolic blood pressure (DBP) and body mass index (BMI). Participants who had attended IOP measurements in both 2010 and 2012 were included in this study. Cross-sectional association of IOP with age was assessed using multivariate liner regression analyses and based on the data of 2010. Longitudinal changes in IOP were assessed by paired t-test. Results A total of 3372 subjects were enrolled in the current analysis (2010 mean [SD] age, 61.9 [7.1] years; 60.2% men). The mean IOP in 2010 was 15.4±2.3 mmHg for women and 15.2±2.3 mmHg for men with an intersex difference (P = 0.029). Cross-sectional analysis showed that IOP was negatively associated with age (P = 0.003, β = -0.033 for women and P<0.001, β = -0.061 for men) adjusted for baseline SBP, DBP and BMI. Paired t-test suggested that IOP was higher in the year 2012 than 2010 in women (P = 0.006) but did not change significantly in men within 2 years (P = 0.345). In addition, the 2-year changes of IOP were not associated with age adjusted for baseline IOP in 2010 (P = 0.249). Conclusion Cross-sectional data suggests that IOP is lower in people with older age. Longitudinal data does not support such findings and thus the identified decreasing pattern with age in cross-sectional analysis is likely caused by cohort effects. PMID:26986222

  3. Automated Retinal Image Analysis for Evaluation of Focal Hyperpigmentary Changes in Intermediate Age-Related Macular Degeneration

    PubMed Central

    Schmitz-Valckenberg, Steffen; Göbel, Arno P.; Saur, Stefan C.; Steinberg, Julia S.; Thiele, Sarah; Wojek, Christian; Russmann, Christoph; Holz, Frank G.; for the MODIAMD-Study Group

    2016-01-01

    Purpose To develop and evaluate a software tool for automated detection of focal hyperpigmentary changes (FHC) in eyes with intermediate age-related macular degeneration (AMD). Methods Color fundus (CFP) and autofluorescence (AF) photographs of 33 eyes with FHC of 28 AMD patients (mean age 71 years) from the prospective longitudinal natural history MODIAMD-study were included. Fully automated to semiautomated registration of baseline to corresponding follow-up images was evaluated. Following the manual circumscription of individual FHC (four different readings by two readers), a machine-learning algorithm was evaluated for automatic FHC detection. Results The overall pixel distance error for the semiautomated (CFP follow-up to CFP baseline: median 5.7; CFP to AF images from the same visit: median 6.5) was larger as compared for the automated image registration (4.5 and 5.7; P < 0.001 and P < 0.001). The total number of manually circumscribed objects and the corresponding total size varied between 637 to 1163 and 520,848 pixels to 924,860 pixels, respectively. Performance of the learning algorithms showed a sensitivity of 96% at a specificity level of 98% using information from both CFP and AF images and defining small areas of FHC (“speckle appearance”) as “neutral.” Conclusions FHC as a high-risk feature for progression of AMD to late stages can be automatically assessed at different time points with similar sensitivity and specificity as compared to manual outlining. Upon further development of the research prototype, this approach may be useful both in natural history and interventional large-scale studies for a more refined classification and risk assessment of eyes with intermediate AMD. Translational Relevance Automated FHC detection opens the door for a more refined and detailed classification and risk assessment of eyes with intermediate AMD in both natural history and future interventional studies. PMID:26966639

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

    PubMed

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

    2016-08-15

    A better understanding of the cellular physiological role that plasma membrane lipids, fatty acids and sterols play in various cellular systems may yield more insight into how cellular and whole organ function is altered during the ageing process. Membrane lipid rafts (MLRs) within the plasma membrane of most cells serve as key organizers of intracellular signalling and tethering points of cytoskeletal components. MLRs are plasmalemmal microdomains enriched in sphingolipids, cholesterol and scaffolding proteins; they serve as a platform for signal transduction, cytoskeletal organization and vesicular trafficking. Within MLRs are the scaffolding and cholesterol binding proteins named caveolin (Cav). Cavs not only organize a multitude of receptors including neurotransmitter receptors (NMDA and AMPA receptors), signalling proteins that regulate the production of cAMP (G protein-coupled receptors, adenylyl cyclases, phosphodiesterases (PDEs)), and receptor tyrosine kinases involved in growth (Trk), but also interact with components that modulate actin and tubulin cytoskeletal dynamics (e.g. RhoGTPases and actin binding proteins). MLRs are essential for the regulation of the physiology of organs such as the brain, and age-related loss of cholesterol from the plasma membrane leads to loss of MLRs, decreased presynaptic vesicle fusion, and changes in neurotransmitter release, all of which contribute to different forms of neurodegeneration. Thus, MLRs provide an active membrane domain that tethers and reorganizes the cytoskeletal machinery necessary for membrane and cellular repair, and genetic interventions that restore MLRs to normal cellular levels may be exploited as potential therapeutic means to reverse the ageing and neurodegenerative processes. PMID:26332795

  5. Age-related changes in lung collagen metabolism. A role for degradation in regulating lung collagen production.

    PubMed

    Mays, P K; McAnulty, R J; Laurent, G J

    1989-08-01

    Lung collagen levels are determined by a balance between synthesis and degradation, processes known to have rapid rates in young animals. Here, we report age-related changes in lung collagen synthesis and degradation in rats at five ages from 1 month to 2 yr. Synthesis rates were determined after injection of [14C]proline with a flooding dose of unlabeled proline, and its appearance as hydroxy-[14C]proline in protein. To determine degradation of newly synthesized collagen, the appearance of hydroxy-[14C]proline, either free or in low-molecular-weight peptides, was compared with hydroxy-[14C]proline in protein. Fractional collagen synthesis rates decreased from 13.51 +/- 0.54%/day at 1 month to 0.97 +/- 0.14%/day at 2 yr of age (p less than 0.05). Total lung collagen production also fell, but only after 15 months, when it decreased from 2.01 +/- 0.16 mg/day at 15 months to 0.54 +/- 0.10 mg/day at 2 yr of age (p less than 0.05). Fractional rates of total collagen degradation, calculated from the difference between rates of synthesis and rates of collagen deposition, decreased 20-fold from 1 month to 2 yr of age. The proportion of newly synthesized collagen degraded increased from 27.6 +/- 3.2% at 1 month to a maximum of 82.3 +/- 1.1% at 15 months. These results suggest that lung collagen synthesis and degradation occur throughout life, and that degradative pathways may play important roles in regulating collagen production during growth and ageing. PMID:2788379

  6. Visceral adipose tissue inflammation is associated with age-related brain changes and ischemic brain damage in aged mice.

    PubMed

    Shin, Jin A; Jeong, Sae Im; Kim, Minsuk; Yoon, Joo Chun; Kim, Hee-Sun; Park, Eun-Mi

    2015-11-01

    Visceral adipose tissue is accumulated with aging. An increase in visceral fat accompanied by low-grade inflammation is associated with several adult-onset diseases. However, the effects of visceral adipose tissue inflammation on the normal and ischemic brains of aged are not clearly defined. To examine the role of visceral adipose tissue inflammation, we evaluated inflammatory cytokines in the serum, visceral adipose tissue, and brain as well as blood-brain barrier (BBB) permeability in aged male mice (20 months) underwent sham or visceral fat removal surgery compared with the young mice (2.5 months). Additionally, ischemic brain injury was compared in young and aged mice with sham and visceral fat removal surgery. Interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels in examined organs were increased in aged mice compared with the young mice, and these levels were reduced in the mice with visceral fat removal. Increased BBB permeability with reduced expression of tight junction proteins in aged sham mice were also decreased in mice with visceral fat removal. After focal ischemic injury, aged mice with visceral fat removal showed a reduction in infarct volumes, BBB permeability, and levels of proinflammatory cytokines in the ischemic brain compared with sham mice, although the neurological outcomes were not significantly improved. In addition, further upregulated visceral adipose tissue inflammation in response to ischemic brain injury was attenuated in mice with visceral fat removal. These results suggest that visceral adipose tissue inflammation is associated with age-related changes in the brain and contributes to the ischemic brain damage in the aged mice. We suggest that visceral adiposity should be considered as a factor affecting brain health and ischemic brain damage in the aged population. PMID:26184082

  7. Age-Related Longitudinal Changes in Metabolic Energy Expenditure during Walking in Boys with Duchenne Muscular Dystrophy

    PubMed Central

    Brehm, Merel-Anne; Kempen, Jiska C. E.; van der Kooi, Anneke J.; de Groot, Imelda J. M.; van den Bergen, Janneke C.; Verschuuren, Jan J. G. M.; Niks, Erik H.; Harlaar, Jaap

    2014-01-01

    Objective The aim of this study was to evaluate age-related changes in metabolic walking energy expenditure in ambulant boys affected by Duchenne muscular dystrophy over a follow-up period of 12 months. Methods At baseline (T1) and 12 months later (T2), metabolic walking energy expenditure was assessed during a 6-minute walk test at comfortable speed in 14 ambulant boys with Duchenne (age range: 6.0-12.5 years, mean 8.2). Outcome measures derived from the assessment included the 6-minute comfortable walking distance (m) and net-nondimensional energy cost relative to speed-matched control cost (SMC-EC, %). Statistical comparisons were made using a two-way repeated measures ANOVA (factors: time (T1 versus T2) and age (<8 years of age (yoa) versus ≥8 yoa)). Results Over the course of the study, a significant decrease of -28m (−8.2%, p = 0.043) was noted in the walked distance at comfortable speed. Besides, SMC-EC increased with 4.4%, although this change was not significant (p = 0.452). Regarding age groups, boys below 8 yoa showed a smaller annual decrease in the walked distance (−15 m) compared to boys above 8 yoa (−37 m). SMC-EC increased with 10% in the older boys, while in the younger boys it decreased (−2.1%). The main effect of age group on walking distance and SMC-EC however was not significant (p>0.158), and also there were no interaction effects (p>0.248). Conclusions The results of our small study suggest that the natural course of walking performance in ambulant boys with Duchenne is characterized by a decrease in comfortable walking distance and an increase in walking energy cost. The rate of energy cost seems to increase with age, while walking distance decreases, which is opposite from the trend in typically developing children. PMID:25506914

  8. Age-related changes in the sulphation of the chondroitin sulphate linkage region from human articular cartilage aggrecan.

    PubMed Central

    Lauder, R M; Huckerby, T N; Brown, G M; Bayliss, M T; Nieduszynski, I A

    2001-01-01

    The chondroitin sulphate (CS) linkage regions have been isolated from human articular cartilage aggrecan (from 10- to 72-year-olds) by chondroitin ABC endolyase digestion and size-exclusion chromatography. Linkage region hexasaccharides have been characterized and their abundance estimated by high-pH anion-exchange chromatography. The basic structure for the CS linkage region oligosaccharides identified from human aggrecan is as follows: DeltaUA(beta1-3)GalNAc[0S/4S/6S](beta1-4)GlcA(beta1-3)Gal[0S/6S](beta1-3)Gal(beta1-4)Xyl, where DeltaUA represents 4,5-unsaturated hexuronic acid, 4S and 6S represent an O-ester sulphate group on C-4 and C-6 respectively, and 0S represents zero sulphation. There are significant age-related changes in the abundance of the various N-acetylgalactosamine (GalNAc) sulphation forms identified, occurring up to approx. 20 years old. During the period from 10 to 20 years old the level of GalNAc 6-sulphation at the linkage region increases from approx. 43% to approx. 75%, while there is a corresponding reduction in unsulphated (approx. 30% to approx. 20%) and 4-sulphated (approx. 25% to approx. 6%) GalNAc residues. There is also an increase in the incidence of linkage region galactose 6-sulphation (approx. 2% to approx. 10%) which was only observed in linkage regions with GalNAc 6-sulphation. Beyond 20 years old there are few changes in the relative abundance of these GalNAc sulphation variants; however, there is a slight increase in the abundance of 6-sulphation between approx. 20 years old and approx. 40 years old and a slight decrease in its abundance beyond approx. 40 years old. Our data show that in the majority of chains from tissues of all ages the GalNAc residue closest to the linkage region is 6-sulphated, but the level of GalNAc 6-sulphation within the linkage region is lower than the average level observed within the repeat region. PMID:11513754

  9. Glutamatergic treatment strategies for age-related memory disorders.

    PubMed

    Müller, W E; Scheuer, K; Stoll, S

    1994-01-01

    Age-related changes of N-methyl-D-aspartate (NMDA) receptors have been found in cortical areas and in the hippocampus of many species. On the basis of a variety of experimental observations it has been suggested that the decrease of NMDA receptor density might be one of the causative factors of the cognitive decline with aging. Based on these findings several strategies have been developed to improve cognition by compensating the NMDA receptor deficits in aging. The most promising approaches are the indirect activation of glutamatergic neurotransmission by agonists of the glycine site or the restoration of the age-related deficit of receptor density by several nootropics. PMID:7997073

  10. Future Global Change and Cognition.

    PubMed

    Lewandowsky, Stephan

    2016-01-01

    The 11 articles in this issue explore how people respond to climate change and other global challenges. The articles pursue three broad strands of enquiry that relate (1) to the effects and causes of "skepticism" about climate change, (2) the purely cognitive challenges that are posed by a complex scientific issue, and (3) the ways in which climate change can be communicated to a wider audience. Cognitive science can contribute to understanding people's responses to global challenges in many ways, and it may also contribute to implementing solutions to those problems. PMID:26749304

  11. Asymmetry, sex differences and age-related changes in the white matter in the healthy elderly: a tract-based study

    PubMed Central

    2011-01-01

    Background Hemispherical asymmetry, sex differences and age-related changes have been reported for the human brain. Meanwhile it was still unclear the presence of the asymmetry or sex differences in the human brain occurred whether as a normal development or as consequences of any pathological changes. The aim of this study was to investigate hemispherical asymmetry, sex differences and age-related changes by using a tract-based analysis in the nerve bundles. Methods 40 healthy elderly subjects underwent magnetic resonance diffusion tensor imaging, and we calculated fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values along the major white matter bundles. Results We identified hemispherical asymmetry in the ADC values for the cingulate fasciculus in the total subject set and in males, and a sex difference in the FA values for the right uncinate fasciculus. For age-related changes, we demonstrated a significant increase in ADC values with advancing age in the right cingulum, left temporal white matter, and a significant decrease in FA values in the right superior longitudinal fasciculus. Conclusion In this study, we found hemispherical asymmetry, sex differences and age-related changes in particular regions of the white matter in the healthy elderly. Our results suggest considering these differences can be important in imaging studies. PMID:21970546

  12. Age-related changes in attentional selection: quality of task set or degradation of task set across time?

    PubMed

    Jackson, Jonathan D; Balota, David A

    2013-09-01

    The present study explores the nature of attentional selection in younger and older adults. Following R. De Jong, E. Berendsen, and R. Cools (1999, Acta Psychologica, Vol. 101, pp. 379-394), we manipulated the response to stimulus interval (RSI) in two attentional selection paradigms to examine if there are age-related differences in the quality of task set and/or the maintenance of task set across time. In Experiment 1, we found that the interference effect in a spatial interference task was (a) overall larger in older adults compared with younger adults, and (b) smaller at the short RSI (200 ms) compared with the long RSI (2000 ms), and (c) not associated with an interaction between age and RSI. The second experiment explored the same variables in a Stroop color interference paradigm. Again, older adults produced a disproportionately larger interference effect than younger adults, the interference effect was smaller at the short RSI compared with the long RSI, and there was no evidence of an interaction between age and RSI. In both experiments, the larger interference effect could not be attributed to age-related general slowing and there was evidence from Vincentile analyses of increasing interference and age effects at the slower response latencies. These results indicate that attentional selection deficits in these two experiments were due to a breakdown in the quality of the task set as opposed to age-related differences in the maintenance of the task set across time. PMID:23834491

  13. Age-Related Change of the Mean Level and Intraindividual Variability of Saccadic Reaction Time Performance in Persons with Intellectual Disabilities

    ERIC Educational Resources Information Center

    Haishi, Koichi; Okuzumi, Hideyuki; Kokubun, Mitsuru

    2013-01-01

    The current study examined age-related change of saccadic reaction time (SRT) in persons with intellectual disabilities (ID). Participants were 29 persons with intellectual disabilities aged between 14 and 34 years whose IQs were between 14 and 70. Participants were divided into Group I (IQ greater than or equal to 35) and Group II (IQ less than…

  14. A Prospective Longitudinal Study of Shyness from Infancy to Adolescence: Stability, Age-Related Changes, and Prediction of Socio-Emotional Functioning

    ERIC Educational Resources Information Center

    Karevold, Evalill; Ystrom, Eivind; Coplan, Robert J.; Sanson, Ann V.; Mathiesen, Kristin S.

    2012-01-01

    This longitudinal, population-based and prospective study investigated the stability, age-related changes, and socio-emotional outcomes of shyness from infancy to early adolescence. A sample of 921 children was followed from ages 1.5 to 12.5 years. Parent-reported shyness was assessed at five time points and maternal- and self-reported social…

  15. [Presbycusis - Age Related Hearing Loss].

    PubMed

    Fischer, N; Weber, B; Riechelmann, H

    2016-07-01

    Presbycusis or age related hearing loss can be defined as a progressive, bilateral and symmetrical sensorineural hearing loss due to age related degeneration of inner ear structures. It can be considered a multifactorial complex disorder with environmental and genetic factors. The molecular, electrophysiological and histological damage at different levels of the inner ear cause a progressive hearing loss, which usually affects the high frequencies of hearing. The resulting poor speech recognition has a negative impact on cognitive, emotional and social function in older adults. Recent investigations revealed an association between hearing impairment and social isolation, anxiety, depression and cognitive decline in elderly. These findings emphasize the importance of diagnosis and treating hearing loss in the elderly population. Hearing aids are the most commonly used devices for treating presbycusis. The technical progress of implantable hearing devices allows an effective hearing rehabilitation even in elderly with severe hearing loss. However, most people with hearing impairments are not treated adequately. PMID:27392191

  16. Myopia for the future or hypersensitivity to reward? Age-related changes in decision making on the Iowa Gambling Task.

    PubMed

    Bauer, A S; Timpe, J C; Edmonds, E C; Bechara, Antoine; Tranel, Daniel; Denburg, Natalie L

    2013-02-01

    It has been shown that older adults perform less well than younger adults on the Iowa Gambling Task (IGT), a real-world type decision-making task that factors together reward, punishment, and uncertainty. To explore the reasons behind this age-related decrement, we administered to an adult life span sample of 265 healthy participants (Mdn age = 62.00 +/- 16.17 years; range [23-88]) 2 versions of the IGT, which have different contingencies for successful performance: A'B'C'D' requires choosing lower immediate reward (paired with lower delayed punishment); E'F'G'H' requires choosing higher immediate punishment (paired with higher delayed reward). There was a significant negative correlation between age and performance on the A'B'C'D' version of the IGT (r = -.16, p = .01), while there was essentially no correlation between age and performance on the E'F'G'H' version (r = -.07, p = .24). In addition, the rate of impaired performance in older participants was significantly higher for the A'B'C'D' version (23%) compared with the E'F'G'H' version (13%). A parsimonious account of these findings is an age-related increase in hypersensitivity to reward, whereby the decisions of older adults are disproportionately influenced by prospects of receiving reward, irrespective of the presence or degree of punishment. PMID:23046455

  17. A review of the equine age-related changes in the immune system: comparisons between human and equine aging, with focus on lung-specific immune-aging.

    PubMed

    Hansen, S; Baptiste, K E; Fjeldborg, J; Horohov, D W

    2015-03-01

    The equine aging process involves many changes to the immune system that may be related to genetics, the level of nutrition, the environment and/or an underlying subclinical disease. Geriatric horses defined as horses above the age of 20, exhibit a decline in body condition, muscle tone and general well-being. It is not known whether these changes contribute to decreased immune function or are the result of declining immune function. Geriatric years are characterized by increased susceptibility to infections and a reduced antibody response to vaccination as a result of changes in the immune system. Humans and horses share many of these age-related changes, with only a few differences. Thus, inflamm-aging and immunosenescence are well-described phenomena in both human and equine research, particularly in relation to the peripheral blood and especially the T-cell compartment. However, the lung is faced with unique challenges because of its constant interaction with the external environment and thus may not share similarities to peripheral blood when considering age-related changes in immune function. Indeed, recent studies have shown discrepancies in cytokine mRNA and protein expression between the peripheral blood and bronchoalveolar lavage immune cells. These results provide important evidence that age-related immune changes or 'dys-functions' are organ-specific. PMID:25497559

  18. Low levels of aluminum can lead to behavioral and morphological changes associated with Alzheimer's disease and age-related neurodegeneration.

    PubMed

    Bondy, Stephen C

    2016-01-01

    Aluminum (Al) is a very common component of the earth's mineral composition. It is not essential element for life and is a constituent of rather inert minerals. Therefore, it has often been regarded as not presenting a significant health hazard. As a result, aluminum-containing agents been used in the preparation of many foodstuffs processing steps and also in elimination of particulate organic matter from water. More recently, the reduced pH of bodies of water resulting from acid rain has led to mobilization of aluminum-containing minerals into a more soluble form, and these have thus entered residential drinking water resources. By this means, the body burden of aluminum in humans has increased. Epidemiological and experimental findings indicate that aluminum is not as harmless as was previously thought, and that aluminum may contribute to the inception and advancement of Alzheimer's disease. Epidemiological data is reinforced by indications that aluminum exposure can result in excess inflammatory activity within the brain. Activation of the immune system not initiated by an infectious agent, typifies the aging brain and is even more augmented in several neurodegenerative diseases. The origin of most age-related neurological disorders is generally not known but as they are largely not of genetic derivation, their development is likely triggered by unknown environmental factors. There is a growing and consistent body of evidence that points to aluminum as being one such significant influence. Evidence is presented that reinforces the likelihood that aluminum is a factor speeding the rate of brain aging. Such acceleration would inevitably enlarge the incidence of age-related neurological diseases. PMID:26687397

  19. The Canine Sand Maze: An Appetitive Spatial Memory Paradigm Sensitive to Age-Related Change in Dogs

    ERIC Educational Resources Information Center

    Salvin, Hannah E.; McGreevy, Paul D.; Sachdev, Perminder S.; Valenzuela, Michael J.

    2011-01-01

    Aged dogs exhibit a spectrum of cognitive abilities including a syndrome similar to Alzheimer's disease. A major impediment to research so far has been the lack of a quick and accurate test of visuospatial memory appropriate for community-based animals. We therefore report on the development and validation of the Canine Sand Maze. A 4.5-m-diameter…

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

    PubMed

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

    2014-09-01

    Progressive age-related changes in skeletal muscle mass and composition, underpin decreases in muscle function, which can inturn lead to impaired mobility and quality of life in older adults. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression in skeletal muscle and are associated with aging. Accumulating evidence suggests that miRNAs play an important role in the age-related changes in skeletal muscle mass, composition and function. At the cellular level, miRNAs have been demonstrated to regulate muscle cell proliferation and differentiation. Furthermore, miRNAs are involved in the transitioning of muscle stem cells from a quiescent, to either an activated or senescence state. Evidence from animal and human studies has shown miRNAs are modulated in muscle atrophy and hypertrophy. In addition, miRNAs have been implicated in changes in muscle fiber composition, fat infiltration and insulin resistance. Both exercise and dietary interventions can combat age-related changes in muscle mass, composition and function, which may be mediated by miRNA modulation in skeletal muscle. Circulating miRNA species derived from myogenic cell populations represent potential biomarkers of aging muscle and the molecular responses to exercise or diet interventions, but larger validation studies are required. In future therapeutic approaches targeting miRNAs, either through exercise, diet or drugs may be able to slow down or prevent the age-related changes in skeletal muscle mass, composition, function, hence help maintain mobility and quality of life in old age. PMID:24833328

  1. A “concrete view” of aging: Event related potentials reveal age-related changes in basic integrative processes in language

    PubMed Central

    Huang, Hsu-Wen; Meyer, Aaron M.; Federmeier, Kara D.

    2012-01-01

    Normal aging is accompanied by changes in both structural and functional cerebral organization. Although verbal knowledge seems to be relatively stable across the lifespan, there are age-related changes in the rapid use of that knowledge during on-line language processing. In particular, aging has been linked to reduce effectiveness in preparing for upcoming words and building an integrated sentence-level representation. The current study assessed whether such age-related changes extend even to much simpler language units, such as modification relations between a centrally presented adjective and a lateralized noun. Adjectives were used to elicit concrete and abstract meanings of the same, polysemous lexical items (e.g., “green book” vs. “interesting book”). Consistent with findings that lexical information is preserved with age, older adults, like younger adults, exhibited concreteness effects at the adjectives, with more negative responses to concrete adjectives over posterior (300–500 ms; N400) and frontal (300–900 ms) channels. However, at the noun, younger adults exhibited concreteness-based predictability effects linked to left hemisphere processing and imagery effects linked to right hemisphere processing, contingent on whether the adjectives and nouns formed a cohesive conceptual unit. In contrast, older adults showed neither effect, suggesting that they were less able to rapidly link the adjective–noun meaning to form an integrated conceptual representation. Age-related changes in language processing may thus be more pervasive than previously realized. PMID:22044648

  2. Age-related changes in skin blood flow at four anatomic sites of the body in males studied by xenon-133

    SciTech Connect

    Tsuchida, Y.

    1990-04-01

    The normal skin blood flow in healthy subjects consisting of 28 males whose ages ranged from 20 to 72 years was measured by the xenon-133 clearance method at four different sites of the body to determine the presence of any age-related changes. The following results were obtained: Significant age-related changes were observed in the skin blood flow of the deltoid region, anterior chest, dorsum of the hand, and dorsum of the foot. Normal skin blood flow was demonstrated to be highly dependent on age and to significantly decrease with age. Average skin blood flow at these four regions of those 70 years of age decreased by 30 to 40 percent when compared to that of those 20 years of age. The skin blood flow at the deltoid region of healthy subjects was higher by 6.3 ml/100 gm per minute than that of patients in poor condition with cancer of the head and neck.

  3. Possible Mechanisms Underlying Aging-Related Changes in Early Diastolic Filling and Long Axis Motion—Left Ventricular Length and Blood Pressure

    PubMed Central

    Peverill, Roger E.; Chou, Bon; Donelan, Lesley; Mottram, Philip M.; Gelman, John S.

    2016-01-01

    Background The transmitral E wave and the peak velocity of early diastolic mitral annular motion (e`) both decrease with age, but the mechanisms underlying these age-related changes are incompletely understood. This study investigated the possible contributions of blood pressure (BP) and left ventricular end-diastolic length (LVEDL) to age-related reductions in E and e`. Methods The study group were 82 healthy adult subjects <55 years of age who were not obese or hypertensive. Transmitral flow and mitral annular motion were recorded using pulsed-wave Doppler. LVEDL was measured from the mitral annular plane to the apical endocardium. Results Age was positively correlated with diastolic BP and septal wall thickness (SWT), inversely correlated with LVEDL (β = -0.25) after adjustment for sex and body surface area, but was not related to left ventricular end-diastolic diameter (LVEDD). Age was also inversely correlated with E (r = -0.36), septal e`(r = -0.53) and lateral e`(r = -0.53). On multivariable analysis, E was inversely correlated with diastolic BP and LVEDD, septal e`was inversely correlated with diastolic BP and positively correlated with SWT and LVEDL, after adjusting for body mass index, whilst lateral e`was inversely correlated with diastolic BP and positively correlated with LVEDL. Conclusion The above findings are consistent with higher BP being a contributor to age-related reductions in both E and e`and shortening of LVEDL with age being a contributor to the age-related reduction in e`. An implication of these findings is that slowing of myocyte relaxation is unlikely to be the sole, and may not be the main, mechanism underlying age-related decreases in E and e`. PMID:27351745

  4. Age-related change of the role of alpha1L-adrenoceptor in canine urethral smooth muscle.

    PubMed

    Suzuki, Y; Moriyama, N; Okaya, Y; Nishimatsu, H; Kawabe, K; Aisaka, K

    1999-10-01

    To examine age-related alteration of the role of alpha1L-adrenoceptor in the urethra, young non-parous and aged parous female dogs were used. In a functional study, we evaluated phenylephrine-induced contraction and antagonistic effects of JTH-601, a newly synthesized alpha1-adrenoceptor antagonist, and prazosin; in a localization survey using autoradiographic technique, we investigated specific [3H]JTH-601 and [3H]tamsulosin binding. Concentration-response curves were obtained for phenylephrine (pD2 = 5.0-5.3). JTH-601 and prazosin antagonized this contraction with pA2 values of 8.2-8.3 and 8.0-8.1, respectively. Specific binding of both [3H]JTH-601 and [3H]tamsulosin were observed in the bladder neck and proximal section of urethra. There were no significant differences of the pD2, pA2, and radio ligand binding between young non-parous and aged parous dogs. PMID:10523074

  5. Age-related changes in prosodic features of maternal speech to prelingually deaf infants with cochlear implants

    PubMed Central

    Kondaurova, Maria V.; Bergeson, Tonya R.; Xu, Huipuing

    2012-01-01

    This study investigated prosodic and structural characteristics of infant-directed speech to hearing-impaired infants as they gain hearing experience with a cochlear implant over a 12-month period of time. Mothers were recorded during a play interaction with their HI infants (N = 27, mean age 18.4 months) at 3, 6, and 12 months post-implantation. Two separate control groups of mothers with age-matched normal-hearing infants (NH-AM) (N = 21, mean age 18.1 months) and hearing experience-matched normal-hearing infants (NH-EM) (N = 24, mean age 3.1 months) were recorded at three testing sessions. Mothers produced less exaggerated pitch characteristics, a larger number of syllables per utterance, and faster speaking rate when interacting with NH-AM as compared to HI infants. Mothers also produced more syllables and demonstrated a trend suggesting faster speaking rate in speech to NH-EM relative to HI infants. Age-related modifications included decreased pitch standard deviation and increased number of syllables in speech to NH-AM infants and increased number of syllables in speech to HI and NH-EM infants across the 12-month period. These results suggest that mothers are sensitive to the hearing status of their infants and modify characteristics of infant-direct speech over time. PMID:24244108

  6. Neural correlates of the age-related changes in motor sequence learning and motor adaptation in older adults

    PubMed Central

    King, Bradley R.; Fogel, Stuart M.; Albouy, Geneviève; Doyon, Julien

    2013-01-01

    As the world's population ages, a deeper understanding of the relationship between aging and motor learning will become increasingly relevant in basic research and applied settings. In this context, this review aims to address the effects of age on motor sequence learning (MSL) and motor adaptation (MA) with respect to behavioral, neurological, and neuroimaging findings. Previous behavioral research investigating the influence of aging on motor learning has consistently reported the following results. First, the initial acquisition of motor sequences is not altered, except under conditions of increased task complexity. Second, older adults demonstrate deficits in motor sequence memory consolidation. And, third, although older adults demonstrate deficits during the exposure phase of MA paradigms, the aftereffects following removal of the sensorimotor perturbation are similar to young adults, suggesting that the adaptive ability of older adults is relatively intact. This paper will review the potential neural underpinnings of these behavioral results, with a particular emphasis on the influence of age-related dysfunctions in the cortico-striatal system on motor learning. PMID:23616757

  7. Glycolytic fast-twitch muscle fiber restoration counters adverse age-related changes in body composition and metabolism.

    PubMed

    Akasaki, Yuichi; Ouchi, Noriyuki; Izumiya, Yasuhiro; Bernardo, Barbara L; Lebrasseur, Nathan K; Walsh, Kenneth

    2014-02-01

    Aging is associated with the development of insulin resistance, increased adiposity, and accumulation of ectopic lipid deposits in tissues and organs. Starting in mid-life there is a progressive decline in lean muscle mass associated with the preferential loss of glycolytic, fast-twitch myofibers. However, it is not known to what extent muscle loss and metabolic dysfunction are causally related or whether they are independent epiphenomena of the aging process. Here, we utilized a skeletal-muscle-specific, conditional transgenic mouse expressing a constitutively active form of Akt1 to examine the consequences of glycolytic, fast-twitch muscle growth in young vs. middle-aged animals fed standard low-fat chow diets. Activation of the Akt1 transgene led to selective skeletal muscle hypertrophy, reversing the loss of lean muscle mass observed upon aging. The Akt1-mediated increase in muscle mass led to reductions in fat mass and hepatic steatosis in older animals, and corrected age-associated impairments in glucose metabolism. These results indicate that the loss of lean muscle mass is a significant contributor to the development of age-related metabolic dysfunction and that interventions that preserve or restore fast/glycolytic muscle may delay the onset of metabolic disease. PMID:24033924

  8. Age-related changes of gene expression in the neocortex: Preliminary data on RNA-Seq of the transcriptome in three functionally distinct cortical areas

    PubMed Central

    NAUMOVA, OKSANA YU.; PALEJEV, DEAN; VLASOVA, NATALIA V.; LEE, MARIA; RYCHKOV, SERGEI YU.; BABICH, OLGA N.; VACCARINO, FLORA M.; GRIGORENKO, ELENA L.

    2012-01-01

    The study of gene expression (i.e., the study of the transcriptome) in different cells and tissues allows us to understand the molecular mechanisms of their differentiation, development and functioning. In this article, we describe some studies of gene-expression profiling for the purposes of understanding developmental (age-related) changes in the brain using different technologies (e.g., DNA-Microarray) and the new and increasingly popular RNA-Seq. We focus on advancements in studies of gene expression in the human brain, which have provided data on the structure and age-related variability of the transcriptome in the brain. We present data on RNA-Seq of the transcriptome in three distinct areas of the neocortex from different ages: mature and elderly individuals. We report that most age-related transcriptional changes affect cellular signaling systems, and, as a result, the transmission of nerve impulses. In general, the results demonstrate the high potential of RNA-Seq for the study of distinctive features of gene expression among cortical areas and the changes in expression through normal and atypical development of the central nervous system. PMID:23062308

  9. Age-Related Changes in the Cardiometabolic Profiles in Singapore Resident Adult Population: Findings from the National Health Survey 2010.

    PubMed

    Loh, Tze Ping; Ma, Stefan; Heng, Derrick; Khoo, Chin Meng

    2016-01-01

    We describe the centile trends of the blood pressure, glycemia and lipid profiles as well as renal function of a representative population who participated in the Singapore National Health Survey in 2010. Representative survey population was sampled in two phases, first using geographical/ residential dwelling type stratification, followed up ethnicity. 2,407 survey participants without any self-reported medical or medication history for diabetes mellitus, hypertension and dyslipidemia were included in this analysis. All biochemistry analyses were performed on Roche platforms. After excluding outliers using Tukey's criteria, the results of the remaining participants were subjected to lambda-mu-sigma (LMS) analysis. In men, systolic blood pressure increased linearly with age. By contrast, an upward inflection around late 40s was seen in women. The diastolic blood pressure was highest in men in the late 30s-50s age group, and in women in the late 50s-60s age group. All glycemia-related parameters, i.e. fasting and 2-hour plasma glucose and HbA1c concentrations increased with age, although the rate of increase differed between the tests. Total cholesterol and LDL-cholesterol concentrations increased with age, which became attenuated between the early 30s and late 50s in men, and declined thereafter. In women, total cholesterol and LDL-cholesterol concentrations gradually increased with age until late 30s, when there is an upward inflection, plateauing after late 50s. Our findings indicate that diagnostic performance of laboratory tests for diabetes may be age-sensitive. Unfavourable age-related cardiovascular risk profiles suggest that the burden of cardiovascular disease in this population will increase with aging population. PMID:27570971

  10. Quantification of age-related changes of α-tocopherol in lysosomal membranes in murine tissues and human fibroblasts.

    PubMed

    König, Jeannette; Besoke, Fabian; Stuetz, Wolfgang; Malarski, Angelika; Jahreis, Gerhard; Grune, Tilman; Höhn, Annika

    2016-05-01

    Considering the biological function of α-tocopherol (α-Toc) as a potent protective factor against oxidative stress, this antioxidant is in the focus of aging research. To understand the role of α-Toc during aging we investigated α-Toc concentrations in young and aged primary human fibroblasts after supplementation with RRR-α-Toc. Additionally, α-Toc contents were determined in brain, kidney, and liver tissue of 10 week-, 18 month-, and 24 month-old mice, which were fed a standard diet containing 100 mg/kg dl-α-tocopheryl acetate. α-Toc concentrations in isolated lysosomes and the expression of the α-Toc transport proteins Niemann Pick C1 (NPC1), Niemann Pick C2 (NPC2), and lipoprotein lipase were also analyzed. Obtained data show a significant age-related increase of α-Toc in murine liver, kidney, and brain tissue as well as in human dermal fibroblasts. Also liver and kidney lysosomes are marked by elevated α-Toc contents with aging. NPC1 and NPC2 protein amounts are significantly decreased in adult and aged murine kidney tissue. Also aged human dermal fibroblasts show decreased NPC1 amounts. Supplementation of young and aged fibroblasts led also to decreased NPC1 amounts, suggesting a direct role of this protein in α-Toc distribution. Our results indicate an age-dependent increase of α-Toc in different murine tissues as well as in human fibroblasts. Furthermore saturation and intracellular distribution of α-Toc seem to be strongly dependent on the availability of this vitamin as well as on the presence of the lysosomal protein NPC1. © 2016 BioFactors, 42(3):307-315, 2016. PMID:27095633

  11. AGE-RELATED CHANGES IN HUMAN TRABECULAR BONE: RELATIONSHIP BETWEEN MICROSTRUCTURAL STRESS AND STRAIN AND DAMAGE MORPHOLOGY

    PubMed Central

    O’Neal, Jessica M.; Nagaraja, Srinidhi; Diab, Tamim; Vidakovic, Brani; Guldberg, Robert E.

    2011-01-01

    Accumulation of microdamage in aging and disease can cause skeletal fragility and is one of several factors contributing to osteoporotic fractures. To better understand the role of microdamage in fragility fracture, the mechanisms of bone failure must be elucidated on a tissue-level scale where interactions between bone matrix properties, the local biomechanical environment, and bone architecture are concurrently examined for their contributions to microdamage formation. A technique combining histological damage assessment of individual trabeculae with linear finite element solutions of trabecular von Mises and principal stress and strain was used to compare the damage initiation threshold between pre-menopausal (32–37 years, n=3 donors) and post-menopausal (71–80 years, n=3 donors) femoral cadaveric bone. Strong associations between damage morphology and stress and strain parameters were observed in both groups, and an age-related decrease in undamaged trabecular von Mises stress was detected. In trabeculae from younger donors, the 95% CI for von Mises stress on undamaged regions ranged from 50.7 – 67.9 MPa, whereas in trabeculae from older donors, stresses were significantly lower (38.7 – 50.2, p<0.01). Local microarchitectural analysis indicated that thinner, rod-like trabeculae oriented along the loading axis are more susceptible to severe microdamage formation in older individuals, while only rod-like architecture was associated with severe damage in younger individuals. This study therefore provides insight into how damage initiation and morphology relate to local trabecular microstructure and the associated stresses and strains under loading. Furthermore, by comparison of samples from pre- and post-menopausal women, the results suggest that trabeculae from younger individuals can sustain higher stresses prior to microdamage initiation. PMID:21724189

  12. Age-Related Changes in the Cardiometabolic Profiles in Singapore Resident Adult Population: Findings from the National Health Survey 2010

    PubMed Central

    Loh, Tze Ping; Ma, Stefan; Heng, Derrick; Khoo, Chin Meng

    2016-01-01

    We describe the centile trends of the blood pressure, glycemia and lipid profiles as well as renal function of a representative population who participated in the Singapore National Health Survey in 2010. Representative survey population was sampled in two phases, first using geographical/ residential dwelling type stratification, followed up ethnicity. 2,407 survey participants without any self-reported medical or medication history for diabetes mellitus, hypertension and dyslipidemia were included in this analysis. All biochemistry analyses were performed on Roche platforms. After excluding outliers using Tukey's criteria, the results of the remaining participants were subjected to lambda-mu-sigma (LMS) analysis. In men, systolic blood pressure increased linearly with age. By contrast, an upward inflection around late 40s was seen in women. The diastolic blood pressure was highest in men in the late 30s-50s age group, and in women in the late 50s-60s age group. All glycemia-related parameters, i.e. fasting and 2-hour plasma glucose and HbA1c concentrations increased with age, although the rate of increase differed between the tests. Total cholesterol and LDL-cholesterol concentrations increased with age, which became attenuated between the early 30s and late 50s in men, and declined thereafter. In women, total cholesterol and LDL-cholesterol concentrations gradually increased with age until late 30s, when there is an upward inflection, plateauing after late 50s. Our findings indicate that diagnostic performance of laboratory tests for diabetes may be age-sensitive. Unfavourable age-related cardiovascular risk profiles suggest that the burden of cardiovascular disease in this population will increase with aging population. PMID:27570971

  13. Age-related hearing loss

    MedlinePlus

    ... is no known single cause of age-related hearing loss. Most commonly, it is caused by changes in the inner ear that occur as you grow older. Your genes and loud noise (from rock concerts or music headphones) may play a large role. The following ...

  14. The canine sand maze: an appetitive spatial memory paradigm sensitive to age-related change in dogs.

    PubMed

    Salvin, Hannah E; McGreevy, Paul D; Sachdev, Perminder S; Valenzuela, Michael J

    2011-01-01

    Aged dogs exhibit a spectrum of cognitive abilities including a syndrome similar to Alzheimer's disease. A major impediment to research so far has been the lack of a quick and accurate test of visuospatial memory appropriate for community-based animals. We therefore report on the development and validation of the Canine Sand Maze. A 4.5-m-diameter circular pool was filled with a sand and powdered food reward mix to a depth of 10 cm. Dogs were given 4 habituation and 16 learning trials which alternated a food reward being half (control trials) or fully-buried (acquisition trials) in a fixed location. After a 90-min break, a probe trial was conducted. Cognitively normal, aged (> 8 years, n  =  11) and young (1-4 years, n  =  11), breed-matched dogs were compared. After correction for differences in control trials, average probe times were 2.97 and 10.81 s for young and aged dogs, respectively. In the probe trial, both groups spent significantly more time in the target quadrant but there was a trend for young dogs to cross a 1 m(2) annulus zone around the buried reward more frequently (2.6 times) than aged dogs (1.5 times). Test-retest reliability in a subset of young dogs (n  =  5) was high. On the basis of these findings, the Canine Sand Maze is presented as a quick, sensitive and nonaversive tool for assessing spatial learning and reference memory in dogs. PMID:21541168

  15. Age-related changes in overcoming proactive interference in associative memory: The role of PFC-mediated executive control processes at retrieval.

    PubMed

    Dulas, Michael R; Duarte, Audrey

    2016-05-15

    Behavioral evidence has shown age-related impairments in overcoming proactive interference in memory, but it is unclear what underlies this deficit. Imaging studies in the young suggest overcoming interference may require several executive control processes supported by the ventrolateral prefrontal cortex (VLPFC) and dorsolateral PFC (DLPFC). The present functional magnetic resonance imaging (fMRI) study investigated whether age-related changes in dissociable executive control processes underlie deficits in overcoming proactive interference in associative memory during retrieval. Participants were tasked with remembering which associate (face or scene) objects were paired with most recently during study, under conditions of high or low proactive interference. Behavioral results demonstrated that, as interference increased, memory performance decreased similarly across groups, with slight associative memory deficits in older adults. Imaging results demonstrated that, across groups, left mid-VLPFC showed increasing activity with increasing interference, though activity did not distinguish correct from incorrect associative memory responses, suggesting this region may not directly serve in successful resolution of proactive interference, per se. Under conditions of high interference, older adults showed reduced associative memory accuracy effects in the DLPFC and anterior PFC. These results suggest that age-related PFC dysfunction may not be ubiquitous. Executive processes supported by ventral regions that detect mnemonic interference may be less affected than processes supported by dorsal and anterior regions that directly resolve interference. PMID:26879623

  16. Adaptive Behavior and Cognitive Function of Adults with Down Syndrome: Modeling Change with Age.

    ERIC Educational Resources Information Center

    Hawkins, Barbara A.; Eklund, Susan J.; James, David R.; Foose, Alice K.

    2003-01-01

    Fifty-eight adults with Down syndrome were assessed longitudinally over 10 years for the purpose of modeling aging-related change in cognitive function and adaptive behavior. Findings provide further evidence of changes in performance with age and include selected effects for participants who completed the study and those lost to follow-up.…

  17. The senescence-accelerated prone mouse (SAMP8): a model of age-related cognitive decline with relevance to alterations of the gene expression and protein abnormalities in Alzheimer's disease.

    PubMed

    Butterfield, D Allan; Poon, H Fai

    2005-10-01

    The senescence-accelerated mouse (SAM) is an accelerated aging model that was established through phenotypic selection from a common genetic pool of AKR/J strain of mice. The SAM model was established in 1981, including nine major senescence-accelerated mouse prone (SAMP) substrains and three major senescence-accelerated mouse resistant (SAMR) substrains, each of which exhibits characteristic disorders. Recently, SAMP8 have drawn attention in gerontological research due to its characteristic learning and memory deficits at old age. Many recent reports provide insight into mechanisms of the cognitive impairment and pathological changes in SAMP8. Therefore, this mini review examines the recent findings of SAMP8 mice abnormalities at the gene and protein levels. The genes and proteins described in this review are functionally categorized into neuroprotection, signal transduction, protein folding/degradation, cytoskeleton/transport, immune response and reactive oxygen species (ROS) production. All of these processes are involved in learning and memory. Although these studies provide insight into the mechanisms that contribute to the learning and memory decline in aged SAMP8 mice, higher throughput techniques of proteomics and genomics are necessary to study the alterations of gene expression and protein abnormalities in SAMP8 mice brain in order to more completely understand the central nervous system dysfunction in this mouse model. The SAMP8 is a good animal model to investigate the fundamental mechanisms of age-related learning and memory deficits at the gene and protein levels. PMID:16026957

  18. Predicting cognitive change within domains

    PubMed Central

    Duff, Kevin; Beglinger, Leigh J.; Moser, David J.; Paulsen, Jane S.

    2010-01-01

    Standardized regression based (SRB) formulas, a method for predicting cognitive change across time, traditionally use baseline performance on a neuropsychological measure to predict future performance on that same measure. However, there are instances in which the same tests may not be given at follow-up assessments (e.g., lack of continuity of provider, avoiding practice effects). The current study sought to expand this methodology by developing SRBs to predict performance on different tests within the same cognitive domain. Using a sample of 127 non-demented community-dwelling older adults assessed at baseline and after one year, two sets of SRBs were developed: 1. those predicting performance on the same test, and 2. those predicting performance on a different test within the same cognitive domain. The domains examined were learning and memory, processing speed, and language. Across both sets of SRBs, one year scores were significantly predicted by baseline scores, especially for the learning and memory and processing speed measures. Although SRBs developed for the same test were comparable to those developed for different tests within the same domain, less variance was accounted for as tests became less similar. The current results lend preliminary support for additional development of SRBs, both for same- and different-tests, as well as beginning to examine domain-based SRBs. PMID:20358479

  19. Principal component structuring of the non-REM Sleep EEG spectrum in older adults yields age-related changes in the sleep and wake drives.

    PubMed

    Putilov, Arcady A; Münch, Mirjam Y; Cajochen, Christian

    2013-12-01

    Age-related disturbances of the sleep-wake cycle can reflect ontogenetic changes in regulatory mechanisms underlying normal and pathological aging, but the exact nature of these changes remains unclear. The present report is the first attempt to apply principal component analysis to the electroencephalographic (EEG) spectrum to examine of whether the observed age-related changes in the objective sleep measures can be linked to the opponent sleep-promoting and wake-promoting processes. The EEG indicators of these processes--scores on the 1st and 2nd principal components of the EEG spectrum, respectively--were compared in 15 older (57-74 years) and 16 younger (20-31 years) healthy volunteers. The scores were calculated for non-REM sleep episodes which occurred during ten 75-min naps scheduled every 150 min throughout a 40-h constant routine protocol. Both, a decrease of the 1st principal component score and an increase of the 2nd principal component score were found to contribute to such most obvious age-related modification of the sleep EEG spectrum as attenuation of EEG slow-wave activity in older people. Therefore, we concluded that the normal aging process can reflect both a weakening of the sleep-promoting process and a strengthening of the wake-promoting process, respectively. Such bidirectional changes in chronoregulatory processes may explain why sleep of older people is characterized by the few profitable and a number of detrimental features (i.e., a better ability to cope with daytime sleepiness and sleep loss vs. difficulty of falling asleep, decreased total nighttime sleep, "lightened" and fragmentized sleep, unwanted early morning awakenings, etc.). PMID:23855458

  20. Age-related changes in trunk neuromuscular activation patterns during a controlled functional transfer task include amplitude and temporal synergies.

    PubMed

    Quirk, D Adam; Hubley-Kozey, Cheryl L

    2014-12-01

    While healthy aging is associated with physiological changes that can impair control of trunk motion, few studies examine how spinal muscle responses change with increasing age. This study examined whether older (over 65 years) compared to younger (20-45 years) adults had higher overall amplitude and altered temporal recruitment patterns of trunk musculature when performing a functional transfer task. Surface electromyograms from twelve bilateral trunk muscle (24) sites were analyzed using principal component analysis, extracting amplitude and temporal features (PCs) from electromyographic waveforms. Two PCs explained 96% of the waveform variance. Three factor ANOVA models tested main effects (group, muscle and reach) and interactions for PC scores. Significant (p<.0125) group interactions were found for all PC scores. Post hoc analysis revealed that relative to younger adults, older adults recruited higher agonist and antagonistic activity, demonstrated continuous activation levels in specific muscle sites despite changing external moments, and had altered temporal synergies within abdominal and back musculature. In summary both older and younger adults recruit highly organized activation patterns in response to changing external moments. Differences in temporal trunk musculature recruitment patterns suggest that older adults experience different dynamic spinal stiffness and loading compared to younger adults during a functional lifting task. PMID:25457424

  1. Morphometric studies of age related changes in normal human breast and their significance for evolution of mammary cancer.

    PubMed Central

    Hutson, S W; Cowen, P N; Bird, C C

    1985-01-01

    Ageing changes in the normal human female breast were studied to determine their significance for the evolution of mammary cancer. Employing the morphometric techniques of point counting and planimetry, objective quantitative measurements were made of the structure of the normal female breast in 58 subjects from the prepubertal to late postreproductive period. The relative amounts of epithelial and connective tissue varied with age, and the epithelial elements (combined lobular and extralobular) were unevenly distributed within the gland, with lower containing more than upper quadrants. The upper outer quadrant, however, usually contained the largest proportion of lobular units, which may relate to the higher incidence of lobular carcinoma found in this quadrant. Involution was shown to be a premenopausal rather than postmenopausal phenomenon. Mammary dysplastic changes were uncommon in all age groups. Images PMID:3973052

  2. Oxidative stress and age-related changes in T cells: is thalassemia a model of accelerated immune system aging?

    PubMed Central

    Ghatreh-Samani, Mahdi; Esmaeili, Nafiseh; Soleimani, Masoud; Asadi-Samani, Majid; Ghatreh-Samani, Keihan

    2016-01-01

    Iron overload in β-thalassemia major occurs mainly due to blood transfusion, an essential treatment for β-thalassemia major patients, which results in oxidative stress. It has been thought that oxidative stress causes elevation of immune system senescent cells. Under this condition, cells normally enhance in aging, which is referred to as premature immunosenescence. Because there is no animal model for immunosenescence, most knowledge on the immunosenescence pattern is based on induction of immunosenescence. In this review, we describe iron overload and oxidative stress in β-thalassemia major patients and how they make these patients a suitable human model for immunosenescence. We also consider oxidative stress in some kinds of chronic virus infections, which induce changes in the immune system similar to β-thalassemia major. In conclusion, a therapeutic approach used to improve the immune system in such chronic virus diseases, may change the immunosenescence state and make life conditions better for β-thalassemia major patients. PMID:27095931

  3. Aging related changes in mixed basal saliva concentration of sodium, potassium and chloride in healthy non medicated humans.

    PubMed

    De Oliveira, Rui; Navas, Eunice; Duran, Carolina; Pinto, Maria; Gutierrez, Jose; Eblen-Zajjur, Antonio

    2014-01-01

    It is well known that the salivary flow is reduced by aging but ionic composition changes associated to aging have been less evaluated. To measure salivary and plasmatic [Na(+)], [K(+)] and [Cl(-)] and to correlate with age in healthy, non-medicated subjects of any gender, 165 healthy participating subjects (over 15 years old) were asked to give sample of 5 mL mix basal saliva in a plastic vial without any stimulation technique, additionally, 5 mL of venous blood was collected. Samples [Na(+)] and [K(+)] were measured by flame photometry (Corning™ M-405) and [Cl(-)] by voltametric chlorometry (Corning™ M-920). Ionic concentrations were expressed as (X±DE; meq.L⁻¹). All three ionic concentrations progressively increased with age, with the lineal regression equation being: [Na(+)] mEq=17.76 + 0.26(Age); r=+0.42; F=31.5; P=0.00001; [K(+)] mEq=13.2+0.15(Age); r=+0.32; F=16.5; P=0.00001; [Cl(-)] mEq=9.05+0.18(Age); r=+0.35; F=7.8; P=0.0071. Age induced changes in salivary ionic concentrations were not associated to blood ionic changes. However, saliva and blood [Na(+)] and [K(+)] were correlated (r=+0.25; F=4.49; P=0.04 and r=+0.30; F=6.98; P=0.01, respectively). Significant association was found among salivary ions: [Na(+)] mEq=9.14+0.99[K(+)] (r=+0.79; F=95.2; P=0.000001); [Cl(-)] mEq=0.95+0.56[Na(+)] (r=0.79; F=106.6; P=0.000001) and [Cl(-)] mEq=3.45+0.69[K(+)] (r=0.73; F=72.5; P=0.000001). These results confirm and measure the impact of aging over the mixed and resting salivary secretion process and suggest that local changes are not related to blood ionic composition. PMID:25101709

  4. [Combined application of electric myo-stimulation and meso-therapy for the correction of age-related changes of the facial skin].

    PubMed

    Rozhanets, A R; Turova, E A; Kul'chitskaia, D B

    2010-01-01

    The objective of the present study was to evaluate effects of mesotherapy (MT) and electrostimulation (EMS) on age-related changes of the facial skin. The secondary objective was to identify factors influencing the therapeutic efficiency of these methods. The study included 60 women aged from 30 to 59 years. All the patients were examined prior to the onset and in the end (after one month) of the corrective treatment. Facial skin conditions were assessed using a Skin XP Pro system and skin microcirculation by laser Doppler flowmetry (LDF). The psychological status of the patients was evaluated with the help of the Well-being-Activity-Mood test. After the primary examination, the participants of the study were randomly divided into two groups. Group 1 (n=30) included women treated by MT and EMS, the control group 2 (n=30) was comprised of the patients who did not receive the above treatment. The results of the study indicate that combine MT + EMS therapy significantly improves the state of facial skin, decreases its pigmentation, reduces the number and depth of wrinkles, enhances skin moisture, improves its elasticity and decreases porosity. Dynamics of these parameters and overall effect of correction were shown to correlate with the severity of skin changes before the treatment. Age-related changes in the facial skin were especially well-apparent in women with the lowered activity level and impaired mood. Characteristics of mood in the course of therapeutic correction correlated with dynamics of skin smoothness and elasticity. PMID:21086592

  5. Age-related changes in proliferation, the numbers of mast cells, eosinophils, and cd45-positive cells in human dermis.

    PubMed

    Gunin, Andrei G; Kornilova, Natalia K; Vasilieva, Olga V; Petrov, Vadim V

    2011-04-01

    Skin aging is an extremely important medical and social problem in the modern world. Therefore, a goal of the present work was to estimate changes in the numbers of fibroblast-like cells, proliferating cells nuclear antigen-positive cells, CD45-positive cells, mast cells, and eosinophils in human dermis at different ages. Skin specimens from human fetuses that died antenatally from 20 to 40 weeks of pregnancy and humans who died from different causes from 1 day to 85 years of life were used for the study. Results showed a decrease in a total number and the number of proliferating cells nuclear antigen-positive fibroblast-like cells in dermis with progression of age. The numbers of CD45-positive cells and mast cells are gradually increased with aging. Eosinophils are almost absent in dermis independently on age. Mast cells are probably a main factor that potentially can be involved in tissue damage and aging changes in skin. Mast cells should be regarded as an important target for anti-aging therapy. PMID:21106704

  6. Season- and age-related reproductive changes based on fecal androgen concentrations in male koalas, Phascolarctos cinereus.

    PubMed

    Kusuda, Satoshi; Hashikawa, Hisashi; Takeda, Masato; Ito, Hideki; Goto, Atsushi; Oguchi, Jun; Doi, Osamu

    2013-01-01

    The purposes of the present study were to clarify age- and season- related androgen patterns, and to compare the reproductive physiology between Japanese captive koala populations and Australian populations. To measure fecal androgens, feces were collected from male koalas (4.2 to 13.8 years of age) kept in Japanese zoos. Fecal androgens were extracted with methanol from the lyophilized samples and determined by enzyme immunoassay using 4-androstene-3,17-dione antibody. Fecal androgen concentration in male koalas increased after sexual maturation and remained relatively high until old age. In the survey with the Japanese zoo studbook of koalas, copulation (conception) month showed a pyramid shape with a peak in March to June (60.7%) in koalas born and reared in Japanese zoos and from July to April with the highest concentration in September to January (69.7%) in Australian institutes. Japanese zoo koala populations have a characteristic physiological cycle adapted to Japan's seasonal changes. The suitable month of year for copulation or conception in Japan is diametrically opposed to that in Australia. Mean fecal androgen concentrations by month in the males born and reared in Japan indicated annual changes with the highest concentration in May and the lowest value in November. Fecal androgen analysis may be a noninvasive alternative tool to monitor circulating testosterone and may be helpful in understanding reproductive activity and physiology in male koalas. PMID:23502854

  7. Season- and Age-related Reproductive Changes Based on Fecal Androgen Concentrations in Male Koalas, Phascolarctos cinereus

    PubMed Central

    KUSUDA, Satoshi; HASHIKAWA, Hisashi; TAKEDA, Masato; ITO, Hideki; GOTO, Atsushi; OGUCHI, Jun; DOI, Osamu

    2013-01-01

    Abstract The purposes of the present study were to clarify age- and season- related androgen patterns, and to compare the reproductive physiology between Japanese captive koala populations and Australian populations. To measure fecal androgens, feces were collected from male koalas (4.2 to 13.8 years of age) kept in Japanese zoos. Fecal androgens were extracted with methanol from the lyophilized samples and determined by enzyme immunoassay using 4-androstene-3,17-dione antibody. Fecal androgen concentration in male koalas increased after sexual maturation and remained relatively high until old age. In the survey with the Japanese zoo studbook of koalas, copulation (conception) month showed a pyramid shape with a peak in March to June (60.7%) in koalas born and reared in Japanese zoos and from July to April with the highest concentration in September to January (69.7%) in Australian institutes. Japanese zoo koala populations have a characteristic physiological cycle adapted to Japan's seasonal changes. The suitable month of year for copulation or conception in Japan is diametrically opposed to that in Australia. Mean fecal androgen concentrations by month in the males born and reared in Japan indicated annual changes with the highest concentration in May and the lowest value in November. Fecal androgen analysis may be a noninvasive alternative tool to monitor circulating testosterone and may be helpful in understanding reproductive activity and physiology in male koalas. PMID:23502854

  8. Age-Related Changes to Human Stratum Corneum Lipids Detected Using Time-of-Flight Secondary Ion Mass Spectrometry Following in Vivo Sampling.

    PubMed

    Starr, Nichola J; Johnson, Daniel J; Wibawa, Judata; Marlow, Ian; Bell, Mike; Barrett, David A; Scurr, David J

    2016-04-19

    This work demonstrates the ability to detect changes in both quantity and spatial distribution of human stratum corneum (SC) lipids from samples collected in vivo. The SC functions as the predominant barrier to the body, protecting against the penetration of xenobiotic substances. Changes to the SC lipid composition have been associated with barrier impairment and consequent skin disorders, and it is therefore important to monitor and quantify changes to this structure. This work demonstrates the first reported use of time-of-flight secondary ion mass spectrometry (ToF-SIMS) to assess physiological changes to human SC as a function of depth. This technique provides exceptional sensitivity and chemical specificity, allowing analysis of single tape stripped samples taken from volunteers. Using this methodology we were able to successfully identify chemical differences in human SC resulting from both intrinsic and extrinsic (photo) aging. Samples were collected from women of two age groups (under 27 and postmenopausal) and from two body sites with varying UV exposure (inner forearm and dorsal hand), and differences were identified using multivariate data analysis. The key finding was the significant aged-related increase and change in spatial distribution of the sterol cholesterol sulfate, a membrane stabilizing lipid. Significant changes in the prevalence of both lignoceric acid (C24:0) and hexacosanoic acid (C26:0) were also observed. This work describes previously unreported age-related chemical changes to human SC, providing an insight into aging mechanisms which may improve the design of both pharmaceutical and cosmetic topical products. PMID:27010630

  9. Age related changes in pelvis size among adolescent and adult females with reference to parturition from Naraingarh, Haryana (India).

    PubMed

    Sharma, Krishan; Gupta, Puneet; Shandilya, Shailza

    2016-08-01

    This research examines the ontogenic patterns of changes in growth during adolescence, pelvis variations and growth during twenties and thirties of age, structural remodeling of pelvis related to childbirth and relationship of pelvis area with physique based on the cross-sectional data on 391 females from the state of Haryana. Peak growth velocity for body height and breadths of skeletal traits occurred between 11 and 12 years, much before mean age of menarche at 13.5 years; while for body weight and body mass index (BMI) occurred between 14 and 15 years, after the mean age of menarche. Untill the age 11 years, 11.87% of growth in stature was remaining, 19.37% for bi-cristal breadth, 25.96% for bi-ischial breadth and 35.82% for pelvic area. The hypothesis of critical value of pelvic width of 240mm at iliocristale for menarche to occur has been only a statistical association. Higher prevalence of malnutrition during pubertal phase than pre- and post-pubertal phases was due to greater nutritional needs during puberty. Among adult females, BMI was very poorly correlated with stature but very strongly correlated with body breadths, body breadth-stature indices and body weight. The body mass and pelvis size continued to change during 20s and first half of 30s. The continued increase of BMI was due to increase in body fat and muscle mass in females 18 years and older. To tease apart age and parturition effects on pelvis variations, the analysis showed that pelvic bones remodeling took place after the first child was born and not after the subsequent births, and it was a sign of childbirth phenotypic plasticity rather than age. Pelvis area was strongly associated with stature, BMI and age. Mean pelvic area of tall females was greater than those of medium and short stature. Females with broad shoulders had significantly greater mean pelvis area than those with narrow shoulders and medium shoulders. Females having thin/lean physique had the smallest mean pelvis area

  10. Age-related changes in soma size of neurons in the spinal cord motor column of the cat.

    PubMed

    Liu, R H; Bertolotto, C; Engelhardt, J K; Chase, M H

    1996-06-28

    The present study was undertaken to examine the effect of the aging process on the soma size and number of motoneurons and interneurons in the motor column of the spinal cord of old cats. Neurons in the motor column were divided into small and large populations based on a bimodal distribution of their soma cross-sectional areas. A 17% decrease in the cross-sectional area of small neurons was observed, this decrease was statistically significant (P < 0.0001). The cross-sectional area of large neurons decreased by only 6%, which was statistically significant (P < 0.05). On the other hand, there was no significant difference in the number of large, small or of these combined population of ventral horn neurons in the aged cats compared with the control animals. This data suggest that neurons in the motor column are not uniformly affected by the aging process because morphological changes are proportionally greater in small neurons than in large neurons. PMID:8817566

  11. Age-related changes in p56lck protein levels and phenotypic distribution of T lymphocytes in young rats.

    PubMed

    Hosea, Heather J; Rector, Edward S; Taylor, Carla G

    2005-03-01

    p56lck is involved in the maturation of T-cells from double negative (DN) into double positive (DP) T-cells. The objective of this experiment was to determine changes in the levels of thymic and splenic T-cell p56lck using Western immunoblotting, along with the proportion and number ofT-cell subsets in thymus, spleen and blood using flow cytometry in growing Sprague-Dawley rats. Thymic p56lck levels were negatively correlated with age (r = - 0.42, p = 0.04) and positively correlated with age in the spleen (r = 0.50, p = 0.01). Nine-week-old rats had a higher percentage of thymic DN and CD8 cells with fewer DP cells compared to younger rats. There were minor differences in the proportions of T-cell subsets in the spleen and blood. T-cell numbers remained proportional to body weight in the lymphoid organs; however, the lower absolute number of T-cells in the younger rats might indicate that they are less able to respond to antigens. PMID:15712602

  12. Proteomic analysis reveals age-related changes in tendon matrix composition, with age- and injury-specific matrix fragmentation.

    PubMed

    Peffers, Mandy J; Thorpe, Chavaunne T; Collins, John A; Eong, Robin; Wei, Timothy K J; Screen, Hazel R C; Clegg, Peter D

    2014-09-12

    Energy storing tendons, such as the human Achilles and equine superficial digital flexor tendon (SDFT), are highly prone to injury, the incidence of which increases with aging. The cellular and molecular mechanisms that result in increased injury in aged tendons are not well established but are thought to result in altered matrix turnover. However, little attempt has been made to fully characterize the tendon proteome nor determine how the abundance of specific tendon proteins changes with aging and/or injury. The aim of this study was, therefore, to assess the protein profile of normal SDFTs from young and old horses using label-free relative quantification to identify differentially abundant proteins and peptide fragments between age groups. The protein profile of injured SDFTs from young and old horses was also assessed. The results demonstrate distinct proteomic profiles in young and old tendon, with alterations in the levels of proteins involved in matrix organization and regulation of cell tension. Furthermore, we identified several new peptide fragments (neopeptides) present in aged tendons, suggesting that there are age-specific cleavage patterns within the SDFT. Proteomic profile also differed between young and old injured tendon, with a greater number of neopeptides identified in young injured tendon. This study has increased the knowledge of molecular events associated with tendon aging and injury, suggesting that maintenance and repair of tendon tissue may be reduced in aged individuals and may help to explain why the risk of injury increases with aging. PMID:25077967

  13. Age-related changes in phase-space distribution of ABPM data in normotensive and hypertensive patients.

    PubMed

    Recordati, Giorgio

    2011-04-26

    The data collected by ambulatory blood pressure monitoring have been studied in the phase-space of R-R interval and blood pressure and their individual distribution quantified by the slope of the regression line through 24-h values. This slope has been termed "ambulatory autonomic reciprocity index" and abbreviated as AARIs and AARId, the "s" and "d" indicating the relation with systolic and diastolic blood pressure respectively. Ambulatory monitoring was performed in 200 normotensive (NT: 135 females) and 200 untreated hypertensive patients (HT: 59 females). The AARIs was: NT: -6.04±2.7 and HT: -4.69±2.4ms/mmHg, respectively (p<0.001); the AARId was: -7.04±2.9 for NT and -5.79±2.8 for HT subjects (p<0.001). When distributed by decades of life the steepest AARIs occurred at the 20-29 decade, while the flattest at the 60-69 decade. At the 60-69 decade and above, the AARIs was similar in both groups (ANOVA o.w. NT: p<0.001; HT: p<0.01). AARIs and AARId were strongly correlated with 24-h variability of R-R interval, either 24-h standard deviation or coefficient of variation (p<0.001), and poorly correlated with 24-h variability of blood pressure. These data suggest that the AARI, when seen in the context of the "Autonomic Space", may be viewed as a 24-h period index of centrally driven cardiovagal function. Being based on both blood pressure and heart rate measurements, the AARI may become clinically useful to address life style changes and pharmacological treatment of hypertensive patients towards optimal results. PMID:21216678

  14. Age-related changes in neural activity during source memory encoding in young, middle-aged and elderly adults.

    PubMed

    Cansino, Selene; Trejo-Morales, Patricia; Hernández-Ramos, Evelia

    2010-07-01

    Source memory, the ability to remember contextual information present at the moment an event occurs, declines gradually during normal aging. The present study addressed whether source memory decline is related to changes in neural activity during encoding across age. Event-related potentials (ERPs) were recorded in three groups of 14 subjects each: young (21-26 years), middle-aged (50-55 years) and older adults (70-77 years). ERPs were recorded while the subjects performed a natural/artificial judgment on images of common objects that were presented randomly in one of the quadrants of the screen (encoding phase). At retrieval, old images mixed with new ones were presented at the center of the screen and the subjects judged whether each image was new or old and, if old, were asked to indicate at which position of the screen the image was presented in the encoding session. The neurophysiological activity recorded during encoding was segregated for the study items according to whether their context was correctly retrieved or not, so as to search for subsequent memory effects (SME). These effects, which consisted of larger amplitude for items subsequently attracting a correct source judgment than an incorrect one, were observed in the three groups, but their onset was delayed across the age groups. The amplitude of the SME was similar across age groups at the frontal and central electrode sites, but was manifested more at the posterior sites in middle-aged and older adults, suggesting that source memory decline may be related to less efficient encoding mechanisms. PMID:20441775

  15. Age-related responses of right ventricle in swim-trained rats: changes in lactate and pyruvate contents and lactate dehydrogenase activity.

    PubMed

    Anitha, V; Asha Devi, S

    1996-09-18

    Age related changes in carbohydrate substrates such as, glucose, glycogen, pyruvic acid and lactic acid and the activity of lactate dehydrogenase (LDH) and LDH isoenzyme profile were evaluated in the right ventricle (RV) of swim-trained rats of 6- (adult), 12- (middle-aged) and 18- (old) months-of-age. Moderate hypertrophy was seen in the heart and RV in response to training in all age groups with the 12 months exhibiting a significant increase. While resting levels of pyruvate and glucose in the RV showed small elevations in adult and middle-aged rats, lactic acid showed reductions in all ages. Glycogen supercompensation was seen in the RV of trained animals. These age-related alterations in RV were associated with decreases in blood lactic acid and glucose in the trained rats belonging to all ages. Total protein of the RV decreased with age and exercise increased the content. Total LDH and M4-LDH activities decreased with age. However, training increased their activities in all ages. These changes in the RV suggests that swimming activity produces adaptations (e.g. increased LDH and M4) in all age groups. Considering the degree of adaptations, it can be suggested that adult and middle-aged are suitable for initiating swim-training programs, but not in old age. PMID:8869911

  16. Age-related neuroinflammation and changes in AKT-GSK-3β and WNT/ β-CATENIN signaling in rat hippocampus

    PubMed Central

    Orellana, Ana Maria Marques; Vasconcelos, Andrea Rodrigues; Leite, Jacqueline Alves; de Sá Lima, Larissa; Andreotti, Diana Zukas; Munhoz, Carolina Demarchi; Kawamoto, Elisa Mitiko; Scavone, Cristoforo

    2015-01-01

    Aging is a multifactorial process associated with an increased susceptibility to neurodegenerative disorders which can be related to chronic inflammation. Chronic inflammation, however, can be characterized by the persistent elevated glucocorticoid (GCs) levels, activation of the proinflammatory transcription factor NF-кB, as well as an increase in cytokines. Interestingly, both NF-кB and cytokines can be even modulated by Glycogen Synthase Kinase 3 beta (GSK-3β) activity, which is a key protein that can intermediate inflammation and metabolism, once it has a critical role in AKT signaling pathway, and can also intermediate WNT/β-CATENIN signaling pathway. The aim of this study was to verify age-related changes in inflammatory status, as well as in the AKT and WNT signaling pathways. Results showed an age-related increase in neuroinflammation as indicated by NF-кB activation, TNF-α and GCs increased levels, a decrease in AKT activation and an increase in GSK-3β activity in both 12- and 24- month old animals. Aging also seems to induce a progressive decrease in canonical WNT/β-CATENIN signaling pathway once there is a decrease in DVL-2 levels and in the transcription of Axin2 gene. Little is known about the DVL-2 regulation as well as its roles in WNT signaling pathway, but for the first time it was suggested that DVL-2 expression can be changed along aging. PMID:26647069

  17. Dopaminergic modulation of incentive motivation in adolescence: age-related changes in signaling, individual differences, and implications for the development of self-regulation

    PubMed Central

    Luciana, Monica; Wahlstrom, Dustin; Porter, James N.; Collins, Paul F.

    2012-01-01

    Behavioral activation that is associated with incentive-reward motivation increases in adolescence relative to childhood and adulthood. This quadratic developmental pattern is generally supported by behavioral and experimental neuroscience findings. We suggest that a focus on changes in dopamine neurotransmission is informative in understanding the mechanism for this adolescent increase in reward-related behavioral activation and subsequent decline into adulthood. We present evidence to indicate that incentive-reward motivation is modulated by mesoaccumbens dopamine and that it increases in adolescence before declining into adulthood due to normative developmental changes at the molecular level. Potential mechanisms of variation in functional mesoaccumbens dopamine transmission are discussed with a focus on the interplay between tonic and phasic modes of DA transmission in modulating both general incentive-motivational biases and the efficacy of reward learning during exposure to novel reward experiences. Interactions between individual difference factors and these age-related trends are discussed. PMID:22390660

  18. The Role of Sensory Modality in Age-Related Distraction: A Critical Review and a Renewed View

    ERIC Educational Resources Information Center

    Guerreiro, Maria J. S.; Murphy, Dana R.; Van Gerven, Pascal W. M.

    2010-01-01

    Selective attention requires the ability to focus on relevant information and to ignore irrelevant information. The ability to inhibit irrelevant information has been proposed to be the main source of age-related cognitive change (e.g., Hasher & Zacks, 1988). Although age-related distraction by irrelevant information has been extensively…

  19. Comparison of age-related changes in in vivo and in vitro measures of testicular steroidogenesis after acute cadmium exposure in the sprague-dawley rat

    SciTech Connect

    Phelps, P.V.; Laskey, J.W.

    1989-01-01

    Previous reports have demonstrated that cadmium- induced testicular necrosis is an age-dependent process. However, little information exists on age-related intestitial cell (IC) damage in the rat after acute exposure to Cd. In-vitro and in-vivo measures of testicular damage were utilized to compare the sensitivity of these measures and to further investigate age-related Cd-induced testicular damage. Testes, epididymides, and seminal-vesicle weights, serum testosterone (sT), hCG-stimulated sT, and basal and stimulated IC testosterone (T) production were compared in rats 21 d following an injection of 2 mg Cd/kg at 9, 37, 67, and 97 d of age. The only Cd-related change noted for immature rats was an 84% reduction in sT. In rats injected when 37 d old, hCG-stimulated sT and epididymides and seminal-vesicle weights, although depressed, were not significantly altered. However, all other measurements were significantly depressed. All measures of testicular damage were significantly depressed in rats injected at 67 and 97 d of age. Overall, in vitro measures were more sensitive indicators of Cd-induced testicular damage than in vivo measures.

  20. Effects of intermittent fasting on age-related changes on Na,K-ATPase activity and oxidative status induced by lipopolysaccharide in rat hippocampus.

    PubMed

    Vasconcelos, Andrea Rodrigues; Kinoshita, Paula Fernanda; Yshii, Lidia Mitiko; Marques Orellana, Ana Maria; Böhmer, Ana Elisa; de Sá Lima, Larissa; Alves, Rosana; Andreotti, Diana Zukas; Marcourakis, Tania; Scavone, Cristoforo; Kawamoto, Elisa Mitiko

    2015-05-01

    Chronic neuroinflammation is a common characteristic of neurodegenerative diseases, and lipopolysaccharide (LPS) signaling is linked to glutamate-nitric oxide-Na,K-ATPase isoforms pathway in central nervous system (CNS) and also causes neuroinflammation. Intermittent fasting (IF) induces adaptive responses in the brain that can suppress inflammation, but the age-related effect of IF on LPS modulatory influence on nitric oxide-Na,K-ATPase isoforms is unknown. This work compared the effects of LPS on the activity of α1,α2,3 Na,K-ATPase, nitric oxide synthase gene expression and/or activity, cyclic guanosine monophosphate, 3-nitrotyrosine-containing proteins, and levels of thiobarbituric acid-reactive substances in CNS of young and older rats submitted to the IF protocol for 30 days. LPS induced an age-related effect in neuronal nitric oxide synthase activity, cyclic guanosine monophosphate, and levels of thiobarbituric acid-reactive substances in rat hippocampus that was linked to changes in α2,3-Na,K-ATPase activity, 3-nitrotyrosine proteins, and inducible nitric oxide synthase gene expression. IF induced adaptative cellular stress-response signaling pathways reverting LPS effects in rat hippocampus of young and older rats. The results suggest that IF in both ages would reduce the risk for deficits on brain function and neurodegenerative disorders linked to inflammatory response in the CNS. PMID:25818175

  1. High resolution magnetic resonance imaging of the calcaneus: age-related changes in trabecular structure and comparison with dual X-ray absorptiometry measurements

    NASA Technical Reports Server (NTRS)

    Ouyang, X.; Selby, K.; Lang, P.; Engelke, K.; Klifa, C.; Fan, B.; Zucconi, F.; Hottya, G.; Chen, M.; Majumdar, S.; Genant, H. K.

    1997-01-01

    A high-resolution magnetic resonance imaging (MRI) protocol, together with specialized image processing techniques, was applied to the quantitative measurement of age-related changes in calcaneal trabecular structure. The reproducibility of the technique was assessed and the annual rates of change for several trabecular structure parameters were measured. The MR-derived trabecular parameters were compared with calcaneal bone mineral density (BMD), measured by dual X-ray absorptiometry (DXA) in the same subjects. Sagittal MR images were acquired at 1.5 T in 23 healthy women (mean age: 49.3 +/- 16.6 [SD]), using a three-dimensional gradient echo sequence. Image analysis procedures included internal gray-scale calibration, bone and marrow segmentation, and run-length methods. Three trabecular structure parameters, apparent bone volume (ABV/TV), intercept thickness (I.Th), and intercept separation (I.Sp) were calculated from the MR images. The short- and long-term precision errors (mean %CV) of these measured parameters were in the ranges 1-2% and 3-6%, respectively. Linear regression of the trabecular structure parameters vs. age showed significant correlation: ABV/TV (r2 = 33.7%, P < 0.0037), I.Th (r2 = 26.6%, P < 0.0118), I.Sp (r2 = 28.9%, P < 0.0081). These trends with age were also expressed as annual rates of change: ABV/TV (-0.52%/year), I.Th (-0.33%/year), and I.Sp (0.59%/year). Linear regression analysis also showed significant correlation between the MR-derived trabecular structure parameters and calcaneal BMD values. Although a larger group of subjects is needed to better define the age-related changes in trabecular structure parameters and their relation to BMD, these preliminary results demonstrate that high-resolution MRI may potentially be useful for the quantitative assessment of trabecular structure.

  2. Lithocholic bile acid accumulated in yeast mitochondria orchestrates a development of an anti-aging cellular pattern by causing age-related changes in cellular proteome

    PubMed Central

    Beach, Adam; Richard, Vincent R; Bourque, Simon; Boukh-Viner, Tatiana; Kyryakov, Pavlo; Gomez-Perez, Alejandra; Arlia-Ciommo, Anthony; Feldman, Rachel; Leonov, Anna; Piano, Amanda; Svistkova, Veronika; Titorenko, Vladimir I

    2015-01-01

    We have previously revealed that exogenously added lithocholic bile acid (LCA) extends the chronological lifespan of the yeast Saccharomyces cerevisiae, accumulates in mitochondria and alters mitochondrial membrane lipidome. Here, we use quantitative mass spectrometry to show that LCA alters the age-related dynamics of changes in levels of many mitochondrial proteins, as well as numerous proteins in cellular locations outside of mitochondria. These proteins belong to 2 regulons, each modulated by a different mitochondrial dysfunction; we call them a partial mitochondrial dysfunction regulon and an oxidative stress regulon. We found that proteins constituting these regulons (1) can be divided into several “clusters”, each of which denotes a distinct type of partial mitochondrial dysfunction that elicits a different signaling pathway mediated by a discrete set of transcription factors; (2) exhibit 3 different patterns of the age-related dynamics of changes in their cellular levels; and (3) are encoded by genes whose expression is regulated by the transcription factors Rtg1p/Rtg2p/Rtg3p, Sfp1p, Aft1p, Yap1p, Msn2p/Msn4p, Skn7p and Hog1p, each of which is essential for longevity extension by LCA. Our findings suggest that LCA-driven changes in mitochondrial lipidome alter mitochondrial proteome and functionality, thereby enabling mitochondria to operate as signaling organelles that orchestrate an establishment of an anti-aging transcriptional program for many longevity-defining nuclear genes. Based on these findings, we propose a model for how such LCA-driven changes early and late in life of chronologically aging yeast cause a stepwise development of an anti-aging cellular pattern and its maintenance throughout lifespan. PMID:25839782

  3. Flavonoid Chrysin prevents age-related cognitive decline via attenuation of oxidative stress and modulation of BDNF levels in aged mouse brain.

    PubMed

    Souza, Leandro Cattelan; Antunes, Michelle Silva; Filho, Carlos Borges; Del Fabbro, Lucian; de Gomes, Marcelo Gomes; Goes, André Tiago Rossito; Donato, Franciele; Prigol, Marina; Boeira, Silvana Peterini; Jesse, Cristiano R

    2015-07-01

    In this study, the effect of Chrysin (5,7-dihydroxyflavone), an important member of the flavonoid family, on memory impairment, oxidative stress and BDNF reduction generated by aging in mice were investigated. Young and aged mice were treated daily per 60days with Chrysin (1 and 10mg/kg; per oral, p.o.) or veichle (10ml/kg; p.o.). Mice were trained and tested in Morris Water Maze task. After the behavioural test, the levels of reactive species (RS), the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), as well as the activity of Na(+), K(+)-ATPase and the levels of brain-derived neurotrophic factor (BDNF) were determined in the prefrontal cortex (PFC) and hippocampus (HC) of mice. Results demonstrated that the age-related memory decline was partially protected by Chrysin at a dose of 1mg/kg, and normalized at the dose of 10mg/kg (p<0.001). Treatment with Chrysin significantly attenuated the increase of RS levels and the inhibition of SOD, CAT and GPx activities of aged mice. Inhibition of Na(+), K(+)-ATPase activity in PFC and HP of aged mice was also attenuated by Chrysin treatment. Moreover, Chrysin marked mitigated the decrease of BDNF levels in the PFC and HC of aged mice. These results demonstrated that flavonoid Chrysin, an antioxidant compound, was able to prevent age-associated memory probably by their free radical scavenger action and modulation of BDNF production. Thus, this study indicates that Chrysin may represent a new pharmacological approach to alleviate the age-related declines during normal age, acting as an anti-aging agent. PMID:25931267

  4. Co-focused ultrasound and optical coherence elastography system for the study of age-related changes of biomechanical properties of crystalline lens in rabbit eyes

    NASA Astrophysics Data System (ADS)

    Wu, Chen; Han, Zhaolong; Wang, Shang; Li, Jiasong; Singh, Manmohan; Liu, Chih-hao; Aglyamov, Salavat; Emelianov, Stanislav; Manns, Fabrice; Larin, Kirill V.

    2015-03-01

    In this study, we utilize a confocal ultrasound and phase-sensitive optical coherence elastography (OCE) system to assess age-related changes in biomechanical properties of the crystalline lens in intact rabbit eyes in situ. Lowamplitude elastic deformations, induced on the surface of the lens by localized acoustic radiation force, were measured using phase-sensitive OCT. The results demonstrate that the displacements induced in young rabbit lenses are significantly larger than those in the mature lenses. Temporal analyses of the elastic waves are also demonstrated significant difference between young and old lenses, indicating that the stiffness of lens increases with the age. These results demonstrate possibility of OCE for completely noninvasive analysis and quantification of lens biomechanical properties, which could be used in many clinical and basic science applications such as surgeries and studies on lens physiology and function.

  5. p16(INK4A) mediates age-related changes in mesenchymal stem cells derived from human dental pulp through the DNA damage and stress response.

    PubMed

    Feng, Xingmei; Xing, Jing; Feng, Guijuan; Huang, Dan; Lu, Xiaohui; Liu, Suzhe; Tan, Wei; Li, Liren; Gu, Zhifeng

    2014-01-01

    Mesenchymal stem cells derived from human dental pulp (DP-MSCs) are characterized by self-renewal and multi-lineage differentiation, which play important roles in regenerative medicine. Autologous transfers, as non-immunogenic, constitute the safest approach in cellular transplantations. However, their use may be limited by age-related changes. In the study, we compared DP-MSCs isolated from human in five age groups: 5-12 y, 12-20 y, 20-35 y, 35-50 y, and >50 y. We tested the effect of age on proliferation, differentiation, senescence-associated β-galactosidase (SA-β-gal), cell cycle and programmed cell death. DP-MSCs showed characteristics of senescence as a function of age. Meanwhile, the expression of p16(INK4A) and γ-H2A.X significantly increased with age, whereas heat shock protein 60 (HSP60) was decreased in the senescent DP-MSCs. Reactive oxygen species (ROS) staining showed the number of ROS-stained cells and the DCFH fluorescent level were higher in the aged group. Further we examined the senescence of DP-MSCs after modulating p16(INK4A) signaling. The results indicated the dysfunction of DP-MSCs was reversed by p16(INK4A) siRNA. In summary, our study indicated p16(INK4A) pathway may play a critical role in DP-MSCs age-related changes and the DNA damage response (DDR) and stress response may be the main mediators of DP-MSCs senescence induced by excessive activation of p16(INK4A) signaling. PMID:25304494

  6. Age-related Changes in Auditory Nerve – Inner Hair Cell Connections, Hair Cell Numbers, Auditory Brain Stem Response and Gap Detection in UM-HET4 Mice

    PubMed Central

    Altschuler, RA; Dolan, DF; Halsey, K; Kanicki, A; Deng, N; Martin, C; Eberle, J; Kohrman, DC; Miller, RA; Schacht, J

    2015-01-01

    This study compared the timing of appearance of three components of age-related hearing loss that determine the pattern and severity of presbycusis: the functional and structural pathologies of sensory cells and neurons and changes in Gap Detection, the latter as an indicator of auditory temporal processing. Using UM-HET4 mice, genetically heterogeneous mice derived from four inbred strains, we studied the integrity of inner and outer hair cells by position along the cochlear spiral, inner hair cell-auditory nerve connections, spiral ganglion neurons, and determined auditory thresholds, as well as pre-pulse and gap inhibition of the acoustic startle reflex (ASR). Comparisons were made between mice of 5-7, 22-24 and 27-29 months of age. There was individual variability among mice in the onset and extent of age-related auditory pathology. At 22-24 months of age a moderate to large loss of outer hair cells was restricted to the apical third of the cochlea and threshold shifts in auditory brain stem response were minimal. There was also a large and significant loss of inner hair cell – auditory nerve connections and a significant reduction in Gap Detection. The expression of Ntf3 in the cochlea was significantly reduced. At 27-29 months of age there was no further change in the mean number of synaptic connections per inner hair cell or in gap detection, but a moderate to large loss of outer hair cells was found across all cochlear turns as well as significantly increased ABR threshold shifts at 4, 12, 24 and 48 kHz. A statistical analysis of correlations on an individual animal basis revealed that neither the hair cell loss nor the ABR threshold shifts correlated with loss of gap detection or with the loss of connections, consistent with independent pathological mechanisms. PMID:25665752

  7. Age-related changes in auditory nerve-inner hair cell connections, hair cell numbers, auditory brain stem response and gap detection in UM-HET4 mice.

    PubMed

    Altschuler, R A; Dolan, D F; Halsey, K; Kanicki, A; Deng, N; Martin, C; Eberle, J; Kohrman, D C; Miller, R A; Schacht, J

    2015-04-30

    This study compared the timing of appearance of three components of age-related hearing loss that determine the pattern and severity of presbycusis: the functional and structural pathologies of sensory cells and neurons and changes in gap detection (GD), the latter as an indicator of auditory temporal processing. Using UM-HET4 mice, genetically heterogeneous mice derived from four inbred strains, we studied the integrity of inner and outer hair cells by position along the cochlear spiral, inner hair cell-auditory nerve connections, spiral ganglion neurons (SGN), and determined auditory thresholds, as well as pre-pulse and gap inhibition of the acoustic startle reflex (ASR). Comparisons were made between mice of 5-7, 22-24 and 27-29 months of age. There was individual variability among mice in the onset and extent of age-related auditory pathology. At 22-24 months of age a moderate to large loss of outer hair cells was restricted to the apical third of the cochlea and threshold shifts in the auditory brain stem response were minimal. There was also a large and significant loss of inner hair cell-auditory nerve connections and a significant reduction in GD. The expression of Ntf3 in the cochlea was significantly reduced. At 27-29 months of age there was no further change in the mean number of synaptic connections per inner hair cell or in GD, but a moderate to large loss of outer hair cells was found across all cochlear turns as well as significantly increased ABR threshold shifts at 4, 12, 24 and 48 kHz. A statistical analysis of correlations on an individual animal basis revealed that neither the hair cell loss nor the ABR threshold shifts correlated with loss of GD or with the loss of connections, consistent with independent pathological mechanisms. PMID:25665752

  8. Age-related changes in collagen synthesis and degradation in rat tissues. Importance of degradation of newly synthesized collagen in regulating collagen production.

    PubMed

    Mays, P K; McAnulty, R J; Campa, J S; Laurent, G J

    1991-06-01

    During developmental growth, collagens are believed to be continuously deposited into an extracellular matrix which is increasingly stabilized by the formation of covalent cross-links throughout life. However, the age-related changes in rates of synthetic and degradative processes are less well understood. In the present study we measured rates of collagen synthesis in vivo using a flooding dose of unlabelled proline given with [14C]proline and determining production of hydroxy[14C]proline. Degradation of newly synthesized collagen was estimated from the amount of free hydroxy [14C]proline in tissues 30 min after injection. Collagen fractional synthesis rates ranged from about 5%/day in skeletal muscle to 20%/day in hearts of rats aged 1 month. At 15 months of age, collagen fractional synthesis rates had decreased markedly in lung and skin, but in skeletal muscle and heart, rates were unchanged. At 24 months of age, synthesis rates had decreased by at least 10-fold in all tissues, compared with rates at 1 month. The proportion of newly synthesized collagen degraded ranged from 6.4 +/- 0.4% in skin to 61.6 +/- 5.0% in heart at 1 month of age. During aging the proportion degraded increased in all tissues to maximal values at 15 months, ranging from 56 +/- 7% in skin to 96 +/- 1% in heart. These data suggest that there are marked age-related changes in rates of collagen metabolism. They also indicate that synthesis is active even in old animals, where the bulk of collagens produced are destined to be degraded. PMID:2049064

  9. Altered Hippocampal Transcript Profile Accompanies an Age-Related Spatial Memory Deficit in Mice

    ERIC Educational Resources Information Center

    Verbitsky, Miguel; Yonan, Amanda L.; Malleret, Gael; Kandel, Eric R.; Gilliam, T. Conrad; Pavlidis, Paul

    2004-01-01

    We have carried out a global survey of age-related changes in mRNA levels in the 57BL/6NIA mouse hippocampus and found a difference in the hippocampal gene expression profile between 2-month-old young mice and 15-month-old middle-aged mice correlated with an age-related cognitive deficit in hippocampal-based explicit memory formation. Middle-aged…

  10. Language Experience Changes Language and Cognitive Ability

    PubMed Central

    Poarch, Gregory

    2014-01-01

    The sustained use of two languages by bilinguals has been shown to induce broad changes in language and cognitive abilities across the lifespan. The largest changes are seen as advantages in executive control, a set of processes responsible for controlled attention, inhibition, and shifting. Moreover, there is evidence that these executive control advantages mitigate cognitive decline in older age and contribute to cognitive reserve. In this paper, we examine some of the evidence for these findings and explain their relation to bilingual language use. These effects are considered in terms of their implications for our understanding of cognitive and brain plasticity. Some implications for social policy are discussed. PMID:25435805

  11. Comparison of age-related changes in in vivo and in vitro measures of testicular steroidogenesis after acute cadmium exposure in the sprague-dawley rat

    SciTech Connect

    Phelps, P.V.; Laskey, J.W. )

    1989-01-01

    Previous reports have demonstrated that cadmium- (Cd-) induced testicular necrosis is an age-dependent process. However, little information exists on age-related intestitial cell (IC) damage in the rat after acute exposure to Cd. In this study in vitro and in vivo measures of testicular damage were utilized to compare the sensitivity of these measures and to further investigate age-related Cd-induced testicular damage. Testes, epididymides, and seminal vesicle weights, serum testosterone (sT), hCG-stimulated sT, and basal and stimulated IC testosterone (T) production were production were compared in rats 21 d following an injection of 2 mg Cd/kg at 9, 37, 67, and 97 d of age. The only Cd-related change noted for immature rats was an 84% reduction in sT. In rats injected when 37 d old, hCG-stimulated sT and epididymides and seminal vesicle weights, although depressed, were not significantly altered. However, all other measurements were significantly depressed. All measures of testicular damage were significantly depressed in rats injected at 67 and 97 d of age. Overall, in vitro measures were more sensitive indicators of Cd-induced testicular damage than in vivo measures. However, sT and hCG-stimulated sT appeared to be useful indicators of Cd effects on the pituitary-gonadal axis. ICs from immature rats (9 d old) were unaffected by Cd exposure, while stimulated T reproduction in ICs from 37-, 67-, and 97-d-old animals was reduced at least 50%. The severity of Cd-induced testicular damage increases with age for all variables measured.

  12. APOL1 Risk Alleles Are Associated with Exaggerated Age-Related Changes in Glomerular Number and Volume in African-American Adults: An Autopsy Study.

    PubMed

    Hoy, Wendy E; Hughson, Michael D; Kopp, Jeffrey B; Mott, Susan A; Bertram, John F; Winkler, Cheryl A

    2015-12-01

    APOL1 genetic variants contribute to kidney disease in African Americans. We assessed correlations between APOL1 profiles and renal histological features in subjects without renal disease. Glomerular number (N glom) and mean glomerular volume (V glom) were measured by the dissector/fractionator method in kidneys of African-American and non-African-American adults without renal disease, undergoing autopsies in Jackson, Mississippi. APOL1 risk alleles were genotyped and the kidney findings were evaluated in the context of those profiles. The proportions of African Americans with none, one, and two APOL1 risk alleles were 38%, 43%, and 19%, respectively; 38% of African Americans had G1 allele variants and 31% of African Americans had G2 allele variants. Only APOL1-positive African Americans had significant reductions in N glom and increases in V glom with increasing age. Regression analysis predicted an annual average loss of 8834 (P=0.03, sex adjusted) glomeruli per single kidney over the first 38 years of adult life in African Americans with two risk alleles. Body mass index above the group medians, but below the obesity definition of ≥ 30 kg/m(2), enhanced the expression of age-related changes in N glom in African Americans with either one or two APOL1 risk alleles. These findings indicate that APOL1 risk alleles are associated with exaggerated age-related nephron loss, probably decaying from a larger pool of smaller glomeruli in early adult life, along with enlargement of the remaining glomeruli. These phenomena might mark mechanisms of accentuated susceptibility to kidney disease in APOL1-positive African Americans. PMID:26038529

  13. Age-related Multiscale Changes in Brain Signal Variability in Pre-task versus Post-task Resting-state EEG.

    PubMed

    Wang, Hongye; McIntosh, Anthony R; Kovacevic, Natasa; Karachalios, Maria; Protzner, Andrea B

    2016-07-01

    Recent empirical work suggests that, during healthy aging, the variability of network dynamics changes during task performance. Such variability appears to reflect the spontaneous formation and dissolution of different functional networks. We sought to extend these observations into resting-state dynamics. We recorded EEG in young, middle-aged, and older adults during a "rest-task-rest" design and investigated if aging modifies the interaction between resting-state activity and external stimulus-induced activity. Using multiscale entropy as our measure of variability, we found that, with increasing age, resting-state dynamics shifts from distributed to more local neural processing, especially at posterior sources. In the young group, resting-state dynamics also changed from pre- to post-task, where fine-scale entropy increased in task-positive regions and coarse-scale entropy increased in the posterior cingulate, a key region associated with the default mode network. Lastly, pre- and post-task resting-state dynamics were linked to performance on the intervening task for all age groups, but this relationship became weaker with increasing age. Our results suggest that age-related changes in resting-state dynamics occur across different spatial and temporal scales and have consequences for information processing capacity. PMID:26942319

  14. Chronic administration of thiamine pyrophosphate decreases age-related histological atrophic testicular changes and improves sexual behavior in male Wistar rats.

    PubMed

    Hernández-Montiel, H L; Vásquez López, C M; González-Loyola, J G; Vega-Anaya, G C; Villagrán-Herrera, M E; Gallegos-Corona, M A; Saldaña, C; Ramos Gómez, M; García Horshman, P; García Solís, P; Solís-S, J C; Robles-Osorio, M L; Ávila Morales, J; Varela-Echavarría, A; Paredes Guerrero, R

    2014-06-01

    Aging is a multifactorial universal process and constitutes the most important risk factor for chronic-degenerative diseases. Although it is a natural process, pathological aging arises when these changes occur quickly and the body is not able to adapt. This is often associated with the generation of reactive oxygen species (ROS), inflammation, and a decrease in the endogenous antioxidant systems, constituting a physiopathological state commonly found in chronic-degenerative diseases. At the testicular level, aging is associated with tissue atrophy, decreased steroidogenesis and spermatogenesis, and sexual behavior disorders. This situation, in addition to the elevated generation of ROS in the testicular steroidogenesis, provides a critical cellular environment causing oxidative damage at diverse cellular levels. To assess the effects of a reduction in the levels of ROS, thiamine pyrophosphate (TPP) was chronically administered in senile Wistar rats. TPP causes an activation of intermediate metabolism routes, enhancing cellular respiration and decreasing the generation of ROS. Our results show an overall decrease of atrophic histological changes linked to aging, with higher levels of serum testosterone, sexual activity, and an increase in the levels of endogenous antioxidant enzymes in TPP-treated animals. These results suggest that TPP chronic administration decreases the progression of age-related atrophic changes by improving the intermediate metabolism, and by increasing the levels of antioxidant enzymes. PMID:24371036

  15. Quantification of Age-Related and per Diopter Accommodative Changes of the Lens and Ciliary Muscle in the Emmetropic Human Eye

    PubMed Central

    Richdale, Kathryn; Sinnott, Loraine T.; Bullimore, Mark A.; Wassenaar, Peter A.; Schmalbrock, Petra; Kao, Chiu-Yen; Patz, Samuel; Mutti, Donald O.; Glasser, Adrian; Zadnik, Karla

    2013-01-01

    Purpose. To calculate age-related and per diopter (D) accommodative changes in crystalline lens and ciliary muscle dimensions in vivo in a single cohort of emmetropic human adults ages 30 to 50 years. Methods. The right eyes of 26 emmetropic adults were examined using ultrasonography, phakometry, anterior segment optical coherence tomography, and high resolution magnetic resonance imaging. Accommodation was measured both subjectively and objectively. Results. In agreement with previous research, older age was linearly correlated with a thicker lens, steeper anterior lens curvature, shallower anterior chamber, and lower lens equivalent refractive index (all P < 0.01). Age was not related to ciliary muscle ring diameter (CMRD) or lens equatorial diameter (LED). With accommodation, lens thickness increased (+0.064 mm/D, P < 0.001), LED decreased (−0.075 mm/D, P < 0.001), CMRD decreased (−0.105 mm/D, P < 0.001), and the ciliary muscle thickened anteriorly (+0.013 to +0.026 mm/D, P < 0.001) and thinned posteriorly (−0.011 to −0.015, P < 0.01). The changes per diopter of accommodation in LED, CMRD, and ciliary muscle thickness were not related to subject age. Conclusions. The per diopter ciliary muscle contraction is age independent, even as total accommodative amplitude declines. Quantifying normal biometric dimensions of the accommodative structures and changes with age and accommodative effort will further the development of new IOLs designed to harness ciliary muscle forces. PMID:23287789

  16. Age-Related Macular Degeneration

    MedlinePlus

    ... this page please turn Javascript on. Age-related Macular Degeneration What is AMD? Click for more information Age-related macular degeneration, ... the macula allows you to see fine detail. AMD Blurs Central Vision AMD blurs the sharp central ...

  17. Structural brain changes in aging: courses, causes and cognitive consequences.

    PubMed

    Fjell, Anders M; Walhovd, Kristine B

    2010-01-01

    The structure of the brain is constantly changing from birth throughout the lifetime, meaning that normal aging, free from dementia, is associated with structural brain changes. This paper reviews recent evidence from magnetic resonance imaging (MRI) studies about age-related changes in the brain. The main conclusions are that (1) the brain shrinks in volume and the ventricular system expands in healthy aging. However, the pattern of changes is highly heterogeneous, with the largest changes seen in the frontal and temporal cortex, and in the putamen, thalamus, and accumbens. With modern approaches to analysis of MRI data, changes in cortical thickness and subcortical volume can be tracked over periods as short as one year, with annual reductions of between 0.5% and 1.0% in most brain areas. (2) The volumetric brain reductions in healthy aging are likely only to a minor extent related to neuronal loss. Rather, shrinkage of neurons, reductions of synaptic spines, and lower numbers of synapses probably account for the reductions in grey matter. In addition, the length of myelinated axons is greatly reduced, up to almost 50%. (3) Reductions in specific cognitive abilities--for instance processing speed, executive functions, and episodic memory--are seen in healthy aging. Such reductions are to a substantial degree mediated by neuroanatomical changes, meaning that between 25% and 100% of the differences between young and old participants in selected cognitive functions can be explained by group differences in structural brain characteristics. PMID:20879692

  18. Cultural Change, Human Activity, and Cognitive Development

    ERIC Educational Resources Information Center

    Gauvain, Mary; Munroe, Robert L.

    2012-01-01

    Differential cognitive performance across cultural contexts has been a standard result in comparative research. Here we discuss how societal changes occurring when a small-scale traditional community incorporates elements from industrialized society may contribute to cognitive development, and we illustrate this with an analysis of the cognitive…

  19. Cognitive Status and Change among Iowa Centenarians

    ERIC Educational Resources Information Center

    Margrett, Jennifer A.; Hsieh, Wen-Hua; Heinz, Melinda; Martin, Peter

    2012-01-01

    Equivocal evidence exists regarding the degree of cognitive stability and prevalence of cognitive impairment in very late life. The objective of the current study was to examine mental status performance and change over time within a sample of Iowa centenarians. The baseline sample consisted of 152 community-dwelling and institutionalized…

  20. Cognitive Impairment and Age-Related Vision Disorders: Their Possible Relationship and the Evaluation of the Use of Aspirin and Statins in a 65 Years-and-Over Sardinian Population.

    PubMed

    Mandas, Antonella; Mereu, Rosa Maria; Catte, Olga; Saba, Antonio; Serchisu, Luca; Costaggiu, Diego; Peiretti, Enrico; Caminiti, Giulia; Vinci, Michela; Casu, Maura; Piludu, Stefania; Fossarello, Maurizio; Manconi, Paolo Emilio; Dessí, Sandra

    2014-01-01

    Neurological disorders (Alzheimer's disease, vascular and mixed dementia) and visual loss (cataract, age-related macular degeneration, glaucoma, and diabetic retinopathy) are among the most common conditions that afflict people of at least 65 years of age. An increasing body of evidence is emerging, which demonstrates that memory and vision impairment are closely, significantly, and positively linked and that statins and aspirin may lessen the risk of developing age-related visual and neurological problems. However, clinical studies have produced contradictory results. Thus, the intent of the present study was to reliably establish whether a relationship exist between various types of dementia and age-related vision disorders, and to establish whether statins and aspirin may or may not have beneficial effects on these two types of disorders. We found that participants with dementia and/or vision problems were more likely to be depressed and displayed worse functional ability in basic and instrumental activities of daily living than controls. Mini mental state examination scores were significantly lower in patients with vision disorders compared to subjects without vision disorders. A closer association with macular degeneration was found in subjects with Alzheimer's disease than in subjects without dementia or with vascular dementia, mixed dementia, or other types of age-related vision disorders. When we considered the associations between different types of dementia and vision disorders and the use of statins and aspirin, we found a significant positive association between Alzheimer's disease and statins on their own or in combination with aspirin, indicating that these two drugs do not appear to reduce the risk of Alzheimer's disease or improve its clinical evolution and may, on the contrary, favor its development. No significant association in statin use alone, aspirin use alone, or the combination of these was found in subjects without vision disorders but

  1. Cognitive Impairment and Age-Related Vision Disorders: Their Possible Relationship and the Evaluation of the Use of Aspirin and Statins in a 65 Years-and-Over Sardinian Population

    PubMed Central

    Mandas, Antonella; Mereu, Rosa Maria; Catte, Olga; Saba, Antonio; Serchisu, Luca; Costaggiu, Diego; Peiretti, Enrico; Caminiti, Giulia; Vinci, Michela; Casu, Maura; Piludu, Stefania; Fossarello, Maurizio; Manconi, Paolo Emilio; Dessí, Sandra

    2014-01-01

    Neurological disorders (Alzheimer’s disease, vascular and mixed dementia) and visual loss (cataract, age-related macular degeneration, glaucoma, and diabetic retinopathy) are among the most common conditions that afflict people of at least 65 years of age. An increasing body of evidence is emerging, which demonstrates that memory and vision impairment are closely, significantly, and positively linked and that statins and aspirin may lessen the risk of developing age-related visual and neurological problems. However, clinical studies have produced contradictory results. Thus, the intent of the present study was to reliably establish whether a relationship exist between various types of dementia and age-related vision disorders, and to establish whether statins and aspirin may or may not have beneficial effects on these two types of disorders. We found that participants with dementia and/or vision problems were more likely to be depressed and displayed worse functional ability in basic and instrumental activities of daily living than controls. Mini mental state examination scores were significantly lower in patients with vision disorders compared to subjects without vision disorders. A closer association with macular degeneration was found in subjects with Alzheimer’s disease than in subjects without dementia or with vascular dementia, mixed dementia, or other types of age-related vision disorders. When we considered the associations between different types of dementia and vision disorders and the use of statins and aspirin, we found a significant positive association between Alzheimer’s disease and statins on their own or in combination with aspirin, indicating that these two drugs do not appear to reduce the risk of Alzheimer’s disease or improve its clinical evolution and may, on the contrary, favor its development. No significant association in statin use alone, aspirin use alone, or the combination of these was found in subjects without vision

  2. Aging-Related Changes in the Nigrostriatal Dopamine System and the Response to MPTP in Nonhuman Primates: Diminished Compensatory Mechanisms as a Prelude to Parkinsonism

    PubMed Central

    Collier, Timothy J.; Lipton, Jack; Daley, Brian F.; Palfi, Stephane; Chu, Yaping; Sortwell, Caryl; Bakay, Roy A.E.; Sladek, John R.; Kordower, Jeffrey H.

    2007-01-01

    Aging is the most prominent risk factor for Parkinson’s disease. Yet, consensus of how advancing age may predispose the dopamine (DA) system to parkinsonism is lacking. Three age-ranges of female rhesus monkeys, 8–9, 15–17 and 21–31 years, received unilateral DA depletion with intracarotid 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Morphological and biochemical analyses of DA-depleted and intact hemispheres revealed three primary findings: 1) The intact striatum exhibited age-related declines in dopamine (DA) and homovanillic acid (HVA) that were present by middle-age; 2) In the MPTP-treated striatum, the compensatory increase in DA activity was absent in old monkeys; and, 3) Age-associated morphological changes included declines in the density of tyrosine hydroxylase (TH) positive fibers in striatum, decreased nigral soma size and optical density of TH, but no significant loss of neurons. These findings suggest that aging produces changes in the nigrostriatal DA system that approach the threshold for expression of parkinsonian features, and that progressive impairment of plasticity may be central to the role of aging in development of parkinsonism. PMID:17254792