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Sample records for age related decline

  1. Age Related Decline in Postural Control Mechanisms.

    ERIC Educational Resources Information Center

    Stelmach, George E.; And Others

    1989-01-01

    Studied voluntary and reflexive mechanisms of postural control of young (N=8) and elderly (N=8) adults through measurement of reflexive reactions to large-fast and small-slow ankle rotation postural disturbances. Found reflexive mechanisms relatively intact for both groups although elderly appeared more disadvantaged when posture was under the…

  2. Neuroanatomical substrates of age-related cognitive decline

    PubMed Central

    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 age-related cognitive changes. Although this conclusion may well be true, it is widely recognized that simple correlations are not sufficient to warrant causal conclusions, and other types of correlational information, such as mediation and correlations between longitudinal brain changes and longitudinal cognitive changes, also have limitations with respect to causal inferences. These issues are discussed, and the existing results on relations of regional volume, white matter hyperintensities, and DTI measures of white matter integrity to age and to measures of cognitive functioning are reviewed. It is concluded that at the current time the evidence that these aspects of brain structure are neuroanatomical substrates of age-related cognitive decline is weak. The final section contains several suggestions concerned with measurement and methodology that may lead to stronger conclusions in the future. PMID:21463028

  3. Age-related decline in global form suppression.

    PubMed

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

    2015-12-01

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

  4. 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…

  5. Cognition enhancers in age-related cognitive decline.

    PubMed

    Riedel, W J; Jolles, J

    1996-04-01

    A review of recently published studies on the effect of cognition enhancers in non-demented human study participants is presented. The heterogeneity of the therapeutic target, age-associated cognitive decline, can be improved by separately treating groups in whom age-extrinsic factors may underlie cognitive pathology. Standardisation of cognitive assessments is necessary, since many different tests are applied to answer the same question. Modelling cognitive dysfunction, either by pharmacological or nonpharmacological means, in humans is highly recommended since it allows hypotheses to be tested in a clearly operationalised way. Predictive validity of the currently applied models for the clinical situation remains a problem, however. The scopolamine (hyoscine) model has, to a reasonable extent, predictive validity for the cholinergic agents. The results of 67 single-dose studies and 30 multiple-dose studies are summarised. All single-dose studies and 14 multiple-dose studies were carried out in young or elderly human volunteers. In 45 of 81 volunteer studies, models of cognitive dysfunction were employed. The scopolamine model was the most used (n = 21); the other studies induced cognitive dysfunction by means of benzodiazepines (8), hypoxia (7), alcohol (5) and sleep-deprivation (4). The remaining 16 multiple-dose studies were clinical trials of a duration varying between 2 weeks and 1 year (average duration was 14 weeks). In these trials, the effects of cognition enhancers were assessed in elderly people in whom impairment of memory, psychomotor performance or cognitive function was determined. These included age-associated memory impairment (AAMI) and age-associated cognitive decline (AACD). There were many studies in which the cognition enhancing properties of substances in humans were reliably demonstrated. The cognition enhancing properties of substances that are widely used, such as caffeine, nicotine and vitamins, may already be active against AACD. New

  6. Age-related decline in emotional prosody discrimination: acoustic correlates.

    PubMed

    Mitchell, Rachel L C; Kingston, Rachel A

    2014-01-01

    It is now accepted that older adults have difficulty recognizing prosodic emotion cues, but it is not clear at what processing stage this ability breaks down. We manipulated the acoustic characteristics of tones in pitch, amplitude, and duration discrimination tasks to assess whether impaired basic auditory perception coexisted with our previously demonstrated age-related prosodic emotion perception impairment. It was found that pitch perception was particularly impaired in older adults, and that it displayed the strongest correlation with prosodic emotion discrimination. We conclude that an important cause of age-related impairment in prosodic emotion comprehension exists at the fundamental sensory level of processing.

  7. 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.

  8. Mechanisms of Age-Related Decline in Memory Search across the Adult Life Span

    ERIC Educational Resources Information Center

    Hills, Thomas T.; Mata, Rui; Wilke, Andreas; Samanez-Larkin, Gregory R.

    2013-01-01

    Three alternative mechanisms for age-related decline in memory search have been proposed, which result from either reduced processing speed (global slowing hypothesis), overpersistence on categories (cluster-switching hypothesis), or the inability to maintain focus on local cues related to a decline in working memory (cue-maintenance hypothesis).…

  9. Aging-associated formaldehyde-induced norepinephrine deficiency contributes to age-related memory decline.

    PubMed

    Mei, Yufei; Jiang, Chun; Wan, You; Lv, Jihui; Jia, Jianping; Wang, Xiaomin; Yang, Xu; Tong, Zhiqian

    2015-08-01

    A norepinephrine (NE) deficiency has been observed in aged rats and in patients with Alzheimer's disease and is thought to cause cognitive disorder. Which endogenous factor induces NE depletion, however, is largely unknown. In this study, we investigated the effects of aging-associated formaldehyde (FA) on the inactivation of NE in vitro and in vivo, and on memory behaviors in rodents. The results showed that age-related DNA demethylation led to hippocampal FA accumulation, and when this occurred, the hippocampal NE content was reduced in healthy male rats of different ages. Furthermore, biochemical analysis revealed that FA rapidly inactivated NE in vitro and that an intrahippocampal injection of FA markedly reduced hippocampal NE levels in healthy adult rats. Unexpectedly, an injection of FA (at a pathological level) or 6-hydroxydopamine (6-OHDA, a NE depletor) can mimic age-related NE deficiency, long-term potentiation (LTP) impairments, and spatial memory deficits in healthy adult rats. Conversely, an injection of NE reversed age-related deficits in both LTP and memory in aged rats. In agreement with the above results, the senescence-accelerated prone 8 (SAMP8) mice also exhibited a severe deficit in LTP and memory associated with a more severe NE deficiency and FA accumulation, when compared with the age-matched, senescence-resistant 1 (SAMR1) mice. Injection of resveratrol (a natural FA scavenger) or NE into SAMP8 mice reversed FA accumulation and NE deficiency and restored the magnitude of LTP and memory. Collectively, these findings suggest that accumulated FA is a critical endogenous factor for aging-associated NE depletion and cognitive decline.

  10. Ageing and apoE change DHA homeostasis: relevance to age-related cognitive decline.

    PubMed

    Hennebelle, Marie; Plourde, Mélanie; Chouinard-Watkins, Raphaël; Castellano, Christian-Alexandre; Barberger-Gateau, Pascale; Cunnane, Stephen C

    2014-02-01

    Epidemiological studies fairly convincingly suggest that higher intakes of fatty fish and n-3 fatty acids are associated with reduced risk of Alzheimer's disease (AD). DHA in plasma is normally positively associated with DHA intake. However, despite being associated with lower fish and DHA intake, unexpectedly, plasma (or brain) DHA is frequently not lower in AD. This review will highlight some metabolic and physiological factors such as ageing and apoE polymorphism that influence DHA homeostasis. Compared with young adults, blood DHA is often slightly but significantly higher in older adults without any age-related cognitive decline. Higher plasma DHA in older adults could be a sign that their fish or DHA intake is higher. However, our supplementation and carbon-13 tracer studies also show that DHA metabolism, e.g. transit through the plasma, apparent retroconversion and β-oxidation, is altered in healthy older compared with healthy young adults. ApoE4 increases the risk of AD, possibly in part because it too changes DHA homeostasis. Therefore, independent of differences in fish intake, changing DHA homeostasis may tend to obscure the relationship between DHA intake and plasma DHA which, in turn, may contribute to making older adults more susceptible to cognitive decline despite older adults having similar or sometimes higher plasma DHA than in younger adults. In conclusion, recent development of new tools such as isotopically labelled DHA to study DHA metabolism in human subjects highlights some promising avenues to evaluate how and why DHA metabolism changes during ageing and AD.

  11. 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

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

    PubMed

    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.

  13. Preventing age-related decline of gut compartmentalization limits microbiota dysbiosis and extends lifespan

    PubMed Central

    Li, Hongjie; Qi, Yanyan; Jasper, Heinrich

    2016-01-01

    Summary Compartmentalization of the gastrointestinal (GI) tract of metazoans is critical for health. GI compartments contain specific microbiota, and microbiota dysbiosis is associated with intestinal dysfunction. Dysbiosis develops in aging intestines, yet how this relates to changes in GI compartmentalization remains unclear. The Drosophila GI tract is an accessible model to address this question. Here we show that the stomach-like copper cell region (CCR) in the middle midgut controls distribution and composition of the microbiota. We find that chronic activation of JAK/Stat signaling in the aging gut induces a metaplasia of the gastric epithelium, CCR decline, and subsequent commensal dysbiosis and epithelial dysplasia along the GI tract. Accordingly, inhibition of JAK/Stat signaling in the CCR specifically prevents age-related metaplasia, commensal dysbiosis and functional decline in old guts, and extends lifespan. Our results establish a mechanism by which age-related chronic inflammation causes the decline of intestinal compartmentalization and microbiota dysbiosis, limiting lifespan. PMID:26867182

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

    PubMed

    Li, Hongjie; Qi, Yanyan; Jasper, Heinrich

    2016-02-10

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

  15. An age-related decline in striatal taurine is correlated with a loss of dopaminergic markers.

    PubMed

    Dawson, R; Pelleymounter, M A; Cullen, M J; Gollub, M; Liu, S

    1999-02-01

    Taurine is present in high concentration in the mammalian brain and is known to decline with aging. The present studies examined the relationship between the loss of striatal neurotransmitters and spatial learning ability in aged male Long-Evans rats. The effects of intrahippocampal infusions of neurotrophic factors-nerve growth factor (NGF) and brain-derived neurotrophic factor-were also examined for their ability to ameliorate the age-related decline in brain amino acid content. Taurine content was found to be significantly reduced in the striatum of aged rats (26 months old) that were impaired in spatial learning performance when compared to young unimpaired rats (5 months old). Aged rats that were behaviorally unimpaired had more modest reductions in taurine. Striatal dopamine content was also significantly reduced in aged learning-impaired rats. There was a significant (p < 0.001) correlation (r=0.61) between the striatal content of taurine and dopamine, but no such correlation was found for other striatal transmitters (glutamate, serotonin, norepinephrine). Treatment with neurotrophins had little effect on the age-related decline in striatal amino acids, although NGF treatment did improve spatial learning. These studies suggest (1) a link between age-related declines in striatal dopamine and taurine and (2) that NGF-induced improvement in spatial learning is not related to mechanisms involving changes in taurine or glutamate content.

  16. 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...

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

    PubMed

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

    2013-01-01

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

  18. Age-related decline of precision and binding in visual working memory.

    PubMed

    Peich, Muy-Cheng; Husain, Masud; Bays, Paul M

    2013-09-01

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

  19. Age-related decline in motor behavior and striatal dopamine transporter in cynomolgus monkeys.

    PubMed

    Yue, Feng; Zeng, Sien; Wu, Di; Yi, Deqiao; Alex Zhang, Y; Chan, Piu

    2012-08-01

    Advanced human aging is associated with progressive declines of motor function and a risk factor for Parkinson's disease, which mainly involves central nigrostriatal dopaminergic system. The present study investigated age-related changes in motor behaviors and alterations of the number of nigrostriatal dopaminergic terminals in non-human primates. A total of 30 cynomolgus monkeys (Macaca fascicularis) of age 3.5-15.5 years were studied. Motor behaviors including upper limb movement time and the amount of overall home cage activity were quantitatively assessed using a modified movement assessment panel and a newly developed webcam-based monitoring system. The function of the dopaminergic system was semi-quantitatively measured by (99m)Tc-TRODAT-1 uptake rates, a dopamine transporter (DAT) specific radiopharmaceutical with SPECT imaging. The results showed a significant decline in motor behaviors associated with aging which were significantly correlated with age-related decreases of (99m)Tc-TRODAT-1 uptake. A further partial correlation analysis independent of age indicated that age contributed to the relationship between striatal DAT levels and motor behaviors. Our results indicate that normal aging-related dopamine physiology influences certain aspects of motor behaviors and suggest that aging-associated dysfunction in the nigrostriatal dopaminergic system may be an important factor contributing to the decline of motor behaviors in aging cynomolgus monkeys.

  20. Genetic architecture of age-related cognitive decline in African Americans

    PubMed Central

    Raj, Towfique; Chibnik, Lori B.; McCabe, Cristin; Wong, Andus; Replogle, Joseph M.; Yu, Lei; Gao, Sujuan; Unverzagt, Frederick W.; Stranger, Barbara; Murrell, Jill; Barnes, Lisa; Hendrie, Hugh C.; Foroud, Tatiana; Krichevsky, Anna; Bennett, David A.; Hall, Kathleen S.; Evans, Denis A.

    2016-01-01

    Objective: To identify genetic risk factors associated with susceptibility to age-related cognitive decline in African Americans (AAs). Methods: We performed a genome-wide association study (GWAS) and an admixture-mapping scan in 3,964 older AAs from 5 longitudinal cohorts; for each participant, we calculated a slope of an individual's global cognitive change from neuropsychological evaluations. We also performed a pathway-based analysis of the age-related cognitive decline GWAS. Results: We found no evidence to support the existence of a genomic region which has a strongly different contribution to age-related cognitive decline in African and European genomes. Known Alzheimer disease (AD) susceptibility variants in the ABCA7 and MS4A loci do influence this trait in AAs. Of interest, our pathway-based analyses returned statistically significant results highlighting a shared risk from lipid/metabolism and protein tyrosine signaling pathways between cognitive decline and AD, but the role of inflammatory pathways is polarized, being limited to AD susceptibility. Conclusions: The genetic architecture of aging-related cognitive in AA individuals is largely similar to that of individuals of European descent. In both populations, we note a surprising lack of enrichment for immune pathways in the genetic risk for cognitive decline, despite strong enrichment of these pathways among genetic risk factors for AD. PMID:28078323

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

    PubMed

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

    2014-01-01

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

  2. Compensatory responses to age-related decline in odor quality acuity: cholinergic neuromodulation and olfactory enrichment.

    PubMed

    Mandairon, Nathalie; Peace, Shane T; Boudadi, Karim; Boxhorn, Christine E; Narla, Venkata Anupama; Suffis, Sara D; Cleland, Thomas A

    2011-12-01

    The perceptual differentiation of odors can be measured behaviorally using generalization gradients. The steepness of these gradients defines a form of olfactory acuity for odor quality that depends on neural circuitry within the olfactory bulb and is regulated by cholinergic activity therein as well as by associative learning. Using this system as a reduced model for age-related cognitive decline, we show that aged mice, while maintaining almost the same baseline behavioral performance as younger mice, are insensitive to the effects of acutely elevated acetylcholine, which sharpens generalization gradients in young adult mice. Moreover, older mice exhibit evidence of chronically elevated acetylcholine levels in the olfactory bulb, suggesting that their insensitivity to further elevated levels of acetylcholine may arise because the maximum capacity of the system to respond to acetylcholine has already been reached. We propose a model in which an underlying, age-related, progressive deficit is mitigated by a compensatory cholinergic feedback loop that acts to retard the behavioral effects of what would otherwise be a substantial age-related decline in olfactory plasticity. We also treated mice with 10-day regimens of olfactory environmental enrichment and/or repeated systemic injections of the acetylcholinesterase inhibitor physostigmine. Each treatment alone sharpened odor quality acuity, but administering both treatments together had no greater effect than either alone. Age was not a significant main effect in this study, suggesting that some capacity for acetylcholine-dependent plasticity is still present in aged mice despite their sharply reduced ability to respond to acute increases in acetylcholine levels. These results suggest a dynamical framework for understanding age-related decline in neural circuit processing in which the direct effects of aging can be mitigated, at least temporarily, by systemic compensatory responses. In particular, a decline in

  3. 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

  4. Age-Related Decline in Cardiorespiratory Fitness among Career Firefighters: Modification by Physical Activity and Adiposity.

    PubMed

    Baur, Dorothee M; Christophi, Costas A; Cook, E Francis; Kales, Stefanos N

    2012-01-01

    Firefighting is a very hazardous occupation, and strenuous fire duties require high levels of physical fitness. In the general adult population, cardiorespiratory fitness (CRF) declines with aging. We sought to investigate the effect of increasing age on CRF in male career firefighters as well as the modifying effects of physical activity and adiposity. We cross-sectionally examined 804 male career firefighters from two Midwestern states. CRF was determined from symptom-limited maximal treadmill exercise testing in metabolic equivalents (METS) following the Bruce protocol. Physical activity self-reports were extracted from responses to a health and lifestyle questionnaire. We found as expected that CRF declines with advancing age; however, the decline is greatly attenuated among leaner firefighters who report more physical activity. Furthermore, in a linear regression model including age, BMI, and variables describing physical activity behaviors, we could predict CRF (R(2) = 0.6286). The total weekly duration of aerobic exercise as well as the duration of weight lifting sessions both had significant impacts on age-related decline. We conclude that firefighters are more likely to maintain the high levels of CRF needed to safely perform their duties if they engage in frequent exercise and maintain healthy weights.

  5. 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

  6. 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

  7. Blueberry-enriched diet ameliorates age-related declines in NMDA receptor-dependent LTP

    PubMed Central

    Bickford, Paula C.; Browning, Michael D.

    2008-01-01

    NMDA receptor-dependent long-term potentiation (LTP) in the hippocampus is widely accepted as a cellular substrate for memory formation. Age-related declines in the expression of both NMDAR-dependent LTP and NMDAR subunit proteins in the CA1 region of the hippocampus have been well characterized and likely underlie age-related memory impairment. In the current study, we examined NMDAR-dependent LTP in young Fischer 344 rats (4 months old) and aged rats (24 months old) given either a control diet or a diet supplemented with blueberry extract for 6–8 weeks. NMDAR-dependent LTP was evoked by high-frequency stimulation (HFS) in the presence of nifedipine, to eliminate voltage-gated calcium channel LTP. Field excitatory postsynaptic potentials (fEPSPs) were increased by 57% 1 h after HFS in young animals, but this potentiation was reduced to 31% in aged animals. Supplementation of the diet with blueberry extract elevated LTP (63%) in aged animals to levels seen in young. The normalization of LTP may be due to the blueberry diet preventing a decline in synaptic strength, as measured by the slope of the fEPSP for a given fiber potential. The blueberry diet did not prevent age-related declines in NMDAR protein expression. However, phosphorylation of a key tyrosine residue on the NR2B subunit, important for increasing NMDAR function, was enhanced by the diet, suggesting that an increase in NMDAR function might overcome the loss in protein. This report provides evidence that dietary alterations later in life may prevent or postpone the cognitive declines associated with aging. PMID:19424850

  8. A Subset of Men With Age-Related Decline in Testosterone Have Gonadotroph Autoantibodies

    PubMed Central

    Ricciuti, Adriana; Travison, Thomas G.; Di Dalmazi, Giulia; Talor, Monica V.; DeVincentiis, Ludovica; Manley, Robert W.; Bhasin, Shalender; Caturegli, Patrizio

    2016-01-01

    Context: Age-related decline in serum testosterone (T) is being increasingly diagnosed. In most men, it associates with low or inappropriately normal gonadotropin levels, which suggests a hypothalamic-pituitary etiology. Autoantibodies against adenohypophyseal cells have been associated with pituitary dysfunction; however, the prevalence of pituitary autoimmunity in this age-related T decline has not been assessed. Objectives: This is a proof-of-concept study with the objective of determining the prevalence of antibodies to gonadotrophs in older men with age-related low T and compare it with healthy young and older eugonadal men. Study Design: This is a cross-sectional case-control study of 182 men. Cases included 100 older men (≥65 years) with age-related low T levels; the control groups were composed of 50 young and 32 older healthy eugonadal men. Serum antibodies against the anterior pituitary gland were measured using a two-step approach: 1) single indirect immunofluorescence (ie, participant serum only) to determine the pattern of cytosolic staining; and 2) double indirect immunofluorescence (ie, participant serum plus a commercial adenohypophyseal hormone antibody) to identify the anterior pituitary cell type recognized by the patient's antibodies). Results: In participants with positive antipituitary antibodies, the granular cytosolic pattern (highly predictive of pituitary autoimmunity) was only seen in older men with age-related low T (4%) and none in control groups (0%, P = .001). Double indirect immunofluorescence confirmed that pituitary antibodies were exclusively directed against the gonadotrophs. Conclusion: A subset of older men with age-related low T levels have specific antibodies against the gonadotrophs. Whether these antibodies are pathogenic and contributory to the age-related decline in T remains to be established. PMID:26963952

  9. Mechanisms of Age-Related Decline in Memory Search Across the Adult Life Span

    PubMed Central

    Hills, Thomas T.; Mata, Rui; Wilke, Andreas; Samanez-Larkin, Gregory R.

    2013-01-01

    Three alternative mechanisms for age-related decline in memory search have been proposed, which result from either reduced processing speed (global slowing hypothesis), overpersistence on categories (cluster-switching hypothesis), or the inability to maintain focus on local cues related to a decline in working memory (cue-maintenance hypothesis). We investigated these 3 hypotheses by formally modeling the semantic recall patterns of 185 adults between 27 to 99 years of age in the animal fluency task (Thurstone, 1938). The results indicate that people switch between global frequency-based retrieval cues and local item-based retrieval cues to navigate their semantic memory. Contrary to the global slowing hypothesis that predicts no qualitative differences in dynamic search processes and the cluster-switching hypothesis that predicts reduced switching between retrieval cues, the results indicate that as people age, they tend to switch more often between local and global cues per item recalled, supporting the cue-maintenance hypothesis. Additional support for the cue-maintenance hypothesis is provided by a negative correlation between switching and digit span scores and between switching and total items recalled, which suggests that cognitive control may be involved in cue maintenance and the effective search of memory. Overall, the results are consistent with age-related decline in memory search being a consequence of reduced cognitive control, consistent with models suggesting that working memory is related to goal perseveration and the ability to inhibit distracting information. PMID:23586941

  10. 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.

  11. Accelerated age-related cognitive decline and neurodegeneration, caused by deficient DNA repair.

    PubMed

    Borgesius, Nils Z; de Waard, Monique C; van der Pluijm, Ingrid; Omrani, Azar; Zondag, Gerben C M; van der Horst, Gijsbertus T J; Melton, David W; Hoeijmakers, Jan H J; Jaarsma, Dick; Elgersma, Ype

    2011-08-31

    Age-related cognitive decline and neurodegenerative diseases are a growing challenge for our societies with their aging populations. Accumulation of DNA damage has been proposed to contribute to these impairments, but direct proof that DNA damage results in impaired neuronal plasticity and memory is lacking. Here we take advantage of Ercc1(Δ/-) mutant mice, which are impaired in DNA nucleotide excision repair, interstrand crosslink repair, and double-strand break repair. We show that these mice exhibit an age-dependent decrease in neuronal plasticity and progressive neuronal pathology, suggestive of neurodegenerative processes. A similar phenotype is observed in mice where the mutation is restricted to excitatory forebrain neurons. Moreover, these neuron-specific mutants develop a learning impairment. Together, these results suggest a causal relationship between unrepaired, accumulating DNA damage, and age-dependent cognitive decline and neurodegeneration. Hence, accumulated DNA damage could therefore be an important factor in the onset and progression of age-related cognitive decline and neurodegenerative diseases.

  12. Enriched childhood experiences moderate age-related motor and cognitive decline

    PubMed Central

    Metzler, Megan J.; Saucier, Deborah M.; Metz, Gerlinde A.

    2012-01-01

    Aging is associated with deterioration of skilled manual movement. Specifically, aging corresponds with increased reaction time, greater movement duration, segmentation of movement, increased movement variability, and reduced ability to adapt to external forces and inhibit previously learned sequences. Moreover, it is thought that decreased lateralization of neural function in older adults may point to increased neural recruitment as a compensatory response to deterioration of key frontal and intra-hemispheric networks, particularly of callosal structures. However, factors that mediate age-related motor decline are not well understood. Here we show that music training in childhood is associated with reduced age-related decline of bimanual and unimanual motor skills in a MIDI keyboard motor learning task. Compared to older adults without music training, older adults with more than a year of music training demonstrated proficient bimanual and unimanual movement, evidenced by enhanced speed and decreased movement errors. Further, this group demonstrated significantly better implicit learning in the weather prediction task, a non-motor task. The performance of older adults with music training in those tasks was comparable to young adults. Older adults, however, displayed greater verbal ability compared to young adults irrespective of a past history of music training. Our results indicate that music training early in life may reduce age-associated decline of neural motor and cognitive networks. PMID:23423702

  13. Motor Skills Enhance Procedural Memory Formation and Protect against Age-Related Decline

    PubMed Central

    Müller, Nils C. J.; Genzel, Lisa; Konrad, Boris N.; Pawlowski, Marcel; Neville, David; Fernández, Guillén; Steiger, Axel

    2016-01-01

    The ability to consolidate procedural memories declines with increasing age. Prior knowledge enhances learning and memory consolidation of novel but related information in various domains. Here, we present evidence that prior motor experience–in our case piano skills–increases procedural learning and has a protective effect against age-related decline for the consolidation of novel but related manual movements. In our main experiment, we tested 128 participants with a sequential finger-tapping motor task during two sessions 24 hours apart. We observed enhanced online learning speed and offline memory consolidation for piano players. Enhanced memory consolidation was driven by a strong effect in older participants, whereas younger participants did not benefit significantly from prior piano experience. In a follow up independent control experiment, this compensatory effect of piano experience was not visible after a brief offline period of 30 minutes, hence requiring an extended consolidation window potentially involving sleep. Through a further control experiment, we rejected the possibility that the decreased effect in younger participants was caused by training saturation. We discuss our results in the context of the neurobiological schema approach and suggest that prior experience has the potential to rescue memory consolidation from age-related cognitive decline. PMID:27333186

  14. Age-Related Declines in Early Sensory Memory: Identification of Rapid Auditory and Visual Stimulus Sequences

    PubMed Central

    Fogerty, Daniel; Humes, Larry E.; Busey, Thomas A.

    2016-01-01

    Age-related temporal-processing declines of rapidly presented sequences may involve contributions of sensory memory. This study investigated recall for rapidly presented auditory (vowel) and visual (letter) sequences presented at six different stimulus onset asynchronies (SOA) that spanned threshold SOAs for sequence identification. Younger, middle-aged, and older adults participated in all tasks. Results were investigated at both equivalent performance levels (i.e., SOA threshold) and at identical physical stimulus values (i.e., SOAs). For four-item sequences, results demonstrated best performance for the first and last items in the auditory sequences, but only the first item for visual sequences. For two-item sequences, adults identified the second vowel or letter significantly better than the first. Overall, when temporal-order performance was equated for each individual by testing at SOA thresholds, recall accuracy for each position across the age groups was highly similar. These results suggest that modality-specific processing declines of older adults primarily determine temporal-order performance for rapid sequences. However, there is some evidence for a second amodal processing decline in older adults related to early sensory memory for final items in a sequence. This selective deficit was observed particularly for longer sequence lengths and was not accounted for by temporal masking. PMID:27199737

  15. Age-related decline in olympic triathlon performance: effect of locomotion mode.

    PubMed

    Bernard, Thierry; Sultana, Frédéric; Lepers, Romuald; Hausswirth, Christophe; Brisswalter, Jeanick

    2010-01-01

    This study describes the decline in performance with age during Olympic triathlon Age Groups World Championships among the different locomotion modes. Mean performance of top 10 performers were analyzed for each group of age using the exponential model proposed by Baker, Tang, and Turner (2003, Experimental Aging Research, 29, 47-65). Comparison in performance decline was done between locomotion modes. Decline in performance in triathlon as a function of age follows an exponential model. A significant interaction effect between age and locomotion mode was observed on performance values. In swimming, a significant decrease was observed close to 5% per year after 45 years. Decline in performance was less pronounced in cycling until 60 years. Analysis of the effect of age in the different locomotion modes of a triathlon could provide information for maintaining quality of life with aging.

  16. Age-related declines in car following performance under simulated fog conditions

    PubMed Central

    Ni, Rui; Kang, Julie J.; Andersen, George J.

    2010-01-01

    The present study examined age-related differences in car following performance when contrast of the driving scene was reduced by simulated fog. Older (mean age of 72.6) and younger (mean age of 21.1) drivers were presented with a car following scenario in a simulator in which a lead vehicle (LV) varied speed according to a sum of three sine wave functions. Drivers were shown an initial following distance of 18m and were asked to maintain headway distance by controlling speed to match changes in LV speed. Five simulated fog conditions were examined ranging from a no fog condition (contrast of 0.55) to a high fog condition (contrast of 0.03). Average LV speed varied across trials (40, 60, or 80 km/h). The results indicated age-related declines in car following performance for both headway distance and RMS (root mean square) error in matching speed. The greatest decline occurred at moderate speeds under the highest fog density condition, with older drivers maintaining a headway distance that was 21% closer than younger drivers. At higher speeds older drivers maintained a greater headway distance than younger drivers. These results suggest that older drivers may be at greater risk for a collision under high fog density and moderate speeds. PMID:20380908

  17. Age-related declines in car following performance under simulated fog conditions.

    PubMed

    Ni, Rui; Kang, Julie J; Andersen, George J

    2010-05-01

    The present study examined age-related differences in car following performance when contrast of the driving scene was reduced by simulated fog. Older (mean age of 72.6) and younger (mean age of 21.1) drivers were presented with a car following scenario in a simulator in which a lead vehicle (LV) varied speed according to a sum of three sine wave functions. Drivers were shown an initial following distance of 18 m and were asked to maintain headway distance by controlling speed to match changes in LV speed. Five simulated fog conditions were examined ranging from a no fog condition (contrast of 0.55) to a high fog condition (contrast of 0.03). Average LV speed varied across trials (40, 60, or 80 km/h). The results indicated age-related declines in car following performance for both headway distance and RMS (root mean square) error in matching speed. The greatest decline occurred at moderate speeds under the highest fog density condition, with older drivers maintaining a headway distance that was 21% closer than younger drivers. At higher speeds older drivers maintained a greater headway distance than younger drivers. These results suggest that older drivers may be at greater risk for a collision under high fog density and moderate speeds.

  18. Neurogenesis in a rat model of age-related cognitive decline.

    PubMed

    Bizon, J L; Lee, H J; Gallagher, M

    2004-08-01

    Age-related decrements in hippocampal neurogenesis have been suggested as a basis for learning impairment during aging. In the current study, a rodent model of age-related cognitive decline was used to evaluate neurogenesis in relation to hippocampal function. New hippocampal cell survival was assessed approximately 1 month after a series of intraperitoneal injections of 5-bromo-2'-deoxyuridine (BrdU). Correlational analyses between individual measures of BrdU-positive cells and performance on the Morris water maze task provided no indication that this measure of neurogenesis was more preserved in aged rats with intact cognitive abilities. On the contrary, among aged rats, higher numbers of BrdU-positive cells in the granule cell layer were associated with a greater degree of impairment on the learning task. Double-labelling studies confirmed that the majority of the BrdU+ cells were of the neuronal phenotype; the proportion of differentiated neurons was not different across a broad range of cognitive abilities. These data demonstrate that aged rats that maintain cognitive function do so despite pronounced reductions in hippocampal neurogenesis. In addition, these findings suggest the interesting possibility that impaired hippocampal function is associated with greater survival of newly generated hippocampal neurons at advanced ages.

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

    PubMed

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

    2016-01-01

    Age-related changes in proprioception are known to affect postural stability, yet the extent to which such changes affect the finger joints is poorly understood despite the importance of finger proprioception in the control of skilled hand movement. We quantified age-related changes in finger proprioception in 37 healthy young, middle-aged, and older adults using two robot-based tasks wherein participants' index and middle fingers were moved by an exoskeletal robot. The first task assessed finger position sense by asking participants to indicate when their index and middle fingers were directly overlapped during a passive crisscross movement; the second task assessed finger movement detection by asking participants to indicate the onset of passive finger movement. When these tasks were completed without vision, finger position sense errors were 48 % larger in older adults compared to young participants (p < 0.05); proprioceptive reaction time was 78 % longer in older adults compared to young adults (p < 0.01). When visual feedback was provided in addition to proprioception, these age-related differences were no longer apparent. No difference between dominant and non-dominant hand performance was found for either proprioception task. These findings demonstrate that finger proprioception is impaired in older adults, and visual feedback can be used to compensate for this deficit. The findings also support the feasibility and utility of the FINGER robot as a sensitive tool for detecting age-related decline in proprioception.

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

    PubMed Central

    Iwasaki, Shinichi; Yamasoba, Tatsuya

    2015-01-01

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

  1. Hypothalamic ΔFosB prevents age-related metabolic decline and functions via SNS

    PubMed Central

    Nagano, Kenichi; Rowe, Glenn C.; Gori, Francesca; Baron, Roland

    2017-01-01

    The ventral hypothalamus (VHT) integrates several physiological cues to maintain glucose homeostasis and energy balance. Aging is associated with increased glucose intolerance but the underlying mechanisms responsible for age-related metabolic decline, including neuronal signaling in the VHT, remain elusive. We have shown that mice with VHT-targeted overexpression of ΔFosB, a splice variant of the AP1 transcription factor FosB, exhibit increased energy expenditure, leading to decreased adiposity. Here, we show that VHT-targeted overexpression of ΔFosB also improves glucose tolerance, increases insulin sensitivity in target organs and thereby suppresses insulin secretion. These effects are also observed by the overexpression of dominant negative JunD, demonstrating that they occur via AP1 antagonism within the VHT. Furthermore, the improved glucose tolerance and insulin sensitivity persisted in aged animals overexpressing ΔFosB in the VHT. These beneficial effects on glucose metabolism were abolished by peripheral sympathectomy and α-adrenergic, but not β-adrenergic, blockade. Taken together, our results show that antagonizing AP1 transcription activity in the VHT leads to a marked improvement in whole body glucose homeostasis via activation of the SNS, conferring protection against age-related impairment in glucose metabolism. These findings may open novel avenues for therapeutic intervention in diabetes and age-related glucose intolerance. PMID:28121620

  2. Early Age-Related Functional Connectivity Decline in High-Order Cognitive Networks

    PubMed Central

    Siman-Tov, Tali; Bosak, Noam; Sprecher, Elliot; Paz, Rotem; Eran, Ayelet; Aharon-Peretz, Judith; Kahn, Itamar

    2017-01-01

    As the world ages, it becomes urgent to unravel the mechanisms underlying brain aging and find ways of intervening with them. While for decades cognitive aging has been related to localized brain changes, growing attention is now being paid to alterations in distributed brain networks. Functional connectivity magnetic resonance imaging (fcMRI) has become a particularly useful tool to explore large-scale brain networks; yet, the temporal course of connectivity lifetime changes has not been established. Here, an extensive cross-sectional sample (21–85 years old, N = 887) from a public fcMRI database was used to characterize adult lifespan connectivity dynamics within and between seven brain networks: the default mode, salience, dorsal attention, fronto-parietal control, auditory, visual and motor networks. The entire cohort was divided into young (21–40 years, mean ± SD: 25.5 ± 4.8, n = 543); middle-aged (41–60 years, 50.6 ± 5.4, n = 238); and old (61 years and above, 69.0 ± 6.3, n = 106) subgroups. Correlation matrices as well as a mixed model analysis of covariance indicated that within high-order cognitive networks a considerable connectivity decline is already evident by middle adulthood. In contrast, a motor network shows increased connectivity in middle adulthood and a subsequent decline. Additionally, alterations in inter-network interactions are noticeable primarily in the transition between young and middle adulthood. These results provide evidence that aging-related neural changes start early in adult life. PMID:28119599

  3. Age-related declines in immune response in a wild mammal are unrelated to immune cell telomere length

    PubMed Central

    Waring, Laura; McDonald, Robbie A.; Delahay, Richard; Young, Andrew

    2016-01-01

    Senescence has been hypothesized to arise in part from age-related declines in immune performance, but the patterns and drivers of within-individual age-related changes in immunity remain virtually unexplored in natural populations. Here, using a long-term epidemiological study of wild European badgers (Meles meles), we (i) present evidence of a within-individual age-related decline in the response of a key immune-signalling cytokine, interferon-gamma (IFNγ), to ex vivo lymphocyte stimulation, and (ii) investigate three putative drivers of individual variation in the rate of this decline (sex, disease and immune cell telomere length; ICTL). That the within-individual rate of age-related decline markedly exceeded that at the population level suggests that individuals with weaker IFNγ responses are selectively lost from this population. IFNγ responses appeared to decrease with the progression of bovine tuberculosis infection (independent of age) and were weaker among males than females. However, neither sex nor disease influenced the rate of age-related decline in IFNγ response. Similarly, while ICTL also declines with age, variation in ICTL predicted neither among- nor within-individual variation in IFNγ response. Our findings provide evidence of within-individual age-related declines in immune performance in a wild mammal and highlight the likely complexity of the mechanisms that generate them. PMID:26888036

  4. Age-related declines in immune response in a wild mammal are unrelated to immune cell telomere length.

    PubMed

    Beirne, Christopher; Waring, Laura; McDonald, Robbie A; Delahay, Richard; Young, Andrew

    2016-02-24

    Senescence has been hypothesized to arise in part from age-related declines in immune performance, but the patterns and drivers of within-individual age-related changes in immunity remain virtually unexplored in natural populations. Here, using a long-term epidemiological study of wild European badgers (Meles meles), we (i) present evidence of a within-individual age-related decline in the response of a key immune-signalling cytokine, interferon-gamma (IFNγ), to ex vivo lymphocyte stimulation, and (ii) investigate three putative drivers of individual variation in the rate of this decline (sex, disease and immune cell telomere length; ICTL). That the within-individual rate of age-related decline markedly exceeded that at the population level suggests that individuals with weaker IFNγ responses are selectively lost from this population. IFNγ responses appeared to decrease with the progression of bovine tuberculosis infection (independent of age) and were weaker among males than females. However, neither sex nor disease influenced the rate of age-related decline in IFNγ response. Similarly, while ICTL also declines with age, variation in ICTL predicted neither among- nor within-individual variation in IFNγ response. Our findings provide evidence of within-individual age-related declines in immune performance in a wild mammal and highlight the likely complexity of the mechanisms that generate them.

  5. Age-related decline in cardiac autonomic function is not attenuated with increased physical activity

    PubMed Central

    Njemanze, Hugo; Warren, Charlotte; Eggett, Christopher; MacGowan, Guy A.; Bates, Matthew G D; Siervo, Mario; Ivkovic, Srdjan; Trenell, Michael I.; Jakovljevic, Djordje G.

    2016-01-01

    Age and physical inactivity are important risk factors for cardiovascular mortality. Heart rate response to exercise (HRRE) and heart rate recovery (HRR), measures of cardiac autonomic function, are strong predictors of mortality. The present study defined the effect of age and physical activity on HRRE and HRR. Healthy women (N=72) grouped according to age (young, 20-30 years; middle, 40-50 years; and older, 65-81 years) and daily physical activity (low active <7500, high active >12,500 steps/day) performed a maximal cardiopulmonary exercise test. The HRRE was defined as an increase in heart rate from rest to 1, 3 and 5 minutes of exercise and at 1/3 of total exercise time, and HRR as the difference in heart rate between peak exercise and 1, 2, and 3 minutes later. Age was associated with a significant decline in HRRE at 1 min and 1/3 of exercise time (r= − 0.27, p=0.04, and r=−0.39, p=0.02) and HRR at 2 min and 3 min (r=−0.35, p=0.01, and r=−0.31, p=0.02). There was no significant difference in HRRE and HRR between high and low-active middle-age and older women (p>0.05). Increased level of habitual physical activity level appears to have a limited effect on age-related decline in cardiac autonomic function in women. PMID:27705949

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

    PubMed Central

    Nunes, Ashley; Kramer, Arthur F.

    2010-01-01

    Previous research has found age-related deficits in a variety of cognitive processes. However, some studies have demonstrated age-related sparing on tasks where individuals have substantial experience, often attained over many decades. Here, the authors examined whether decades of experience in a fast-paced demanding profession, air traffic control (ATC), would enable older controllers to perform at high levels of proficiency. The authors also investigated whether older controllers would show diminished age-related decrements on domain-relevant cognitive abilities. Both young and old controllers and noncontrollers performed a battery of cognitive and ATC tasks. Results indicate that although high levels of experience can reduce the magnitude of age-related decline on the component processes that underlie complex task performance, this sparing is limited in scope. More important, however, the authors observed experience-based sparing on simulated ATC tasks, with the sparing being most evident on the more complex air traffic control tasks. These results suggest that given substantial experience, older adults may be quite capable of performing at high levels of proficiency on fast-paced demanding real-world tasks. The implications of these findings for global skilled labor shortages are discussed. PMID:19309213

  7. Are ancient proteins responsible for the age-related decline in health and fitness?

    PubMed

    Truscott, Roger John Willis

    2010-02-01

    There are a number of sites in the body where proteins are present for decades and sometimes for all of our lives. Over a period of many years, such proteins are subject to two types of modifications. The first results from the intrinsic instability of certain amino acid residues and leads to deamidation, racemization, and truncation. The second type can be traced to relentless covalent modification of such ancient proteins by reactive biochemicals produced during cellular metabolism.The accumulation of both types of posttranslational modifications over time may have important consequences for the properties of tissues that contain such proteins. It is proposed that the age-related decline in function of organs such as the eye, heart, brain, and lung, as well as skeletal components, comes about, in part, from the posttranslational modification of these long-lived proteins. Examples are provided in which this may be an important factor in the etiology of age-related conditions. As the properties of these proteins alter inexorably over time, the molecular changes contribute to a gradual decline in the function of individual organs and also tissues such as joints. This cumulative degeneration of old proteins at multiple sites in the body may also constrain the ultimate life span of the individual. The human lens may be particularly useful for discovering which reactive metabolites in the body are of most importance for posttranslational modification of long-lived proteins.

  8. Increased bone morphogenetic protein signaling contributes to age-related declines in neurogenesis and cognition

    PubMed Central

    Meyers, Emily A.; Gobeske, Kevin T.; Bond, Allison M.; Jarrett, Jennifer C.; Peng, Chian-Yu; Kessler, John A.

    2015-01-01

    Aging is associated with decreased neurogenesis in the hippocampus and diminished hippocampus-dependent cognitive functions. Expression of bone morphogenetic protein 4 (BMP4) increases with age by more than 10-fold in the mouse dentate gyrus while levels of the BMP inhibitor, noggin, decrease. This results in a profound 30-fold increase in phosphorylated-SMAD1/5/8, the effector of canonical BMP signaling. Just as observed in mice, a profound increase in expression of BMP4 is observed in the dentate gyrus of humans with no known cognitive abnormalities. Inhibition of BMP signaling either by overexpression of noggin or transgenic manipulation not only increases neurogenesis in aging mice, but remarkably, is associated with a rescue of cognitive deficits to levels comparable to young mice. Additive benefits are observed when combining inhibition of BMP signaling and environmental enrichment. These findings indicate that increased BMP signaling contributes significantly to impairments in neurogenesis and to cognitive decline associated with aging, and identify this pathway as a potential druggable target for reversing age-related changes in cognition. PMID:26827654

  9. Context Memory Decline in Middle Aged Adults is Related to Changes in Prefrontal Cortex Function.

    PubMed

    Kwon, Diana; Maillet, David; Pasvanis, Stamatoula; Ankudowich, Elizabeth; Grady, Cheryl L; Rajah, M Natasha

    2016-06-01

    The ability to encode and retrieve spatial and temporal contextual details of episodic memories (context memory) begins to decline at midlife. In the current study, event-related fMRI was used to investigate the neural correlates of context memory decline in healthy middle aged adults (MA) compared with young adults (YA). Participants were scanned while performing easy and hard versions of spatial and temporal context memory tasks. Scans were obtained at encoding and retrieval. Significant reductions in context memory retrieval accuracy were observed in MA, compared with YA. The fMRI results revealed that overall, both groups exhibited similar patterns of brain activity in parahippocampal cortex, ventral occipito-temporal regions and prefrontal cortex (PFC) during encoding. In contrast, at retrieval, there were group differences in ventral occipito-temporal and PFC activity, due to these regions being more activated in MA, compared with YA. Furthermore, only in YA, increased encoding activity in ventrolateral PFC, and increased retrieval activity in occipital cortex, predicted increased retrieval accuracy. In MA, increased retrieval activity in anterior PFC predicted increased retrieval accuracy. These results suggest that there are changes in PFC contributions to context memory at midlife.

  10. Dietary anthocyanin intake and age-related decline in lung function: longitudinal findings from the VA Normative Aging Study123

    PubMed Central

    Mehta, Amar J; Cassidy, Aedín; Litonjua, Augusto A; Sparrow, David; Vokonas, Pantel; Schwartz, Joel

    2016-01-01

    Background: It is unknown whether habitual intake of dietary flavonoids, known for their antioxidative and anti-inflammatory properties, affects longitudinal change in lung function. Objective: We investigated whether different flavonoid subclasses present in the habitual diet were associated with beneficial changes in lung function over time in the elderly. Design: This longitudinal analysis included 839 participants from the VA (Veterans Affairs) Normative Aging Study whose lung function [forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)] was measured at 2 and up to 5 visits between 1992 and 2008 (n = 2623 measurements). Yearly average intake of major flavonoid subclasses (anthocyanins, flavanones, flavan-3-ols, flavonols, flavones, and polymers) was calculated from food-frequency questionnaires at each visit. We estimated adjusted differences in annual change in lung function associated with each flavonoid subclass, categorized into quartiles, in linear mixed-effects regression models after adjustment for lifestyle and dietary confounders. Results: Strong inverse associations were found between anthocyanin intake and age-related decline in lung function. Independent of dietary and nondietary risk factors, slower rates of FEV1 and FVC decline by 23.6 (95% CI: 16.6, 30.7) and 37.3 (95% CI: 27.8, 46.8) mL/y, respectively, were observed in participants in the fourth quartile of intake compared with participants in the first quartile (P-trend < 0.0001). The protective associations observed for anthocyanin intake were present in both current/former and never smokers. Compared with no or very low intakes, an intake of ≥2 servings of anthocyanin-rich blueberries/wk was associated with slower decline in FEV1 and FVC by 22.5 (95% CI: 10.8, 34.2) and 37.9 (95% CI: 22.1, 53.7) mL/y, respectively. To a lesser extent, higher flavan-3-ol intake was also associated with slower lung function decline. Conclusions: An attenuation of age-related lung function

  11. 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…

  12. Endurance running program reverses the age related declines in peak oxygen consumption

    SciTech Connect

    Cartee, G.D.; Farrar, R.P.

    1986-03-01

    This study was designed to determine whether aging per se produces a decline in peak oxygen consumption (peak VO/sub 2/) or whether that decline may be due to the documented reduction in spontaneous activity. Male F344 rats, at the initial ages of 4 and 18 mos. of age, were divided into trained and untrained groups (YUT, YT, OUT, and OT). The trained groups ran up to 60 min/day 5 days/wk at a speed of 20m/min for 6 mos. The OUT rats demonstrated a 12% decline in peak VO/sub 2/ when compared to YUT rats. The OT rats had the same peak VO/sub 2/ as the YUT, but a 13% lower peak VO/sub 2/ than the YT. Representative enzymes of the TCA cycle, B oxidation, and electron transport system from gastrocnemius homogenates all declined in the OUT compared to YUT (14 to 24%). /sup 14/C-palmitate oxidation declined 45% in the OUT gastrocnemius compared to YUT. The carnitine values of the OUT were not significantly lower than the YUT and could not account for the large depression in palmitate oxidation. In contrast to the peak VO/sub 2/ which increased in OT only up to YUT values, the oxidative capacity of the skeletal muscle of OT was increased above the YUT group values equal to those of YT.

  13. Alzheimer’s Disease and Age-Related Memory Decline (Preclinical)

    PubMed Central

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

    2011-01-01

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

  14. Age-Related Declines in the Fidelity of Newly Acquired Category Representations

    ERIC Educational Resources Information Center

    Davis, Tyler; Love, Bradley C.; Maddox, W. Todd

    2012-01-01

    We present a theory suggesting that the ability to build category representations that reflect the nuances of category structures in the environment depends upon clustering mechanisms instantiated in an MTL-PFC-based circuit. Because function in this circuit declines with age, we predict that the ability to build category representations will be…

  15. Age-related decline in oligodendrogenesis retards white matter repair in mice

    PubMed Central

    Miyamoto, Nobukazu; Pham, Loc-Duyen D.; Hayakawa, Kazuhide; Matsuzaki, Toshinori; Seo, Ji Hae; Magnain, Caroline; Ayata, Cenk; Kim, Kyu-Won; Boas, David; Lo, Eng H.; Arai, Ken

    2013-01-01

    Background/Purpose Aging is one of the major risk factors for white matter injury in cerebrovascular disease. However, the effects of age on the mechanisms of injury/repair in white matter remain to be fully elucidated. Here, we ask if compared to young brains, white matter regions in older brains may be more vulnerable in part due to decreased rates of compensatory oligodendrogenesis after injury. Methods A mouse model of prolonged cerebral hypoperfusion was prepared by bilateral common carotid artery stenosis in 2-month and 8-month old mice. Matching in vitro studies were performed by subjecting oligodendrocyte precursor cells (OPCs) to sub-lethal 7-day CoCl2 treatment to induce chemical hypoxic stress. Results Baseline myelin density in the corpus callosum was similar in 2-month and 8-month old mice. But after induction of prolonged cerebral hypoperfusion, older mice showed more severe white matter injury together with worse deficits in working memory. The numbers of newborn oligodendrocytes and their precursors were increased by cerebral hypoperfusion in young mice, whereas these endogenous responses were significantly dampened in older mice. Defects in CREB signaling may be involved because activating CREB with the type-III phosphodiesterase inhibitor cilostazol in older mice restored the differentiation of OPCs, alleviated myelin loss and improved cognitive dysfunction during cerebral hypoperfusion. Cell culture systems confirmed that cilostazol promoted the differentiation of OPCs. Conclusions An age-related decline in CREB-mediated oligodendrogenesis may compromise endogenous white matter repair mechanisms, and therefore, drugs that activate CREB signaling provide a potential therapeutic approach for treating white matter injury in aging brains. PMID:23881957

  16. Does lifelong training temper age-related decline in sport performance? Interpreting differences between cross-sectional and longitudinal data.

    PubMed

    Young, Bradley W; Weir, Patricia L; Starkes, Janet L; Medic, Nikola

    2008-01-01

    In the face of remarkable aging trends in North American society, organized sport/physical activity is an important vehicle for promoting physical health, and a domain in which long-term participation might mitigate pessimistic trends for age decline. This investigation examined patterns of age-related decline in performance for 45 Masters runners who rigorously trained continuously for at least a decade. Longitudinal data for age and performance were collected for 200 m, 1500 m, and 10 km events retrospectively across participants' careers. Cross-sectional (CS) data representing normal patterns of aging were derived from online archives. Longitudinal data reflected within-participant training effects whereas CS data did not. Second-order regression analyses were performed separately for each data type and quadratic beta coefficients, indicative of accelerated age decline, were compared for CS and longitudinal samples on a within-event basis. Results showed evidence of accelerated decline with advancing age for both samples, although rates for longitudinal samples were moderated for the 200 m and 1500 m events. Findings for the long-distance event were anomalous. Results provide evidence for moderated age-decline in physical performance measures for individuals who sustain engagement in organized sport for lengthy periods. Discussion focuses on methodological considerations for advancing future research that contrasts CS and longitudinal samples, and the importance of encouraging sport involvement opportunities to aging individuals.

  17. Pupillary responses and memory-guided visual search reveal age-related and Alzheimer's-related memory decline.

    PubMed

    Dragan, Michelle C; Leonard, Timothy K; Lozano, Andres M; McAndrews, Mary Pat; Ng, Karen; Ryan, Jennifer D; Tang-Wai, David F; Wynn, Jordana S; Hoffman, Kari L

    2017-03-30

    Episodic memory - composed of memory for unique spatiotemporal experiences - is known to decline with aging, and even more severely in Alzheimer 's disease (AD). Memory for trial-unique objects in spatial scenes depends on the integrity of the hippocampus and interconnected structures that are among the first areas affected in AD. We reasoned that memory for objects-in-scenes would be impaired with aging, and that further impairments would be observed in AD. We asked younger adults, healthy older adults, older adults at-risk for developing cognitive impairments, and older adults with probable early AD to find changing items ('targets') within images of natural scenes, measuring repeated-trial changes in search efficiency and pupil diameter. Compared to younger adults, older adults took longer to detect target objects in repeated scenes, they required more fixations and those fixations were more dispersed. Whereas individuals with AD showed some benefit of memory in this task, they had substantially longer detection times, and more numerous, dispersed fixations on repeated scenes compared to age-matched older adults. Correspondingly, pupillary responses to novel and repeated scenes were diminished with aging and further in AD, and the memory-related changes were weaker with aging and absent in AD. Our results suggest that several nonverbal measures from memory-guided visual search tasks can index aging and Alzheimer's disease status, including pupillary dynamics. The task measurements are sensitive to the integrity of brain structures that are associated with Alzheimer's-related neurodegeneration, the task is well tolerated across a range of abilities, and thus, it may prove useful in early diagnostics and longitudinal tracking of memory decline.

  18. Edited magnetic resonance spectroscopy detects an age-related decline in brain GABA levels.

    PubMed

    Gao, Fei; Edden, Richard A E; Li, Muwei; Puts, Nicolaas A J; Wang, Guangbin; Liu, Cheng; Zhao, Bin; Wang, Huiquan; Bai, Xue; Zhao, Chen; Wang, Xin; Barker, Peter B

    2013-09-01

    Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain. Although measurements of GABA levels in vivo in the human brain using edited proton magnetic resonance spectroscopy ((1)H-MRS) have been established for some time, it is has not been established how regional GABA levels vary with age in the normal human brain. In this study, 49 healthy men and 51 healthy women aged between 20 and 76 years were recruited and J-difference edited spectra were recorded at 3T to determine the effect of age on GABA levels, and to investigate whether there are regional and gender differences in GABA in mesial frontal and parietal regions. Because the signal detected at 3.02 ppm using these experimental parameters is also expected to contain contributions from both macromolecules (MM) and homocarnosine, in this study the signal is labeled GABA+ rather than GABA. Significant negative correlations were observed between age and GABA+ in both regions studied (GABA+/Cr: frontal region, r=-0.68, p<0.001, parietal region, r=-0.54, p<0.001; GABA+/NAA: frontal region, r=-0.58, p<0.001, parietal region, r=-0.49, p<0.001). The decrease in GABA+ with age in the frontal region was more rapid in women than men. Evidence of a measureable decline in GABA is important in considering the neurochemical basis of the cognitive decline that is associated with normal aging.

  19. Edited Magnetic Resonance Spectroscopy Detects an Age-Related Decline in Nonhuman Primate Brain GABA Levels

    PubMed Central

    Killiany, Ronald J.

    2016-01-01

    Recent research had shown a correlation between aging and decreasing Gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the brain. However, how GABA level varies with age in the medial portion of the brain has not yet been studied. The purpose of this study was to investigate the GABA level variation with age focusing on the posterior cingulate cortex, which is the “core hub” of the default mode network. In this study, 14 monkeys between 4 and 21 years were recruited, and MEGA-PRESS MRS was performed to measure GABA levels, in order to explore a potential link between aging and GABA. Our results showed that a correlation between age and GABA+/Creatine ratio was at the edge of significance (r = −0.523, p = 0.081). There was also a near-significant trend between gray matter/white matter ratio and the GABA+/Creatine ratio (r = −0.518, p = 0.0848). Meanwhile, the correlation between age and grey matter showed no significance (r = −0.028, p = 0.93). Therefore, age and gray matter/white matter ratio account for different part of R-squared (adjusted R-squared = 0.5187) as independent variables for predicting GABA levels. Adjusted R-squared is about 0.5 for two independent variables. These findings suggest that there is internal neurochemical variation of GABA levels in the nonhuman primates associated with normal aging and structural brain decline. PMID:27660760

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

    PubMed

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

    2013-12-01

    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.

  1. Imaging mass spectrometry demonstrates age-related decline in human adipose plasticity

    PubMed Central

    Fazeli, Pouneh K.; Kim, Soomin; Lun, Mingyue; Zuflacht, Jonah P.; Milian, Jessica; Lee, Hang; Francois-Saint-Cyr, Hugues; Horreard, Francois; Larson, David; Rosen, Evan D.; Lee, Richard T.; Lechene, Claude P.; Steinhauser, Matthew L.

    2017-01-01

    Quantification of stable isotope tracers has revealed the dynamic state of living tissues. A new form of imaging mass spectrometry quantifies isotope ratios in domains much smaller than a cubic micron, enabling measurement of cell turnover and metabolism with stable isotope tracers at the single-cell level with a methodology we refer to as multi-isotope imaging mass spectrometry. In a first-in-human study, we utilize stable isotope tracers of DNA synthesis and de novo lipogenesis to prospectively measure cell birth and adipocyte lipid turnover. In a study of healthy adults, we elucidate an age-dependent decline in new adipocyte generation and adipocyte lipid turnover. A linear regression model suggests that the aging effect could be mediated by a decline in insulin-like growth factor-1 (IGF-1). This study therefore establishes a method for measurement of cell turnover and metabolism in humans with subcellular resolution while implicating the growth hormone/IGF-1 axis in adipose tissue aging. PMID:28289709

  2. Mobility decline in old age.

    PubMed

    Rantakokko, Merja; Mänty, Minna; Rantanen, Taina

    2013-01-01

    Mobility is important for community independence. With increasing age, underlying pathologies, genetic vulnerabilities, physiological and sensory impairments, and environmental barriers increase the risk for mobility decline. Understanding how mobility declines is paramount to finding ways to promote mobility in old age.

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

    ERIC Educational Resources Information Center

    Nunes, Ashley; Kramer, Arthur F.

    2009-01-01

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

  4. The Role of RFamide-Related Peptide-3 in Age-Related Reproductive Decline in Female Rats

    PubMed Central

    Geraghty, Anna C.; Muroy, Sandra E.; Kriegsfeld, Lance J.; Bentley, George E.; Kaufer, Daniela

    2016-01-01

    Reproductive senescence, the point in time when females cease to show estrous cyclicity, is associated with endocrine changes in the hypothalamus, pituitary, and gonads. However, the mechanisms triggering this transition are not well understood. To gain a better understanding of the top-down control of the transition from reproductive competence to a state of reproductive senescence, we investigated middle-aged female rats exhibiting varying degrees of reproductive decline, including individuals with normal cycles, irregular cycles, and complete cessation of cycles. We identified hormonal changes in the brain that manifest before ovarian cycles exhibit any deterioration. We found that females exhibit an increase in RFamide-related peptide-3 (RFRP3) mRNA expression in the hypothalamus in middle age prior to changes in estrous cycle length. This increase is transient and followed by subsequent decreases in kisspeptin (KiSS1) and gonadotropin-releasing hormone (GnRH) mRNA expression. Expression of RFRP3 and its receptor also increased locally in the ovaries with advancing age. While it is well known that aging is associated with decreased GnRH release and downstream disruption of the hypothalamic–pituitary–gonadal (HPG) axis, herein, we provide evidence that reproductive senescence is likely triggered by alterations in a network of regulatory neuropeptides upstream of the GnRH system. PMID:27445974

  5. Resting-state networks associated with cognitive processing show more age-related decline than those associated with emotional processing.

    PubMed

    Nashiro, Kaoru; Sakaki, Michiko; Braskie, Meredith N; Mather, Mara

    2017-03-11

    Correlations in activity across disparate brain regions during rest reveal functional networks in the brain. Although previous studies largely agree that there is an age-related decline in the "default mode network," how age affects other resting-state networks, such as emotion-related networks, is still controversial. Here we used a dual-regression approach to investigate age-related alterations in resting-state networks. The results revealed age-related disruptions in functional connectivity in all 5 identified cognitive networks, namely the default mode network, cognitive-auditory, cognitive-speech (or speech-related somatosensory), and right and left frontoparietal networks, whereas such age effects were not observed in the 3 identified emotion networks. In addition, we observed age-related decline in functional connectivity in 3 visual and 3 motor/visuospatial networks. Older adults showed greater functional connectivity in regions outside 4 out of the 5 identified cognitive networks, consistent with the dedifferentiation effect previously observed in task-based functional magnetic resonance imaging studies. Both reduced within-network connectivity and increased out-of-network connectivity were correlated with poor cognitive performance, providing potential biomarkers for cognitive aging.

  6. 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

  7. The age-related performance decline in Ironman triathlon starts earlier in swimming than in cycling and running.

    PubMed

    Käch, Ilja; Rüst, Christoph A; Nikolaidis, Pantelis T; Rosemann, Thomas; Knechtle, Beat

    2017-02-21

    In Ironman triathlon, the number of overall male and female finishers increased in the last 30 years, while an improvement in performance has been reported. Studies concluding these numbers only analysed the top ten athletes per age group instead of all finishers, therefore a selection bias might have occurred. The aim of the present study was to investigate participation, performance and the age-related performance decline of all pro and age group triathletes ranked in all Ironman triathlons held worldwide between 2002 and 2015. Split and overall race times of 329,066 (80%) male and 81,815 (20%) female athletes competing in 253 different Ironman triathlon races were analysed. The number of finishers increased in all age groups with exception of women in age group 75-79 years. In pro athletes, performance improved in all disciplines. In age group athletes, performance improved in younger age groups for running (18-24 to 40-44 years) and older age groups for swimming (50-54 to 65-69 years) and cycling (35-39 to 55-59 years), while it impaired in younger age groups for swimming (18-24 to 45-49 years) and cycling (18-24 to 30-34), and older age groups in running (45-49 to 70-74 years). The age-related performance decline started in women in age group 25-29 years in swimming and in age group 30-34 years in cycling, running and overall race time, whereas it started in men in age group 25-29 years in swimming and in age group 35-39 years in cycling, running and overall race time. For athletes and coaches, performance improved in younger age groups for running and older age groups for swimming and cycling and the age-related decline in performance started earlier in swimming than in cycling and running. In summary, women should start competing in Ironman triathlon before the age of 30 years and men before the age of 35 years to achieve their personal best Ironman race time.

  8. 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.

  9. Cortical grey matter content is associated with both age and bimanual performance, but is not observed to mediate age-related behavioural decline.

    PubMed

    van Ruitenbeek, Peter; Serbruyns, Leen; Solesio-Jofre, Elena; Meesen, Raf; Cuypers, Koen; Swinnen, Stephan P

    2017-01-01

    Declines in both cortical grey matter and bimanual coordination performance are evident in healthy ageing. However, the relationship between ageing, bimanual performance, and grey matter loss remains unclear, particularly across the whole adult lifespan. Therefore, participants (N = 93, range 20-80 years) performed a complex Bimanual Tracking Task, and structural brain images were obtained using magnetic resonance imaging. Analyses revealed that age correlated negatively with task performance. Voxel-based morphometry analysis revealed that age was associated with grey matter declines in task-relevant cortical areas and that grey matter in these areas was negatively associated with task performance. However, no evidence for a mediating effect of grey matter in age-related bimanual performance decline was observed. We propose a new hypothesis that functional compensation may account for the observed absence of mediation, which is in line with the observed pattern of increased inter-individual variance in performance with age.

  10. Parkinson's disease accelerates age-related decline in haptic perception by altering somatosensory integration.

    PubMed

    Konczak, Jürgen; Sciutti, Alessandra; Avanzino, Laura; Squeri, Valentina; Gori, Monica; Masia, Lorenzo; Abbruzzese, Giovanni; Sandini, Giulio

    2012-11-01

    This study investigated how Parkinson's disease alters haptic perception and the underlying mechanisms of somatosensory and sensorimotor integration. Changes in haptic sensitivity and acuity (the abilities to detect and to discriminate between haptic stimuli) due to Parkinson's disease were systematically quantified and contrasted to the performance of healthy older and young adults. Using a robotic force environment, virtual contours of various curvatures were presented. Participants explored these contours with their hands and indicated verbally whether they could detect or discriminate between two contours. To understand what aspects of sensory or sensorimotor integration are altered by ageing and disease, we manipulated the sensorimotor aspect of the task: the robot either guided the hand along the contour or the participant actively moved the hand. Active exploration relies on multimodal sensory and sensorimotor integration, while passive guidance only requires sensory integration of proprioceptive and tactile information. The main findings of the study are as follows: first, a decline in haptic precision can already be observed in adults before the age of 70 years. Parkinson's disease may lead to an additional decrease in haptic sensitivity well beyond the levels typically seen in middle-aged and older adults. Second, the haptic deficit in Parkinson's disease is general in nature. It becomes manifest as a decrease in sensitivity and acuity (i.e. a smaller perceivable range and a diminished ability to discriminate between two perceivable haptic stimuli). Third, thresholds during both active and passive exploration are elevated, but not significantly different from each other. That is, active exploration did not enhance the haptic deficit when compared to passive hand motion. This implies that Parkinson's disease affects early stages of somatosensory integration that ultimately have an impact on processes of sensorimotor integration. Our results suggest that

  11. Glutamate cysteine ligase and the age-related decline in cellular glutathione: The therapeutic potential of γ-glutamylcysteine.

    PubMed

    Ferguson, Gavin; Bridge, Wallace

    2016-03-01

    A consistent underlying index of aging is a decline in the cellular levels of the tripeptide glutathione (GSH). GSH is an essential thiol antioxidant produced in the cytosol of all cells and plays a key role in protecting against oxidative stress by neutralising free radicals and reactive oxygen species (ROS). The decline in GSH has been associated with changes in the expression and activity of the rate-limiting enzyme glutamate cysteine ligase (GCL), which produces the intermediate dipeptide γ-glutamylcysteine (γ-GC). The molecular mechanisms that affect these age-related changes remain unclear due to the complexity of GCL regulation. Impairment of the transcriptional activity of Nrf2 has been demonstrated to contribute to GCL dysregulation in aged rats. However, considering the complex nature of GCL regulation, relatively little research has been conducted to investigate the age-associated post-transcriptional controls of the enzyme. Defining these unknown mechanisms may inform our understanding of the aetiology of many age-related diseases and assist in formulating appropriate therapeutic strategies. This review focuses on the suitability of treatment with exogenous γ-GC to raise GSH levels by circumventing the age-related dysregulation of the rate-limiting step of GSH, providing promise for future research for the treatment of chronic oxidative stress-related diseases.

  12. Age-related decline in the responsiveness of motor cortex to plastic forces reverses with levodopa or cerebellar stimulation.

    PubMed

    Kishore, Asha; Popa, Traian; James, Praveen; Yahia-Cherif, Lydia; Backer, Febina; Varughese Chacko, Lijo; Govind, Preetha; Pradeep, Salini; Meunier, Sabine

    2014-11-01

    The plasticity of motor cortex is integral for motor memory and skills acquisition but it declines with aging. Forty healthy volunteers, across 6 decades, were tested to examine the (a) age-dependency of motor cortex responsiveness to plasticity induction, as measured from the response to paired associative stimulation (PAS) and the (b) effect of aging on the cerebellar modulation of motor cortex response to PAS. We examined if reduced dopaminergic transmission was involved in the age-related decline of response to PAS by retesting 10 of the older subjects after a single dose of levodopa. There was a substantial decline in the motor cortex response to PAS with aging, which was restored by levodopa in the older subjects. The cerebellar modulation of motor cortex response to PAS was less vulnerable to aging and a single session of cerebellar inhibition reinstated the cortical responsiveness in older subjects. Both levodopa and cerebellar inhibition can be tested for their ability to enhance motor skills acquisition and motor performance in the elderly individuals.

  13. The Rate of Age-Related Olfactory Decline Among the General Population of Older U.S. Adults

    PubMed Central

    Wroblewski, Kristen E.; Kern, David W.; Schumm, L. Philip; McClintock, Martha K.

    2015-01-01

    Background. Age-related olfactory loss (presbyosmia) is a prevalent sensory impairment with a large public health impact. In cross-sectional analyses, we found striking health disparities in olfactory function among older U.S. adults. Here, we report a 5-year follow-up to determine the magnitude of within-person olfactory decline. Methods. The National Social Life, Health, and Aging Project (NSHAP) interviewed a probability sample of home-dwelling older U.S. adults (57–85 years) in 2005–2006 (Wave 1) and reinterviewed them in 2010–2011 (Wave 2), assessing demographics, social life, and health, including olfaction. Odor identification was measured with a 5-item version of the Sniffin’ Sticks (0–5 correct). Fourteen hundred and thirty-six respondents provided olfaction data in both waves. Multivariate linear and logistic regression were used to model the association between change in olfactory performance and demographic, health, and psychosocial factors. Results. Odor identification declined most rapidly among older individuals (0.25 additional errors per 5 years for each decade of age, p < .001) and in men (0.17 additional errors per 5 years compared to women, p = .005). Among those with perfect scores in Wave 1, African Americans declined more rapidly than Whites (p = .04). Neither socioeconomic status, health conditions, cognition, mental health, alcohol use nor smoking was associated with change in olfaction (p > .05, all). Conclusions. The rate of olfactory decline increases with age and is greater among men than women despite adjusting for differences in psychosocial and health conditions, indicating physiologic factors as drivers. African Americans are more likely to experience initial olfactory decline, consistent with an earlier onset of aging among this subgroup. PMID:26253908

  14. Education and Age-Related Cognitive Decline: The Contribution of Mental Workload.

    ERIC Educational Resources Information Center

    Bosma, H.; van Boxtel, M. P. J.; Ponds, R. W. H. M.; Houx, P. J. H.; Jolles, J.

    2003-01-01

    Longitudinal data from a Dutch study of 708 older adults showed that persons with low educational attainment experienced more decline in information processing speed, memory, and cognitive function. About 42% of the variance was explained by low stimulus or challenge in work. Decline was independent of crystallized intelligence. (Contains 24…

  15. Age-related declines in exploratory behavior and markers of hippocampal plasticity are attenuated by prenatal choline supplementation in rats.

    PubMed

    Glenn, Melissa J; Kirby, Elizabeth D; Gibson, Erin M; Wong-Goodrich, Sarah J; Mellott, Tiffany J; Blusztajn, Jan K; Williams, Christina L

    2008-10-27

    Supplemental choline in the maternal diet produces a lasting enhancement in memory in offspring that resists age-related decline and is accompanied by neuroanatomical, neurophysiological and neurochemical changes in the hippocampus. The present study was designed to examine: 1) if prenatal choline supplementation alters behaviors that contribute to risk or resilience in cognitive aging, and 2) whether, at old age (25 months), prenatally choline-supplemented rats show evidence of preserved hippocampal plasticity. A longitudinal design was used to look at exploration of an open field, with and without objects, at 1 and 24 months of age in male and female rats whose mothers were fed a diet supplemented with choline (SUP; 5 mg/kg choline chloride) or not supplemented (CON; 1.1 mg/kg choline chloride) on embryonic days 12-17. Aging caused a significant decline in open field exploration that was more pronounced in males but interest in novel objects was maintained in both sexes. Prenatal choline supplementation attenuated, but did not prevent age-related decline in exploration in males and increased object exploration in young females. Following behavioral assessment, rats were euthanized to assess markers of hippocampal plasticity. Aged SUP males and females had more newly proliferated cells in the hippocampal dentate gyrus and protein levels of vascular endothelial growth factor (VEGF) and neurotrophin-3 (NT-3) were significantly elevated in female SUP rats in comparison to all other groups. Taken together, these findings provide the first evidence that prenatal choline supplementation causes changes in exploratory behaviors over the lifespan and preserves some features of hippocampal plasticity that can be seen even at 2 years of age.

  16. Genetic background influences age-related decline in visual and nonvisual retinal responses, circadian rhythms, and sleep☆

    PubMed Central

    Banks, Gareth; Heise, Ines; Starbuck, Becky; Osborne, Tamzin; Wisby, Laura; Potter, Paul; Jackson, Ian J.; Foster, Russell G.; Peirson, Stuart N.; Nolan, Patrick M.

    2015-01-01

    The circadian system is entrained to the environmental light/dark cycle via retinal photoreceptors and regulates numerous aspects of physiology and behavior, including sleep. These processes are all key factors in healthy aging showing a gradual decline with age. Despite their importance, the exact mechanisms underlying this decline are yet to be fully understood. One of the most effective tools we have to understand the genetic factors underlying these processes are genetically inbred mouse strains. The most commonly used reference mouse strain is C57BL/6J, but recently, resources such as the International Knockout Mouse Consortium have started producing large numbers of mouse mutant lines on a pure genetic background, C57BL/6N. Considering the substantial genetic diversity between mouse strains we expect there to be phenotypic differences, including differential effects of aging, in these and other strains. Such differences need to be characterized not only to establish how different mouse strains may model the aging process but also to understand how genetic background might modify age-related phenotypes. To ascertain the effects of aging on sleep/wake behavior, circadian rhythms, and light input and whether these effects are mouse strain-dependent, we have screened C57BL/6J, C57BL/6N, C3H-HeH, and C3H-Pde6b+ mouse strains at 5 ages throughout their life span. Our data show that sleep, circadian, and light input parameters are all disrupted by the aging process. Moreover, we have cataloged a number of strain-specific aging effects, including the rate of cataract development, decline in the pupillary light response, and changes in sleep fragmentation and the proportion of time spent asleep. PMID:25179226

  17. Functional magnetic resonance imaging in aging and dementia: detection of age-related cognitive changes and prediction of cognitive decline.

    PubMed

    Woodard, John L; Sugarman, Michael A

    2012-01-01

    Functional magnetic resonance imaging (fMRI) allows for dynamic observation of the neural substrates of cognitive processing, which makes it a valuable tool for studying brain changes that may occur with both normal and pathological aging. fMRI studies have revealed that older adults frequently exhibit a greater magnitude and extent activation of the blood-oxygen-level-dependent signal compared to younger adults. This additional activation may reflect compensatory recruitment associated with functional and structural deterioration of neural resources. Increased activation has also been associated with several risk factors for Alzheimer's disease (AD), including the apolipoprotein ε4 allele. Longitudinal studies have also demonstrated that fMRI may have predictive utility in determining which individuals are at the greatest risk of developing cognitive decline. This chapter will review the results of a number of task-activated fMRI studies of older adults, focusing on both healthy aging and neuropathology associated with AD. We also discuss models that account for cognitive aging processes, including the hemispheric asymmetry reduction in older adults (HAROLD) and scaffolding theory of aging and cognition (STAC) models. Finally, we discuss methodological issues commonly associated with fMRI research in older adults.

  18. Musical training orchestrates coordinated neuroplasticity in auditory brainstem and cortex to counteract age-related declines in categorical vowel perception.

    PubMed

    Bidelman, Gavin M; Alain, Claude

    2015-01-21

    Musicianship in early life is associated with pervasive changes in brain function and enhanced speech-language skills. Whether these neuroplastic benefits extend to older individuals more susceptible to cognitive decline, and for whom plasticity is weaker, has yet to be established. Here, we show that musical training offsets declines in auditory brain processing that accompanying normal aging in humans, preserving robust speech recognition late into life. We recorded both brainstem and cortical neuroelectric responses in older adults with and without modest musical training as they classified speech sounds along an acoustic-phonetic continuum. Results reveal higher temporal precision in speech-evoked responses at multiple levels of the auditory system in older musicians who were also better at differentiating phonetic categories. Older musicians also showed a closer correspondence between neural activity and perceptual performance. This suggests that musicianship strengthens brain-behavior coupling in the aging auditory system. Last, "neurometric" functions derived from unsupervised classification of neural activity established that early cortical responses could accurately predict listeners' psychometric speech identification and, more critically, that neurometric profiles were organized more categorically in older musicians. We propose that musicianship offsets age-related declines in speech listening by refining the hierarchical interplay between subcortical/cortical auditory brain representations, allowing more behaviorally relevant information carried within the neural code, and supplying more faithful templates to the brain mechanisms subserving phonetic computations. Our findings imply that robust neuroplasticity conferred by musical training is not restricted by age and may serve as an effective means to bolster speech listening skills that decline across the lifespan.

  19. Lifelong strength training mitigates the age-related decline in efferent drive.

    PubMed

    Unhjem, Runar; Nygård, Mona; van den Hoven, Lene T; Sidhu, Simranjit K; Hoff, Jan; Wang, Eivind

    Recently, we documented age-related attenuation of efferent drive to contracting skeletal muscle. It remains elusive if this indication of reduced muscle strength is present with lifelong strength training. For this purpose, we examined evoked potentials in the calf muscles of 11 [71 ± 4 (SD) yr] strength-trained master athletes (MA) contrasted with 10 (71 ± 4 yr) sedentary (SO) and 11 (73 ± 6 yr) recreationally active (AO) old subjects, as well as 9 (22 ± 2 yr) young controls. As expected, MA had higher leg press maximal strength (MA, 185 ± 32 kg; AO, 128 ± 15 kg; SO, 106 ± 11 kg; young, 147 ± 22 kg, P < 0.01) and rate of force development (MA, 5,588 ± 2,488 N/s; AO, 2,156 ± 1,100 N/s; SO, 2,011 ± 825 N/s; young, 3,663 ± 1,140 N/s, P < 0.05) than the other groups. MA also exhibited higher musculus soleus normalized V waves during maximal voluntary contractions (MVC) [maximal V wave amplitude/maximal M wave during MVC (Vsup/Msup); 0.28 ± 0.15] than AO (0.13 ± 0.06, P < 0.01) and SO (0.11 ± 0.05, P < 0.01), yet lower than young (0.45 ± 0.12, P < 0.01). No differences were apparent between the old groups in H reflex recorded at rest or during MVC [maximal H reflex amplitude/maximal M wave during rest (Hmax/Mmax); maximal H reflex amplitude during MVC/maximal M wave during MVC (Hsup/Msup)], and all were lower (P < 0.01) than young. MA (34.4 ± 2.1 ms) had shorter (P < 0.05) H reflex latency compared with AO (36.4 ± 3.7 ms) and SO (37.3 ± 3.2 ms), but longer (P < 0.01) than young (30.7 ± 2.0 ms). Using interpolated twitch analysis, MA (89 ± 7%) had plantar flexion voluntary activation similar to young (90 ± 6%), and this was higher (P < 0.05), or tended to be higher (P = 0.06-0.09), than SO (83 ± 10%) and AO (84 ± 5%). These observations suggest that lifelong strength training has a protective effect against age-related attenuation of efferent drive. In contrast, no beneficial effect seems to derive from habitual recreational activity, indicating

  20. Age-related decline of the cytochrome c oxidase subunit expression in the auditory cortex of the mimetic aging rat model associated with the common deletion.

    PubMed

    Zhong, Yi; Hu, Yujuan; Peng, Wei; Sun, Yu; Yang, Yang; Zhao, Xueyan; Huang, Xiang; Zhang, Honglian; Kong, Weijia

    2012-12-01

    The age-related deterioration in the central auditory system is well known to impair the abilities of sound localization and speech perception. However, the mechanisms involved in the age-related central auditory deficiency remain unclear. Previous studies have demonstrated that mitochondrial DNA (mtDNA) deletions accumulated with age in the auditory system. Also, a cytochrome c oxidase (CcO) deficiency has been proposed to be a causal factor in the age-related decline in mitochondrial respiratory activity. This study was designed to explore the changes of CcO activity and to investigate the possible relationship between the mtDNA common deletion (CD) and CcO activity as well as the mRNA expression of CcO subunits in the auditory cortex of D-galactose (D-gal)-induced mimetic aging rats at different ages. Moreover, we explored whether peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM) were involved in the changes of nuclear- and mitochondrial-encoded CcO subunits in the auditory cortex during aging. Our data demonstrated that d-gal-induced mimetic aging rats exhibited an accelerated accumulation of the CD and a gradual decline in the CcO activity in the auditory cortex during the aging process. The reduction in the CcO activity was correlated with the level of CD load in the auditory cortex. The mRNA expression of CcO subunit III was reduced significantly with age in the d-gal-induced mimetic aging rats. In contrast, the decline in the mRNA expression of subunits I and IV was relatively minor. Additionally, significant increases in the mRNA and protein levels of PGC-1α, NRF-1 and TFAM were observed in the auditory cortex of D-gal-induced mimetic aging rats with aging. These findings suggested that the accelerated accumulation of the CD in the auditory cortex may induce a substantial decline in CcO subunit III and lead to a significant decline in the Cc

  1. Aging- and task-related resilience decline is linked to food responsiveness in highly social honey bees.

    PubMed

    Speth, Martin T; Kreibich, Claus D; Amdam, Gro V; Münch, Daniel

    2015-05-01

    Conventional invertebrate models of aging have provided striking examples for the influence of food- and nutrient-sensing on lifespan and stress resilience. On the other hand, studies in highly social insects, such as honey bees, have revealed how social context can shape very plastic life-history traits, for example flexible aging dynamics in the helper caste (workers). It is, however, not understood how food perception and stress resilience are connected in honey bee workers with different social task behaviors and aging dynamics. To explore this linkage, we tested if starvation resilience, which normally declines with age, depends on food responsiveness in honey bees. We studied two typically non-senesced groups of worker bees with different social task behaviors: mature nurses (caregivers) and mature foragers (food collectors). In addition, we included a group of old foragers for which functional senescence is well-established. Bees were individually scored for their food perception by measuring the gustatory response to different sucrose concentrations. Subsequently, individuals were tested for survival under starvation stress. We found that starvation stress resilience, but not gustatory responsiveness differed between workers with different social task behaviors (mature nurses vs. mature foragers). In addition starvation stress resilience differed between foragers with different aging progressions (mature foragers vs. old foragers). Control experiments confirmed that differences in starvation resilience between mature nurses and mature foragers were robust against changing experimental conditions, such as water provision and activity. For all worker groups we established that individuals with low gustatory responsiveness were more resilient to starvation stress. Finally, for the group of rapidly aging foragers we found that low food responsiveness was linked to a delayed age-related decline in starvation resilience. Our study highlights associations between

  2. Stuck in default mode: inefficient cross-frequency synchronization may lead to age-related short-term memory decline.

    PubMed

    Pinal, Diego; Zurrón, Montserrat; Díaz, Fernando; Sauseng, Paul

    2015-04-01

    Aging-related decline in short-term memory capacity seems to be caused by deficient balancing of task-related and resting state brain networks activity; however, the exact neural mechanism underlying this deficit remains elusive. Here, we studied brain oscillatory activity in healthy young and old adults during visual information maintenance in a delayed match-to-sample task. Particular emphasis was on long range phase:amplitude coupling of frontal alpha (8-12 Hz) and posterior fast oscillatory activity (>30 Hz). It is argued that through posterior fast oscillatory activity nesting into the excitatory or the inhibitory phase of frontal alpha wave, long-range networks can be efficiently coupled or decoupled, respectively. On the basis of this mechanism, we show that healthy, elderly participants exhibit a lack of synchronization in task-relevant networks while maintaining synchronized regions of the resting state network. Lacking disconnection of this resting state network is predictive of aging-related short-term memory decline. These results support the idea of inefficient orchestration of competing brain networks in the aging human brain and identify the neural mechanism responsible for this control breakdown.

  3. Grape Powder Improves Age-Related Decline in Mitochondrial and Kidney Functions in Fischer 344 Rats

    PubMed Central

    Ali, Quaisar

    2016-01-01

    We examined the effects and mechanism of grape powder- (GP-) mediated improvement, if any, on aging kidney function. Adult (3-month) and aged (21-month) Fischer 344 rats were treated without (controls) and with GP (1.5% in drinking water) and kidney parameters were measured. Control aged rats showed higher levels of proteinuria and urinary kidney injury molecule-1 (KIM-1), which decreased with GP treatment in these rats. Renal protein carbonyls (protein oxidation) and gp91phox-NADPH oxidase levels were high in control aged rats, suggesting oxidative stress burden in these rats. GP treatment in aged rats restored these parameters to the levels of adult rats. Moreover, glomerular filtration rate and sodium excretion were low in control aged rats suggesting compromised kidney function, which improved with GP treatment in aged rats. Interestingly, low renal mitochondrial respiration and ATP levels in control aged rats were associated with reduced levels of mitochondrial biogenesis marker MtTFA. Also, Nrf2 proteins levels were reduced in control aged rats. GP treatment increased levels of MtTFA and Nrf2 in aged rats. These results suggest that GP by potentially regulating Nrf2 improves aging mitochondrial and kidney functions. PMID:27528887

  4. Gender differences in age-related decline in glomerular filtration rates in healthy people and chronic kidney disease patients

    PubMed Central

    2010-01-01

    Background Since men with chronic kidney disease (CKD) progress faster than women, an accurate assessment of CKD progression rates should be based on gender differences in age-related decline of glomerular filtration rate (GFR) in healthy individuals. Methods A Chinese sample population from a stratified, multistage, and clustered CKD screening study was classified into healthy, at-risk, and CKD groups. The gender differences in estimated GFR (eGFR) and age-related eGFR decline were calculated for each group after controlling for blood pressure, fasting glucose levels, serum lipids levels, education level, and smoking status. After referencing to the healthy group, gender-specific multivariate-adjusted rates of decline in eGFR and differences in the rates of decline were calculated for both CKD and at-risk groups. Results The healthy, at-risk, and CKD groups consisted of 4569, 7434, and 1573 people, respectively. In all the 3 groups, the multivariate-adjusted eGFRs in men were lower than the corresponding eGFRs in women. In addition, in the healthy and at-risk groups, the rates of decline in eGFR in men were lower than the corresponding rates of decline in women (healthy group: 0.51 mL·min-1·1.73 m-2·yr-1 vs. 0.74 mL·min-1·1.73 m-2·yr-1 and at-risk group: 0.60 mL·min-1·1.73 m-2·yr-1 vs. 0.73 mL·min-1·1.73 m-2·yr-1). However, in the CKD group, the rates of decline in eGFR in men were similar to those in women (0.96 mL·min-1·1.73 m-2·yr-1 vs. 0.91 mL·min-1·1.73 m-2·yr-1). However, after referencing to the healthy group, the rates of decline in eGFR in men in the at-risk and CKD groups were greater faster than the corresponding rates in women (at-risk group: 0.10 mL·min-1·1.73 m-2·yr-1 vs. -0.03 mL·min-1·1.73 m-2·yr-1 and CKD group: 0.44 mL·min-1·1.73 m-2·yr-1 vs. 0.15 mL·min-1·1.73 m-2·yr-1). Conclusion To accurately assess gender differences in CKD progression rates, gender differences in age-related decline in GFR should be considered

  5. Neural correlates of age-related visual search decline: a combined ERP and sLORETA study.

    PubMed

    Lorenzo-López, Laura; Amenedo, Elena; Pascual-Marqui, Roberto D; Cadaveira, Fernando

    2008-06-01

    Differences in the neural systems underlying visual search processes for young (n=17, mean age 19.6+/-1.9) and older (n=22, mean age 68.5+/-6) subjects were investigated combining the Event-Related Potential (ERP) technique with standardized Low-Resolution brain Electromagnetic Tomography (sLORETA) analyses. Behavioral results showed an increase in mean reaction times (RTs) and a reduction in hit rates with age. The ERPs were significantly different between young and older subjects at the P3 component, showing longer latencies and lower amplitudes in older subjects. These ERP results suggest an age-related decline in the intensity and speed of visual processing during visual search that imply a reduction in attentional resources with normal aging. The sLORETA data revealed a significantly reduced neural differentiation in older subjects, who recruited bilateral prefrontal regions in a nonselective manner for the different search arrays. Finally, sLORETA between-group comparisons revealed that relative to young subjects, older subjects showed significantly reduced activity in anterior cingulate cortex as well as in numerous limbic and occipitotemporal regions contributing to visual search processes. These findings provide evidence that the neural circuit supporting this cognitive process is vulnerable to normal aging. All these attentional factors could contribute to poorer performance of older compared to young subjects in visual search tasks.

  6. Rapid iterative negative geotaxis (RING): a new method for assessing age-related locomotor decline in Drosophila.

    PubMed

    Gargano, Julia Warner; Martin, Ian; Bhandari, Poonam; Grotewiel, Michael S

    2005-05-01

    Age-related behavioral declines are common manifestations of aging in animals. Negative geotaxis, an innate escape response during which flies ascend the wall of a cylinder after being tapped to its bottom, is one of the behaviors that senesces in Drosophila. Many laboratories, including ours, have used a variety of negative geotaxis assays based on the performance of single flies. To circumvent limitations of single-fly assays, we developed a new method for assessing negative geotaxis called rapid iterative negative geotaxis (RING). In RING assays, digital photography is used to document negative geotaxis in multiple groups of animals simultaneously. We show that performance in RING assays is not influenced by the density of flies being tested, the time of day, or repeated testing. We used the RING assay to demonstrate that negative geotaxis declines with the age of animals as previously shown in single fly studies and that senescence of negative geotaxis is sensitive to genetic background. Finally, we used RING assays to show that long-lived Indy and chico mutants exhibit delayed senescence of negative geotaxis. Our results demonstrate that RING is a powerful method for assessing negative geotaxis that should facilitate the search for manipulations that influence behavioral aging in Drosophila.

  7. Functional decline in old age

    PubMed Central

    Hébert, R

    1997-01-01

    Functional decline is a common condition, occurring each year in nearly 12% of Canadians 75 years of age and older. The model of functional health proposed by the World Health Organization (WHO) represents a useful theoretical framework and is the basis for the SMAF (Système de measure de l'autonomie fonctionelle or Functional Autonomy Measurement System), an instrument that measures functional autonomy. The functional decline syndrome, in which functional autonomy is diminished or lost, may present as an acute condition, i.e., a medical emergency for which the patient must be admitted to a geriatric assessment unit. The subacute form is a more insidious condition in which the patient requires comprehensive assessment and a rehabilitation program. A preventive approach based on screening of those at risk and early intervention should prevent or delay the appearance of functional decline or diminish its consequences. Effective strategies for the prevention of or rehabilitation from functional decline will help reduce the incidence of disabilities and the period of dependence near the end of life. These strategies are absolute prerequisites for controlling sociohealth expenses and, most importantly, for allowing people to live independently in old age. PMID:9347774

  8. Investigation of age-related decline of microfibril-associated glycoprotein-1 in human skin through immunohistochemistry study.

    PubMed

    Zheng, Qian; Chen, Siming; Chen, Ying; Lyga, John; Wyborski, Russell; Santhanam, Uma

    2013-01-01

    During aging, the reduction of elastic and collagen fibers in dermis can lead to skin atrophy, fragility, and aged appearance, such as increased facial wrinkling and sagging. Microfibril-associated glycoprotein-1 (MAGP-1) is an extracellular matrix protein critical for elastic fiber assembly. It integrates and stabilizes the microfibril and elastin matrix network that helps the skin to endure mechanical stretch and recoil. However, the observation of MAGP-1 during skin aging and its function in the dermis has not been established. To better understand age-related changes in the dermis, we investigated MAGP-1 during skin aging and photoaging, using a combination of in vitro and in vivo studies. Gene expression by microarray was performed using human skin biopsies from young and aged female donors. In addition, immunofluorescence analysis on the MAGP-1 protein was performed in dermal fibroblast cultures and in human skin biopsies. Specific antibodies against MAGP-1 and fibrillin-1 were used to examine protein expression and extracellular matrix structure in the dermis via biopsies from donors of multiple age groups. A reduction of the MAGP-1 gene and protein levels were observed in human skin with increasing age and photoexposure, indicating a loss of the functional MAGP-1 fiber network and a lack of structural support in the dermis. Loss of MAGP-1 around the hair follicle/pore areas was also observed, suggesting a possible correlation between MAGP-1 loss and enlarged pores in aged skin. Our findings demonstrate that a critical "pre-elasticity" component, MAGP-1, declines with aging and photoaging. Such changes may contribute to age-related loss of dermal integrity and perifollicular structural support, which may lead to skin fragility, sagging, and enlarged pores.

  9. 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…

  10. 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.

  11. Common SIRT1 variants modify the effect of abdominal adipose tissue on aging-related lung function decline.

    PubMed

    Curjuric, Ivan; Imboden, Medea; Bridevaux, Pierre-Olivier; Gerbase, Margaret W; Haun, Margot; Keidel, Dirk; Kumar, Ashish; Pons, Marco; Rochat, Thierry; Schikowski, Tamara; Schindler, Christian; von Eckardstein, Arnold; Kronenberg, Florian; Probst-Hensch, Nicole M

    2016-06-01

    Lung function is an independent predictor of mortality and serves as an aging marker in never smokers. The protein sirtuin-1 of gene SIRT1 has profound anti-inflammatory effects and regulates metabolic pathways. Its suggested longevity effects on lower organisms remain poorly studied in humans. In 1132 never smokers of the population-based SAPALDIA cohort, we investigated associations between single nucleotide polymorphisms (SNPs; rs730821, rs10997868, rs10823116) of SIRT1 and aging-related lung function decline over 11 years in terms of change in forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, and forced expiratory flow between 25 and 75 % of FVC (FEF25-75) using multiple linear regression models. Interactions between the SIRT1 SNPs and adiposity parameters (body mass index (BMI), its change and weight gain) were tested by including multiplicative interaction terms into the models. SIRT1 polymorphisms exhibited no main effects, but modified the association between obesity measures and FEV1/FVC and FEF25-75 decline (p = 0.009-0.046). Per risk allele, FEV1/FVC decline was accelerated up to -0.5 % (95 % CI -1.0 to 0 %) and -0.7 % (-1.3 to -0.2 %) over interquartile range increases in BMI (2.4 kg/m(2)) or weight (6.5 kg), respectively. For FEF25-75 decline, corresponding estimates were -57 mL/s (-117 to 4 mL/s) and -76 mL/s (-1429 to -9 mL/s). Interactions were not present in participants with genetically lowered C-reactive protein concentrations. Genetic variation in SIRT1 might therefore affect lung function and human longevity by modifying subclinical inflammation arising from abdominal adipose tissue.

  12. Age-related hearing loss: prevention of threshold declines, cell loss and apoptosis in spiral ganglion neurons

    PubMed Central

    Zhu, Xiaoxia; Walton, Joseph P.

    2016-01-01

    Age-related hearing loss (ARHL) -presbycusis - is the most prevalent neurodegenerative disease and number one communication disorder of our aged population; and affects hundreds of millions of people worldwide. Its prevalence is close to that of cardiovascular disease and arthritis, and can be a precursor to dementia. The auditory perceptual dysfunction is well understood, but knowledge of the biological bases of ARHL is still somewhat lacking. Surprisingly, there are no FDA-approved drugs for treatment. Based on our previous studies of human subjects, where we discovered relations between serum aldosterone levels and the severity of ARHL, we treated middle age mice with aldosterone, which normally declines with age in all mammals. We found that hearing thresholds and suprathreshold responses significantly improved in the aldosterone-treated mice compared to the non-treatment group. In terms of cellular and molecular mechanisms underlying this therapeutic effect, additional experiments revealed that spiral ganglion cell survival was significantly improved, mineralocorticoid receptors were upregulated via post-translational protein modifications, and age-related intrinsic and extrinsic apoptotic pathways were blocked by the aldosterone therapy. Taken together, these novel findings pave the way for translational drug development towards the first medication to prevent the progression of ARHL. PMID:27667674

  13. Age-related hearing loss: prevention of threshold declines, cell loss and apoptosis in spiral ganglion neurons.

    PubMed

    Frisina, Robert D; Ding, Bo; Zhu, Xiaoxia; Walton, Joseph P

    2016-09-23

    Age-related hearing loss (ARHL) -presbycusis - is the most prevalent neurodegenerative disease and number one communication disorder of our aged population; and affects hundreds of millions of people worldwide. Its prevalence is close to that of cardiovascular disease and arthritis, and can be a precursor to dementia. The auditory perceptual dysfunction is well understood, but knowledge of the biological bases of ARHL is still somewhat lacking. Surprisingly, there are no FDA-approved drugs for treatment. Based on our previous studies of human subjects, where we discovered relations between serum aldosterone levels and the severity of ARHL, we treated middle age mice with aldosterone, which normally declines with age in all mammals. We found that hearing thresholds and suprathreshold responses significantly improved in the aldosterone-treated mice compared to the non-treatment group. In terms of cellular and molecular mechanisms underlying this therapeutic effect, additional experiments revealed that spiral ganglion cell survival was significantly improved, mineralocorticoid receptors were upregulated via post-translational protein modifications, and age-related intrinsic and extrinsic apoptotic pathways were blocked by the aldosterone therapy. Taken together, these novel findings pave the way for translational drug development towards the first medication to prevent the progression of ARHL.

  14. Rate of cognitive decline in relation to sex after 60 years-of-age: a systematic review.

    PubMed

    Ferreira, Leandro; Ferreira Santos-Galduróz, Ruth; Ferri, Cleusa Pinheiro; Fernandes Galduróz, José Carlos

    2014-01-01

    Some studies have shown differences in specific cognitive ability domains between the sexes at 60 years-of-age. However is important to analyze whether the rate of cognitive decline is also similar between the sexes after this age. The present study examined previously published literature to investigate whether cognitive decline is distinct between men and women after the age of 60 years. A systematic review was carried out with the PubMed, LILACS and PsycINFO databases (2001-2011) using the following search terms: aging, aged, cognitive function, mild cognitive impairment, mental health and cognition. We analyzed longitudinal research that used neuropsychological tests for evaluating cognitive function, showed results separated by sex and that excluded participants with dementia. Elderly women showed better performance in tests of episodic memory, whereas elderly men had a better visuospatial ability. Only one study detected distinct rates of cognitive decline in specific tests between the sexes. Despite differences observed in some domains, most of the studies showed that this rate is similar between the sexes until the age of 80 years. It is unclear whether sex influences the rate of cognitive decline after the age of 80 years. The present review observed that sex does not determine the rate of cognitive decline between 60 and 80 years-of-age. The contextual and cultural factors that involve men and women might determine a distinct decline between them, rather than sex alone.

  15. Neural stem cell deforestation as the main force driving the age-related decline in adult hippocampal neurogenesis.

    PubMed

    Encinas, Juan M; Sierra, Amanda

    2012-02-14

    Newborn neurons derived from radial glia-like stem cells located in the dentate gyrus integrate into the adult hippocampal circuitry and participate in memory formation, spatial learning, pattern separation, fear conditioning, and anxiety. This process takes place throughout the life span of mammals, including humans; however, it follows a sharp declining curve. New neurons are generated abundantly during youth but very scarcely in the aged brain. The absolute number of newly generated neurons, or neurogenic output, is determined at different levels along the neurogenic cascade: the activation of quiescent stem cells; the mitotic potential of proliferating precursors; and the survival of neuronal fate-committed precursors. A continuous depletion of the hippocampal neural stem cell pool has been recently proposed as the main force underlying the age-related decline of neurogenesis, in contrast to the previous view of population of neural stem cells whose number remains constant but loses its ability to bear fruit. Nevertheless, the diminished neurogenic output may be reflecting other phenomena such as decreased mitotic capability of proliferating progenitors, decreased survival or changes in differentiation. We describe herein the most important events in determining the amount of neurogenesis in the dentate gyrus and examine the literature to understand the effects of age throughout the cascade.

  16. Visual discrimination in noise: behavioural correlates of age-related cortical decline.

    PubMed

    Arena, Amanda; Hutchinson, Claire V; Shimozaki, Steven S; Long, Mike D

    2013-04-15

    Neurophysiological evidence has consistently shown that, compared to younger animals, single neurons in aged mammalian visual cortex exhibit reduced selectivity to stimulus direction and orientation. It has been suggested that this may be due, in part, to increased internal noise in the aged visual system. This study measured contrast thresholds for judging the motion direction (left vs. right) and spatial orientation (vertical vs. horizontal) of sinusoidal gratings presented alone and with additive noise in young (20-29 years) and older (65-79 years) adults. Compared to their young counterparts, older adults demonstrated reduced sensitivity to direction and orientation when no noise was present. However, when gratings were presented in conjunction with additive noise, older adults required a greater increase in external noise to elicit a corresponding reduction in sensitivity. Subsequent analysis assessing equivalent noise and sampling efficiency attributed performance differences to an increase in equivalent noise with age.

  17. Initiation of calorie restriction in middle-aged male rats attenuates aging-related motoric decline and bradykinesia without increased striatal dopamine

    PubMed Central

    Salvatore, Michael F.; Terrebonne, Jennifer; Fields, Victoria; Nodurft, Danielle; Runfalo, Cori; Latimer, Brian; Ingram, Donald K.

    2015-01-01

    Aging-related bradykinesia affects ~15% of those reaching age 65 and 50% of those reaching their 80s. Given this high risk and lack of pharmacological therapeutics, non-invasive lifestyle strategies should be identified to diminish its risk and identify the neurobiological targets to reduce aging-related bradykinesia. Early-life, long-term calorie restriction (CR) attenuates aging-related bradykinesia in rodents. Here, we addressed whether CR initiation at middle age could attenuate aging-related bradykinesia and motoric decline measured as rotarod performance. A 30% CR regimen was implemented for 6 months duration in 12-month old male Brown-Norway Fischer 344 F1 hybrid rats after establishing individual baseline locomotor activities. Locomotor capacity was assessed every 6 weeks thereafter. The ad libitum (AL) group exhibited predictably decreased locomotor activity, except movement speed, out to 18 months of age. In contrast, in the CR group, movement number and horizontal activity did not decrease during the 6-month trial and aging-related decline in rotarod performance was attenuated. The response to CR was influenced by baseline locomotor activity. The lower the locomotor activity level at baseline, the greater the response to CR. Rats in the lower 50th percentile surpassed their baseline level of activity, whereas rats in the top 50th percentile decreased at 6 weeks and then returned to baseline by 12 weeks of CR. We hypothesized that nigrostriatal dopamine tissue content would be greater in the CR group and observed a modest increase only in substantia nigra with no group differences in striatum, nucleus accumbens, or ventral tegmental area. These results indicate initiation of CR at middle age may reduce aging-related bradykinesia and, furthermore, subjects with below average locomotor activity may increase baseline activity. Sustaining nigral DA neurotransmission may be one component of preserving locomotor capabilities during aging. PMID:26610387

  18. Age-related decline in prostacyclin synthesis by human aortic endothelial cells. Qualitative and quantitative analysis.

    PubMed Central

    Tokunaga, O.; Yamada, T.; Fan, J. L.; Watanabe, T.

    1991-01-01

    To investigate the functional alteration of human aortic endothelial cells with aging, prostacyclin synthesis was qualitatively and quantitatively examined. The endothelial cells of human aortas and umbilical veins or inferior vena cavae were immunohistochemically examined and found positive for prostacyclin, but the intensity of aortic endothelial cells from older subjects was low. In addition to the endothelial cells, smooth muscle cells in the thickened intima, not the media, of the aorta were also immunoreactive. Endothelial cells were successfully cultured from human aortas obtained from infants through aged subjects and were subdivided into three groups: young, middle, and old. Prostacyclin synthesis by endothelial cells from all types of blood vessels was extremely great at the primary culture, but decreased abruptly in the following subcultures. Among the aortic endothelial cells, the young group synthesized the largest amount of prostacyclin in a conventional culture condition, with synthesis progressively decreasing in the older groups. The in vitro prostacyclin biosynthesis was supported by the qualitative analysis on the tissue sections. These results indicate that prostacyclin synthesis of the aortic endothelial cells decreases with age, but intimal smooth muscle cells potentially have a back-up mechanism and substitute this synthesis to some extent. The decreased synthesis of prostacyclin with age may play an important role in the development and advancement of thrombosis and atherosclerosis. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:1707240

  19. Age-related decline in thermal adaptation capacities: an evoked potentials study.

    PubMed

    Kemp, Jennifer; Després, Olivier; Pebayle, Thierry; Dufour, André

    2014-06-01

    Aging is associated with changes in thermosensitivity and decreases in the functionality of the autonomic thermoregulation. The underlying mechanisms are, however, not fully understood. Elderly subjects may undergo functional changes in the integration process of the thermal sensory system, especially in their thermal adaptation capacities. To verify this hypothesis, we compared thermal evoked responses in younger and older subjects exposed to thermoneutral (27 °C) and warm (30 °C) environments. In the warm environment, the amplitudes of thermal evoked potentials (EPs) were significantly lower in older than in younger subjects, whereas in the thermoneutral environment, the EP amplitudes were similar in both groups. These findings suggest that thermal adaptation capacities are reduced in elderly individuals, due to a dysfunction of C-fibers with aging, particularly expressed by lowered adaptation capacities to temperature variations.

  20. Is It Possible to Delay or Prevent Age-Related Cognitive Decline?

    PubMed Central

    2016-01-01

    Already in the 90s, Khachaturian stated that postponing dementia onset by five years would decrease the prevalence of the late onset dementia by 50%. After two decades of lack of success in dementia drug discovery and development, and knowing that worldwide, currently 36 million patients have been diagnosed with Alzheimer's disease, a number that will double by 2030 and triple by 2050, the World Health Organization and the Alzheimer's Disease International declared that prevention of cognitive decline was a 'public health priority.' Numerous longitudinal studies and meta-analyses were conducted to analyze the risk and protective factors for dementia. Among the 93 identified risk factors, seven major modifiable ones should be considered: low education, sedentary lifestyle, midlife obesity, midlife smoking, hypertension, diabetes, and midlife depression. Three other important modifiable risk factors should also be added to this list: midlife hypercholesterolemia, late life atrial fibrillation, and chronic kidney disease. After their identification, numerous authors attempted to establish dementia risk scores; however, the proposed values were not convincing. Identifying the possible interventions, able to either postpone or delay dementia has been an important challenge. Observational studies focused on a single life-style intervention increased the global optimism concerning these possibilities. However, a recent extensive literature review of the randomized control trials (RCTs) conducted before 2014 yielded negative results. The first results of RCTs of multimodal interventions (Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability, Multidomain Alzheimer Prevention Study, and Prediva) brought more optimism. Lastly, interventions targeting compounds of beta amyloid started in 2012 and no results have yet been published. PMID:27688858

  1. Women's intentions to use fertility preservation to prevent age-related fertility decline.

    PubMed

    Ter Keurst, Anne; Boivin, Jacky; Gameiro, Sofia

    2016-01-01

    The optimal age to cryopreserve oocytes for later use is before 36 years. Current users are on average 38 years old. In this cross-sectional study an online survey was constructed about the factors associated with the intentions of childless women aged 28-35 years to use fertility preservation (FP). Questions were derived from the Theory of Planned Behaviour (attitudes and subjective norms regarding FP and perceived behaviour control to do FP) and the Health Belief Model (perceived susceptibility of infertility, perceived severity of childlessness, barriers and benefits of FP and cue to use FP). Also addressed were parenthood goals, fertility knowledge and intentions to use FP within 2 years. The data were analysed using structural equation modelling. The Health Belief Model showed a good fit to the data (χ(2) [14, n = 257] = 13.63, P = 0.477; CFI = 1.000: RMSEA = 00, 90% CI [0.00-0.06]). Higher intentions to use FP were associated with feeling susceptible to infertility, considering FP useful to achieve parenthood, perceiving the implications of infertility as severe, expecting to have children at a later age and having fewer ethical concerns. This suggests an increase of fertility awareness is necessary for the optimal use of FP.

  2. An olive oil-derived antioxidant mixture ameliorates the age-related decline of skeletal muscle function.

    PubMed

    Pierno, Sabata; Tricarico, Domenico; Liantonio, Antonella; Mele, Antonietta; Digennaro, Claudio; Rolland, Jean-François; Bianco, Gianpatrizio; Villanova, Luciano; Merendino, Alessandro; Camerino, Giulia Maria; De Luca, Annamaria; Desaphy, Jean-François; Camerino, Diana Conte

    2014-02-01

    Age-related skeletal muscle decline is characterized by the modification of sarcolemma ion channels important to sustain fiber excitability and to prevent metabolic dysfunction. Also, calcium homeostasis and contractile function are impaired. In the aim to understand whether these modifications are related to oxidative damage and can be reverted by antioxidant treatment, we examined the effects of in vivo treatment with an waste water polyphenolic mixture (LACHI MIX HT) supplied by LACHIFARMA S.r.l. Italy containing hydroxytirosol (HT), gallic acid, and homovanillic acid on the skeletal muscles of 27-month-old rats. After 6-week treatment, we found an improvement of chloride ClC-1 channel conductance, pivotal for membrane electrical stability, and of ATP-dependent potassium channel activity, important in coupling excitability with fiber metabolism. Both of them were analyzed using electrophysiological techniques. The treatment also restored the resting cytosolic calcium concentration, the sarcoplasmic reticulum calcium release, and the mechanical threshold for contraction, an index of excitation-contraction coupling mechanism. Muscle weight and blood creatine kinase levels were preserved in LACHI MIX HT-treated aged rats. The antioxidant activity of LACHI MIX HT was confirmed by the reduction of malondialdehyde levels in the brain of the LACHI MIX HT-treated aged rats. In comparison, the administration of purified HT was less effective on all the parameters studied. Although muscle function was not completely recovered, the present study provides evidence of the beneficial effects of LACHI MIX HT, a natural compound, to ameliorate skeletal muscle functional decline due to aging-associated oxidative stress.

  3. Accelerated age-related olfactory decline among type 1 Usher patients

    PubMed Central

    Ribeiro, João Carlos; Oliveiros, Bárbara; Pereira, Paulo; António, Natália; Hummel, Thomas; Paiva, António; Silva, Eduardo D.

    2016-01-01

    Usher Syndrome (USH) is a rare disease with hearing loss, retinitis pigmentosa and, sometimes, vestibular dysfunction. A phenotype heterogeneity is reported. Recent evidence indicates that USH is likely to belong to an emerging class of sensory ciliopathies. Olfaction has recently been implicated in ciliopathies, but the scarce literature about olfaction in USH show conflicting results. We aim to evaluate olfactory impairment as a possible clinical manifestation of USH. Prospective clinical study that included 65 patients with USH and 65 normal age-gender-smoking-habits pair matched subjects. A cross culturally validated version of the Sniffin’ Sticks olfaction test was used. Young patients with USH have significantly better olfactory scores than healthy controls. We observe that USH type 1 have a faster ageing olfactory decrease than what happens in healthy subjects, leading to significantly lower olfactory scores in older USH1 patients. Moreover, USH type 1 patients showed significantly higher olfactory scores than USH type 2, what can help distinguishing them. Olfaction represents an attractive tool for USH type classification and pre diagnostic screening due to the low cost and non-invasive nature of the testing. Olfactory dysfunction should be considered among the spectrum of clinical manifestations of Usher syndrome. PMID:27329700

  4. 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

    2014-10-17

    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.

  5. Are Delta-Aminolevulinate Dehydratase Inhibition and Metal Concentrations Additional Factors for the Age-Related Cognitive Decline?

    PubMed Central

    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.; Ávila, 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. Time-restricted feeding attenuates age-related cardiac decline in Drosophila

    PubMed Central

    Gill, Shubhroz; Le, Hiep D.; Melkani, Girish C.; Panda, Satchidananda

    2015-01-01

    Summary Circadian clocks orchestrate periods of rest or activity and feeding or fasting over the course of a 24 h day and maintain homeostasis. To assess whether a consolidated 24 h cycle of feeding and fasting can sustain health, we explored the effect of time-restricted feeding (TRF; food access limited to daytime 12 h every day) on neural, peripheral and cardiovascular physiology in Drosophila melanogaster. We detected improved sleep, prevention of body weight gain and deceleration of cardiac aging under TRF, even when caloric intake and expenditure were unchanged. We used temporal gene expression profiling and validation through classical genetics to identify the TCP-1 Ring Complex (TRiC) chaperonin, the mitochondrial electron transport chain complexes and the circadian clock as pathways mediating the benefits of TRF. PMID:25766238

  7. 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

  8. 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.

  9. 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

  10. 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.

  11. Age-Related Decline of Neutrophilic Inflammation Is Associated with Better Postoperative Prognosis in Non-eosinophilic Nasal Polyps

    PubMed Central

    Kim, Dae Woo; Kim, Dong-Kyu; Jo, Ara; Jin, Hong Ryul; Eun, Kyoung Mi; Mo, Ji-Hun; Cho, Seong H.

    2016-01-01

    Background Innate and adaptive immune responses change with increasing age and affect the course of diseases. Previous study investigated immunologic alteration in Western nasal polyps (NP) which is mostly eosinophilic. However, there are no reports regarding age-related immune changes of non-eosinophilic NP (NE-NP) which is a predominant subtype in Asian population. Methods A total of 153 subjects, including 20 with control, 63 with chronic rhinosinusitis (CRS) without NP (CRSsNP), and 70 with CRS with NP were enrolled. Age-related changes in computed tomography (CT), cytokines and clinical information were investigated. Tissue samples were analyzed for protein levels of IL-5, IL-17A, IL-23, interferon (IFN)-γ, CCL-11, and CXCL-8, using Luminex immunoassay and for mRNA expression levels of interleukin (IL)-5, IL-17A, IL-23p19, IFN-γ, CCL-11, CXCL-1, CXCL-2, CXCL-8, and CXCR2 by quantitative RT-PCR. Immunohistochemistry (IHC) was performed for the number of inflammatory cells. Results We observed that Lund-Mackay CT scores decreased with age in NE-NP. The number of human neutrophil elastase-positive cells and myeloperoxidase gene expression decreased in older patients with NE-NP, but not in control subjects, CRSsNP, and E-NP. Neutrophil-associated cytokines including IL-17A and IL-23, were negatively correlated with age in NE-NP at the protein and mRNA levels. Additionally, the expression of CXCR2, a receptor for CXCL-1 and CXCL-2, was decreased with age in NE-NP. However, there were no age-related changes in blood neutrophil count, and neutrophil-recruiting chemokines such as CXCL-1, CXCL-2, and CXCL-8. Elderly NE-NP patients showed better endoscopic scores at 12 months after surgery compared with the non-elderly. Conclusion Age-related decline in neutrophil inflammation may favorably affect postoperative results in elderly patients with NE-NP. PMID:26849431

  12. 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.

  13. Age-related decline in Kv3.1b expression in the mouse auditory brainstem correlates with functional deficits in the medial olivocochlear efferent system.

    PubMed

    Zettel, Martha L; Zhu, Xiaoxia; O'Neill, William E; Frisina, Robert D

    2007-06-01

    Kv3.1b channel protein is widely distributed in the mammalian auditory brainstem, but studies have focused mainly on regions critical for temporal processing, including the medial nucleus of the trapezoid body (MNTB) and anteroventral cochlear nucleus (AVCN). Because temporal processing declines with age, this study was undertaken to determine if the expression of Kv3.1b likewise declines, and if changes are specific to these nuclei. Immunocytochemistry using an anti-Kv3.1b antibody was performed, and the relative optical density of cells and neuropil was determined from CBA/CaJ mice of four age groups. Declines in expression in AVCN, MNTB, and lateral superior olive (35, 26, and 23%) were found, but changes were limited to neuropil. Interestingly, cellular optical density declines were found in superior paraolivary nucleus, ventral nucleus of the trapezoid body, and lateral nucleus of the trapezoid body (24, 29, and 26%), which comprise the medial olivocochlear (MOC) feedback system. All declines occurred by middle age (15 months old). No age-related changes were found in the remaining regions of cochlear nucleus or in the inferior colliculus. Contralateral suppression of distortion-product otoacoustic emission amplitudes of age-matched littermates also declined by middle age, suggesting a correlation between Kv3.1 expression and MOC function. In search of more direct evidence for such a correlation, Kv3.1b knockout mice were examined. Knockouts show poor MOC function as compared to +/+ and +/- genotypes. Thus, Kv3.1b expression declines in MOC neurons by middle age, and these changes appear to correlate with functional declines in efferent activity in both middle-aged CBA mice and Kv3.1b knockout mice.

  14. 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…

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

    PubMed

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

    2014-04-01

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

  16. Early-life infection is a vulnerability factor for aging-related glial alterations and cognitive decline.

    PubMed

    Bilbo, Staci D

    2010-07-01

    There is significant individual variability in cognitive decline during aging, suggesting the existence of "vulnerability factors" for eventual deficits. Neuroinflammation may be one such factor; increased glial reactivity is a common outcome of aging, which in turn is associated with numerous neurodegenerative conditions. Early-life infection leads to cognitive impairment in conjunction with an inflammatory challenge in young adulthood, which led us to explore whether it might also accelerate the cognitive decline associated with aging. Rats were treated on postnatal day 4 with PBS or Escherichia coli, and then tested for learning and memory at 2 or 16months of age, using two fear-conditioning tasks (context pre-exposure and ambiguous cue), and a spatial water maze task. Neonatally-infected rats exhibited memory impairments in both the ambiguous cue fear-conditioning task and in the water maze, but only at 16months. There were no differences in anxiety between groups. Neonatally-infected rats also exhibited greater aging-induced increases in glial markers (CD11b and MHCII on microglia, and GFAP on astrocytes), as well as selective changes in NMDA receptor subunit expression within the hippocampus, but not in amygdala or parietal cortex compared to controls. Taken together, these data suggest that early-life infection leads to less successful cognitive aging, which may be linked to changes in glial reactivity.

  17. Greater Age-Related Decline in Markers of Physical, Mental and Cognitive Health among Israeli Older Adults Exposed to Lifetime Cumulative Adversity

    PubMed Central

    Shrira, Amit

    2013-01-01

    Objectives This longitudinal investigation addressed whether and how lifetime cumulative adversity and depressive symptoms moderated age-related decline in markers of physical, mental and cognitive health. Method 1,248 older adults (mean age = 62 at Wave 1) who completed the first two waves of the Israeli component of the Survey of Health, Ageing and Retirement in Europe (SHARE-Israel) reported on exposure to potentially traumatic life events, depressive symptoms, and three outcomes – disability, quality of life and cognitive markers. Results Age was related to greater functional decline in outcome measures across the two waves (i.e., increase in disability and decrease in quality of life and cognitive functioning). This age-related decline became stronger as lifetime adversity increased. A three-way interaction showed that the greatest age-related functional decline in outcome measures was especially salient among those with high level of lifetime adversity and high level of depressive symptoms. Conclusion Lifetime cumulative adversity is associated with a more noticeable process of age-related dysfunction across various markers of health. Although the majority of older adults are resilient to lifetime adversity, prevention and intervention programs should be aimed at mitigating the pronounced senescence observed when adversity accumulated to a large degree, and especially when it is accompanied with high level of distress. PMID:24328416

  18. 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.

  19. Looking for age-related growth decline in natural forests: unexpected biomass patterns from tree rings and simulated mortality

    USGS Publications Warehouse

    Foster, Jane R.; D'Amato, Anthony W.; Bradford, John B.

    2014-01-01

    Forest biomass growth is almost universally assumed to peak early in stand development, near canopy closure, after which it will plateau or decline. The chronosequence and plot remeasurement approaches used to establish the decline pattern suffer from limitations and coarse temporal detail. We combined annual tree ring measurements and mortality models to address two questions: first, how do assumptions about tree growth and mortality influence reconstructions of biomass growth? Second, under what circumstances does biomass production follow the model that peaks early, then declines? We integrated three stochastic mortality models with a census tree-ring data set from eight temperate forest types to reconstruct stand-level biomass increments (in Minnesota, USA). We compared growth patterns among mortality models, forest types and stands. Timing of peak biomass growth varied significantly among mortality models, peaking 20–30 years earlier when mortality was random with respect to tree growth and size, than when mortality favored slow-growing individuals. Random or u-shaped mortality (highest in small or large trees) produced peak growth 25–30 % higher than the surviving tree sample alone. Growth trends for even-aged, monospecific Pinus banksiana or Acer saccharum forests were similar to the early peak and decline expectation. However, we observed continually increasing biomass growth in older, low-productivity forests of Quercus rubra, Fraxinus nigra, and Thuja occidentalis. Tree-ring reconstructions estimated annual changes in live biomass growth and identified more diverse development patterns than previous methods. These detailed, long-term patterns of biomass development are crucial for detecting recent growth responses to global change and modeling future forest dynamics.

  20. Looking for age-related growth decline in natural forests: unexpected biomass patterns from tree rings and simulated mortality.

    PubMed

    Foster, Jane R; D'Amato, Anthony W; Bradford, John B

    2014-05-01

    Forest biomass growth is almost universally assumed to peak early in stand development, near canopy closure, after which it will plateau or decline. The chronosequence and plot remeasurement approaches used to establish the decline pattern suffer from limitations and coarse temporal detail. We combined annual tree ring measurements and mortality models to address two questions: first, how do assumptions about tree growth and mortality influence reconstructions of biomass growth? Second, under what circumstances does biomass production follow the model that peaks early, then declines? We integrated three stochastic mortality models with a census tree-ring data set from eight temperate forest types to reconstruct stand-level biomass increments (in Minnesota, USA). We compared growth patterns among mortality models, forest types and stands. Timing of peak biomass growth varied significantly among mortality models, peaking 20-30 years earlier when mortality was random with respect to tree growth and size, than when mortality favored slow-growing individuals. Random or u-shaped mortality (highest in small or large trees) produced peak growth 25-30% higher than the surviving tree sample alone. Growth trends for even-aged, monospecific Pinus banksiana or Acer saccharum forests were similar to the early peak and decline expectation. However, we observed continually increasing biomass growth in older, low-productivity forests of Quercus rubra, Fraxinus nigra, and Thuja occidentalis. Tree-ring reconstructions estimated annual changes in live biomass growth and identified more diverse development patterns than previous methods. These detailed, long-term patterns of biomass development are crucial for detecting recent growth responses to global change and modeling future forest dynamics.

  1. Age-related declines in thirst and salt appetite responses in male Fischer 344×Brown Norway rats.

    PubMed

    Thunhorst, Robert L; Beltz, Terry; Johnson, Alan Kim

    2014-08-01

    The F344×BN strain is the first generational cross between Fischer 344 (F344) and Brown Norway (BN) rats. The F344×BN strain is widely used in aging studies as it is regarded as a model of "healthy" aging (Sprott, 1991). In the present work, male F344×BN rats aged 4mo (young, n=6) and 20mo (old, n=9) received a series of experimental challenges to body fluid homeostasis to determine their thirst and salt appetite responses. Corresponding urinary responses were measured in some of the studies. Following sodium depletion, old rats ingested less saline solution (0.3M NaCl) than young rats on a body weight basis, but both ages drank enough saline solution to completely repair the accrued sodium deficits. Following intracellular dehydration, old rats drank less water than young rats, again on a body weight basis, and were less able than young rats to drink amounts of water proportionate to the osmotic challenge. Compared with young rats, old rats drank less of both water and saline solution after combined food and fluid restriction, and also were refractory to the stimulatory effects of low doses of captopril on water drinking and sodium ingestion. Age differences in urinary water and sodium excretion could not account for the age differences in accumulated water and sodium balances. These results extend observations of diminished behavioral responses of aging animals to the F344×BN rat strain and support the idea that impairments in behavior contribute more to the waning ability of aging animals to respond to body fluid challenges than do declines in kidney function. In addition, the results suggest that behavioral defense of sodium homeostasis is less diminished with age in the F344×BN strain compared to other strains so far studied.

  2. Age-related decline of autocrine pituitary adenylate cyclase-activating polypeptide impairs angiogenic capacity of rat cerebromicrovascular endothelial cells.

    PubMed

    Banki, Eszter; Sosnowska, Danuta; Tucsek, Zsuzsanna; Gautam, Tripti; Toth, Peter; Tarantini, Stefano; Tamas, Andrea; Helyes, Zsuzsanna; Reglodi, Dora; Sonntag, William E; Csiszar, Anna; Ungvari, Zoltan

    2015-06-01

    Aging impairs angiogenic capacity of cerebromicrovascular endothelial cells (CMVECs) promoting microvascular rarefaction, but the underlying mechanisms remain elusive. PACAP is an evolutionarily conserved neuropeptide secreted by endothelial cells and neurons, which confers important antiaging effects. To test the hypothesis that age-related changes in autocrine PACAP signaling contributes to dysregulation of endothelial angiogenic capacity, primary CMVECs were isolated from 3-month-old (young) and 24-month-old (aged) Fischer 344 x Brown Norway rats. In aged CMVECs, expression of PACAP was decreased, which was associated with impaired capacity to form capillary-like structures, impaired adhesiveness to collagen (assessed using electric cell-substrate impedance sensing [ECIS] technology), and increased apoptosis (caspase3 activity) when compared with young cells. Overexpression of PACAP in aged CMVECs resulted in increased formation of capillary-like structures, whereas it did not affect cell adhesion. Treatment with recombinant PACAP also significantly increased endothelial tube formation and inhibited apoptosis in aged CMVECs. In young CMVECs shRNA knockdown of autocrine PACAP expression significantly impaired tube formation capacity, mimicking the aging phenotype. Cellular and mitochondrial reactive oxygen species production (dihydroethidium and MitoSox fluorescence, respectively) were increased in aged CMVECs and were unaffected by PACAP. Collectively, PACAP exerts proangiogenic effects and age-related dysregulation of autocrine PACAP signaling may contribute to impaired angiogenic capacity of CMVECs in aging.

  3. Age-Related Decline of Autocrine Pituitary Adenylate Cyclase-Activating Polypeptide Impairs Angiogenic Capacity of Rat Cerebromicrovascular Endothelial Cells

    PubMed Central

    Banki, Eszter; Sosnowska, Danuta; Tucsek, Zsuzsanna; Gautam, Tripti; Toth, Peter; Tarantini, Stefano; Tamas, Andrea; Helyes, Zsuzsanna; Reglodi, Dora; Sonntag, William E.; Csiszar, Anna

    2015-01-01

    Aging impairs angiogenic capacity of cerebromicrovascular endothelial cells (CMVECs) promoting microvascular rarefaction, but the underlying mechanisms remain elusive. PACAP is an evolutionarily conserved neuropeptide secreted by endothelial cells and neurons, which confers important antiaging effects. To test the hypothesis that age-related changes in autocrine PACAP signaling contributes to dysregulation of endothelial angiogenic capacity, primary CMVECs were isolated from 3-month-old (young) and 24-month-old (aged) Fischer 344 x Brown Norway rats. In aged CMVECs, expression of PACAP was decreased, which was associated with impaired capacity to form capillary-like structures, impaired adhesiveness to collagen (assessed using electric cell-substrate impedance sensing [ECIS] technology), and increased apoptosis (caspase3 activity) when compared with young cells. Overexpression of PACAP in aged CMVECs resulted in increased formation of capillary-like structures, whereas it did not affect cell adhesion. Treatment with recombinant PACAP also significantly increased endothelial tube formation and inhibited apoptosis in aged CMVECs. In young CMVECs shRNA knockdown of autocrine PACAP expression significantly impaired tube formation capacity, mimicking the aging phenotype. Cellular and mitochondrial reactive oxygen species production (dihydroethidium and MitoSox fluorescence, respectively) were increased in aged CMVECs and were unaffected by PACAP. Collectively, PACAP exerts proangiogenic effects and age-related dysregulation of autocrine PACAP signaling may contribute to impaired angiogenic capacity of CMVECs in aging. PMID:25136000

  4. Rapamycin increases grip strength and attenuates age-related decline in maximal running distance in old low capacity runner rats.

    PubMed

    Xue, Qian-Li; Yang, Huanle; Li, Hui-Fen; Abadir, Peter M; Burks, Tyesha N; Koch, Lauren G; Britton, Steven L; Carlson, Joshua; Chen, Laura; Walston, Jeremy D; Leng, Sean X

    2016-04-01

    Rapamycin is known to extend lifespan. We conducted a randomized placebo-controlled study of enteric rapamycin-treatment to evaluate its effect on physical function in old low capacity runner (LCR) rats, a rat model selected from diverse genetic background for low intrinsic aerobic exercise capacity without genomic manipulation and characterized by increased complex disease risks and aging phenotypes. The study was performed in 12 male and 16 female LCR rats aged 16-22 months at baseline. The treatment group was fed with rapamycin-containing diet pellets at approximately 2.24mg/kg body weight per day and the placebo group with the same diet without rapamycin for six months. Observation was extended for additional 2 months. Physical function measurements include grip strength measured as maximum tensile force using a rat grip strength meter and maximum running distance (MRD) using rat physical treadmill test. The results showed that rapamycin improved grip strength by 13% (p=.036) and 60% (p=.001) from its baseline in female and male rats, respectively. Rapamycin attenuated MRD decline by 66% (p=.001) and 46% (p=.319) in females and males, respectively. These findings provide initial evidence for beneficial effect of rapamycin on physical functioning in an aging rat model of high disease risks with significant implication in humans.

  5. Age-related cognitive decline and associations with sex, education and apolipoprotein E genotype across ethnocultural groups and geographic regions: a collaborative cohort study

    PubMed Central

    Lipnicki, Darren M.; Crawford, John D.; Thalamuthu, Anbupalam; Castro-Costa, Erico; Stephan, Blossom C. M.; Lipton, Richard B.; Katz, Mindy J.; Ritchie, Karen; Scali, Jacqueline; Ancelin, Marie-Laure; Scarmeas, Nikolaos; Yannakoulia, Mary; Dardiotis, Efthimios; Lam, Linda C. W.; Fung, Ada W. T.; Vaccaro, Roberta; Davin, Annalisa; Kim, Ki Woong; Han, Ji Won; Kim, Tae Hui; Cherbuin, Nicolas; Butterworth, Peter; Scazufca, Marcia; Kumagai, Shuzo; Chen, Sanmei; Narazaki, Kenji; Lobo, Antonio; Lopez-Anton, Raúl; Santabárbara, Javier; Sachdev, Perminder S.

    2017-01-01

    Background The prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E ε4 allele (APOE*4) carrier status were associated with decline. Methods and findings We harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42,170 individuals aged 54–105 y (42% male), including 3.3% with dementia at baseline. The studies began between 1989 and 2011, with all but three ongoing, and each had 2–16 assessment waves (median = 3) and a follow-up duration of 2–15 y. We analyzed standardized Mini-Mental State Examination (MMSE) and memory, processing speed, language, and executive functioning test scores using linear mixed models, adjusted for sex and education, and meta-analytic techniques. Performance on all cognitive measures declined with age, with the most rapid rate of change pooled across cohorts a moderate -0.26 standard deviations per decade (SD/decade) (95% confidence interval [CI] [-0.35, -0.16], p < 0.001) for processing speed. Rates of decline accelerated slightly with age, with executive functioning showing the largest additional rate of decline with every further decade of age (-0.07 SD/decade, 95% CI [-0.10, -0.03], p = 0.002). There was a considerable degree of heterogeneity in the associations across cohorts, including a slightly faster decline (p = 0.021) on the MMSE for Asians (-0.20 SD/decade, 95% CI [-0.28, -0.12], p < 0.001) than for whites (-0.09 SD/decade, 95% CI [-0.16, -0.02], p = 0.009). Males declined on the MMSE at a slightly slower rate than females (difference = 0

  6. Central insulin-like growth factor-1 (IGF-1) restores whole-body insulin action in a model of age-related insulin resistance and IGF-1 decline.

    PubMed

    Huffman, Derek M; Farias Quipildor, Gabriela; Mao, Kai; Zhang, Xueying; Wan, Junxiang; Apontes, Pasha; Cohen, Pinchas; Barzilai, Nir

    2016-02-01

    Low insulin-like growth factor-1 (IGF-1) signaling is associated with improved longevity, but is paradoxically linked with several age-related diseases in humans. Insulin-like growth factor-1 has proven to be particularly beneficial to the brain, where it confers protection against features of neuronal and cognitive decline. While aging is characterized by central insulin resistance in the face of hyperinsulinemia, the somatotropic axis markedly declines in older humans. Thus, we hypothesized that increasing IGF-1 in the brain may prove to be a novel therapeutic alternative to overcome central insulin resistance and restore whole-body insulin action in aging. Utilizing hyperinsulinemic-euglycemic clamps, we show that old insulin-resistant rats with age-related declines in IGF-1 level demonstrate markedly improved whole-body insulin action, when treated with central IGF-1, as compared to central vehicle or insulin (P < 0.05). Furthermore, central IGF-1, but not insulin, suppressed hepatic glucose production and increased glucose disposal rates in aging rats (P < 0.05). Taken together, IGF-1 action in the brain and periphery provides a 'balance' between its beneficial and detrimental actions. Therefore, we propose that strategies aimed at 'tipping the balance' of IGF-1 action centrally are the optimal approach to achieve healthy aging and longevity in humans.

  7. Aging, Terminal Decline, and Terminal Drop

    ERIC Educational Resources Information Center

    Palmore, Erdman; Cleveland, William

    1976-01-01

    Data from a 20-year longitudinal study of persons over 60 were analyzed by step-wise multiple regression to test for declines in function with age, for terminal decline (linear relationship to time before death), and for terminal drop (curvilinear relationship to time before death). There were no substantial terminal drop effects. (Author)

  8. 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.

  9. Sex Differences in Age-Related Decline of Urinary Insulin-Like Growth Factor-Binding Protein-3 Levels in Adult Bonobos and Chimpanzees

    PubMed Central

    Behringer, Verena; Wudy, Stefan A.; Blum, Werner F.; Stevens, Jeroen M. G.; Remer, Thomas; Boesch, Christophe; Hohmann, Gottfried

    2016-01-01

    There is increasing interest in the characterization of normative senescence in humans. To assess to what extent aging patterns in humans are unique, comparative data from closely related species, such as non-human primates, can be very useful. Here, we use data from bonobos and chimpanzees, two closely related species that share a common ancestor with humans, to explore physiological markers that are indicative of aging processes. Many studies on aging in humans focus on the somatotropic axis, consisting of growth hormone (GH), insulin-like growth factors (IGFs), and IGF binding proteins (IGFBPs). In humans, IGFBP-3 levels decline steadily with increasing age. We used urinary IGFBP-3 levels as an alternative endocrine marker for IGF-I to identify the temporal pattern known to be related with age-related changes in cell proliferation, growth, and apoptosis. We measured urinary IGFBP-3 levels in samples from 71 bonobos and 102 chimpanzees. Focusing on samples from individuals aged 10 years or older, we found that urinary IGFBP-3 levels decline in both ape species with increasing age. However, in both species, females start with higher urinary IGFBP-3 levels than males, experience a steeper decline with increasing age, and converge with male levels around the age of 30–35 years. Our measurements of urinary IGFBP-3 levels indicate that bonobos and chimpanzees mirror human patterns of age-related decline in IGFBP-3 in older individuals (<10 years) of both sexes. Moreover, such as humans, both ape species show sex-specific differences in IGFBP-3 levels with females having higher levels than males, a result that correlates with sex differences in life expectancy. Using changes in urinary IGFBP-3 levels as a proxy for changes in GH and IGF-I levels that mark age-related changes in cell proliferation, this approach provides an opportunity to investigate trade-offs in life-history strategies in cross-sectional and in longitudinal studies, both in captivity and in

  10. 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

  11. Use it or lose it? SES mitigates age-related decline in a recency/recognition task

    PubMed Central

    Czernochowski, Daniela; Fabiani, Monica; Friedman, David

    2008-01-01

    An important goal of aging research is to determine factors leading to individual differences that might compensate for some of the deleterious effects of aging on cognition. To determine whether socio-economic status (SES) plays a role in mitigating age-related decrements in the recollection of contextual details, we categorized older participants into low- and high-SES groups. Event-related potentials (ERPs) and behavioral data were recorded in a picture memory task involving recency and recognition judgments. Young, old-low and old-high SES groups did not differ in recognition performance. However, on recency judgments, old-low subjects performed at chance, whereas old-high subjects did not differ significantly from young adults. Consistent with their preserved recency performance, a long-duration frontal negativity was significantly larger for recency compared to recognition trials in the ERPs of the old-high SES group only. These data suggest that older adults with higher SES levels can use strategies to compensate for the adverse effects of aging in complex source memory tasks by recruiting additional neural resources apparently not required by the young. PMID:17280741

  12. Age-related loss of muscle mass and bone strength in mice is associated with a decline in physical activity and serum leptin.

    PubMed

    Hamrick, Mark W; Ding, Ke-Hong; Pennington, Catherine; Chao, Yuh J; Wu, Yii-Der; Howard, Boyd; Immel, David; Borlongan, Cesario; McNeil, Paul L; Bollag, Wendy B; Curl, Walton W; Yu, Jack; Isales, Carlos M

    2006-10-01

    The mechanisms underlying age-related loss of muscle and bone tissue are poorly understood but are thought to involve changes in sex hormone status, physical activity, and circulating levels of inflammatory cytokines. This study attempts to develop an animal model useful for evaluating these mechanisms in vivo. Male C57BL/6 mice were included for study at 3, 6, 12, 18, 24, and 29 months of age. Endocortical mineralizing surface, serum leptin, body weight, and percentage of body fat all increased between 6 and 12 months of age as activity level declined. Serum levels of the inflammatory marker IL-6 increased significantly after 12 months of age, following the observed increase in body weight and percent body fat. Hindlimb muscle mass declined significantly between 18 and 24 months of age, both absolutely and relative to total body mass, with a further decline ( approximately 15%) between 24 and 29 months. Loss of muscle mass after 18 months of age was accompanied by a significant increase in bone resorption, as indicated by serum pyridinoline cross-links, and a significant decrease in fat mass, serum leptin, bone strength, bone mineral density, and vertical cage activity. No significant changes in serum testosterone with aging were detected in the mice, as levels were essentially constant between 6 and 29 months. Our data show that mice lose a significant amount of muscle and bone tissue with age, and this loss of musculoskeletal tissue is accompanied by a drop in serum leptin and preceded by a significant decrease in physical activity.

  13. Age-Related Wayfinding Differences in Real Large-Scale Environments: Detrimental Motor Control Effects during Spatial Learning Are Mediated by Executive Decline?

    PubMed Central

    Taillade, Mathieu; Sauzéon, Hélène; Arvind Pala, Prashant; Déjos, Marie; Larrue, Florian; Gross, Christian; N’Kaoua, Bernard

    2013-01-01

    The aim of this study was to evaluate motor control activity (active vs. passive condition) with regards to wayfinding and spatial learning difficulties in large-scale spaces for older adults. We compared virtual reality (VR)-based wayfinding and spatial memory (survey and route knowledge) performances between 30 younger and 30 older adults. A significant effect of age was obtained on the wayfinding performances but not on the spatial memory performances. Specifically, the active condition deteriorated the survey measure in all of the participants and increased the age-related differences in the wayfinding performances. Importantly, the age-related differences in the wayfinding performances, after an active condition, were further mediated by the executive measures. All of the results relative to a detrimental effect of motor activity are discussed in terms of a dual task effect as well as executive decline associated with aging. PMID:23843992

  14. Higher serum cholesterol is associated with intensified age-related neural network decoupling and cognitive decline in early- to mid-life.

    PubMed

    Spielberg, Jeffrey M; Sadeh, Naomi; Leritz, Elizabeth C; McGlinchey, Regina E; Milberg, William P; Hayes, Jasmeet P; Salat, David H

    2017-03-31

    Mounting evidence indicates that serum cholesterol and other risk factors for cardiovascular disease intensify normative trajectories of age-related cognitive decline. However, the neural mechanisms by which this occurs remain largely unknown. To understand the impact of cholesterol on brain networks, we applied graph theory to resting-state fMRI in a large sample of early- to mid-life Veterans (N = 206, Meanage  = 32). A network emerged (centered on the banks of the superior temporal sulcus) that evidenced age-related decoupling (i.e., decreased network connectivity with age), but only in participants with clinically-elevated total cholesterol (≥180 mg/dL). Crucially, decoupling in this network corresponded to greater day-to-day disability and mediated age-related declines in psychomotor speed. Finally, examination of network organization revealed a pattern of age-related dedifferentiation for the banks of the superior temporal sulcus, again present only with higher cholesterol. More specifically, age was related to decreasing within-module communication (indexed by Within-Module Degree Z-Score) and increasing between-module communication (indexed by Participation Coefficient), but only in participants with clinically-elevated cholesterol. Follow-up analyses indicated that all findings were driven by low-density lipoprotein (LDL) levels, rather than high-density lipoprotein (HDL) or triglycerides, which is interesting as LDL levels have been linked to increased risk for cardiovascular disease, whereas HDL levels appear inversely related to such disease. These findings provide novel insight into the deleterious effects of cholesterol on brain health and suggest that cholesterol accelerates the impact of age on neural trajectories by disrupting connectivity in circuits implicated in integrative processes and behavioral control. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

  15. Age-related decline in task switching is linked to both global and tract-specific changes in white matter microstructure.

    PubMed

    Jolly, Todd A D; Cooper, Patrick S; Rennie, Jaime L; Levi, Christopher R; Lenroot, Rhoshel; Parsons, Mark W; Michie, Patricia T; Karayanidis, Frini

    2017-03-01

    Task-switching performance relies on a broadly distributed frontoparietal network and declines in older adults. In this study, they investigated whether this age-related decline in task switching performance was mediated by variability in global or regional white matter microstructural health. Seventy cognitively intact adults (43-87 years) completed a cued-trials task switching paradigm. Microstructural white matter measures were derived using diffusion tensor imaging (DTI) analyses on the diffusion-weighted imaging (DWI) sequence. Task switching performance decreased with increasing age and radial diffusivity (RaD), a measure of white matter microstructure that is sensitive to myelin structure. RaD mediated the relationship between age and task switching performance. However, the relationship between RaD and task switching performance remained significant when controlling for age and was stronger in the presence of cardiovascular risk factors. Variability in error and RT mixing cost were associated with RaD in global white matter and in frontoparietal white matter tracts, respectively. These findings suggest that age-related increase in mixing cost may result from both global and tract-specific disruption of cerebral white matter linked to the increased incidence of cardiovascular risks in older adults. Hum Brain Mapp 38:1588-1603, 2017. © 2016 Wiley Periodicals, Inc.

  16. Long-term ginsenoside Rg1 supplementation improves age-related cognitive decline by promoting synaptic plasticity associated protein expression in C57BL/6J mice.

    PubMed

    Yang, Lumeng; Zhang, Jing; Zheng, Kunmu; Shen, Hui; Chen, Xiaochun

    2014-03-01

    In aging individuals, age-related cognitive decline is the most common cause of memory impairment. Among the remedies, ginsenoside Rg1, a major active component of ginseng, is often recommended for its antiaging effects. However, its role in improving cognitive decline during normal aging remains unknown and its molecular mechanism partially understood. This study employed a scheme of Rg1 supplementation for female C57BL/6J mice, which started at the age of 12 months and ended at 24 months, to investigate the effects of Rg1 supplementation on the cognitive performance. We found that Rg1 supplementation improved the performance of aged mice in behavior test and significantly upregulated the expression of synaptic plasticity-associated proteins in hippocampus, including synaptophysin, N-methyl-D-aspartate receptor subunit 1, postsynaptic density-95, and calcium/calmodulin-dependent protein kinase II alpha, via promoting mammalian target of rapamycin pathway activation. These data provide further support for Rg1 treatment of cognitive degeneration during aging.

  17. Depressive Mood and Testosterone Related to Declarative Verbal Memory Decline in Middle-Aged Caregivers of Children with Eating Disorders.

    PubMed

    Romero-Martínez, Ángel; Ruiz-Robledillo, Nicolás; Moya-Albiol, Luis

    2016-03-04

    Caring for children diagnosed with a chronic psychological disorder such as an eating disorder (ED) can be used as a model of chronic stress. This kind of stress has been reported to have deleterious effects on caregivers' cognition, particularly in verbal declarative memory of women caregivers. Moreover, high depressive mood and variations in testosterone (T) levels moderate this cognitive decline. The purpose of this study was to characterize whether caregivers of individuals with EDs (n = 27) show declarative memory impairments compared to non-caregivers caregivers (n = 27), using for this purpose a standardized memory test (Rey's Auditory Verbal Learning Test). Its purpose was also to examine the role of depressive mood and T in memory decline. Results showed that ED caregivers presented high depressive mood, which was associated to worse verbal memory performance, especially in the case of women. In addition, all caregivers showed high T levels. Nonetheless, only in the case of women caregivers did T show a curvilinear relationship with verbal memory performance, meaning that the increases of T were associated to the improvement in verbal memory performance, but only up to a certain point, as after such point T continued to increase and memory performance decreased. Thus, chronic stress due to caregiving was associated to disturbances in mood and T levels, which in turn was associated to verbal memory decline. These findings should be taken into account in the implementation of intervention programs for helping ED caregivers cope with caregiving situations and to prevent the risk of a pronounced verbal memory decline.

  18. Aerobic exercise prevents age-dependent cognitive decline and reduces anxiety-related behaviors in middle-aged and old rats.

    PubMed

    Pietrelli, A; Lopez-Costa, J; Goñi, R; Brusco, A; Basso, N

    2012-01-27

    Recent research involving human and animals has shown that aerobic exercise of moderate intensity produces the greatest benefit on brain health and behavior. In this study we investigated the effects on cognitive function and anxiety-related behavior in rats at different ages of aerobic exercise, performed regularly throughout life. We designed an aerobic training program with the treadmill running following the basic principles of human training, and assuming that rats have the same physiological adaptations. The intensity was gradually adjusted to the fitness level and age, and maintained at 60-70% of maximum oxygen consumption (max.VO(2)). In middle age (8 months) and old age (18 months), we studied the cognitive response with the radial maze (RM), and anxiety-related behaviors with the open field (OF) and the elevated plus maze (EPM). Aerobically trained (AT) rats had a higher cognitive performance measured in the RM, showing that exercise had a cumulative and amplifier effect on memory and learning. The analysis of age and exercise revealed that the effects of aerobic exercise were modulated by age. Middle-aged AT rats were the most successful animals; however, the old AT rats met the criteria more often than the middle-aged sedentary controls (SC), indicating that exercise could reverse the negative effects of sedentary life, partially restore the cognitive function, and protect against the deleterious effects of aging. The results in the OF and EPM showed a significant decrease in key indicators of anxiety, revealing that age affected most of the analyzed variables, and that exercise had a prominent anxiolytic effect, particularly strong in old age. In conclusion, our results indicated that regular and chronic aerobic exercise has time and dose-dependent, neuroprotective and restorative effects on physiological brain aging, and reduces anxiety-related behaviors.

  19. Age-related decline in the osteogenic potential of human bone marrow cells cultured in three-dimensional collagen sponges.

    PubMed

    Mueller, S M; Glowacki, J

    2001-01-01

    Studies with human and animal culture systems indicate that a sub-population of bone marrow stromal cells has the potential to differentiate into osteoblasts. There are conflicting reports on the effects of age on human marrow-derived osteogenic cells. In this study, we used a three dimensional (3D) culture system and quantitative RT-PCR methods to test the hypothesis that the osteogenic potential of human bone marrow stromal cells decreases with age. Marrow was obtained from 39 men aged 37 to 86 years, during the course of total hip arthroplasty. Low-density mononuclear cells were seeded onto 3D collagen sponges and cultured for 3 weeks. Histological sections of sponges were stained for alkaline phosphatase activity and were scored as positive or negative. In the group < or = 50 years, 7 of 11 samples (63%) were positive, whereas only 5 of 19 (26%) of the samples in the group > or = 60 years were positive (p = 0.0504). As revealed by RT-PCR, there was no expression of alkaline phosphatase or collagen type I mRNA before culture, however there were strong signals after 3 weeks, an indication of osteoblast differentiation in vitro. We performed a quantitative, competitive RT-PCR assay with 8 samples (age range 38-80) and showed that the group < or = 50 years had 3-fold more mRNA for alkaline phosphatase than the group > or = 60 years (p = 0.021). There was a significant decrease with age (r = - 0.78, p = 0.028). These molecular and histoenzymatic data indicate that the osteogenic potential of human bone marrow cells decreases with age.

  20. Central Determinants of Age-Related Declines in Motor Function (Annals of the New York Academy of Sciences. Volume 515)

    DTIC Science & Technology

    1988-01-18

    treatment - for example, with nootropics, as wa. demonstrated with piracetam and pyritinol. " " When motor tasks are performed under more strenuous...5-hydroxytryptophan, clonazepam, valproate, lisuride, piracetam Tics: clonidine, neuroleptics, tetrabenazine, clonazepam Restlessness & Akathisia...models of aging and dementia, little is known of its pharmacological actions in improving cognitive performance." Piracetam , a com- pound with a number

  1. Metabolomic and flux-balance analysis of age-related decline of hypoxia tolerance in Drosophila muscle tissue

    PubMed Central

    Coquin, Laurence; Feala, Jacob D; McCulloch, Andrew D; Paternostro, Giovanni

    2008-01-01

    The fruitfly Drosophila melanogaster is increasingly used as a model organism for studying acute hypoxia tolerance and for studying aging, but the interactions between these two factors are not well known. Here we show that hypoxia tolerance degrades with age in post-hypoxic recovery of whole-body movement, heart rate and ATP content. We previously used 1H NMR metabolomics and a constraint-based model of ATP-generating metabolism to discover the end products of hypoxic metabolism in flies and generate hypotheses for the biological mechanisms. We expand the reactions in the model using tissue- and age-specific microarray data from the literature, and then examine metabolomic profiles of thoraxes after 4 h at 0.5% O2 and after 5 min of recovery in 40- versus 3-day-old flies. Model simulations were constrained to fluxes calculated from these data. Simulations suggest that the decreased ATP production during reoxygenation seen in aging flies can be attributed to reduced recovery of mitochondrial respiration pathways and concomitant overdependence on the acetate production pathway as an energy source. PMID:19096360

  2. Decline in Proliferation and Immature Neuron Markers in the Human Subependymal Zone during Aging: Relationship to EGF- and FGF-Related Transcripts

    PubMed Central

    Weissleder, Christin; Fung, Samantha J.; Wong, Matthew W.; Barry, Guy; Double, Kay L.; Halliday, Glenda M.; Webster, Maree J.; Weickert, Cynthia Shannon

    2016-01-01

    Neuroblasts exist within the human subependymal zone (SEZ); however, it is debated to what extent neurogenesis changes during normal aging. It is also unknown how precursor proliferation may correlate with the generation of neuronal and glial cells or how expression of growth factors and receptors may change throughout the adult lifespan. We found evidence of dividing cells in the human SEZ (n D 50) in conjunction with a dramatic age-related decline (21-103 years) of mRNAs indicative of proliferating cells (Ki67) and immature neurons (doublecortin). Microglia mRNA (ionized calcium-binding adapter molecule 1) increased during aging, whereas transcript levels of stem/precursor cells (glial fibrillary acidic protein delta and achaete-scute homolog 1), astrocytes (vimentin and pan-glial fibrillary acidic protein), and oligodendrocytes (oligodendrocyte lineage transcription factor 2) remained stable. Epidermal growth factor receptor (EGFR) and fibroblast growth factor 2 (FGF2) mRNAs increased throughout adulthood, while transforming growth factor alpha (TGFα), EGF, Erb-B2 receptor tyrosine kinase 4 (ErbB4) and FGF receptor 1 (FGFR1) mRNAs were unchanged across adulthood. Cell proliferation mRNA positively correlated with FGFR1 transcripts. Immature neuron and oligodendrocyte marker expression positively correlated with TGFα and ErbB4 mRNAs, whilst astrocyte transcripts positively correlated with EGF, FGF2, and FGFR1 mRNAs. Microglia mRNA positively correlated with EGF and FGF2 expression. Our findings indicate that neurogenesis in the human SEZ continues well into adulthood, although proliferation and neuronal differentiation may decline across adulthood. We suggest that mRNA expression of EGF- and FGF-related family members do not become limited during aging and may modulate neuronal and glial fate determination in the SEZ throughout human life. PMID:27932973

  3. 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

  4. 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.

  5. Cognitive control adjustments in healthy older and younger adults: Conflict adaptation, the error-related negativity (ERN), and evidence of generalized decline with age.

    PubMed

    Larson, Michael J; Clayson, Peter E; Keith, Cierra M; Hunt, Isaac J; Hedges, Dawson W; Nielsen, Brent L; Call, Vaughn R A

    2016-03-01

    Older adults display alterations in neural reflections of conflict-related processing. We examined response times (RTs), error rates, and event-related potential (ERP; N2 and P3 components) indices of conflict adaptation (i.e., congruency sequence effects) a cognitive control process wherein previous-trial congruency influences current-trial performance, along with post-error slowing, correct-related negativity (CRN), error-related negativity (ERN) and error positivity (Pe) amplitudes in 65 healthy older adults and 94 healthy younger adults. Older adults showed generalized slowing, had decreased post-error slowing, and committed more errors than younger adults. Both older and younger adults showed conflict adaptation effects; magnitude of conflict adaptation did not differ by age. N2 amplitudes were similar between groups; younger, but not older, adults showed conflict adaptation effects for P3 component amplitudes. CRN and Pe, but not ERN, amplitudes differed between groups. Data support generalized declines in cognitive control processes in older adults without specific deficits in conflict adaptation.

  6. Age-related neurogenesis decline in the subventricular zone is associated with specific cell cycle regulation changes in activated neural stem cells

    PubMed Central

    Daynac, Mathieu; Morizur, Lise; Chicheportiche, Alexandra; Mouthon, Marc-André; Boussin, François D.

    2016-01-01

    Although neural stem cells (NSCs) sustain continuous neurogenesis throughout the adult lifespan of mammals, they progressively exhibit proliferation defects that contribute to a sharp reduction in subventricular neurogenesis during aging. However, little is known regarding the early age-related events in neurogenic niches. Using a fluorescence-activated cell sorting technique that allows for the prospective purification of the main neurogenic populations from the subventricular zone (SVZ), we demonstrated an early decline in adult neurogenesis with a dramatic loss of progenitor cells in 4 month-old young adult mice. Whereas the activated and quiescent NSC pools remained stable up to 12 months, the proliferative status of activated NSCs was already altered by 6 months, with an overall extension of the cell cycle resulting from a specific lengthening of G1. Whole genome analysis of activated NSCs from 2- and 6-month-old mice further revealed distinct transcriptomic and molecular signatures, as well as a modulation of the TGFβ signalling pathway. Our microarray study constitutes a cogent identification of new molecular players and signalling pathways regulating adult neurogenesis and its early modifications. PMID:26893147

  7. Do plasma melatonin concentrations decline with age?

    NASA Technical Reports Server (NTRS)

    Zeitzer, J. M.; Daniels, J. E.; Duffy, J. F.; Klerman, E. B.; Shanahan, T. L.; Dijk, D. J.; Czeisler, C. A.

    1999-01-01

    PURPOSE: Numerous reports that secretion of the putative sleep-promoting hormone melatonin declines with age have led to suggestions that melatonin replacement therapy be used to treat sleep problems in older patients. We sought to reassess whether the endogenous circadian rhythm of plasma melatonin concentration changes with age in healthy drug-free adults. METHODS: We analyzed the amplitude of plasma melatonin profiles during a constant routine in 34 healthy drug-free older subjects (20 women and 14 men, aged 65 to 81 years) and compared them with 98 healthy drug-free young men (aged 18 to 30 years). RESULTS: We could detect no significant difference between a healthy and drug-free group of older men and women as compared to one of young men in the endogenous circadian amplitude of the plasma melatonin rhythm, as described by mean 24-hour average melatonin concentration (70 pmol/liter vs 73 pmol/liter, P = 0.97), or the duration (9.3 hours vs 9.1 hours, P = 0.43), mean (162 pmol/liter vs 161 pmol/liter, P = 0.63), or integrated area (85,800 pmol x min/liter vs 86,700 pmol x min/liter, P = 0.66) of the nocturnal peak of plasma melatonin. CONCLUSION: These results do not support the hypothesis that reduction of plasma melatonin concentration is a general characteristic of healthy aging. Should melatonin replacement therapy or melatonin supplementation prove to be clinically useful, we recommend that an assessment of endogenous melatonin be carried out before such treatment is used in older patients.

  8. A phytochemical-rich diet may explain the absence of age-related decline in visual acuity of Amazonian hunter-gatherers in Ecuador.

    PubMed

    London, Douglas S; Beezhold, Bonnie

    2015-02-01

    Myopia is absent in undisturbed hunter-gatherers but ubiquitous in modern populations. The link between dietary phytochemicals and eye health is well established, although transition away from a wild diet has reduced phytochemical variety. We hypothesized that when larger quantities and greater variety of wild, seasonal phytochemicals are consumed in a food system, there will be a reduced prevalence of degenerative-based eye disease as measured by visual acuity. We compared food systems and visual acuity across isolated Amazonian Kawymeno Waorani hunter-gatherers and neighboring Kichwa subsistence agrarians, using dietary surveys, dietary pattern observation, and Snellen Illiterate E visual acuity examinations. Hunter-gatherers consumed more food species (130 vs. 63) and more wild plants (80 vs. 4) including 76 wild fruits, thereby obtaining larger variety and quantity of phytochemicals than agrarians. Visual acuity was inversely related to age only in agrarians (r = -.846, P < .001). As hypothesized, when stratified by age (<40 and ≥ 40 years), Mann-Whitney U tests revealed that hunter-gatherers maintained high visual acuity throughout life, whereas agrarian visual acuity declined (P values < .001); visual acuity of younger participants was high across the board, however, did not differ between groups (P > .05). This unusual absence of juvenile-onset vision problems may be related to local, organic, whole food diets of subsistence food systems isolated from modern food production. Our results suggest that intake of a wider variety of plant foods supplying necessary phytochemicals for eye health may help maintain visual acuity and prevent degenerative eye conditions as humans age.

  9. Age-related changes in the bimanual advantage and in brain oscillatory activity during tapping movements suggest a decline in processing sensory reafference.

    PubMed

    Sallard, Etienne; Spierer, Lucas; Ludwig, Catherine; Deiber, Marie-Pierre; Barral, Jérôme

    2014-02-01

    Deficits in the processing of sensory reafferences have been suggested as accounting for age-related decline in motor coordination. Whether sensory reafferences are accurately processed can be assessed based on the bimanual advantage in tapping: because of tapping with an additional hand increases kinesthetic reafferences, bimanual tapping is characterized by a reduced inter-tap interval variability than unimanual tapping. A suppression of the bimanual advantage would thus indicate a deficit in sensory reafference. We tested whether elderly indeed show a reduced bimanual advantage by measuring unimanual (UM) and bimanual (BM) self-paced tapping performance in groups of young (n = 29) and old (n = 27) healthy adults. Electroencephalogram was recorded to assess the underlying patterns of oscillatory activity, a neurophysiological mechanism advanced to support the integration of sensory reafferences. Behaviorally, there was a significant interaction between the factors tapping condition and age group at the level of the inter-tap interval variability, driven by a lower variability in BM than UM tapping in the young, but not in the elderly group. This result indicates that in self-paced tapping, the bimanual advantage is absent in elderly. Electrophysiological results revealed an interaction between tapping condition and age group on low beta band (14-20 Hz) activity. Beta activity varied depending on the tapping condition in the elderly but not in the young group. Source estimations localized this effect within left superior parietal and left occipital areas. We interpret our results in terms of engagement of different mechanisms in the elderly depending on the tapping mode: a 'kinesthetic' mechanism for UM and a 'visual imagery' mechanism for BM tapping movement.

  10. Feather corticosterone levels are related to age and future body condition, but not to subsequent fitness, in a declining migratory songbird

    PubMed Central

    Boves, Than J.; Fairhurst, Graham D.; Rushing, Clark S.; Buehler, David A.

    2016-01-01

    In migratory species, breeding and non-breeding locations are geographically separate, yet the effects of conditions from one stage may carry over to affect a subsequent stage. Ideally, to understand the mechanisms and implications of ‘carry-over effects’, one would need to follow individuals throughout the year, quantify potential environmental causal factors and physiological mediators during multiple life-history stages, and measure downstream fitness. Owing to current limitations of tracking technology, this is impossible for small, long-distance migrants, so indirect methods to characterize carry-over effects are required. Corticosterone (CORT) is a suspected physiological mediator of carry-over effects, but when collected from blood it provides only a physiological snapshot at that point in time. When extracted from feathers, however, feather corticosterone (CORTf) provides a measure of responses to stressors from previous, and longer, time periods. We collected feathers grown during two life-history stages (post-breeding and subsequent wintering) from individuals of two age classes of a rapidly declining migratory songbird, the cerulean warbler (Setophaga cerulea), on their breeding grounds and quantified CORTf concentrations. We then monitored reproduction and survival of individuals and analysed relationships among CORTf and age, body condition and future fitness. Compared with older males, second-year males had higher CORTf concentrations during both stages. When controlling for age and year, body condition at capture was positively related to CORTf concentrations from winter (especially for older birds). However, we found no relationships between CORTf and fitness (as defined by reproduction and survival). Thus, elevated CORT may represent a beneficial physiological response (e.g. hyperphagia prior to migration), particularly for certain life-history stages, and may mediate the condition in which individuals transition between stages. But for those

  11. Higher mortality and impaired elimination of bacteria in aged mice after intracerebral infection with E. coli are associated with an age-related decline of microglia and macrophage functions.

    PubMed

    Schütze, Sandra; Ribes, Sandra; Kaufmann, Annika; Manig, Anja; Scheffel, Jörg; Redlich, Sandra; Bunkowski, Stephanie; Hanisch, Uwe-Karsten; Brück, Wolfgang; Nau, Roland

    2014-12-30

    Incidence and mortality of bacterial meningitis are strongly increased in aged compared to younger adults demanding new strategies to improve prevention and therapy of bacterial central nervous system (CNS) infections the elderly. Here, we established a geriatric mouse model for an intracerebral E. coli infection which reflects the clinical situation in aged patients: After intracerebral challenge with E. coli K1, aged mice showed a higher mortality, a faster development of clinical symptoms, and a more pronounced weight loss. Elimination of bacteria and systemic inflammatory response were impaired in aged mice, however, the number of infiltrating leukocytes and microglial cells in the CNS of aged and young mice did not differ substantially. In vitro, primary microglial cells and peritoneal macrophages from aged mice phagocytosed less E. coli and released less NO and cyto-/chemokines compared to cells from young mice both without activation and after stimulation by agonists of TLR 2, 4, and 9. Our results suggest that the age-related decline of microglia and macrophage functions plays an essential role for the higher susceptibility of aged mice to intracerebral infections. Strategies to improve the phagocytic potential of aged microglial cells and macrophages appear promising for prevention and treatment of CNS infections in elderly patients.

  12. Late onset of dietary restriction reverses age-related decline of malate-aspartate shuttle enzymes in the liver and kidney of mice.

    PubMed

    Goyary, Danswrang; Sharma, Ramesh

    2008-02-01

    Dietary restriction (DR) influences several physiological processes, retards the incidences and severity of various age-related diseases and extends lifespan of various animal species. The effect of DR on the activities of malate-aspartate shuttle enzymes, viz. cytosolic and mitochondrial aspartate aminotransferase (c- and m-AsAT) and malate dehydrogenase (c- and m-MDH) was investigated in the liver and kidney of adult (5-months) and old (21-months) male mice. The results show that the activity (U/mg protein) of both c- and m-MDH and AsAT is decreased significantly in the liver and kidney of old mice compared to adult ones. However, DR in old mice reverses significantly the enzyme activities to a level closer to adult animals. Polyacrylamide gel electrophoresis (PAGE) and specific staining of c-AsAT, one of the selected isoenzymes of the shuttle, showed a similar pattern of activity expression as observed by activity measurements in both the tissues studied. Slot blot analysis of c-AsAT confirmed the lower protein content of this isoenzyme in old mice compared to adult ones and a higher level in old-dietary restricted mice. Thus, our results suggest that the late onset of DR in older mice reverses decline in malate-aspartate shuttle enzymes and that it may allow a better metabolic regulation in older animals.

  13. Brain network changes and memory decline in aging.

    PubMed

    Beason-Held, Lori L; Hohman, Timothy J; Venkatraman, Vijay; An, Yang; Resnick, Susan M

    2016-06-18

    One theory of age-related cognitive decline proposes that changes within the default mode network (DMN) of the brain impact the ability to successfully perform cognitive operations. To investigate this theory, we examined functional covariance within brain networks using regional cerebral blood flow data, measured by (15)O-water PET, from 99 participants (mean baseline age 68.6 ± 7.5) in the Baltimore Longitudinal Study of Aging collected over a 7.4 year period. The sample was divided in tertiles based on longitudinal performance on a verbal recognition memory task administered during scanning, and functional covariance was compared between the upper (improvers) and lower (decliners) tertile groups. The DMN and verbal memory networks (VMN) were then examined during the verbal memory scan condition. For each network, group differences in node-to-network coherence and individual node-to-node covariance relationships were assessed at baseline and in change over time. Compared with improvers, decliners showed differences in node-to-network coherence and in node-to-node relationships in the DMN but not the VMN during verbal memory. These DMN differences reflected greater covariance with better task performance at baseline and both increasing and declining covariance with declining task performance over time for decliners. When examined during the resting state alone, the direction of change in DMN covariance was similar to that seen during task performance, but node-to-node relationships differed from those observed during the task condition. These results suggest that disengagement of DMN components during task performance is not essential for successful cognitive performance as previously proposed. Instead, a proper balance in network processes may be needed to support optimal task performance.

  14. Divergence of Age-Related Differences in Social-Communication: Improvements for Typically Developing Youth but Declines for Youth with Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Wallace, Gregory L.; Dudley, Katerina; Anthony, Laura; Pugliese, Cara E.; Orionzi, Bako; Clasen, Liv; Lee, Nancy Raitano; Giedd, Jay N.; Martin, Alex; Raznahan, Armin; Kenworthy, Lauren

    2017-01-01

    Although social-communication difficulties and repetitive behaviors are hallmark features of autism spectrum disorder (ASD) and persist across the lifespan, very few studies have compared age-related differences in these behaviors between youth with ASD and same-age typically developing (TD) peers. We examined this issue using SRS-2 (Social…

  15. Reduced release and binding of perforin at the immunological synapse underlies the age-related decline in natural killer cell cytotoxicity.

    PubMed

    Hazeldine, Jon; Hampson, Peter; Lord, Janet M

    2012-10-01

    Physiological aging is accompanied by a marked reduction in natural killer (NK) cell cytotoxicity (NKCC) at the single cell level, but the underlying mechanisms are unknown. To address this issue, we isolated NK cells from healthy young (≤ 35 years) and old (≤ 60 years) subjects and examined the effect of age on events fundamental to the process of NKCC. Simultaneous assessment of NKCC and NK cell-target cell conjugate formation revealed a marked age-associated decline in NK cell killing but comparable conjugate formation, indicating a post-target cell binding defect was responsible for impaired NKCC. Despite a reduction in the proportion of NK cells expressing the activatory receptor NKp46, NK cells from old donors were not hyporesponsive to stimulation, as no age-associated difference was observed in the expression of the early activation marker CD69 following target cell coculture. Furthermore, intracellular levels of the key cytotoxic effector molecules perforin and granzyme B, and the fusion of secretory lysosomes with the NK cell membrane were also similar between the two groups. However, when we examined the binding of the pore-forming protein perforin to the surface of its target cell, an event that correlated strongly with target cell lysis, we found the percentage of perforin positive target cells was lower following coculture with NK cells from old subjects. Underlying this reduction in binding was an age-associated impairment in perforin secretion, which was associated with defective polarization of lytic granules towards the immunological synapse. We propose that reduced perforin secretion underlies the reduction in NKCC that accompanies physiological aging.

  16. Age Differences in Fluid Intelligence: Contributions of General Slowing and Frontal Decline

    ERIC Educational Resources Information Center

    Bugg, Julie M.; Zook, Nancy A.; DeLosh, Edward L.; Davalos, Deana B.; Davis, Hasker P.

    2006-01-01

    The current study examined the contributions of general slowing and frontal decline to age differences in fluid intelligence. Participants aged 20-89 years completed Block Design, Matrix Reasoning, simple reaction time, choice reaction time, Wisconsin Card Sorting, and Tower of London tasks. Age-related declines in fluid intelligence, speed of…

  17. Do glutathione levels decline in aging human brain?

    PubMed

    Tong, Junchao; Fitzmaurice, Paul S; Moszczynska, Anna; Mattina, Katie; Ang, Lee-Cyn; Boileau, Isabelle; Furukawa, Yoshiaki; Sailasuta, Napapon; Kish, Stephen J

    2016-04-01

    For the past 60 years a major theory of "aging" is that age-related damage is largely caused by excessive uncompensated oxidative stress. The ubiquitous tripeptide glutathione is a major antioxidant defense mechanism against reactive free radicals and has also served as a marker of changes in oxidative stress. Some (albeit conflicting) animal data suggest a loss of glutathione in brain senescence, which might compromise the ability of the aging brain to meet the demands of oxidative stress. Our objective was to establish whether advancing age is associated with glutathione deficiency in human brain. We measured reduced glutathione (GSH) levels in multiple regions of autopsied brain of normal subjects (n=74) aged one day to 99 years. Brain GSH levels during the infancy/teenage years were generally similar to those in the oldest examined adult group (76-99 years). During adulthood (23-99 years) GSH levels remained either stable (occipital cortex) or increased (caudate nucleus, frontal and cerebellar cortices). To the extent that GSH levels represent glutathione antioxidant capacity, our postmortem data suggest that human brain aging is not associated with declining glutathione status. We suggest that aged healthy human brains can maintain antioxidant capacity related to glutathione and that an age-related increase in GSH levels in some brain regions might possibly be a compensatory response to increased oxidative stress. Since our findings, although suggestive, suffer from the generic limitations of all postmortem brain studies, we also suggest the need for "replication" investigations employing the new (1)H MRS imaging procedures in living human brain.

  18. Cardiorespiratory Fitness and Accelerated Cognitive Decline With Aging

    PubMed Central

    2014-01-01

    Background. Growing evidence suggests that self-reported physical activity accounts for variability in cognitive function among older adults, and aerobic intervention may improve cognitive function in this population. However, much less is known about the longitudinal association between direct measures of cardiorespiratory fitness and cognitive function across the life span. The present study examined the prospective association between symptom-limited maximal oxygen consumption (VO2max) and longitudinal performance on a comprehensive neuropsychological battery. Methods. Up to 1,400 participants aged 19–94 years underwent initial VO2max assessment and completed subsequent tests of memory, attention, perceptuomotor speed, language, and executive function, in addition to cognitive screening measures, on up to six occasions (mean, M = 2; standard deviation, SD = 1) for up to 18 years (M = 7, SD = 3). Mixed-effects regression models were adjusted for demographic, biomedical, and behavioral confounders. Results. Analyses revealed significant longitudinal associations between baseline VO2max and trajectory of performance on multiple measures of verbal and visual memory, as well as on a cognitive screening test (all ps < .05). Individuals with lower VO2max demonstrated accelerated trajectories of cognitive decline over time. Conclusions. Baseline cardiorespiratory fitness is related to longitudinal neuropsychological performance, and memory appears to be a particularly vulnerable domain. Evidence that aerobic fitness is associated with accelerated cognitive decline emphasizes the possible importance of behavioral interventions to optimize cognitive aging over time. PMID:24192540

  19. Does Bilingual Language Control Decline in Older Age?

    PubMed Central

    Ivanova, Iva; Murillo, Mayra; Montoya, Rosa I.; Gollan, Tamar H.

    2016-01-01

    We investigated age-related decline of bilingual language control. Thirteen older and 13 younger bilinguals performed a verbal fluency task (completing the same letter and semantic categories in each language and switching languages after every category), and a non-linguistic flanker task. In letter fluency, bilinguals produced fewer correct responses after switching languages, suggesting inhibition of the previously-used language. However, this testing-order effect did not differ between groups and older bilinguals produced few wrong-language intrusions, implying intact ability to apply inhibition in older age. In contrast, age-related deficits in the flanker task were robust, implying dissociations between language control and domain-general executive control. In semantic fluency, there were no testing-order effects but older bilinguals produced more intrusions than younger bilinguals, and more intrusions than in letter fluency. Thus, bilinguals may flexibly modulate the degree of inhibition when they can benefit from semantic priming between languages, but less efficiently so in older age. PMID:28090222

  20. Age-Related Decline in Brain and Hepatic Clearance of Amyloid-Beta is Rectified by the Cholinesterase Inhibitors Donepezil and Rivastigmine in Rats.

    PubMed

    Mohamed, Loqman A; Qosa, Hisham; Kaddoumi, Amal

    2015-05-20

    In Alzheimer's disease (AD), accumulation of brain amyloid-β (Aβ) depends on imbalance between production and clearance of Aβ. Several pathways for Aβ clearance have been reported including transport across the blood-brain barrier (BBB) and hepatic clearance. The incidence of AD increases with age and failure of Aβ clearance correlates with AD. The cholinesterase inhibitors (ChEIs) donepezil and rivastigmine are used to ease the symptoms of dementia associated with AD. Besides, both drugs have been reported to provide neuroprotective and disease-modifying effects. Here, we investigated the effect of ChEIs on age-related reduced Aβ clearance. Findings from in vitro and in vivo studies demonstrated donepezil and rivastigmine to enhance (125)I-Aβ40 clearance. Also, the increase in brain and hepatic clearance of (125)I-Aβ40 was more pronounced in aged compared to young rats, and was associated with significant reduction in brain Aβ endogenous levels determined by ELISA. Furthermore, the enhanced clearance was concomitant with up-regulation in the expression of Aβ major transport proteins P-glycoprotein and LRP1. Collectively, our findings that donepezil and rivastigmine enhance Aβ clearance across the BBB and liver are novel and introduce an additional mechanism by which both drugs could affect AD pathology. Thus, optimizing their clinical use could help future drug development by providing new drug targets and possible mechanisms involved in AD pathology.

  1. The Effects of Aerobic Exercise on Cognitive and Neural Decline in Aging and Cardiovascular Disease

    PubMed Central

    Alosco, Michael L.; Forman, Daniel E.

    2015-01-01

    Aging is characterized by a decline in cognitive functions, particularly in the domains of executive function, processing speed and episodic memory. These age-related declines are exacerbated by cardiovascular disease (CVD) and cardiovascular risk factors (hypertension, diabetes, obesity, elevated total cholesterol). Structural and functional alterations in brain regions, including the fronto-parietal and medial temporal lobes, have been linked to age- and CVD-related cognitive decline. Multiple recent studies indicate that aerobic exercise programs may slow the progression of age-related neural changes and reduce the risk for mild cognitive impairment as well as dementia. We review age- and CVD-related decline in cognition and the underlying changes in brain morphology and function, and then clarify the impact of aerobic exercise on moderating these patterns. PMID:25750853

  2. The Effects of Aerobic Exercise on Cognitive and Neural Decline in Aging and Cardiovascular Disease.

    PubMed

    Hayes, Scott M; Alosco, Michael L; Forman, Daniel E

    2014-12-01

    Aging is characterized by a decline in cognitive functions, particularly in the domains of executive function, processing speed and episodic memory. These age-related declines are exacerbated by cardiovascular disease (CVD) and cardiovascular risk factors (hypertension, diabetes, obesity, elevated total cholesterol). Structural and functional alterations in brain regions, including the fronto-parietal and medial temporal lobes, have been linked to age- and CVD-related cognitive decline. Multiple recent studies indicate that aerobic exercise programs may slow the progression of age-related neural changes and reduce the risk for mild cognitive impairment as well as dementia. We review age- and CVD-related decline in cognition and the underlying changes in brain morphology and function, and then clarify the impact of aerobic exercise on moderating these patterns.

  3. Oxidative stress and aberrant signaling in aging and cognitive decline

    PubMed Central

    Dröge, Wulf; Schipper, Hyman M

    2007-01-01

    Brain aging is associated with a progressive imbalance between antioxidant defenses and intracellular concentrations of reactive oxygen species (ROS) as exemplified by increases in products of lipid peroxidation, protein oxidation, and DNA oxidation. Oxidative conditions cause not only structural damage but also changes in the set points of redox-sensitive signaling processes including the insulin receptor signaling pathway. In the absence of insulin, the otherwise low insulin receptor signaling is strongly enhanced by oxidative conditions. Autophagic proteolysis and sirtuin activity, in turn, are downregulated by the insulin signaling pathway, and impaired autophagic activity has been associated with neurodegeneration. In genetic studies, impairment of insulin receptor signaling causes spectacular lifespan extension in nematodes, fruit flies, and mice. The predicted effects of age-related oxidative stress on sirtuins and autophagic activity and the corresponding effects of antioxidants remain to be tested experimentally. However, several correlates of aging have been shown to be ameliorated by antioxidants. Oxidative damage to mitochondrial DNA and the electron transport chain, perturbations in brain iron and calcium homeostasis, and changes in plasma cysteine homeostasis may altogether represent causes and consequences of increased oxidative stress. Aging and cognitive decline thus appear to involve changes at multiple nodes within a complex regulatory network. PMID:17517043

  4. Trade off situation between thymus and growth hormone: age-related decline of growth hormone is a cause of thymic involution but favorable for elongation of lifespan.

    PubMed

    Hirokawa, Katsuiku; Utsuyama, Masanori; Kikuchi, Yuko

    2016-02-01

    High level of growth hormone (GH) is necessary for the activation of thymic function to promote T cell differentiation in the early stage of animal life. In the later stage of the life, administration of GH promotes the development of immune system and rejuvenates declined immune function of elderly people. By contraries, GH deficiency is favorable for the longer lifespan, as hypo-pituitary dwarf mice such as Ames and Snell dwarf mice exhibit longer lifespan than control. Furthermore over-expression of heterologous or homologous GH in transgenic mice shortens the lifespan. Ecuadorians carrying mutations of GH receptor gene are short in height, but exhibited low frequency of malignancy and no cases of diabetes. These data indicate that GH is necessary for the development of thymus dependent immune system but GH deficiency is favorable for long life span and decreases occurrence of cancer and DM. This situation is a kind of trade off situation between the immune system and GH. Thus the early decline of high level of GH occurring shortly after the birth is a cause of early decline of thymic functions, but favorable for longer lifespan. This situation could be a kind of trade off situation between thymus and GH.

  5. Building a better hormone therapy? How understanding the rapid effects of sex steroid hormones could lead to new therapeutics for age-related memory decline.

    PubMed

    Frick, Karyn M

    2012-02-01

    A wealth of data collected in recent decades has demonstrated that ovarian sex-steroid hormones, particularly 17β-estradiol (E2), are important trophic factors that regulate the function of cognitive regions of the brain such as the hippocampus. The loss of hormone cycling at menopause is associated with cognitive decline and dementia in women, and the onset of memory decline in animal models. However, hormone therapy is not currently recommended to prevent or treat cognitive decline, in part because of its detrimental side effects. In this article, it is proposed that investigations of the rapid effects of E2 on hippocampal function be used to further the design of new drugs that mimic the beneficial effects of E2 on memory without the side effects of current therapies. A conceptual model is presented for elucidating the molecular and biochemical mechanisms through which sex-steroid hormones modulate memory, and a specific hypothesis is proposed to account for the rapid memory-enhancing effects of E2. Empirical support for this hypothesis is discussed as a means of stimulating the consideration of new directions for the development of hormone-based therapies to preserve memory function in menopausal women.

  6. Acetyl-L-carnitine supplementation reverses the age-related decline in carnitine palmitoyltransferase 1 (CPT1) activity in interfibrillar mitochondria without changing the L-carnitine content in the rat heart.

    PubMed

    Gómez, Luis A; Heath, Shi-Hua D; Hagen, Tory M

    2012-01-01

    The aging heart displays a loss of bioenergetic reserve capacity partially mediated through lower fatty acid utilization. We investigated whether the age-related impairment of cardiac fatty acid catabolism occurs, at least partially, through diminished levels of L-carnitine, which would adversely affect carnitine palmitoyltransferase 1 (CPT1), the rate-limiting enzyme for fatty acyl-CoA uptake into mitochondria for β-oxidation. Old (24-28 mos) Fischer 344 rats were fed±acetyl-L-carnitine (ALCAR; 1.5% [w/v]) for up to four weeks prior to sacrifice and isolation of cardiac interfibrillar (IFM) and subsarcolemmal (SSM) mitochondria. IFM displayed a 28% (p<0.05) age-related loss of CPT1 activity, which correlated with a decline (41%, p<0.05) in palmitoyl-CoA-driven state 3 respiration. Interestingly, SSM had preserved enzyme function and efficiently utilized palmitate. Analysis of IFM CPT1 kinetics showed both diminished V(max) and K(m) (60% and 49% respectively, p<0.05) when palmitoyl-CoA was the substrate. However, no age-related changes in enzyme kinetics were evident with respect to L-carnitine. ALCAR supplementation restored CPT1 activity in heart IFM, but not apparently through remediation of L-carnitine levels. Rather, ALCAR influenced enzyme activity over time, potentially by modulating conditions in the aging heart that ultimately affect palmitoyl-CoA binding and CPT1 kinetics.

  7. NR2A-Containing NMDARs in the Prefrontal Cortex Are Required for Working Memory and Associated with Age-Related Cognitive Decline.

    PubMed

    McQuail, Joseph A; Beas, B Sofia; Kelly, Kyle B; Simpson, Kailey L; Frazier, Charles J; Setlow, Barry; Bizon, Jennifer L

    2016-12-14

    Working memory, the ability to temporarily maintain representational knowledge, is a foundational cognitive process that can become compromised in aging and neuropsychiatric disease. NMDA receptor (NMDAR) activation in prefrontal cortex (PFC) is necessary for the pyramidal neuron activity believed to enable working memory; however, the distinct biophysical properties and localization of NMDARs containing NR2A and NR2B subunits suggest unique roles for NMDAR subtypes in PFC neural activity and working memory. Experiments herein show that working memory depends on NR2A- but not NR2B-NMDARs in PFC of rats and that NR2A-NMDARs mediate the majority of evoked NMDAR currents on layer 2/3 PFC pyramidal neurons. Moreover, attenuated expression of the NR2A but not the NR2B subunit in PFC associates with naturally occurring working memory impairment in aged rats. Finally, NMDAR currents and working memory are enhanced in aged rats by promoting activation of the NR2A-enriched synaptic pool of PFC NMDARs. These results implicate NR2A-NMDARs in normal working memory and suggest novel treatment strategies for improving working memory in cognitive disorders.

  8. Aging in male primates: reproductive decline, effects of calorie restriction and future research potential

    PubMed Central

    Sitzmann, Brandon D.; Urbanski, Henryk F.

    2008-01-01

    Although less dramatic than in females, male mammals experience decreasing reproductive function during aging. In primates, multiple facets of the hypothalamic-pituitary-gonadal axis show evidence of gradual age-related decline, including behavioral, neuroendocrine and endocrine alterations such as decreased testosterone levels, reduced circulating dehydroepiandrosterone sulfate (DHEAS) levels, increased numbers of sperm abnormalities, and a general decline in physiological responses. In this review we consider a range of age-related changes in males. These measures, including more subtle aging characteristics, are interesting additional indices for detecting the timing of age-related changes in behavioral, neuroendocrine, and endocrine responses. Evidence of potential effects of calorie restriction as an intervention in reproductive aging is also discussed. A discernable decline occurs in both metabolic and reproductive endocrine processes during male aging. This cascade of events includes neuroendocrine and behavioral changes; biomarkers such as circulating DHEAS also show clear age-related decline. The varied changes that occur during male aging are considered in the context of primate aging in general. PMID:19424865

  9. The Hippocampal Neuroproteome with Aging and Cognitive Decline: Past Progress and Future Directions

    PubMed Central

    VanGuilder, Heather D.; Freeman, Willard M.

    2011-01-01

    Although steady progress on understanding brain aging has been made over recent decades through standard anatomical, immunohistochemical, and biochemical techniques, the biological basis of non-neurodegenerative cognitive decline with aging remains to be determined. This is due in part to technical limitations of traditional approaches, in which only a small fraction of neurobiologically relevant proteins, mRNAs or metabolites can be assessed at a time. With the development and refinement of proteomic technologies that enable simultaneous quantitative assessment of hundreds to thousands of proteins, neuroproteomic studies of brain aging and cognitive decline are becoming more widespread. This review focuses on the contributions of neuroproteomic investigations to advances in our understanding of age-related deficits of hippocampus-dependent spatial learning and memory. Accumulating neuroproteomic data demonstrate that hippocampal aging involves common themes of dysregulated metabolism, increased oxidative stress, altered protein processing, and decreased synaptic function. Additionally, growing evidence suggests that cognitive decline does not represent a “more aged” phenotype, but rather is associated with specific neuroproteomic changes that occur in addition to age-related alterations. Understanding if and how age-related changes in the hippocampal neuroproteome contribute to cognitive decline and elucidating the pathways and processes that lead to cognitive decline are critical objectives that remain to be achieved. Progress in the field and challenges that remain to be addressed with regard to animal models, behavioral testing, and proteomic reporting are also discussed. PMID:21647399

  10. Age-related changes in triathlon performances.

    PubMed

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

    2010-04-01

    The aim of this study was two-fold: i) to analyse age-related declines in swimming, cycling, and running performances for Olympic and Ironman triathlons, and ii) to compare age-related changes in these three disciplines between the Olympic and Ironman triathlons. Swimming, cycling, running and total time performances of the top 10 males between 20 and 70 years of age (in 5 years intervals) were analysed for two consecutive world championships (2006 and 2007) for Olympic and Ironman distances. There was a lesser age-related decline in cycling performance (p<0.01) compared with running and swimming after 55 years of age for Olympic distance and after 50 years of age for Ironman distance. With advancing age, the performance decline was less pronounced (p<0.01) for Olympic than for Ironman triathlon in cycling (>55 years) and running (>50 years), respectively. In contrast, an age-related decline in swimming performance seemed independent of triathlon distance. The age-related decline in triathlon performance is specific to the discipline, with cycling showing less declines in performance with age than swimming and running. The magnitude of the declines in cycling and running performance at Ironman distance is greater than at Olympic distance, suggesting that task duration exerts an important influence on the magnitude of the age-associated changes in triathlon performance.

  11. The neurobiology of speech perception decline in aging.

    PubMed

    Bilodeau-Mercure, Mylène; Lortie, Catherine L; Sato, Marc; Guitton, Matthieu J; Tremblay, Pascale

    2015-03-01

    Speech perception difficulties are common among elderlies; yet the underlying neural mechanisms are still poorly understood. New empirical evidence suggesting that brain senescence may be an important contributor to these difficulties has challenged the traditional view that peripheral hearing loss was the main factor in the etiology of these difficulties. Here, we investigated the relationship between structural and functional brain senescence and speech perception skills in aging. Following audiometric evaluations, participants underwent MRI while performing a speech perception task at different intelligibility levels. As expected, with age speech perception declined, even after controlling for hearing sensitivity using an audiological measure (pure tone averages), and a bioacoustical measure (DPOAEs recordings). Our results reveal that the core speech network, centered on the supratemporal cortex and ventral motor areas bilaterally, decreased in spatial extent in older adults. Importantly, our results also show that speech skills in aging are affected by changes in cortical thickness and in brain functioning. Age-independent intelligibility effects were found in several motor and premotor areas, including the left ventral premotor cortex and the right supplementary motor area (SMA). Age-dependent intelligibility effects were also found, mainly in sensorimotor cortical areas, and in the left dorsal anterior insula. In this region, changes in BOLD signal modulated the relationship between age and speech perception skills suggesting a role for this region in maintaining speech perception in older ages. These results provide important new insights into the neurobiology of speech perception in aging.

  12. [Age related macular degeneration].

    PubMed

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

    2011-02-01

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

  13. IANA task force on nutrition and cognitive decline with aging.

    PubMed

    Gillette Guyonnet, S; Abellan Van Kan, G; Andrieu, S; Barberger Gateau, P; Berr, C; Bonnefoy, M; Dartigues, J F; de Groot, L; Ferry, M; Galan, P; Hercberg, S; Jeandel, C; Morris, M C; Nourhashemi, F; Payette, H; Poulain, J P; Portet, F; Roussel, A M; Ritz, P; Rolland, Y; Vellas, B

    2007-01-01

    Cognitive impairment can be influenced by a number of factors. The potential effect of nutrition has become a topic of increasing scientific and public interest. In particular, there are arguments that nutrients (food and/or supplements) such as vitamins, trace minerals, lipids, can affect the risk of cognitive decline and dementia, especially in frail elderly people at risk of deficiencies. Our objective in this paper is to review data relating diet to risk of cognitive decline and dementia, especially Alzheimer's disease (AD). We chose to focus our statements on homocysteine-related vitamins (B-vitamins), antioxidant nutrients (vitamins E and C, carotenoids, flavonoids, enzymatic cofactors) and dietary lipids. Results of epidemiological studies may sometimes appeared conflicting; however, certain associations are frequently found. High intake of saturated and trans-unsaturated (hydrogenated) fats were positively associated with increased risk of AD, whereas intake of polyunsaturated and monounsaturated fats were protective against cognitive decline in the elderly in prospective studies. Fish consumption has been associated with lower risk of AD in longitudinal cohort studies. Moreover, epidemiologic data suggest a protective role of the B-vitamins, especially vitamins B9 and B12, on cognitive decline and dementia. Finally, the results on antioxidant nutrients may suggest the importance of having a balanced combination of several antioxidant nutrients to exert a significant effect on the prevention of cognitive decline and dementia, while taking into account the potential adverse effects of these nutrients. There is no lack of attractive hypotheses to support research on the relationships between nutrition and cognitive decline. It is important to stress the need to develop further prospective studies of sufficiently long duration, including subjects whose diet is monitored at a sufficiently early stage or at least before disease or cognitive decline exist. Meta

  14. Consumption of alcoholic beverages and cognitive decline at middle age: the Doetinchem Cohort Study.

    PubMed

    Nooyens, Astrid C J; Bueno-de-Mesquita, H Bas; van Gelder, Boukje M; van Boxtel, Martin P J; Verschuren, W M Monique

    2014-02-01

    Accelerated cognitive decline increases the risk of dementia. Slowing down the rate of cognitive decline leads to the preservation of cognitive functioning in the elderly, who can live independently for a longer time. Alcohol consumption may influence the rate of cognitive decline. The aim of the present study was to evaluate the associations between the total consumption of alcoholic beverages and different types of alcoholic beverages and cognitive decline at middle age. In 2613 men and women of the Doetinchem Cohort Study, aged 43-70 years at baseline (1995-2002), cognitive function (global cognitive function and the domains memory, speed and flexibility) was assessed twice, with a 5-year time interval. In linear regression analyses, the consumption of different types of alcoholic beverages was analysed in relation to cognitive decline, adjusting for confounders. We observed that, in women, the total consumption of alcoholic beverages was inversely associated with the decline in global cognitive function over a 5-year period (P for trend = 0·02), while no association was observed in men. Regarding the consumption of different types of alcoholic beverages in men and women together, red wine consumption was inversely associated with the decline in global cognitive function (P for trend < 0·01) as well as memory (P for trend < 0·01) and flexibility (P for trend = 0·03). Smallest declines were observed at a consumption of about 1·5 glasses of red wine per d. No other types of alcoholic beverages were associated with cognitive decline. In conclusion, only (moderate) red wine consumption was consistently associated with less strong cognitive decline. Therefore, it is most likely that non-alcoholic substances in red wine are responsible for any cognition-preserving effects.

  15. Age-associated Cognitive Decline: Insights into Molecular Switches and Recovery Avenues

    PubMed Central

    Konar, Arpita; Singh, Padmanabh; Thakur, Mahendra K.

    2016-01-01

    Age-associated cognitive decline is an inevitable phenomenon that predisposes individuals for neurological and psychiatric disorders eventually affecting the quality of life. Scientists have endeavored to identify the key molecular switches that drive cognitive decline with advancing age. These newly identified molecules are then targeted as recovery of cognitive aging and related disorders. Cognitive decline during aging is multi-factorial and amongst several factors influencing this trajectory, gene expression changes are pivotal. Identifying these genes would elucidate the neurobiological underpinnings as well as offer clues that make certain individuals resilient to withstand the inevitable age-related deteriorations. Our laboratory has focused on this aspect and investigated a wide spectrum of genes involved in crucial brain functions that attribute to senescence induced cognitive deficits. We have recently identified master switches in the epigenome regulating gene expression alteration during brain aging. Interestingly, these factors when manipulated by chemical or genetic strategies successfully reverse the age-related cognitive impairments. In the present article, we review findings from our laboratory and others combined with supporting literary evidences on molecular switches of brain aging and their potential as recovery targets. PMID:27114845

  16. The rate of change in declining steroid hormones: a new parameter of healthy aging in men?

    PubMed Central

    Walther, Andreas; Philipp, Michel; Lozza, Niclà; Ehlert, Ulrike

    2016-01-01

    Research on healthy aging in men has increasingly focused on age-related hormonal changes. Testosterone (T) decline is primarily investigated, while age-related changes in other sex steroids (dehydroepiandrosterone [DHEA], estradiol [E2], progesterone [P]) are mostly neglected. An integrated hormone parameter reflecting aging processes in men has yet to be identified. 271 self-reporting healthy men between 40 and 75 provided both psychometric data and saliva samples for hormone analysis. Correlation analysis between age and sex steroids revealed negative associations for the four sex steroids (T, DHEA, E2, and P). Principal component analysis including ten salivary analytes identified a principal component mainly unifying the variance of the four sex steroid hormones. Subsequent principal component analysis including the four sex steroids extracted the principal component of declining steroid hormones (DSH). Moderation analysis of the association between age and DSH revealed significant moderation effects for psychosocial factors such as depression, chronic stress and perceived general health. In conclusion, these results provide further evidence that sex steroids decline in aging men and that the integrated hormone parameter DSH and its rate of change can be used as biomarkers for healthy aging in men. Furthermore, the negative association of age and DSH is moderated by psychosocial factors. PMID:27589836

  17. The rate of change in declining steroid hormones: a new parameter of healthy aging in men?

    PubMed

    Walther, Andreas; Philipp, Michel; Lozza, Niclà; Ehlert, Ulrike

    2016-09-20

    Research on healthy aging in men has increasingly focused on age-related hormonal changes. Testosterone (T) decline is primarily investigated, while age-related changes in other sex steroids (dehydroepiandrosterone [DHEA], estradiol [E2], progesterone [P]) are mostly neglected. An integrated hormone parameter reflecting aging processes in men has yet to be identified. 271 self-reporting healthy men between 40 and 75 provided both psychometric data and saliva samples for hormone analysis. Correlation analysis between age and sex steroids revealed negative associations for the four sex steroids (T, DHEA, E2, and P). Principal component analysis including ten salivary analytes identified a principal component mainly unifying the variance of the four sex steroid hormones. Subsequent principal component analysis including the four sex steroids extracted the principal component of declining steroid hormones (DSH). Moderation analysis of the association between age and DSH revealed significant moderation effects for psychosocial factors such as depression, chronic stress and perceived general health. In conclusion, these results provide further evidence that sex steroids decline in aging men and that the integrated hormone parameter DSH and its rate of change can be used as biomarkers for healthy aging in men. Furthermore, the negative association of age and DSH is moderated by psychosocial factors.

  18. An Age-Associated Decline in Thymic Output Differs in Dog Breeds According to Their Longevity

    PubMed Central

    Holder, Angela; Mella, Stephanie; Palmer, Donald B.; Aspinall, Richard; Catchpole, Brian

    2016-01-01

    The age associated decline in immune function is preceded in mammals by a reduction in thymic output. Furthermore, there is increasing evidence of a link between immune competence and lifespan. One approach to determining thymic output is to quantify signal joint T cell receptor excision circles (sj-TRECs), a method which has been developed and used in several mammalian species. Life expectancy and the rate of aging vary in dogs depending upon their breed. In this study, we quantified sj-TRECs in blood samples from dogs of selected breeds to determine whether there was a relationship between longevity and thymic output. In Labrador retrievers, a breed with a median expected lifespan of 11 years, there was an age-associated decline in sj-TREC values, with the greatest decline occurring before 5 years of age, but with sj-TREC still detectable in some geriatric animals, over 13 years of age. In large short-lived breeds (Burnese mountain dogs, Great Danes and Dogue de Bordeaux), the decline in sj-TREC values began earlier in life, compared with small long-lived breeds (Jack Russell terriers and Yorkshire terriers), and the presence of animals with undetectable sj-TRECs occurred at a younger age in the short-lived breeds. The study findings suggest that age-associated changes in canine sj-TRECs are related to breed differences in longevity, and this research highlights the use of dogs as a potential model of immunosenescence. PMID:27824893

  19. Body mass and cognitive decline are indirectly associated via inflammation among aging adults.

    PubMed

    Bourassa, Kyle; Sbarra, David A

    2017-02-01

    Inflammatory models of neurodegeneration suggest that higher circulating levels of inflammation can lead to cognitive decline. Despite established independent associations between greater body mass, increased inflammation, and cognitive decline, no prior research has explored whether markers of systemic inflammation might mediate the association between body mass and changes in cognitive functioning. To test such a model, we used two longitudinal subsamples (ns=9066; 12,561) of aging adults from the English Longitudinal Study of Ageing (ELSA) study, which included two cognitive measures components of memory and executive functioning, as well as measurements of body mass and systemic inflammation, assessed via C-reactive protein (CRP). Greater body mass was indirectly associated with declines in memory and executive functioning over 6years via relatively higher levels of CRP. Our results suggest that systemic inflammation is one biologically plausible mechanism through which differences in body mass might influence changes in cognitive functioning among aging adults.

  20. Flavonol Intake and Cognitive Decline in Middle-Aged Adults.

    PubMed

    Root, Martin; Ravine, Erin; Harper, Anne

    2015-12-01

    Cognitive decline occurs with age and may be slowed by dietary measures, including increased intake of dietary phytochemicals. However, evidence from large and long-term studies of flavonol intake is limited. Dietary intakes of flavonols were assessed from a large biracial study of 10,041 subjects, aged 45-64, by analysis of a food frequency questionnaire administered at visit 1 of triennial visits. Cognitive function was assessed at visits 2 and 4 with the following three cognitive performance tests: the delayed word recall test, the revised Wechsler Adult Intelligence Scale digit symbol subtest, and the word fluency test of the Multilingual Aphasia Examination. The change in each score over 6 years was calculated, and a combined standardized change score was calculated. Generalized linear models controlled for age, ethnicity, gender, education level, energy intake, current smoking, physical activity, body mass index, diabetes, and vitamin C intake. Total flavonols across quintiles of intake were positively associated with preserved combined cognitive function (P<.001). This pattern with preserved combined cognitive function was consistent for the three major individual flavonols in the diet, myricetin, kaempferol, and quercetin (each P<.001). The positive association with total flavonols was strongest for the digit symbol subtest (P<.001). In this cohort, flavonol intake was correlated with protected cognitive function over time.

  1. Aerobic dive limit does not decline in an aging pinniped.

    PubMed

    Hindle, Allyson G; Mellish, Jo-Ann E; Horning, Markus

    2011-11-01

    Apneustic hunters such as diving mammals exploit body oxygen stores while submerged; therefore, any decline in oxygen handling at advanced life stages could critically impair foraging ability. We calculated the aerobic dive limit (cADL = 17.9 ± 4.4  min SD) from blood and muscle oxygen stores and published metabolic rates of Weddell seals within (9-16 years, n = 24) and beyond peak-reproductive age (17-27 years, n = 26), to investigate (1) senescent constraints in apneustic hunting, and (2) whether mass or age primarily determines oxygen stores and ADL in older seals. We compared cADL with behavioral ADL from 5,275 free-ranging dives (bADL = 24.0 ± 5.3 min, n = 18 females). We observed no changes in Weddell seal oxygen stores, its determinants, or in ADLs late in life. Oxygen stores were better predicted by mass than age, consistent with published findings for young adults. Hematological panels (n = 6) were consistent across mass and age, though hematocrit (females > males, 6% elevation) and mean corpuscular hemoglobin content (females < males, 8% reduction) varied by sex. Whole blood viscosity was decreased with increasing mass in females and was higher than in males overall (+18%). This was largely due to elevated hematocrit in females, although plasma viscosity also varied under some conditions. Females had higher blood volume and elevated blood oxygen stores (vol% body mass), which did not translate into significantly higher cADL (18.1 vs. 17.1 min for males). Neither cADL nor bADL were mass- or age-dependent.

  2. Mitochondrial Aging and Physical Decline: Insights From Three Generations of Women

    PubMed Central

    Hebert, Sadie L.; Marquet-de Rougé, Perrine; Lanza, Ian R.; McCrady-Spitzer, Shelly K.; Levine, James A.; Middha, Sumit; Carter, Rickey E.; Klaus, Katherine A.; Therneau, Terry M.; Highsmith, Edward W.

    2015-01-01

    Decline in mitochondrial DNA (mtDNA) copy number, function, and accumulation of mutations and deletions have been proposed to contribute to age-related physical decline, based on cross sectional studies in genetically unrelated individuals. There is wide variability of mtDNA and functional measurements in many population studies and therefore we assessed mitochondrial function and physical function in 18 families of grandmothers, mothers, and daughters who share the same maternally inherited mtDNA sequence. A significant age-related decline in mtDNA copy number, mitochondrial protein expression, citrate synthase activity, cytochrome c oxidase content, and VO2 peak were observed. Also, a lower abundance of SIRT3, accompanied by an increase in acetylated skeletal muscle proteins, was observed in grandmothers. Muscle tissue–based full sequencing of mtDNA showed greater than 5% change in minor allele frequency over a lifetime in two locations, position 189 and 408 in the noncoding D-loop region but no changes were noted in blood cells mtDNA. The decline in oxidative capacity and muscle function with age in three generations of women who share the same mtDNA sequence are associated with a decline in muscle mtDNA copy number and reduced protein deacetylase activity of SIRT3. PMID:26297939

  3. Lifelong physical exercise delays age-associated skeletal muscle decline.

    PubMed

    Zampieri, S; Pietrangelo, L; Loefler, S; Fruhmann, H; Vogelauer, M; Burggraf, S; Pond, A; Grim-Stieger, M; Cvecka, J; Sedliak, M; Tirpáková, V; Mayr, W; Sarabon, N; Rossini, K; Barberi, L; De Rossi, M; Romanello, V; Boncompagni, S; Musarò, A; Sandri, M; Protasi, F; Carraro, U; Kern, H

    2015-02-01

    Aging is usually accompanied by a significant reduction in muscle mass and force. To determine the relative contribution of inactivity and aging per se to this decay, we compared muscle function and structure in (a) male participants belonging to a group of well-trained seniors (average of 70 years) who exercised regularly in their previous 30 years and (b) age-matched healthy sedentary seniors with (c) active young men (average of 27 years). The results collected show that relative to their sedentary cohorts, muscle from senior sportsmen have: (a) greater maximal isometric force and function, (b) better preserved fiber morphology and ultrastructure of intracellular organelles involved in Ca(2+) handling and ATP production, (c) preserved muscle fibers size resulting from fiber rescue by reinnervation, and (d) lowered expression of genes related to autophagy and reactive oxygen species detoxification. All together, our results indicate that: (a) skeletal muscle of senior sportsmen is actually more similar to that of adults than to that of age-matched sedentaries and (b) signaling pathways controlling muscle mass and metabolism are differently modulated in senior sportsmen to guarantee maintenance of skeletal muscle structure, function, bioenergetic characteristics, and phenotype. Thus, regular physical activity is a good strategy to attenuate age-related general decay of muscle structure and function (ClinicalTrials.gov: NCT01679977).

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

    PubMed

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

    2014-01-01

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

  5. Intellectual Decline.

    ERIC Educational Resources Information Center

    Guilford, J.P.

    In investigations of decline of intellectual status with age, cross-sectional and longitudinal studies give divergent results--the former show almost universal declines in test performances among older groups while the latter often show gains. Although few structure-of-intellect (SI) factors have been explored in relation to adult ages, two kinds…

  6. Cognitive declines in healthy aging: evidence from multiple aspects of interference resolution.

    PubMed

    Pettigrew, Corinne; Martin, Randi C

    2014-06-01

    The present study tested the hypothesis that older adults show age-related deficits in interference resolution, also referred to as inhibitory control. Although oftentimes considered as a unitary aspect of executive function, various lines of work support the notion that interference resolution may be better understood as multiple constructs, including resistance to proactive interference (PI) and response-distractor inhibition (e.g., Friedman & Miyake, 2004). Using this dichotomy, the present study assessed whether older adults (relative to younger adults) show impaired performance across both, 1, or neither of these interference resolution constructs. To do so, we used multiple tasks to tap each construct and examined age effects at both the single task and latent variable levels. Older adults consistently demonstrated exaggerated interference effects across resistance to PI tasks. Although the results for the response-distractor inhibition tasks were less consistent at the individual task level analyses, age effects were evident on multiple tasks, as well as at the latent variable level. However, results of the latent variable modeling suggested declines in interference resolution are best explained by variance that is common to the 2 interference resolution constructs measured herein. Furthermore, the effect of age on interference resolution was found to be both distinct from declines in working memory, and independent of processing speed. These findings suggest multiple cognitive domains are independently sensitive to age, but that declines in the interference resolution constructs measured herein may originate from a common cause.

  7. Age-related macular degeneration.

    PubMed

    Lim, Laurence S; Mitchell, Paul; Seddon, Johanna M; Holz, Frank G; Wong, Tien Y

    2012-05-05

    Age-related macular degeneration is a major cause of blindness worldwide. With ageing populations in many countries, more than 20% might have the disorder. Advanced age-related macular degeneration, including neovascular age-related macular degeneration (wet) and geographic atrophy (late dry), is associated with substantial, progressive visual impairment. Major risk factors include cigarette smoking, nutritional factors, cardiovascular diseases, and genetic markers, including genes regulating complement, lipid, angiogenic, and extracellular matrix pathways. Some studies have suggested a declining prevalence of age-related macular degeneration, perhaps due to reduced exposure to modifiable risk factors. Accurate diagnosis combines clinical examination and investigations, including retinal photography, angiography, and optical coherence tomography. Dietary anti-oxidant supplementation slows progression of the disease. Treatment for neovascular age-related macular degeneration incorporates intraocular injections of anti-VEGF agents, occasionally combined with other modalities. Evidence suggests that two commonly used anti-VEGF therapies, ranibizumab and bevacizumab, have similar efficacy, but possible differences in systemic safety are difficult to assess. Future treatments include inhibition of other angiogenic factors, and regenerative and topical therapies.

  8. In the aging housefly aconitase is the only citric acid cycle enzyme to decline significantly.

    PubMed

    Yarian, Connie S; Sohal, Rajindar S

    2005-04-01

    The main objective of this study was to determine if the activities of the mitochondrial citric acid cycle enzymes are altered during the normal aging process. Flight muscle mitochondria of houseflies of different ages were used as a model system because of their apparent age-related decline in bioenergetic efficiency, evident as a failure of flying ability. The maximal activities of each of the citric acid cycle enzymes were determined in preparations of mitochondria from flies of relatively young, middle, and old age. Aconitase was the only enzyme exhibiting altered activity during aging. The maximal activity of aconitase from old flies was decreased by 44% compared to that from young flies while the other citric acid cycle enzymes showed no change in activity with age. It is suggested that the selective age-related decrease in aconitase activity is likely to contribute to a decline in the efficiency of mitochondrial bioenergetics, as well as result in secondary effects associated with accumulation of citrate and redox-active iron.

  9. 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…

  10. Cohort Differences in Cognitive Aging and Terminal Decline in the Seattle Longitudinal Study

    PubMed Central

    Gerstorf, Denis; Ram, Nilam; Hoppmann, Christiane; Willis, Sherry L.; Schaie, K. Warner

    2011-01-01

    Life span researchers have long been interested in how and why fundamental aspects of human ontogeny differ between cohorts of people who have lived through different historical epochs. When examined at the same age, later born cohorts are often cognitively and physically fitter than earlier born cohorts. Less is known, however, about cohort differences in the rate of cognitive aging and if, at the very end of life, pervasive mortality-related processes overshadow and minimize cohort differences. We used data on 5 primary mental abilities from the Seattle Longitudinal Study (Schaie, 2005) to compare both age-related and mortality-related changes between earlier born cohorts (1886–1913) and later born cohorts (1914–1948). Our models covary for several individual and cohort differences in central indicators of life expectancy, education, health, and gender. Age-related growth models corroborate and extend earlier findings by documenting level differences at age 70 of up to 0.50 SD and less steep rates of cognitive aging on all abilities between 50 and 80 years of age favoring the later born cohort. In contrast, mortality-related models provide limited support for positive cohort differences. The later born cohort showed steeper mortality-related declines. We discuss possible reasons why often reported positive secular trends in age-related processes may not generalize to the vulnerable segment of the population that is close to death and suggest routes for further inquiry. PMID:21517155

  11. Parenchyma cell respiration and survival in secondary xylem: does metabolic activity decline with cell age?

    PubMed

    Spicer, R; Holbrook, N M

    2007-08-01

    Sapwood respiration often declines towards the sapwood/heartwood boundary, but it is not known if parenchyma metabolic activity declines with cell age. We measured sapwood respiration in five temperate species (sapwood age range of 5-64 years) and expressed respiration on a live cell basis by quantifying living parenchyma. We found no effect of parenchyma age on respiration in two conifers (Pinus strobus, Tsuga canadensis), both of which had significant amounts of dead parenchyma in the sapwood. In angiosperms (Acer rubrum, Fraxinus americana, Quercus rubra), both bulk tissue and live cell respiration were reduced by about one-half in the oldest relative to the youngest sapwood, and all sapwood parenchyma remained alive. Conifers and angiosperms had similar bulk tissue respiration despite a smaller proportion of parenchyma in conifers (5% versus 15-25% in angiosperms), such that conifer parenchyma respired at rates about three times those of angiosperms. The fact that 5-year-old parenchyma cells respired at the same rate as 25-year-old cells in conifers suggests that there is no inherent or intrinsic decline in respiration as a result of cellular ageing. In contrast, it is not known whether differences observed in cellular respiration rates of angiosperms are a function of age per se, or whether active regulation of metabolic rate or positional effects (e.g. proximity to resources and/or hormones) could be the cause of reduced respiration in older sapwood.

  12. Moving Forward: Age Effects on the Cerebellum Underlie Cognitive and Motor Declines

    PubMed Central

    Bernard, Jessica A.; Seidler, Rachael D.

    2014-01-01

    Though the cortical contributions to age-related declines in motor and cognitive performance are well-known, the potential contributions of the cerebellum are less clear. The diverse functions of the cerebellum make it an important structure to investigate in aging. Here, we review the extant literature on this topic. To date, there is evidence to indicate that there are morphological age differences in the cerebellum that are linked to motor and cognitive behavior. Cerebellar morphology is often as good as -- or even better -- at predicting performance than the prefrontal cortex. We also touch on the few studies using functional neuroimaging and connectivity analyses that further implicate the cerebellum in age-related performance declines. Importantly, we provide a conceptual framework for the cerebellum influencing age differences in performance, centered on the notion of degraded internal models. The evidence indicating that cerebellar age differences associate with performance highlights the need for additional work in this domain to further elucidate the role of the cerebellum in age differences in movement control and cognitive function. PMID:24594194

  13. Age-associated losses of brain volume predict longitudinal cognitive declines over 8 to 20 years.

    PubMed

    Rabbitt, Patrick; Ibrahim, Said; Lunn, Mary; Scott, Marietta; Thacker, Neil; Hutchinson, Charles; Horan, Michael; Pendleton, Neil; Jackson, Alan

    2008-01-01

    Absolute differences in global brain volume predict differences in cognitive ability among healthy older adults. However, absolute differences confound lifelong differences in brain size with amounts of age-related shrinkage. Measurements of cerebrospinal fluid (CSF) volume were made to estimate age-related shrinkage in 93 healthy volunteers aged 63 to 86 years. Their current levels of brain shrinkage predicted their amounts of decline over the previous 8 to 20 years on repeated assessments during a longitudinal study on the Cattell "Culture Fair" Intelligence Test, on two tests of information processing speed, and marginally on the Wechsler Adult Intelligence Scale (D. Wechsler, 1981), but not on three memory tests. Loss of brain volume is an effective marker both for current cognitive status and for amounts and rates of previous age-related cognitive losses.

  14. Intracellular calcium buffering declines in aging adrenergic nerves.

    PubMed

    Tsai, H; Hewitt, C W; Buchholz, J N; Duckles, S P

    1997-01-01

    Stimulation-evoked norepinephrine release from rat tail artery adrenergic nerves increased with advancing age in the Fischer-344 rat when function of norepinephrine uptake mechanisms and prejunctional alpha-2 adrenoceptors were blocked. When calcium channels were bypassed with the ionophore, ionomycin (4 microM), norepinephrine release from aged nerves (20 months) was still elevated as compared to 6-month-old nerves. Norepinephrine release stimulated by high K+ was also higher in 20-month nerves. The intracellular calcium chelator, 1,2 bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetomethylester (BAPTA/AM), was used to determine whether age-related increases in norepinephrine release could be reversed with the addition of an artificial intracellular calcium buffer. Exposure to BAPTA/AM decreased stimulation-evoked norepinephrine release in both old and young tail arteries; however, the effect was significantly greater in older arteries. When mitochondrial calcium uptake was compromised using the uncoupler of mitochondrial oxidative phosphorylation, dinitrophenol, BAPTA caused a further decrease in stimulation-evoked norepinephrine release in 20-month tail arteries with much less effect in 6-month-old nerves. These results suggest that intracellular calcium buffering is less efficient in older nerves.

  15. Hot Topics in Research: Preventive Neuroradiology in Brain Aging and Cognitive Decline.

    PubMed

    Raji, C A; Eyre, H; Wei, S H; Bredesen, D E; Moylan, S; Law, M; Small, G; Thompson, P M; Friedlander, R M; Silverman, D H; Baune, B T; Hoang, T A; Salamon, N; Toga, A W; Vernooij, M W

    2015-10-01

    Preventive neuroradiology is a new concept supported by growing literature. The main rationale of preventive neuroradiology is the application of multimodal brain imaging toward early and subclinical detection of brain disease and subsequent preventive actions through identification of modifiable risk factors. An insightful example of this is in the area of age-related cognitive decline, mild cognitive impairment, and dementia with potentially modifiable risk factors such as obesity, diet, sleep, hypertension, diabetes, depression, supplementation, smoking, and physical activity. In studying this link between lifestyle and cognitive decline, brain imaging markers may be instrumental as quantitative measures or even indicators of early disease. The purpose of this article is to provide an overview of the major studies reflecting how lifestyle factors affect the brain and cognition aging. In this hot topics review, we will specifically focus on obesity and physical activity.

  16. Epigenetics of Aging and Aging-related Disease

    PubMed Central

    2014-01-01

    Aging is associated with a wide range of human disorders, including cancer, diabetes, cardiovascular, and neurodegenerative diseases. Long thought to be an inexorable road toward decline and diseases, aging is in fact remarkably plastic. Such plasticity could be harnessed to approach age-related diseases from a novel perspective. Although many studies have focused on the genes that impact aging, the nongenetic regulation of aging is gaining increasing attention. Specifically, aging is associated with profound epigenetic changes, resulting in alterations of gene expression and disturbances in broad genome architecture and the epigenomic landscape. The potential reversibility of these epigenetic changes that occur as a hallmark of aging offers exciting opportunities to alter the trajectory of age-related diseases. This short review highlights key epigenetic players in the regulation of aging, as well as both future goals and challenges to the utilization of epigenetic strategies to delay and reverse the main diseases of aging. PMID:24833581

  17. Epigenetics of aging and aging-related disease.

    PubMed

    Brunet, Anne; Berger, Shelley L

    2014-06-01

    Aging is associated with a wide range of human disorders, including cancer, diabetes, cardiovascular, and neurodegenerative diseases. Long thought to be an inexorable road toward decline and diseases, aging is in fact remarkably plastic. Such plasticity could be harnessed to approach age-related diseases from a novel perspective. Although many studies have focused on the genes that impact aging, the nongenetic regulation of aging is gaining increasing attention. Specifically, aging is associated with profound epigenetic changes, resulting in alterations of gene expression and disturbances in broad genome architecture and the epigenomic landscape. The potential reversibility of these epigenetic changes that occur as a hallmark of aging offers exciting opportunities to alter the trajectory of age-related diseases. This short review highlights key epigenetic players in the regulation of aging, as well as both future goals and challenges to the utilization of epigenetic strategies to delay and reverse the main diseases of aging.

  18. Multiple stressor effects in relation to declining amphibian populations

    USGS Publications Warehouse

    2003-01-01

    This book represents the work of several authors who participated in the symposium entitled 'Multiple Stressor Effects in Relation to Declining Amphibian Populations' convened 16-17 April, 2002, in Pittsburgh, Pennsylvania. Declines of amphibian populations of varying severity have been observed for many years, and in the last 8 to 10 years considerable progress has been made in documenting the status and distribution of a range of amphibian species. Habitat alteration and destruction are likely linked to many amphibian declines, but a variety of other factors, both anthropogenic and natural, have been observed or proposed to have caused declines or extinctions of amphibian populations. Unfortunately, determining the environmental causes for the decline of many species has proven difficult. The goals of this symposium were three-fold. First, highlight ASTM's historic role in providing a forum for the standardization of amphibian toxicity test methods and the characterization of adverse effects potentially associated with chemical stressors. Second, demonstrate through case studies the current state of technical 'tools' available to biologists, ecologists, environmental scientists and natural resource professionals for assessing amphibian populations exposed to various environmental stressors. And third, characterize a process that brings a range of interdisciplinary technical and management tools to the tasks of causal analysis, especially as those relate to a multiple stressor risk assessment 'mind-set.' As part of the symposium, scientists and resource management professionals from diverse fields including ecotoxicology and chemistry, ecology and field biology, conservation biology, and natural resource management and policy contributed oral presentations and posters that addressed topics related to declining amphibian populations and the role that various stressors have in those losses. The papers contained in this publication reflect the commitment of ASTM

  19. Education does not slow cognitive decline with aging: 12-year evidence from the victoria longitudinal study.

    PubMed

    Zahodne, Laura B; Glymour, M Maria; Sparks, Catharine; Bontempo, Daniel; Dixon, Roger A; MacDonald, Stuart W S; Manly, Jennifer J

    2011-11-01

    Although the relationship between education and cognitive status is well-known, evidence regarding whether education moderates the trajectory of cognitive change in late life is conflicting. Early studies suggested that higher levels of education attenuate cognitive decline. More recent studies using improved longitudinal methods have not found that education moderates decline. Fewer studies have explored whether education exerts different effects on longitudinal changes within different cognitive domains. In the present study, we analyzed data from 1014 participants in the Victoria Longitudinal Study to examine the effects of education on composite scores reflecting verbal processing speed, working memory, verbal fluency, and verbal episodic memory. Using linear growth models adjusted for age at enrollment (range, 54-95 years) and gender, we found that years of education (range, 6-20 years) was strongly related to cognitive level in all domains, particularly verbal fluency. However, education was not related to rates of change over time for any cognitive domain. Results were similar in individuals older or younger than 70 at baseline, and when education was dichotomized to reflect high or low attainment. In this large longitudinal cohort, education was related to cognitive performance but unrelated to cognitive decline, supporting the hypothesis of passive cognitive reserve with aging.

  20. Functional aging in the nervous system contributes to age-dependent motor activity decline in C. elegans.

    PubMed

    Liu, Jie; Zhang, Bi; Lei, Haoyun; Feng, Zhaoyang; Liu, Jianfeng; Hsu, Ao-Lin; Xu, X Z Shawn

    2013-09-03

    Aging is characterized by a progressive decline in multiple physiological functions (i.e., functional aging). As animals age, they exhibit a gradual loss in motor activity, but the underlying mechanisms remain unclear. Here we approach this question in C. elegans by functionally characterizing its aging nervous system and muscles. We find that motor neurons exhibit a progressive functional decline, beginning in early life. Surprisingly, body-wall muscles, which were previously thought to undergo functional aging, do not manifest such a decline until mid-late life. Notably, motor neurons first develop a deficit in synaptic vesicle fusion followed by that in quantal size and vesicle docking/priming, revealing specific functional deteriorations in synaptic transmission. Pharmacological stimulation of synaptic transmission can improve motor activity in aged animals. These results uncover a critical role for the nervous system in age-dependent motor activity decline in C. elegans and provide insights into how functional aging occurs in this organism.

  1. Age-dependent decline of nogo-a protein in the mouse cerebrum.

    PubMed

    Kumari, Anita; Thakur, M K

    2014-11-01

    Nogo-A, a myelin-associated neurite growth inhibitory protein, is implicated in synaptic plasticity. It binds to its receptor namely the Nogo-66 receptor1 (NgR1) and regulates filamentous (F) actin dynamics via small GTPases of the Rho family, RhoA kinase (ROCK), LimK and cofilin. These proteins are associated with the structural plasticity, one of the components of synaptic plasticity, which is known to decline with normal aging. So, the level of Nogo-A and its receptor NgR1 are likely to vary during normal brain aging. However, it is not clearly understood how the levels of Nogo-A and its receptor NgR1 change in the cerebrum during aging. Several studies show an age- and gender-dependent decline in synaptic plasticity. Therefore, the present study was planned to analyze the relative changes in the mRNA and protein levels of Nogo-A and NgR1 in both male and female mice cerebrum during normal aging. Western blot analysis has shown decrease in Nogo-A protein level during aging in both male and female mice cerebrum. This was further confirmed by immunofluorescence analysis. RT-PCR analysis of Nogo-A mRNA showed no significant difference in the above-mentioned groups. This was also supported by in situ hybridization. NgR1 protein and its mRNA expression levels showed no significant alteration with aging in the cerebrum of both male and female mice. Taken together, we speculate that the downregulation of Nogo-A protein might have a role in the altered synaptic plasticity during aging.

  2. Adiposity, muscle mass, and muscle strength in relation to functional decline in older persons.

    PubMed

    Schaap, Laura A; Koster, Annemarie; Visser, Marjolein

    2013-01-01

    Aging is associated with changes in body composition and muscle strength. This review aimed to determine the relation between different body composition measures and muscle strength measures and functional decline in older men and women. By use of relevant databases (PubMed, Embase, and CINAHL) and keywords in a search from 1976 to April 2012, 50 articles were reviewed that met the inclusion criteria (written in English, a prospective, longitudinal design, involving older persons aged 65 years or more, and at least one of the measures that follow: body mass index (BMI), waist circumference, waist/hip ratio, midarm circumference, fat mass, muscle fat infiltration, muscle mass, or strength as independent variables and a measure of functional decline as outcome measure). Meta-analyses were performed and revealed that BMI ≥30 and low muscle strength were associated with functional decline (pooled odds ratio (OR) = 1.60, 95% confidence interval (CI): 1.43, 1.80, for BMI ≥30 and OR = 1.86, 95% CI: 1.32, 2.64, for muscle strength). Low muscle mass was not significantly associated with functional decline (pooled OR = 1.19, 95% CI: 0.98, 1.45). Future intervention research should focus on positive changes in body composition to prevent onset or worsening of functional decline in old age.

  3. Decline of executive processes affects identification of emotional facial expression in aging.

    PubMed

    García-Rodríguez, Beatriz; Fusari, Anna; Fernández-Guinea, Sara; Frank, Ana; Molina, José Antonio; Ellgring, Heiner

    2011-02-01

    The current study examined the hypothesis that old people have a selective deficit in the identification of emotional facial expressions (EFEs) when the task conditions require the mechanism of the central executive. We have used a Dual Task (DT) paradigm to assess the role of visuo-spatial interference of working memory when processing emotional faces under two conditions: DT at encoding and DT at retrieval. Previous studies have revealed a loss of the ability to identify specific emotional facial expressions (EFEs) in old age. This has been consistently associated with a decline of the ability to coordinate the performance of two tasks concurrently. Working memory is usually tested using DT paradigms. Regarding to aging, there is evidence that with DT performance during encoding the costs are substantial. In contrast, the introduction of a secondary task after the primary task (i.e. at retrieval), had less detrimental effects on primary task performance in either younger or older adults. Our results demonstrate that aging is associated with higher DT costs when EFEs are identified concurrently with a visuo-spatial task. In contrast, there was not a significant age-related decline when the two tasks were presented sequentially. This suggests a deficit of the central executive rather than visuo-spatial memory deficits. The current data provide further support for the hypothesis that emotional processing is "top-down" controlled, and suggest that the deficits in emotional processing of old people depend, above all, on specific cognitive impairment.

  4. Quantitative T2 mapping of white matter: applications for ageing and cognitive decline

    NASA Astrophysics Data System (ADS)

    Knight, Michael J.; McCann, Bryony; Tsivos, Demitra; Dillon, Serena; Coulthard, Elizabeth; Kauppinen, Risto A.

    2016-08-01

    In MRI, the coherence lifetime T2 is sensitive to the magnetic environment imposed by tissue microstructure and biochemistry in vivo. Here we explore the possibility that the use of T2 relaxometry may provide information complementary to that provided by diffusion tensor imaging (DTI) in ageing of healthy controls (HC), Alzheimer’s disease (AD) and mild cognitive impairment (MCI). T2 and diffusion MRI metrics were quantified in HC and patients with MCI and mild AD using multi-echo MRI and DTI. We used tract-based spatial statistics (TBSS) to evaluate quantitative MRI parameters in white matter (WM). A prolonged T2 in WM was associated with AD, and able to distinguish AD from MCI, and AD from HC. Shorter WM T2 was associated with better cognition and younger age in general. In no case was a reduction in T2 associated with poorer cognition. We also applied principal component analysis, showing that WM volume changes independently of  T2, MRI diffusion indices and cognitive performance indices. Our data add to the evidence that age-related and AD-related decline in cognition is in part attributable to WM tissue state, and much less to WM quantity. These observations suggest that WM is involved in AD pathology, and that T2 relaxometry is a potential imaging modality for detecting and characterising WM in cognitive decline and dementia.

  5. 3T hippocampal glutamate-glutamine complex reflects verbal memory decline in aging.

    PubMed

    Nikolova, Simona; Stark, Shauna M; Stark, Craig E L

    2017-03-18

    The hippocampus is a critical site for alterations that are responsible for age-related changes in memory. Here, we present a relatively novel approach of examining the relationship between memory performance and glutamate-glutamine levels using short echo time magnetic resonance spectroscopy. Specifically, we investigated the relationship between Glx (a composite of glutamate and glutamine) levels in the hippocampus, performance on a word-recall task, and resting-state functional connectivity. While there was no overall difference in Glx intensity between young and aging adults, we identified a positive correlation between delayed word-list recall and Glx, bilaterally in older adults, but not in young adults. Collapsed across age, we also discovered a negative relationship between Glx intensity and resting-state functional connectivity between the anterior hippocampus and regions in the subcallosal gyrus. These findings demonstrate the possible utility of Glx in identifying age-related changes in the brain and behavior and provide encouragement that magnetic resonance spectroscopy can be useful in predicting age-related decline before any physical abnormalities are present.

  6. Causes of sexual decline in aging married men: Germany and America.

    PubMed

    Mazur, A; Mueller, U; Krause, W; Booth, A

    2002-04-01

    Married men in Germany (n=48) and America (n=50) between 50 and 80 years old, none in poor health, provided comparable information on sexual behavior and attitudes, and gave saliva samples from which testosterone was assayed. Sexuality declines with age, as expected. Neither testosterone nor psychological depression explain levels of sexuality. In both nations, wife's desire for intercourse, subject's ability to maintain an erection, and subject's imagination about other women, explain certain aspects of sexuality. Subject's health and marital satisfaction are related to sexuality among Americans but not among Germans. Behavioral models for the two nations are compared.

  7. Demographic and clinical characteristics related to cognitive decline in Alzheimer disease in China

    PubMed Central

    Peng, Dantao; Shi, Zhihong; Xu, Jun; Shen, Lu; Xiao, Shifu; Zhang, Nan; Li, Yi; Jiao, Jinsong; Wang, Yan-Jiang; Liu, Shuai; Zhang, Meilin; Wang, Meng; Liu, Shuling; Zhou, Yuying; Zhang, Xiao; Gu, Xiao-hua; Yang, Ce-ce; Wang, Yu; Jiao, Bin; Tang, Beisha; Wang, Jinhuan; Yu, Tao; Ji, Yong

    2016-01-01

    Abstract Alzheimer disease (AD) is the most frequent cause of dementia. AD diagnosis, progression, and treatment have not been analyzed nationwide in China. The primary aim of this study was to analyze demographic and clinical characteristics related to cognitive decline in AD patients treated at outpatient clinics in China. We performed a retrospective study of 1993 AD patients at 10 cognitive centers across 8 cities in China from March 2011 to October 2014. Of these, 891 patients were followed for more than 1 year. The mean age at diagnosis was 72.0 ± 10.0 years (range 38–96 years), and the mean age at onset of AD was 69.8 ± 9.5 years. Most patients (65.1%) had moderate to severe symptoms at the time of diagnosis, and mean Mini-Mental State Examination at diagnosis was 15.7 ± 7.7. AD patients showed significant cognitive decline at 12 months after diagnosis. Having more than 9 years of formal education was an independent risk factor related to rapid cognitive decline [odds ratio (OR) = 1.80; 95% confidence interval (95% CI): 1.11–2.91]. Early-onset AD patients experienced more rapid cognitive decline than late-onset patients (OR = 1.83; 95% CI: 1.09–3.06). Most AD patients in China had moderate to severe symptoms at the time of diagnosis and experienced significant cognitive decline within 1 year. Rapid cognitive decline in AD was related to having a higher educational level and younger age of onset. PMID:27367978

  8. Cognitive training and Bacopa monnieri: Evidence for a combined intervention to alleviate age associated cognitive decline.

    PubMed

    McPhee, Grace M; Downey, Luke A; Noble, Anthony; Stough, Con

    2016-10-01

    As the elderly population grows the impact of age associated cognitive decline as well as neurodegenerative diseases such as Alzheimer's disease and dementia will increase. Ageing is associated with consistent impairments in cognitive processes (e.g., processing speed, memory, executive function and learning) important for work, well-being, life satisfaction and overall participation in society. Recently, there has been increased effort to conduct research examining methods to improve cognitive function in older citizens. Cognitive training has been shown to improve performance in some cognitive domains; including memory, processing speed, executive function and attention in older adults. These cognitive changes are thought to be related to improvements in brain connectivity and neural circuitry. Bacopa monnieri has also been shown to improve specific domains of cognition, sensitive to age associated cognitive decline (particularly processing speed and memory). These Bacopa monnieri dependent improvements may be due to the increase in specific neuro-molecular mechanisms implicated in the enhancement of neural connections in the brain (i.e. synaptogenesis). In particular, a number of animal studies have shown Bacopa monnieri consumption upregulates calcium dependent kinases in the synapse and post-synaptic cell, crucial for strengthening and growing connections between neurons. These effects have been shown to occur in areas important for cognitive processes, such as the hippocampus. As Bacopa monnieri has shown neuro-molecular mechanisms that encourage synaptogenesis, while cognitive training enhances brain connectivity, Bacopa monnieri supplementation could theoretically enhance and strengthen synaptic changes acquired through cognitive training. Therefore, the current paper hypothesises that the combination of these two interventions could improve cognitive outcomes, over and above the effects of administrating these interventions independently, as an effective

  9. Early age decline in DNA repair capacity in the liver: in depth profile of differential gene expression

    PubMed Central

    Guedj, Avital; Geiger-Maor, Anat; Galun, Eithan; Amsalem, Hagai; Rachmilewitz, Jacob

    2016-01-01

    Aging is associated with progressive decline in cell function and with increased damage to macromolecular components. DNA damage, in the form of double-strand breaks (DSBs), increases with age and in turn, contributes to the aging process and age-related diseases. DNA strand breaks triggers a set of highly orchestrated signaling events known as the DNA damage response (DDR), which coordinates DNA repair. However, whether the accumulation of DNA damage with age is a result of decreased repair capacity, remains to be determined. In our study we showed that with age there is a decline in the resolution of foci containing γH2AX and pKAP-1 in diethylnitrosamine (DEN)-treated mouse livers, already evident at a remarkably early age of 6-months. Considerable age-dependent differences in global gene expression profiles in mice livers after exposure to DEN, further affirmed these age related differences in the response to DNA damage. Functional analysis identified p53 as the most overrepresented pathway that is specifically enhanced and prolonged in 6-month-old mice. Collectively, our results demonstrated an early decline in DNA damage repair that precedes ‘old age’, suggesting this may be a driving force contributing to the aging process rather than a phenotypic consequence of old age. PMID:27922819

  10. A review of new insights on the association between hearing loss and cognitive decline in ageing.

    PubMed

    Fortunato, S; Forli, F; Guglielmi, V; De Corso, E; Paludetti, G; Berrettini, S; Fetoni, A R

    2016-06-01

    Age-related hearing loss (ARHL) has a multifactorial pathogenesis and it is an inevitable hearing impairment associated with reduction of communicative skills related to ageing. Increasing evidence has linked ARHL to more rapid progression of cognitive decline and incidental dementia. Many aspects of daily living of elderly people have been associated to hearing abilities, showing that hearing loss (HL) affects the quality of life, social relationships, motor skills, psychological aspects and function and morphology in specific brain areas. Epidemiological and clinical studies confirm the assumption of a relationship between these conditions. However, the mechanisms are still unclear and are reviewed herein. Long-term hearing deprivation of auditory inputs can impact cognitive performance by decreasing the quality of communication leading to social isolation and depression and facilitate dementia. On the contrary, the limited cognitive skills may reduce the cognitive resources available for auditory perception, increasing the effects of HL. In addition, hearing loss and cognitive decline may reflect a 'common cause' on the auditory pathway and brain. In fact, some pathogenetic factors are recongised in common microvascular disease factors such as diabetes, atherosclerosis and hypertension. Interdisciplinary efforts to investigate and address HL in the context of brain and cognitive ageing are needed. Surprisingly, few studies have been adressed on the effectiveness of hearing aids in changing the natural history of cognitive decline. Effective interventions with hearing aids or cochlear implant may improve social and emotional function, communication, cognitive function and positively impact quality of life. The aim of this review is to overview new insights on this challenging topic and provide new ideas for future research.

  11. Does Sensory Function Decline Independently or Concomitantly with Age? Data from the Baltimore Longitudinal Study of Aging

    PubMed Central

    Gadkaree, Shekhar K.; Sun, Daniel Q.; Li, Carol; Lin, Frank R.; Ferrucci, Luigi; Simonsick, Eleanor M.

    2016-01-01

    Objectives. To investigate whether sensory function declines independently or in parallel with age within a single individual. Methods. Cross-sectional analysis of Baltimore Longitudinal Study of Aging (BLSA) participants who underwent vision (visual acuity threshold), proprioception (ankle joint proprioceptive threshold), vestibular function (cervical vestibular-evoked myogenic potential), hearing (pure-tone average audiometric threshold), and Health ABC physical performance battery testing. Results. A total of 276 participants (mean age 70 years, range 26–93) underwent all four sensory tests. The function of all four systems declined with age. After age adjustment, there were no significant associations between sensory systems. Among 70–79-year-olds, dual or triple sensory impairment was associated with poorer physical performance. Discussion. Our findings suggest that beyond the common mechanism of aging, other distinct (nonshared) etiologic mechanisms may contribute to decline in each sensory system. Multiple sensory impairments influence physical performance among individuals in middle old-age (age 70–79). PMID:27774319

  12. Aging process, cognitive decline and Alzheimer`s disease: can strength training modulate these responses?

    PubMed

    Portugal, Eduardo Matta Mello; Vasconcelos, Poliane Gomes Torres; Souza, Renata; Lattari, Eduardo; Monteiro-Junior, Renato Sobral; Machado, Sergio; Deslandes, Andrea Camaz

    2015-01-01

    Some evidence shows that aerobic training can attenuate the aging effects on the brain structures and functions. However, the strength exercise effects are poorly discussed. Thus, in the present study, the effects of strength training on the brain in elderly people and Alzheimer`s disease (AD) patients were revised. Furthermore, it a biological explanation relating to strength training effects on the brain is proposed. Brain atrophy can be related to neurotransmission dysfunction, like oxidative stress, that generates mitochondrial damage and reduced brain metabolism. Another mechanism is related to amyloid deposition and amyloid tangles, that can be related to reductions on insulin-like growth factor I concentrations. The brain-derived neurotrophic factor also presents reduction during aging process and AD. These neuronal dysfunctions are also related to cerebral blood flow decline that influence brain metabolism. All of these alterations contribute to cognitive impairment and AD. After a long period of strength training, the oxidative stress can be reduced, the brain-derived neurotrophic factor and insulin-like growth factor I serum concentrations enhance, and the cognitive performance improves. Considering these results, we can infer that strength training can be related to increased neurogenesis, neuroplasticity and, consequently, counteracts aging effects on the brain. The effect of strength training as an additional treatment of AD needs further investigation.

  13. A greater decline in female facial attractiveness during middle age reflects women's loss of reproductive value.

    PubMed

    Maestripieri, Dario; Klimczuk, Amanda C E; Traficonte, Daniel M; Wilson, M Claire

    2014-01-01

    Facial attractiveness represents an important component of an individual's overall attractiveness as a potential mating partner. Perceptions of facial attractiveness are expected to vary with age-related changes in health, reproductive value, and power. In this study, we investigated perceptions of facial attractiveness, power, and personality in two groups of women of pre- and post-menopausal ages (35-50 years and 51-65 years, respectively) and two corresponding groups of men. We tested three hypotheses: (1) that perceived facial attractiveness would be lower for older than for younger men and women; (2) that the age-related reduction in facial attractiveness would be greater for women than for men; and (3) that for men, there would be a larger increase in perceived power at older ages. Eighty facial stimuli were rated by 60 (30 male, 30 female) middle-aged women and men using online surveys. Our three main hypotheses were supported by the data. Consistent with sex differences in mating strategies, the greater age-related decline in female facial attractiveness was driven by male respondents, while the greater age-related increase in male perceived power was driven by female respondents. In addition, we found evidence that some personality ratings were correlated with perceived attractiveness and power ratings. The results of this study are consistent with evolutionary theory and with previous research showing that faces can provide important information about characteristics that men and women value in a potential mating partner such as their health, reproductive value, and power or possession of resources.

  14. Vitamin D prevents cognitive decline and enhances hippocampal synaptic function in aging rats

    PubMed Central

    Latimer, Caitlin S.; Brewer, Lawrence D.; Searcy, James L.; Chen, Kuey-Chu; Popović, Jelena; Kraner, Susan D.; Thibault, Olivier; Blalock, Eric M.; Landfield, Philip W.; Porter, Nada M.

    2014-01-01

    Vitamin D is an important calcium-regulating hormone with diverse functions in numerous tissues, including the brain. Increasing evidence suggests that vitamin D may play a role in maintaining cognitive function and that vitamin D deficiency may accelerate age-related cognitive decline. Using aging rodents, we attempted to model the range of human serum vitamin D levels, from deficient to sufficient, to test whether vitamin D could preserve or improve cognitive function with aging. For 5–6 mo, middle-aged F344 rats were fed diets containing low, medium (typical amount), or high (100, 1,000, or 10,000 international units/kg diet, respectively) vitamin D3, and hippocampal-dependent learning and memory were then tested in the Morris water maze. Rats on high vitamin D achieved the highest blood levels (in the sufficient range) and significantly outperformed low and medium groups on maze reversal, a particularly challenging task that detects more subtle changes in memory. In addition to calcium-related processes, hippocampal gene expression microarrays identified pathways pertaining to synaptic transmission, cell communication, and G protein function as being up-regulated with high vitamin D. Basal synaptic transmission also was enhanced, corroborating observed effects on gene expression and learning and memory. Our studies demonstrate a causal relationship between vitamin D status and cognitive function, and they suggest that vitamin D-mediated changes in hippocampal gene expression may improve the likelihood of successful brain aging. PMID:25267625

  15. Age-dependent decline in fin regenerative capacity in the short-lived fish Nothobranchius furzeri

    PubMed Central

    Wendler, Sebastian; Hartmann, Nils; Hoppe, Beate; Englert, Christoph

    2015-01-01

    The potential to regenerate declines with age in a wide range of organisms. A popular model system to study the mechanisms of regeneration is the fin of teleost fish, which has the ability to fully regrow upon amputation. Here, we used the short-lived killifish Nothobranchius furzeri to analyse the impact of aging on fin regeneration in more detail. We observed that young fish were able to nearly completely (98%) regenerate their amputated caudal fins within 4 weeks, whereas middle-aged fish reached 78%, old fish 57% and very old fish 46% of their original fin size. The difference in growth rate between young and old fish was already significant at 3 days post amputation (dpa) and increased with time. We therefore hypothesized that early events are crucial for the age-related differences in regenerative capacity. Indeed, we could observe a higher percentage of proliferating cells in early regenerating fin tissue of young fish compared with aged fish and larger fractions of apoptotic cells in aged fish. Furthermore, young fish showed peak upregulation of several genes involved in fgf and wnt/β-catenin signalling at an earlier time point than old fish. Our findings suggest that regenerative processes are initiated earlier and that regeneration overall is more efficient in younger fish. PMID:26121607

  16. Age-dependent decline in fin regenerative capacity in the short-lived fish Nothobranchius furzeri.

    PubMed

    Wendler, Sebastian; Hartmann, Nils; Hoppe, Beate; Englert, Christoph

    2015-10-01

    The potential to regenerate declines with age in a wide range of organisms. A popular model system to study the mechanisms of regeneration is the fin of teleost fish, which has the ability to fully regrow upon amputation. Here, we used the short-lived killifish Nothobranchius furzeri to analyse the impact of aging on fin regeneration in more detail. We observed that young fish were able to nearly completely (98%) regenerate their amputated caudal fins within 4 weeks, whereas middle-aged fish reached 78%, old fish 57% and very old fish 46% of their original fin size. The difference in growth rate between young and old fish was already significant at 3 days post amputation (dpa) and increased with time. We therefore hypothesized that early events are crucial for the age-related differences in regenerative capacity. Indeed, we could observe a higher percentage of proliferating cells in early regenerating fin tissue of young fish compared with aged fish and larger fractions of apoptotic cells in aged fish. Furthermore, young fish showed peak upregulation of several genes involved in fgf and wnt/β-catenin signalling at an earlier time point than old fish. Our findings suggest that regenerative processes are initiated earlier and that regeneration overall is more efficient in younger fish.

  17. Strial microvascular pathology and age-associated endocochlear potential decline in NOD congenic mice

    PubMed Central

    Ohlemiller, Kevin K.; Rice, Mary E. Rybak; Gagnon, Patricia M.

    2008-01-01

    NOD/ShiLtJ (previously NOD/LtJ) inbred mice show polygenic autoimmune disease and are commonly used to model autoimmune-related Type I diabetes, as well as Sjogren’s syndrome. They also show rapidly progressing hearing loss, partly due to the combined effects of Cdh23ahl and Ahl2. Congenic NOD.NON-H2nb1/LtJ mice, which carry corrective alleles within the H2 histocompatibility gene complex, are free from diabetes and other overt signs of autoimmune disease, but still exhibit rapidly progressive hearing loss. Here we show that cochlear pathology in these congenics broadly includes hair cell and neuronal loss, plus endocochlear potential (EP) decline from initially normal values after 2 months of age. The EP reduction follows often dramatic degeneration of capillaries in stria vascularis, with resulting strial degeneration. The cochlear modiolus in the congenic mice also features perivascular inclusions that resemble those in some mouse autoimmune models. We posit that cochlear hair cell/neural and strial pathology in NOD.NON-H2nb1 mice arise independently. While sensory cell loss may be closely tied to Cdh23ahl and Ahl2, the strial microvascular pathology and modiolar anomalies we observe may arise from alleles on the NOD background related to immune function. Age-associated EP decline in NOD.NON-H2nb1 mice may model forms of strial age-related hearing loss caused principally by microvascular disease. The remarkable strial capillary loss in these mice may also be useful for studying the relation between strial vascular insufficiency and strial function. PMID:18727954

  18. Fast but fleeting: adaptive motor learning processes associated with aging and cognitive decline.

    PubMed

    Trewartha, Kevin M; Garcia, Angeles; Wolpert, Daniel M; Flanagan, J Randall

    2014-10-01

    Motor learning has been shown to depend on multiple interacting learning processes. For example, learning to adapt when moving grasped objects with novel dynamics involves a fast process that adapts and decays quickly-and that has been linked to explicit memory-and a slower process that adapts and decays more gradually. Each process is characterized by a learning rate that controls how strongly motor memory is updated based on experienced errors and a retention factor determining the movement-to-movement decay in motor memory. Here we examined whether fast and slow motor learning processes involved in learning novel dynamics differ between younger and older adults. In addition, we investigated how age-related decline in explicit memory performance influences learning and retention parameters. Although the groups adapted equally well, they did so with markedly different underlying processes. Whereas the groups had similar fast processes, they had different slow processes. Specifically, the older adults exhibited decreased retention in their slow process compared with younger adults. Within the older group, who exhibited considerable variation in explicit memory performance, we found that poor explicit memory was associated with reduced retention in the fast process, as well as the slow process. These findings suggest that explicit memory resources are a determining factor in impairments in the both the fast and slow processes for motor learning but that aging effects on the slow process are independent of explicit memory declines.

  19. Melatonin improves age-induced fertility decline and attenuates ovarian mitochondrial oxidative stress in mice

    PubMed Central

    Song, Chao; Peng, Wei; Yin, Songna; Zhao, Jiamin; Fu, Beibei; Zhang, Jingcheng; Mao, Tingchao; Wu, Haibo; Zhang, Yong

    2016-01-01

    Increasing evidence shows that melatonin protected against age-related mitochondrial oxidative damage. However, the protective effects of melatonin against ovarian aging has not been explored. Young Kunming females (aged 2–3 months) were fed with melatonin added to drinking water for 6 or 12 months (mo). We found that long-term (12 mo) melatonin treatment significantly reduced ovarian aging, as indicated by substantial increases in litter size, pool of follicles, and telomere length as well as oocyte quantity and quality. Melatonin treatment suppressed ovarian mitochondrial oxidative damage by decreasing mitochondrial reactive oxygen species (mROS) generation, inhibiting apoptosis, repressing collapse of mitochondrial membrane potential and preserving respiratory chain complex activities. Female mice fed with melatonin had enhanced mitochondrial antioxidant activities, thus reducing the risk of mitochondrial oxidative damage cause by free radicals. Notably, melatonin treatment enhanced SIRT3 activity but not the protein expression level, and increased the binding affinity of FoxO3a to the promoters of both superoxide dismutase 2 (SOD2) and catalase (CAT). In conclusion, melatonin exerted protection against aging-induced fertility decline and maintenance of mitochondrial redox balance. PMID:27731402

  20. Joint dysfunction and functional decline in middle age myostatin null mice.

    PubMed

    Guo, Wen; Miller, Andrew D; Pencina, Karol; Wong, Siu; Lee, Amanda; Yee, Michael; Toraldo, Gianluca; Jasuja, Ravi; Bhasin, Shalender

    2016-02-01

    Since its discovery as a potent inhibitor for muscle development, myostatin has been actively pursued as a drug target for age- and disease-related muscle loss. However, potential adverse effects of long-term myostatin deficiency have not been thoroughly investigated. We report herein that male myostatin null mice (mstn(-/-)), in spite of their greater muscle mass compared to wild-type (wt) mice, displayed more significant functional decline from young (3-6months) to middle age (12-15months) than age-matched wt mice, measured as gripping strength and treadmill endurance. Mstn(-/-) mice displayed markedly restricted ankle mobility and degenerative changes of the ankle joints, including disorganization of bone, tendon and peri-articular connective tissue, as well as synovial thickening with inflammatory cell infiltration. Messenger RNA expression of several pro-osteogenic genes was higher in the Achilles tendon-bone insertion in mstn(-/-) mice than wt mice, even at the neonatal age. At middle age, higher plasma concentrations of growth factors characteristic of excessive bone remodeling were found in mstn(-/-) mice than wt controls. These data collectively indicate that myostatin may play an important role in maintaining ankle and wrist joint health, possibly through negative regulation of the pro-osteogenic WNT/BMP pathway.

  1. Declining plant nitrogen supply and carbon accumulation in ageing primary boreal forest ecosystems

    NASA Astrophysics Data System (ADS)

    Högberg, Mona N.; Yarwood, Stephanie A.; Trumbore, Susan; Högberg, Peter

    2016-04-01

    Boreal forest soils are commonly characterized by a low plant nitrogen (N) supply. A high tree below-ground allocation of carbon (C) to roots and soil microorganisms in response to the shortage of N may lead to high microbial immobilisation of N, thus aggravating the N limitation. We studied the N supply at a Swedish boreal forest ecosystem chronosequence created by new land rising out of the sea due to iso-static rebound. The youngest soils develop with meadows by the coast, followed by a zone of dinitrogen fixing alder trees, and primary boreal conifer forest on ground up to 560 years old. With increasing ecosystem age, the proportion of microbial C out of the total soil C pool from the youngest to the oldest coniferous ecosystem was constant (c. 1-1.5%), whereas immobilised N (microbial N out of total soil N) increased and approached the levels commonly observed in similar boreal coniferous forests (c. 6-7 %), whereas gross N mineralization declined. Simultaneously, plant foliar N % decreased and the natural abundance of N-15 in the soil increased. More specifically, the difference in N-15 between plant foliage and soil increased, which is related to greater retention of N-15 relative to N-14 by ectomycorrhizal fungi as N is taken up from the soil and some N is transferred to the plant host. In the conifer forest, where these changes were greatest, we found increased fungal biomass in the F- and H-horizons of the mor-layer, in which ectomycorrhizal fungi are known to dominate (the uppermost horizon with litter and moss is dominated by saprotrophic fungi). Hence, we propose that the decreasing N supply to the plants and the subsequent decline in plant production in ageing boreal forests is linked to high tree belowground C allocation to C limited ectomycorrhizal fungi (and other soil microorganisms), a strong sink for available soil N. Data on organic matter C-14 suggested that the largest input of recently fixed plant C occurred in the younger coniferous forest

  2. Genotoxicity of two polycyclic aromatic hydrocarbons declines as they age in soil

    SciTech Connect

    Alexander, R.R.; Alexander, M. )

    1999-06-01

    Rifampicin-resistant mutations were induced in Pseudomonas putida A11rUV growing in soil containing 9,10-dimethyl-1,2-benzanthracene and benzo[a]pyrene. Aging of the compounds for 7 d caused a marked decrease in the mutation rates, and the number of mutants was further reduced after 15 d of aging. Longer persistence of the compound in soil did not further diminish the number of mutants. Vigorous solvent extraction showed that the concentration of the compounds had not diminished with the marked decline in genotoxicity. The data demonstrate that genotoxicity of such compounds aged in soil declines with little or no loss of the compound.

  3. Preclinical Magnetic Resonance Imaging and Spectroscopy Studies of Memory, Aging, and Cognitive Decline

    PubMed Central

    Febo, Marcelo; Foster, Thomas C.

    2016-01-01

    Neuroimaging provides for non-invasive evaluation of brain structure and activity and has been employed to suggest possible mechanisms for cognitive aging in humans. However, these imaging procedures have limits in terms of defining cellular and molecular mechanisms. In contrast, investigations of cognitive aging in animal models have mostly utilized techniques that have offered insight on synaptic, cellular, genetic, and epigenetic mechanisms affecting memory. Studies employing magnetic resonance imaging and spectroscopy (MRI and MRS, respectively) in animal models have emerged as an integrative set of techniques bridging localized cellular/molecular phenomenon and broader in vivo neural network alterations. MRI methods are remarkably suited to longitudinal tracking of cognitive function over extended periods permitting examination of the trajectory of structural or activity related changes. Combined with molecular and electrophysiological tools to selectively drive activity within specific brain regions, recent studies have begun to unlock the meaning of fMRI signals in terms of the role of neural plasticity and types of neural activity that generate the signals. The techniques provide a unique opportunity to causally determine how memory-relevant synaptic activity is processed and how memories may be distributed or reconsolidated over time. The present review summarizes research employing animal MRI and MRS in the study of brain function, structure, and biochemistry, with a particular focus on age-related cognitive decline. PMID:27468264

  4. Determinants of VO2 max decline with aging: an integrated perspective.

    PubMed

    Betik, Andrew C; Hepple, Russell T

    2008-02-01

    Aging is associated with a progressive decline in the capacity for physical activity. Central to this decline is a reduction in the maximal rate of oxygen utilization, or VO2 max. This critical perspective examines the roles played by the factors that determine the rate of muscle oxygen delivery versus those that determine the utilization of oxygen by muscle as a means of probing the reasons for VO2 max decline with aging. Reductions in muscle oxygen delivery, principally due to reduced cardiac output and perhaps also a maldistribution of cardiac output, appear to play the dominant role up until late middle age. On the other hand, there is a decline in skeletal muscle oxidative capacity with aging, due in part to mitochondrial dysfunction, which appears to play a particularly important role in extreme old age (senescence) where skeletal muscle VO2 max is observed to decline by approximately 50% even under conditions of similar oxygen delivery as young adult muscle. It is noteworthy that at least the structural aspects of the capillary bed do not appear to be reduced in a manner that would compromise the capacity for muscle oxygen diffusion even in senescence.

  5. Knock-in reporter mice demonstrate that DNA repair by non-homologous end joining declines with age.

    PubMed

    Vaidya, Amita; Mao, Zhiyong; Tian, Xiao; Spencer, Brianna; Seluanov, Andrei; Gorbunova, Vera

    2014-07-01

    Accumulation of genome rearrangements is a characteristic of aged tissues. Since genome rearrangements result from faulty repair of DNA double strand breaks (DSBs), we hypothesized that DNA DSB repair becomes less efficient with age. The Non-Homologous End Joining (NHEJ) pathway repairs a majority of DSBs in vertebrates. To examine age-associated changes in NHEJ, we have generated an R26NHEJ mouse model in which a GFP-based NHEJ reporter cassette is knocked-in to the ROSA26 locus. In this model, NHEJ repair of DSBs generated by the site-specific endonuclease, I-SceI, reconstitutes a functional GFP gene. In this system NHEJ efficiency can be compared across tissues of the same mouse and in mice of different age. Using R26NHEJ mice, we found that NHEJ efficiency was higher in the skin, lung, and kidney fibroblasts, and lower in the heart fibroblasts and brain astrocytes. Furthermore, we observed that NHEJ efficiency declined with age. In the 24-month old animals compared to the 5-month old animals, NHEJ efficiency declined 1.8 to 3.8-fold, depending on the tissue, with the strongest decline observed in the skin fibroblasts. The sequence analysis of 300 independent NHEJ repair events showed that, regardless of age, mice utilize microhomology sequences at a significantly higher frequency than expected by chance. Furthermore, the frequency of microhomology-mediated end joining (MMEJ) events increased in the heart and lung fibroblasts of old mice, suggesting that NHEJ becomes more mutagenic with age. In summary, our study provides a versatile mouse model for the analysis of NHEJ in a wide range of tissues and demonstrates that DNA repair by NHEJ declines with age in mice, which could provide a mechanism for age-related genomic instability and increased cancer incidence with age.

  6. Feature-selective attention in healthy old age: a selective decline in selective attention?

    PubMed

    Quigley, Cliodhna; Müller, Matthias M

    2014-02-12

    Deficient selection against irrelevant information has been proposed to underlie age-related cognitive decline. We recently reported evidence for maintained early sensory selection when older and younger adults used spatial selective attention to perform a challenging task. Here we explored age-related differences when spatial selection is not possible and feature-selective attention must be deployed. We additionally compared the integrity of feedforward processing by exploiting the well established phenomenon of suppression of visual cortical responses attributable to interstimulus competition. Electroencephalogram was measured while older and younger human adults responded to brief occurrences of coherent motion in an attended stimulus composed of randomly moving, orientation-defined, flickering bars. Attention was directed to horizontal or vertical bars by a pretrial cue, after which two orthogonally oriented, overlapping stimuli or a single stimulus were presented. Horizontal and vertical bars flickered at different frequencies and thereby elicited separable steady-state visual-evoked potentials, which were used to examine the effect of feature-based selection and the competitive influence of a second stimulus on ongoing visual processing. Age differences were found in feature-selective attentional modulation of visual responses: older adults did not show consistent modulation of magnitude or phase. In contrast, the suppressive effect of a second stimulus was robust and comparable in magnitude across age groups, suggesting that bottom-up processing of the current stimuli is essentially unchanged in healthy old age. Thus, it seems that visual processing per se is unchanged, but top-down attentional control is compromised in older adults when space cannot be used to guide selection.

  7. Forest stand structure, productivity, and age mediate climatic effects on aspen decline.

    PubMed

    Bell, David M; Bradford, John B; Lauenroth, William K

    2014-08-01

    Because forest stand structure, age, and productivity can mediate the impacts of climate on quaking aspen (Populus tremuloides) mortality, ignoring stand-scale factors limits inference on the drivers of recent sudden aspen decline. Using the proportion of aspen trees that were dead as an index of recent mortality at 841 forest inventory plots, we examined the relationship of this mortality index to forest structure and climate in the Rocky Mountains and Intermountain Western United States. We found that forest structure explained most of the patterns in mortality indices, but that variation in growing-season vapor pressure deficit and winter precipitation over the last 20 years was important. Mortality index sensitivity to precipitation was highest in forests where aspen exhibited high densities, relative basal areas, quadratic mean diameters, and productivities, whereas sensitivity to vapor pressure deficit was highest in young forest stands. These results indicate that the effects of drought on mortality may be mediated by forest stand development, competition with encroaching conifers, and physiological vulnerabilities of large trees to drought. By examining mortality index responses to both forest structure and climate, we show that forest succession cannot be ignored in studies attempting to understand the causes and consequences of sudden aspen decline.

  8. Forest stand structure, productivity, and age mediate climatic effects on aspen decline

    USGS Publications Warehouse

    Bell, David M.; Bradford, John B.; Lauenroth, William K.

    2014-01-01

    Because forest stand structure, age, and productivity can mediate the impacts of climate on quaking aspen (Populus tremuloides) mortality, ignoring stand-scale factors limits inference on the drivers of recent sudden aspen decline. Using the proportion of aspen trees that were dead as an index of recent mortality at 841 forest inventory plots, we examined the relationship of this mortality index to forest structure and climate in the Rocky Mountains and Intermountain Western United States. We found that forest structure explained most of the patterns in mortality indices, but that variation in growing-season vapor pressure deficit and winter precipitation over the last 20 years was important. Mortality index sensitivity to precipitation was highest in forests where aspen exhibited high densities, relative basal areas, quadratic mean diameters, and productivities, whereas sensitivity to vapor pressure deficit was highest in young forest stands. These results indicate that the effects of drought on mortality may be mediated by forest stand development, competition with encroaching conifers, and physiological vulnerabilities of large trees to drought. By examining mortality index responses to both forest structure and climate, we show that forest succession cannot be ignored in studies attempting to understand the causes and consequences of sudden aspen decline.

  9. Increased deoxythymidine triphosphate levels is a feature of relative cognitive decline

    PubMed Central

    Desler, Claus; Frederiksen, Jane H.; Angleys, Maria; Maynard, Scott; Keijzers, Guido; Fagerlund, Birgitte; Mortensen, Erik Lykke; Osler, Merete; Lauritzen, Martin; Bohr, Vilhelm A.; Rasmussen, Lene Juel

    2016-01-01

    Mitochondrial bioenergetics, mitochondrial reactive oxygen species (ROS) and cellular levels of nucleotides have been hypothesized as early indicators of Alzheimer’s disease (AD). Utilizing relative decline of cognitive ability as a predictor of AD risk, we evaluated the correlation between change of cognitive ability and mitochondrial bioenergetics, ROS and cellular levels of deoxyribonucleotides. Change of cognitive abilities, scored at ages of approximately 20 and 57 was determined for a cohort of 1985 male participants. Mitochondrial bioenergetics, mitochondrial ROS and whole-cell levels of deoxyribonucleotide triphosphates were measured in peripheral blood mononuclear cells (PBMCs) from a total of 103 selected participants displaying the most pronounced relative cognitive decline and relative cognitive improvement. We show that relative cognitive decline is associated with higher PBMC content of deoxythymidine-triphosphate (dTTP) (20%), but not mitochondrial bioenergetics parameters measured in this study or mitochondrial ROS. Levels of dTTP in PBMCs are indicators of relative cognitive change suggesting a role of deoxyribonucleotides in the etiology of AD. PMID:26408413

  10. Lifelong bilingualism contributes to cognitive reserve against white matter integrity declines in aging.

    PubMed

    Gold, Brian T; Johnson, Nathan F; Powell, David K

    2013-11-01

    Recent evidence suggests that lifelong bilingualism may contribute to cognitive reserve (CR) in normal aging. However, there is currently no neuroimaging evidence to suggest that lifelong bilinguals can retain normal cognitive functioning in the face of age-related neurodegeneration. Here we explored this issue by comparing white matter (WM) integrity and gray matter (GM) volumetric patterns of older adult lifelong bilinguals (N=20) and monolinguals (N=20). The groups were matched on a range of relevant cognitive test scores and on the established CR variables of education, socioeconomic status and intelligence. Participants underwent high-resolution structural imaging for assessment of GM volume and diffusion tensor imaging (DTI) for assessment of WM integrity. Results indicated significantly lower microstructural integrity in the bilingual group in several WM tracts. In particular, compared to their monolingual peers, the bilingual group showed lower fractional anisotropy and/or higher radial diffusivity in the inferior longitudinal fasciculus/inferior fronto-occipital fasciculus bilaterally, the fornix, and multiple portions of the corpus callosum. There were no group differences in GM volume. Our results suggest that lifelong bilingualism contributes to CR against WM integrity declines in aging.

  11. Frequency of M-cadherin-stained satellite cells declines in human muscles during aging.

    PubMed

    Sajko, Spela; Kubínová, Lucie; Cvetko, Erika; Kreft, Marko; Wernig, Anton; Erzen, Ida

    2004-02-01

    To answer the question of whether the satellite cell pool in human muscle is reduced during aging, we detected satellite cells in 30- microm-thick transverse sections under the confocal microscope by binding of M-cadherin antibody. The basal lamina was detected with laminin. Nuclei were stained with bisbenzimide or propidium iodide. Satellite cells were counted by applying the disector method and unbiased sampling design. To determine if there are age-related differences in muscle fiber types, morphometric characteristics of muscle fibers were examined on thin sections stained for myofibrillar ATPase. Autopsy samples of vastus lateralis muscle from six young (28.7 +/- 2.3 years) and six old (70.8 +/- 1.3 years) persons who had suffered sudden death were analyzed. Numbers of satellite cells per fiber length (Nsc/Lfib) and number of satellite cells per total number of nuclei (satellite cell nuclei + myonuclei) (Nsc/Nnucl) were significantly lower in the old group (p < 0.05). We demonstrate the importance of proper sampling and counting in estimation of sparsely distributed structures such as satellite cells. Our results support the hypothesis that the satellite cell fraction declines during aging.

  12. Lifelong Bilingualism Contributes to Cognitive Reserve against White Matter Integrity Declines in Aging

    PubMed Central

    Gold, Brian T.; Johnson, Nathan F.; Powell, David K.

    2013-01-01

    Recent evidence suggests that lifelong bilingualism may contribute to cognitive reserve (CR) in normal aging. However, there is currently no neuroimaging evidence to suggest that lifelong bilinguals can retain normal cognitive functioning in the face of age-related neurodegeneration. Here we explored this issue by comparing white matter (WM) integrity and gray matter (GM) volumetric patterns of older adult lifelong bilinguals (N = 20) and monolinguals (N = 20). The groups were matched on a range of relevant cognitive test scores and on the established CR variables of education, socioeconomic status and intelligence. Participants underwent high-resolution structural imaging for assessment of GM volume and diffusion tensor imaging (DTI) for assessment of WM integrity. Results indicated significantly lower microstructural integrity in the bilingual group in several WM tracts. In particular, compared to their monolingual peers, the bilingual group showed lower fractional anisotropy and/or higher radial diffusivity in the inferior longitudinal fasciculus/inferior fronto-occipital fasciculus bilaterally, the fornix, and multiple portions of the corpus callosum. There were no group differences in GM volume. Our results suggest that lifelong bilingualism contributes to CR against WM integrity declines in aging. PMID:24103400

  13. Evidence of disease-related amphibian decline in Colorado

    USGS Publications Warehouse

    Muths, Erin; Corn, Paul Stephen; Pessier, Allan P.; Green, D. Earl

    2003-01-01

    The recent discovery of a pathogenic fungus (Batrachochytrium dendrobatidis) associated with declines of frogs in the American and Australian tropics, suggests that at least the proximate cause, may be known for many previously unexplained amphibian declines. We have monitored boreal toads in Colorado since 1991 at four sites using capturea??recapture of adults and counts of egg masses to examine the dynamics of this metapopulation. Numbers of male toads declined in 1996 and 1999 with annual survival rate averaging 78% from 1991 to 1994, 45% in 1995 and 3% between 1998 and 1999. Numbers of egg masses also declined. An etiological diagnosis of chytridiomycosis consistent with infections by the genus Batrachochytrium was made in six wild adult toads. Characteristic histomorphological features (i.e. intracellular location, shape of thalli, presence of discharge tubes and rhizoids) of chytrid organisms, and host tissue response (acanthosis and hyperkeratosis) were observed in individual toads. These characteristics were indistinguishable from previously reported mortality events associated with chytrid fungus. We also observed epizootiological features consistent with mortality events associated with chytrid fungus: an increase in the ratio of female:male toads captured, an apparent spread of mortalities within the metapopulation and mortalities restricted to post metamorphic animals. Eleven years of population data suggest that this metapopulation of toads is in danger of extinction, pathological and epizootiological evidence indicates that B. dendrobatidis has played a proximate role in this process

  14. Slowing Down: Age-Related Neurobiological Predictors of Processing Speed

    PubMed Central

    Eckert, Mark A.

    2011-01-01

    Processing speed, or the rate at which tasks can be performed, is a robust predictor of age-related cognitive decline and an indicator of independence among older adults. This review examines evidence for neurobiological predictors of age-related changes in processing speed, which is guided in part by our source based morphometry findings that unique patterns of frontal and cerebellar gray matter predict age-related variation in processing speed. These results, together with the extant literature on morphological predictors of age-related changes in processing speed, suggest that specific neural systems undergo declines and as a result slow processing speed. Future studies of processing speed – dependent neural systems will be important for identifying the etiologies for processing speed change and the development of interventions that mitigate gradual age-related declines in cognitive functioning and enhance healthy cognitive aging. PMID:21441995

  15. Declines with Age in Childhood Asthma Symptoms and Health Care Use. An Adjustment for Evaluations

    PubMed Central

    Ko, Yi-An; Clark, Noreen M.

    2014-01-01

    Rationale: Asthma is a variable condition with an apparent tendency for a natural decline in asthma symptoms and health care use occurring as children age. As a result, asthma interventions using a pre-post design may overestimate the intervention effect when no proper control group is available. Objectives: Investigate patterns of natural decline over time with increasing age in asthma symptoms and health care use of children. Develop a statistical procedure that enables adjustment that accounts for expected declines in these outcomes and is useable when intervention evaluations must rely solely on pre-post data. Methods: Mixed-effects models with mixture distributions were used to describe the pattern of symptoms and health care use in 3,021 children aged 2 to 15 years in a combined sample from three controlled trials. An adaptive least squares estimation was used to account for overestimation of intervention effects and make adjustments for pre-post only data. Termed “Adjustment for Natural Declines in Asthma Outcomes (ANDAO),” the adjustment method uses bootstrap sampling to create control cohorts comparable to subjects in the intervention study from existing control subjects. ANDAO accounts for expected declines in outcomes and is beneficial when intervention evaluations must rely solely on pre-post data. Measurements and Main Results: Children under 10 years of age experienced 18% (95% confidence interval, 15–21%) fewer symptom days and 28% (95% confidence interval, 24–32%) fewer symptom nights with each additional year of age. The decline was less than 10% after age 10 years, depending on baseline asthma severity. Emergency department visits declined regardless of baseline symptom frequency (P = 0.02). The adjustment method corrected estimates to within 2.4% of true effects through simulations using control cohorts. Conclusions: Because of the declines in symptoms and health care use expected with increasing age of children with asthma, pre

  16. Age-Related Macular Degeneration

    MedlinePlus

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

  17. Fertility Decline, Gender Composition of Families, and Expectations of Old Age Support

    PubMed Central

    Allendorf, Keera

    2017-01-01

    Recent fertility declines in non-Western countries may have the potential to transform gender systems. One pathway for such transformations is the creation of substantial proportions of families with children of only one gender. Such families, particularly those with only daughters, may facilitate greater symmetry between sons and daughters. This article explores whether such shifts may influence gendered expectations of old age support. In keeping with patriarchal family systems, old age support is customarily provided by sons, but not daughters, in India. Using data from the 2005 Indian Human Development Survey, I find that women with sons overwhelmingly expect old age support from a son. By contrast, women with only daughters largely expect support from a daughter or a source besides a child. These findings suggest that fertility decline may place demographic pressure on gendered patterns of old age support and the gender system more broadly.

  18. Replacement Migration: Is It a Solution to Declining and Ageing Populations?

    ERIC Educational Resources Information Center

    United Nations, New York, NY. Dept. of Economic and Social Affairs.

    The United Nations (UN) Population Division monitors fertility, mortality, and migration trends for all countries as a basis for producing the official UN population estimates and projections. Among recent demographic trends, two are prominent: (1) population decline and (2) population aging. Focusing on these two critical trends, a study…

  19. C-reactive protein and genetic variants and cognitive decline in old age: The PROSPER Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plasma concentrations of C-reactive protein (CRP), a marker of chronic inflammation, have been associated with cognitive impairment in old age. However, it is unknown whether CRP is causally linked to cognitive decline. Within the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) tri...

  20. Declines with Age in Childhood Asthma Symptoms and Health Care Use: An Adjustment for Evaluations

    ERIC Educational Resources Information Center

    Ko, Yi-An; Song, Peter X. K.; Clark, Noreen M.

    2014-01-01

    Rationale: Asthma is a variable condition with an apparent tendency for a natural decline in asthma symptoms and health care use occurring as children age. As a result, asthma interventions using a pre-post design may overestimate the intervention effect when no proper control group is available. Objectives: Investigate patterns of natural decline…

  1. Cognitive Decline in Patients with Chronic Hydrocephalus and Normal Aging: ‘Growing into Deficits’

    PubMed Central

    de Beer, Marlijn H.; Scheltens, Philip

    2016-01-01

    Background/Aim To explore the theory of ‘growing into deficits’, a concept known from developmental neurology, in a series of cases with chronic hydrocephalus (CH). Methods Patients were selected from the Amsterdam Dementia Cohort and underwent extensive dementia screening. Results Twelve patients with CH were selected, in whom Alzheimer's disease was considered unlikely, based on biomarker information and follow-up. Mean Mini-Mental State Examination score was 24 (range 7-30). Most patients were functioning on a level of mild dementia [Clinical Dementia Rating score of 0.5 in 8/11 (66.7%) patients]. On neuropsychological examination, memory and executive functions, as well as processing speed were most frequently impaired. Conclusion In our opinion, the theory of ‘growing into deficits’ shows a parallel with the clinical course of CH and normal aging when Alzheimer's disease was considered very unlikely, because most of these patients were functioning well for a very large part of their lives. The altered cerebrospinal fluid dynamics might make the brain more vulnerable to aging-related changes, leading to a faster cognitive decline in CH patients compared to healthy subjects, especially in case of concomitant brain damage such as traumatic brain injury or meningitis. PMID:27920793

  2. Does a physically active lifestyle attenuate decline in all cognitive functions in old age?

    PubMed

    Ballesteros, Soledad; Mayas, Julia; Reales, Jose Manuel

    2013-07-01

    In this study, the performance of a group of 20 physically active older adults was compared with that of a group of 20 sedentary healthy older adults while performing a series of cognitive tasks. These tasks were designed to assess processes that deteriorate most with age, namely executive control (assessed with the Wisconsin Card Sorting Task) and processing speed (simple and choice reaction time tasks). A repetition priming task that does not decline with age, involving attended and unattended picture outlines at encoding, was also included as a control task. The results show that a physically active lifestyle has a positive influence on executive control, processing speed, and controlled processing. As expected, a physically active lifestyle did not enhance repetition priming for attended stimuli, nor did it produce priming for unattended stimuli at encoding. Both groups exhibited robust priming for attended stimuli and no priming for unattended ones. Executive control functions are of vital importance for independent living in old age. These results have practical implications for enhancing the cognitive processes that decline most in old age. Promoting a physically active lifestyle throughout adulthood could significantly reduce the decline of effortful executive control functions in old age.

  3. Symptoms and lung function decline in a middle-aged cohort of males and females in Australia

    PubMed Central

    Abramson, Michael J; Kaushik, Sonia; Benke, Geza P; Borg, Brigitte M; Smith, Catherine L; Dharmage, Shyamali C; Thompson, Bruce R

    2016-01-01

    Background The European Community Respiratory Health Survey is a major international study designed to assess lung health in adults. This Australian follow-up investigated changes in symptoms between sexes and the roles of asthma, smoking, age, sex, height, and change in body mass index (ΔBMI) on lung function decline (LFD), which is a major risk factor for chronic obstructive pulmonary disease (COPD). Methods LFD was measured as the rate of decline over time in FEV1 (mL/year) (ΔFEV1) and FVC (ΔFVC) between 1993 and 2013. Multiple linear regression was used to estimate associations between risk factors and LFD, separately for males and females. Multiple logistic regression was used to assess sex differences and changes in respiratory symptoms over time. Results In Melbourne, 318 subjects (53.8% females) participated. The prevalence of most respiratory symptoms had either remained relatively stable over 20 years or decreased (significantly so for wheeze). The exception was shortness of breath after activity, which had increased. Among the 262 subjects who completed spirometry, current smoking declined from 20.2% to 7.3%. Overall mean (± standard deviation) FEV1 declined by 23.1 (±17.1) and FVC by 22.9 (±20.2) mL/year. Predictors of ΔFEV1 in males were age, maternal smoking, and baseline FEV1; and in females they were age, ΔBMI, baseline FEV1, and pack-years in current smokers. Decline in FVC was predicted by baseline FVC, age, and ΔBMI in both sexes; however, baseline FVC predicted steeper decline in females than males. Conclusion Most respiratory symptoms remained stable or decreased over time in both sexes. Age, baseline lung function, and change in BMI were associated with the rate of decline in both sexes. However, obesity and personal smoking appear to put females at higher risk of LFD than males. Health promotion campaigns should particularly target females to prevent COPD. PMID:27307725

  4. Oxidative stress induces the decline of brain EPO expression in aging rats.

    PubMed

    Li, Xu; Chen, Yubao; Shao, Siying; Tang, Qing; Chen, Weihai; Chen, Yi; Xu, Xiaoyu

    2016-10-01

    Brain Erythropoietin (EPO), an important neurotrophic factor and neuroprotective factor, was found to be associated with aging. Studies found EPO expression was significantly decreased in the hippocampus of aging rat compared with that of the youth. But mechanisms of the decline of the brain EPO during aging remain unclear. The present study utilized a d-galactose (d-gal)-induced aging model in which the inducement of aging was mainly oxidative injury, to explore underlying mechanisms for the decline of brain EPO in aging rats. d-gal-induced aging rats (2months) were simulated by subcutaneously injecting with d-gal at doses of 50mg·kg(-1), 150mg·kg(-1) and 250mg·kg(-1) daily for 8weeks while the control group received vehicle only. These groups were all compared with the aging rats (24months) which had received no other treatment. The cognitive impairment was assessed using Morris water maze (MWM) in the prepared models, and the amount of β-galactosidase, the lipid peroxidation product malondialdehyde (MDA) level and the superoxide dismutase (SOD) activity in the hippocampus was examined by assay kits. The levels of EPO, EPOR, p-JAK2 and hypoxia-inducible factor-2α (HIF-2α) in the hippocampus were detected by western blot. Additionally, the correlation coefficient between EPO/EPOR expression and MDA level was analyzed. The MWM test showed that compared to control group, the escape latency was significantly extended and the times of crossing the platform was decreased at the doses of 150mg·kg(-1) and 250mg·kg(-1) (p<0.05). Also, the amount of β-galactosidase and the MDA level in the hippocampus were significantly increased but the SOD activity was significantly decreased (p<0.05, 0.01 and 0.01, respectively). Similar to aging rats, the expressions of EPO, EPOR, p-JAK2, and HIF-2αin the brain of d-gal-treated rats were significantly decreased (p<0.05) at 150mg·kg(-1) and 250mg·kg(-1). Interestingly, negative correlations were found between EPOR (r=-0

  5. Perception and Cognition in the Ageing Brain: A Brief Review of the Short- and Long-Term Links between Perceptual and Cognitive Decline

    PubMed Central

    Roberts, Katherine L.; Allen, Harriet A.

    2016-01-01

    Ageing is associated with declines in both perception and cognition. We review evidence for an interaction between perceptual and cognitive decline in old age. Impoverished perceptual input can increase the cognitive difficulty of tasks, while changes to cognitive strategies can compensate, to some extent, for impaired perception. While there is strong evidence from cross-sectional studies for a link between sensory acuity and cognitive performance in old age, there is not yet compelling evidence from longitudinal studies to suggest that poor perception causes cognitive decline, nor to demonstrate that correcting sensory impairment can improve cognition in the longer term. Most studies have focused on relatively simple measures of sensory (visual and auditory) acuity, but more complex measures of suprathreshold perceptual processes, such as temporal processing, can show a stronger link with cognition. The reviewed evidence underlines the importance of fully accounting for perceptual deficits when investigating cognitive decline in old age. PMID:26973514

  6. Mathematical modelling of decline in follicle pool during female reproductive ageing.

    PubMed

    Thilagam, Alagu

    2016-03-01

    The factors which govern the subtle links between follicle loss and mammalian female reproductive ageing remain unclear despite extensive studies undertaken to understand the critical physiological and biochemical mechanisms that underly the accelerated decline in follicle numbers in women older than 37 years. It is not certain whether there is a sole control by the ovary or whether other factors which affect ageing also intersect with the ovarian effect. There is convincing experimental evidence for an interplay of several processes that seem to influence the follicle loss-female reproductive ageing links, with specific hormones (follicle-stimulating hormone, anti-Müllerian hormone, dehydroepiandrosterone) noted to play important roles in follicular dynamics and ovarian ageing. In this work, we examine the subtle links between the rate of follicular decline with ageing and the role of hormones via a series of non-autonomous equations. Simulation results based on the time evolution of the number of ovarian follicles and biochemical changes in the ovarian environment influenced by hormone levels is compared with empirical data based on follicle loss-reproductive ageing correlation studies.

  7. Decline of photosynthetic capacity with leaf age and position in two tropical pioneer tree species.

    PubMed

    Kitajima, Kaoru; Mulkey, Stephen S; Samaniego, Mirna; Joseph Wright, S

    2002-12-01

    The effect of leaf age on photosynthetic capacity, a critical parameter in the theory of optimal leaf longevity, was studied for two tropical pioneer tree species, Cecropia longipes and Urera caracasana, in a seasonally dry forest in Panama. These species continuously produce short-lived leaves (74 and 93 d, respectively) during the rainy season (May-December) on orthotropic branches. However, they differ in leaf production rate, maximum number of leaves per branch, light environment experienced by the leaves, leaf mass per unit area, and nitrogen content. Light-saturated photosynthetic rates for marked leaves of known ages (±1 wk) were measured with two contrasting schemes (repeated measurements vs. chronosequence within branch), which overall produced similar results. In both species, photosynthetic rates and nitrogen use efficiency were negatively correlated with leaf age and positively correlated with light availability. Photosynthetic rates declined faster with leaf age in Cecropia than in Urera as predicted by the theory. The rate of decline was faster for leaves on branches with faster leaf turnover rates. Nitrogen per unit leaf area decreased with leaf age only for Urera. Leaf mass per unit area increased with leaf age, either partly (in Cecropia) or entirely (in Urera) due to ash accumulation.

  8. Relative value of diverse brain MRI and blood-based biomarkers for predicting cognitive decline in the elderly

    NASA Astrophysics Data System (ADS)

    Madsen, Sarah K.; Ver Steeg, Greg; Daianu, Madelaine; Mezher, Adam; Jahanshad, Neda; Nir, Talia M.; Hua, Xue; Gutman, Boris A.; Galstyan, Aram; Thompson, Paul M.

    2016-03-01

    Cognitive decline accompanies many debilitating illnesses, including Alzheimer's disease (AD). In old age, brain tissue loss also occurs along with cognitive decline. Although blood tests are easier to perform than brain MRI, few studies compare brain scans to standard blood tests to see which kinds of information best predict future decline. In 504 older adults from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we first used linear regression to assess the relative value of different types of data to predict cognitive decline, including 196 blood panel biomarkers, 249 MRI biomarkers obtained from the FreeSurfer software, demographics, and the AD-risk gene APOE. A subset of MRI biomarkers was the strongest predictor. There was no specific blood marker that increased predictive accuracy on its own, we found that a novel unsupervised learning method, CorEx, captured weak correlations among blood markers, and the resulting clusters offered unique predictive power.

  9. Inhibition of CaMKK2 Reverses Age-Associated Decline in Bone Mass

    PubMed Central

    Pritchard, Zachary J.; Cary, Rachel L.; Yang, Chang; Novack, Deborah V.; Voor, Michael J.; Sankar, Uma

    2016-01-01

    Decline in bone formation is a major contributing factor to the loss of bone mass associated with aging. We previously showed that the genetic ablation of the tissue-restricted and multifunctional Ca2+/calmodulin (CaM)-dependent protein kinase kinase 2 (CaMKK2) stimulates trabecular bone mass accrual, mainly by promoting anabolic pathways and inhibiting catabolic pathways of bone remodeling. In this study, we investigated whether inhibition of this kinase using its selective cell-permeable inhibitor STO-609 will stimulate bone formation in 32 week old male WT mice and reverse age-associated of decline in bone volume and strength. Tri-weekly intraperitoneal injections of saline or STO-609 (10 μM) were performed for six weeks followed by metabolic labeling with calcein and alizarin red. New bone formation was assessed by dynamic histomorphometry whereas micro-computed tomography was employed to measure trabecular bone volume, microarchitecture and femoral mid-shaft geometry. Cortical and trabecular bone biomechanical properties were assessed using three-point bending and punch compression methods respectively. Our results reveal that as they progress from 12 to 32 weeks of age, WT mice sustain a significant decline in trabecular bone volume, microarchitecture and strength as well as cortical bone strength. However, treatment of the 32 week old WT mice with STO-609 stimulated apposition of new bone and completely reversed the age-associated decrease in bone volume, quality, as well as trabecular and cortical bone strength. We also observed that regardless of age, male Camkk2−/− mice possessed significantly elevated trabecular bone volume, microarchitecture and compressive strength as well as cortical bone strength compared to age-matched WT mice, implying that the chronic loss of this kinase attenuates age-associated decline in bone mass. Further, whereas STO-609 treatment and/or the absence of CaMKK2 significantly enhanced the femoral midshaft geometry, the

  10. [Treatment options for age-related infertility].

    PubMed

    Belaisch-Allart, Joëlle

    2010-06-20

    There has been a consistent trend towards delayed childbearing in most Western countries. Treatment options for age-related infertility includes controlled ovarian hyperstimulation with intrauterine insemination and in vitro fertilization (IVF). A sharp decline in pregnancy rate with advancing female age is noted with assisted reproductive technologies (ART) including IVF. Evaluation and treatment of infertility should not be delayed in women 35 years and older. No treatment other than oocyte donation has been shown to be effective for women over 40 and for those with compromised ovarian reserve, but its pratice is not easy in France hence the procreative tourism. As an increasing number of couples choose to postpone childbearing, they should be informed that maternal age is an important risk factor for failure to conceive.

  11. Exploring Experiences and Perceptions of Aging and Cognitive Decline Across Diverse Racial and Ethnic Groups

    PubMed Central

    Schuh, Holly; Sherzai, Dean; Belliard, Juan Carlos; Montgomery, Susanne B.

    2015-01-01

    Objective: To explore how older adults from three prominent ethnoracial groups experience cognitive decline and aging. Method: Semistructured key informant interviews (KIIs) and focus groups (FGs) were conducted with caregivers, experts, and older adults. Results: (N = 75). Fifteen KIIs regarding cognitive aging issues were conducted among health care professionals and community-based agencies serving older adults. Eight FGs included family caregivers and physicians, and six FGs with Latino, African American, and White older adult community members. Major themes included (a) personal expectations about aging, (b) societal value of older adults, (c) model of care preferred, and (d) community concerns. An overarching theme was a sense of loss associated with aging; however, how this loss was experienced and dealt with varied. Discussion: Distinct patterns of concerns and views are important to understand for the development of programs aimed at meeting the needs of diverse older adult community members to improve health outcomes. PMID:26925436

  12. Age-related eye disease.

    PubMed

    Voleti, Vinod B; Hubschman, Jean-Pierre

    2013-05-01

    As with many organs, compromised function of the eye is accompanied with age and has become increasingly prevalent with the aging population. When decreased visual loss becomes significant, patients' ability to perform activities of daily living becomes compromised. This decrease in function is met with morbidity and mortality, as well as a large socioeconomic burden throughout the world. This review summarizes the most common age-related eye diseases, including cataract, glaucoma, diabetic retinopathy, retinal vein occlusion, and age-related macular degeneration. Although our understanding of the genetic and biochemical pathways of these diseases is sill at its primitive stages, we have become able to help our patients improve the quality of life as they age.

  13. Use of the Internet as a prevention tool against cognitive decline in normal aging

    PubMed Central

    Klimova, Blanka

    2016-01-01

    Recent demographic trends indicate that older people appear to be one of the fastest growing population groups worldwide. In the year 2000, people older than 65 years represented 12.4% of the population. This number is expected to rise to 19% by 2030, particularly in developed countries. Therefore, there is sustained effort at both national and international levels to prolong the active life of these people as long as possible. Since the present older generation at the age of 55 years is already digitally literate, the use of technologies is one of the solutions. The purpose of this study is to discuss the role of the Internet in the prevention of cognitive decline in normal aging. The author examines clinical studies that exploit the use of the Internet, including online training programs, in the prevention of cognitive decline in healthy older individuals. The findings of the clinical studies indicate that the use of the Internet, especially online cognitive training programs, may have a positive effect on the improvement of cognitive functions in healthy older adults. Nevertheless, larger sample longitudinal randomized controlled clinical trials aimed at the prevention of cognitive decline among healthy older adults are needed. PMID:27672317

  14. Sub-Clinical Cognitive Decline and Resting Cerebral Blood Flow in Middle Aged Men

    PubMed Central

    Henriksen, Otto Mølby; Hansen, Naja Liv; Osler, Merete; Mortensen, Erik Lykke; Hallam, Dorte Merete; Pedersen, Esben Thade; Chappell, Michael; Lauritzen, Martin Johannes; Rostrup, Egill

    2017-01-01

    Background Although dementia is associated with both global and regional cerebral blood flow (CBF) changes, little is known about cerebral perfusion in the early pre-clinical stages of cognitive decline preceding overt cognitive dysfunction. The aim of this study was to investigate the association of early sub-clinical cognitive decline with CBF. Materials and Methods The study participants were recruited from a cohort of Danish men born in 1953. Based on a regression model we selected men who performed better (Group A, n = 94) and poorer (Group B, n = 95) on cognitive testing at age 57 than expected from testing at age 20. Participants underwent supplementary cognitive testing, blood sampling and MRI including measurements of regional and global CBF. Results Regional CBF was lower in group B than in group A in the posterior cingulate gyrus and the precuneus. The associations were attenuated when corrected for global atrophy, but remained significant in regions of interest based analysis adjusting for regional gray matter volume and vascular risk factors. No influence of group on global CBF was observed. Conclusions We conclude that early sub-clinical cognitive decline is associated with reduced perfusion in the precuneus and posterior cingulate gyrus independently of regional atrophy and vascular risk factors, but cannot be statistically separated from an association with global atrophy. PMID:28095458

  15. Cognitive Decline and Reorganization of Functional Connectivity in Healthy Aging: The Pivotal Role of the Salience Network in the Prediction of Age and Cognitive Performances

    PubMed Central

    La Corte, Valentina; Sperduti, Marco; Malherbe, Caroline; Vialatte, François; Lion, Stéphanie; Gallarda, Thierry; Oppenheim, Catherine; Piolino, Pascale

    2016-01-01

    Normal aging is related to a decline in specific cognitive processes, in particular in executive functions and memory. In recent years a growing number of studies have focused on changes in brain functional connectivity related to cognitive aging. A common finding is the decreased connectivity within multiple resting state networks, including the default mode network (DMN) and the salience network. In this study, we measured resting state activity using fMRI and explored whether cognitive decline is related to altered functional connectivity. To this end we used a machine learning approach to classify young and old participants from functional connectivity data. The originality of the approach consists in the prediction of the performance and age of the subjects based on functional connectivity by using a machine learning approach. Our findings showed that the connectivity profile between specific networks predicts both the age of the subjects and their cognitive abilities. In particular, we report that the connectivity profiles between the salience and visual networks, and the salience and the anterior part of the DMN, were the features that best predicted the age. Moreover, independently of the age of the subject, connectivity between the salience network and various specific networks (i.e., visual, frontal) predicted episodic memory skills either based on a standard assessment or on an autobiographical memory task, and short-term memory binding. Finally, the connectivity between the salience and the frontal networks predicted inhibition and updating performance, but this link was no longer significant after removing the effect of age. Our findings confirm the crucial role of episodic memory and executive functions in cognitive aging and suggest a pivotal role of the salience network in neural reorganization in aging. PMID:27616991

  16. Cognitive Decline and Reorganization of Functional Connectivity in Healthy Aging: The Pivotal Role of the Salience Network in the Prediction of Age and Cognitive Performances.

    PubMed

    La Corte, Valentina; Sperduti, Marco; Malherbe, Caroline; Vialatte, François; Lion, Stéphanie; Gallarda, Thierry; Oppenheim, Catherine; Piolino, Pascale

    2016-01-01

    Normal aging is related to a decline in specific cognitive processes, in particular in executive functions and memory. In recent years a growing number of studies have focused on changes in brain functional connectivity related to cognitive aging. A common finding is the decreased connectivity within multiple resting state networks, including the default mode network (DMN) and the salience network. In this study, we measured resting state activity using fMRI and explored whether cognitive decline is related to altered functional connectivity. To this end we used a machine learning approach to classify young and old participants from functional connectivity data. The originality of the approach consists in the prediction of the performance and age of the subjects based on functional connectivity by using a machine learning approach. Our findings showed that the connectivity profile between specific networks predicts both the age of the subjects and their cognitive abilities. In particular, we report that the connectivity profiles between the salience and visual networks, and the salience and the anterior part of the DMN, were the features that best predicted the age. Moreover, independently of the age of the subject, connectivity between the salience network and various specific networks (i.e., visual, frontal) predicted episodic memory skills either based on a standard assessment or on an autobiographical memory task, and short-term memory binding. Finally, the connectivity between the salience and the frontal networks predicted inhibition and updating performance, but this link was no longer significant after removing the effect of age. Our findings confirm the crucial role of episodic memory and executive functions in cognitive aging and suggest a pivotal role of the salience network in neural reorganization in aging.

  17. Obesity-induced oxidative stress, accelerated functional decline with age and increased mortality in mice

    PubMed Central

    Zhang, Yiqiang; Fischer, Kathleen E.; Soto, Vanessa; Liu, Yuhong; Sosnowska, Danuta; Richardson, Arlan; Salmon, Adam B.

    2015-01-01

    Obesity is a serious chronic disease that increases the risk of numerous co-morbidities including metabolic syndrome, cardiovascular disease and cancer as well as increases risk of mortality leading some to suggest this represents accelerated aging. Obesity is associated with significant increases in oxidative stress in vivo and, despite the well-explored relationship between oxidative stress and aging, the role this plays in the increased mortality of obese subjects remains an unanswered question. Here, we addressed this by undertaking a comprehensive, longitudinal study of a group of high fat-fed obese mice and assessed both their changes in oxidative stress and in their performance in physiological assays known to decline with aging. In female C57BL/6J mice fed a high-fat diet starting in adulthood, mortality was significantly increased in high fat-fed mice as was oxidative damage in vivo. High fat-feeding significantly accelerated the decline in performance in several assays, including activity, gait, and rotarod. However, we also found that obesity had little effect on other markers and actually improved performance in grip strength, a marker of muscular function. Together, this first comprehensive assessment of longitudinal functional changes in high fat-fed mice suggests that obesity may induce segmental acceleration of some of the aging process. PMID:25558793

  18. Aging and factors related to running economy.

    PubMed

    Quinn, Timothy J; Manley, Michelle J; Aziz, Jason; Padham, Jamie L; MacKenzie, Allison M

    2011-11-01

    The purpose of this study was to investigate the relationship that age has on factors affecting running economy (RE) in competitive distance runners. Fifty-one male and female subelite distance runners (Young [Y]: 18-39 years [n = 18]; Master [M]: 40-59 years [n = 22]; and Older [O]: 60-older [n = 11]) were measured for RE, step rate, lactate threshold (LT), VO2max, muscle strength and endurance, flexibility, power, and body composition. An RE test was conducted at 4 different velocities (161, 188, 215, and 241 m·min(-1)), with subjects running for 5 minutes at each velocity. The steady-state VO2max during the last minute of each stage was recorded and plotted vs. speed, and a regression equation was formulated. A 1 × 3 analysis of variance revealed no differences in the slopes of the RE regression lines among age groups (y = 0.1827x - 0.2974; R2 = 0.9511 [Y]; y = 0.1988x - 1.0416; R2 = 0.9697 [M]; y = 0.1727x + 3.0252; R2 = 0.9618 [O]). The VO2max was significantly lower in the O group compared to in the Y and M groups (Y = 64.1 ± 3.2; M = 56.8 ± 2.7; O = 44.4 ± 1.7 mlO2·kg(-1)·min(-1)). The maximal heart rate and velocity @ LT were significantly different among all age groups (Y = 197 ± 4; M = 183 ± 2; O = 170 ± 6 b·min(-1) and Y = 289.7 ± 27.0; M = 251.5 ± 32.9; O = 212.3 ± 24.6 m·min(-1), respectively). The VO2max @ LT was significantly lower in the O group compared to in the Y and M groups (Y = 50.3 ± 2.0; M = 48.8 ± 2.9; O = 34.9 ± 3.2 mlO2·kg(-1)·min(-1)). The O group was significantly lower than in the Y and M groups in flexibility, power, and upper body strength. Multiple regression analyses showed that strength and power were significantly related to running velocity. The results from this cross-sectional analysis suggest that age-related declines in running performance are associated with declines in maximal and submaximal cardiorespiratory variables and declines in strength and power, not because of declines in running economy.

  19. Age-dependent decline in motor evoked potential (MEP) amplitude: with a comment on changes in Parkinson's disease.

    PubMed

    Eisen, A; Siejka, S; Schulzer, M; Calne, D

    1991-06-01

    Peak-to-peak measurement of the maximum amplitude motor evoked potential (MAXMEP) elicited by 20 consecutive transcranial magnetic stimuli recorded from the contracting thenar and hypothenar muscles measured 9.8 +/- 2.0 mV and 7.25 +/- 2.9 mV respectively (P less than 0.01). The ratio of MAXMEP/CMAP measured 92.6 +/- 25.8% and 54.8 +/- 12.3% respectively (P less than 0.001). Repeat studies showed good individual reproducibility. Amplitudes declined linearly with age (r = -0.836 for thenar MAXMEP P less than 0.001). It is argued that MAXMEP related to age is more meaningful than the MEP/CMAP wave ratio and is proportional to the number of fast conducting cortical motor neurons excited. In 7/18 patients with Parkinson's disease (PD) MAXMEP was increased; in 2 other patients MAXMEP was decreased for their age.

  20. Adverse Vascular Risk is Related to Cognitive Decline in Older Adults

    PubMed Central

    Jefferson, Angela L.; Hohman, Timothy J.; Liu, Dandan; Haj-Hassan, Shereen; Gifford, Katherine A.; Benson, Elleena M.; Skinner, Jeannine S.; Lu, Zengqi; Sparling, Jamie; Sumner, Emily C.; Bell, Susan; Ruberg, Frederick L.

    2014-01-01

    Background Cardiovascular disease (CVD) and related risk factors are associated with Alzheimer’s disease (AD). This association is less well-defined in normal cognition (NC) or prodromal AD (mild cognitive impairment (MCI)). Objective Cross-sectionally and longitudinally relate a vascular risk index to cognitive outcomes among elders free of clinical dementia. Methods 3117 MCI (74±8 years, 56% female) and 6603 NC participants (72±8 years, 68% female) were drawn from the National Alzheimer’s Coordinating Center. A composite measure of vascular risk was defined using the Framingham Stroke Risk Profile (FSRP) score (i.e., age, systolic blood pressure, anti-hypertensive medication, diabetes, cigarette smoking, CVD history, atrial fibrillation). Ordinary linear regressions and generalized linear mixed models related baseline FSRP to cross-sectional and longitudinal cognitive outcomes, separately for NC and MCI, adjusting for age, sex, race, education, and follow-up time (in longitudinal models). Results In NC participants, increasing FSRP was related to worse baseline global cognition, information processing speed, and sequencing abilities (p-values<0.0001) and a worse longitudinal trajectory on all cognitive measures (p-values<0.0001). In MCI, increasing FSRP correlated with worse longitudinal delayed memory (p=0.004). In secondary models using an age-excluded FSRP score, associations persisted in NC participants for global cognition, naming, information processing speed, and sequencing abilities. Conclusions An adverse vascular risk profile is associated with worse cognitive trajectory, especially global cognition, naming, and information processing speed, among NC elders. Future studies are needed to understand how effective management of CVD and related risk factors can modify cognitive decline to identify the ideal timeframe for primary prevention implementation. PMID:25471188

  1. Visual ageing: unspecific decline of the responses to luminance and colour.

    PubMed

    Fiorentini, A; Porciatti, V; Morrone, M C; Burr, D C

    1996-11-01

    We have investigated whether ageing affects selectively the responses to equiluminant patterns of pure colour contrast. In two groups of subjects (mean ages 29 and 72 yr) contrast thresholds were measured psychophysically for the detection and for the discrimination of the direction of motion of drifting gratings. The gratings were modulated either in pure luminance contrast (and uniform colour), or pure chromatic contrast (red-green equiluminant gratings). In subjects of the same age groups, visual evoked potentials (VEP) were recorded in response to gratings with either pure luminance contrast or pure colour contrast sinusoidally reversed in contrast at various temporal frequencies. It was shown that psychophysical contrast sensitivity for equiluminant patterns deteriorates significantly with age, and VEP latency increases. However, these effects of ageing on the responses to patterns of pure colour contrast are substantially the same as those observed in the same subjects for stimuli with pure luminance contrast. The results suggest that ageing causes a small and unspecific decline of the response of the visual system to luminance and colour contrast.

  2. Reduced Nrf2 expression mediates the decline in neural stem cell function during a critical middle-age period.

    PubMed

    Corenblum, Mandi J; Ray, Sneha; Remley, Quentin W; Long, Min; Harder, Bryan; Zhang, Donna D; Barnes, Carol A; Madhavan, Lalitha

    2016-08-01

    Although it is known that the regenerative function of neural stem/progenitor cells (NSPCs) declines with age, causal mechanisms underlying this phenomenon are not understood. Here, we systematically analyze subventricular zone (SVZ) NSPCs, in various groups of rats across the aging spectrum, using in vitro and in vivo histological and behavioral techniques. These studies indicate that although NSPC function continuously declines with advancing age, there is a critical time period during middle age (13-15 months) when a striking reduction in NSPC survival and regeneration (proliferation and neuronal differentiation) occurs. The studies also indicate that this specific temporal pattern of NSPC deterioration is functionally relevant at a behavioral level and correlates with the decreasing expression of the redox-sensitive transcription factor, Nrf2, in the NSPCs. When Nrf2 expression was suppressed in 'young' NSPCs, using short interfering RNAs, the survival and regeneration of the NSPCs was significantly compromised and mirrored 'old' NSPCs. Conversely, Nrf2 overexpression in 'old' NSPCs rendered them similar to 'young' NSPCs, and they showed increased survival and regeneration. Furthermore, examination of newborn Nrf2 knockout (Nrf2 -/-) mice revealed a lower number of SVZ NSPCs in these animals, when compared to wild-type controls. In addition, the proliferative and neurogenic potential of the NSPCs was also compromised in the Nrf2-/- mice. These results identify a novel regulatory role for Nrf2 in NSPC function during aging and have important implications for developing NSPC-based strategies to support healthy aging and to treat age-related neurodegenerative disorders.

  3. [Age-related macular degeneration].

    PubMed

    Budzinskaia, M V

    2014-01-01

    The review provides an update on the pathogenesis and new treatment modalities for neovascular age-related macular degeneration (AMD). The impact of polymorphism in particular genes, including complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2/LOC387715), and serine peptidase (HTRA1), on AMD development is discussed. Clinical presentations of different forms of exudative AMD, that is classic, occult, or more often mixed choroidal neovascularization, retinal angiomatous proliferation, and choroidal polypoidal vasculopathy, are described. Particular attention is paid to the results of recent clinical trials and safety issues around the therapy.

  4. Systematic review of the evidence relating FEV1 decline to giving up smoking

    PubMed Central

    2010-01-01

    Background The rate of forced expiratory volume in 1 second (FEV1) decline ("beta") is a marker of chronic obstructive pulmonary disease risk. The reduction in beta after quitting smoking is an upper limit for the reduction achievable from switching to novel nicotine delivery products. We review available evidence to estimate this reduction and quantify the relationship of smoking to beta. Methods Studies were identified, in healthy individuals or patients with respiratory disease, that provided data on beta over at least 2 years of follow-up, separately for those who gave up smoking and other smoking groups. Publications to June 2010 were considered. Independent beta estimates were derived for four main smoking groups: never smokers, ex-smokers (before baseline), quitters (during follow-up) and continuing smokers. Unweighted and inverse variance-weighted regression analyses compared betas in the smoking groups, and in continuing smokers by amount smoked, and estimated whether beta or beta differences between smoking groups varied by age, sex and other factors. Results Forty-seven studies had relevant data, 28 for both sexes and 19 for males. Sixteen studies started before 1970. Mean follow-up was 11 years. On the basis of weighted analysis of 303 betas for the four smoking groups, never smokers had a beta 10.8 mL/yr (95% confidence interval (CI), 8.9 to 12.8) less than continuing smokers. Betas for ex-smokers were 12.4 mL/yr (95% CI, 10.1 to 14.7) less than for continuing smokers, and for quitters, 8.5 mL/yr (95% CI, 5.6 to 11.4) less. These betas were similar to that for never smokers. In continuing smokers, beta increased 0.33 mL/yr per cigarette/day. Beta differences between continuing smokers and those who gave up were greater in patients with respiratory disease or with reduced baseline lung function, but were not clearly related to age or sex. Conclusion The available data have numerous limitations, but clearly show that continuing smokers have a beta that

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

    PubMed

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

    2015-09-23

    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-induced deficits in

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  7. Age-Related Macular Degeneration.

    PubMed

    Mehta, Sonia

    2015-09-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. AMD is diagnosed based on characteristic retinal findings in individuals older than 50. Early detection and treatment are critical in increasing the likelihood of retaining good and functional vision.

  8. Population declines of tuna and relatives depend on their speed of life

    PubMed Central

    Juan-Jordá, M. J.; Mosqueira, I.; Freire, J.; Dulvy, N. K.

    2015-01-01

    Larger-bodied species in a wide range of taxonomic groups including mammals, fishes and birds tend to decline more steeply and are at greater risk of extinction. Yet, the diversity in life histories is governed not only by body size, but also by time-related traits. A key question is whether this size-dependency of vulnerability also holds, not just locally, but globally across a wider range of environments. We test the relative importance of size- and time-related life-history traits and fishing mortality in determining population declines and current exploitation status in tunas and their relatives. We use high-quality datasets of half a century of population trajectories combined with population-level fishing mortalities and life-history traits. Time-related traits (e.g. growth rate), rather than size-related traits (e.g. maximum size), better explain the extent and rate of declines and current exploitation status across tuna assemblages, after controlling for fishing mortality. Consequently, there is strong geographical patterning in population declines, such that populations with slower life histories (found at higher cooler latitudes) have declined most and more steeply and have a higher probability of being overfished than populations with faster life histories (found at tropical latitudes). Hence, the strong, temperature-driven, latitudinal gradients in life-history traits may underlie the global patterning of population declines, fisheries collapses and local extinctions. PMID:26156763

  9. Normal tear protein profiles and age-related changes.

    PubMed Central

    McGill, J I; Liakos, G M; Goulding, N; Seal, D V

    1984-01-01

    The specific and non-specific tear proteins have been analysed by means of the ELISA technique to establish the normal and age-related values. There is a linear and related decline of lysozyme and lactoferrin with age, and a similar but unrelated reduction in tear volume. IgA levels gradually decline, while caeruloplasmin and IgG both increase after the fifth decade. The results suggest that tear IgG and caeruloplasmin are probably transudates from the serum, that IgA is secreted independently of tear volume, and that lysozyme and lactoferrin are secreted at the same site but independently of tear volume. PMID:6712908

  10. Height-related growth declines in ponderosa pine are not due to carbon limitation.

    PubMed

    Sala, Anna; Hoch, Günter

    2009-01-01

    Decreased gas exchange as trees grow tall has been proposed to explain age-related growth declines in trees. We examined changes of mobile carbon stores (starch, sugars and lipids) with tree height in ponderosa pine (Pinus ponderosa) at two sites differing in water availability, and tested the following hypotheses: (1) carbon supply does not become increasingly limited as trees grow tall; rather, the concentration of mobile carbon compounds increases with tree height reflecting greater reductions of carbon sink activities relative to carbon assimilation; and (2) increases of stored mobile carbon compounds with tree height are greater in drier sites. Height-related growth reductions were associated with significant increases of non-structural carbohydrates (NSC) and lipid concentrations in all tissues in the upper canopy and of NSC in the bole. Lipid concentrations in the bole decreased with tree height, but such decrease is not necessarily inconsistent with non-limiting carbon supply in tall trees. Furthermore, we found stronger increases of mobile carbon stores with tree height at the dry site relative to the moist site. Our results provide first direct evidence that carbon supply does not limit growth in tall trees and that decreases of water availability might negatively impact growth processes more than net-photosynthesis.

  11. Decline of lymphatic vessel density and function in murine skin during aging.

    PubMed

    Karaman, Sinem; Buschle, Dorina; Luciani, Paola; Leroux, Jean-Christophe; Detmar, Michael; Proulx, Steven T

    2015-10-01

    Lymphatic vessels play important roles in the pathogenesis of many conditions that have an increased prevalence in the elderly population. However, the effects of the aging process on the lymphatic system are still relatively unknown. We have applied non-invasive imaging and whole-mount staining techniques to assess the lymphatic vessel function and morphology in three different age groups of mice: 2 months (young), 7 months (middle-aged), and 18 months (aged). We first developed and validated a new method to quantify lymphatic clearance from mouse ear skin, using a lymphatic-specific near-infrared tracer. Using this method, we found that there is a prominent decrease in lymphatic vessel function during aging since the lymphatic clearance was significantly delayed in aged mice. This loss of function correlated with a decreased lymphatic vessel density and a reduced lymphatic network complexity in the skin of aged mice as compared to younger controls. The blood vascular leakage in the skin was slightly increased in the aged mice, indicating that the decreased lymphatic function was not caused by a reduced capillary filtration in aged skin. The decreased function of lymphatic vessels with aging might have implications for the pathogenesis of a number of aging-related diseases.

  12. Preclinical cognitive decline in late middle-aged asymptomatic apolipoprotein E-e4/4 homozygotes: a replication study.

    PubMed

    Caselli, R J; Osborne, D; Reiman, E M; Hentz, J G; Barbieri, C J; Saunders, A M; Hardy, J; Graff-Radford, N R; Hall, G R; Alexander, G E

    2001-08-15

    In a previous cross-sectional study of 100 asymptomatic individuals aged 49-69, we reported age-related decline in immediate and delayed memory that was steeper in apolipoprotein E (apoE)-e4/4 homozygotes than in members of other genetic subgroups. These findings were preliminarily based upon the statistical problem of multiple comparisons. We therefore sought to replicate these findings in a new cohort. From 1998 to 2000, 80 asymptomatic residents of Maricopa County, AZ were recruited through newspaper ads. 20 apoE-e4/4 homozygotes, 20 e3/4 heterozygotes, and 40 e4 noncarriers were matched (1:1:2) by age, gender, and years of education. All had normal neurologic and psychiatric examinations, including Folstein minimental status exam (MMSE) and Hamilton depression scale, and underwent a battery of neuropsychological tests identical to those in our previous study. The groups were well-matched for age (55.9+/-5.9 years), gender (60% women), and education (15.9+/-2.2 years), and were demographically similar to our previous cohort. Complex figure test recall was lower in e3/4 heterozygotes than noncarriers, but there was no significant difference between e4/4 homozygotes and noncarriers. There were no other significant differences in mean test scores between groups, but Wechsler adult intelligence scale-revised (WAIS-R) digit span showed a significant negative correlation with age in the e4/4 homozygote group relative to e4 noncarriers (p=0.008) as we had found in our previous study. In conclusion, we found a significant negative correlation of WAIS-R digit span with age in apoE-e4/4 homozygotes relative to e4 noncarriers in two separate cohorts, possibly reflecting an age-related effect on frontal lobe function in this genetic subgroup.

  13. Understanding the Declining Canadian Homicide Rate: A Test of Holinger's Relative Cohort Size Hypothesis

    ERIC Educational Resources Information Center

    Leenaars, Antoon A.; Lester, David

    2004-01-01

    Homicide rates in Canada have shown a decline since 1975, but there has been little empirical study of this trend. P. Holinger (1987) predicted and confirmed that the size of the cohort aged 15-24 in the United States population was associated with the rise and fall of the homicide rate in that country. This study was designed to test this…

  14. Circuit mechanisms encoding odors and driving aging-associated behavioral declines in Caenorhabditis elegans

    PubMed Central

    Leinwand, Sarah G; Yang, Claire J; Bazopoulou, Daphne; Chronis, Nikos; Srinivasan, Jagan; Chalasani, Sreekanth H

    2015-01-01

    Chemosensory neurons extract information about chemical cues from the environment. How is the activity in these sensory neurons transformed into behavior? Using Caenorhabditis elegans, we map a novel sensory neuron circuit motif that encodes odor concentration. Primary neurons, AWCON and AWA, directly detect the food odor benzaldehyde (BZ) and release insulin-like peptides and acetylcholine, respectively, which are required for odor-evoked responses in secondary neurons, ASEL and AWB. Consistently, both primary and secondary neurons are required for BZ attraction. Unexpectedly, this combinatorial code is altered in aged animals: odor-evoked activity in secondary, but not primary, olfactory neurons is reduced. Moreover, experimental manipulations increasing neurotransmission from primary neurons rescues aging-associated neuronal deficits. Finally, we correlate the odor responsiveness of aged animals with their lifespan. Together, these results show how odors are encoded by primary and secondary neurons and suggest reduced neurotransmission as a novel mechanism driving aging-associated sensory neural activity and behavioral declines. DOI: http://dx.doi.org/10.7554/eLife.10181.001 PMID:26394000

  15. Respiratory function decline and DNA mutation in mitochondria, oxidative stress and altered gene expression during aging.

    PubMed

    Wei, Yau-Huei; Wu, Shi-Bei; Ma, Yi-Shing; Lee, Hsin-Chen

    2009-01-01

    Aging is a biological process that is characterized by the gradual loss of physiological function and increases in the susceptibility to disease of an individual. During the aging process, a wide spectrum of alterations in mitochondria and mitochondrial DNA (mtDNA) has been observed in somatic tissues of humans and animals. This is associated with the decline in mitochondrial respiratory function; excess production of the reactive oxygen species (ROS); increase in the oxidative damage to mtDNA, lipids and proteins in mitochondria; accumulation of point mutations and large-scale deletions of mtDNA; and altered expression of genes involved in intermediary metabolism. It has been demonstrated that the ROS may cause oxidative damage and mutations of mtDNA and alterations of the expression of several clusters of genes in aging tissues and senescent cells. We found that intracellular levels of hydrogen peroxide (H2O2) and oxidative damage to DNA in the tissue cells and skin fibroblasts of old donors were higher than those of young donors. In H2O2-induced senescent skin fibroblasts, we observed an increase in the protein expression and activity levels of manganese-dependent superoxide dismutase and a concurrent decrease in the activity of cytochrome c oxidase and the rate of oxygen consumption. Moreover, the mRNA and protein expression levels of pyruvate dehydrogenase (PDH) were decreased but those of PDH kinase and lactate dehydrogenase were increased in senescent skin fibroblasts. The changes in the expression of these enzymes suggest a metabolic shift from mitochondrial respiration to glycolysis as a major supply of ATP in aging human cells. On the other hand, recent studies on mitochondrial mutant mice, which carry a proofreading deficient subunit of DNA polymerase gamma, revealed that mtDNA mutations accumulated in somatic tissues in the mice that displayed prominent features of aging. Taken together, we suggest that the respiratory function decline and increase in

  16. Progressive deterioration of thalamic nuclei relates to cortical network decline in schizophrenia.

    PubMed

    Cobia, Derin J; Smith, Matthew J; Salinas, Ilse; Ng, Charlene; Gado, Mokhtar; Csernansky, John G; Wang, Lei

    2017-02-01

    Thalamic abnormalities are considered part of the complex pathophysiology of schizophrenia, particularly the involvement of specific thalamic nuclei. The goals of this study were to: introduce a novel atlas-based parcellation scheme for defining various thalamic nuclei; compare their integrity in a schizophrenia sample against healthy individuals at baseline and follow-up time points, as well as rates of change over time; examine relationships between the nuclei and abnormalities in known connected cortical regions; and finally, to determine if schizophrenia-related thalamic nuclei changes relate to cognitive functioning and clinical symptoms. Subjects were from a larger longitudinal 2-year follow-up study, schizophrenia (n=20) and healthy individuals (n=20) were group-matched for age, gender, and recent-alcohol use. We used high-dimensional brain mapping to obtain thalamic morphology, and applied a novel atlas-based method for delineating anterior, mediodorsal, and pulvinar nuclei. Results from cross sectional GLMs revealed group differences in bilateral mediodorsal and anterior nuclei, while longitudinal models revealed significant group-by-time interactions for the mediodorsal and pulvinar nuclei. Cortical correlations were the strongest for the pulvinar in frontal, temporal and parietal regions, followed by the mediodorsal nucleus in frontal regions, but none in the anterior nucleus. Thalamic measures did not correlate with cognitive and clinical scores at any time point or longitudinally. Overall, findings revealed a pattern of persistent progressive abnormalities in thalamic nuclei that relate to advancing cortical decline in schizophrenia, but not with measures of behavior.

  17. Cohorts based on Decade of Death: No Evidence for Secular Trends Favoring Later Cohorts in Cognitive Aging and Terminal Decline in the AHEAD Study

    PubMed Central

    Hülür, Gizem; Infurna, Frank J.; Ram, Nilam; Gerstorf, Denis

    2012-01-01

    Studies of birth-year cohorts examined over the same age range often report secular trends favoring later-born cohorts, who are cognitively fitter and show less steep cognitive declines than earlier-born cohorts. However, there is initial evidence that those advantages of later-born cohorts do not carry into the last years of life, suggesting that pervasive mortality-related processes minimize differences that were apparent earlier in life. Elaborating this work from an alternative perspective on cohort differences, we compared rates of cognitive aging and terminal decline in episodic memory between cohorts based on the year participants had died, earlier (between 1993 and 1999) or later in historical time (between 2000 and 2010). Specifically, we compared trajectories of cognitive decline in two death-year cohorts of participants in the Asset and Health Dynamics among the Oldest Old (AHEAD) Study that were matched on age at death and education and controlled for a variety of additional covariates. Results revealed little evidence of secular trends favoring later cohorts. To the contrary, the cohort that died in the 2000s showed a less favorable trajectory of age-related memory decline than the cohort who died in the 1990s. In examinations of change in relation to time-to-death, the cohort dying in the 2000s experienced even steeper terminal declines than the cohort dying in the 1990s. We suggest that secular increases in “manufacturing” survival may exacerbate age- and mortality-related cognitive declines among the oldest old. PMID:23046001

  18. Do Changes in Lifestyle Engagement Moderate Cognitive Decline in Normal Aging? Evidence from the Victoria Longitudinal Study

    PubMed Central

    Small, Brent J.; Dixon, Roger A.; McArdle, John J.; Grimm, Kevin J.

    2013-01-01

    Objective Do lifestyle activities buffer normal aging-related declines in cognitive performance? The emerging literature will benefit from theoretically broader measurement of both lifestyle activities and cognitive performance, and longer-term longitudinal designs complemented with dynamic statistical analyses. We examine the temporal ordering of changes in lifestyle activities and changes in cognitive neuropsychological performance in older adults. Method We assembled data (n = 952) across a 12-year (5-wave) period from the Victoria Longitudinal Study. Latent Change Score models were applied to examine whether (and in which temporal order) changes in physical, social, or cognitive lifestyle activities were related to changes in three domains of cognitive performance. Results Two main results reflect the dynamic coupling among changes in lifestyle activities and cognition. First, reductions in cognitive lifestyle activities were associated with subsequent declines in measures of verbal speed, episodic memory, and semantic memory. Second, poorer cognitive functioning was related to subsequent decrements in lifestyle engagement, especially in social activities. Conclusions The results support the dual contention that (a) lifestyle engagement may buffer some of the cognitive changes observed in late life, and (b) persons who are exhibiting poorer cognitive performance may also relinquish some lifestyle activities. PMID:22149165

  19. Age-dependent cognitive decline in the APP23 model precedes amyloid deposition.

    PubMed

    Van Dam, Debby; D'Hooge, Rudi; Staufenbiel, Matthias; Van Ginneken, Chris; Van Meir, Frans; De Deyn, Peter P

    2003-01-01

    Heterozygous APP23 mice, expressing human amyloid-precursor protein with the Swedish double mutation and control littermates, were subjected to behavioral and neuromotor tasks at the age of 6-8 weeks, 3 and 6 months. A hidden-platform Morris-type water maze showed an age-dependent decline of spatial memory capacities in the APP23 model. From the age of 3 months onwards, the APP23 mice displayed major learning and memory deficits as demonstrated by severely impaired learning curves during acquisition and impaired probe trial performance. In addition to the cognitive deficit, APP23 mice displayed disturbed activity patterns. Overnight cage-activity recording showed hyperactivity in the transgenics for the three age groups tested. However, a short 2-h recording during dusk phase demonstrated lower activity levels in 6-month-old APP23 mice as compared to controls. Moreover, at this age, APP23 mice differed from control littermates in exploration and activity levels in the open-field paradigm. These findings are reminiscent of disturbances in circadian rhythms and activity observed in Alzheimer patients. Determination of plaque-associated human amyloid-beta 1-42 peptides in brain revealed a fivefold increase in heterozygous APP23 mice at 6 months as compared to younger transgenics. This increase coincided with the first appearance of plaques in hippocampus and neocortex. Spatial memory deficits preceded plaque formation and increase in plaque-associated amyloid-beta 1-42 peptides, but probe trial performance did correlate negatively with soluble amyloid-beta brain concentration in 3-month-old APP23 mutants. Detectable plaque formation is not the (only) causal factor contributing to memory defects in the APP23 model.

  20. Age-related changes in ultra-triathlon performances

    PubMed Central

    2012-01-01

    Background The age-related decline in performance has been investigated in swimmers, runners and triathletes. No study has investigated the age-related performance decline in ultra-triathletes. The purpose of this study was to analyse the age-related declines in swimming, cycling, running and overall race time for both Triple Iron ultra-triathlon (11.4-km swimming, 540-km cycling and 126.6-km running) and Deca Iron ultra-triathlon (38-km swimming, 1,800-km cycling and 420-km running). Methods The age and performances of 423 male Triple Iron ultra-triathletes and 119 male Deca Iron ultra-triathletes were analysed from 1992 to 2010 using regression analyses and ANOVA. Results The mean age of the finishers was significantly higher for Deca Iron ultra-triathletes (41.3 ± 3.1 years) compared to a Triple Iron ultra-triathletes (38.5 ± 3.3 years) (P < 0.05). For both ultra-distances, the fastest overall race times were achieved between the ages of 25 and 44 years. Deca Iron ultra-triathletes achieved the same level of performance in swimming and cycling between 25 and 54 years of age. Conclusions The magnitudes of age-related declines in performance in the three disciplines of ultra-triathlon differ slightly between Triple and Deca Iron ultra-triathlon. Although the ages of Triple Iron ultra-triathletes were on average younger compared to Deca Iron ultra-triathletes, the fastest race times were achieved between 25 and 44 years for both distances. Further studies should investigate the motivation and training of ultra-triathletes to gain better insights in ultra-triathlon performance. PMID:23849327

  1. Age-related macular degeneration

    PubMed Central

    Querques, Giuseppe; Avellis, Fernando Onofrio; Querques, Lea; Bandello, Francesco; Souied, Eric H

    2011-01-01

    Clinical question: Is there any new knowledge about the pathogenesis and treatment of age-related macular degeneration (AMD)? Results: We now understand better the biochemical and pathological pathways involved in the genesis of AMD. Treatment of exudative AMD is based on intravitreal injection of new antivascular endothelial growth factor drugs for which there does not yet exist a unique recognized strategy of administration. No therapies are actually available for atrophic AMD, despite some experimental new pharmacological approaches. Implementation: strategy of administration, safety of intravitreal injection PMID:21654887

  2. Why Adult Stem Cell Functionality Declines with Age? Studies from the Fruit Fly Drosophila Melanogaster Model Organism

    PubMed Central

    Gonen, Oren; Toledano, Hila

    2014-01-01

    Highly regenerative adult tissues are supported by rare populations of stem cells that continuously divide to self-renew and generate differentiated progeny. This process is tightly regulated by signals emanating from surrounding cells to fulfill the dynamic demands of the tissue. One of the hallmarks of aging is slow and aberrant tissue regeneration due to deteriorated function of stem and supporting cells. Several Drosophila regenerative tissues are unique in that they provide exact identification of stem and neighboring cells in whole-tissue anatomy. This allows for precise tracking of age-related changes as well as their targeted manipulation within the tissue. In this review we present the stem cell niche of Drosophila testis, ovary and intestine and describe the major changes and phenotypes that occur in the course of aging. Specifically we discuss changes in both intrinsic properties of stem cells and their microenvironment that contribute to the decline in tissue functionality. Understanding these mechanisms in adult Drosophila tissues will likely provide new paradigms in the field of aging. PMID:24955030

  3. Age-related macular degeneration.

    PubMed

    Cheung, Lily K; Eaton, Angie

    2013-08-01

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

  4. The Impact of Declining Smoking on Radon-Related Lung Cancer in the United States

    PubMed Central

    Alshanqeety, Omar; Warner, Kenneth E.; Lantz, Paula M.; Courant, Paul N.

    2011-01-01

    Objectives. We examined the effect of current patterns of smoking rates on future radon-related lung cancer. Methods. We combined the model developed by the National Academy of Science's Committee on Health Risks of Exposure to Radon (the BEIR VI committee) for radon risk assessment with a forecasting model of US adult smoking prevalence to estimate proportional decline in radon-related deaths during the present century with and without mitigation of high-radon houses. Results. By 2025, the reduction in radon mortality from smoking reduction (15 percentage points) will surpass the maximum expected reduction from remediation (12 percentage points). Conclusions. Although still a genuine source of public health concern, radon-induced lung cancer is likely to decline substantially, driven by reductions in smoking rates. Smoking decline will reduce radon deaths more that remediation of high-radon houses, a fact that policymakers should consider as they contemplate the future of cancer control. PMID:21228294

  5. Leg strength declines with advancing age despite habitual endurance exercise in active older adults.

    PubMed

    Marcell, Taylor J; Hawkins, Steven A; Wiswell, Robert A

    2014-02-01

    Age-associated loss of muscle mass (sarcopenia) and strength (dynapenia) is associated with a loss of independence that contributes to falls, fractures, and nursing home admissions, whereas regular physical activity has been suggested to offset these losses. The purpose of this study was to evaluate the effect of habitual endurance exercise on muscle mass and strength in active older adults. A longitudinal analysis of muscle strength (≈4.8 years apart) was performed on 59 men (age at start of study: 58.6 ± 7.3 years) and 35 women (56.9 ± 8.2 years) who used endurance running as their primary mode of exercise. There were no changes in fat-free mass although body fat increased minimally (1.0-1.5%). Training volume (km·wk, d·wk) decreased in both the men and women. There was a significant loss of both isometric knee extension (≈5% per year) and knee flexion (≈3.6% per year) strength in both the men and women. However, there was no significant change in either isokinetic concentric or eccentric torque of the knee extensors. Our data demonstrated a significant decline in isometric knee extensor and knee flexor strength although there were no changes in body mass in this group of very active older men and women. Our data support newer exercise guidelines for older Americans suggesting resistance training be an integral component of a fitness program and that running alone was not sufficient to prevent the loss in muscle strength (dynapenia) with aging.

  6. Thalamic structures and associated cognitive functions: Relations with age and aging

    PubMed Central

    Fama, Rosemary; Sullivan, Edith V.

    2015-01-01

    The thalamus, with its cortical, subcortical, and cerebellar connections, is a critical node in networks supporting cognitive functions known to decline in normal aging, including component processes of memory and executive functions of attention and information processing. The macrostructure, microstructure, and neural connectivity of the thalamus changes across the adult lifespan. Structural and functional magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) have demonstrated, regional thalamic volume shrinkage and microstructural degradation, with anterior regions generally more compromised than posterior regions. The integrity of selective thalamic nuclei and projections decline with advancing age, particularly those in thalamofrontal, thalamoparietal, and thalamolimbic networks. This review presents studies that assess the relations between age and aging and the structure, function, and connectivity of the thalamus and associated neural networks and focuses on their relations with processes of attention, speed of information processing, and working and episodic memory. PMID:25862940

  7. White matter tract covariance patterns predict age-declining cognitive abilities

    PubMed Central

    Gazes, Yunglin; Bowman, F. DuBois; Razlighi, Qolamreza R.; O’Shea, Deirdre; Stern, Yaakov; Habeck, Christian

    2015-01-01

    Previous studies investigating the relationship of white matter (WM) integrity to cognitive abilities and aging and have either focused on a global measure or a few selected WM tracts. Ideally, contribution from all of the WM tracts should be evaluated at the same time. However, the high collinearity among WM tracts precludes systematic examination of WM tracts simultaneously without sacrificing statistical power due to stringent multiple-comparison corrections. Multivariate covariance techniques enable comprehensive simultaneous examination of all WM tracts without being penalized for high collinearity among observations. Method In this study, Scaled Subprofile Modeling (SSM) was applied to the mean integrity of 18 major WM tracts to extract covariance patterns that optimally predicted four cognitive abilities (perceptual speed, episodic memory, fluid reasoning, and vocabulary) in 346 participants across ages 20 to 79 years old. Using expression of the covariance patterns, age-independent effects of white matter integrity on cognition and the indirect effect of WM integrity on age-related differences in cognition were tested separately, but inferences from the indirect analyses were cautiously made given cross-sectional data set was used in the analysis. Results A separate covariance pattern was identified that significantly predicted each cognitive ability after controlling for age except for vocabulary, but Age by WM covariance pattern interactions were not significant for any of the three abilities. Furthermore, each of the patterns mediated the effect of age on the respective cognitive ability. A distinct set of WM tracts was most influential in each of the three patterns. The WM covariance pattern accounting for fluid reasoning showed the most number of influential WM tracts whereas the episodic memory pattern showed the least number. Conclusion Specific patterns of WM tracts make significant contributions to the age-related differences in perceptual speed

  8. Taste-related sensations in old age.

    PubMed

    Ogawa, T; Annear, M J; Ikebe, K; Maeda, Y

    2017-03-02

    The sense of taste is important as it allows for assessment of nutritional value, safety and quality of foods as well as for food enjoyment and quality of life. Several factors are suggested to be associated with taste sensitivity, and higher prevalence of taste disorder has been reported among older adults. This review focused on the reported causes and correlates of taste decline in older adults, with the aim to consolidating existing evidence and identifying gaps and limitations. Using a scoping review methodology, we sought relevant literature from the last 20 years. Search terms included taste, gustatory sense, older adults and geriatric. Considered research was limited to reports that involved research participants over 60 years old, papers written in English, and manuscripts published after 1995. We have consolidated available evidences on the influences on taste-related sensations among international cohorts of older adults. Influences can be reflected under the topics of physiological changes in the sensory organs, physiological and behavioural variables related to taste sensation. This review identified three areas of historic and current research endeavour related to studies of taste sensation in older subjects: physiological changes in the sensory organs, factors related to the ageing of the individual and behavioural variables affecting taste-related sensation. Key limitations and gaps in the current literature include notable lack of consideration of potential confounding, mediating and moderating effects, while future research is indicated in the areas of measuring the quality of health and life. As global population ageing accelerates in the coming decades, maintaining taste sensations and sensitivity in older adults will be a key measure to ensuring quality of health and life.

  9. The Declining Relative Status of Black Women Workers, 1980-2002

    ERIC Educational Resources Information Center

    Dozier, Raine

    2010-01-01

    During the 1980s and 1990s, industrial restructuring led to a marked increase in wage inequality. Women, however, were not as negatively affected by declining manufacturing employment because their pay was relatively low within the industry, and their already high representation in the service sector provided access to newly created opportunities.…

  10. Declining well yields related to depth in fractured rocks - Use of an exponential equation

    SciTech Connect

    Page, R.W. )

    1993-03-01

    In southwestern Nevada County, where most wells are drilled into granitic or metamorphic rocks, well yields were found to decrease with increasing well depth. Data from that report indicated that declining well yields in the area probably could be approximated by an exponential equation. The purpose of this report is to demonstrate that an exponential equation can be used to approximate declining well yields related to depth in hard-rock areas of granitic and metamorphic rocks in the western foothills of the Sierra Nevada. The scope includes applying this equation to data from southwestern Nevada County, California.

  11. Age-Related Changes in Visual Pseudoneglect

    ERIC Educational Resources Information Center

    Schmitz, Remy; Peigneux, Philippe

    2011-01-01

    Pseudoneglect is a slight but consistent leftward attentional bias commonly observed in healthy young populations, purportedly explained by right hemispheric dominance. It has been suggested that normal aging might be associated with a decline of the right hemisphere. According to this hypothesis, a few studies have shown that elderly tend to…

  12. Decline of Phosphotransfer and Substrate Supply Metabolic Circuits Hinders ATP Cycling in Aging Myocardium

    PubMed Central

    Nemutlu, Emirhan; Gupta, Anu; Zhang, Song; Viqar, Maria; Holmuhamedov, Ekhson; Terzic, Andre; Jahangir, Arshad; Dzeja, Petras

    2015-01-01

    Integration of mitochondria with cytosolic ATP-consuming/ATP-sensing and substrate supply processes is critical for muscle bioenergetics and electrical activity. Whether age-dependent muscle weakness and increased electrical instability depends on perturbations in cellular energetic circuits is unknown. To define energetic remodeling of aged atrial myocardium we tracked dynamics of ATP synthesis-utilization, substrate supply, and phosphotransfer circuits through adenylate kinase (AK), creatine kinase (CK), and glycolytic/glycogenolytic pathways using 18O stable isotope-based phosphometabolomic technology. Samples of intact atrial myocardium from adult and aged rats were subjected to 18O-labeling procedure at resting basal state, and analyzed using the 18O-assisted HPLC-GC/MS technique. Characteristics for aging atria were lower inorganic phosphate Pi[18O], γ-ATP[18O], β-ADP[18O], and creatine phosphate CrP[18O] 18O-labeling rates indicating diminished ATP utilization-synthesis and AK and CK phosphotransfer fluxes. Shift in dynamics of glycolytic phosphotransfer was reflected in the diminished G6P[18O] turnover with relatively constant glycogenolytic flux or G1P[18O] 18O-labeling. Labeling of G3P[18O], an indicator of G3P-shuttle activity and substrate supply to mitochondria, was depressed in aged myocardium. Aged atrial myocardium displayed reduced incorporation of 18O into second (18O2), third (18O3), and fourth (18O4) positions of Pi[18O] and a lower Pi[18O]/γ-ATP[18 O]-labeling ratio, indicating delayed energetic communication and ATP cycling between mitochondria and cellular ATPases. Adrenergic stress alleviated diminished CK flux, AK catalyzed β-ATP turnover and energetic communication in aging atria. Thus, 18O-assisted phosphometabolomics uncovered simultaneous phosphotransfer through AK, CK, and glycolytic pathways and G3P substrate shuttle deficits hindering energetic communication and ATP cycling, which may underlie energetic vulnerability of aging

  13. Decline of Phosphotransfer and Substrate Supply Metabolic Circuits Hinders ATP Cycling in Aging Myocardium.

    PubMed

    Nemutlu, Emirhan; Gupta, Anu; Zhang, Song; Viqar, Maria; Holmuhamedov, Ekhson; Terzic, Andre; Jahangir, Arshad; Dzeja, Petras

    2015-01-01

    Integration of mitochondria with cytosolic ATP-consuming/ATP-sensing and substrate supply processes is critical for muscle bioenergetics and electrical activity. Whether age-dependent muscle weakness and increased electrical instability depends on perturbations in cellular energetic circuits is unknown. To define energetic remodeling of aged atrial myocardium we tracked dynamics of ATP synthesis-utilization, substrate supply, and phosphotransfer circuits through adenylate kinase (AK), creatine kinase (CK), and glycolytic/glycogenolytic pathways using 18O stable isotope-based phosphometabolomic technology. Samples of intact atrial myocardium from adult and aged rats were subjected to 18O-labeling procedure at resting basal state, and analyzed using the 18O-assisted HPLC-GC/MS technique. Characteristics for aging atria were lower inorganic phosphate Pi[18O], γ-ATP[18O], β-ADP[18O], and creatine phosphate CrP[18O] 18O-labeling rates indicating diminished ATP utilization-synthesis and AK and CK phosphotransfer fluxes. Shift in dynamics of glycolytic phosphotransfer was reflected in the diminished G6P[18O] turnover with relatively constant glycogenolytic flux or G1P[18O] 18O-labeling. Labeling of G3P[18O], an indicator of G3P-shuttle activity and substrate supply to mitochondria, was depressed in aged myocardium. Aged atrial myocardium displayed reduced incorporation of 18O into second (18O2), third (18O3), and fourth (18O4) positions of Pi[18O] and a lower Pi[18O]/γ-ATP[18 O]-labeling ratio, indicating delayed energetic communication and ATP cycling between mitochondria and cellular ATPases. Adrenergic stress alleviated diminished CK flux, AK catalyzed β-ATP turnover and energetic communication in aging atria. Thus, 18O-assisted phosphometabolomics uncovered simultaneous phosphotransfer through AK, CK, and glycolytic pathways and G3P substrate shuttle deficits hindering energetic communication and ATP cycling, which may underlie energetic vulnerability of aging

  14. The Association of Levels of and Decline in Grip Strength in Old Age with Trajectories of Life Course Occupational Position

    PubMed Central

    Fritzell, Johan; Hoffmann, Rasmus

    2016-01-01

    Background The study of the influence of life course occupational position (OP) on health in old age demands analysis of time patterns in both OP and health. We study associations between life course time patterns of OP and decline in grip strength in old age. Methods We analyze 5 waves from the Survey of Health Ageing and Retirement in Europe (n = 5108, ages 65–90). We use a pattern-mixture latent growth model to predict the level and decline in grip strength in old age by trajectory of life course OP. We extend and generalize the structured regression approach to establish the explanatory power of different life course models for both the level and decline of grip strength. Results Grip strength declined linearly by 0.70 kg (95% CI -0.74;-0.66) for men and 0.42 kg (95% CI -0.45;-0.39) for women per year. The level of men’s grip strength can best be explained by a critical period during midlife, with those exposed to low OP during this period having 1.67 kg (95% CI -2.33;-1.00) less grip strength. These differences remain constant over age. For women, no association between OP and levels of or decline in grip strength was found. Conclusions Men’s OP in midlife seems to be a critical period for the level of grip strength in old age. Inequalities remain constant over age. The integration of the structured regression approach and latent growth modelling offers new possibilities for life course epidemiology. PMID:27232696

  15. Antiphospholipid antibodies, brain infarcts, and cognitive and motor decline in aging (ABICMA): design of a community-based, longitudinal, clinical-pathological study.

    PubMed

    Arvanitakis, Zoe; Brey, Robin L; Rand, Jacob H; Schneider, Julie A; Leurgans, Sue E; Yu, Lei; Buchman, Aron S; Arfanakis, Konstantinos; Fleischman, Debra A; Boyle, Patricia A; Bennett, David A; Levine, Steven R

    2013-01-01

    The overall goal of the Antiphospholipid Antibodies, Brain Infarcts, and Cognitive and Motor Decline in Aging study is to test the hypothesis that antiphospholipid antibodies (aPL) are associated with an increased risk of pathologically proven brain infarcts and are related to cognitive and motor decline in aging. Putative biologic mechanisms underlying the association of aPL with infarcts and the relation of aPL with clinical outcomes of cognitive and motor impairment, including vascular and other processes, will be examined. The design of this longitudinal, clinical-pathologic study involves quantifying four aPL assays, and relating these to brain infarcts, and to cognitive and motor decline. Vascular mechanisms assessed using antemortem magnetic resonance neuroimaging and postmortem neuropathology, as well as nonvascular mechanisms of inflammation and blood-brain barrier permeability alterations will be examined as plausible mediators of the relation of aPL to cognitive and motor impairment. We will take advantage of antemortem biological specimens (longitudinally collected sera and plasma from which aPL, annexins, C-reactive protein, and matrix metalloproteinases will be quantified), and clinical, neuroimaging, and postmortem neuropathologic data from about 800 elderly, community-dwelling women and men who have agreed to brain autopsy at the time of death, participating in one of two ongoing studies of aging: the Religious Orders Study and the Memory and Aging Project.

  16. A TOMM40 poly-T variant modulates gene expression and is associated with vocabulary ability and decline in nonpathologic aging.

    PubMed

    Payton, A; Sindrewicz, P; Pessoa, V; Platt, H; Horan, M; Ollier, W; Bubb, V J; Pendleton, N; Quinn, J P

    2016-03-01

    The Translocase of Outer Mitochondrial Membrane 40 Homolog and Apolipoprotein E (TOMM40-APOE) locus has been associated with a number of age-related phenotypes in humans including nonpathologic cognitive aging, late-onset Alzheimer's disease, and longevity. Here, we investigate the influence of the TOMM40 intron 6 poly-T variant (rs10524523) on TOMM40 gene expression and cognitive abilities and decline in a cohort of 1613 community-dwelling elderly volunteers who had been followed for changes in cognitive functioning over a period of 14 years (range = 12-18 years). We showed that the shorter length poly-T variants were found to act as a repressor of luciferase gene expression in reporter gene constructs. Expression was reduced to approximately half of that observed for the very long variant. We further observed that the shorter poly-T variant was significantly associated with reduced vocabulary ability and a slower rate of vocabulary decline with age compared to the very long poly-T variants. No significant associations were observed for memory, fluid intelligence or processing speed, although the direction of effect, where the short variant was correlated with reduced ability and slower rate of decline was observed for all tests. Our results indicate that the poly-T variant has the ability to interact with transcription machinery and differentially modulate reporter gene expression and influence vocabulary ability and decline with age.

  17. Involuntary Capture and Voluntary Reorienting of Attention Decline in Middle-Aged and Old Participants

    PubMed Central

    Correa-Jaraba, Kenia S.; Cid-Fernández, Susana; Lindín, Mónica; Díaz, Fernando

    2016-01-01

    The main aim of this study was to examine the effects of aging on event-related brain potentials (ERPs) associated with the automatic detection of unattended infrequent deviant and novel auditory stimuli (Mismatch Negativity, MMN) and with the orienting to these stimuli (P3a component), as well as the effects on ERPs associated with reorienting to relevant visual stimuli (Reorienting Negativity, RON). Participants were divided into three age groups: (1) Young: 21–29 years old; (2) Middle-aged: 51–64 years old; and (3) Old: 65–84 years old. They performed an auditory-visual distraction-attention task in which they were asked to attend to visual stimuli (Go, NoGo) and to ignore auditory stimuli (S: standard, D: deviant, N: novel). Reaction times (RTs) to Go visual stimuli were longer in old and middle-aged than in young participants. In addition, in all three age groups, longer RTs were found when Go visual stimuli were preceded by novel relative to deviant and standard auditory stimuli, indicating a distraction effect provoked by novel stimuli. ERP components were identified in the Novel minus Standard (N-S) and Deviant minus Standard (D-S) difference waveforms. In the N-S condition, MMN latency was significantly longer in middle-aged and old participants than in young participants, indicating a slowing of automatic detection of changes. The following results were observed in both difference waveforms: (1) the P3a component comprised two consecutive phases in all three age groups—an early-P3a (e-P3a) that may reflect the orienting response toward the irrelevant stimulation and a late-P3a (l-P3a) that may be a correlate of subsequent evaluation of the infrequent unexpected novel or deviant stimuli; (2) the e-P3a, l-P3a, and RON latencies were significantly longer in the Middle-aged and Old groups than in the Young group, indicating delay in the orienting response to and the subsequent evaluation of unattended auditory stimuli, and in the reorienting of

  18. Chronic intake of red wine polyphenols by young rats prevents aging-induced endothelial dysfunction and decline in physical performance: role of NADPH oxidase.

    PubMed

    Dal-Ros, Stéphanie; Zoll, Joffrey; Lang, Anne-Laure; Auger, Cyril; Keller, Nathalie; Bronner, Christian; Geny, Bernard; Schini-Kerth, Valérie B

    2011-01-14

    Aging is associated with oxidative stress-mediated endothelial dysfunction and decline in physical performance, which promote cardiovascular diseases. This study examined whether chronic intake of red wine polyphenols (RWPs), a rich source of natural antioxidants, prevents aging-related impairment of vascular function and physical exercise capacity. Vascular reactivity from 12, 20 and 40 week-old rats was assessed in organ chambers. Rats received from week 16 to 40 either solvent, RWPs or the antioxidant and NADPH oxidase inhibitor, apocynin. Aging was associated with blunted endothelium-dependent relaxations, oxidative stress (dihydroethidine staining), and an upregulation of eNOS, arginase I, NADPH oxidase p22phox and nox1 subunits, and AT1 and AT2 receptors (assessed by immunohistochemistry) in the mesenteric artery. RWPs and apocynin improved the endothelial dysfunction, normalized oxidative stress and the expression of the different proteins. RWPs also improved aging-related decline in physical exercise. Thus, intake of RWPs protects against aging-induced endothelial dysfunction and decline in physical performance. These effects likely involve the ability of RWPs to normalize oxidative stress and the expression of proteins involved in the formation of NO and the angiotensin II pathway.

  19. Declining Statewide Trends in Motor Vehicle Crashes and Injury-Related Hospital Admissions

    PubMed Central

    Dischinger, Patricia C.; Ryb, Gabriel E.; Kufera, Joseph A.; Ho, Shiu M.

    2013-01-01

    Numbers of crashes, rates of police-reported injury severity, and hospital admission rates were calculated for the ten year period between 2001 and 2010 in Maryland. Comparisons were made for two 5-year periods of 2001–2005 and 2006–2010. Crash characteristics remained similar for the two five-year periods, but there was a significant increase in occupant age. Declines in police-reported injury severity were noted for each of four age groups: 16–29, 30–54, 55–64, and 65+, with smaller declines among older occupants. In addition, there were significant declines in hospital admissions, comparing the two time periods. Although reductions in crashes may be attributable to various roadway, behavioral, and other safety improvement efforts, reductions in hospital admission rates most likely reflect major improvements in crashworthiness implemented during the past decade. For those admitted to hospitals, significant increases in injury severity were noted between the first and second time periods. There was an association between age and ISS, a measure of total bodily injury, with the highest ISS scores noted for the youngest and oldest groups (16–29 and 55+, respectively). In addition, there was a significant increase in the mean age over time, from 39 in 2001 to 43 in 2010, p<.001. In general, the incidence and severity of injuries increased for all body regions. There was also a significant increase in hospital mortality, although length of hospital stay remained the same. Given these trends, increased efforts need to focus on both injury prevention and treatment for the increasing population of older, sometimes frail, vehicle occupants. PMID:24406962

  20. Neuroanatomy accounts for age-related changes in risk preferences

    PubMed Central

    Grubb, Michael A.; Tymula, Agnieszka; Gilaie-Dotan, Sharon; Glimcher, Paul W.; Levy, Ifat

    2016-01-01

    Many decisions involve uncertainty, or ‘risk', regarding potential outcomes, and substantial empirical evidence has demonstrated that human aging is associated with diminished tolerance for risky rewards. Grey matter volume in a region of right posterior parietal cortex (rPPC) is predictive of preferences for risky rewards in young adults, with less grey matter volume indicating decreased tolerance for risk. That grey matter loss in parietal regions is a part of healthy aging suggests that diminished rPPC grey matter volume may have a role in modulating risk preferences in older adults. Here we report evidence for this hypothesis and show that age-related declines in rPPC grey matter volume better account for age-related changes in risk preferences than does age per se. These results provide a basis for understanding the neural mechanisms that mediate risky choice and a glimpse into the neurodevelopmental dynamics that impact decision-making in an aging population. PMID:27959326

  1. Decline in relative abundance of bottlenose dolphins exposed to long-term disturbance.

    PubMed

    Bejder, Lars; Samuels, Amy; Whitehead, Hal; Gales, Nick; Mann, Janet; Connor, Richard; Heithaus, Mike; Watson-Capps, Jana; Flaherty, Cindy; Krützen, Michael

    2006-12-01

    Studies evaluating effects of human activity on wildlife typically emphasize short-term behavioral responses from which it is difficult to infer biological significance or formulate plans to mitigate harmful impacts. Based on decades of detailed behavioral records, we evaluated long-term impacts of vessel activity on bottlenose dolphins (Tursiops sp.) in Shark Bay, Australia. We compared dolphin abundance within adjacent 36-km2 tourism and control sites, over three consecutive 4.5-year periods wherein research activity was relatively constant but tourism levels increased from zero, to one, to two dolphin-watching operators. A nonlinear logistic model demonstrated that there was no difference in dolphin abundance between periods with no tourism and periods in which one operator offered tours. As the number of tour operators increased to two, there was a significant average decline in dolphin abundance (14.9%; 95% CI=-20.8 to -8.23), approximating a decline of one per seven individuals. Concurrently, within the control site, the average increase in dolphin abundance was not significant (8.5%; 95% CI=-4.0 to +16.7). Given the substantially greater presence and proximity of tour vessels to dolphins relative to research vessels, tour-vessel activity contributed more to declining dolphin numbers within the tourism site than research vessels. Although this trend may not jeopardize the large, genetically diverse dolphin population of Shark Bay, the decline is unlikely to be sustainable for local dolphin tourism. A similar decline would be devastating for small, closed, resident, or endangered cetacean populations. The substantial effect of tour vessels on dolphin abundance in a region of low-level tourism calls into question the presumption that dolphin-watching tourism is benign.

  2. Incident Subjective Cognitive Decline Does Not Predict Mortality in the Elderly – Results from the Longitudinal German Study on Ageing, Cognition, and Dementia (AgeCoDe)

    PubMed Central

    Roehr, Susanne; Luck, Tobias; Heser, Kathrin; Fuchs, Angela; Ernst, Annette; Wiese, Birgitt; Werle, Jochen; Bickel, Horst; Brettschneider, Christian; Koppara, Alexander; Pentzek, Michael; Lange, Carolin; Prokein, Jana; Weyerer, Siegfried; Mösch, Edelgard; König, Hans-Helmut; Maier, Wolfgang; Scherer, Martin

    2016-01-01

    Objective Subjective cognitive decline (SCD) might represent the first symptomatic representation of Alzheimer’s disease (AD), which is associated with increased mortality. Only few studies, however, have analyzed the association of SCD and mortality, and if so, based on prevalent cases. Thus, we investigated incident SCD in memory and mortality. Methods Data were derived from the German AgeCoDe study, a prospective longitudinal study on the epidemiology of mild cognitive impairment (MCI) and dementia in primary care patients over 75 years covering an observation period of 7.5 years. We used univariate and multivariate Cox regression analyses to examine the relationship of SCD and mortality. Further, we estimated survival times by the Kaplan Meier method and case-fatality rates with regard to SCD. Results Among 971 individuals without objective cognitive impairment, 233 (24.0%) incidentally expressed SCD at follow-up I. Incident SCD was not significantly associated with increased mortality in the univariate (HR = 1.0, 95% confidence interval = 0.8–1.3, p = .90) as well as in the multivariate analysis (HR = 0.9, 95% confidence interval = 0.7–1.2, p = .40). The same applied for SCD in relation to concerns. Mean survival time with SCD was 8.0 years (SD = 0.1) after onset. Conclusion Incident SCD in memory in individuals with unimpaired cognitive performance does not predict mortality. The main reason might be that SCD does not ultimately lead into future cognitive decline in any case. However, as prevalence studies suggest, subjectively perceived decline in non-memory cognitive domains might be associated with increased mortality. Future studies may address mortality in such other cognitive domains of SCD in incident cases. PMID:26766555

  3. Suppression of the aging-associated decline in physical performance by a combination of resveratrol intake and habitual exercise in senescence-accelerated mice.

    PubMed

    Murase, Takatoshi; Haramizu, Satoshi; Ota, Noriyasu; Hase, Tadashi

    2009-08-01

    The decline in physical performance with increasing age is a crucial problem in our aging society. We examined the effects of resveratrol, a natural polyphenolic compound present in grapes, in combination with habitual exercise on the aging-associated decline in physical performance in senescence-accelerated prone mice (SAMP1). The endurance capacity of SAMP1 mice undergoing an exercise regimen (SAMP1-Ex) decreased over 12 weeks whereas that of SAMP1 mice fed 0.2% (w/w) resveratrol along with exercise (SAMP1-ExRes) remained significantly higher. In the SAMP1-ExRes group, there was a significant increase in oxygen consumption and skeletal muscle mRNA levels of mitochondrial function-related enzymes. These results suggest that the intake of resveratrol, together with habitual exercise, is beneficial for suppressing the aging-related decline in physical performance and that these effects are attributable, at least in part, to improved mitochondrial function in skeletal muscle.

  4. Introduction to Aging, Cancer, and Age-related Diseases.

    PubMed

    Perry, Daniel P

    2010-06-01

    A rising tide of chronic age-dependent diseases, co-morbidities, and geriatric syndromes--a veritable Silver Tsunami--will soon present serious challenges for North America, Europe, Japan, and other industrialized nations. Meanwhile, a growing number of scientists, led by biogerontologists, maintain that the key to blunting the societal impact of large-scale decline and disability among older populations lies with better understanding and potential manipulation of biological mechanisms of aging itself. Well-characterized interventions that slow aging and extend health and vigor in animal models may be forerunners of technologies that preserve additional years of healthy productive life in humans. What will it take to validate these momentous insights from biogerontology and their potential applications for human populations? What are the points of resistance for key opinion leaders and policy makers? And how can biogerontologists make common cause with those outside the discipline to inform larger and more politically powerful audiences?

  5. Physiological neuronal decline in healthy aging human brain - An in vivo study with MRI and short echo-time whole-brain (1)H MR spectroscopic imaging.

    PubMed

    Ding, Xiao-Qi; Maudsley, Andrew A; Sabati, Mohammad; Sheriff, Sulaiman; Schmitz, Birte; Schütze, Martin; Bronzlik, Paul; Kahl, Kai G; Lanfermann, Heinrich

    2016-08-15

    Knowledge of physiological aging in healthy human brain is increasingly important for neuroscientific research and clinical diagnosis. To investigate neuronal decline in normal aging brain eighty-one healthy subjects aged between 20 and 70years were studied with MRI and whole-brain (1)H MR spectroscopic imaging. Concentrations of brain metabolites N-acetyl-aspartate (NAA), choline (Cho), total creatine (tCr), myo-inositol (mI), and glutamine+glutamate (Glx) in ratios to internal water, and the fractional volumes of brain tissue were estimated simultaneously in eight cerebral lobes and in cerebellum. Results demonstrated that an age-related decrease in gray matter volume was the largest contribution to changes in brain volume. Both lobar NAA and the fractional volume of gray matter (FVGM) decreased with age in all cerebral lobes, indicating that the decreased NAA was predominantly associated with decreased gray matter volume and neuronal density or metabolic activity. In cerebral white matter Cho, tCr, and mI increased with age in association with increased fractional volume, showing altered cellular membrane turn-over, energy metabolism, and glial activity in human aging white matter. In cerebellum tCr increased while brain tissue volume decreased with age, showing difference to cerebral aging. The observed age-related metabolic and microstructural variations suggest that physiological neuronal decline in aging human brain is associated with a reduction of gray matter volume and neuronal density, in combination with cellular aging in white matter indicated by microstructural alterations and altered energy metabolism in the cerebellum.

  6. Idiom understanding in adulthood: examining age-related differences.

    PubMed

    Hung, Pei-Fang; Nippold, Marilyn A

    2014-03-01

    Idioms are figurative expressions such as hold your horses, kick the bucket, and lend me a hand, which commonly occur in everyday spoken and written language. Hence, the understanding of these expressions is essential for daily communication. In this study, we examined idiom understanding in healthy adults in their 20s, 40s, 60s and 80s (n=30 per group) to determine if performance would show an age-related decline. Participants judged their own familiarity with a set of 20 idioms, explained the meaning of each, described a situation in which the idiom could be used, and selected the appropriate interpretation from a set of choices. There was no evidence of an age-related decline on any tasks. Rather, the 60s group reported greater familiarity and offered better explanations than did the 20s group. Moreover, greater familiarity with idioms was associated with better understanding in adults.

  7. Age-Related Differences in Muscular Strength and Muscular Endurance among Female Masters Swimmers.

    ERIC Educational Resources Information Center

    Dummer, Gail M.; And Others

    1985-01-01

    This study investigated age-related differences in muscular strength and muscular endurance among 73 female masters swimmers aged 24 to 71 years. While an age-related decline in muscular strength was apparent, the results failed to reveal a similar trend for endurance, suggesting that swimming influences endurance more than strength among women.…

  8. Pathophysiology of ageing, longevity and age related diseases

    PubMed Central

    Bürkle, Alexander; Caselli, Graziella; Franceschi, Claudio; Mariani, Erminia; Sansoni, Paolo; Santoni, Angela; Vecchio, Giancarlo; Witkowski, Jacek M; Caruso, Calogero

    2007-01-01

    On April 18, 2007 an international meeting on Pathophysiology of Ageing, Longevity and Age-Related Diseases was held in Palermo, Italy. Several interesting topics on Cancer, Immunosenescence, Age-related inflammatory diseases and longevity were discussed. In this report we summarize the most important issues. However, ageing must be considered an unavoidable end point of the life history of each individual, nevertheless the increasing knowledge on ageing mechanisms, allows envisaging many different strategies to cope with, and delay it. So, a better understanding of pathophysiology of ageing and age-related disease is essential for giving everybody a reasonable chance for living a long and enjoyable final part of the life. PMID:17683521

  9. Overcoming Age-Related Differences

    ERIC Educational Resources Information Center

    Agullo, Gloria Luque

    2006-01-01

    One of the most controversial issues in foreign language (FL) teaching is the age at which language learning should start. Nowadays it is recognized that in second language contexts maturational constraints make an early start advisable, but there is still disagreement regarding the problem of when to start or the best way to learn in foreign…

  10. Obesity and related consequences to ageing.

    PubMed

    Jura, Magdalena; Kozak, Leslie P

    2016-02-01

    Obesity has become a major public health problem. Given the current increase in life expectancy, the prevalence of obesity also raises steadily among older age groups. The increase in life expectancy is often accompanied with additional years of susceptibility to chronic ill health associated with obesity in the elderly. Both obesity and ageing are conditions leading to serious health problems and increased risk for disease and death. Ageing is associated with an increase in abdominal obesity, a major contributor to insulin resistance and the metabolic syndrome. Obesity in the elderly is thus a serious concern and comprehension of the key mechanisms of ageing and age-related diseases has become a necessary matter. Here, we aimed to identify similarities underlying mechanisms related to both obesity and ageing. We bring together evidence that age-related changes in body fat distribution and metabolism might be key factors of a vicious cycle that can accelerate the ageing process and onset of age-related diseases.

  11. Do testosterone declines during the transition to marriage and fatherhood relate to men's sexual behavior? Evidence from the Philippines.

    PubMed

    Gettler, Lee T; McDade, Thomas W; Agustin, Sonny S; Feranil, Alan B; Kuzawa, Christopher W

    2013-11-01

    Testosterone (T) is thought to help facilitate trade-offs between mating and parenting in humans. Across diverse cultural settings married men and fathers have lower T than other men and couples' sexual activity often declines during the first years of marriage and after having children. It is unknown whether these behavioral and hormonal changes are related. Here we use longitudinal data from a large study in the Philippines (n=433) to test this model. We show that among unmarried non-fathers at baseline (n=153; age: 21.5 ± 0.3 years) who became newly married new fathers by follow-up (4.5 years later), those who experienced less pronounced longitudinal declines in T reported more frequent intercourse with their partners at follow-up (p<0.01) compared to men with larger declines in T. Controlling for duration of marriage, findings were similar for men transitioning from unmarried to married (without children) (p<0.05). Men who remained unmarried and childless throughout the study period did not show similar T-sexual activity outcomes. Among newly married new fathers, subjects who had frequent intercourse both before and after the transition to married fatherhood had more modest declines in T compared to peers who had less frequent sex (p<0.001). Our findings are generally consistent with theoretical expectations and cross-species empirical observations regarding the role of T in male life history trade-offs, particularly in species with bi-parental care, and add to evidence that T and sexual activity have bidirectional relationships in human males.

  12. Nutrition and age-related eye diseases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vision loss among the elderly is an important health problem. Approximately one person in three has some form of vision-reducing eye disease by the age of 65 [1]. Age-related cataract, age-related macular degeneration (AMD), diabetic retinopathy and glaucoma are the major diseases resulting in visu...

  13. Conservation status of polar bears (Ursus maritimus) in relation to projected sea-ice declines.

    PubMed

    Regehr, Eric V; Laidre, Kristin L; Akçakaya, H Resit; Amstrup, Steven C; Atwood, Todd C; Lunn, Nicholas J; Obbard, Martyn; Stern, Harry; Thiemann, Gregory W; Wiig, Øystein

    2016-12-01

    Loss of Arctic sea ice owing to climate change is the primary threat to polar bears throughout their range. We evaluated the potential response of polar bears to sea-ice declines by (i) calculating generation length (GL) for the species, which determines the timeframe for conservation assessments; (ii) developing a standardized sea-ice metric representing important habitat; and (iii) using statistical models and computer simulation to project changes in the global population under three approaches relating polar bear abundance to sea ice. Mean GL was 11.5 years. Ice-covered days declined in all subpopulation areas during 1979-2014 (median -1.26 days year(-1)). The estimated probabilities that reductions in the mean global population size of polar bears will be greater than 30%, 50% and 80% over three generations (35-41 years) were 0.71 (range 0.20-0.95), 0.07 (range 0-0.35) and less than 0.01 (range 0-0.02), respectively. According to IUCN Red List reduction thresholds, which provide a common measure of extinction risk across taxa, these results are consistent with listing the species as vulnerable. Our findings support the potential for large declines in polar bear numbers owing to sea-ice loss, and highlight near-term uncertainty in statistical projections as well as the sensitivity of projections to different plausible assumptions.

  14. Conservation status of polar bears (Ursus maritimus) in relation to projected sea-ice declines

    PubMed Central

    Akçakaya, H. Resit; Amstrup, Steven C.; Atwood, Todd C.; Lunn, Nicholas J.; Obbard, Martyn; Stern, Harry; Thiemann, Gregory W.; Wiig, Øystein

    2016-01-01

    Loss of Arctic sea ice owing to climate change is the primary threat to polar bears throughout their range. We evaluated the potential response of polar bears to sea-ice declines by (i) calculating generation length (GL) for the species, which determines the timeframe for conservation assessments; (ii) developing a standardized sea-ice metric representing important habitat; and (iii) using statistical models and computer simulation to project changes in the global population under three approaches relating polar bear abundance to sea ice. Mean GL was 11.5 years. Ice-covered days declined in all subpopulation areas during 1979–2014 (median −1.26 days year−1). The estimated probabilities that reductions in the mean global population size of polar bears will be greater than 30%, 50% and 80% over three generations (35–41 years) were 0.71 (range 0.20–0.95), 0.07 (range 0–0.35) and less than 0.01 (range 0–0.02), respectively. According to IUCN Red List reduction thresholds, which provide a common measure of extinction risk across taxa, these results are consistent with listing the species as vulnerable. Our findings support the potential for large declines in polar bear numbers owing to sea-ice loss, and highlight near-term uncertainty in statistical projections as well as the sensitivity of projections to different plausible assumptions. PMID:27928000

  15. Stability and decline in gross motor function among children and youth with cerebral palsy aged 2 to 21 years.

    PubMed

    Hanna, Steven E; Rosenbaum, Peter L; Bartlett, Doreen J; Palisano, Robert J; Walter, Stephen D; Avery, Lisa; Russell, Dianne J

    2009-04-01

    This paper reports the construction of gross motor development curves for children and youth with cerebral palsy (CP) in order to assess whether function is lost during adolescence. We followed children previously enrolled in a prospective longitudinal cohort study for an additional 4 years, as they entered adolescence and young adulthood. The resulting longitudinal dataset comprised 3455 observations of 657 children with CP (369 males, 288 females), assessed up to 10 times, at ages ranging from 16 months to 21 years. Motor function was assessed using the 66-item Gross Motor Function Measure (GMFM-66). Participants were classified using the Gross Motor Function Classification System (GMFCS). We assessed the loss of function in adolescence by contrasting a model of function that assumes no loss with a model that allows for a peak and subsequent decline. We found no evidence of functional decline, on average, for children in GMFCS Levels I and II. However, in Levels III, IV, and V, average GMFM-66 was estimated to peak at ages 7 years 11 months, 6 years 11 months, and 6 years 11 months respectively, before declining by 4.7, 7.8, and 6.4 GMFM-66 points, in Levels III, IV, and V respectively, as these adolescents became young adults. We show that these declines are clinically significant.

  16. What Is Age-Related Macular Degeneration?

    MedlinePlus

    ... of Low Vision Age-Related Macular Degeneration Vision Simulator AMD Pictures and Videos: What Does Macular Degeneration ... degeneration as part of the body's natural aging process. There are different kinds of macular problems, but ...

  17. Serum and Muscle Interleukin-15 Levels Decrease in Aging Mice; Correlation with Declines in Soluble Interleukin-15 Receptor Alpha Expression

    PubMed Central

    Quinn, LeBris S.; Anderson, Barbara G.; Strait-Bodey, Lena; Wolden-Hanson, Tami

    2009-01-01

    Interleukin-15 (IL-15) is a skeletal muscle-derived cytokine with favorable effects on muscle mass and body composition. Modulation of IL-15 levels has been suggested as a treatment for sarcopenia and age-associated increases in adiposity. However, it is unclear whether IL-15 levels change during aging, as measurement of IL-15 at physiological concentrations in mice has been technically difficult, and translational regulation of IL-15 is complex. Moreover, the IL-15 receptor alpha (IL-15Rα) can comprise part of a membrane-associated receptor complex, or appear as a soluble form which stabilizes IL-15 and facilitates IL-15 secretion. Here, we report measurement of physiological levels of murine IL-15, and determine that muscle and serum IL-15 levels decline progressively with age. However, expression of IL-15 mRNA and membrane-associated subunits of the IL-15 receptor did not change with age in muscle. Expression of soluble IL-15Rα (sIL-15Rα) mRNA declined 5-fold with age, and serum IL-15 levels correlated highly with muscle sIL-15 mRNA expression, suggesting declines in sIL-15Rα expression lead to decreased circulating IL-15 levels during aging. These findings complement studies which described several single-nucleotide polymorphisms in the human IL-15Rα gene which impact muscularity and adiposity, and provide a technical basis for further investigation of IL-15 and the sIL-15Rα in determining body composition in aging mice, as a model for humans. PMID:19854259

  18. Relational learning and transitive expression in aging and amnesia.

    PubMed

    Ryan, Jennifer D; D'Angelo, Maria C; Kamino, Daphne; Ostreicher, Melanie; Moses, Sandra N; Rosenbaum, R Shayna

    2016-02-01

    Aging has been associated with a decline in relational memory, which is critically supported by the hippocampus. By adapting the transitivity paradigm (Bunsey and Eichenbaum (1996) Nature 379:255-257), which traditionally has been used in nonhuman animal research, this work examined the extent to which aging is accompanied by deficits in relational learning and flexible expression of relational information. Older adults' performance was additionally contrasted with that of amnesic case DA to understand the critical contributions of the medial temporal lobe, and specifically, the hippocampus, which endures structural and functional changes in healthy aging. Participants were required to select the correct choice item (B versus Y) based on the presented sample item (e.g., A). Pairwise relations must be learned (A->B, B->C, C->D) so that ultimately, the correct relations can be inferred when presented with a novel probe item (A->C?Z?). Participants completed four conditions of transitivity that varied in terms of the degree to which the stimuli and the relations among them were known pre-experimentally. Younger adults, older adults, and DA performed similarly when the condition employed all pre-experimentally known, semantic, relations. Older adults and DA were less accurate than younger adults when all to-be-learned relations were arbitrary. However, accuracy improved for older adults when they could use pre-experimentally known pairwise relations to express understanding of arbitrary relations as indexed through inference judgments. DA could not learn arbitrary relations nor use existing knowledge to support novel inferences. These results suggest that while aging has often been associated with an emerging decline in hippocampal function, prior knowledge can be used to support novel inferences. However, in case DA, significant damage to the hippocampus likely impaired his ability to learn novel relations, while additional damage to ventromedial prefrontal and

  19. A decline in PABPN1 induces progressive muscle weakness in oculopharyngeal muscle dystrophy and in muscle aging.

    PubMed

    Anvar, Seyed Yahya; Raz, Yotam; Verway, Nisha; van der Sluijs, Barbara; Venema, Andrea; Goeman, Jelle J; Vissing, John; van der Maarel, Silvère M; 't Hoen, Peter A C; van Engelen, Baziel G M; Raz, Vered

    2013-06-01

    Oculopharyngeal muscular dystrophy (OPMD) is caused by trinucleotide repeat expansion mutations in Poly(A) binding protein 1 (PABPN1). PABPN1 is a regulator of mRNA stability and is ubiquitously expressed. Here we investigated how symptoms in OPMD initiate only at midlife and why a subset of skeletal muscles is predominantly affected. Genome-wide RNA expression profiles from Vastus lateralis muscles human carriers of expanded-PABPN1 at pre-symptomatic and symptomatic stages were compared with healthy controls. Major expression changes were found to be associated with age rather than with expression of expanded-PABPN1, instead transcriptomes of OPMD and elderly muscles were significantly similar (P<0.05). Using k-means clustering we identified age-dependent trends in both OPMD and controls, but trends were often accelerated in OPMD. We report an age-regulated decline in PABPN1 levels in Vastus lateralis muscles from the fifth decade. In concurrence with severe muscle degeneration in OPMD, the decline in PABPN1 accelerated in OPMD and was specific to skeletal muscles. Reduced PABPN1 levels (30% to 60%) in muscle cells induced myogenic defects and morphological signatures of cellular aging in proportion to PABPN1 expression levels. We suggest that PABPN1 levels regulate muscle cell aging and OPMD represents an accelerated muscle aging disorder.

  20. Aging related changes in determinants of muscle force generating capacity: a comparison of muscle aging in men and male rodents.

    PubMed

    Ballak, Sam B; Degens, Hans; de Haan, Arnold; Jaspers, Richard T

    2014-03-01

    Human aging is associated with a progressive decline in skeletal muscle mass and force generating capacity, however the exact mechanisms underlying these changes are not fully understood. Rodents models have often been used to enhance our understanding of mechanisms of age-related changes in human skeletal muscle. However, to what extent age-related alterations in determinants of muscle force generating capacity observed in rodents resemble those in humans has not been considered thoroughly. This review compares the effect of aging on muscle force generating determinants (muscle mass, fiber size, fiber number, fiber type distribution and muscle specific tension), in men and male rodents at similar relative age. It appears that muscle aging in male F344*BN rat resembles that in men most; 32-35-month-old rats exhibit similar signs of muscle weakness to those of 70-80-yr-old men, and the decline in 36-38-month-old rats is similar to that in men aged over 80 yrs. For male C57BL/6 mice, age-related decline in muscle force generating capacity seems to occur only at higher relative age than in men. We conclude that the effects on determinants of muscle force differ between species as well as within species, but qualitatively show the same pattern as that observed in men.

  1. Age-dependent decline and association with stunting of Giardia duodenalis infection among schoolchildren in rural Huye district, Rwanda.

    PubMed

    Heimer, Jakob; Staudacher, Olga; Steiner, Florian; Kayonga, Yvette; Havugimana, Jean Marie; Musemakweri, Andre; Harms, Gundel; Gahutu, Jean-Bosco; Mockenhaupt, Frank P

    2015-05-01

    Giardia duodenalis infection is highly prevalent and a cause of underweight in pre-school children in rural Rwanda. The present study aimed at assessing the age-pattern of Giardia infection and its manifestation in older children, i.e., during school age. Stool samples were collected from 622 schoolchildren at two schools in the Huye district of southern Rwanda (rural, 301; urban, 321) and subjected to G. duodenalis specific PCR assays. Clinical and anthropometric data, socio-economic status and factors potentially associated with G. duodenalis infection were assessed. Of the 622 children (mean age, 10.4 years), 35.7% were infected with G. duodenalis (rural, 43.9%; urban, 28.0%; P<0.0001). Only few indicators of low socio-economic status were found to be associated with infection. In rural but not urban schoolchildren, infection prevalence declined significantly with age. G. duodenalis infection more than doubled the odds of stunting in both rural (adjusted OR, 2.35 (95%CI, 1.25-4.41)) and urban children (adjusted OR, 2.27 (95%CI, 1.01-5.09)). In the study area of rural southern Rwanda, G. duodenalis prevalence among children declined throughout school-age. The data suggest that while lacking overt clinical manifestation at high endemicity, G. duodenalis infection is a common cause of stunting in schoolchildren.

  2. Microsurgeons do better--tactile training might prevent the age-dependent decline of the sensibility of the hand.

    PubMed

    Schmauss, Daniel; Megerle, Kai; Weinzierl, Andrea; Agua, Kariem; Cerny, Michael; Schmauss, Verena; Lohmeyer, Joern A; Machens, Hans-Guenther; Erne, Holger

    2015-12-01

    Recent data demonstrate that the normal sensibility of the hand seems to be age-dependent with the best values in the third decade and a consecutive deterioration afterwards. However, it is not clear if long-term tactile training might prevent this age-dependent decline. We evaluated sensibility of the hand in 125 surgeons aged between 26 and 75 years who perform microsurgical operations, thereby undergoing regular tactile training. We examined sensibility of the radial digital nerve of the index finger (N3) and the ulnar digital nerve of the small finger (N10) using static and moving two-point discrimination (2PD) tests and compared the results to 154 age-matched individuals without specific long-term tactile training. We found significantly lower static and moving 2PD values for the sixth, seventh, and eighth decade of life in the microsurgery group compared to the control group (p < 0.05). This study demonstrates that long-term tactile training might prevent the known age-dependent decline of the sensibility of the hand.

  3. 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…

  4. Age-related aspects of addiction

    PubMed Central

    Koechl, Birgit; Unger, Annemarie; Fischer, Gabriele

    2013-01-01

    Research has shown that substance use, abuse and addiction are not limited to a specific age group. Problems related to substance addiction are an important cause of morbidity in the population aged 65 and above, especially the abuse of prescription drugs and legal substances. A lack of evidence-based studies and tailored treatment options for the aging population is evident. Appropriate and effective health-care is an important goal to improve health-related quality of life of elderly people. Research in the increasingly aging population needs to include an age- and gender-sensitive approach. PMID:22722821

  5. Dysregulation of the Bmi-1/p16(Ink⁴a) pathway provokes an aging-associated decline of submandibular gland function.

    PubMed

    Yamakoshi, Kimi; Katano, Satoshi; Iida, Mayu; Kimura, Hiromi; Okuma, Atsushi; Ikemoto-Uezumi, Madoka; Ohtani, Naoko; Hara, Eiji; Maruyama, Mitsuo

    2015-08-01

    Bmi-1 prevents stem cell aging, at least partly, by blocking expression of the cyclin-dependent kinase inhibitor p16(Ink4a) . Therefore, dysregulation of the Bmi-1/p16(Ink4a) pathway is considered key to the loss of tissue homeostasis and development of associated degenerative diseases during aging. However, because Bmi-1 knockout (KO) mice die within 20 weeks after birth, it is difficult to determine exactly where and when dysregulation of the Bmi-1/p16(Ink4a) pathway occurs during aging in vivo. Using real-time in vivo imaging of p16(Ink4a) expression in Bmi-1-KO mice, we uncovered a novel function of the Bmi-1/p16(Ink4a) pathway in controlling homeostasis of the submandibular glands (SMGs), which secrete saliva into the oral cavity. This pathway is dysregulated during aging in vivo, leading to induction of p16(Ink4a) expression and subsequent declined SMG function. These findings will advance our understanding of the molecular mechanisms underlying the aging-related decline of SMG function and associated salivary gland hypofunction, which is particularly problematic among the elderly.

  6. Declining Effectiveness of Herpes Zoster Vaccine in Adults Aged ≥60 Years.

    PubMed

    Tseng, Hung Fu; Harpaz, Rafael; Luo, Yi; Hales, Craig M; Sy, Lina S; Tartof, Sara Y; Bialek, Stephanie; Hechter, Rulin C; Jacobsen, Steven J

    2016-06-15

    Understanding long-term effectiveness of herpes zoster (HZ) vaccine is critical for determining vaccine policy. 176 078 members of Kaiser Permanente ≥60 years vaccinated with HZ vaccine and three matched unvaccinated members were included. Hazard ratios and 95% confidence intervals (CIs) associated with vaccination at each year following vaccination were estimated by Cox regression model. The effectiveness of HZ vaccine decreased from 68.7% (95% CI, 66.3%-70.9%) in the first year to 4.2% (95% CI, -24.0% to 25.9%) in the eighth year. This rapid decline in effectiveness of HZ vaccine suggests that a revaccination strategy may be needed, if feasible.

  7. Overview of age-related ocular conditions.

    PubMed

    Akpek, Esen K; Smith, Roderick A

    2013-05-01

    The United States is an aging society. The number of Americans 65 years or older is expected to more than double over the next 40 years, from 40.2 million in 2010 to 88.5 million in 2050, with aging baby boomers accounting for most of the increase. As the society ages, the prevalence of age-related diseases, including diseases of the eye, will continue to increase. By 2020, age-related macular degeneration, one of the leading causes of vision loss, is expected to affect 2.95 million individuals in the United States. Likewise, the prevalence of open-angle glaucoma, estimated at 2.2 million in 2000, is projected to increase by 50%, to 3.36 million by 2020. As the eye ages, it undergoes a number of physiologic changes that may increase susceptibility to disease. Environmental and genetic factors are also major contributors to the development of age-related ocular diseases. This article reviews the physiology of the aging eye and the epidemiology and pathophysiology of 4 major age-related ocular diseases: age-related macular degeneration, glaucoma, diabetic retinopathy, and dry eye.

  8. Functional Decline in Children Undergoing Selective Dorsal Rhizotomy after Age 10

    ERIC Educational Resources Information Center

    MacWilliams, Bruce A.; Johnson, Barbara A.; Shuckra, Amy L.; D'Astous, Jacques L.

    2011-01-01

    Aim: To compare function and gait in a group of children older than most children who received selective dorsal rhizotomy (SDR) with age- and function-matched peers who received either orthopedic surgery or no surgical intervention. Method: A retrospective study examined ambulatory children with diplegic cerebral palsy, aged between 10 years and…

  9. Reproductive Performance of a Declining Forest Passerine in Relation to Environmental and Social Factors: Implications for Species Conservation

    PubMed Central

    Grendelmeier, Alex; Arlettaz, Raphaël; Gerber, Michael; Pasinelli, Gilberto

    2015-01-01

    Identifying factors influencing a species' ecological niche and demography is a prerequisite for species conservation. However, our understanding of the interplay between demographic rates and biotic/abiotic factors is still poor for most species of conservation concern. We evaluated relevance of eight hypotheses relating to timing of breeding, temporal nest exposure, nest concealment, topography, tree structure, predation risk and disturbance, density dependence and weather for explaining variation in reproductive performance of the declining wood warbler Phylloscopus sibilatrix in northern Switzerland. Reproductive performance was monitored with cameras at 136 nests from 2010 to 2012 and was associated to temporal exposure, timing of breeding and concealment of nests. Daily nest survival was positively related to the number of grass and sedge tussocks, nest concealment and nest age. Clutch size and number of fledglings decreased, the later in the season a nest was initiated. Nest survival over an average nesting period of 31 days was 46.9 ± 0.07% (mean ± SE), daily nest survival rate was 0.976 ± 0.002. As for many ground-breeding birds, nest predation was the principal cause of nest failure, accounting for 79% of all nest losses. Conservation measures should aim at increasing the area of relatively homogenous forest stands featuring suitable habitats characterized by abundant and accessible grass and sedge tussocks. In managed forests, such conditions can be found in stands of middle age (i.e. pole wood) with little to no shrub layer. PMID:26172954

  10. Association of Apolipoprotein E-e4 and Dementia Declines with Age

    PubMed Central

    Valerio, Daniel; Raventos, Henriette; Schmeidler, James; Beeri, Michal S.; Villalobos, Lara Mora; Bolaños, Patricia; Carrión-Baralt, José R.; Fornaguera, Jaime; Silverman, Jeremy M.

    2014-01-01

    Objective To study the association of dementia with APOE-e4 and its interaction with age in a nonagenarian Costa Ricans (N-sample) and a general elderly contrast group (GE-sample). Methods In both case-control studies, participants were cognitively intact or demented. The N-sample (N=112) was at least age 90; the GE-sample (N=98) was at least age 65. Results Dementia and APOE-e4 were not significantly associated in the N-sample, but were in the GE-sample. There was a significant interaction of age with APOE-e4 in the N-sample, but not in the GE-sample. Descriptively dividing the N-sample at the median (age 93) showed a group interaction: APOE-e4 was more associated with dementia in the younger N-sample than in the older N-sample, where six of seven APOE-e4 carriers were cognitively intact. Conclusions The results support the reduction in association of APOE-e4 with dementia in extreme old age, consistent with a survivor effect model for successful cognitive aging. PMID:24731780

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

    PubMed

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

    2017-01-01

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

  12. Language in the aging brain: the network dynamics of cognitive decline and preservation.

    PubMed

    Shafto, Meredith A; Tyler, Lorraine K

    2014-10-31

    Language is a crucial and complex lifelong faculty, underpinned by dynamic interactions within and between specialized brain networks. Whereas normal aging impairs specific aspects of language production, most core language processes are robust to brain aging. We review recent behavioral and neuroimaging evidence showing that language systems remain largely stable across the life span and that both younger and older adults depend on dynamic neural responses to linguistic demands. Although some aspects of network dynamics change with age, there is no consistent evidence that core language processes are underpinned by different neural networks in younger and older adults.

  13. Genetic and pharmacological evidence that G2019S LRRK2 confers a hyperkinetic phenotype, resistant to motor decline associated with aging

    PubMed Central

    Longo, Francesco; Russo, Isabella; Shimshek, Derya R.; Greggio, Elisa; Morari, Michele

    2014-01-01

    The leucine-rich repeat kinase 2 mutation G2019S in the kinase-domain is the most common genetic cause of Parkinson's disease. To investigate the impact of the G2019S mutation on motor activity in vivo, a longitudinal phenotyping approach was developed in knock-in (KI) mice bearing this kinase-enhancing mutation. Two cohorts of G2019S KI mice and wild-type littermates (WT) were subjected to behavioral tests, specific for akinesia, bradykinesia and overall gait ability, at different ages (3, 6, 10, 15 and 19 months). The motor performance of G2019S KI mice remained stable up to the age of 19 months and did not show the typical age-related decline in immobility time and stepping activity of WT. Several lines of evidence suggest that enhanced LRRK2 kinase activity is the main contributor to the observed hyperkinetic phenotype of G2019S KI mice: i) KI mice carrying a LRRK2 kinase-dead mutation (D1994S KD) showed a similar progressive motor decline as WT; ii) two LRRK2 kinase inhibitors, H-1152 and Nov-LRRK2-11, acutely reversed the hyperkinetic phenotype of G2019S KI mice, while being ineffective in WT or D1994S KD animals. LRRK2 target engagement in vivo was further substantiated by reduction of LRRK2 phosphorylation at Ser935 in the striatum and cortex at efficacious doses of Nov-LRRK2-11, and in the striatum at efficacious doses of H-1152. In summary, expression of the G2019S mutation in the mouse LRRK2 gene confers a hyperkinetic phenotype that is resistant to age-related motor decline, likely via enhancement of LRRK2 kinase activity. This study provides an in vivo model to investigate the effects of LRRK2 inhibitors on motor function. PMID:25107341

  14. Decline and Decadence in Iraq and Syria after the Age of Avicenna?

    PubMed Central

    Joosse, N. Peter; Pormann, Peter E.

    2010-01-01

    Summary 'Abd al-Laṭīf al-Baghdādī's (d. 1231) work Book of the Two Pieces ofAdvice (Kitāb al Nasīḥatayn) challenges the idea that Islamic medicine declined after the twelfth century AD. Moreover, it offers some interesting insights into the social history of medicine. 'Abd al-Laṭīf advocated using the framework of Greek medical epistemology to criticize the rationalist physicians of his day; he argued that female and itinerant practitioners, relying on experience, were superior to some rationalists. He lambasted contemporaneous medical education because it put too much faith in a restricted number of textbooks such as the Canon by Ibn Sīnā (Avicenna, d. 1037) or imperfect abridgments. PMID:20632731

  15. Alpha-synuclein levels in blood plasma decline with healthy aging.

    PubMed

    Koehler, Niklas K U; Stransky, Elke; Meyer, Mirjam; Gaertner, Susanne; Shing, Mona; Schnaidt, Martina; Celej, Maria S; Jovin, Thomas M; Leyhe, Thomas; Laske, Christoph; Batra, Anil; Buchkremer, Gerhard; Fallgatter, Andreas J; Wernet, Dorothee; Richartz-Salzburger, Elke

    2015-01-01

    There is unequivocal evidence that alpha-synuclein plays a pivotal pathophysiological role in neurodegenerative diseases, and in particular in synucleinopathies. These disorders present with a variable extent of cognitive impairment and alpha-synuclein is being explored as a biomarker in CSF, blood serum and plasma. Considering key events of aging that include proteostasis, alpha-synuclein may not only be useful as a marker for differential diagnosis but also for aging per se. To explore this hypothesis, we developed a highly specific ELISA to measure alpha-synuclein. In healthy males plasma alpha-synuclein levels correlated strongly with age, revealing much lower concentrations in older (avg. 58.1 years) compared to younger (avg. 27.6 years) individuals. This difference between the age groups was enhanced after acidification of the plasmas (p<0.0001), possibly reflecting a decrease of alpha-synuclein-antibody complexes or chaperone activity in older individuals. Our results support the concept that alpha-synuclein homeostasis may be impaired early on, possibly due to disturbance of the proteostasis network, a key component of healthy aging. Thus, alpha-synuclein may be a novel biomarker of aging, a factor that should be considered when analyzing its presence in biological specimens.

  16. DNA damage and repair in telomeres: relation to aging.

    PubMed Central

    Kruk, P A; Rampino, N J; Bohr, V A

    1995-01-01

    We have established a method for the detection of DNA damage and its repair in human telomeres, the natural ends of chromosomes which are necessary for replication and critical for chromosomal stability. We find that ultraviolet light-induced pyrimidine dimers in telomeric DNA are repaired less efficiently than endogenous genes but more efficiently than inactive, noncoding regions. We have also measured telomeric length, telomeric DNA damage, and its repair in relation to the progression of aging. Telomeres are shorter in fibroblasts from an old donor compared to fibroblasts from a young donor, shortest in cells from a patient with the progeroid disorder Werner syndrome, and relatively long in fibroblasts from a patient with Alzheimer disease. Telomeric DNA repair efficiency is lower in cells from an old donor than in cells from a young donor, normal in Alzheimer cells, and slightly lower in Werner cells. It is possible that this decline in telomeric repair with aging is of functional significance to an age-related decline in genomic stability. Images Fig. 1 Fig. 2 PMID:7816828

  17. Ambrosia fungi in the insect-fungi symbiosis in relation to cork oak decline.

    PubMed

    Henriques, Joana; Inácio, Maria Lurdes; Sousa, Edmundo

    2006-09-01

    Ambrosia fungi live associated with beetles (Scolytidae and Platypodidae) in host trees and act as a food source for the insects. The symbiotic relation is important to the colonizing strategies of host trees by beetles. Ambrosia fungi are dimorphic: they grow as ambrosial form and as mycelium. The fungi are highly specialized, adapted to a specific beetle and to the biotope where they both live. In addition other fungi have been found such as tree pathogenic fungi that may play a role in insects host colonization success. Saprophytic fungi are also present in insects galleries. These may decompose cellulose and/or be antagonistic to other less beneficial fungi. This paper summarizes the importance of ambrosia fungi and the interaction with insects and hosts. The possibility of the transport of pathogenic fungi by Platypus cylindrus to cork oak thus contributing for its decline is discussed.

  18. CANTAB object recognition and language tests to detect aging cognitive decline: an exploratory comparative study

    PubMed Central

    Cabral Soares, Fernanda; de Oliveira, Thaís Cristina Galdino; de Macedo, Liliane Dias e Dias; Tomás, Alessandra Mendonça; Picanço-Diniz, Domingos Luiz Wanderley; Bento-Torres, João; Bento-Torres, Natáli Valim Oliver; Picanço-Diniz, Cristovam Wanderley

    2015-01-01

    Objective The recognition of the limits between normal and pathological aging is essential to start preventive actions. The aim of this paper is to compare the Cambridge Neuropsychological Test Automated Battery (CANTAB) and language tests to distinguish subtle differences in cognitive performances in two different age groups, namely young adults and elderly cognitively normal subjects. Method We selected 29 young adults (29.9±1.06 years) and 31 older adults (74.1±1.15 years) matched by educational level (years of schooling). All subjects underwent a general assessment and a battery of neuropsychological tests, including the Mini Mental State Examination, visuospatial learning, and memory tasks from CANTAB and language tests. Cluster and discriminant analysis were applied to all neuropsychological test results to distinguish possible subgroups inside each age group. Results Significant differences in the performance of aged and young adults were detected in both language and visuospatial memory tests. Intragroup cluster and discriminant analysis revealed that CANTAB, as compared to language tests, was able to detect subtle but significant differences between the subjects. Conclusion Based on these findings, we concluded that, as compared to language tests, large-scale application of automated visuospatial tests to assess learning and memory might increase our ability to discern the limits between normal and pathological aging. PMID:25565785

  19. Bone fragility and decline in stem cells in prematurely aging DNA repair deficient trichothiodystrophy mice.

    PubMed

    Diderich, Karin E M; Nicolaije, Claudia; Priemel, Matthias; Waarsing, Jan H; Day, Judd S; Brandt, Renata M C; Schilling, Arndt F; Botter, Sander M; Weinans, Harrie; van der Horst, Gijsbertus T J; Hoeijmakers, Jan H J; van Leeuwen, Johannes P T M

    2012-08-01

    Trichothiodystrophy (TTD) is a rare, autosomal recessive nucleotide excision repair (NER) disorder caused by mutations in components of the dual functional NER/basal transcription factor TFIIH. TTD mice, carrying a patient-based point mutation in the Xpd gene, strikingly resemble many features of the human syndrome and exhibit signs of premature aging. To examine to which extent TTD mice resemble the normal process of aging, we thoroughly investigated the bone phenotype. Here, we show that female TTD mice exhibit accelerated bone aging from 39 weeks onwards as well as lack of periosteal apposition leading to reduced bone strength. Before 39 weeks have passed, bones of wild-type and TTD mice are identical excluding a developmental defect. Albeit that bone formation is decreased, osteoblasts in TTD mice retain bone-forming capacity as in vivo PTH treatment leads to increased cortical thickness. In vitro bone marrow cell cultures showed that TTD osteoprogenitors retain the capacity to differentiate into osteoblasts. However, after 13 weeks of age TTD females show decreased bone nodule formation. No increase in bone resorption or the number of osteoclasts was detected. In conclusion, TTD mice show premature bone aging, which is preceded by a decrease in mesenchymal stem cells/osteoprogenitors and a change in systemic factors, identifying DNA damage and repair as key determinants for bone fragility by influencing osteogenesis and bone metabolism.

  20. The DrugAge database of aging-related drugs.

    PubMed

    Barardo, Diogo; Thornton, Daniel; Thoppil, Harikrishnan; Walsh, Michael; Sharifi, Samim; Ferreira, Susana; Anžič, Andreja; Fernandes, Maria; Monteiro, Patrick; Grum, Tjaša; Cordeiro, Rui; De-Souza, Evandro Araújo; Budovsky, Arie; Araujo, Natali; Gruber, Jan; Petrascheck, Michael; Fraifeld, Vadim E; Zhavoronkov, Alexander; Moskalev, Alexey; de Magalhães, João Pedro

    2017-03-16

    Aging is a major worldwide medical challenge. Not surprisingly, identifying drugs and compounds that extend lifespan in model organisms is a growing research area. Here, we present DrugAge (http://genomics.senescence.info/drugs/), a curated database of lifespan-extending drugs and compounds. At the time of writing, DrugAge contains 1316 entries featuring 418 different compounds from studies across 27 model organisms, including worms, flies, yeast and mice. Data were manually curated from 324 publications. Using drug-gene interaction data, we also performed a functional enrichment analysis of targets of lifespan-extending drugs. Enriched terms include various functional categories related to glutathione and antioxidant activity, ion transport and metabolic processes. In addition, we found a modest but significant overlap between targets of lifespan-extending drugs and known aging-related genes, suggesting that some but not most aging-related pathways have been targeted pharmacologically in longevity studies. DrugAge is freely available online for the scientific community and will be an important resource for biogerontologists.

  1. Age-related changes in cognitive conflict processing: an event-related potential study.

    PubMed

    Mager, Ralph; Bullinger, Alex H; Brand, Serge; Schmidlin, Maria; Schärli, Heinz; Müller-Spahn, Franz; Störmer, Robert; Falkenstein, Michael

    2007-12-01

    Cognitive tasks involving conflicting stimuli and responses are associated with an early age-related decline in performance. Conflict and conflict-induced interference can be stimulus- or response-related. In classical stimulus-response compatibility tasks, such as the Stroop task, the event-related potential (ERP) usually reveals a greater negativity on incongruent versus congruent trials which has often been linked with conflict processing. However, it is unclear whether this negativity is related to stimulus- or response-related conflict, thus rendering the meaning of age-related changes inconclusive. In the present study, a modified Stroop task was used to focus on stimulus-related interference processes while excluding response-related interference. Since we intended to study work-relevant effects ERPs and performance were determined in young (about 30 years old) and middle-aged (about 50 years old) healthy subjects (total n=80). In the ERP, a broad negativity developed after incongruent versus congruent stimuli between 350 and 650 ms. An age-related increase of the latency and amplitude of this negativity was observed. These results indicate age-related alterations in the processing of conflicting stimuli already in middle age.

  2. Hypermaintenance and hypofunction of aged spermatogonia: insight from age-related increase of Plzf expression.

    PubMed

    Ferder, Ianina C; Wang, Ning

    2015-06-30

    Like stem cells in other tissues, spermatogonia, including spermatogonial stem cells (SSCs) at the foundation of differentiation hierarchy, undergo age-related decline in function. The promyelocytic leukemia zinc finger (Plzf) protein plays an essential role in spermatogonia maintenance by preventing their differentiation. To evaluate whether there is an age-related change in Plzf expression, we found that aged mouse testes exhibited a robust "Plzf overexpression" phenotype, in that they showed not only a higher frequency of Plzf-expressing cells but also an increased level of Plzf expression in these cells. Moreover, some Plzf-expressing cells in aged testes even aberrantly appeared in the differentiating spermatogonia compartment, which is usually low or negative for Plzf expression. Importantly, ectopic Plzf expression in F9 cells suppressed retinoic acid (RA)-induced Stra8 activation, a gene required for meiosis initiation. These data, together with our observation of a lack of meiosis-initiating spermatocytes associated with high Plzf-expressing spermatogonia in the aged testes, particularly in the degenerative seminiferous tubules, suggest that age-related increase in Plzf expression represents a novel molecular signature of spermatogonia aging by functionally arresting their differentiation.

  3. Age-related similarities and differences in monitoring spatial cognition.

    PubMed

    Ariel, Robert; Moffat, Scott D

    2017-03-31

    Spatial cognitive performance is impaired in later adulthood but it is unclear whether the metacognitive processes involved in monitoring spatial cognitive performance are also compromised. Inaccurate monitoring could affect whether people choose to engage in tasks that require spatial thinking and also the strategies they use in spatial domains such as navigation. The current experiment examined potential age differences in monitoring spatial cognitive performance in a variety of spatial domains including visual-spatial working memory, spatial orientation, spatial visualization, navigation, and place learning. Younger and older adults completed a 2D mental rotation test, 3D mental rotation test, paper folding test, spatial memory span test, two virtual navigation tasks, and a cognitive mapping test. Participants also made metacognitive judgments of performance (confidence judgments, judgments of learning, or navigation time estimates) on each trial for all spatial tasks. Preference for allocentric or egocentric navigation strategies was also measured. Overall, performance was poorer and confidence in performance was lower for older adults than younger adults. In most spatial domains, the absolute and relative accuracy of metacognitive judgments was equivalent for both age groups. However, age differences in monitoring accuracy (specifically relative accuracy) emerged in spatial tasks involving navigation. Confidence in navigating for a target location also mediated age differences in allocentric navigation strategy use. These findings suggest that with the possible exception of navigation monitoring, spatial cognition may be spared from age-related decline even though spatial cognition itself is impaired in older age.

  4. Incentive relativity in middle aged rats.

    PubMed

    Justel, N; Mustaca, A; Boccia, M; Ruetti, E

    2014-01-24

    Response to a reinforcer is affected by prior experience with different reward values of that reward, a phenomenon known as incentive relativity. Two different procedures to study this phenomenon are the incentive downshift (ID) and the consummatory anticipatory negative contrast (cANC), the former is an emotional-cognitive protocol and the latter cognitive one. Aged rodents, as also well described in aged humans, exhibit alterations in cognitive functions. The main goal of this work was to evaluate the effect of age in the incentive' assessment using these two procedures. The results indicated that aged rats had an adequate assessment of the rewards but their performance is not completely comparable to that of young subjects. They recover faster from the ID and they had a cognitive impairment in the cANC. The results are discussed in relation to age-related changes in memory and emotion.

  5. Effects of Assistive Technology on Functional Decline in People Aging with a Disability

    ERIC Educational Resources Information Center

    Wilson, Dorothy J.; Mitchell, Judith M.; Kemp, Bryan J.; Adkins, Rodney H.; Mann, William

    2009-01-01

    This study used a randomized control group design to investigate the impact of an assistive technology and home modification intervention on function for individuals who are aging with a disability. There were 91 participants with polio, rheumatoid arthritis, cerebral palsy, spinal cord injury, stroke, and other impairments. Outcome data were…

  6. Aging Labels: The Decline of Control and the Fall of Self-Esteem.

    ERIC Educational Resources Information Center

    Rodin, Judith; Langer, Ellen

    1980-01-01

    Describes studies that investigate how labeling and stigmatization of the elderly might contribute to behavior that would confirm prevalent stereotypes of old age and lead to lowered self esteem and diminished feelings of control. Also discusses suggested strategies for social change. (Author/GC)

  7. Cohort Differences in Cognitive Aging and Terminal Decline in the Seattle Longitudinal Study

    ERIC Educational Resources Information Center

    Gerstorf, Denis; Ram, Nilam; Hoppmann, Christiane; Willis, Sherry L.; Schaie, K. Warner

    2011-01-01

    Life span researchers have long been interested in how and why fundamental aspects of human ontogeny differ between cohorts of people who have lived through different historical epochs. When examined at the same age, later born cohorts are often cognitively and physically fitter than earlier born cohorts. Less is known, however, about cohort…

  8. Aging-dependent decline of IL-10 producing B cells coincides with production of antinuclear antibodies but not rheumatoid factors.

    PubMed

    van der Geest, Kornelis S M; Lorencetti, Pedro G; Abdulahad, Wayel H; Horst, Gerda; Huitema, Minke; Roozendaal, Caroline; Kroesen, Bart-Jan; Brouwer, Elisabeth; Boots, Annemieke M H

    2016-03-01

    Aging is associated with development of autoimmunity. Loss of B cell tolerance in the elderly is suggested by an increased prevalence of anti-nuclear antibodies (ANAs) and rheumatoid factors (RFs). Accumulating evidence indicates that B cells also impact autoimmunity via secretion of cytokines. So far, few studies have directly assessed the effect of aging on the latter B cell function. Here, we determined if and how human aging influences the production of cytokines by B cells. In a cross-sectional study, we found that absolute numbers of circulating B cells were similar in 31 young (ages 19-39) and 73 old (age ≥ 60) individuals. Numbers of transitional B cells (CD19(+)CD27(-)CD38(High)CD24(High)) were decreased in old individuals, whereas numbers of naive and memory B cell subsets were comparable in young and old individuals. Short-term in vitro stimulation of whole blood samples revealed that numbers of B cells capable of producing TNF-α were similar in young and old individuals. In contrast, B cells capable of IL-10 production were decreased in old subjects. This decline of IL-10(+) B cells was observed in old individuals that were ANA positive, and in those that were negative for both ANAs and RFs. However, IL-10(+) B cells were remarkably well retained in the circulation of old subjects that were RF positive. Thus, pro-inflammatory TNF-α(+) B cells are retained in the elderly, whereas IL-10(+) B cells generally decline. In addition, our findings indicate that IL-10(+) B cells may differentially impact the development of ANAs and RFs in the elderly.

  9. Relations of age and personality dimensions to cognitive ability factors.

    PubMed

    Costa, P T; Fozard, J L; McCrae, R R; Bosśe, R

    1976-11-01

    The relation between three cognitive ability factors - Information Processing Ability (IPA), Manual Dexterity (MD), and Pattern Analysis Capability (PAC) - and three personality dimensions - Anxiety, Extraversion, and Openness to Experience - were examined in three age groups. Subjects were 969 male volunteers ranging in age from 25 to 82. Subjects high in anixety scored lower on all three cognitive factors; subjects open to experience scored higher on IPA and PAC; and introverted subjects scored higher on PAC. Most of these effects remained when the education and socio-economic status were held constant in covariance analyses. Older subjects performed less well than younger ones on MD and PAC, but not on IPA. While personality has some influence on cognitive performance, the declines with age in performance on some cognitive tasks are not mediated by personality.

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

    ClinicalTrials.gov

    2017-01-12

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

  11. Calibrating the Decline Rate - Peak Luminosity Relation for Type Ia Supernovae

    NASA Astrophysics Data System (ADS)

    Rust, Bert W.; Pruzhinskaya, Maria V.; Thijsse, Barend J.

    2015-08-01

    The correlation between peak luminosity and rate of decline in luminosity for Type I supernovae was first studied by B. W. Rust [Ph.D. thesis, Univ. of Illinois (1974) ORNL-4953] and Yu. P. Pskovskii [Sov. Astron., 21 (1977) 675] in the 1970s. Their work was little-noted until Phillips rediscovered the correlation in 1993 [ApJ, 413 (1993) L105] and attempted to derive a calibration relation using a difference quotient approximation Δm15(B) to the decline rate after peak luminosity Mmax(B). Numerical differentiation of data containing measuring errors is a notoriously unstable calculation, but Δm15(B) remains the parameter of choice for most calibration methods developed since 1993. To succeed, it should be computed from good functional fits to the lightcurves, but most workers never exhibit their fits. In the few instances where they have, the fits are not very good. Some of the 9 supernovae in the Phillips study required extinction corrections in their estimates of the Mmax(B), and so were not appropriate for establishing a calibration relation. Although the relative uncertainties in his Δm15(B) estimates were comparable to those in his Mmax(B) estimates, he nevertheless used simple linear regression of the latter on the former, rather than major-axis regression (total least squares) which would have been more appropriate.Here we determine some new calibration relations using a sample of nearby "pure" supernovae suggested by M. V. Pruzhinskaya [Astron. Lett., 37 (2011) 663]. Their parent galaxies are all in the NED collection, with good distance estimates obtained by several different methods. We fit each lightcurve with an optimal regression spline obtained by B. J. Thijsse's spline2 [Comp. in Sci. & Eng., 10 (2008) 49]. The fits, which explain more that 99% of the variance in each case, are better than anything heretofore obtained by stretching "template" lightcurves or fitting combinations of standard lightcurves. We use the fits to compute estimates of

  12. B-Vitamin Intake and Biomarker Status in Relation to Cognitive Decline in Healthy Older Adults in a 4-Year Follow-Up Study

    PubMed Central

    Hughes, Catherine F.; Ward, Mary; Tracey, Fergal; Hoey, Leane; Molloy, Anne M.; Pentieva, Kristina; McNulty, Helene

    2017-01-01

    Advancing age can be associated with an increase in cognitive dysfunction, a spectrum of disability that ranges in severity from mild cognitive impairment to dementia. Folate and the other B-vitamins involved in one-carbon metabolism are associated with cognition in ageing but the evidence is not entirely clear. The hypothesis addressed in this study was that lower dietary intake or biomarker status of folate and/or the metabolically related B-vitamins would be associated with a greater than expected rate of cognitive decline over a 4-year follow-up period in healthy older adults. Participants (aged 60–88 years; n = 155) who had been previously screened for cognitive function were reassessed four years after initial investigation using the Mini-Mental State Examination (MMSE). At the 4-year follow-up assessment when participants were aged 73.4 ± 7.1 years, mean cognitive MMSE scores had declined from 29.1 ± 1.3 at baseline to 27.5 ± 2.4 (p < 0.001), but some 27% of participants showed a greater than expected rate of cognitive decline (i.e., decrease in MMSE > 0.56 points per year). Lower vitamin B6 status, as measured using pyridoxal-5-phosphate (PLP; <43 nmol/L) was associated with a 3.5 times higher risk of accelerated cognitive decline, after adjustment for age and baseline MMSE score (OR, 3.48; 95% CI, 1.58 to 7.63; p < 0.05). Correspondingly, lower dietary intake (0.9–1.4 mg/day) of vitamin B6 was also associated with a greater rate of cognitive decline (OR, 4.22; 95% CI, 1.28–13.90; p < 0.05). No significant relationships of dietary intake or biomarker status with cognitive decline were observed for the other B-vitamins. In conclusion, lower dietary and biomarker status of vitamin B6 at baseline predicted a greater than expected rate of cognitive decline over a 4-year period in healthy older adults. Vitamin B6 may be an important protective factor in helping maintain cognitive health in ageing. PMID:28075382

  13. Aging-Related Hormone Changes in Men

    MedlinePlus

    Healthy Lifestyle Men's health Aging-related hormone changes in men — sometimes called male menopause — are different from those ... to erectile dysfunction and other sexual issues. Make healthy lifestyle choices. Eat a healthy diet and include physical ...

  14. Translational strategies in aging and age-related disease.

    PubMed

    Armanios, Mary; de Cabo, Rafael; Mannick, Joan; Partridge, Linda; van Deursen, Jan; Villeda, Saul

    2015-12-01

    Aging is a risk factor for several of the world's most prevalent diseases, including neurodegenerative disorders, cancer, cardiovascular disease and metabolic disease. Although our understanding of the molecular pathways that contribute to the aging process and age-related disease is progressing through the use of model organisms, how to apply this knowledge in the clinic is less clear. In September, Nature Medicine, in collaboration with the Volkswagen Foundation, hosted a conference at the beautiful Herrenhausen Palace in Hannover, Germany with the goal of broadening our understanding of the aging process and its meaning as a 'risk factor' in disease. Here, several of the speakers at that conference answer questions posed by Nature Medicine.

  15. The decline of theory of mind in old age is (partly) mediated by developmental changes in domain-general abilities.

    PubMed

    Rakoczy, Hannes; Harder-Kasten, Antje; Sturm, Lioba

    2012-02-01

    Following up on existing, mixed findings in the literature on social cognition in old age different aspects of theory of mind were investigated in younger and older adults. In line with some previous findings, older participants--though matched with the younger ones on crystallized abilities--performed significantly worse both on tasks requiring the ascription of complex intentional attitudes to story protagonists and on tasks of recognizing subtle emotional expressions from video displays. Control analyses showed, however, that these deficits are partly explained by domain-general declines in processing speed and executive function. The implications of these findings for the nature of social cognition and its fate in old age are discussed.

  16. Spatio-Temporal Variation in Age Structure and Abundance of the Endangered Snail Kite: Pooling across Regions Masks a Declining and Aging Population

    PubMed Central

    Kendall, William L.; Fletcher, Robert J.; Kitchens, Wiley M.

    2016-01-01

    While variation in age structure over time and space has long been considered important for population dynamics and conservation, reliable estimates of such spatio-temporal variation in age structure have been elusive for wild vertebrate populations. This limitation has arisen because of problems of imperfect detection, the potential for temporary emigration impacting assessments of age structure, and limited information on age. However, identifying patterns in age structure is important for making reliable predictions of both short- and long-term dynamics of populations of conservation concern. Using a multistate superpopulation estimator, we estimated region-specific abundance and age structure (the proportion of individuals within each age class) of a highly endangered population of snail kites for two separate regions in Florida over 17 years (1997–2013). We find that in the southern region of the snail kite—a region known to be critical for the long-term persistence of the species—the population has declined significantly since 1997, and during this time, it has increasingly become dominated by older snail kites (> 12 years old). In contrast, in the northern region—a region historically thought to serve primarily as drought refugia—the population has increased significantly since 2007 and age structure is more evenly distributed among age classes. Given that snail kites show senescence at approximately 13 years of age, where individuals suffer higher mortality rates and lower breeding rates, these results reveal an alarming trend for the southern region. Our work illustrates the importance of accounting for spatial structure when assessing changes in abundance and age distribution and the need for monitoring of age structure in imperiled species. PMID:27681854

  17. Spatio-temporal variation in age structure and abundance of the endangered snail kite: Pooling across regions masks a declining and aging population

    USGS Publications Warehouse

    Reichert, Brian E.; Kendall, William; Fletcher, Robert J.; Kitchens, Wiley M.

    2016-01-01

    While variation in age structure over time and space has long been considered important for population dynamics and conservation, reliable estimates of such spatio-temporal variation in age structure have been elusive for wild vertebrate populations. This limitation has arisen because of problems of imperfect detection, the potential for temporary emigration impacting assessments of age structure, and limited information on age. However, identifying patterns in age structure is important for making reliable predictions of both short- and long-term dynamics of populations of conservation concern. Using a multistate superpopulation estimator, we estimated region-specific abundance and age structure (the proportion of individuals within each age class) of a highly endangered population of snail kites for two separate regions in Florida over 17 years (1997–2013). We find that in the southern region of the snail kite—a region known to be critical for the long-term persistence of the species—the population has declined significantly since 1997, and during this time, it has increasingly become dominated by older snail kites (> 12 years old). In contrast, in the northern region—a region historically thought to serve primarily as drought refugia—the population has increased significantly since 2007 and age structure is more evenly distributed among age classes. Given that snail kites show senescence at approximately 13 years of age, where individuals suffer higher mortality rates and lower breeding rates, these results reveal an alarming trend for the southern region. Our work illustrates the importance of accounting for spatial structure when assessing changes in abundance and age distribution and the need for monitoring of age structure in imperiled species.

  18. Relative age effect in Japanese male athletes.

    PubMed

    Nakata, Hiroki; Sakamoto, Kiwako

    2011-10-01

    The present study investigated the relative age effect, a biased distribution of elite athletes' birthdates, in Japanese male athletes. Japan applies a unique annual-age grouping for sport and education, which is from April 1 to March 31 of the following year. A total of 4,318 male athletes was evaluated from 12 sports: baseball, soccer, basketball, volleyball, handball, golf, horse racing, rugby, American football, sumo, Ekiden (track and field in long distance), and badminton. They played in the top level of Japanese leagues for each sport in 2010. The distribution of the birth dates was examined in each sport and showed significant relative age effect in baseball, soccer, volleyball, Ekiden, basketball, sumo, and horse racing, but not in all sports. The findings suggest that although the school year in Japan starts on April 1, significant relative age effects are observed in some sporting events.

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

    PubMed

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

    2016-05-01

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

  20. Phospholipase A2 – nexus of aging, oxidative stress, neuronal excitability, and functional decline of the aging nervous system? Insights from a snail model system of neuronal aging and age-associated memory impairment

    PubMed Central

    Hermann, Petra M.; Watson, Shawn N.; Wildering, Willem C.

    2014-01-01

    The aging brain undergoes a range of changes varying from subtle structural and physiological changes causing only minor functional decline under healthy normal aging conditions, to severe cognitive or neurological impairment associated with extensive loss of neurons and circuits due to age-associated neurodegenerative disease conditions. Understanding how biological aging processes affect the brain and how they contribute to the onset and progress of age-associated neurodegenerative diseases is a core research goal in contemporary neuroscience. This review focuses on the idea that changes in intrinsic neuronal electrical excitability associated with (per)oxidation of membrane lipids and activation of phospholipase A2 (PLA2) enzymes are an important mechanism of learning and memory failure under normal aging conditions. Specifically, in the context of this special issue on the biology of cognitive aging we portray the opportunities offered by the identifiable neurons and behaviorally characterized neural circuits of the freshwater snail Lymnaea stagnalis in neuronal aging research and recapitulate recent insights indicating a key role of lipid peroxidation-induced PLA2 as instruments of aging, oxidative stress and inflammation in age-associated neuronal and memory impairment in this model system. The findings are discussed in view of accumulating evidence suggesting involvement of analogous mechanisms in the etiology of age-associated dysfunction and disease of the human and mammalian brain. PMID:25538730

  1. Estimated Glomerular Filtration Rate Decline Is a Better Risk Factor for Outcomes of Systemic Disease-Related Nephropathy than for Outcomes of Primary Renal Diseases

    PubMed Central

    Chen, Chyong-Mei; Cheng, Chi-Hung; Wu, Ming-Ju; Chen, Cheng-Hsu; Yu, Tung-Min; Shu, Kuo-Hsiung

    2014-01-01

    Background Currently, the contribution of kidney function decline in renal and patient outcomes is unclear. There are few data on the associations of different etiologies of estimated glomerular filtration rate (eGFR) decline with outcomes in multidisciplinary care. The purpose of this investigation was to establish whether eGFR decline in patients with disease is an important risk factor for developing end-stage renal disease (ESRD) and death. Methods From December 1, 2001 to December 31, 2011, 5097 adults with chronic kidney disease (CKD) received biochemical tests, physical examinations, a pathological examination, and a comprehensive questionnaire. We used linear regression models and multivariate Cox proportional hazards model to examine the outcome of eGFR decline in renal diseases with different etiologies. Results Mean age was 68.1±16.1 (standard deviation, SD) years, and 63.3% patients were male. In the studied cohort, 58.2% of the patients had systemic disease-related nephropathy (SDRN), 29.4% had primary renal diseases (PRDs), and 12.4% had other etiologies. The eGFR decline in SDRN had a significant association with dialysis in the Cox proportional hazards model [crude hazard ratio (HR) = 1.07, 95% confidence interval (CI), 1.04 to 1.10; adjusted HR 1.05, 95% CI, 1.02 to 1.08]. Diabetic nephropathy (DN) had the most severe eGFR decline in CKD stages 3, 4, and 5, and all contributed to the initiation of dialysis and death regardless of whether DN with or without eGFR decline was considered to be the cause. Although hypertensive nephropathy (HN) was related to significant acceleration of eGFR decline, it did not lead to poor outcome. There were still discrepancies between eGFR decline and outcomes in PRDs, hypertensive nephropathy, and lupus nephritis. Conclusions eGFR decline and CKD staging provide an informative guide for physicians to make proper clinical judgments in the treatment of CKD, especially SDRN. Poor control of the underlying systemic

  2. Hhip haploinsufficiency sensitizes mice to age-related emphysema.

    PubMed

    Lao, Taotao; Jiang, Zhiqiang; Yun, Jeong; Qiu, Weiliang; Guo, Feng; Huang, Chunfang; Mancini, John Dominic; Gupta, Kushagra; Laucho-Contreras, Maria E; Naing, Zun Zar Chi; Zhang, Li; Perrella, Mark A; Owen, Caroline A; Silverman, Edwin K; Zhou, Xiaobo

    2016-08-09

    Genetic variants in Hedgehog interacting protein (HHIP) have consistently been associated with the susceptibility to develop chronic obstructive pulmonary disease and pulmonary function levels, including the forced expiratory volume in 1 s (FEV1), in general population samples by genome-wide association studies. However, in vivo evidence connecting Hhip to age-related FEV1 decline and emphysema development is lacking. Herein, using Hhip heterozygous mice (Hhip(+/-)), we observed increased lung compliance and spontaneous emphysema in Hhip(+/-) mice starting at 10 mo of age. This increase was preceded by increases in oxidative stress levels in the lungs of Hhip(+/-) vs. Hhip(+/+) mice. To our knowledge, these results provide the first line of evidence that HHIP is involved in maintaining normal lung function and alveolar structures. Interestingly, antioxidant N-acetyl cysteine treatment in mice starting at age of 5 mo improved lung function and prevented emphysema development in Hhip(+/-) mice, suggesting that N-acetyl cysteine treatment limits the progression of age-related emphysema in Hhip(+/-) mice. Therefore, reduced lung function and age-related spontaneous emphysema development in Hhip(+/-) mice may be caused by increased oxidative stress levels in murine lungs as a result of haploinsufficiency of Hhip.

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

    ERIC Educational Resources Information Center

    Smith, Theresa Marie

    2008-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  5. Aging-related inflammation in osteoarthritis.

    PubMed

    Greene, M A; Loeser, R F

    2015-11-01

    It is well accepted that aging is an important contributing factor to the development of osteoarthritis (OA). The mechanisms responsible appear to be multifactorial and may include an age-related pro-inflammatory state that has been termed "inflamm-aging." Age-related inflammation can be both systemic and local. Systemic inflammation can be promoted by aging changes in adipose tissue that result in increased production of cytokines such as interleukin (IL)-6 and tumor necrosis factor-α (TNFα). Numerous studies have shown an age-related increase in blood levels of IL-6 that has been associated with decreased physical function and frailty. Importantly, higher levels of IL-6 have been associated with an increased risk of knee OA progression. However, knockout of IL-6 in male mice resulted in worse age-related OA rather than less OA. Joint tissue cells, including chondrocytes and meniscal cells, as well as the neighboring infrapatellar fat in the knee joint, can be a local source of inflammatory mediators that increase with age and contribute to OA. An increased production of pro-inflammatory mediators that include cytokines and chemokines, as well as matrix-degrading enzymes important in joint tissue destruction, can be the result of cell senescence and the development of the senescence-associated secretory phenotype (SASP). Further studies are needed to better understand the basis for inflamm-aging and its role in OA with the hope that this work will lead to new interventions targeting inflammation to reduce not only joint tissue destruction but also pain and disability in older adults with OA.

  6. Needs in Nursing Homes and Their Relation with Cognitive and Functional Decline, Behavioral and Psychological Symptoms

    PubMed Central

    Ferreira, Ana Rita; Dias, Cláudia Camila; Fernandes, Lia

    2016-01-01

    Unmet needs are becoming acknowledged as better predictors of the worst prognostic outcomes than common measures of functional or cognitive decline. Their accurate assessment is a pivotal component of effective care delivery, particularly in institutionalized care where little is known about the needs of its residents, many of whom suffer from dementia and show complex needs. The aims of this study were to describe the needs of an institutionalized sample and to analyze its relationship with demographic and clinical characteristics. A cross-sectional study was conducted with a sample from three nursing homes. All residents were assessed with a comprehensive protocol that included Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS-15), Neuropsychiatric Inventory (NPI) and Adults and Older Adults Functional Inventory (IAFAI). To identify needs, the Camberwell Assessment of Need for the Elderly (CANE) was used. The final sample included 175 residents with a mean age of 81 standard deviation (SD = 10) years. From these, 58.7% presented cognitive deficit (MMSE) and 45.2% depressive symptoms (GDS). Statistically significant negative correlations were found between MMSE score and met (rs = −0.425), unmet (rs = −0.369) and global needs (rs = −0.565). Data also showed significant correlations between depressive symptoms and unmet (rs = 0.683) and global needs (rs = 0.407), and between behavioral and psychological symptoms (BPSD) and unmet (rs = 0.181) and global needs (rs = 0.254). Finally, significant correlations between functional impairment and met (rs = 0.642), unmet (rs = 0.505) and global needs (rs = 0.796) were also found. These results suggest that in this sample, more unmet needs are associated with the worst outcomes measured. This is consistent with previous findings and seems to demonstrate that the needs of those institutionalized elderly remain under-diagnosed and untreated. PMID:27148044

  7. Respiratory training as strategy to prevent cognitive decline in aging: a randomized controlled trial

    PubMed Central

    Ferreira, Leandro; Tanaka, Kátia; Santos-Galduróz, Ruth Ferreira; Galduróz, José Carlos Fernandes

    2015-01-01

    Background Inadequate oxygenation may cause lesions and brain atrophy during aging. Studies show a positive association between pulmonary function and the cognitive performance of individuals from middle age on. Objective To investigate the effect of aerobic physical exercises and respiratory training on the blood oxygenation, pulmonary functions, and cognition of the elderly. Design This was a randomized and controlled trial with three parallel groups. A total of 195 community-dwelling elderly were assessed for eligibility; only n=102 were included and allocated into the three groups, but after 6 months, n=68 were analyzed in the final sample. Participants were randomized into a social interaction group (the control group), an aerobic exercise group (the “walking” group), or a respiratory training group (the “breathing” group). The main outcome measures were the Wechsler Adult Intelligence Scale, Wechsler Memory Scale, Wisconsin Card Sorting Test, respiratory muscular strength, cirtometry (thoracic–abdominal circumference); oxygen saturation in arterial blood (SpO2), and hemogram. Results No differences were observed for any of the blood parameters. Aerobic exercise and respiratory training were effective in improving the pulmonary parameters. Better cognitive performance was observed for the breathing group as regards abstraction and mental flexibility. The walking group remained stable in the cognitive performance of most of the tests, except attention. The control group presented worst performance in mental manipulation of information, abstraction, mental flexibility, and attention. Conclusion Our results showed that both the walking and breathing groups presented improvement of pulmonary function. However, only the breathing group showed improved cognitive function (abstraction, mental flexibility). The improvement in cognitive functions cannot be explained by blood parameters, such as SpO2, erythrocytes, hemoglobin, and hematocrit. PMID:25848235

  8. Gender Relations and Applied Research on Aging

    ERIC Educational Resources Information Center

    Calasanti, Toni

    2010-01-01

    As a concept in gerontology, gender appears as lists of traits learned through socialization when theorized at all. I argue for a framework that theorizes the intersections of relations of gender inequality with those of age. This framework holds that men and women gain resources and bear responsibilities, in relation to one another, by virtue of…

  9. [Impact of thymic function in age-related immune deterioration].

    PubMed

    Ferrando-Martínez, Sara; de la Fuente, Mónica; Guerrero, Juan Miguel; Leal, Manuel; Muñoz-Fernández, M Ángeles

    2013-01-01

    Age-related biological deterioration also includes immune system deterioration and, in consequence, a rise in the incidence and prevalence of infections and cancers, as well as low responses to vaccination strategies. Out of all immune cell subsets, T-lymphocytes seem to be involved in most of the age-related defects. Since T-lymphocytes mature during their passage through the thymus, and the thymus shows an age-related process of atrophy, thymic regression has been proposed as the triggering event of this immune deterioration in elderly people. Historically, it has been accepted that the young thymus sets the T-lymphocyte repertoire during the childhood, whereupon atrophy begins until the elderly thymus is a non-functional evolutionary trace. However, a rising body of knowledge points toward the thymus functioning during adulthood. In the elderly, higher thymic function is associated with a younger immune system, while thymic function failure is associated with all-cause mortality. Therefore, any new strategy focused on the improvement of the elderly quality of life, especially those trying to influence the immune system, should take into account, together with peripheral homeostasis, thymus function as a key element in slowing down age-related decline.

  10. Future Declines of Coronary Heart Disease Mortality in England and Wales Could Counter the Burden of Population Ageing

    PubMed Central

    Guzman Castillo, Maria; Gillespie, Duncan O. S.; Allen, Kirk; Bandosz, Piotr; Schmid, Volker; Capewell, Simon; O’Flaherty, Martin

    2014-01-01

    Background Coronary Heart Disease (CHD) remains a major cause of mortality in the United Kingdom. Yet predictions of future CHD mortality are potentially problematic due to population ageing and increase in obesity and diabetes. Here we explore future projections of CHD mortality in England & Wales under two contrasting future trend assumptions. Methods In scenario A, we used the conventional counterfactual scenario that the last-observed CHD mortality rates from 2011 would persist unchanged to 2030. The future number of deaths was calculated by applying those rates to the 2012–2030 population estimates. In scenario B, we assumed that the recent falling trend in CHD mortality rates would continue. Using Lee-Carter and Bayesian Age Period Cohort (BAPC) models, we projected the linear trends up to 2030. We validate our methods using past data to predict mortality from 2002–2011. Then, we computed the error between observed and projected values. Results In scenario A, assuming that 2011 mortality rates stayed constant by 2030, the number of CHD deaths would increase 62% or approximately 39,600 additional deaths. In scenario B, assuming recent declines continued, the BAPC model (the model with lowest error) suggests the number of deaths will decrease by 56%, representing approximately 36,200 fewer deaths by 2030. Conclusions The decline in CHD mortality has been reasonably continuous since 1979, and there is little reason to believe it will soon halt. The commonly used assumption that mortality will remain constant from 2011 therefore appears slightly dubious. By contrast, using the BAPC model and assuming continuing mortality falls offers a more plausible prediction of future trends. Thus, despite population ageing, the number of CHD deaths might halve again between 2011 and 2030. This has implications for how the potential benefits of future cardiovascular strategies might best be calculated and presented. PMID:24918442

  11. The endoplasmic reticulum stress response in aging and age-related diseases

    PubMed Central

    Brown, Marishka K.; Naidoo, Nirinjini

    2012-01-01

    The endoplasmic reticulum(ER) is a multifunctional organelle within which protein folding, lipid biosynthesis, and calcium storage occurs. Perturbations such as energy or nutrient depletion, disturbances in calcium or redox status that disrupt ER homeostasis lead to the misfolding of proteins, ER stress and up-regulation of several signaling pathways coordinately called the unfolded protein response (UPR). The UPR is characterized by the induction of chaperones, degradation of misfolded proteins and attenuation of protein translation. The UPR plays a fundamental role in the maintenance of cellular homeostasis and thus is central to normal physiology. However, sustained unresolved ER stress leads to apoptosis. Aging linked declines in expression and activity of key ER molecular chaperones and folding enzymes compromise proper protein folding and the adaptive response of the UPR. One mechanism to explain age associated declines in cellular functions and age-related diseases is a progressive failure of chaperoning systems. In many of these diseases, proteins or fragments of proteins convert from their normally soluble forms to insoluble fibrils or plaques that accumulate in a variety of organs including the liver, brain or spleen. This group of diseases, which typically occur late in life includes Alzheimer's, Parkinson's, type II diabetes and a host of less well known but often equally serious conditions such as fatal familial insomnia. The UPR is implicated in many of these neurodegenerative and familial protein folding diseases as well as several cancers and a host of inflammatory diseases including diabetes, atherosclerosis, inflammatory bowel disease and arthritis. This review will discuss age-related changes in the ER stress response and the role of the UPR in age-related diseases. PMID:22934019

  12. Age trajectories of physiological indices in relation to healthy life course.

    PubMed

    Arbeev, Konstantin G; Ukraintseva, Svetlana V; Akushevich, Igor; Kulminski, Alexander M; Arbeeva, Liubov S; Akushevich, Lucy; Culminskaya, Irina V; Yashin, Anatoliy I

    2011-03-01

    We analysed relationship between the risk of onset of "unhealthy life" (defined as the onset of cancer, cardiovascular diseases, or diabetes) and longitudinal changes in body mass index, diastolic blood pressure, hematocrit, pulse pressure, pulse rate, and serum cholesterol in the Framingham Heart Study (Original Cohort) using the stochastic process model of human mortality and aging. The analyses demonstrate how decline in resistance to stresses and adaptive capacity accompanying human aging can be evaluated from longitudinal data. We showed how these components of the aging process, as well as deviation of the trajectories of physiological indices from those minimising the risk at respective ages, can lead to an increase in the risk of onset of unhealthy life with age. The results indicate the presence of substantial gender difference in aging related decline in stress resistance and adaptive capacity, which can contribute to differences in the shape of the sex-specific patterns of incidence rates of aging related diseases.

  13. Early decline in glucose transport and metabolism precedes shift to ketogenic system in female aging and Alzheimer's mouse brain: implication for bioenergetic intervention.

    PubMed

    Ding, Fan; Yao, Jia; Rettberg, Jamaica R; Chen, Shuhua; Brinton, Roberta Diaz

    2013-01-01

    We previously demonstrated that mitochondrial bioenergetic deficits in the female brain accompanied reproductive senescence and was accompanied by a shift from an aerobic glycolytic to a ketogenic phenotype. Herein, we investigated the relationship between systems of fuel supply, transport and mitochondrial metabolic enzyme expression/activity during aging (3-15 months) in the hippocampus of nontransgenic (nonTg) background and 3xTgAD female mice. Results indicate that during female brain aging, both nonTg and 3xTgAD brains undergo significant decline in glucose transport, as detected by FDG-microPET, between 6-9 months of age just prior to the transition into reproductive senescence. The deficit in brain metabolism was sustained thereafter. Decline in glucose transport coincided with significant decline in neuronal glucose transporter expression and hexokinase activity with a concomitant rise in phosphorylated/inactivated pyruvate dehydrogenase. Lactate utilization declined in parallel to the decline in glucose transport suggesting lactate did not serve as an alternative fuel. An adaptive response in the nonTg hippocampus was a shift to transport and utilization of ketone bodies as an alternative fuel. In the 3xTgAD brain, utilization of ketone bodies as an alternative fuel was evident at the earliest age investigated and declined thereafter. The 3xTgAD adaptive response was to substantially increase monocarboxylate transporters in neurons while decreasing their expression at the BBB and in astrocytes. Collectively, these data indicate that the earliest change in the metabolic system of the aging female brain is the decline in neuronal glucose transport and metabolism followed by decline in mitochondrial function. The adaptive shift to the ketogenic system as an alternative fuel coincided with decline in mitochondrial function. Translationally, these data provide insights into the earliest events in bioenergetic aging of the female brain and provide potential

  14. Pathophysiology of age-related diseases

    PubMed Central

    Campisi, Giuseppina; Chiappelli, Martina; De Martinis, Massimo; Franco, Vito; Ginaldi, Lia; Guiglia, Rosario; Licastro, Federico; Lio, Domenico

    2009-01-01

    A Symposium regarding the Pathophysiology of Successful and Unsuccessful Ageing was held in Palermo, Italy on 7-8 April 2009. Three lectures from that Symposium by G. Campisi, L. Ginaldi and F. Licastro are here summarized. Ageing is a complex process which negatively impacts on the development of various bodily systems and its ability to function. A long life in a healthy, vigorous, youthful body has always been one of humanity's greatest dreams. Thus, a better understanding of the pathophysiology of age-related diseases is urgently required to improve our understanding of maintaining good health in the elderly and to program possible therapeutic intervention. PMID:19737378

  15. Mood, Memory and Movement: An Age-Related Neurodegenerative Complex?

    PubMed Central

    Granholm, Ann-Charlotte; Boger, Heather; Emborg, Marina E.

    2009-01-01

    The following review was constructed as a concept paper based on a recent workshop on neurodegenerative disease sponsored by the National Institute on Aging (NIA), the American Geriatric Society (AGS), and the John A. Hartford Foundation. The meeting was entitled “Thinking, moving and feeling: Common underlying mechanisms? 4th Annual Bedside-to-Bench Conference” and had the purpose to connect current basic and clinical findings on common brain-related alterations occurring with aging such as depression, movement disorders, and cognitive decline. Many prominent researchers expressed their opinion on aging and it was revealed that age-related brain dysfunction of any kind seems to share several risk factors and/or pathways. But can something be done to actively achieve “successful aging”? In this review, based largely on the workshop and current literature, we have summarized some of the current theories for depression, movement and cognitive impairment with aging, as well as potential preventive measures. We have also summarized the emerging need for relevant animal models and how these could be developed and utilized. PMID:20021382

  16. Net aboveground biomass declines of four major forest types with forest ageing and climate change in western Canada's boreal forests.

    PubMed

    Chen, Han Y H; Luo, Yong

    2015-10-01

    Biomass change of the world's forests is critical to the global carbon cycle. Despite storing nearly half of global forest carbon, the boreal biome of diverse forest types and ages is a poorly understood component of the carbon cycle. Using data from 871 permanent plots in the western boreal forest of Canada, we examined net annual aboveground biomass change (ΔAGB) of four major forest types between 1958 and 2011. We found that ΔAGB was higher for deciduous broadleaf (DEC) (1.44 Mg ha(-1)  year(-1) , 95% Bayesian confidence interval (CI), 1.22-1.68) and early-successional coniferous forests (ESC) (1.42, CI, 1.30-1.56) than mixed forests (MIX) (0.80, CI, 0.50-1.11) and late-successional coniferous (LSC) forests (0.62, CI, 0.39-0.88). ΔAGB declined with forest age as well as calendar year. After accounting for the effects of forest age, ΔAGB declined by 0.035, 0.021, 0.032 and 0.069 Mg ha(-1)  year(-1) per calendar year in DEC, ESC, MIX and LSC forests, respectively. The ΔAGB declines resulted from increased tree mortality and reduced growth in all forest types except DEC, in which a large biomass loss from mortality was accompanied with a small increase in growth. With every degree of annual temperature increase, ΔAGB decreased by 1.00, 0.20, 0.55 and 1.07 Mg ha(-1)  year(-1) in DEC, ESC, MIX and LSC forests, respectively. With every cm decrease of annual climatic moisture availability, ΔAGB decreased 0.030, 0.045 and 0.17 Mg ha(-1)  year(-1) in ESC, MIX and LSC forests, but changed little in DEC forests. Our results suggest that persistent warming and decreasing water availability have profound negative effects on forest biomass in the boreal forests of western Canada. Furthermore, our results indicate that forest responses to climate change are strongly dependent on forest composition with late-successional coniferous forests being most vulnerable to climate changes in terms of aboveground biomass.

  17. Cognitive performance and age-related changes in the hippocampal proteome

    PubMed Central

    Freeman, Willard M.; VanGuilder, Heather D.; Bennett, Colleen; Sonntag, William E.

    2008-01-01

    Declining cognitive performance is associated with increasing age, even in the absence of overt pathological processes. We and others have reported that declining cognitive performance is associated with age-related changes in brain glucose utilization, long-term potentiation and paired-pulse facilitation, protein expression, neurotransmitter levels, and trophic factors. However, it is unclear whether these changes are causes or symptoms of the underlying alterations in dendritic and synaptic morphology that occur with age. In this study, we examined the hippocampal proteome for age- and cognition-associated changes in behaviorally stratified young and old rats, using 2-DIGE and MS/MS-MS. Comparison of old cognitively intact with old cognitively impaired animals revealed additional changes that would not have been detected otherwise. Interestingly, not all age-related changes in protein expression were associated with cognitive decline, and distinct differences in protein expression were found when comparing old cognitively intact with old cognitively impaired rats. A large number of protein changes with age were related to the glycolysis/gluconeogenesis pathway. In total, the proteomic changes suggest that age-related alterations act synergistically with other perturbations to result in cognitive decline. This study also demonstrates the importance of examining behaviorally-defined animals in proteomic studies, as comparison of young to old animals regardless of behavioral performance would have failed to detect many cognitive impairment-specific protein expression changes evident when behavioral stratification data was used. PMID:19135133

  18. Audience Design and Social Relations in Aging.

    PubMed

    Keller-Cohen, Deborah

    2015-10-01

    This study asks two questions: (1) Do older adults modify their language based on age of the listener (audience design)? (2) Does social contact affect audience design in older adults? Older adults (n = 34; mean age = 82) engaged in an instructions task with two fictive listeners (a child and an adult) to test these questions. Results show that older adults used a greater total number of propositions and rapport-building devices and a lower type-token ratio when giving instructions to the child compared to the adult listener. Adults with more social interactions used more propositions when talking to a child. In addition, satisfaction with interactions was significantly positively related to task-tracking devices and negatively related to rapport-building devices by older adults. These results suggest that audience design and social relations are worth further study in language maintenance in older age.

  19. Oxygen isotope in archaeological bioapatites from India: Implications to climate change and decline of Bronze Age Harappan civilization

    PubMed Central

    Sarkar, Anindya; Mukherjee, Arati Deshpande; Bera, M. K.; Das, B.; Juyal, Navin; Morthekai, P.; Deshpande, R. D.; Shinde, V. S.; Rao, L. S.

    2016-01-01

    The antiquity and decline of the Bronze Age Harappan civilization in the Indus-Ghaggar-Hakra river valleys is an enigma in archaeology. Weakening of the monsoon after ~5 ka BP (and droughts throughout the Asia) is a strong contender for the Harappan collapse, although controversy exists about the synchroneity of climate change and collapse of civilization. One reason for this controversy is lack of a continuous record of cultural levels and palaeomonsoon change in close proximity. We report a high resolution oxygen isotope (δ18O) record of animal teeth-bone phosphates from an archaeological trench itself at Bhirrana, NW India, preserving all cultural levels of this civilization. Bhirrana was part of a high concentration of settlements along the dried up mythical Vedic river valley ‘Saraswati’, an extension of Ghaggar river in the Thar desert. Isotope and archaeological data suggest that the pre-Harappans started inhabiting this area along the mighty Ghaggar-Hakra rivers fed by intensified monsoon from 9 to 7 ka BP. The monsoon monotonically declined after 7 ka yet the settlements continued to survive from early to mature Harappan time. Our study suggests that other cause like change in subsistence strategy by shifting crop patterns rather than climate change was responsible for Harappan collapse. PMID:27222033

  20. Oxygen isotope in archaeological bioapatites from India: Implications to climate change and decline of Bronze Age Harappan civilization

    NASA Astrophysics Data System (ADS)

    Sarkar, Anindya; Mukherjee, Arati Deshpande; Bera, M. K.; Das, B.; Juyal, Navin; Morthekai, P.; Deshpande, R. D.; Shinde, V. S.; Rao, L. S.

    2016-05-01

    The antiquity and decline of the Bronze Age Harappan civilization in the Indus-Ghaggar-Hakra river valleys is an enigma in archaeology. Weakening of the monsoon after ~5 ka BP (and droughts throughout the Asia) is a strong contender for the Harappan collapse, although controversy exists about the synchroneity of climate change and collapse of civilization. One reason for this controversy is lack of a continuous record of cultural levels and palaeomonsoon change in close proximity. We report a high resolution oxygen isotope (δ18O) record of animal teeth-bone phosphates from an archaeological trench itself at Bhirrana, NW India, preserving all cultural levels of this civilization. Bhirrana was part of a high concentration of settlements along the dried up mythical Vedic river valley ‘Saraswati’, an extension of Ghaggar river in the Thar desert. Isotope and archaeological data suggest that the pre-Harappans started inhabiting this area along the mighty Ghaggar-Hakra rivers fed by intensified monsoon from 9 to 7 ka BP. The monsoon monotonically declined after 7 ka yet the settlements continued to survive from early to mature Harappan time. Our study suggests that other cause like change in subsistence strategy by shifting crop patterns rather than climate change was responsible for Harappan collapse.

  1. Oxygen isotope in archaeological bioapatites from India: Implications to climate change and decline of Bronze Age Harappan civilization.

    PubMed

    Sarkar, Anindya; Mukherjee, Arati Deshpande; Bera, M K; Das, B; Juyal, Navin; Morthekai, P; Deshpande, R D; Shinde, V S; Rao, L S

    2016-05-25

    The antiquity and decline of the Bronze Age Harappan civilization in the Indus-Ghaggar-Hakra river valleys is an enigma in archaeology. Weakening of the monsoon after ~5 ka BP (and droughts throughout the Asia) is a strong contender for the Harappan collapse, although controversy exists about the synchroneity of climate change and collapse of civilization. One reason for this controversy is lack of a continuous record of cultural levels and palaeomonsoon change in close proximity. We report a high resolution oxygen isotope (δ(18)O) record of animal teeth-bone phosphates from an archaeological trench itself at Bhirrana, NW India, preserving all cultural levels of this civilization. Bhirrana was part of a high concentration of settlements along the dried up mythical Vedic river valley 'Saraswati', an extension of Ghaggar river in the Thar desert. Isotope and archaeological data suggest that the pre-Harappans started inhabiting this area along the mighty Ghaggar-Hakra rivers fed by intensified monsoon from 9 to 7 ka BP. The monsoon monotonically declined after 7 ka yet the settlements continued to survive from early to mature Harappan time. Our study suggests that other cause like change in subsistence strategy by shifting crop patterns rather than climate change was responsible for Harappan collapse.

  2. Language of the aging brain: Event-related potential studies of comprehension in older adults

    PubMed Central

    Wlotko, Edward W.; Lee, Chia-Lin; Federmeier, Kara D.

    2010-01-01

    Normal aging brings increased richness in knowledge and experience as well as declines in cognitive abilities. Event-related brain potential (ERP) studies of language comprehension corroborate findings showing that the structure and organization of semantic knowledge remains relatively stable with age. Highlighting the advantages of the temporal and functional specificity of ERPs, this survey focuses on age-related changes in higher-level processes required for the successful comprehension of meaning representations built from multiple words. Older adults rely on different neural pathways and cognitive processes during normal, everyday comprehension, including a shift away from the predictive use of sentential context, differential recruitment of neural resources, and reduced engagement of controlled processing. Within age groups, however, there are important individual differences that, for example, differentiate a subset of older adults whose processing patterns more closely resemble that of young adults, providing a window into cognitive skills and abilities that may mediate or moderate age-related declines. PMID:20823949

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

    PubMed

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

    2009-01-01

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

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

    PubMed

    Turlea, C

    2012-01-01

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

  5. Retrospective investigation of captive red wolf reproductive success in relation to age and inbreeding.

    PubMed

    Lockyear, K M; Waddell, W T; Goodrowe, K L; MacDonald, S E

    2009-05-01

    The critically endangered red wolf (Canis rufus) has been subject to a strictly managed captive breeding program for three decades. A retrospective demographic analysis of the captive population was performed based on data from the red wolf studbook. Data analyses revealed a decrease in the effective population size relative to the total population size, and changes in age structure and inbreeding coefficients over time. To varying degrees, the probability of successful breeding and litter sizes declined in association with increasing dam age and sire inbreeding coefficients. Neonate survival also declined with increasing dam age. Recent changes in strategies regarding breed-pair recommendations have resulted in moderate increases in reproductive success.

  6. Age-Related Changes in Processing Speed: Unique Contributions of Cerebellar and Prefrontal Cortex

    PubMed Central

    Eckert, Mark A.; Keren, Noam I.; Roberts, Donna R.; Calhoun, Vince D.; Harris, Kelly C.

    2010-01-01

    Age-related declines in processing speed are hypothesized to underlie the widespread changes in cognition experienced by older adults. We used a structural covariance approach to identify putative neural networks that underlie age-related structural changes associated with processing speed for 42 adults ranging in age from 19 to 79 years. To characterize a potential mechanism by which age-related gray matter changes lead to slower processing speed, we examined the extent to which cerebral small vessel disease influenced the association between age-related gray matter changes and processing speed. A frontal pattern of gray matter and white matter variation that was related to cerebral small vessel disease, as well as a cerebellar pattern of gray matter and white matter variation were uniquely related to age-related declines in processing speed. These results demonstrate that at least two distinct factors affect age-related changes in processing speed, which might be slowed by mitigating cerebral small vessel disease and factors affecting declines in cerebellar morphology. PMID:20300463

  7. Declining Physical Performance Associates with Serum FasL, miR-21, and miR-146a in Aging Sprinters

    PubMed Central

    Alen, Markku; Suominen, Harri; Kovanen, Vuokko; Korhonen, Marko T.

    2017-01-01

    Aging is associated with systemic inflammation and cellular apoptosis accelerating physiological dysfunctions. Whether physically active way of life affects these associations is unclear. This study measured the levels of serum inflammatory and apoptotic molecules, their change over 10 years, and their associations with physical performance in sprint-trained male athletes. HsCRP, cell counts, HGB, FasL, miR-21, and miR-146a were measured cross-sectionally (n = 67, 18–90 yrs) and serum FasL, miR-21, and miR-146a and their aging-related associations with physical performance were assessed over a 10-year follow-up (n = 49, 50–90 yrs). The cross-sectional study showed positive age correlations for neutrophils and negative for lymphocytes, red blood cells, HGB, FasL, and miR-146a. During the 10-year follow-up, FasL decreased (P = 0.017) and miR-21 (P < 0.001) and miR-146a (P = 0.005) levels increased. When combining the molecule levels, aging, and physical performance, FasL associated with countermovement jump and bench press (P < 0.001), miR-21 and miR-146a with knee flexion (P = 0.023; P < 0.001), and bench press (P = 0.004; P < 0.001) and miR-146a with sprint performance (P < 0.001). The studied serum molecules changed in an age-dependent manner and were associated with declining physical performance. They have potential as biomarkers of aging-related processes influencing the development of physiological dysfunctions. Further research is needed focusing on the origins and targets of circulating microRNAs to clarify their function in various tissues with aging. PMID:28127562

  8. Age-dependent decline in density of human nerve and spinal ganglia neurons expressing the α3 isoform of Na/K-ATPase

    PubMed Central

    Romanovsky, Dmitry; Mrak, Robert E.; Dobretsov, Maxim

    2015-01-01

    Ambulatory instability and falls are a major source of morbidity in the elderly. Age-related loss of tendon reflexes is a major contributing factor to this morbidity, and deterioration of the afferent limb of the stretch reflex is a potential contributing factor to such age-dependent loss of tendon reflexes. To evaluate this, we assessed the number and distribution of muscle spindle afferent fibers in human sacral spinal ganglia (S1) and tibial nerve samples obtained at autopsy, using immunohistochemical staining for the α3 isoform of Na+,K+-ATPase (α3NKA), a marker of muscle spindle afferents. Across all age groups, an average of 26±4% of myelinated fibers of tibial nerve and 17±2% of ganglion neuronal profiles were α3NKA-positive (n=8 per group). Subject age explained 85% of the variability in these counts. The relative frequency of α3NKA-labeled fibers/neurons starts to decline during the 5th decade of life, approaching half that of young adult values in 65-year-old subjects. At all ages, α3NKA-positive neurons were among the largest of spinal ganglia neurons. However, as compared to younger subjects, the population of α3NKA-positive neurons from advanced-age subjects showed diminished numbers of large (both moderately and strongly labeled), and medium-sized (strongly labeled) profiles. Considering the critical significance of ion transport by NKA for neuronal activity, our data suggest that functional impairment and, also, most likely atrophy and/or degeneration of muscle spindle afferents, are mechanisms underlying loss of tendon reflexes with age. The larger and more strongly α3NKA-expressing spindle afferents appear to be proportionally more vulnerable. PMID:26386295

  9. Distinct aspects of frontal lobe structure mediate age-related differences in fluid intelligence and multitasking

    PubMed Central

    Kievit, Rogier A.; Davis, Simon W.; Mitchell, Daniel J.; Taylor, Jason R.; Duncan, John; Tyler, Lorraine K.; Brayne, Carol; Bullmore, Ed; Calder, Andrew; Cusack, Rhodri; Dalgleish, Tim; Matthews, Fiona; Marslen-Wilson, William; Rowe, James; Shafto, Meredith; Campbell, Karen; Cheung, Teresa; Geerligs, Linda; McCarrey, Anna; Tsvetanov, Kamen; Williams, Nitin; Bates, Lauren; Emery, Tina; Erzinçlioglu, Sharon; Gadie, Andrew; Gerbase, Sofia; Georgieva, Stanimira; Hanley, Claire; Parkin, Beth; Troy, David; Allen, Jodie; Amery, Gillian; Amunts, Liana; Barcroft, Anne; Castle, Amanda; Dias, Cheryl; Dowrick, Jonathan; Fair, Melissa; Fisher, Hayley; Goulding, Anna; Grewal, Adarsh; Hale, Geoff; Hilton, Andrew; Johnson, Frances; Johnston, Patricia; Kavanagh-Williamson, Thea; Kwasniewska, Magdalena; McMinn, Alison; Norman, Kim; Penrose, Jessica; Roby, Fiona; Rowland, Diane; Sargeant, John; Squire, Maggie; Stevens, Beth; Stoddart, Aldabra; Stone, Cheryl; Thompson, Tracy; Yazlik, Ozlem; Barnes, Dan; Dixon, Marie; Hillman, Jaya; Mitchell, Joanne; Villis, Laura; Henson, Richard N.A.

    2014-01-01

    Ageing is characterized by declines on a variety of cognitive measures. These declines are often attributed to a general, unitary underlying cause, such as a reduction in executive function owing to atrophy of the prefrontal cortex. However, age-related changes are likely multifactorial, and the relationship between neural changes and cognitive measures is not well-understood. Here we address this in a large (N=567), population-based sample drawn from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) data. We relate fluid intelligence and multitasking to multiple brain measures, including grey matter in various prefrontal regions and white matter integrity connecting those regions. We show that multitasking and fluid intelligence are separable cognitive abilities, with differential sensitivities to age, which are mediated by distinct neural subsystems that show different prediction in older versus younger individuals. These results suggest that prefrontal ageing is a manifold process demanding multifaceted models of neurocognitive ageing. PMID:25519467

  10. Distinct aspects of frontal lobe structure mediate age-related differences in fluid intelligence and multitasking.

    PubMed

    Kievit, Rogier A; Davis, Simon W; Mitchell, Daniel J; Taylor, Jason R; Duncan, John; Henson, Richard N A

    2014-12-18

    Ageing is characterized by declines on a variety of cognitive measures. These declines are often attributed to a general, unitary underlying cause, such as a reduction in executive function owing to atrophy of the prefrontal cortex. However, age-related changes are likely multifactorial, and the relationship between neural changes and cognitive measures is not well-understood. Here we address this in a large (N=567), population-based sample drawn from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) data. We relate fluid intelligence and multitasking to multiple brain measures, including grey matter in various prefrontal regions and white matter integrity connecting those regions. We show that multitasking and fluid intelligence are separable cognitive abilities, with differential sensitivities to age, which are mediated by distinct neural subsystems that show different prediction in older versus younger individuals. These results suggest that prefrontal ageing is a manifold process demanding multifaceted models of neurocognitive ageing.

  11. Driving and Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Owsley, Cynthia; McGwin, Gerald, Jr.

    2008-01-01

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

  12. Depression in Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Casten, Robin; Rovner, Barry

    2008-01-01

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

  13. Parallel declines in cognition, motivation, and locomotion in aging mice: association with immune gene upregulation in the medial prefrontal cortex

    PubMed Central

    Bordner, Kelly A.; Kitchen, Robert R.; Carlyle, Becky; George, Elizabeth D.; Mahajan, Milind C.; Mane, Shrikant M.; Taylor, Jane R.; Simen, Arthur A.

    2013-01-01

    Aging in humans is associated with parallel changes in cognition, motivation, and motoric performance. Based on the human aging literature, we hypothesized that this constellation of age-related changes is mediated by the medial prefrontal cortex and that it would be observed in aging mice. Toward this end, we performed detailed assessments of cognition, motivation, and motoric behavior in aging mice. We assessed behavioral and cognitive performance in C57Bl/6 mice aged 6, 18, and 24 months, and followed this with microarray analysis of tissue from the medial prefrontal cortex and analysis of serum cytokine levels. Multivariate modeling of these data suggested that the age-related changes in cognition, motivation, motor performance, and prefrontal immune gene expression were highly correlated. Peripheral cytokine levels were also correlated with these variables, but less strongly than measures of prefrontal immune gene upregulation. To determine whether the observed immune gene expression changes were due to prefrontal microglial cells, we isolated CD11b-positive cells from the prefrontal cortex and subject them to next-generation RNA sequencing. Many of the immune changes present in whole medial prefrontal cortex were enriched in this cell population. These data suggest that, as in humans, cognition, motivation, and motoric performance in the mouse change together with age and are strongly associated with CNS immune gene upregulation. PMID:21453768

  14. [The relationship between the polymorphism of immunity genes and both aging and age-related diseases].

    PubMed

    Ruan, Qing-Wei; Yu, Zhuo-Wei; Bao, Zhi-Jun; Ma, Yong-Xing

    2013-07-01

    Aging is acommon, progressive and irreversible state of multi-cell dysfunction. Immune aging mainly includes the declines of regenerative capacity and lymphoid lineage differentiation potential, the hyporesponsive to infection and vaccination, the hyperresponsive in the context of inflammatory pathology, and the increased risk of autoimmunity. The dysfunction of aged immune system accelerates the occurrence of aging and age-related diseases. The mutation of immunity genes that affect immune responses accelerates or slows aging process and age-related diseases. The frequencies of acquired immunity genes, such as immune protective HLA II DRB1*11 and DRB*16-associated haplotype, are increased in the longevity populations. The increased susceptibility of immune inflammatory response, morbidity and mortality in the elderly is often associated with decreased frequencies of anti-inflammatory factor IL-10 -1082G allele, TNF-β1 haplotype cnd10T/C, cnd25G/G, -988C/C, -800G/A, low proinflammatory fator TNFa level related extended TNF-A genotype -1031C/C, -863C/A, -857C/C, IL-6-174 CC and IFN-γ+874 T allele as well. The innate immunity genes, such as highly expressed anti-inflammatory +896 G KIR4 allele, CCR5Δ32 variant, -765 C Cox-2 allele, -1708 G and 21 C 5-Lox alleles are detected in centenarians. In age-related diseases, a higher CMV-specific IgG antibody level in elderly individuals is associated with a decreased frequency of KIR haplotypes KIR2DS5 and A1B10 and an increased frequency of MBL2 haplotypes LYPB, LYQC and HYPD that result in the absence of MBL2 protein. The increased frequencies of CRP ATG haplotypes and CFH 402 His allele indicate high mortality in the elderly. In the present study, we review the advances in the polymorphism and haplotype of innate and adoptive immunity genes, and their association with both aging and age-related diseases. To strengthen the analysis of extended haplotypes, epigenetic studies of immunity genes and genetic study of

  15. 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.

  16. Auditory white noise reduces age-related fluctuations in balance.

    PubMed

    Ross, J M; Will, O J; McGann, Z; Balasubramaniam, R

    2016-09-06

    Fall prevention technologies have the potential to improve the lives of older adults. Because of the multisensory nature of human balance control, sensory therapies, including some involving tactile and auditory noise, are being explored that might reduce increased balance variability due to typical age-related sensory declines. Auditory white noise has previously been shown to reduce postural sway variability in healthy young adults. In the present experiment, we examined this treatment in young adults and typically aging older adults. We measured postural sway of healthy young adults and adults over the age of 65 years during silence and auditory white noise, with and without vision. Our results show reduced postural sway variability in young and older adults with auditory noise, even in the absence of vision. We show that vision and noise can reduce sway variability for both feedback-based and exploratory balance processes. In addition, we show changes with auditory noise in nonlinear patterns of sway in older adults that reflect what is more typical of young adults, and these changes did not interfere with the typical random walk behavior of sway. Our results suggest that auditory noise might be valuable for therapeutic and rehabilitative purposes in older adults with typical age-related balance variability.

  17. Statistical physics of age related macular degeneration

    NASA Astrophysics Data System (ADS)

    Family, Fereydoon; Mazzitello, K. I.; Arizmendi, C. M.; Grossniklaus, H. E.

    Age-related macular degeneration (AMD) is the leading cause of blindness beyond the age of 50 years. The most common pathogenic mechanism that leads to AMD is choroidal neovascularization (CNV). CNV is produced by accumulation of residual material caused by aging of retinal pigment epithelium cells (RPE). The RPE is a phagocytic system that is essential for renewal of photoreceptors (rods and cones). With time, incompletely degraded membrane material builds up in the form of lipofuscin. Lipofuscin is made of free-radical-damaged protein and fat, which forms not only in AMD, but also Alzheimer disease and Parkinson disease. The study of lipofuscin formation and growth is important, because of their association with cellular aging. We introduce a model of non-equilibrium cluster growth and aggregation that we have developed for studying the formation and growth of lipofuscin in the aging RPE. Our results agree with a linear growth of the number of lipofuscin granules with age. We apply the dynamic scaling approach to our model and find excellent data collapse for the cluster size distribution. An unusual feature of our model is that while small particles are removed from the RPE the larger ones become fixed and grow by aggregation.

  18. The age of astronomy-related organizations

    NASA Astrophysics Data System (ADS)

    Heck, A.

    1999-03-01

    The age of currently active astronomy-related organizations is investigated from comprehensive and up-to-date samples. Results for professional institutions, associations, planetariums, and public observatories are commented, as well as specific distributions for astronomy-related publishers and software producers. Some events had a clear impact on the rate of foundation of astronomy-related organizations, such as World War I and II, the beginning of space exploration and the landing of man on the Moon, but not all of them affected in the same way Western Europe and North America. It is still premature to assess the impact of the end of the Cold War. A category such as the software producers would of course not exist nor prosper without the advent of the computer age and the subsequent electronic networking of the planet. Other aspects are discussed in the paper.

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

    PubMed

    Michels, Stephan; Kurz-Levin, Malaika

    2009-03-01

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

  20. 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.

  1. The effect of artesian-pressure decline on confined aquifer systems and its relation to land subsidence

    USGS Publications Warehouse

    Green, J.H.

    1964-01-01

    Ground water in the Southwestern United States is derived chiefly from unconsolidated to semiconsolidated alluvial deposits. Where these deposits contain confined water, they may be susceptible to compaction and related land- surface subsidence, if artesian pressures are reduced. Compaction of artesian-aquifer systems can be estimated from core tests if the artesian-pressure decline is known. Compaction occurs chiefly in the finer grained deposits ; porosity decrease is greater near the top of the confined aquifer than near the bottom. Because most of the compaction of these aquifer systems is permanent, the storage coefficient during the initial decline of artesian pressure greatly exceeds the storage coefficient during a subsequent pressure decline through the same depth range, after an intervening period of pressure recovery.

  2. Supplementation with Lactobacillus plantarum WCFS1 Prevents Decline of Mucus Barrier in Colon of Accelerated Aging Ercc1−/Δ7 Mice

    PubMed Central

    van Beek, Adriaan A.; Sovran, Bruno; Hugenholtz, Floor; Meijer, Ben; Hoogerland, Joanne A.; Mihailova, Violeta; van der Ploeg, Corine; Belzer, Clara; Boekschoten, Mark V.; Hoeijmakers, Jan H. J.; Vermeij, Wilbert P.; de Vos, Paul; Wells, Jerry M.; Leenen, Pieter J. M.; Nicoletti, Claudio; Hendriks, Rudi W.; Savelkoul, Huub F. J.

    2016-01-01

    Although it is clear that probiotics improve intestinal barrier function, little is known about the effects of probiotics on the aging intestine. We investigated effects of 10-week bacterial supplementation of Lactobacillus plantarum WCFS1, Lactobacillus casei BL23, or Bifidobacterium breve DSM20213 on gut barrier and immunity in 16-week-old accelerated aging Ercc1−/Δ7 mice, which have a median lifespan of ~20 weeks, and their wild-type littermates. The colonic barrier in Ercc1−/Δ7 mice was characterized by a thin (< 10 μm) mucus layer. L. plantarum prevented this decline in mucus integrity in Ercc1−/Δ7 mice, whereas B. breve exacerbated it. Bacterial supplementations affected the expression of immune-related genes, including Toll-like receptor 4. Regulatory T cell frequencies were increased in the mesenteric lymph nodes of L. plantarum- and L. casei-treated Ercc1−/Δ7 mice. L. plantarum- and L. casei-treated Ercc1−/Δ7 mice showed increased specific antibody production in a T cell-dependent immune response in vivo. By contrast, the effects of bacterial supplementation on wild-type control mice were negligible. Thus, supplementation with L. plantarum – but not with L. casei and B. breve – prevented the decline in the mucus barrier in Ercc1−/Δ7 mice. Our data indicate that age is an important factor influencing beneficial or detrimental effects of candidate probiotics. These findings also highlight the need for caution in translating beneficial effects of probiotics observed in young animals or humans to the elderly. PMID:27774093

  3. Prevention of age-related macular degeneration

    PubMed Central

    Koo, Simon Chi Yan; Chan, Clement Wai Nang

    2010-01-01

    Age-related macular degeneration (AMD) is one of the leading causes of blindness in the developed world. Although effective treatment modalities such as anti-VEGF treatment have been developed for neovascular AMD, there is still no effective treatment for geographical atrophy, and therefore the most cost-effective management of AMD is to start with prevention. This review looks at current evidence on preventive measures targeted at AMD. Modalities reviewed include (1) nutritional supplements such as the Age-Related Eye Disease Study (AREDS) formula, lutein and zeaxanthin, omega-3 fatty acid, and berry extracts, (2) lifestyle modifications, including smoking and body-mass-index, and (3) filtering sunlight, i.e. sunglasses and blue-blocking intraocular lenses. In summary, the only proven effective preventive measures are stopping smoking and the AREDS formula. PMID:20862519

  4. [Aged woman's vulnerability related to AIDS].

    PubMed

    Silva, Carla Marins; Lopes, Fernanda Maria do Valle Martins; Vargens, Octavio Muniz da Costa

    2010-09-01

    This article is a systhematic literature review including the period from 1994 to 2009, whose objective was to discuss the aged woman's vulnerability in relation to Acquired Imunodeficiency Syndrome (Aids). The search for scientific texts was accomplished in the following databases: Biblioteca Virtual em Saúde, Scientific Eletronic Library Online (SciELO), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) and Medical Literature Analysis and Retrieval System Online (MEDLINE). The descriptors used were vulnerability, woman and Aids. Eighteen texts were analyzed, including articles in scientific journals, thesis and dissertations. As a conclusion, it was noted that aged women and vulnerability to Aids are directly related, through gender characteristics including submission and that were built historical and socially. We consider as fundamental the development of studies which may generate publications accessible to women, in order to help them see themselves as persons vulnerable to Aids contagion just for being women.

  5. Embryonic diapause in the Australian plague locust relative to parental experience of cumulative photophase decline.

    PubMed

    Deveson, Edward D; Woodman, James D

    2014-11-01

    The Australian plague locust Chortoicetes terminifera (Walker) exhibits facultative embryonic diapause during autumn. To approximate natural photoperiod changes during late summer and autumn, locust nymphs were reared under different total declines in laboratory photophase (-0.5, -0.75, -1.0, -1.25, -1.5, -1.75, -2 h each lowered in 15 min steps) in a 24 h photoperiod to quantify any effect on the subsequent production of diapause eggs. Induction of diapause eggs was significantly affected by accumulated photoperiod decline experienced by the parental generation throughout all development stages from mid-instar nymph to fledgling adult. The incidence of embryonic diapause ranged from nil at -0.5 h to 86.6% diapause at -2 h. Continued declines in photoperiod for post-teneral locusts (transitioned from -1h until fledging to -1.75 h) produced a further increase in the proportion of diapause eggs. The results were unaffected by time spent at any given photoperiod, despite a previously indicated maximal inductive photoperiod of 13.5h being used as the mid-point of all treatments. Implications for the seasonal timing processes of photoperiodism in C. terminifera, which has a high migratory capacity and a latitudinal cline in the timing of diapause egg production across a broad geographic range, are discussed.

  6. Relation between acute and long-term cognitive decline after surgery: Influence of metabolic syndrome☆

    PubMed Central

    Gambús, P.L; Trocóniz, I.F.; Feng, X.; Gimenez-Milá, M.; Mellado, R.; Degos, V.; Vacas, S.; Maze, M.

    2015-01-01

    Introduction The relationship between persistent postoperative cognitive decline and the more common acute variety remains unknown; using data acquired in preclinical studies of postoperative cognitive decline we attempted to characterize this relationship. Methods Low capacity runner (LCR) rats, which have all the features of the metabolic syndrome, were compared postoperatively with high capacity runner (HCR) rats for memory, assessed by trace fear conditioning (TFC) on the 7th postoperative day, and learning and memory (probe trial [PT]) assessed by the Morris water-maze (MWM) at three months postoperatively. Rate of learning (AL) data from the MWM test, were estimated by non-linear mixed effects modeling. The individual rat's TFC result at postoperative day (POD) 7 was correlated with its AL and PT from the MWM data sets at postoperative day POD 90. Results A single exponential decay model best described AL in the MWM with LCR and surgery (LCR–SURG) being the only significant covariates; first order AL rate constant was 0.07 s−1 in LCR–SURG and 0.16 s−1 in the remaining groups (p<0.05). TFC was significantly correlated with both AL (R = 0.74; p < 0.0001) and PT (R = 0.49; p < 0.01). Conclusion Severity of memory decline at 1 week after surgery presaged long-lasting deteriorations in learning and memory. PMID:26164200

  7. Decline in cytochrome c oxidase activity in rat-brain mitochondria with aging. Role of peroxidized cardiolipin and beneficial effect of melatonin.

    PubMed

    Petrosillo, Giuseppe; De Benedictis, Valentina; Ruggiero, Francesca M; Paradies, Giuseppe

    2013-10-01

    Reactive oxygen species (ROS) are considered a key factor in mitochondrial dysfunction associated with brain aging process. Mitochondrial respiration is an important source of ROS and hence a potential contributor to brain functional changes with aging. In this study, we examined the effect of aging on cytochrome c oxidase activity and other bioenergetic processes such as oxygen consumption, membrane potential and ROS production in rat brain mitochondria. We found a significant age-dependent decline in the cytochrome c oxidase activity which was associated with parallel changes in state 3 respiration, membrane potential and with an increase in H2O2 generation. The cytochrome aa3 content was practically unchanged in mitochondria from young and aged animals. The age-dependent decline of cytochrome c oxidase activity could be restored, in situ, to the level of young animals, by exogenously added cardiolipin. In addition, exposure of brain mitochondria to peroxidized cardiolipin resulted in an inactivation of this enzyme complex. It is suggested that oxidation/depletion of cardiolipin could be responsible, at least in part, for the decline of cytochrome c oxidase and mitochondrial dysfunction in brain aging. Melatonin treatment of old animals largely prevented the age-associated alterations of mitochondrial bioenergetic parameters. These results may prove useful in elucidating the molecular mechanisms underlying mitochondrial dysfunction associated with brain aging process, and may have implications in etiopathology of age-associated neurodegenerative disorders and in the development of potential treatment strategies.

  8. Depression in Age-Related Macular Degeneration.

    PubMed

    Casten, Robin; Rovner, Barry

    2008-01-01

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

  9. Age-related changes to the neural correlates of working memory which emerge after midlife.

    PubMed

    Macpherson, Helen N; White, David J; Ellis, Kathryn A; Stough, Con; Camfield, David; Silberstein, Richard; Pipingas, Andrew

    2014-01-01

    Previous research has indicated that the neural processes which underlie working memory change with age. Both age-related increases and decreases to cortical activity have been reported. This study investigated which stages of working memory are most vulnerable to age-related changes after midlife. To do this we examined age-differences in the 13 Hz steady state visually evoked potential (SSVEP) associated with a spatial working memory delayed response task. Participants were 130 healthy adults separated into a midlife (40-60 years) and an older group (61-82 years). Relative to the midlife group, older adults demonstrated greater bilateral frontal activity during encoding and this pattern of activity was related to better working memory performance. In contrast, evidence of age-related under activation was identified over left frontal regions during retrieval. Findings from this study suggest that after midlife, under-activation of frontal regions during retrieval contributes to age-related decline in working memory performance.

  10. Preventing painful age-related bone fractures

    PubMed Central

    Thompson, Michelle L; Chartier, Stephane R; Mitchell, Stefanie A

    2016-01-01

    Age-related bone fractures are usually painful and have highly negative effects on a geriatric patient’s functional status, quality of life, and survival. Currently, there are few analgesic therapies that fully control bone fracture pain in the elderly without significant unwanted side effects. However, another way of controlling age-related fracture pain would be to preemptively administer an osteo-anabolic agent to geriatric patients with high risk of fracture, so as to build new cortical bone and prevent the fracture from occurring. A major question, however, is whether an osteo-anabolic agent can stimulate the proliferation of osteogenic cells and build significant amounts of new cortical bone in light of the decreased number and responsiveness of osteogenic cells in aging bone. To explore this question, geriatric and young mice, 20 and 4 months old, respectively, received either vehicle or a monoclonal antibody that sequesters sclerostin (anti-sclerostin) for 28 days. From days 21 to 28, animals also received sustained administration of the thymidine analog, bromodeoxyuridine (BrdU), which labels the DNA of dividing cells. Animals were then euthanized at day 28 and the femurs were examined for cortical bone formation, bone mineral density, and newly borne BrdU+ cells in the periosteum which is a tissue that is pivotally involved in the formation of new cortical bone. In both the geriatric and young mice, anti-sclerostin induced a significant increase in the thickness of the cortical bone, bone mineral density, and the proliferation of newly borne BrdU+ cells in the periosteum. These results suggest that even in geriatric animals, anti-sclerostin therapy can build new cortical bone and increase the proliferation of osteogenic cells and thus reduce the likelihood of painful age-related bone fractures. PMID:27837171

  11. The "Open-Earedness" Hypothesis and the Development of Age-Related Aesthetic Reactions to Music in Elementary School Children

    ERIC Educational Resources Information Center

    Kopiez, Reinhard; Lehmann, Marco

    2008-01-01

    This study investigates age-related changes in musical preference in elementary school children. The tolerance towards unconventional musical styles has been called "open-earedness" (Hargreaves, 1982a), and it is assumed to decline with increasing age. Musical preferences of 186 students from grade 1 to 4 (age range: 6-10 years) were…

  12. Age-related crosslink in skin collagen

    SciTech Connect

    Yamauchi, M.; Mechanic, G.

    1986-05-01

    A stable crosslinking amino acid was isolated from mature bovine skin collagen and its structure was identified as histidinohydroxylysinonorleucine (HHL) using fast atom bombardment mass spectrometry and /sup 1/H, /sup 13/C-NMR. This newly identified crosslink has a linkage between C-2 histidine and C-6 of lysine in the latter's portion of hydroxylysinonorleucine. Quantitative studies using various aged samples of cow and human skin collagen indicated that this acid-heat stable nonreducible compound was the major age-related crosslink. In case of cow skin collagen, for example, during early embryonic development (3 and 5 month old embryos) the content of HHL stayed less than 0.01 residue/mole of collagen, however from the middle of gestation period (7 month old embryo) through the maturation stage it showed rapid increase with age and reached approximately 0.5 residues/mole of collagen in the 3 year old animal. Small increments (up to 0.65 res/mole of collagen) were observed in the 9 year old cow. The amounts of the crosslink unlike pyridinoline do not decrease with aging. Similar patterns were observed in human skin collagen.

  13. Physics of Age Related Macular Degeneration

    NASA Astrophysics Data System (ADS)

    Family, Fereydoon

    2009-11-01

    Age-related macular degeneration (AMD) is the leading cause of blindness beyond the age of 50 years. The most common pathogenic mechanism that leads to AMD is choroidal neovascularization (CNV). CNV is produced by accumulation of residual material caused by aging of retinal pigment epithelium cells (RPE). The RPE is a phagocytic system that is essential for renewal of photoreceptors (rods and cones). With time, incompletely degraded membrane material builds up in the form of lipofuscin. Lipofuscin is made of free-radical-damaged protein and fat, which forms not only in AMD, but also Alzheimer's disease, and Parkinson's disease. The study of lipofuscin formation and growth is important, because of their association with cellular aging. In this talk I will discuss a model of non-equilibrium cluster growth that we have developed for studying the formation and growth of lipofuscin in AMD [K.I. Mazzitello, C.M. Arizmendi, Fereydoon Family, H. E. Grossniklaus, Physical Review E (2009)]. I will also present an overview of our theoretical and computational efforts in modeling some other aspects of the physics of AMD, including CNV and the breakdown of Bruch's membrane [Ongoing collaboration with Abbas Shirinifard and James A. Glazier, Biocomplexity Institute and Department of Physics, Indiana University, Y. Jiang, Los Alamos, and Hans E. Grossniklaus, Department of Ophthalmology, Emory University].

  14. Mechanisms of age-related bone loss.

    PubMed

    Mosekilde, L

    2001-01-01

    The human skeleton is formed and modelled during childhood and youth through the influence of hormones and daily mechanical usage. Around the age of 20-25 years, the skeleton achieves its maximum mass and strength. Thereafter, and throughout adult life, bone is lost at an almost constant rate due to the dynamic bone turnover process: the remodelling process. During this process, small packets of bone are renewed by teams of bone cells coupled together in time and space. In an adult human skeleton there will be 1-2 million active remodelling sites at any time point. The vast number of turnover units combined with a slightly negative balance at the completion of each process leads to the age-related loss of bone mass mentioned above and, concomitantly, to loss of structural continuity and strength. The magnitude of this loss will be determined by hormonal factors, nutrition and mechanical usage. As a consequence of the remodelling process, the bone tissue of the skeleton will always be younger than the age of the individual. However, as a consequence of the remodelling process, osteopenia and osteoporotic fractures will also occur. In this article, the remodelling-induced changes in the human spine will be used as an example of ageing bone.

  15. Self-Efficacy Moderates the Relation Between Declines in Physical Activity and Perceived Social Support in High School Girls

    PubMed Central

    Saunders, Ruth P.; Motl, Robert W.; Dowda, Marsha; Pate, Russell R.

    2009-01-01

    Objective To test whether self-efficacy for overcoming barriers to physical activity has direct, indirect (i.e., mediated), or moderating relations with naturally occurring change in perceived social support and declines in physical activity during high school. Methods Latent growth modeling was used with measures completed in the 8th, 9th, and 12th grades by a cohort of 195 Black and White girls. Results Self-efficacy was stable and moderated the relation between changes in physical activity and perceived social support. Girls who maintained a perception of strong social support had less of a decline in physical activity if they also had high self-efficacy. However, girls having high self-efficacy had a greater decline in physical activity if they perceived declines in social support. Conclusions Randomized controlled trials of physical activity interventions based on social cognitive theory should consider that the influence of girls’ perceptions of social support on their physical activity may differ according to their efficacy beliefs about barriers to physical activity. PMID:18812410

  16. Hippocampal Volume Is Related to Cognitive Decline and Fornicial Diffusion Measures in Multiple Sclerosis

    PubMed Central

    Koenig, Katherine A.; Sakaie, Ken E.; Lowe, Mark J.; Lin, Jian; Stone, Lael; Bermel, Robert A.; Beall, Erik B.; Rao, Stephen M.; Trapp, Bruce D.; Phillips, Micheal D.

    2014-01-01

    Purpose To assess for associations between hippocampal atrophy and measures of cognitive function, hippocampal magnetization transfer ratio (MTR), and diffusion measures of the fornix, the largest efferent white matter tract from the hippocampus, in patients with multiple sclerosis (MS) and controls. Materials and Methods A total of 53 patients with MS and 20 age- and sex-matched healthy controls participated in cognitive testing and scanning including high spatial-resolution diffusion imaging and a T1-MPRAGE scan. Hippocampal volume and fornicial thickness measures were calculated and compared to mean values of fornicial transverse diffusivity, mean diffusivity, longitudinal diffusivity, fractional anisotropy, mean hippocampal MTR, and scores on measures of episodic memory, processing speed, and working memory tasks. Results In patients with MS, hippocampal volume was significantly related to fornicial diffusion measures (P < 7 × 10−4) and to measures of verbal (P = 0.030) and visual spatial (P = 0.004) episodic memory and a measure of information processing speed (P < 0.037). Discussion These results highlight the role of the hippocampus in cognitive dysfunction in patients with MS and suggest that measures of hippocampal atrophy could be used to capture aspects of disease progression. PMID:24512796

  17. How Cell Number and Cellular Properties of Blood-Banked Red Blood Cells of Different Cell Ages Decline during Storage

    PubMed Central

    Tuo, Wei-Wei; Wang, Di; Liang, Wen-Jing; Huang, Yao-Xiong

    2014-01-01

    Aims Numerous studies have suggested that transfusion of red blood cells (RBCs) stored over a long period of time may induce harmful effects due to storage-induced lesions. However, the underlying mechanisms responsible for this damage have not been identified. Furthermore, it is unclear why and how up to 30% of long-stored RBCs disappear from the circulation within 24 hours after transfusion. The aim of this study was to determine how the cell number of RBCs of different ages changes during storage and how these cells undergo cumulative structural and functional changes with storage time. Methods and Results We used Percoll centrifugation to fractionate the RBCs in blood bank stored RBC units into different aged sub-populations and then measured the number of intact cells in each sub-population as well the cells’ biomechanical and biochemical parameters as functions of the storage period. We found that the RBC units stored for ≤ 14 days could be separated into four fractions: the top or young cell fraction, two middle fractions, and the lower or old fraction. However, after 14 days of storage, the cell number and cellular properties declined rapidly whereby the units stored for 21 days only exhibited the three lower fractions and not the young fraction. The cell number within a unit stored for 21 days decreased by 23% compared to a fresh unit and the cells that were lost had hemolyzed into harmful membrane fragments, microparticles, and free hemoglobin. All remaining cells exhibited cellular properties similar to those of senescent cells. Conclusion In RBC units stored for greater than 14 days, there were fewer intact cells with no healthy cells present, as well as harmful membrane fragments, microparticles, and free hemoglobin. Therefore, transfusion of these stored units would not likely help patients and may induce a series of clinical problems. PMID:25167052

  18. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  20. 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…

  1. Evidence of long term global decline in the Earth's thermospheric densities apparently related to anthropogenic effects

    NASA Astrophysics Data System (ADS)

    Keating, G. M.; Tolson, R. H.; Bradford, M. S.

    2000-05-01

    A study was performed of the long-term orbital decay of five Earth satellites with perigee altitudes averaging near 350km. To decouple long-term trend measurements from the effects of solar variability, measurements were evaluated during the years of solar minimum (1976, 1986 and 1996). Atmospheric densities derived from these essentially global measurements showed substantial evidence of a decline averaging 9.8 ± 2.5% in thermospheric density over 20 years pointing toward a long-term cooling of the upper atmosphere. Increases in greenhouse gases induced by human activity are hypothesized to warm the Earth's surface and lower atmosphere, but strongly cool the upper atmosphere. Assuming that the 10% increase in CO2 over these 20 years caused cooling resulting in the 10% decline in density, a doubling of CO2 could cause the thermospheric densities measured near 350km to decrease by a factor of 3. This decrease may shrink the altitude of a constant density surface by 40km before the end of the 21st century.

  2. Age-related eye disease and gender.

    PubMed

    Zetterberg, Madeleine

    2016-01-01

    Worldwide, the prevalence of moderate to severe visual impairment and blindness is 285 millions, with 65% of visually impaired and 82% of all blind people being 50 years and older. Meta-analyses have shown that two out of three blind people are women, a gender discrepancy that holds true for both developed and developing countries. Cataract accounts for more than half of all blindness globally and gender inequity in access to cataract surgery is the major cause of the higher prevalence of blindness in women. In addition to gender differences in cataract surgical coverage, population-based studies on the prevalence of lens opacities indicate that women have a higher risk of developing cataract. Laboratory as well as epidemiologic studies suggest that estrogen may confer antioxidative protection against cataractogenesis, but the withdrawal effect of estrogen in menopause leads to increased risk of cataract in women. For the other major age-related eye diseases; glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy, data are inconclusive. Due to anatomic factors, angle closure glaucoma is more common in women, whereas the dominating glaucoma type; primary open-angle glaucoma (POAG), is more prevalent in men. Diabetic retinopathy also has a male predominance and vascular/circulatory factors have been implied both in diabetic retinopathy and in POAG. For AMD, data on gender differences are conflicting although some studies indicate increased prevalence of drusen and neovascular AMD in women. To conclude, both biologic and socioeconomic factors must be considered when investigating causes of gender differences in the prevalence of age-related eye disease.

  3. Age associated declines in muscle mass, strength, power, and physical performance: impact on fear of falling and quality of life

    Technology Transfer Automated Retrieval System (TEKTRAN)

    SUMMARY: This 3 year longitudinal study among older adults showed that declining muscle mass, strength, power, and physical performance are independent contributing factors to increased fear of falling, while declines of muscle mass and physical performance contribute to deterioration of quality of ...

  4. Using an eHealth Intervention to Stimulate Health Behavior for the Prevention of Cognitive Decline in Dutch Adults: A Study Protocol for the Brain Aging Monitor

    PubMed Central

    2015-01-01

    Background Internet-delivered intervention programs are an effective way of changing health behavior in an aging population. The same population has an increasing number of people with cognitive decline or cognitive impairments. Modifiable lifestyle risk factors such as physical activity, nutrition, smoking, alcohol consumption, sleep, and stress all influence the probability of developing neurodegenerative diseases such as Alzheimer’s disease. Objective This study aims to answer two questions: (1) Is the use of a self-motivated, complex eHealth intervention effective in changing multiple health behaviors related to cognitive aging in Dutch adults in the work force, especially those aged 40 and over? and (2) Does this health behavior change result in healthier cognitive aging patterns and contribute to preventing or delaying future onset of neurodegenerative syndromes? Methods The Brain Aging Monitor study uses a quasi-experimental 2-year pre-posttest design. The Brain Aging Monitor is an online, self-motivated lifestyle intervention program. Recruitment is done both in medium to large organizations and in the Dutch general population over the age of 40. The main outcome measure is the relationship between lifestyle change and cognitive aging. The program uses different strategies and modalities such as Web content, email, online newsletters, and online games to aid its users in behavior change. To build self-regulatory skills, the Brain Aging Monitor offers its users goal-setting activities, skill-building activities, and self-monitoring. Results Study results are expected to be published in early 2016. Conclusions This study will add to the body of evidence on the effectiveness of eHealth intervention programs with the combined use of state-of-the-art applied games and established behavior change techniques. This will lead to new insights on how to use behavior change techniques and theory in multidimensional lifestyle eHealth research, and how these techniques

  5. Neural correlates of cognitive aging during the perception of facial age: the role of relatively distant and local texture information

    PubMed Central

    Komes, Jessica; Schweinberger, Stefan R.; Wiese, Holger

    2015-01-01

    Previous event-related potential (ERP) research revealed that older relative to younger adults show reduced inversion effects in the N170 (with more negative amplitudes for inverted than upright faces), suggestive of impairments in face perception. However, as these studies used young to middle-aged faces only, this finding may reflect preferential processing of own- relative to other-age faces rather than age-related decline. We conducted an ERP study in which young and older participants categorized young and old upright or inverted faces by age. Stimuli were presented either unfiltered or low-pass filtered at 30, 20, or 10 cycles per image (CPI). Response times revealed larger inversion effects, with slower responses for inverted faces, for young faces in young participants. Older participants did not show a corresponding effect. ERPs yielded a trend toward reduced N170 inversion effects in older relative to younger adults independent of face age. Moreover, larger inversion effects for young relative to old faces were detected, and filtering resulted in smaller N170 amplitudes. The reduced N170 inversion effect in older adults may reflect age-related changes in neural correlates of face perception. A smaller N170 inversion effect for old faces may indicate that facial changes with age hamper early face perception stages. PMID:26441790

  6. Flavonoids and Age Related Disease: Risk, benefits and critical windows

    PubMed Central

    Prasain, JK; Carlson, SH; Wyss, JM

    2010-01-01

    Plant derived products are consumed by a large percentage of the population to prevent, delay and ameliorate disease burden; however, relatively little is known about the efficacy, safety and underlying mechanisms of these traditional health products, especially when taken in concert with pharmaceutical agents. The flavonoids are a group of plant metabolites that are common in the diet and appear to provide some health benefits. While flavonoids are primarily derived from soy, many are found in fruits, nuts and more exotic sources, e.g., kudzu. Perhaps the strongest evidence for the benefits of flavonoids in diseases of aging relates to their effect on components of the metabolic syndrome. Flavonoids from soy, grape seed, kudzu and other sources all lower arterial pressure in hypertensive animal models and in a limited number of tests in humans. They also decrease the plasma concentration of lipids and buffer plasma glucose. The underlying mechanisms appear to include antioxidant actions, central nervous system effects, gut transport alterations, fatty acid sequestration and processing, PPAR activation and increases in insulin sensitivity. In animal models of disease, dietary flavonoids also demonstrate a protective effect against cognitive decline, cancer and metabolic disease. However, research also indicates that the flavonoids can be detrimental in some settings and, therefore, are not universally safe. Thus, as the population ages, it is important to determine the impact of these agents on prevention/attenuation of disease, including optimal exposure (intake, timing/duration) and potential contraindications. PMID:20181448

  7. Age-related changes in conditioned flavor preference in rats.

    PubMed

    Renteria, Adam F; Silbaugh, Bryant C; Tolentino, Jerlyn C; Gilbert, Paul E

    2008-03-17

    Age-related changes have been documented in regions of the brain shown to process reward information. However, few studies have examined the effects of aging on associative memory for reward. The present study tested 7- and 24-month-old rats on a conditioned flavor preference task. Half of the rats in each age group received an unsweetened grape-flavored solution (CS-) on odd-numbered days and a sweetened cherry-flavored solution (CS+) on even-numbered days. The remaining rats in each age group received a sweetened grape-flavored solution (CS+) on odd-numbered days and an unsweetened cherry-flavored solution (CS-) on even-numbered days. During the acquisition phase of testing, the designated solution (CS+ or CS-) was presented to each rat for 15 min daily across six consecutive days. On the preference phase, each rat received unsweetened cherry and unsweetened grape-flavored solutions simultaneously for 15 min daily across four consecutive days. The 7-month-old rats showed a significant preference for the flavor that was previously sweetened during the acquisition phase (CS+) compared to the previously unsweetened solution (CS-) when the two unsweetened solutions were presented simultaneously during the preference phase of testing. In contrast, the 24-month-old rats did not show a preference and consumed roughly equal amounts of the previously sweetened (CS+) and unsweetened (CS-) solutions. Thus, the data suggest that the ability to form flavor-reward associations declines with increasing age, resulting in impaired conditioned flavor preference.

  8. Age-related differences in pulmonary effects of acute and ...

    EPA Pesticide Factsheets

    Ozone (O3) is known to induce adverse pulmonary and systemic health effects. Importantly, children and older persons are considered at-risk populations for O3-induced dysfunction, yet the mechanisms accounting for the age-related pulmonary responses to O3 are uncertain. In this study, we examined age-related susceptibility to O3 using 1 mo (adolescent), 4 mo (young adult), 12 mo (adult) and 24 mo (senescent) male Brown Norway rats exposed to filtered air or O3 (0.25and 1.00 ppm), 6 h/day, two days/week for 1 week (acute) or 13 weeks (subchronic). Ventilatory function, assessed by whole-body plethysmography, and bronchoalveolar lavage fluid (BALF) biomarkers of injury and inflammation were used to examine O3-induced pulmonary effects.Relaxation time declined in all ages following the weekly exposures; however, this effect persisted only in the 24 mo rats following a five days recovery, demonstrating an inability to induce adaptation commonly seen with repeated O3 exposures. PenH was increased in all groups with an augmented response in the 4 mo rats following the subchronic O3 exposures. O3 led to increased breathing frequency and minute volume in the 1 and 4 mo animals. Markers ofpulmonary permeability were increased in all age groups. Elevations in BALF γ-glutamyl transferase activity and lung inflammation following an acute O3 exposure were noted in only the 1 and 4 mo rats, which likely received an increased effective O3 dose. These data demonstrate that ado

  9. Lifestyle-Related Factors Contributing to Decline in Knee Extension Strength among Elderly Women: A Cross-Sectional and Longitudinal Cohort Study

    PubMed Central

    Kojima, Narumi; Kim, Miji; Saito, Kyoko; Yoshida, Hideyo; Yoshida, Yuko; Hirano, Hirohiko; Obuchi, Shuichi; Shimada, Hiroyuki; Suzuki, Takao; Kim, Hunkyung

    2015-01-01

    This cross-sectional and 4-year longitudinal cohort study aimed to clarify how various lifestyle-related variables affect knee extension strength in elderly Japanese women. The participants were community-dwelling women (n = 575) living in the Itabashi Ward of Tokyo, Japan aged 75–85 years at baseline (in 2008) who returned for a follow-up examination 4 years later (in 2012). Maximum isometric knee extension strength in the dominant leg was measured during comprehensive medical check-ups at baseline and follow-up. Interviews with participants included questions on their history of 11 diseases and lifestyle-related factors such as physical activity as well as dietary, smoking, and drinking habits. Cross-sectional and longitudinal analyses yielded inconsistent results regarding the associations between lifestyle-related factors and knee extension strength. While going out more frequently and regular physical exercise positively affected baseline knee extension strength, they did not affect knee extension strength in the longitudinal analysis. The longitudinal analysis revealed that more frequent intake of soy products or green and yellow vegetables at baseline decreased age-related knee extension strength decline. The inconsistent results from the cross-sectional and longitudinal analyses indicate that conducting both types of analyses is crucial for researching this type of subject. The present study demonstrates that the age-related decline in muscle strength is lower in those who frequently eat soy products or green and yellow vegetables. Thus, recommending higher intake of soy products, and green and yellow vegetables for the elderly might help maintain their muscle health. PMID:26177292

  10. Nox-2-Mediated Phenotype Loss of Hippocampal Parvalbumin Interneurons Might Contribute to Postoperative Cognitive Decline in Aging Mice

    PubMed Central

    Qiu, Li-Li; Luo, Dan; Zhang, Hui; Shi, Yun S.; Li, Yan-Jun; Wu, Dan; Chen, Jiang; Ji, Mu-Huo; Yang, Jian-Jun

    2016-01-01

    Postoperative cognitive decline (POCD) is a common complication following anesthesia and surgery, especially in elderly patients; however, the precise mechanisms of POCD remain unclear. Here, we investigated whether nicotinamide adenine dinucleotide phosphate (NADPH) oxidase mediated-abnormalities in parvalbumin (PV) interneurons play an important role in the pathophysiology of POCD. The animal model was established using isoflurane anesthesia and exploratory laparotomy in 16-month-old male C57BL/6 mice. For interventional experiments, mice were chronically treated with the NADPH oxidase inhibitor apocynin (APO). Open field and fear conditioning behavioral tests were performed on day 6 and 7 post-surgery, respectively. In a separate experiment, brain tissue was harvested and subjected to biochemical analysis. Primary hippocampal neurons challenged with lipopolysaccharide (LPS) in vitro were used to investigate the mechanisms underlying the oxidative stress-induced abnormalities in PV interneurons. Our results showed that anesthesia and surgery induced significant hippocampus-dependent memory impairment, which was accompanied by PV interneuron phenotype loss and increased expression of interleukin-1β (IL-1β), markers of oxidative stress and NADPH oxidase 2 (Nox2) in the hippocampus. In addition, LPS exposure increased Nox2 level and decreased the expression of PV and the number of excitatory synapses onto PV interneurons in the primary hippocampal neurons. Notably, treatment with APO reversed these abnormalities. Our study suggests that Nox2-derived reactive oxygen species (ROS) production triggers, at least in part, anesthesia- and surgery-induced hippocampal PV interneuron phenotype loss and consequent cognitive impairment in aging mice. PMID:27790135

  11. The Implications for Everyday Life of Incident Self-Reported Visual Decline among People over Age 65 Living in the Community.

    ERIC Educational Resources Information Center

    Branch, Laurence G.; And Others

    1989-01-01

    Examined consequences of vision loss among older adults. Respondents reporting visual decline were older than those reporting good vision, but not different in any other demographic characteristic, use of formal support and health services, or activities of daily living (ADL) functioning. Controlling for age and sex, vision loss was associated…

  12. Reversal of age-associated decline in immune response to Pnu-imune vaccine by supplementation with the steroid hormone dehydroepiandrosterone.

    PubMed Central

    Garg, M; Bondada, S

    1993-01-01

    Recently, we reported that murine antibody responses to the 23-valent pneumococcal polysaccharide (Pnu-Imune) vaccine declined with age. Here we present data to support the concept that age-associated immune defects are not only due to intrinsic defects in immune cells but are also due to extrinsic factors emanating from the neuroendocrine system. We found that supplementation with dehydroepiandrosterone, a steroid hormone known to be reduced in the aged, corrects the immune deficiency of aged mice and significantly enhanced their splenic immune responses to the Pnu-Imune vaccine. PMID:8478117

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

    PubMed

    Timmons, James A

    2017-01-01

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

  14. Animal models of age related macular degeneration.

    PubMed

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

    2012-08-01

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

  15. Animal models of age related macular degeneration

    PubMed Central

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

    2013-01-01

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

  16. Controls on declining carbon balance with leaf age among 10 woody species in Australian woodland: do leaves have zero daily net carbon balances when they die?

    PubMed

    Reich, Peter B; Falster, Daniel S; Ellsworth, David S; Wright, Ian J; Westoby, Mark; Oleksyn, Jacek; Lee, Tali D

    2009-01-01

    * Here, we evaluated how increased shading and declining net photosynthetic capacity regulate the decline in net carbon balance with increasing leaf age for 10 Australian woodland species. We also asked whether leaves at the age of their mean life-span have carbon balances that are positive, zero or negative. * The net carbon balances of 2307 leaves on 53 branches of the 10 species were estimated. We assessed three-dimensional architecture, canopy openness, photosynthetic light response functions and dark respiration rate across leaf age sequences on all branches. We used YPLANT to estimate light interception and to model carbon balance along the leaf age sequences. * As leaf age increased to the mean life-span, increasing shading and declining photosynthetic capacity each separately reduced daytime carbon gain by approximately 39% on average across species. Together, they reduced daytime carbon gain by 64% on average across species. * At the age of their mean life-span, almost all leaves had positive daytime carbon balances. These per leaf carbon surpluses were of a similar magnitude to the estimated whole-plant respiratory costs per leaf. Thus, the results suggest that a whole-plant economic framework, including respiratory costs, may be useful in assessing controls on leaf longevity.

  17. Stress-Induced Declines in Soybean N2 Fixation Are Related to Nodule Sucrose Synthase Activity.

    PubMed Central

    Gordon, A. J.; Minchin, F. R.; Skot, L.; James, C. L.

    1997-01-01

    Soybean (Glycine max L.) plants were subjected to a number of treatments (drought, 10 mM nitrate, 150 mM NaCl, shoot meristem removal, and removal of approximately 50% of the nodules) to test the hypothesis that metabolic responses contribute to the regulation of N2 fixation. Nitrogenase activity was correlated with the activity of nodule sucrose synthase (SS), but not with that of glutamine oxoglutarate amino transferase. Leghemoglobin levels and other enzyme activities were not significantly or consistently affected by the treatments. SS mRNA was greatly reduced in nodules of drought-, salt-, and nitrate-treated plants; however, this was not correlated with changes in soluble carbohydrate, starch, amino acids, or ureides. Leghemoglobin mRNA was only slightly affected by the treatments. The time course of drought stress showed a decline in the SS transcript level by 1 d, but levels of leghemoglobin, glutamine synthetase, and ascorbate peroxidase mRNA were not markedly affected by 4 d. SS activity at 4 d was reduced by 46%. We propose that N2 fixation in soybean nodules is mediated by both the oxygen-diffusion barrier and the potential to metabolize sucrose via SS. The response to environmental perturbation may involve down-regulation of the nodule SS gene. PMID:12223754

  18. Medical bioremediation of age-related diseases

    PubMed Central

    Mathieu, Jacques M; Schloendorn, John; Rittmann, Bruce E; Alvarez, Pedro JJ

    2009-01-01

    Catabolic insufficiency in humans leads to the gradual accumulation of a number of pathogenic compounds associated with age-related diseases, including atherosclerosis, Alzheimer's disease, and macular degeneration. Removal of these compounds is a widely researched therapeutic option, but the use of antibodies and endogenous human enzymes has failed to produce effective treatments, and may pose risks to cellular homeostasis. Another alternative is "medical bioremediation," the use of microbial enzymes to augment missing catabolic functions. The microbial genetic diversity in most natural environments provides a resource that can be mined for enzymes capable of degrading just about any energy-rich organic compound. This review discusses targets for biodegradation, the identification of candidate microbial enzymes, and enzyme-delivery methods. PMID:19358742

  19. LMN diet, rich in polyphenols and polyunsaturated fatty acids, improves mouse cognitive decline associated with aging and Alzheimer's disease.

    PubMed

    Fernández-Fernández, Laura; Comes, Gemma; Bolea, Irene; Valente, Tony; Ruiz, Jessica; Murtra, Patricia; Ramirez, Bartolomé; Anglés, Neus; Reguant, Jordi; Morelló, José Ramón; Boada, Mercè; Hidalgo, Juan; Escorihuela, Rosa María; Unzeta, Mercedes

    2012-03-17

    We examined whether LMN diet, reported to induce neurogenesis in adult mice, was able to antagonize the age-related behavioural impairment and neuropathology in wild type (WT) mice and Tg2576 mice, a mouse model of Alzheimer's disease (AD). Thirteen-month-old mice (once the amyloid (Aβ) plaques were formed) were fed with the LMN diet for 5 months, and in the last 2 months of the regimen they received a battery of behavioural tests. In general, both aging and (to a higher extent) Tg2576 genotype deteriorated sensorimotor reflexes, exploratory behaviour in the hole board, activity (but not anxiety) in the elevated plus-maze, ambulation in the home cage during the dark phase, and spatial learning in the Morris water maze. LMN diet did not affect the detrimental effects observed in sensorimotor reflexes, but clearly reversed the effects of both aging and Tg2576 genotype. This behavioural amelioration was correlated with a 70% increase in cellular proliferation in subventricular zone (SVZ) of the brain, but did not correlate with a decrease of amyloid plaques. In contrast, administration of LMN diet to 10 months old mice (before the plaques are formed) strongly suggested a putative delay in the formation of plaques, as indicated by a decreasing tendency of soluble and fibrillar Aβ levels in hippocampus which correlated with a decrease in Aβ (1-40, 1-42) plasma content. Herein we describe for the first time that LMN diet rich in polyphenols, dry fruits and cocoa, was able to decrease behavioural deterioration caused by aging and Tg2576 genotype and to delay the Aβ plaque formation. These results corroborate the increasing importance of polyphenols as human dietary supplements in amelioration of the cognitive impairment during aging and neurological disorders such as AD.

  20. Age Metallicity Relation in the LMC

    NASA Astrophysics Data System (ADS)

    Kontizas, E.; Dapergolas, A.; Kontizas, M.; Nordström, B.; Andersen, J.; Prantzos, N.; Kaltcheva, N.

    The age metallicity relation (AMR) is known to be very important for understanding the chemical evolution in a galaxy. LMC, our nearest galaxy offers an ideal target for such studies, considering that with the SMC and our Galaxy are an interacting group, influencing each other's star formation rate and production of metals. An observing program for the determination of AMR from a study of small open LMC clusters using Stroemgren phorometry has been initiated. Three observing runs were granted with the 1.5m Danish Telescope at La Silla. We report on our search within 8 clusters, scattered all over the LMC to cover a wide spatial distribution and metallicity. CMDs using Stroemgren photometry have been produced, in order to find the age of the stellar content. The available isochrones used, although very few are able to give us a good age estimate. The calibration of the y, b, v, magnitudes and colours to metallicity used, is the one by Richter et al. (A&A, 1999), to obtain the adopted metallicities of the clusters. Although our sample is still small, a clear trend is observed in AMR showing a significant increase of metallicity with age. Comparison with previous AMRs from other investigations shows good agreement within the errors. The bursting model of chemical evolution by Pagel and Tautvaisiene (MNRAS, 1999) shows that the burst of star formation (SF) produces a change of slope in their AMRs from 2 Gyr to the present time, the burst assumed to occur from -0.4 dex to 0.0 dex. Although our sample is small the observed trend favours the expected change of the AMRs rather towards the 1 Gyr. Therefore our observations support a bursting model of chemical evolution. More obervations are needed and new theoretical models to strengthen these results. Finally it is found that all young metal rich clusters occupy the central LMC regions whereas the old metal poor ones are found in the LMC periphery giving evidence for a metallicity gradient as well. We would like to

  1. Examining the Relation between Hearing Loss and Successful Aging

    ERIC Educational Resources Information Center

    Hefferly, Michael

    2009-01-01

    A decline in social engagement has a negative impact on numerous elements considered critical for successful aging. Because many social and productive activities require effective communication skills for individuals to remain fully engaged, it was hypothesized that self-perceived hearing problems limit the frequency of engagement in social and…

  2. Mitochondrial ROS regulate oxidative damage and mitophagy but not age-related muscle fiber atrophy

    PubMed Central

    Sakellariou, Giorgos K.; Pearson, Timothy; Lightfoot, Adam P.; Nye, Gareth A.; Wells, Nicola; Giakoumaki, Ifigeneia I.; Vasilaki, Aphrodite; Griffiths, Richard D.; Jackson, Malcolm J.; McArdle, Anne

    2016-01-01

    Age-related loss of skeletal muscle mass and function is a major contributor to morbidity and has a profound effect on the quality of life of older people. The potential role of age-dependent mitochondrial dysfunction and cumulative oxidative stress as the underlying cause of muscle aging remains a controversial topic. Here we show that the pharmacological attenuation of age-related mitochondrial redox changes in muscle with SS31 is associated with some improvements in oxidative damage and mitophagy in muscles of old mice. However, this treatment failed to rescue the age-related muscle fiber atrophy associated with muscle atrophy and weakness. Collectively, these data imply that the muscle mitochondrial redox environment is not a key regulator of muscle fiber atrophy during sarcopenia but may play a key role in the decline of mitochondrial organelle integrity that occurs with muscle aging. PMID:27681159

  3. IQ as moderator of terminal decline in perceptual and motor speed, spatial, and verbal ability: Testing the cognitive reserve hypothesis in a population-based sample followed from age 70 until death.

    PubMed

    Thorvaldsson, Valgeir; Skoog, Ingmar; Johansson, Boo

    2017-03-01

    Terminal decline (TD) refers to acceleration in within-person cognitive decline prior to death. The cognitive reserve hypothesis postulates that individuals with higher IQ are able to better tolerate age-related increase in brain pathologies. On average, they will exhibit a later onset of TD, but once they start to decline, their trajectory is steeper relative to those with lower IQ. We tested these predictions using data from initially nondemented individuals (n = 179) in the H70-study repeatedly measured at ages 70, 75, 79, 81, 85, 88, 90, 92, 95, 97, 99, and 100, or until death, on cognitive tests of perceptual-and-motor-speed and spatial and verbal ability. We quantified IQ using the Raven's Coloured Progressive Matrices (RCPM) test administrated at age 70. We fitted random change point TD models to the data, within a Bayesian framework, conditioned on IQ, age of death, education, and sex. In line with predictions, we found that 1 additional standard deviation on the IQ scale was associated with a delay in onset of TD by 1.87 (95% highest density interval [HDI; 0.20, 4.08]) years on speed, 1.96 (95% HDI [0.15, 3.54]) years on verbal ability, but only 0.88 (95% HDI [-0.93, 3.49]) year on spatial ability. Higher IQ was associated with steeper rate of decline within the TD phase on measures of speed and verbal ability, whereas results on spatial ability were nonconclusive. Our findings provide partial support for the cognitive reserve hypothesis and demonstrate that IQ can be a significant moderator of cognitive change trajectories in old age. (PsycINFO Database Record

  4. Age-related consequences of childhood obesity.

    PubMed

    Kelsey, Megan M; Zaepfel, Alysia; Bjornstad, Petter; Nadeau, Kristen J

    2014-01-01

    The severity and frequency of childhood obesity has increased significantly over the past three to four decades. The health effects of increased body mass index as a child may significantly impact obese youth as they age. However, many of the long-term outcomes of childhood obesity have yet to be studied. This article examines the currently available longitudinal data evaluating the effects of childhood obesity on adult outcomes. Consequences of obesity include an increased risk of developing the metabolic syndrome, cardiovascular disease, type 2 diabetes and its associated retinal and renal complications, nonalcoholic fatty liver disease, obstructive sleep apnea, polycystic ovarian syndrome, infertility, asthma, orthopedic complications, psychiatric disease, and increased rates of cancer, among others. These disorders can start as early as childhood, and such early onset increases the likelihood of early morbidity and mortality. Being obese as a child also increases the likelihood of being obese as an adult, and obesity in adulthood also leads to obesity-related complications. This review outlines the evidence for childhood obesity as a predictor of adult obesity and obesity-related disorders, thereby emphasizing the importance of early intervention to prevent the onset of obesity in childhood.

  5. The Dilemma of Decline.

    ERIC Educational Resources Information Center

    Abramowitz, Susan

    This paper, one of two related documents, examines the impact of declining enrollments on educational expenditures. It highlights population and social changes that have contributed to the decline and discusses the general financing of schools. Finally, the paper discusses strategies state policymakers can use to manage decline, including…

  6. Nut consumption and age-related disease.

    PubMed

    Grosso, G; Estruch, R

    2016-02-01

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

  7. [Fertility decline in Spain].

    PubMed

    Arango, J

    1987-01-01

    The historical processes of secular fertility decline in Spain and Portugal are not well understood. Very few microdemographic studies of small geographic regions or particular social strata have been done. A contribution by David Reher to the First Spanish-Portuguese-Italian Historical Demography Conference on the fertility decline in the interior province of Cuenca, Spain, uses the own-children method to analyze changes in marital fertility in the 19th and 20th centuries. Reher discovered a slight fertility decline of perhaps 15% which occurred between the end of the 18th century and 1860-75. The fertility decline did not resume until after the Spanish Civil War, and then it was a very gradual and continuous process. When instead of the total female population, women aged 35-39 were studied, unequivocal signs of fertility control appeared. Conscious fertility control thus appears to have begun among older women limiting rather than spacing births. Reher's analysis by social groups demonstrates that fertility declined first and more rapidly in the nonagricultural and urban populations and among the higher income groups. The fertility decline in Cuenca was certainly not identical to that in most of Spain, but may have been fairly typical of a large part of the interior. Another contribution to the Historical Demography Conference, by Anna Cabre and Isabel Pujadas, analyzes fertility trends and cyclical fluctuations in 20th century Cataluna, arguing that they must be placed in historical perspective if recent changes are to be understood and plausible projections made. Their work demonstrates the value of selecting a relatively homogeneous geographic unit for analysis. The contribution of Margarita Delgado to the conference analyzed interregional fertility differences in contemporary Spain. The high legitimate fertility of the south of Spain is accentuated by high nuptiality rates. In central Spain, the combination of high legitimate fertility rates and low

  8. Cognitive and neuropsychological underpinnings of relational and conjunctive working memory binding across age.

    PubMed

    van Geldorp, Bonnie; Parra, Mario A; Kessels, Roy P C

    2015-01-01

    The ability to form associations (i.e., binding) is critical for memory formation. Recent studies suggest that aging specifically affects relational binding (associating separate features) but not conjunctive binding (integrating features within an object). Possibly, this dissociation may be driven by the spatial nature of the studies so far. Alternatively, relational binding may simply require more attentional resources. We assessed relational and conjunctive binding in three age groups and we included an interfering task (i.e., an articulatory suppression task). Binding was examined in a working memory (WM) task using non-spatial features: shape and colour. Thirty-one young adults (mean age = 22.35), 30 middle-aged adults (mean age = 54.80) and 30 older adults (mean age = 70.27) performed the task. Results show an effect of type of binding and an effect of age but no interaction between type of binding and age. The interaction between type of binding and interference was significant. These results indicate that aging affects relational binding and conjunctive binding similarly. However, relational binding is more susceptible to interference than conjunctive binding, which suggests that relational binding may require more attentional resources. We suggest that a general decline in WM resources associated with frontal dysfunction underlies age-related deficits in WM binding.

  9. Are declines in physical performance associated with a reduction in skill-related performance during professional soccer match-play?

    PubMed

    Carling, Christopher; Dupont, Gregory

    2011-01-01

    The aim of this study was to determine whether declines in physical performance in a professional soccer team during match-play were associated with reductions in skill-related performance. Computerized tracking of performance in midfield players (n = 11) showed that total distance and distance covered in high-speed running (>14.4 km · h⁻¹) were greater in the first versus second half of games (both P < 0.001) and in the first versus the final 15 min of play (P < 0.05). Analysis of high-speed running across 5-min periods showed that more distance was covered in the first versus the final game period, and in the peak period of activity compared with the following period and game mean for other periods (all P < 0.05). Analysis of skill-related measures revealed no significant decline between halves, across 15-min intervals or in the 5-min period following that of peak high-speed activity compared with the game mean for other 5-min periods. In contrast, frequencies of passing, ball possessions, and duels were greater in the first 5-min than in the final 5-min period (P < 0.05). Neither physical nor skill-related performance was affected across three consecutive games within a period of ≤7 days. The results suggest that the players were generally able to maintain skill-related performance throughout games and when competing in successive matches within a short time.

  10. Decline of tactile acuity in aging: a study of body site, blood flow, and lifetime habits of smoking and physical activity.

    PubMed

    Stevens, Joseph C; Alvarez-Reeves, Marty; Dipietro, Loretta; Mack, Gary W; Green, Barry G

    2003-01-01

    Tactile acuity of 60 older subjects (> or = 65 years) and 19 younger subjects (18-28 years) was assessed by two-point gap thresholds at the upper and lower surfaces of the forefinger, at the upper and lower surfaces of the feet, and at the volar surface of the forearm. The older subjects were assigned to one of four groups of 15 subjects each, depending on reported lifetime habits of physical activity and smoking: (1) active smokers, (2) active nonsmokers, (3) inactive smokers, and (4) inactive nonsmokers. Peripheral blood flow was assessed at the forefinger, foot, and forearm by means of laser-Doppler imaging and skin temperature recordings, under resting conditions and during and after a 5-min exposure to mild cooling (28 degrees C). Consistent with previous studies, tactile acuity thresholds in the foot and finger averaged about 80% higher in the older subjects than in the younger subjects, but only about 22% higher in the forearm. Although the upper surface of the fingertip was more sensitive than the lower surface in both younger and older subjects, the age-related decline in tactile acuity was nearly identical on both sides of the finger and foot. The latter finding refutes the hypothesis that the larger effect of aging in the extremities results from greater physical wear and tear on the contact surfaces of the hands and feet. Self-reported lifetime histories of physical activity and smoking were not significantly associated with measures of cutaneous blood flow or tactile thresholds. Possible reasons for this lack of association are discussed, including the inherent limitations of testing only healthy older subjects, and the concept of "successful aging".

  11. Age-related Changes in the Fracture Resistance of Male Fischer F344 Rat Bone

    PubMed Central

    Uppuganti, Sasidhar; Granke, Mathilde; Makowski, Alexander J.; Does, Mark D.; Nyman, Jeffry S.

    2015-01-01

    In addition to the loss in bone volume that occurs with age, there is a decline in material properties. To test new therapies or diagnostic tools that target such properties as material strength and toughness, a pre-clinical model of aging would be useful in which changes in bone are similar to those that occur with aging in humans. Toward that end, we hypothesized that similar to human bone, the estimated toughness and material strength of cortical bone at the apparent-level decreases with age in the male Fischer F344 rat. In addition, we tested whether the known decline in trabecular architecture in rats translated to an age-related decrease in vertebra (VB) strength and whether non-X-ray techniques could quantify tissue changes at micron and sub-micron length scales. Bones were harvested from 6-, 12-, and 24-month (mo.) old rats (n=12 per age). Despite a loss in trabecular bone with age, VB compressive strength was similar among the age groups. Similarly, whole-bone strength (peak force) in bending was maintained (femur) or increased (radius) with aging. There was though an age-related decrease in post-yield toughness (radius) and bend