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Sample records for assembly age-related increases

  1. Parkinson's disease brain mitochondria have impaired respirasome assembly, age-related increases in distribution of oxidative damage to mtDNA and no differences in heteroplasmic mtDNA mutation abundance

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    Keeney Paula M

    2009-09-01

    Full Text Available Abstract Background Sporadic Parkinson's disease (sPD is a nervous system-wide disease that presents with a bradykinetic movement disorder and is frequently complicated by depression and cognitive impairment. sPD likely has multiple interacting causes that include increased oxidative stress damage to mitochondrial components and reduced mitochondrial bioenergetic capacity. We analyzed mitochondria from postmortem sPD and CTL brains for evidence of oxidative damage to mitochondrial DNA (mtDNA, heteroplasmic mtDNA point mutations and levels of electron transport chain proteins. We sought to determine if sPD brains possess any mtDNA genotype-respiratory phenotype relationships. Results Treatment of sPD brain mtDNA with the mitochondrial base-excision repair enzyme 8-oxyguanosine glycosylase-1 (hOGG1 inhibited, in an age-dependent manner, qPCR amplification of overlapping ~2 kbase products; amplification of CTL brain mtDNA showed moderate sensitivity to hOGG1 not dependent on donor age. hOGG1 mRNA expression was not different between sPD and CTL brains. Heteroplasmy analysis of brain mtDNA using Surveyor nuclease® showed asymmetric distributions and levels of heteroplasmic mutations across mtDNA but no patterns that statistically distinguished sPD from CTL. sPD brain mitochondria displayed reductions of nine respirasome proteins (respiratory complexes I-V. Reduced levels of sPD brain mitochondrial complex II, III and V, but not complex I or IV proteins, correlated closely with rates of NADH-driven electron flow. mtDNA levels and PGC-1α expression did not differ between sPD and CTL brains. Conclusion PD brain mitochondria have reduced mitochondrial respiratory protein levels in complexes I-V, implying a generalized defect in respirasome assembly. These deficiencies do not appear to arise from altered point mutational burden in mtDNA or reduction of nuclear signaling for mitochondrial biogenesis, implying downstream etiologies. The origin of age-related

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

    Science.gov (United States)

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

    2014-10-01

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

  3. Parkinson's disease brain mitochondria have impaired respirasome assembly, age-related increases in distribution of oxidative damage to mtDNA and no differences in heteroplasmic mtDNA mutation abundance

    OpenAIRE

    Keeney Paula M; Dunham Lisa D; Morton Stephanie L; Arthur Charles R; Bennett James P

    2009-01-01

    Abstract Background Sporadic Parkinson's disease (sPD) is a nervous system-wide disease that presents with a bradykinetic movement disorder and is frequently complicated by depression and cognitive impairment. sPD likely has multiple interacting causes that include increased oxidative stress damage to mitochondrial components and reduced mitochondrial bioenergetic capacity. We analyzed mitochondria from postmortem sPD and CTL brains for evidence of oxidative damage to mitochondrial DNA (mtDNA...

  4. Age-related increase in prostacyclin production in the rat aorta.

    Science.gov (United States)

    Panganamala, R V; Hanumaiah, B; Merola, A J

    1981-02-01

    Normal Sprague-Dawley rats convert a substantial percentage of exogenous arachidonic acid to prostacyclin. This conversion can be quantitated by an aqueous sampling technique utilizing thin layer chromatography and liquid scintillation counting. There is a clear age-related increase in this conversion that can be demonstrated in aortas from rats of 3 weeks to 20 weeks of age. PMID:7017783

  5. No evidence of age-related increases in unconscious plagiarism during free recall.

    Science.gov (United States)

    Perfect, Timothy John; Defeldre, Anne-Catherine; Elliman, Rachel; Dehon, Hedwige

    2011-07-01

    In three experiments younger and older participants took part in a group generation task prior to a delayed recall task. In each, participants were required to recall the items that they had generated, avoiding plagiarism errors. All studies showed the same pattern: older adults did not plagiarise their partners any more than younger adults did. However, older adults were more likely than younger adults to intrude with entirely novel items not previously generated by anyone. These findings stand in opposition to the single previous demonstration of age-related increases in plagiarism during recall.

  6. An examination of black/white differences in the rate of age-related mortality increase

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    Andrew Fenelon

    2013-09-01

    Full Text Available BACKGROUND The rate of mortality increase with age among adults is typically used as a measure of the rate of functional decline associated with aging or senescence. While black and white populations differ in the level of mortality, mortality also rises less rapidly with age for blacks than for whites, leading to the well-known black/white mortality "crossover". OBJECTIVE This paper investigates black/white differences in the rate of mortality increase with age for major causes of death in order to examine the factors responsible for the black/white crossover. METHODS The analysis considers two explanations for the crossover: selective survival and age misreporting. Mortality is modeled using a Gompertz model for 11 causes of death from ages 50-84 among blacks and whites by sex. RESULTS Mortality increases more rapidly with age for whites than for blacks for nearly all causes of death considered. The all-cause mortality rate of mortality increase is nearly two percentage points higher for whites. The analysis finds evidence for both selective survival and age misreporting, although age misreporting is a more prominent explanation among women. CONCLUSIONS The black/white mortality crossover reflects large differences in the rate of age-related mortality increase. Instead of reflecting the impact of specific causes of death, this pattern exists across many disparate disease conditions, indicating the need for a broad explanation.

  7. Age-related neural correlates of cognitive task performance under increased postural load.

    NARCIS (Netherlands)

    Impe, A. Van; Bruijn, S.M.; Coxon, J.P.; Wenderoth, N.; Sunaert, S.; Duysens, J.E.J.; Swinnen, S.P.

    2013-01-01

    Behavioral studies suggest that postural control requires increased cognitive control and visuospatial processing with aging. Consequently, performance can decline when concurrently performing a postural and a demanding cognitive task. We aimed to identify the neural substrate underlying this effect

  8. Better stay together: pair bond duration increases individual fitness independent of age-related variation

    OpenAIRE

    Sánchez-Macouzet, Oscar; Rodríguez, Cristina; Drummond, Hugh

    2014-01-01

    Prolonged pair bonds have the potential to improve reproductive performance of socially monogamous animals by increasing pair familiarity and enhancing coordination and cooperation between pair members. However, this has proved very difficult to test robustly because of important confounds such as age and reproductive experience. Here, we address limitations of previous studies and provide a rigorous test of the mate familiarity effect in the socially monogamous blue-footed booby, Sula neboux...

  9. Autism and increased paternal age related changes in global levels of gene expression regulation.

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    Mark D Alter

    Full Text Available A causal role of mutations in multiple general transcription factors in neurodevelopmental disorders including autism suggested that alterations in global levels of gene expression regulation might also relate to disease risk in sporadic cases of autism. This premise can be tested by evaluating for changes in the overall distribution of gene expression levels. For instance, in mice, variability in hippocampal-dependent behaviors was associated with variability in the pattern of the overall distribution of gene expression levels, as assessed by variance in the distribution of gene expression levels in the hippocampus. We hypothesized that a similar change in variance might be found in children with autism. Gene expression microarrays covering greater than 47,000 unique RNA transcripts were done on RNA from peripheral blood lymphocytes (PBL of children with autism (n = 82 and controls (n = 64. Variance in the distribution of gene expression levels from each microarray was compared between groups of children. Also tested was whether a risk factor for autism, increased paternal age, was associated with variance. A decrease in the variance in the distribution of gene expression levels in PBL was associated with the diagnosis of autism and a risk factor for autism, increased paternal age. Traditional approaches to microarray analysis of gene expression suggested a possible mechanism for decreased variance in gene expression. Gene expression pathways involved in transcriptional regulation were down-regulated in the blood of children with autism and children of older fathers. Thus, results from global and gene specific approaches to studying microarray data were complimentary and supported the hypothesis that alterations at the global level of gene expression regulation are related to autism and increased paternal age. Global regulation of transcription, thus, represents a possible point of convergence for multiple etiologies of autism and other

  10. Resveratrol prevents age-related memory and mood dysfunction with increased hippocampal neurogenesis and microvasculature, and reduced glial activation.

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    Kodali, Maheedhar; Parihar, Vipan K; Hattiangady, Bharathi; Mishra, Vikas; Shuai, Bing; Shetty, Ashok K

    2015-01-28

    Greatly waned neurogenesis, diminished microvasculature, astrocyte hypertrophy and activated microglia are among the most conspicuous structural changes in the aged hippocampus. Because these alterations can contribute to age-related memory and mood impairments, strategies efficacious for mitigating these changes may preserve cognitive and mood function in old age. Resveratrol, a phytoalexin found in the skin of red grapes having angiogenic and antiinflammatory properties, appears ideal for easing these age-related changes. Hence, we examined the efficacy of resveratrol for counteracting age-related memory and mood impairments and the associated detrimental changes in the hippocampus. Two groups of male F344 rats in late middle-age having similar learning and memory abilities were chosen and treated with resveratrol or vehicle for four weeks. Analyses at ~25 months of age uncovered improved learning, memory and mood function in resveratrol-treated animals but impairments in vehicle-treated animals. Resveratrol-treated animals also displayed increased net neurogenesis and microvasculature, and diminished astrocyte hypertrophy and microglial activation in the hippocampus. These results provide novel evidence that resveratrol treatment in late middle age is efficacious for improving memory and mood function in old age. Modulation of the hippocampus plasticity and suppression of chronic low-level inflammation appear to underlie the functional benefits mediated by resveratrol.

  11. Better stay together: pair bond duration increases individual fitness independent of age-related variation.

    Science.gov (United States)

    Sánchez-Macouzet, Oscar; Rodríguez, Cristina; Drummond, Hugh

    2014-07-01

    Prolonged pair bonds have the potential to improve reproductive performance of socially monogamous animals by increasing pair familiarity and enhancing coordination and cooperation between pair members. However, this has proved very difficult to test robustly because of important confounds such as age and reproductive experience. Here, we address limitations of previous studies and provide a rigorous test of the mate familiarity effect in the socially monogamous blue-footed booby, Sula nebouxii, a long-lived marine bird with a high divorce rate. Taking advantage of a natural disassociation between age and pair bond duration in this species, and applying a novel analytical approach to a 24 year database, we found that those pairs which have been together for longer establish their clutches five weeks earlier in the season, hatch more of their eggs and produce 35% more fledglings, regardless of age and reproductive experience. Our results demonstrate that pair bond duration increases individual fitness and further suggest that synergistic effects between a male and female's behaviour are likely to be involved in generating a mate familiarity effect. These findings help to explain the age- and experience-independent benefits of remating and their role in life-history evolution. PMID:24827435

  12. Early and exudative age-related macular degeneration is associated with increased plasma levels of soluble TNF receptor II

    DEFF Research Database (Denmark)

    Faber, Carsten; Jehs, Tina; Juel, Helene Baek;

    2015-01-01

    and other proteins implicated in AMD pathogenesis. The purpose of this study was to test whether increased plasma levels of cytokines were present in patients with AMD. METHODS: We conducted a case-control study. Age-related macular degeneration status was assessed using standardized multimodal imaging...... forms of AMD and 74 controls. Significantly increased levels of sTNFRII were observed in patients with early or exudative AMD (p age, sex and smoking history, the level of sTNFRII remained a significant predictor for prevalence of AMD with odds ratios...... at 3.0 in the middle and 3.6 in the highest tertiles. Levels of IL15, IL18 and IFNγ were low and not associated with AMD. CONCLUSIONS: Increased plasma level of sTNFRII is found to be associated with AMD. The data supports the observations of low-grade, systemic inflammatory alterations in patients...

  13. Age-related macular degeneration is associated with increased proportion of CD56(+) T cells in peripheral blood

    DEFF Research Database (Denmark)

    Faber, Carsten; Singh, Amardeep; Krüger Falk, Mads;

    2013-01-01

    PURPOSE: To examine the association between age-related changes in the T-cell compartment and prevalence of age-related macular degeneration (AMD). DESIGN: Case-control study. PARTICIPANTS: A total of 117 AMD cases and 106 controls were included prospectively. METHODS: Fresh-drawn peripheral blood...... samples were processed for flow cytometric analysis of T-cell populations. Plasma samples were analyzed for anti-cytomegalovirus (CMV) immunoglobulin (Ig)G and complement factor H (CFH) Y402H genotype. The diagnosis of AMD was made according to the Clinical Age-Related Maculopathy Staging System. MAIN...

  14. Lifelong Cyclic Mechanical Strain Promotes Large Elastic Artery Stiffening: Increased Pulse Pressure and Old Age-Related Organ Failure.

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    Thorin-Trescases, Nathalie; Thorin, Eric

    2016-05-01

    The arterial wall is under a huge mechanical constraint imposed by the cardiac cycle that is bound to generate damage with time. Each heartbeat indeed imposes a pulsatile pressure that generates a vascular stretch. Lifetime accumulation of pulsatile stretches will eventually induce fatigue of the elastic large arterial walls, such as aortic and carotid artery walls, promoting their stiffening that will gradually perturb the normal blood flow and local pressure within the organs, and lead to organ failure. The augmented pulse pressure induced by arterial stiffening favours left ventricular hypertrophy because of the repeated extra work against stiff high-pressure arteries, and tissue damage as a result of excessive pulsatile pressure transmitted into the microcirculation, especially in low resistance/high-flow organs such as the brain and kidneys. Vascular aging is therefore characterized by the stiffening of large elastic arteries leading to a gradual increase in pulse pressure with age. In this review we focus on the effect of age-related stiffening of large elastic arteries. We report the clinical evidence linking arterial stiffness and organ failure and discuss the molecular pathways that are activated by the increase of mechanical stress in the wall. We also discuss the possible interventions that could limit arterial stiffening with age, such as regular aerobic exercise training, and some pharmacological approaches. PMID:26961664

  15. Age-related decreases in SYN levels associated with increases in MAP-2, apoE, and GFAP levels in the rhesus macaque prefrontal cortex and hippocampus

    OpenAIRE

    Haley, Gwendolen E.; Kohama, Steven G.; Urbanski, Henryk F.; Raber, Jacob

    2010-01-01

    Loss of synaptic integrity in the hippocampus and prefrontal cortex (PFC) may play an integral role in age-related cognitive decline. Previously, we showed age-related increases in the dendritic marker microtubule associated protein 2 (MAP-2) and the synaptic marker synaptophysin (SYN) in mice. Similarly, apolipoprotein E (apoE), involved in lipid transport and metabolism, and glial fibrillary acidic protein (GFAP), a glia specific marker, increase with age in rodents. In this study, we asses...

  16. Environmental enrichment improves age-related immune system impairment: long-term exposure since adulthood increases life span in mice.

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    Arranz, Lorena; De Castro, Nuria M; Baeza, Isabel; Maté, Ianire; Viveros, Maria Paz; De la Fuente, Mónica

    2010-08-01

    Age-related changes in immunity have been shown to highly influence morbidity and mortality. The aim of the present work was to study the effects of environmental enrichment (EE) (8-16 weeks) on several functions and oxidative stress parameters of peritoneal leukocytes, previously described as health and longevity markers, in mice at different ages, namely adult (44 +/- 4 weeks), old (69 +/- 4 weeks), and very old (92 +/- 4 weeks). Mortality rates were monitored in control and enriched animals, and effects on survival of long-term exposure to EE until natural death were determined. The results showed that exposure to EE was efficient in improving the function (i.e., macrophage chemotaxis and phagocytosis, lymphocyte chemotaxis and proliferation, natural killer cell activity, interleukin-2 and tumor necrosis factor-alpha levels) and decreasing the oxidative-inflammatory stress (i.e., lowered oxidized glutathione content, xanthine oxidase activity, expression of Toll-like receptors 2 and 4 on CD4 and CD8 cells, and increased reduced glutathione and glutathione peroxidase and catalase activities) of immune cells. These positive effects of EE were especially remarkable in animals at older ages. Importantly, long-term exposure to EE from adult age and until natural death stands out as a useful strategy to extend longevity. Thus, the present work confirms the importance of maintaining active mental and/or physical activity aiming to improve quality of life in terms of immunity, and demonstrates that this active life must be initiated at early stages of the aging process and preserved until death to improve life span.

  17. Age-related deficits in selective attention during encoding increase demands on episodic reconstruction during context retrieval: An ERP study.

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    James, Taylor; Strunk, Jonathan; Arndt, Jason; Duarte, Audrey

    2016-06-01

    Previous event-related potential (ERP) and neuroimaging evidence suggests that directing attention toward single item-context associations compared to intra-item features at encoding improves context memory performance and reduces demands on strategic retrieval operations in young and older adults. In everyday situations, however, there are multiple event features competing for our attention. It is not currently known how selectively attending to one contextual feature while attempting to ignore another influences context memory performance and the processes that support successful retrieval in the young and old. We investigated this issue in the current ERP study. Young and older participants studied pictures of objects in the presence of two contextual features: a color and a scene, and their attention was directed to the object's relationship with one of those contexts. Participants made context memory decisions for both attended and unattended contexts and rated their confidence in those decisions. Behavioral results showed that while both groups were generally successful in applying selective attention during context encoding, older adults were less confident in their context memory decisions for attended features and showed greater dependence in context memory accuracy for attended and unattended contextual features (i.e., hyper-binding). ERP results were largely consistent between age groups but older adults showed a more pronounced late posterior negativity (LPN) implicated in episodic reconstruction processes. We conclude that age-related suppression deficits during encoding result in reduced selectivity in context memory, thereby increasing subsequent demands on episodic reconstruction processes when sought after details are not readily retrieved. PMID:27094851

  18. Heterogeneous nuclear ribonucleoprotein A3 is the liver nuclear protein binding to age related increase element RNA of the factor IX gene.

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    Toshiyuki Hamada

    Full Text Available BACKGROUND: In the ASE/AIE-mediated genetic mechanism for age-related gene regulation, a recently identified age-related homeostasis mechanism, two genetic elements, ASE (age-related stability element and AIE (age-related increase element as a stem-loop forming RNA, play critical roles in producing specific age-related expression patterns of genes. PRINCIPAL FINDING: We successfully identified heterogeneous nuclear ribonucleoprotein A3 (hnRNP A3 as a major mouse liver nuclear protein binding to the AIE-derived RNAs of human factor IX (hFIX as well as mouse factor IX (mFIX genes. HnRNP A3 bound to the AIE RNA was not phosphorylated at its Ser(359, while hnRNP A3 in the mouse liver nuclear extracts was a mixture of phosphorylated and unphosphorylated Ser(359. HepG2 cells engineered to express recombinant hFIX transduced with adenoviral vectors harboring an effective siRNA against hnRNP A3 resulted in a substantial reduction in hFIX expression only in the cells carrying a hFIX expression vector with AIE, but not in the cells carrying a hFIX expression vector without AIE. The nuclear hnRNP A3 protein level in the mouse liver gradually increased with age, while its mRNA level stayed age-stable. CONCLUSIONS: We identified hnRNP A3 as a major liver nuclear protein binding to FIX-AIE RNA. This protein plays a critical role in age-related gene expression, likely through an as yet unidentified epigenetic mechanism. The present study assigned a novel functional role to hnRNP A3 in age-related regulation of gene expression, opening up a new avenue for studying age-related homeostasis and underlying molecular mechanisms.

  19. Resveratrol Prevents Age-Related Memory and Mood Dysfunction with Increased Hippocampal Neurogenesis and Microvasculature, and Reduced Glial Activation

    OpenAIRE

    Kodali, Maheedhar; Parihar, Vipan K; Hattiangady, Bharathi; Mishra, Vikas; Shuai, Bing; Shetty, Ashok K.

    2015-01-01

    Greatly waned neurogenesis, diminished microvasculature, astrocyte hypertrophy and activated microglia are among the most conspicuous structural changes in the aged hippocampus. Because these alterations can contribute to age-related memory and mood impairments, strategies efficacious for mitigating these changes may preserve cognitive and mood function in old age. Resveratrol, a phytoalexin found in the skin of red grapes having angiogenic and antiinflammatory properties, appears ideal for e...

  20. Age-Related Decrease in Heat Shock 70-kDa Protein 8 in Cerebrospinal Fluid Is Associated with Increased Oxidative Stress.

    Science.gov (United States)

    Loeffler, David A; Klaver, Andrea C; Coffey, Mary P; Aasly, Jan O; LeWitt, Peter A

    2016-01-01

    Age-associated declines in protein homeostasis mechanisms ("proteostasis") are thought to contribute to age-related neurodegenerative disorders. The increased oxidative stress which occurs with aging can activate a key proteostatic process, chaperone-mediated autophagy. This study investigated age-related alteration in cerebrospinal fluid (CSF) concentrations of heat shock 70-kDa protein 8 (HSPA8), a molecular chaperone involved in proteostatic mechanisms including chaperone-mediated autophagy, and its associations with indicators of oxidative stress (8-hydroxy-2'-deoxyguanosine [8-OHdG] and 8-isoprostane) and total anti-oxidant capacity. We examined correlations between age, HSPA8, 8-OHdG, 8-isoprostane, and total antioxidant capacity (TAC) in CSF samples from 34 healthy subjects ranging from 20 to 75 years of age. Age was negatively associated with HSPA8 (ρ = -0.47; p = 0.005). An age-related increase in oxidative stress was indicated by a positive association between age and 8-OHdG (ρ = 0.61; p = 0.0001). HSPA8 was moderately negatively associated with 8-OHdG (ρ = -0.58; p = 0.0004). Age and HSPA8 were weakly associated with 8-isoprostane and TAC (range of ρ values: -0.15 to 0.16). Our findings in this exploratory study suggest that during healthy aging, CSF HSPA8 may decrease, perhaps due in part to an increase in oxidative stress. Our results also suggest that 8-OHdG may be more sensitive than 8-isoprostane for measuring oxidative stress in CSF. Further studies are indicated to determine if our findings can be replicated with a larger cohort, and if the age-related decrease in HSPA8 in CSF is reflected by a similar change in the brain. PMID:27507943

  1. Macrophage-derived IL-18 and increased fibrinogen deposition are age-related inflammatory signatures of vascular remodeling

    OpenAIRE

    Rodriguez-Menocal, Luis; Faridi, Mohd. Hafeez; Martinez, Laisel; Lina A Shehadeh; Juan C. Duque; Wei, Yuntao; Mesa, Annia; Pena, Angela; Gupta, Vineet; Pham, Si M.; Vazquez-Padron, Roberto I.

    2014-01-01

    Aging has been associated with pathological vascular remodeling and increased neointimal hyperplasia. The understanding of how aging exacerbates this process is fundamental to prevent cardiovascular complications in the elderly. This study proposes a mechanism by which aging sustains leukocyte adhesion, vascular inflammation, and increased neointimal thickness after injury. The effect of aging on vascular remodeling was assessed in the rat balloon injury model using microarray analysis, immun...

  2. Sensorimotor and cognitive factors associated with the age-related increase of visual field dependence: a cross-sectional study.

    Science.gov (United States)

    Agathos, Catherine P; Bernardin, Delphine; Huchet, Delphine; Scherlen, Anne-Catherine; Assaiante, Christine; Isableu, Brice

    2015-08-01

    Reliance on the visual frame of reference for spatial orientation (or visual field dependence) has been reported to increase with age. This has implications on old adults' daily living tasks as it affects stability, attention, and adaptation capacities. However, the nature and underlying mechanisms of this increase are not well defined. We investigated sensorimotor and cognitive factors possibly associated with increased visual field dependence in old age, by considering functions that are both known to degrade with age and important for spatial orientation and sensorimotor control: reliance on the (somatosensory-based) egocentric frame of reference, visual fixation stability, and attentional processing of complex visual scenes (useful field of view, UFOV). Twenty young, 18 middle-aged, and 20 old adults completed a visual examination, three tests of visual field dependence (RFT, RDT, and GEFT), a test of egocentric dependence (subjective vertical estimation with the body erect and tilted at 70°), a visual fixation task, and a test of visual attentional processing (UFOV®). Increased visual field dependence with age was associated with reduced egocentric dependence, visual fixation stability, and visual attentional processing. In addition, visual fixation instability and reduced UFOV were correlated. Results of middle-aged adults fell between those of the young and old, revealing the progressive nature of the age effects we evaluated. We discuss results in terms of reference frame selection with respect to ageing as well as visual and non-visual information processing. Inter-individual differences amongst old adults are highlighted and discussed with respect to the functionality of increased visual field dependence.

  3. Glutathione S-Transferase P1 (GSTP1 gene polymorphism increases age-related susceptibility to hepatocellular carcinoma

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    Kuo Wu-Hsien

    2010-03-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC is one of the most frequent malignant neoplasms in the world. Genetic polymorphism has been reported to be a factor increasing the risk of HCC. Phase II enzymes such as glutathione s-transferases (GSTP1, GSTA1 play important roles in protecting cells against damage induced by carcinogens. The aim of this study was to estimate the relationship of the GSTP1 and GSTA1 gene polymorphisms to HCC risk and clinico-pathological status. Methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP was used to measure GSTP1 (A→G and GSTA1 (C→T gene polymorphisms in 386 healthy controls and 177 patients with HCC. Results Neither gene polymorphism was associated with the clinico-pathological status of HCC and serum expression of liver-related clinico-pathological markers. No association between the GSTA1 gene polymorphism and HCC susceptibility was found. However, in the younger group, aged ≤ 57 years, individuals with AG or GG alleles of GSTP1 had a 2.18-fold (95%CI = 1.09-4.36; p = 0.02 and 5.64-fold (95%CI = 1.02-31.18; p = 0.04 risk, respectively, of developing HCC compared to individuals with AA alleles, after adjusting for other confounders. Conclusion AG and GG alleles of GSTP1 gene polymorphisms may be considered as factors increasing the susceptibility to and risk of HCC in Taiwanese aged ≤ 57 years.

  4. That's a good one! Belief in efficacy of mnemonic strategies contributes to age-related increase in associative memory.

    Science.gov (United States)

    Daugherty, Ana M; Ofen, Noa

    2015-08-01

    The development of associative memory during childhood may be influenced by metacognitive factors. Here, one aspect of metamemory function--belief in strategy efficacy-was tested for a role in the effective use of encoding strategies. A sample of 61 children and adults (8-25 years of age) completed an associative recognition memory test and were assessed on belief in the efficacy of encoding strategies. Independent of age, belief ratings identified two factors: "deep" and "shallow" encoding strategies. Although the strategy factor structure was stable across age, adolescents and adults were more likely to prefer using a deep encoding strategy, whereas children were equally likely to prefer a shallow strategy. Belief ratings of deep encoding strategies increased with age and, critically, accounted for better associative recognition. PMID:25854595

  5. Age-related increased prevalence of asthma and nasal polyps in chronic rhinosinusitis and its association with altered IL-6 trans-signaling.

    Science.gov (United States)

    Cho, Seong H; Kim, Dae Woo; Lee, Sun H; Kolliputi, Narasaiah; Hong, Seung J; Suh, Lydia; Norton, James; Hulse, Kathryn E; Seshadri, Sudarshan; Conley, David B; Kern, Robert C; Tan, Bruce K; Peters, Anju; Grammer, Leslie C; Schleimer, Robert P

    2015-11-01

    We report that S100 proteins were reduced in patients with chronic rhinosinusitis (CRS). S100A8/9, which is important in epithelial barrier function, was particularly decreased in elderly patients with CRS. Epithelial expression of S100A8/9 is partly regulated by the IL-6 trans-signaling pathway. The goal of this study was to investigate whether or not age-related reduction of S100A8/9 in CRS is associated with blunting of IL-6 trans-signaling. The levels of IL-6, soluble IL-6 receptor (sIL-6R), soluble gp130 (sgp130), and S100A8/9 from control subjects (n = 10), and patients with CRS without nasal polyps (n = 13) and those with CRS with nasal polyps (CRSwNP) (n = 14), were measured by ELISA. Age-related differences in the level of each protein were investigated. Normal human bronchial epithelial cells were cultured in air-liquid interface and stimulated with IL-6/sIL-6R and tumor necrosis factor (TNF)-α with or without the addition of sgp130, a natural inhibitor of IL-6 trans-signaling. There was a significant age-related decline in S100A8/9 and an increase in sgp130 in nasal tissue samples from patients with CRSwNP, although there was no age-related difference in IL-6/sIL-6R production. Additionally, expression of the S100A8/9 gene and protein was increased significantly by IL-6/sIL-6R plus TNF-α in normal human bronchial epithelial cells. This increase was blocked by sgp130. These results suggest that increased sgp130 in older patients may inhibit IL-6 trans-signaling, impair barrier function, and decrease S1008/9 production in elderly patients with CRSwNP. Restoration of barrier function by targeting sgp130 may be a novel treatment strategy. PMID:26266960

  6. Mitochondrial DNA Variants of Respiratory Complex I that Uniquely Characterize Haplogroup T2 Are Associated with Increased Risk of Age-Related Macular Degeneration

    OpenAIRE

    SanGiovanni, John Paul; Arking, Dan E.; Sudha K. Iyengar; Elashoff, Michael; Clemons, Traci E.; Reed, George F.; Henning, Alice K.; Sivakumaran, Theru A; Xu, Xuming; DeWan, Andrew; Agrón, Elvira; Rochtchina, Elena; Carolyn M Sue; Wang, Jie Jin; Mitchell, Paul

    2009-01-01

    Background Age-related macular degeneration (AMD), a chronic neurodegenerative and neovascular retinal disease, is the leading cause of blindness in elderly people of western European origin. While structural and functional alterations in mitochondria (mt) and their metabolites have been implicated in the pathogenesis of chronic neurodegenerative and vascular diseases, the relationship of inherited variants in the mitochondrial genome and mt haplogroup subtypes with advanced AMD has not been ...

  7. An Anthocyanin-Rich Extract of Acai (Euterpe precatoria Mart.) Increases Stress Resistance and Retards Aging-Related Markers in Caenorhabditis elegans.

    Science.gov (United States)

    Peixoto, Herbenya; Roxo, Mariana; Krstin, Sonja; Röhrig, Teresa; Richling, Elke; Wink, Michael

    2016-02-17

    Acai fruits (Euterpe precatoria) are rich in antioxidant anthocyanins. Acai consumption is believed to have many health benefits; however, relevant detailed scientific investigations are limited. The current study aimed to investigate an anthocyanin-rich extract from E. precatoria fruits (AE) with regard to its antioxidant and antiaging properties using the model organism Caenorhabditis elegans. AE can protect the worms against oxidative stress and can ameliorate accumulation of reactive oxygen species in vivo. The expression of stress-response genes, such as sod-3::GFP, was upregulated while hsp-16::GFP was down-regulated after AE treatment. Studies with DAF-16/FOXO mutants indicated that some of the antioxidant effects are mediated by this transcription factor. AE can modulate the development of age-related markers, such as pharyngeal pumping. Despite the apparent antioxidant activity, no lifespan-prolonging effect was observed. PMID:26809379

  8. An Anthocyanin-Rich Extract of Acai (Euterpe precatoria Mart.) Increases Stress Resistance and Retards Aging-Related Markers in Caenorhabditis elegans.

    Science.gov (United States)

    Peixoto, Herbenya; Roxo, Mariana; Krstin, Sonja; Röhrig, Teresa; Richling, Elke; Wink, Michael

    2016-02-17

    Acai fruits (Euterpe precatoria) are rich in antioxidant anthocyanins. Acai consumption is believed to have many health benefits; however, relevant detailed scientific investigations are limited. The current study aimed to investigate an anthocyanin-rich extract from E. precatoria fruits (AE) with regard to its antioxidant and antiaging properties using the model organism Caenorhabditis elegans. AE can protect the worms against oxidative stress and can ameliorate accumulation of reactive oxygen species in vivo. The expression of stress-response genes, such as sod-3::GFP, was upregulated while hsp-16::GFP was down-regulated after AE treatment. Studies with DAF-16/FOXO mutants indicated that some of the antioxidant effects are mediated by this transcription factor. AE can modulate the development of age-related markers, such as pharyngeal pumping. Despite the apparent antioxidant activity, no lifespan-prolonging effect was observed.

  9. A New Baroreceptor Sensitivity-Restoring Ca-Channel Blocker Diminishes Age-Related Morning Blood Pressure Increase in Hypertensive Patients: Open-Label Monitoring of Azelnidipine Treatment for Hypertension in the Early Morning (At-HOME Study

    Directory of Open Access Journals (Sweden)

    Mitsunori Sugiyama

    2010-01-01

    Full Text Available Background: Morning blood pressure (BP surge, which exhibits an age-related increase, is a risk factor for stroke in elderly hypertensive patients, independently of the 24-h BP level. We studied the effect of the new baroreceptor sensitivity (BRS-restoring Ca-channel blocker (CCB azelnidipine (AZ on this age-related morning BP increase. Methods: We conducted a 16-week prospective study to clarify the effect of morning dosing of AZ on home BPs measured in the morning and in the evening in 2,546 hypertensive patients (mean age, 65.1 years; female, 53.6%. Results: At baseline, ME-Dif (morning systolic BP [SBP]–evening SBP increased with age, independently of ME-Ave (average of the morning and evening SBPs. This age-related increase of ME-Dif was exaggerated by regular alcohol drinking and beta-blocker use. After AZ treatment (14.3 ± 3.6 mg/day, ME-AV and ME-Dif were significantly reduced independently of each other, with reductions of –18.1 ± 15.6 and –2.5 ± 13.2 mmHg, respectively (both p < 0.001. AZ treatment decreased age-related increase in ME-Dif particularly in patients who were regular consumers of alcohol and in beta-blocker users. Conclusions: The new BRS-restoring CCB AZ significantly reduced age-related increase in morning BP and had some potential benefit on cardiovascular protection in hypertension, particularly in elderly patients and/or consumers of alcohol.

  10. Difficulties in demonstrating long term immunity in FeLV vaccinated cats due to increasing age-related resistance to infection

    Directory of Open Access Journals (Sweden)

    Wilson Stephen

    2012-07-01

    Full Text Available Abstract Background Feline leukaemia virus (FeLV is a pathogen causing fatal illness in cats worldwide, and as such there is a high demand for products to protect against disease. The duration of immunity provided by an inactivated FeLV vaccine, Versifel FeLV, when administered to cats of the target age was determined. Kittens received two vaccinations when aged 7 to 9 weeks old, and were subsequently challenged up to 36 months later with the FeLV-A Glasgow isolate. Results In all studies, all of the younger aged control kittens showed persistent FeLV p27 antigenaemia confirming that the challenge virus was severe and efficacious. In contrast, the control cats did not show the required level of persistent antigenaemia, with a maximum of 45% cats affected in the middle duration study and only 10% in the longer study. However, apart from one animal in the short duration study, all of the cats vaccinated with Versifel FeLV were negative for persistent antigenaemia and can be considered treatment successes. Conclusion In conclusion, we have shown that although age-related resistance to infection with a virulent FeLV challenge is evident from as early as 10 months of age, vaccination with Versifel FeLV may aid in the protection of cats from FeLV related disease up to three years after primary vaccination as kittens.

  11. Physical activity opposes the age-related increase in skeletal muscle and plasma endothelin-1 levels and normalizes plasma endothelin-1 levels in individuals with essential hypertension

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Mortensen, Stefan Peter; Hellsten, Ylva

    2013-01-01

    age on endothelin-1 levels in plasma and skeletal muscle and endothelin receptors in skeletal muscle in human subjects. METHODS: In study 1, normotensive (46 ± 1 years, n = 11) and hypertensive (47 ± 1 years, n = 10) subjects were studied before and after 8 weeks of aerobic exercise training. In study...... 2, young (23 ± 1 years, n = 8), older lifelong sedentary (66 ± 2 years, n = 8) and older lifelong endurance-trained (62 ± 2 years, n = 8) subjects were studied in a cross-sectional design. RESULTS: Skeletal muscle and plasma endothelin-1 levels were increased with age and plasma endothelin-1 levels...... were higher in hypertensive than normotensive individuals. Eight weeks of exercise training normalized plasma endothelin-1 levels in the hypertensive subjects and increased the protein expression of the ET(A) receptor in skeletal muscle of normotensive subjects. Similarly, individuals that had...

  12. Age-related skin changes

    Directory of Open Access Journals (Sweden)

    Božanić Snežana

    2012-01-01

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

  13. Folate and age-related disease

    NARCIS (Netherlands)

    Durga, J.

    2004-01-01

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

  14. Age-Related Changes in the Misinformation Effect.

    Science.gov (United States)

    Sutherland, Rachel; Hayne, Harlene

    2001-01-01

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

  15. Age-Related White Matter Changes

    Directory of Open Access Journals (Sweden)

    Yun Yun Xiong

    2011-01-01

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

  16. Age-related oral changes.

    LENUS (Irish Health Repository)

    Mckenna, Gerald

    2010-10-01

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

  17. Immunology of age related macular degeneration

    Institute of Scientific and Technical Information of China (English)

    Kijlstra Aize; Yang Peizeng

    2011-01-01

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

  18. Bucket Brigades to Increase Productivity in a Luxury Assembly Line

    Directory of Open Access Journals (Sweden)

    Filippo De Carlo

    2013-08-01

    Full Text Available One of the most challenging issues in manual assembly lines is to achieve the best balance of workloads. There are many analytic approaches to solve this problem, but they are often neglected, since they are time-consuming and require high level engineering skills. Fashion bags packaging lines must comply with a number of different products with low production volumes, while the organization of the line is often under the mere responsibility of the foreman, who balances workloads in an empirical way. The aim of this work is to evaluate the effectiveness of the arrangement of bucket brigades (BBs for an assembly line of luxury handbags. To do this, it was decided to perform a testing activity in a company producing fashion handbags in order to compare the self-made design with the BBs and with a simple assembly line balancing problem algorithm. The originality of this research lies in the fact that there are no studies in the literature on BBs applied to the packaging of highly variable small batches. The results were excellent, showing the advantages of BBs in terms of flexibility, the reduction of work in the process and the ability to handle small anomalies.

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

    Science.gov (United States)

    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. PMID:20623902

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

    Science.gov (United States)

    2016-08-16

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

  1. A participatory and integrative approach to increase productivity and comfort in assembly

    NARCIS (Netherlands)

    Looze, M. de; Rhijn, G. van; Tuinzaad, B.; Deursen, J. van

    2000-01-01

    Manufacturers of manually assembled products are more and more forced to improve the flow of assembly orders together with a more efficient employment, in order to meet increasing demands on short delivery times, high product variety, good quality and low manufacturing costs. At the same time, the h

  2. Sarcopenia and Age-Related Endocrine Function

    Directory of Open Access Journals (Sweden)

    Kunihiro Sakuma

    2012-01-01

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

  3. Nut consumption and age-related disease.

    Science.gov (United States)

    Grosso, G; Estruch, R

    2016-02-01

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

  4. Pharmacogenetics and Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Stephen G. Schwartz

    2011-01-01

    Full Text Available Pharmacogenetics seeks to explain interpatient variability in response to medications by investigating genotype-phenotype correlations. There is a small but growing body of data regarding the pharmacogenetics of both nonexudative and exudative age-related macular degeneration. Most reported data concern polymorphisms in the complement factor H and age-related maculopathy susceptibility 2 genes. At this time, the data are not consistent and no definite conclusions may be drawn. As clinical trials data continue to accumulate, these relationships may become more apparent.

  5. GENETICS OF HUMAN AGE RELATED DISORDERS.

    Science.gov (United States)

    Srivastava, I; Thukral, N; Hasija, Y

    2015-01-01

    Aging is an inevitable biological phenomenon. The incidence of age related disorders (ARDs) such as cardiovascular diseases, cancer, arthritis, dementia, osteoporosis, diabetes, neurodegenerative diseases increase rapidly with aging. ARDs are becoming a key social and economic trouble for the world's elderly population (above 60 years), which is expected to reach 2 billion by 2050. Advancement in understanding of genetic associations, particularly through genome wide association studies (GWAS), has revealed a substantial contribution of genes to human aging and ARDs. In this review, we have focused on the recent understanding of the extent to which genetic predisposition may influence the aging process. Further analysis of the genetic association studies through pathway analysis several genes associated with multiple ARDs have been highlighted such as apolipoprotein E (APOE), brain-derived neurotrophic factor (BDNF), cadherin 13 (CDH13), CDK5 regulatory subunit associated protein 1 (CDKAL-1), methylenetetrahydrofolate reductase (MTHFR), disrupted in schizophrenia 1 (DISC1), nitric oxide synthase 3 (NOS3), paraoxonase 1 (PON1), indicating that these genes could play a pivotal role in ARD causation. These genes were found to be significantly enriched in Jak-STAT signalling pathway, asthma and allograft rejection. Further, interleukin-6 (IL-6), insulin (INS), vascular endothelial growth factor A (VEGFA), estrogen receptor1 (ESR1), transforming growth factor, beta 1(TGFB1) and calmodulin 1 (CALM1) were found to be highly interconnected in network analysis. We believe that extensive research on the presence of common genetic variants among various ARDs may facilitate scientists to understand the biology behind ARDs causation. PMID:26856084

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    Among primates, humans exhibit the most profound degree of age-related brain volumetric decline in particular regions, such as the hippocampus and the frontal lobe. Recent studies have shown that our closest living relatives, the chimpanzees, experience little to no volumetric decline in gray and...... of 11 major sulci of the chimpanzee brains were also measured. We found that chimpanzees showed increased gyrification with age and a cubic relationship between age and white matter volume. For the association between age and sulcus depth and width, the results were mostly non......-significant with the exception of one negative correlation between age and the fronto-orbital sulcus. In short, results showed that chimpanzees exhibit few age-related changes in global cortical organization, sulcus folding and sulcus width. These findings support previous studies and the theory that the age-related changes...

  7. Depression in Age-Related Macular Degeneration

    Science.gov (United States)

    Casten, Robin; Rovner, Barry

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Jason Steffener

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

  9. Cep70 promotes microtubule assembly in vitro by increasing microtubule elongation

    Institute of Scientific and Technical Information of China (English)

    Xingjuan Shi; Jun Wang; Yunfan Yang; Yuan Ren; Jun Zhou; Dengwen Li

    2012-01-01

    Microtubules are dynamic cytoskeletal polymers present in all eukaryotic cells,In animal cells,they are organized by the centrosome,the major microtubule-organizing center.Many centrosomal proteins act coordinately to modulate microtubule assembly and organization.Our previous work has shown that Cep70,a novel centrosomal protein regulates microtubule assembly and organization in mammalian cells.However,the molecular details remain to be investigated,in this study,we investigated the molecular mechanism of how Cep70 regulates microtubule assembly using purified proteins.Our data showed that Cep70 increased the microtubule length without affecting the microtubule number in the purified system.These results demonstrate that Cep70 could directly regulate microtubule assembly by promoting microtubule elongation instead of microtubule nucleation.

  10. Animal models of age related macular degeneration

    OpenAIRE

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

    2012-01-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the ...

  11. Macular carotenoids and age-related maculopathy

    OpenAIRE

    O'Connell, E; Neelam, K.; Nolan, John; Eong, K. G. A.; BEATTY, S

    2006-01-01

    Lutein (L) and zeaxanthin (Z) are concentrated at the macula, where they are collectively known as macular pigment (MP), and where they are believed to play a major role in protecting retinal tissues against oxidative stress. Whilst the exact pathogenesis of age-related maculopathy (ARM) remains unknown, the disruption of cellular processes by oxidative stress may play an important role. Manipulation of dietary intake of L and Z has been shown to augment MP, thereby raising hopes that dietary...

  12. Oxidation stress role in age-related cataractogenesis

    Directory of Open Access Journals (Sweden)

    Žorić Lepša

    2010-01-01

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

  13. Age-related decrease of meiotic cohesins in human oocytes.

    Directory of Open Access Journals (Sweden)

    Makiko Tsutsumi

    Full Text Available Aneuploidy in fetal chromosomes is one of the causes of pregnancy loss and of congenital birth defects. It is known that the frequency of oocyte aneuploidy increases with the human maternal age. Recent data have highlighted the contribution of cohesin complexes in the correct segregation of meiotic chromosomes. In mammalian oocytes, cohesion is established during the fetal stages and meiosis-specific cohesin subunits are not replenished after birth, raising the possibility that the long meiotic arrest of oocytes facilitates a deterioration of cohesion that leads to age-related increases in aneuploidy. We here examined the cohesin levels in dictyate oocytes from different age groups of humans and mice by immunofluorescence analyses of ovarian sections. The meiosis-specific cohesin subunits, REC8 and SMC1B, were found to be decreased in women aged 40 and over compared with those aged around 20 years (P<0.01. Age-related decreases in meiotic cohesins were also evident in mice. Interestingly, SMC1A, the mitotic counterpart of SMC1B, was substantially detectable in human oocytes, but little expressed in mice. Further, the amount of mitotic cohesins of mice slightly increased with age. These results suggest that, mitotic and meiotic cohesins may operate in a coordinated way to maintain cohesions over a sustained period in humans and that age-related decreases in meiotic cohesin subunits impair sister chromatid cohesion leading to increased segregation errors.

  14. Age-related hair pigment loss.

    Science.gov (United States)

    Tobin, Desmond J

    2015-01-01

    Humans are social animals that communicate disproportionately via potent genetic signals imbued in the skin and hair, including racial, ethnic, health, gender, and age status. For the vast majority of us, age-related hair pigment loss becomes the inescapable signal of our disappearing youth. The hair follicle (HF) pigmentary unit is a wonderful tissue for studying mechanisms generally regulating aging, often before this becomes evident elsewhere in the body. Given that follicular melanocytes (unlike those in the epidermis) are regulated by the hair growth cycle, this cycle is likely to impact the process of aging in the HF pigmentary unit. The formal identification of melanocyte stem cells in the mouse skin has spurred a flurry of reports on the potential involvement of melanocyte stem cell depletion in hair graying (i.e., canities). Caution is recommended, however, against simple extrapolation of murine data to humans. Regardless, hair graying in both species is likely to involve an age-related imbalance in the tissue's oxidative stress handling that will impact not only melanogenesis but also melanocyte stem cell and melanocyte homeostasis and survival. There is some emerging evidence that the HF pigmentary unit may have regenerative potential, even after it has begun to produce white hair fibers. It may therefore be feasible to develop strategies to modulate some aging-associated changes to maintain melanin production for longer. PMID:26370651

  15. Risk factors for age-related maculopathy.

    LENUS (Irish Health Repository)

    Connell, Paul P

    2012-02-01

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

  16. Psychophysical function in age-related maculopathy.

    LENUS (Irish Health Repository)

    Neelam, Kumari

    2012-02-01

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

  17. Age-related degradation of Westinghouse 480-volt circuit breakers

    International Nuclear Information System (INIS)

    An aging assessment of Westinghouse DS-series low-voltage air circuit breakers was performed as part of the Nuclear Plant Aging Research (NPAR) program. The objectives of this study are to characterize age-related degradation within the breaker assembly and to identify maintenance practices to mitigate their effect. Since this study has been promulgated by the failures of the reactor trip breakers at the McGuire Nuclear Station in July 1987, results relating to the welds in the breaker pole lever welds are also discussed. The design and operation of DS-206 and DS-416 breakers were reviewed. Failure data from various national data bases were analyzed to identify the predominant failure modes, causes, and mechanisms. Additional operating experiences from one nuclear station and two industrial breaker-service companies were obtained to develop aging trends of various subcomponents. The responses of the utilities to the NRC Bulletin 88-01, which discusses the center pole lever welds, were analyzed to assess the final resolution of failures of welds in the reactor trips. Maintenance recommendations, made by the manufacturer to mitigate age-related degradation were reviewed, and recommendations for improving the monitoring of age-related degradation are discussed. As described in Volume 2 of this NUREG, the results from a test program to assess degradation in breaker parts through mechanical cycling are also included. The testing has characterized the cracking of center-pole lever welds, identified monitoring techniques to determine aging in breakers, and provided information to augment existing maintenance programs. Recommendations to improve breaker reliability using effective maintenance, testing, and inspection programs are suggested. 13 refs., 21 figs., 8 tabs

  18. Inflammation in age-related macular degeneration.

    Science.gov (United States)

    Ozaki, Ema; Campbell, Matthew; Kiang, Anna-Sophia; Humphries, Marian; Doyle, Sarah L; Humphries, Peter

    2014-01-01

    Age-related macular degeneration (AMD) is the leading cause of legal blindness in elderly individuals in the developed world, affecting 30-50 million people worldwide. AMD primarily affects the macular region of the retina that is responsible for the majority of central, color and daytime vision. The presence of drusen, extracellular protein aggregates that accumulate under the retinal pigment epithelium (RPE), is a major pathological hallmark in the early stages of the disease. The end stage 'dry' and 'wet' forms of the disease culminate in vision loss and are characterized by focal degeneration of the RPE and cone photoreceptors, and choroidal neovascularization (CNV), respectively. Being a multifactorial and genetically heterogeneous disease, the pathophysiology of AMD remains unclear, yet, there is ample evidence supporting immunological and inflammatory processes. Here, we review the recent literature implicating some of these immune processes in human AMD and in animal models. PMID:24664703

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

    Science.gov (United States)

    Iwamoto, Toshihiko; Hanyu, Haruo; Umahara, Takahiko

    2013-10-01

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

  20. Macular carotenoids and age-related maculopathy.

    Science.gov (United States)

    O'Connell, Eamonn; Neelam, Kumari; Nolan, John; Au Eong, Kah-Guan; Beatty, Stephan

    2006-11-01

    Lutein (L) and zeaxanthin (Z) are concentrated at the macula, where they are collectively known as macular pigment (MP), and where they are believed to play a major role in protecting retinal tissues against oxidative stress. Whilst the exact pathogenesis of age-related maculopathy (ARM) remains unknown, the disruption of cellular processes by oxidative stress may play an important role. Manipulation of dietary intake of L and Z has been shown to augment MP, thereby raising hopes that dietary supplementation with these carotenoids might prevent, delay, or modify the course of ARM. This article discusses the scientific rationale supporting the hypothesis that L and Z are protective against ARM, and presents the recent evidence germane to this theory. PMID:17160199

  1. The suprachiasmatic nucleus: age-related decline in biological rhythms.

    Science.gov (United States)

    Nakamura, Takahiro J; Takasu, Nana N; Nakamura, Wataru

    2016-09-01

    Aging is associated with changes in sleep duration and quality, as well as increased rates of pathologic/disordered sleep. While several factors contribute to these changes, emerging research suggests that age-related changes in the mammalian central circadian clock within the suprachiasmatic nucleus (SCN) may be a key factor. Prior work from our group suggests that circadian output from the SCN declines because of aging. Furthermore, we have previously observed age-related infertility in female mice, caused by a mismatch between environmental light-dark cycles and the intrinsic, internal biological clocks. In this review, we address regulatory mechanisms underlying circadian rhythms in mammals and summarize recent literature describing the effects of aging on the circadian system. PMID:26915078

  2. Age-Related Changes in Trabecular and Cortical Bone Microstructure

    Directory of Open Access Journals (Sweden)

    Huayue Chen

    2013-01-01

    Full Text Available The elderly population has substantially increased worldwide. Aging is a complex process, and the effects of aging are myriad and insidious, leading to progressive deterioration of various organs, including the skeleton. Age-related bone loss and resultant osteoporosis in the elderly population increase the risk for fractures and morbidity. Osteoporosis is one of the most common conditions associated with aging, and age is an independent risk factor for osteoporotic fractures. With the development of noninvasive imaging techniques such as computed tomography (CT, micro-CT, and high resolution peripheral quantitative CT (HR-pQCT, imaging of the bone architecture provides important information about age-related changes in bone microstructure and estimates of bone strength. In the past two decades, studies of human specimens using imaging techniques have revealed decreased bone strength in older adults compared with younger adults. The present paper addresses recently studied age-related changes in trabecular and cortical bone microstructure based primarily on HR-pQCT and micro-CT. We specifically focus on the three-dimensional microstructure of the vertebrae, femoral neck, and distal radius, which are common osteoporotic fracture sites.

  3. Adverse environmental conditions influence age-related innate immune responsiveness

    Directory of Open Access Journals (Sweden)

    Amankwa Joseph

    2009-05-01

    Full Text Available Abstract Background- The innate immune system plays an important role in the recognition and induction of protective responses against infectious pathogens, whilst there is increasing evidence for a role in mediating chronic inflammatory diseases at older age. Despite indications that environmental conditions can influence the senescence process of the adaptive immune system, it is not known whether the same holds true for the innate immune system. Therefore we studied whether age-related innate immune responses are similar or differ between populations living under very diverse environmental conditions. Methods- We compared cross-sectional age-related changes in ex vivo innate cytokine responses in a population living under affluent conditions in the Netherlands (age 20–68 years old, n = 304 and a population living under adverse environmental conditions in Ghana (age 23–95 years old, n = 562. Results- We found a significant decrease in LPS-induced Interleukin (IL-10 and Tumor Necrosis Factor (TNF production with age in the Dutch population. In Ghana a similar age-related decline in IL-10 responses to LPS, as well as to zymosan, or LPS plus zymosan, was observed. TNF production, however, did not show an age-associated decline, but increased significantly with age in response to co-stimulation with LPS and zymosan. Conclusion- We conclude that the decline in innate cytokine responses is an intrinsic ageing phenomenon, while pathogen exposure and/or selective survival drive pro-inflammatory responses under adverse living conditions.

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

    Directory of Open Access Journals (Sweden)

    Tohru Tanigawa

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

  5. Dietary approaches that delay age-related diseases.

    Science.gov (United States)

    Everitt, Arthur V; Hilmer, Sarah N; Brand-Miller, Jennie C; Jamieson, Hamish A; Truswell, A Stewart; Sharma, Anita P; Mason, Rebecca S; Morris, Brian J; Le Couteur, David G

    2006-01-01

    Reducing food intake in lower animals such as the rat decreases body weight, retards many aging processes, delays the onset of most diseases of old age, and prolongs life. A number of clinical trials of food restriction in healthy adult human subjects running over 2-15 years show significant reductions in body weight, blood cholesterol, blood glucose, and blood pressure, which are risk factors for the development of cardiovascular disease and diabetes. Lifestyle interventions that lower energy balance by reducing body weight such as physical exercise can also delay the development of diabetes and cardiovascular disease. In general, clinical trials are suggesting that diets high in calories or fat along with overweight are associated with increased risk for cardiovascular disease, type 2 diabetes, some cancers, and dementia. There is a growing literature indicating that specific dietary constituents are able to influence the development of age-related diseases, including certain fats (trans fatty acids, saturated, and polyunsaturated fats) and cholesterol for cardiovascular disease, glycemic index and fiber for diabetes, fruits and vegetables for cardiovascular disease, and calcium and vitamin D for osteoporosis and bone fracture. In addition, there are dietary compounds from different functional foods, herbs, and neutraceuticals such as ginseng, nuts, grains, and polyphenols that may affect the development of age-related diseases. Long-term prospective clinical trials will be needed to confirm these diet-disease relationships. On the basis of current research, the best diet to delay age-related disease onset is one low in calories and saturated fat and high in wholegrain cereals, legumes, fruits and vegetables, and which maintains a lean body weight. Such a diet should become a key component of healthy aging, delaying age-related diseases and perhaps intervening in the aging process itself. Furthermore, there are studies suggesting that nutrition in childhood and

  6. Aging, frailty and age-related diseases.

    Science.gov (United States)

    Fulop, T; Larbi, A; Witkowski, J M; McElhaney, J; Loeb, M; Mitnitski, A; Pawelec, G

    2010-10-01

    The concept of frailty as a medically distinct syndrome has evolved based on the clinical experience of geriatricians and is clinically well recognizable. Frailty is a nonspecific state of vulnerability, which reflects multisystem physiological change. These changes underlying frailty do not always achieve disease status, so some people, usually very elderly, are frail without a specific life threatening illness. Current thinking is that not only physical but also psychological, cognitive and social factors contribute to this syndrome and need to be taken into account in its definition and treatment. Together, these signs and symptoms seem to reflect a reduced functional reserve and consequent decrease in adaptation (resilience) to any sort of stressor and perhaps even in the absence of extrinsic stressors. The overall consequence is that frail elderly are at higher risk for accelerated physical and cognitive decline, disability and death. All these characteristics associated with frailty can easily be applied to the definition and characterization of the aging process per se and there is little consensus in the literature concerning the physiological/biological pathways associated with or determining frailty. It is probably true to say that a consensus view would implicate heightened chronic systemic inflammation as a major contributor to frailty. This review will focus on the relationship between aging, frailty and age-related diseases, and will highlight possible interventions to reduce the occurrence and effects of frailty in elderly people. PMID:20559726

  7. Age Related Change in Thyroid Function

    Directory of Open Access Journals (Sweden)

    Shakila Rahman, Nasim Jahan, Nayma Sultana

    2012-12-01

    Full Text Available AbstractBackground: Thyroid hormones play a vital role in metabolism, sensitivity of tissues to other hormones and also in oxygen consumption of almost all cells of the body. However, mild to moderate decrease in function of thyroid gland may occur with advancing age even in apparently healthy elderly subjects.Objectives: To observe age related change in thyroid function status in apparently healthy elderly subjects in Bangladesh.Methods: This cross sectional study was carried out in the Department of Physiology, Sir Salimullah Medical College, Dhaka between 1st January 2011 and 31st December 2011. Sixty apparently healthy elderly subjects of both sexes aged 50 to 75 years were taken as study group. They were collected from Probin Nibash Hitoishi Shangha, Agargaon, Dhaka. In addition, 30 apparently healthy young adult subjects aged 20-40 years were included as control. For assessment of thyroid function, serum free thyroxine (FT4, free triiodothyronine (FT3 and thyroid stimulating hormone (TSH levels were estimated by ELISA method. Statistical analysis was done by one way ANOVA, Bonferroni test and Pearson’s Correlation Coefficient test as applicable.Results: In this study, mean serum free thyroxine (FT4 and free triiodothyronine (FT3 levels were significantly (p<0.001 lower and serum thyroid stimulating hormone (TSH level was significantly (p<0.001 higher in apparently healthy elderly subjects in comparison to those of the healthy young subjects. Again, serum FT4 and FT3 levels were negatively correlated whereas serum TSH level was positively correlated with age of the subjects.Conclusion: The present study revealed a progressive decrease in thyroid function with advancement of age.

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

    Science.gov (United States)

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

    2016-03-01

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

  9. Age-Related Loss of Muscle Mass and Strength

    Directory of Open Access Journals (Sweden)

    Geoffrey Goldspink

    2012-01-01

    Full Text Available Age-related muscle wasting and increased frailty are major socioeconomic as well as medical problems. In the quest to extend quality of life it is important to increase the strength of elderly people sufficiently so they can carry out everyday tasks and to prevent them falling and breaking bones that are brittle due to osteoporosis. Muscles generate the mechanical strain that contributes to the maintenance of other musculoskeletal tissues, and a vicious circle is established as muscle loss results in bone loss and weakening of tendons. Molecular and proteomic approaches now provide strategies for preventing age-related muscle wasting. Here, attention is paid to the role of the GH/IGF-1 axis and the special role of the IGFI-Ec (mechano growth factor/MGF which is derived from the IGF-I gene by alternative splicing. During aging MGF levels decline but when administered MGF activates the muscle satellite (stem cells that “kick start” local muscle repair and induces hypertrophy.

  10. Age-related differences in moral identity across adulthood.

    Science.gov (United States)

    Krettenauer, Tobias; Murua, Lourdes Andrea; Jia, Fanli

    2016-06-01

    In this study, age-related differences in adults' moral identity were investigated. Moral identity was conceptualized a context-dependent self-structure that becomes differentiated and (re)integrated in the course of development and that involves a broad range of value-orientations. Based on a cross-sectional sample of 252 participants aged 14 to 65 years (148 women, M = 33.5 years, SD = 16.9) and a modification of the Good Self-Assessment, it was demonstrated that mean-level of moral identity (averaged across the contexts of family, school/work, and community) significantly increased in the adult years, whereas cross-context differentiation showed a nonlinear trend peaking at the age of 25 years. Value-orientations that define individuals' moral identity shifted so that self-direction and rule-conformity became more important with age. Age-related differences in moral identity were associated with, but not fully attributable to changes in personality traits. Overall, findings suggest that moral identity development is a lifelong process that starts in adolescence but expands well into middle age. (PsycINFO Database Record PMID:27124654

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

    Directory of Open Access Journals (Sweden)

    Zhenyang Zhao

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

  12. Age-related differences in electroencephalogram connectivity and network topology.

    Science.gov (United States)

    Knyazev, Gennady G; Volf, Nina V; Belousova, Ludmila V

    2015-05-01

    To better understand age-related differences in brain function and behavior, connectivity between brain regions was estimated from electroencephalogram source time series in eyes closed versus eyes open resting condition. In beta band, decrease of connectivity upon eyes opening was more pronounced in younger than in older participants. The extent of this decrease was associated with reaction time in attention tasks, and this relationship was fully mediated by participants' age, implying that physiological processes, which lead to age-related slowing, include changes in beta reactivity. Graph-theoretical analysis showed a decrease of modularity and clustering in beta and gamma band networks in older adults, implying that age makes brain networks more random. The overall number of nodes identified as hubs in posterior cortical regions decreased in older participants. At the same time, increase of connectedness of anterior nodes, probably reflecting compensatory activation of the anterior attentional system, was observed in beta-band network of older adults. These findings show that normal aging mostly affects interactions in beta band, which are probably involved in attentional processes. PMID:25766772

  13. Auditory white noise reduces age-related fluctuations in balance.

    Science.gov (United States)

    Ross, J M; Will, O J; McGann, Z; Balasubramaniam, R

    2016-09-01

    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. PMID:27495013

  14. Age-related aneuploidy through cohesion exhaustion

    OpenAIRE

    Jessberger, Rolf

    2012-01-01

    Pregnancy in older women is problematic, as oocytes are particularly prone to chromosome missegregation, and aneuploidy increases with age. Sister chromatid cohesion is weakened or lost with age, having a major impact in age-dependent aneuploidy, as discussed here.

  15. Age-related consequences of childhood obesity.

    Science.gov (United States)

    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. PMID:24434909

  16. Age-related differences in neurotoxicity produced by organophosphorus and N-methyl carbamate pesticides

    Science.gov (United States)

    Potential pesticide effects in infants and toddlers have received much attention in the scientific literature and the public media, including the concern for increased response to acute or shortterm exposures. Age-related differences in the acute neurotoxicity of acetylcholinest...

  17. PTEN, Longevity and Age-Related Diseases

    Directory of Open Access Journals (Sweden)

    Izak S. Tait

    2013-12-01

    Full Text Available Since the discovery of PTEN, this protein has been shown to be an effective suppressor of cancer and a contributor to longevity. This report will review, in depth, the associations between PTEN and other molecules, its mutations and regulations in order to present how PTEN can be used to increase longevity. This report will collect recent research of PTEN and use this to discuss PTEN’s role in caloric restriction, antioxidative defense of DNA-damage and the role it plays in suppressing tumors. The report will also discuss that variety of ways that PTEN can be compromised, through mutations, complete loss of alleles and its main antagonist, the PI3K/AKT pathway.

  18. Precursors of Age-Related Macular Degeneration

    DEFF Research Database (Denmark)

    Munch, Inger Christine; Linneberg, Allan; Larsen, Michael

    2013-01-01

    by questionnaire. Digital grayscale fundus photographs were recorded in red-free illumination and graded for the presence of macular drusen >63µm in either eye and the presence of 20 or more small, hard macular drusen as a mean of both eyes. RESULTS: Macular drusen >63µm were associated with the level of physical......PURPOSE: To investigate associations of small, hard macular drusen and larger macular drusen with obesity-related risk factors. METHODS: Cross-sectional study of 888 subjects aged 30-60 years characterized using anthropometric measurements and blood sample analyses. Physical activity was assessed.......0005). A waist circumference in the top quartile increased the odds for drusen >63µm in men whereas in women having a waist circumference in the middle quartiles reduced these odds. The presence of 20 or more small, hard macular drusen was associated with lower levels of serum high-density lipoprotein...

  19. The Neural Consequences of Age-Related Hearing Loss.

    Science.gov (United States)

    Peelle, Jonathan E; Wingfield, Arthur

    2016-07-01

    During hearing, acoustic signals travel up the ascending auditory pathway from the cochlea to auditory cortex; efferent connections provide descending feedback. In human listeners, although auditory and cognitive processing have sometimes been viewed as separate domains, a growing body of work suggests they are intimately coupled. Here, we review the effects of hearing loss on neural systems supporting spoken language comprehension, beginning with age-related physiological decline. We suggest that listeners recruit domain general executive systems to maintain successful communication when the auditory signal is degraded, but that this compensatory processing has behavioral consequences: even relatively mild levels of hearing loss can lead to cascading cognitive effects that impact perception, comprehension, and memory, leading to increased listening effort during speech comprehension. PMID:27262177

  20. Age-related hypoxia in CNS pathology.

    Science.gov (United States)

    Bădescu, George Mihai; Fîlfan, Mădălina; Ciobanu, Ovidiu; Dumbravă, DănuŢ Adrian; Popa-Wagner, Aurel

    2016-01-01

    Although neuropathological conditions differ in the etiology of the inflammatory response, cellular and molecular mechanisms of neuroinflammation are probably similar in aging, hypertension, depression and cognitive impairment. Moreover, a number of common risk factors such as obesity, hypertension, diabetes and atherosclerosis are increasingly understood to act as "silent contributors" to neuroinflammation and can underlie the development of disorders such as cerebral small vessel disease (cSVD) and subsequent dementia. On the other hand, acute neuroinflammation, such as in response to traumatic or cerebral ischemia, aggravates the acute damage and can lead to a number of pathological such as depression, post-stroke dementia and potentially neurodegeneration. All of those sequelae impair recovery and most of them provide the ground for further cerebrovascular events and a vicious cycle develops. Therefore, understanding the mechanisms associated with vascular dementia, stroke and related complications is of paramount importance in improving current preventive and therapeutic interventions. Likewise, understanding of molecular factors and pathways associated with neuroinflammation will eventually enable the discovery and implementation of new diagnostic and therapeutic strategies indicated in a wide range of neurological conditions. PMID:27151686

  1. Age-related changes in murine T cell function

    NARCIS (Netherlands)

    C.S. Vissinga (Christine)

    1988-01-01

    textabstractThe aim of the studies presented here was to obtain a more detailed and integrated picture of the age-related changes in cellular immunity. The age-related changes of cellular immunity were studied by in vivo induction of DTH responses to a variety of antigens (Chapters 2 and 3). The res

  2. eNOS-uncoupling in age-related erectile dysfunction.

    Science.gov (United States)

    Johnson, J M; Bivalacqua, T J; Lagoda, G A; Burnett, A L; Musicki, B

    2011-01-01

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

  3. Age-related changes in ultra-triathlon performances

    OpenAIRE

    Knechtle, Beat; Rüst, Christoph,; Knechtle, Patrizia; Rosemann, Thomas; Lepers, Romuald

    2012-01-01

    International audience BackgroundThe 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...

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

    Directory of Open Access Journals (Sweden)

    Mark A Eckert

    2011-03-01

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

  5. New Clues to Age-Related Hearing Loss

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2006-03-01

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

  7. Age-Related Deterioration of Rod Vision in Mice

    OpenAIRE

    Kolesnikov, Alexander V.; Fan, Jie; Crouch, Rosalie K.; Kefalov, Vladimir J.

    2010-01-01

    Even in healthy individuals, aging leads to deterioration in visual acuity, contrast sensitivity, visual field, and dark adaptation. Little is known about the neural mechanisms that drive the age-related changes of the retina and more specifically of photoreceptors. According to one hypothesis, the age-related deterioration in rod function is due to the limited availability of 11-cis-retinal for rod pigment formation. To determine how aging affects rod photoreceptors and to test the retinoid ...

  8. Antioxidant Micronutrients in the Prevention of Age-related Diseases

    OpenAIRE

    Polidori M

    2003-01-01

    The role and functions of antioxidant micronutrients such as ascorbate (vitamin C), a-tocopherol (vitamin E) and carotenoids that are provided through the diet in aging and in the prevention of age-related diseases are discussed in the present work. In general, a healthy lifestyle involving regular exercise and avoidance of tobacco or alcohol abuse are the key to the prevention of several age-related diseases including cardiovascular diseases, dementia and cancer. A balanced and regular nutri...

  9. Risk factors of age-related macular degeneration in Argentina

    Directory of Open Access Journals (Sweden)

    María Eugenia Nano

    2013-04-01

    Full Text Available PURPOSES: To assess the risk factors of age-related macular degeneration in Argentina using a case-control study. METHODS: Surveys were used for subjects' antioxidant intake, age/gender, race, body mass index, hypertension, diabetes (and type of treatment, smoking, sunlight exposure, red meat consumption, fish consumption, presence of age-related macular degeneration and family history of age-related macular degeneration. Main effects models for logistic regression and ordinal logistic regression were used to analyze the results. RESULTS: There were 175 cases and 175 controls with a mean age of 75.4 years and 75.5 years, respectively, of whom 236 (67.4% were female. Of the cases with age-related macular degeneration, 159 (45.4% had age-related macular degeneration in their left eyes, 154 (44.0% in their right eyes, and 138 (39.4% in both eyes. Of the cases with age-related macular degeneration in their left eyes, 47.8% had the dry type, 40.3% had the wet type, and the type was unknown for 11.9%. The comparable figures for right eyes were: 51.9%, 34.4%, and 13.7%, respectively. The main effects model was dominated by higher sunlight exposure (OR [odds ratio]: 3.3 and a family history of age-related macular degeneration (OR: 4.3. Other factors included hypertension (OR: 2.1, smoking (OR: 2.2, and being of the Mestizo race, which lowered the risk of age-related macular degeneration (OR: 0.40. Red meat/fish consumption, body mass index, and iris color did not have an effect. Higher age was associated with progression to more severe age-related macular degeneration. CONCLUSION: Sunlight exposure, family history of age-related macular degeneration, and an older age were the significant risk factors. There may be other variables, as the risk was not explained very well by the existing factors. A larger sample may produce different and better results.

  10. Stromal Fibroblast in Age-Related Cancer: Role in Tumorigenesis and Potential as Novel Therapeutic Target.

    Science.gov (United States)

    Elkhattouti, Abdelouahid; Hassan, Mohamed; Gomez, Christian R

    2015-01-01

    Incidence of most common cancers increases with age due to accumulation of damage to cells and tissues. Stroma, the structure close to the basement membrane, is gaining increased attention from clinicians and researchers due to its increasingly, yet incompletely understood role in the development of age-related cancer. With advanced age, stroma generates a pro-tumorigenic microenvironment, exemplified by the senescence-associated secretory phenotype (SASP). Components of the SASP, such as cytokines, chemokines, and high energy metabolites are main drivers of age-related cancer initiation and sustain its progression. Our purpose is to provide insight into the mechanistic role of the stroma, with particular emphasis on stromal fibroblasts, on the development of age-related tumors. We also present evidence of the potential of the stroma as target for tumor therapy. Likewise, a rationale for age-related antitumor therapy targeting the stroma is presented. We expect to foster debate on the underlining basis of age-related cancer pathobiology. We also would like to promote discussion on novel stroma-based anticancer therapeutic strategies tailored to treat the elderly. PMID:26284191

  11. Stromal Fibroblast in Age-related Cancer: Role in Tumorigenesis and Potential as Novel Therapeutic Target

    Directory of Open Access Journals (Sweden)

    Abdelouahid eElkhattouti

    2015-07-01

    Full Text Available Incidence of most common cancers increases with age due to accumulation of damage to cells and tissues. Stroma, the structure close to the basement membrane, is gaining increased attention from clinicians and researchers due to its increasingly, yet incompletely understood role in the development of age-related cancer. With advanced age, stroma generates a pro-tumorigenic microenvironment, exemplified by the secretory-associated specific phenotype (SASP. Components of the SASP such as cytokines, chemokines, and high energy metabolites are main drivers of age-related cancer initiation and sustain its progression. Our purpose is to provide insight into the mechanistic role of the stroma, with particular emphasis on stromal fibroblasts, on the development of age-related tumors. We also present evidence of the potential of the stroma as target for tumor therapy. Likewise, a rationale for age-related antitumor therapy targeting the stroma is presented. We expect to foster debate on the underlining basis of age-related cancer pathobiology. We also would like to promote discussion on novel stroma-based anticancer therapeutic strategies tailored to treat the elderly.

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

    Science.gov (United States)

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

    2016-05-01

    The neural cell adhesion molecule (NCAM) is involved in developmental processes and age-associated cognitive decline; however, little is known concerning the effects of NCAM in the visual system during aging. Using anatomical, electrophysiological, and behavioral assays, we analyzed age-related changes in visual function of NCAM deficient (-/-) and wild-type mice. Anatomical analyses indicated that aging NCAM -/- mice had fewer retinal ganglion cells, thinner retinas, and fewer photoreceptor cell layers than age-matched controls. Electroretinogram testing of retinal function in young adult NCAM -/- mice showed a 2-fold increase in a- and b-wave amplitude compared with wild-type mice, but the retinal activity dropped dramatically to control levels when the animals reached 10 months. In behavioral tasks, NCAM -/- mice had no visual pattern discrimination ability and showed premature loss of vision as they aged. Together, these findings demonstrate that NCAM plays significant roles in the adult visual system in establishing normal retinal anatomy, physiology and function, and in maintaining vision during aging. PMID:27103522

  13. Age-Related Macular Degeneration: A Scientometric Analysis

    Science.gov (United States)

    Ramin, Shahrokh; Soheilian, Masoud; Habibi, Gholamreza; Ghazavi, Roghayeh; Gharebaghi, Reza; Heidary, Fatemeh

    2015-01-01

    Age-related macular degeneration (ARMD) is a major cause of central blindness among working aged adults across the world. Systematic research planning on any subject, including ARMD is in need of solid data regarding previous efforts in this field and to identify the gaps in the research. This study aimed to elucidate the most important trends, directions, and gap in this subject. The data extracted from the Institute for Scientific Information were used to perform a bibliometric analysis of the scientific productions (1993–2013) about ARMD. Specific parameters related to ARMD were analyzed to obtain a view of the topic’s structure, history, and document relationships. Additionally, the trends and authors in the most influential publications were analyzed. The number of articles in this field was found constantly increasing. Most highly cited articles addressed genetic epidemiology and clinical research topics in this field. During the past 3 years, there has been a trend toward biomarker research. Through performing the first scientometric survey on ARMD research, we analyzed the characteristics of papers and the trends in scientific production. We also identified some of the critical gaps in the current research efforts that would help in large-scale research strategic planning. PMID:26060829

  14. Mechanism of Inflammation in Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Francesco Parmeggiani

    2012-01-01

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

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

    Science.gov (United States)

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

    2013-08-01

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

  16. Age-Related Macular Degeneration: A Scientometric Analysis.

    Science.gov (United States)

    Ramin, Shahrokh; Soheilian, Masoud; Habibi, Gholamreza; Ghazavi, Roghayeh; Gharebaghi, Reza; Heidary, Fatemeh

    2015-01-01

    Age-related macular degeneration (ARMD) is a major cause of central blindness among working aged adults across the world. Systematic research planning on any subject, including ARMD is in need of solid data regarding previous efforts in this field and to identify the gaps in the research. This study aimed to elucidate the most important trends, directions, and gap in this subject. The data extracted from the Institute for Scientific Information were used to perform a bibliometric analysis of the scientific productions (1993-2013) about ARMD. Specific parameters related to ARMD were analyzed to obtain a view of the topic's structure, history, and document relationships. Additionally, the trends and authors in the most influential publications were analyzed. The number of articles in this field was found constantly increasing. Most highly cited articles addressed genetic epidemiology and clinical research topics in this field. During the past 3 years, there has been a trend toward biomarker research. Through performing the first scientometric survey on ARMD research, we analyzed the characteristics of papers and the trends in scientific production. We also identified some of the critical gaps in the current research efforts that would help in large-scale research strategic planning. PMID:26060829

  17. Age-related infertility and unexplained infertility: an intricate clinical dilemma.

    Science.gov (United States)

    Somigliana, Edgardo; Paffoni, Alessio; Busnelli, Andrea; Filippi, Francesca; Pagliardini, Luca; Vigano, Paola; Vercellini, Paolo

    2016-07-01

    A diagnosis of unexplained infertility is commonly made when clinical investigations fail to identify any obvious barriers to conception. As a consequence, unexplained infertility includes several heterogeneous conditions, one being women with age-related infertility. However, the latter represent a peculiar and different situation. Women with age-related infertility may have a different prognosis and may benefit from different treatments. Unfortunately, since fecundity declines with age, discerning between unexplained infertility and age-related infertility becomes more and more difficult as the woman's age increases. In this opinion, with the use of a mathematical model we show that the rate of false positive diagnoses of unexplained infertility increases rapidly after 35 years of age. Using a threshold of 2 years of unfruitful, regular unprotected intercourse, this rate exceeds 50% in women starting pregnancy seeking after 37 years. The scenario is much worse using a threshold of 1 year. From a clinical perspective, extrapolating results obtained in a population of young women with unexplained infertility to those with age-related infertility is not justified. It is noteworthy that, if Assisted Reproductive Technologies are unable to overcome age-related infertility, the older women erroneously labeled with unexplained infertility may receive inappropriate therapies. These may expose women to unjustified risks and waste financial resources. Unfortunately, the available literature about older women is scanty and does not provide valid evidence. Randomized controlled trials aimed at identifying the most suitable clinical management of older women with a normal infertility work-up are pressingly needed. PMID:27060173

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

    Science.gov (United States)

    Alexandru, Malciolu Radu; Alexandra, Nica Maria

    2016-01-01

    Age-related macular degeneration (AMD) is referred to as the leading cause of irreversible visual loss in developed countries, with a profound effect on the quality of life. The neovascular form of AMD is characterized by the formation of subretinal choroidal neovascularization, leading to sudden and severe visual loss. Research has identified the vascular endothelial growth factor (VEGF) as an important pathophysiological component in neovascular AMD and its intraocular inhibition as one of the most efficient therapies in medicine. The introduction of anti-VEGF as a standard treatment in wet AMD has led to a great improvement in the prognosis of patients, allowing recovery and maintenance of visual function in the vast majority of cases. However, the therapeutic benefit is accompanied by a difficulty in maintaining the treatment schedule due to the increase in the amount of patients, stress of monthly assessments, as well as the associated economic burden. Therefore, treatment strategies have evolved from fixed monthly dosing, to individualized regimens, aiming for comparable results, with fewer injections. One such protocol is called "pro re nata", or "treat and observe". Patients are given a loading dose of 3 monthly injections, followed by an as-needed decision to treat, based on the worsening of visual acuity, clinical evidence of the disease activity on fundoscopy, or OCT evidence of retinal thickening in the presence of intra or subretinal fluid. A different regimen is called "treat and extend", in which the interval between injections is gradually increased, once the disease stabilization is achieved. This paper aims to review the currently available anti-VEGF agents--bevacizumab, ranibizumab, aflibercept, and the aforementioned treatment strategies. PMID:27220225

  19. Antioxidant Micronutrients in the Prevention of Age-related Diseases

    Directory of Open Access Journals (Sweden)

    Polidori M

    2003-01-01

    Full Text Available The role and functions of antioxidant micronutrients such as ascorbate (vitamin C, a-tocopherol (vitamin E and carotenoids that are provided through the diet in aging and in the prevention of age-related diseases are discussed in the present work. In general, a healthy lifestyle involving regular exercise and avoidance of tobacco or alcohol abuse are the key to the prevention of several age-related diseases including cardiovascular diseases, dementia and cancer. A balanced and regular nutrition with at least five portions of fruit and vegetables per day is a critical constituent of such a healthy lifestyle.

  20. Age-related variations in the microstructure of human tibial cancellous bone

    DEFF Research Database (Denmark)

    Ding, Ming; Odgaard, A; Linde, F;

    2002-01-01

    A thorough understanding of the microstructure of cancellous bone is crucial for diagnosis, prophylaxis, and treatment of age-related skeletal diseases. Until now, little has been known about age-related variations in the microstructure of peripheral cancellous bone. This study quantified age......-related changes in the three-dimensional (3D) microstructure of human tibial cancellous bone. One hundred and sixty cylindrical cancellous bone specimens were produced from 40 normal proximal tibiae from 40 donors, aged 16-85 years. These specimens were micro-computed tomography (micro-CT) scanned......, and microstructural properties were determined. The specimens were then tested in compression to obtain Young's modulus. The degree of anisotropy, mean marrow space volume, and bone surface-to-volume ratio increased significantly with age. Bone volume fraction, mean trabecular volume, and bone surface density...

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

    Directory of Open Access Journals (Sweden)

    Aleksandra Ławniczak

    2012-06-01

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

  2. Age-Related Differences in the Production of Textual Descriptions

    Science.gov (United States)

    Marini, Andrea; Boewe, Anke; Caltagirone, Carlo; Carlomagno, Sergio

    2005-01-01

    Narratives produced by 69 healthy Italian adults were analyzed for age-related changes of microlinguistic, macrolinguistic and informative aspects. The participants were divided into five age groups (20-24, 25-39, 40-59, 60-74, 75-84). One single-picture stimulus and two cartoon sequences were used to elicit three stories per subject. Age-related…

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

    Science.gov (United States)

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

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2000-01-01

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

  5. Neuroanatomical Substrates of Age-Related Cognitive Decline

    Science.gov (United States)

    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…

  6. PPARα agonist, fenofibrate, ameliorates age-related renal injury.

    Science.gov (United States)

    Kim, Eun Nim; Lim, Ji Hee; Kim, Min Young; Kim, Hyung Wook; Park, Cheol Whee; Chang, Yoon Sik; Choi, Bum Soon

    2016-08-01

    The kidney ages quickly compared with other organs. Expression of senescence markers reflects changes in the energy metabolism in the kidney. Two important issues in aging are mitochondrial dysfunction and oxidative stress. Peroxisome proliferator-activated receptor α (PPARα) is a member of the ligand-activated nuclear receptor superfamily. PPARα plays a major role as a transcription factor that regulates the expression of genes involved in various processes. In this study, 18-month-old male C57BL/6 mice were divided into two groups, the control group (n=7) and the fenofibrate-treated group (n=7) was fed the normal chow plus fenofibrate for 6months. The PPARα agonist, fenofibrate, improved renal function, proteinuria, histological change (glomerulosclerosis and tubular interstitial fibrosis), inflammation, and apoptosis in aging mice. This protective effect against age-related renal injury occurred through the activation of AMPK and SIRT1 signaling. The activation of AMPK and SIRT1 allowed for the concurrent deacetylation and phosphorylation of their target molecules and decreased the kidney's susceptibility to age-related changes. Activation of the AMPK-FOXO3a and AMPK-PGC-1α signaling pathways ameliorated oxidative stress and mitochondrial dysfunction. Our results suggest that activation of PPARα and AMPK-SIRT1 signaling may have protective effects against age-related renal injury. Pharmacological targeting of PPARα and AMPK-SIRT1 signaling molecules may prevent or attenuate age-related pathological changes in the kidney. PMID:27130813

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

    DEFF Research Database (Denmark)

    Trinquier, Anne Marie-Pierre Emilie; Kassem, Moustapha

    2011-01-01

    in the alterations of osteoblastogenesis and the resulting decline in bone formation with aging. Notably, the age-related osteoblast dysfunctions and defective bone formation are caused by a number of extrinsic clinical factors that inhibit anabolic signaling pathways in bone. Thus, targeting these pathways can...

  8. Translational strategies in aging and age-related disease

    NARCIS (Netherlands)

    Armanios, M.; Cabo, R. de; Mannick, J.; Partridge, L.; Deursen, J. van; Villeda, S.

    2015-01-01

    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 thr

  9. Effects of vitrectomy on age-related macular degeneration

    NARCIS (Netherlands)

    Roller, A. Brock; Mahajan, Vinit B.; Boldt, H. Culver; Abramoff, M.D.; Russell, Stephen R.; Folk, James C.

    2010-01-01

    Purpose To determine whether vitrectomy alters the long-term progression of age-related macular degeneration (AMD). Design Retrospective case-control study. Participants Forty-four eyes of 22 patients with AMD who underwent vitrectomy in 1 eye were included in the study. The progression of AMD at

  10. Nutritional influences on epigenetics and age-related disease

    Science.gov (United States)

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

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  12. Operation experience of WWER-440 fuel assemblies and measures to increase fuel reliability

    International Nuclear Information System (INIS)

    The paper presents technical data for the fuel cycles used in 14 WWER-440 reactors of B-213 type situated outside CIS-territory on the basis of the 2001 operational results. The paper reflects the dynamics of average and maximum fuel burnup as well as information on the annual rate of the leaking fuel rods for the above reactor group identified during the 1997-2001 discharge period. As an example of work performed by RIAR in 2001 the paper brings forth the PIE-results of a leaking WWER-440 fuel assemblies (FAs). It is reported that the reason behind the leaking and failed fuel rods of the FA was interaction with a foreign object being in the coolant flow. The paper describes the measures taken by the NPPs together with the Supplier (JSC TVEL) and Manufacturer (JSC MSZ) to enhance the fuel operational safety. (author)

  13. Lipids, lipid genes, and incident age-related macular degeneration : the three continent age-related macular degeneration consortium

    NARCIS (Netherlands)

    Klein, Ronald; Myers, Chelsea E; Buitendijk, Gabriëlle H S; Rochtchina, Elena; Gao, Xiaoyi; de Jong, Paulus T V M; Sivakumaran, Theru A; Burlutsky, George; McKean-Cowdin, Roberta; Hofman, Albert; Iyengar, Sudha K; Lee, Kristine E; Stricker, Bruno H; Vingerling, Johannes R; Mitchell, Paul; Klein, Barbara E K; Klaver, Caroline C W; Wang, Jie Jin

    2014-01-01

    PURPOSE: To describe associations of serum lipid levels and lipid pathway genes to the incidence of age-related macular degeneration (AMD). DESIGN: Meta-analysis. METHODS: setting: Three population-based cohorts. population: A total of 6950 participants from the Beaver Dam Eye Study (BDES), Blue Mou

  14. Lipids, lipid genes, and incident age-related macular degeneration: The three continent age-related macular degeneration consortium

    NARCIS (Netherlands)

    R. Klein (Ronald); C.E. Myers (Chelsea); G.H.S. Buitendijk (Gabrielle); E. Rochtchina (Elena); X. Gao (Xiaoyi); P.T.V.M. de Jong (Paulus); T.A. Sivakumaran (Theru); G. Burlutsky (George); R. McKean-Cowdin (Roberta); A. Hofman (Albert); S.K. Iyengar (Sudha); K.E. Lee (Kristine); B.H. Stricker; J.R. Vingerling (Hans); P. Mitchell (Paul); B.E.K. Klein (Barbara); C.C.W. Klaver (Caroline); J.J. Wang (Jie Jin)

    2014-01-01

    textabstractPurpose To describe associations of serum lipid levels and lipid pathway genes to the incidence of age-related macular degeneration (AMD). Design Meta-analysis. Methods setting: Three population-based cohorts. population: A total of 6950 participants from the Beaver Dam Eye Study (BDES),

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

    Directory of Open Access Journals (Sweden)

    Zheng Q

    2013-12-01

    Full Text Available Qian Zheng, Siming Chen, Ying Chen, John Lyga, Russell Wyborski, Uma SanthanamGlobal Research and Development, Avon Products Inc., Suffern, New York, USAAbstract: 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

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

    Science.gov (United States)

    McMullin, J A; Marshall, V W

    2001-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Wei Fan

    2016-05-01

    Full Text Available Age-related macular degeneration (AMD is a leading cause of vision loss affecting tens of millions of elderly worldwide. Early AMD is characterized by the appearance of soft drusen, as well as pigmentary changes in the retinal pigment epithelium (RPE. These soft, confluent drusen can progress into two forms of advanced AMD: geographic atrophy (GA, or dry AMD or choroidal neovascularization (CNV, or wet AMD. Both forms of AMD result in a similar clinical progression in terms of loss of central vision. The exact mechanism for developing early AMD, as well as triggers responsible for progressing to advanced stage of disease, is still largely unknown. However, significant evidence exists demonstrating a complex interplay of genetic and environmental factors as causes of AMD progression. Multiple genes and/or single nucleotide polymorphisms (SNPs have been found associated with AMD, including various genes involved in the complement pathway, lipid metabolism and extracellular matrix (ECM remodeling. Of the known genetic contributors to disease risk, the CFH Y402H and HTRA1/ARMS polymorphisms contribute to more than 50% of the genetic risk for AMD. Environmentally, oxidative stress plays a critical role in many aging diseases including cardiovascular disease, cancer, Alzheimer’s disease and AMD. Due to the exposure to sunlight and high oxygen concentration, the oxidative stress burden is higher in the eye than other tissues, which can be further complicated by additional oxidative stressors such as smoking. Increasingly, evidence is accumulating suggesting that functional abnormalities of the innate immune system incurred via high risk genotypes may be contributing to the pathogenesis of AMD by altering the inflammatory homeostasis in the eye, specifically in the handling of oxidation products. As the eye in non-pathological instances maintains a low level of inflammation despite the presence of a relative abundance of potentially inflammatory

  18. The Theory Behind the Age-Related Positivity Effect

    OpenAIRE

    Reed, Andrew E.; Carstensen, Laura L.

    2012-01-01

    The “positivity effect” refers to an age-related trend that favors positive over negative stimuli in cognitive processing. Relative to their younger counterparts, older people attend to and remember more positive than negative information. Since the effect was initially identified and the conceptual basis articulated (Mather and Carstensen, 2005) scores of independent replications and related findings have appeared in the literature. Over the same period, a number of investigations have faile...

  19. Within-Cohort Age-Related Differences in Cognitive Functioning

    OpenAIRE

    Salthouse, Timothy A.

    2013-01-01

    It is widely accepted that the level of cognitive functioning can be influenced by characteristics of the environment that change over time. Many developmental researchers have referred to these influences as cohort effects, and have used year of birth as the basis for determining cohort membership. Furthermore, age-related differences in cognitive functioning are sometimes assumed to be primarily attributable to cohort differences, which implies that differences between birth cohorts should ...

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

    Science.gov (United States)

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

    2014-01-01

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

  1. Nutritional Supplements in Support of Resistance Exercise to Counter Age-Related Sarcopenia12

    OpenAIRE

    Phillips, Stuart M.

    2015-01-01

    Age-related sarcopenia, composed of myopenia (a decline in muscle mass) and dynapenia (a decline in muscle strength), can compromise physical function, increase risk of disability, and lower quality of life in older adults. There are no available pharmaceutical treatments for this condition, but evidence shows resistance training (RT) is a viable and relatively low-cost treatment with an exceptionally positive side effect profile. Further evidence suggests that RT-induced increases in muscle ...

  2. Age-related memory impairments due to reduced blood glucose responses to epinephrine

    OpenAIRE

    Morris, Ken A.; Chang, Qing; Mohler, Eric G.; Gold, Paul E.

    2009-01-01

    Increases in blood glucose levels are an important component of the mechanisms by which epinephrine enhances memory formation. The present experiments addressed the hypothesis that a dysfunction in the blood glucose response to circulating epinephrine contributes to age-related memory impairments. Doses of epinephrine and glucagon that significantly increased blood glucose levels in young adult rats were far less effective at doing so in two-year-old rats. In young rats, epinephrine and gluco...

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

    Directory of Open Access Journals (Sweden)

    Brittni N. Frederiksen

    2015-01-01

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

  4. Age-related changes to the neural correlates of working memory which emerge after midlife

    Directory of Open Access Journals (Sweden)

    Helen N Macpherson

    2014-04-01

    Full Text Available 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 13Hz 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 to 60 years and an older group (61 to 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.

  5. Age-related changes to the neural correlates of working memory which emerge after midlife

    Science.gov (United States)

    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. PMID:24795625

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2014-12-01

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

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

    Science.gov (United States)

    Lever, Anne G; Geurts, Hilde M

    2016-06-01

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

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

    Science.gov (United States)

    Lever, Anne G; Geurts, Hilde M

    2016-06-01

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

  10. [Age-related Macular Degeneration in the Japanese].

    Science.gov (United States)

    Yoshimura, Nagahisa

    2016-03-01

    Age-related macular degeneration (AMD) in the Japanese often shows different clinical features from those described in Caucasians. For example, we often observe choroidal neovascularization (CNV) in elderly patients without drusen in the fundus. The high incidence of polypoidal choroidal vasculopathy (PCV) in AMD among Japanese is well-known. The reason why such differences occur in clinical manifestations of AMD has been one of my main interests. In this review article, I will discuss the characteristics of AMD in the Japanese population, as found in our recent study. I. Prevalence and clinical characteristics of AMD in the Japanese population. Cohort studies are important to determine the prevalence and incidence of diseases. In Japan, cohort studies began to be carried out rather late compared with Western countries. Although good cohort studies from Japan are reported in the literature, the size of the cohorts was not sufficiently large to determine the prevalence of AMD. However, a recent meta-analysis of Asian cohorts has shown that the prevalence of late AMD in Asians is not different from that reported in Caucasians. On the other hand, the prevalence of early AMD appears lower in the Japanese than in Caucasians. Recently, we have published the results of the Nagahama Cohort study. In this cohort study, we found a high prevalence of drusen. It seems that the incidence of dry AMD is likely to increase among Japanese. In Japan, most retina specialists classify AMD into three categories : typical AMD, PCV, and retinal angiomatous proliferation (RAP). However, there are no definite diagnostic criteria to distinguish between the three conditions. To compare the clinical features of Japanese and Western cases of AMD, and to determine the incidence of the three types of AMD, we exchanged data about 100 consecutive cases between Kyoto University and Centre d'Ophtalmologie de Paris, France. Interestingly, the diagnoses made by the two institutes were not always in

  11. Age-related changes in the testes and prostate of the Beagle dog

    International Nuclear Information System (INIS)

    Age-related changes in the histologic morphology of the Beagle dog prostate and testes must be separated from those changes that may result from the testing of experimental compounds. The prostate and testes of healthy age-matched Beagle dogs 3 to 14 yr of age were obtained. Serum to evaluate testosterone levels was also obtained from each dog at the time of euthanasia. Tissue sections from the prostate and testes were examined by light microscopy for both qualitative and quantitative morphologic assessment. A statistically significant increase in prostatic weight with increased age was noted. Significant morphometric findings in the prostate included a decrease in the relative percent of epithelial cells and an increase in the relative lumen size of glandular acini with increased age. The absolute volume of prostate interstitial tissue and inflammation showed a statistically significant increase with age. Stereological analysis of the testes showed a decrease in the relative percent epithelium with increasing age. No distinct age-related trend could be detected in serum testosterone levels. Serum testosterone levels did not correlate with the morphologic age-related changes observed in the testes or prostate. (author)

  12. Transplantation of retinal pigment epithelial cells - a possible future treatment for age-related macular degeneration

    DEFF Research Database (Denmark)

    Wiencke, Anne Katrine

    2001-01-01

    ophthalmology, age-related macular degeneration, retinal pigment epithelial cells, transplantation, treatment......ophthalmology, age-related macular degeneration, retinal pigment epithelial cells, transplantation, treatment...

  13. Transplantation of retinal pigment epithelial cells - a possible future treatment for age-related macular degeneration

    DEFF Research Database (Denmark)

    Wiencke, Anne Katrine

    2001-01-01

    ophthalmology, age-related macular degeneration, transplantation, retinal pigment epithelial cells, treatment......ophthalmology, age-related macular degeneration, transplantation, retinal pigment epithelial cells, treatment...

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

    Science.gov (United States)

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

    2006-09-01

    Squalamine lactate inhibits angiogenesis by a long-lived, intracellular mechanism of action. The drug is taken up into activated endothelial cells through caveolae, small invaginations in the cellular membrane. Subsequently, the drug binds to and "chaperones" calmodulin to an intracellular membrane compartment and blocks angiogenesis at several levels. A series of basic investigations, preclinical studies, and human clinical trials have begun to establish the proof of concept, efficacy, and safety parameters for use of squalamine lactate as a therapeutic agent for exudative age-related macular degeneration and several types of malignancies. PMID:16935213

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

    OpenAIRE

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

    2013-01-01

    Demand–withdraw communication is a set of conflict-related behaviors in which one partner blames or pressures while the other partner withdraws or avoids. The present study examined age-related changes in these behaviors longitudinally over the course of later life stages. One hundred twenty-seven middle-aged and older long-term married couples were observed at 3 time points across 13 years as they engaged in a conversation about an area of relationship conflict. Husbands’ and wives’ demand–w...

  16. What effects has the cataract surgery on the development and progression of Age-Related Macular Degeneration (AMD)?

    OpenAIRE

    Bockelbrink, A; Rasch, A; Roll, S.; Willich, SN; Greiner, W

    2006-01-01

    Background The cataract (Cataracta senilis) is the most frequent eye disease of elderly people worldwide. In Germany, the cataract operation - with currently 450,000 interventions each year the most frequent operation in ophthalmology - can be seen as routine surgery. The age related macular degeneration (AMD) is a further one of the most common, age-related eye diseases and the most frequent cause of blindness of elderly people in industrial nations. Due to demographic changes an increasing ...

  17. What effects has the cataract surgery on the development and progression of Age-Related Macular Degeneration (AMD)?

    OpenAIRE

    Willich, Stefan N.; Roll, Stephanie; Rasch, Andrej; Bockelbrink, Angelina; Greiner, Wolfgang

    2006-01-01

    Background: The cataract (Cataracta senilis) is the most frequent eye disease of elderly people worldwide. In Germany, the cataract operation - with currently 450,000 interventions each year the most frequent operation in ophthalmology – can be seen as routine surgery. The age related macular degeneration (AMD) is a further one of the most common, age-related eye diseases and the most frequent cause of blindness of elderly people in industrial nations. Due to demographic changes an increasing...

  18. KCNQ channels regulate age-related memory impairment.

    Directory of Open Access Journals (Sweden)

    Sonia Cavaliere

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

  19. Learning and aging related changes in intrinsic neuronal excitability

    Directory of Open Access Journals (Sweden)

    Fernando A Oliveira

    2010-02-01

    Full Text Available A goal of many laboratories that study aging is to find a key cellular change(s that can be manipulated and restored to a young-like state, and thus, reverse the age-related cognitive deficits. We have chosen to focus our efforts on the alteration of intrinsic excitability (as reflected by the postburst afterhyperpolarization, AHP during the learning process in hippocampal pyramidal neurons. We have consistently found that the postburst AHP is significantly reduced in hippocampal pyramidal neurons from young adults that have successfully learned a hippocampus-dependent task. In the context of aging, the baseline intrinsic excitability of hippocampal neurons is decreased and therefore cognitive learning is impaired. In aging animals that are able to learn, neuron changes in excitability similar to those seen in young neurons during learning occur. Our challenge, then, is to understand how and why excitability changes occur in neurons from aging brains and cause age-associated learning impairments. After understanding the changes, we should be able to formulate strategies for reversing them, thus making old neurons function more as they did when they were young. Such a reversal should rescue the age-related cognitive deficits.

  20. NSAIDs may protect against age-related brain atrophy

    Directory of Open Access Journals (Sweden)

    Barbara B Bendlin

    2010-09-01

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

  1. Processing Speed and Memory Mediate Age-Related Differences in Decision Making

    OpenAIRE

    Henninger, Debra E.; Madden, David J.; Huettel, Scott A.

    2010-01-01

    Decision making under risk changes with age. Most commonly characterized have been increases in risk-aversion with age, although older adults may also be risk-seeking in some decision contexts. An important, and unanswered, question is whether these changes in decision making reflect a direct effect of aging or, alternatively, an indirect effect caused by age-related changes in specific cognitive processes. In the current study, older adults (mean = 71 years) and younger adults (mean = 24 yea...

  2. Patients’ knowledge and perspectives on wet age-related macular degeneration and its treatment

    OpenAIRE

    Kandula, Sushma; Jeffrey C Lamkin; Albanese, Teresa; Deepak P Edward

    2010-01-01

    Summary: There have been no studies examining the level of understanding age-related macular degeneration (ARMD) patients have about their disease, or their perceptions about intraocular injections as treatment. In this study, patient knowledge about ARMD risk factors was low but patients appeared more optimistic than fearful when confronted with intraocular antivascular endothelial growth factor (anti-VEGF) injections as treatment. Purpose: In recent years there has been an increase in our u...

  3. Spermidine Feeding Decreases Age-Related Locomotor Activity Loss and Induces Changes in Lipid Composition

    OpenAIRE

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

    2014-01-01

    Spermidine is a natural polyamine involved in many important cellular functions, whose supplementation in food or water increases life span and stress resistance in several model organisms. In this work, we expand spermidine's range of age-related beneficial effects by demonstrating that it is also able to improve locomotor performance in aged flies. Spermidine's mechanism of action on aging has been primarily related to general protein hypoacetylation that subsequently induces autophagy. Her...

  4. Complement C1q Activates Canonical Wnt Signaling and Promotes Aging-Related Phenotypes

    OpenAIRE

    Atsuhiko T. Naito; Sumida, Tomokazu; Nomura, Seitaro; Liu, Mei-Lan; Higo, Tomoaki; NAKAGAWA, AKITO; Okada, Katsuki; Sakai, Taku; Hashimoto, Akihito; Hara, Yurina; Shimizu, Ippei; Zhu, Weidong; Toko, Haruhiro; Katada, Akemi; Akazawa, Hiroshi

    2012-01-01

    Wnt signaling plays critical roles in development of various organs and pathogenesis of many diseases, and augmented Wnt signaling has recently been implicated in mammalian aging and aging-related phenotypes. We here report that complement C1q activates canonical Wnt signaling and promotes aging-associated decline in tissue regeneration. Serum C1q concentration is increased with aging, and Wnt signaling activity is augmented during aging in the serum and in multiple tissues of wild-type mice,...

  5. What determines age-related disease: do we know all the right questions?

    OpenAIRE

    Juckett, David A.

    2009-01-01

    The average human lifespan has increased throughout the last century due to the mitigation of many infectious diseases. More people now die of age-related diseases than ever before, but these diseases have been resistant to elimination. Progress has been made in treatments and preventative measures to delay the onsets of these diseases, but most cancers and vascular diseases are still with us and they kill about the same fraction of the population year after year. For example, US Caucasian fe...

  6. Templated assembly of photoswitches significantly increases the energy-storage capacity of solar thermal fuels

    Energy Technology Data Exchange (ETDEWEB)

    Kucharski, TJ; Ferralis, N; Kolpak, AM; Zheng, JO; Nocera, DG; Grossman, JC

    2014-04-13

    Large-scale utilization of solar-energy resources will require considerable advances in energy-storage technologies to meet ever-increasing global energy demands. Other than liquid fuels, existing energy-storage materials do not provide the requisite combination of high energy density, high stability, easy handling, transportability and low cost. New hybrid solar thermal fuels, composed of photoswitchable molecules on rigid, low-mass nanostructures, transcend the physical limitations of molecular solar thermal fuels by introducing local sterically constrained environments in which interactions between chromophores can be tuned. We demonstrate this principle of a hybrid solar thermal fuel using azobenzene-functionalized carbon nanotubes. We show that, on composite bundling, the amount of energy stored per azobenzene more than doubles from 58 to 120 kJ mol(-1), and the material also maintains robust cyclability and stability. Our results demonstrate that solar thermal fuels composed of molecule-nanostructure hybrids can exhibit significantly enhanced energy-storage capabilities through the generation of template-enforced steric strain.

  7. Templated assembly of photoswitches significantly increases the energy-storage capacity of solar thermal fuels

    Science.gov (United States)

    Kucharski, Timothy J.; Ferralis, Nicola; Kolpak, Alexie M.; Zheng, Jennie O.; Nocera, Daniel G.; Grossman, Jeffrey C.

    2014-05-01

    Large-scale utilization of solar-energy resources will require considerable advances in energy-storage technologies to meet ever-increasing global energy demands. Other than liquid fuels, existing energy-storage materials do not provide the requisite combination of high energy density, high stability, easy handling, transportability and low cost. New hybrid solar thermal fuels, composed of photoswitchable molecules on rigid, low-mass nanostructures, transcend the physical limitations of molecular solar thermal fuels by introducing local sterically constrained environments in which interactions between chromophores can be tuned. We demonstrate this principle of a hybrid solar thermal fuel using azobenzene-functionalized carbon nanotubes. We show that, on composite bundling, the amount of energy stored per azobenzene more than doubles from 58 to 120 kJ mol-1, and the material also maintains robust cyclability and stability. Our results demonstrate that solar thermal fuels composed of molecule-nanostructure hybrids can exhibit significantly enhanced energy-storage capabilities through the generation of template-enforced steric strain.

  8. Templated assembly of photoswitches significantly increases the energy-storage capacity of solar thermal fuels.

    Science.gov (United States)

    Kucharski, Timothy J; Ferralis, Nicola; Kolpak, Alexie M; Zheng, Jennie O; Nocera, Daniel G; Grossman, Jeffrey C

    2014-05-01

    Large-scale utilization of solar-energy resources will require considerable advances in energy-storage technologies to meet ever-increasing global energy demands. Other than liquid fuels, existing energy-storage materials do not provide the requisite combination of high energy density, high stability, easy handling, transportability and low cost. New hybrid solar thermal fuels, composed of photoswitchable molecules on rigid, low-mass nanostructures, transcend the physical limitations of molecular solar thermal fuels by introducing local sterically constrained environments in which interactions between chromophores can be tuned. We demonstrate this principle of a hybrid solar thermal fuel using azobenzene-functionalized carbon nanotubes. We show that, on composite bundling, the amount of energy stored per azobenzene more than doubles from 58 to 120 kJ mol(-1), and the material also maintains robust cyclability and stability. Our results demonstrate that solar thermal fuels composed of molecule-nanostructure hybrids can exhibit significantly enhanced energy-storage capabilities through the generation of template-enforced steric strain.

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

    Science.gov (United States)

    Turlea, C

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2002-01-01

    cause of blindness among Caucasian individuals in developed countries. Blindness resulting from AMD rarely occurs before age 70, and most cases occur after age 80. The age-standardised 1-year incidence of legal blindness resulting from AMD is 212 cases per million. Two-thirds of AMD cases have CNV......Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterised by the appearance of drusen in the macula, accompanied by choroidal neovascularisation (CNV) or geographic atrophy. The disease is more common in Caucasian...... individuals than in pigmented races. In predominantly Caucasian populations, the age-standardised prevalence of AMD in at least one eye is 7760 cases per million. The age-standardised cumulated 1-year incidence of AMD in at least one eye is 1051 cases per million individuals. AMD is the most important single...

  11. Counteracting age-related loss of skeletal muscle mass

    DEFF Research Database (Denmark)

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

    2016-01-01

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

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

    DEFF Research Database (Denmark)

    Kassem, Moustapha

    2006-01-01

    -engineered organs) to restore the functions of damaged or defective tissues and organs and thus to "rejuvenate" the failing aging body. One of the most important sources for cellular medicine is embryonic and adult (somatic) stem cells (SSCs). One example of SCCs with enormous clinical potential is the mesenchymal......Aging is associated with a progressive failing of tissues and organs of the human body leading to a large number of age-related diseases. Regenerative medicine is an emerging clinical discipline that aims to employ cellular medicines (normal cells, ex vivo expanded cells, or tissue...... stem cells (MSCs) that are present in the bone marrow and are able to differentiate into cell types such as osteoblasts, chondrocytes, endothelial cells, and probably also neuron-like cells. Because of the ease of their isolation and their extensive differentiation potential, MSCs are among the first...

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

    Science.gov (United States)

    Lemaire, Patrick

    2016-03-01

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

  14. Radiation Therapy for Neovascular Age-related Macular Degeneration

    International Nuclear Information System (INIS)

    In the enormity of the public health burden imposed by age-related macular degeneration (ARMD), much effort has been directed toward identifying effective and efficient treatments. Currently, anti-vascular endothelial growth factor (VEGF) injections have demonstrated considerably efficacy in treating neovascular ARMD, but patients require frequent treatment to fully benefit. Here, we review the rationale and evidence for radiation therapy of ARMD. The results of early photon external beam radiation therapy are included to provide a framework for the sequential discussion of evidence for the usage of stereotactic radiation therapy, proton therapy, and brachytherapy. The evidence suggests that these 3 modern modalities can provide a dose-dependent benefit in the treatment of ARMD. Most importantly, preliminary data suggest that all 3 can be used in conjunction with anti-VEGF therapeutics, thereby reducing the frequency of anti-VEGF injections required to maintain visual acuity

  15. Age-related differences in multiple task monitoring.

    Science.gov (United States)

    Todorov, Ivo; Del Missier, Fabio; Mäntylä, Timo

    2014-01-01

    Coordinating multiple tasks with narrow deadlines is particularly challenging for older adults because of age related decline in cognitive control functions. We tested the hypothesis that multiple task performance reflects age- and gender-related differences in executive functioning and spatial ability. Young and older adults completed a multitasking session with four monitoring tasks as well as separate tasks measuring executive functioning and spatial ability. For both age groups, men exceeded women in multitasking, measured as monitoring accuracy. Individual differences in executive functioning and spatial ability were independent predictors of young adults' monitoring accuracy, but only spatial ability was related to sex differences. For older adults, age and executive functioning, but not spatial ability, predicted multitasking performance. These results suggest that executive functions contribute to multiple task performance across the adult life span and that reliance on spatial skills for coordinating deadlines is modulated by age.

  16. Translational strategies in aging and age-related disease.

    Science.gov (United States)

    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. PMID:26646495

  17. Gulliver meets Descartes: early modern concepts of age-related memory loss.

    Science.gov (United States)

    Schäfer, Daniel

    2003-03-01

    Age-related memory loss was a marginal issue in medical discussions during early modern times and until well into the second half of the 17th century. There are many possible explanations: the lack of similar traditions in antiquity and in the Middle Ages, insufficient physiological and morphological knowledge of the brain, and the underlying conflict between idealistic and materialistic perspectives on the functions of the soul and the conditions of these in old age. After these boundaries had been pushed back by the influence of Cartesianism and Iatromechanism, the problem of age-related memory loss was increasingly regarded as a physical illness and began to receive more attention. This trend first occurred in medicine, before spreading to the literary world, where the novel "Gulliver's Travels" is one clear and famous example. PMID:12785108

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

    Directory of Open Access Journals (Sweden)

    Margaret Markiewicz

    2013-01-01

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

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

    Science.gov (United States)

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

    2016-05-31

    The underlying relation between Parkinson's disease (PD) etiopathology and its major risk factor, aging, is largely unknown. In light of the causative link between genome stability and aging, we investigate a possible nexus between DNA damage accumulation, aging, and PD by assessing aging-related DNA repair pathways in laboratory animal models and humans. We demonstrate that dermal fibroblasts from PD patients display flawed nucleotide excision repair (NER) capacity and that Ercc1 mutant mice with mildly compromised NER exhibit typical PD-like pathological alterations, including decreased striatal dopaminergic innervation, increased phospho-synuclein levels, and defects in mitochondrial respiration. Ercc1 mouse mutants are also more sensitive to the prototypical PD toxin MPTP, and their transcriptomic landscape shares important similarities with that of PD patients. Our results demonstrate that specific defects in DNA repair impact the dopaminergic system and are associated with human PD pathology and might therefore constitute an age-related risk factor for PD. PMID:27210754

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

    Science.gov (United States)

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

    2014-05-01

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

  1. Age-Related Differences in Muscle Shear Moduli in the Lower Extremity.

    Science.gov (United States)

    Akagi, Ryota; Yamashita, Yota; Ueyasu, Yuta

    2015-11-01

    This study investigated the age-related differences in shear moduli of the rectus femoris muscle (RF), the lateral head of the gastrocnemius muscle (LG) and the soleus muscle (SOL) using shear wave ultrasound elastography. Thirty-one young individuals and 49 elderly individuals volunteered for this study. The shear modulus of RF was determined at 50% of the thigh length, and those of LG and SOL were determined at 30% of the lower leg length. RF and LG shear moduli were significantly higher in young individuals than in elderly individuals, but there was no age-related difference in SOL shear modulus. From the standpoint of an index reflecting muscle mechanical properties, it is suggested that the lower muscle shear moduli of RF and LG are the reason for the decreased explosive muscle strength in the lower extremity and the increased risk of falls for elderly individuals.

  2. Seismic response of base isolated auxiliary building with age related degradation

    International Nuclear Information System (INIS)

    The aging of an isolator affects not only the mechanical properties of the isolator but also the dynamic properties of the upper structure, such as the change in stiffness, deformation capacity, load bearing capacity, creep, and damping. Therefore, the seismic response of base isolated structures will change with time. The floor response in the base isolated nuclear power plants (NPPs) can be particularly changed because of the change in stiffness and damping for the isolator. The increased seismic response due to the aging of isolator can cause mechanical problems for many equipment located in the NPPs. Therefore, it is necessary to evaluate the seismic response of base isolated NPPs with age related degradation. In this study, the seismic responses for a base isolated auxiliary building of SHIN KORI 3 and 4 with age related degradation were investigated using a nonlinear time history analysis. Floor response spectrums (FRS) were presented with time for identifying the change in seismic demand under the aging of isolator

  3. Age-related degradation of Westinghouse 480-volt circuit breakers

    International Nuclear Information System (INIS)

    After the McGuire event in 1987 relating to failure of the center pole weld in one of its reactor trip breakers, activities were initiated by the NRC to investigate the probable causes. A review of operating experience suggested that the burning of coils, jamming of the operating mechanism, and deterioration of the contacts dominated the breakers failures. Although failures of the pole shaft weld were not included as one of the generic problems, the NRC augmented inspection team had suspected that these welds were substandard which led them to crack prematurely. A DS-416 low voltage air circuit breaker manufactured by Westinghouse was mechanically cycled to identify age-related degradations. This accelerated aging test was conducted for over 36,000 cycles during nine months. Three separate pole shafts, one with a 60 degree weld, one with a 120 degree and one with a 180 degree were used to characterize the cracking in the pole level welds. In addition, three different operating mechanisms and several other parts were replaced as they became inoperable. The testing yielded many useful results. The burning of the closing coils was found to be the effect of binding in the linkages that are connected to this device. Among the seven welds on the pole shaft, number-sign 1 and number-sign 3 were the critical ones which cracked first to cause misalignment of the pole levers, which, in turn, had led to many problems with the operating mechanism including the burning of coils, excessive wear in certain parts, and overstressed linkages. Based on these findings, a maintenance program is suggested to alleviate the age-related degradations that occur due to mechanical cycling of this type of breaker. 3 refs., 39 figs., 7 tabs

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

    Science.gov (United States)

    Smith, Paul F

    2016-01-01

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

  5. Age-Related Neurochemical Changes in the Vestibular Nuclei

    Directory of Open Access Journals (Sweden)

    Paul eSmith

    2016-03-01

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

  6. Age-related structural and functional changes in the cochlear nucleus.

    Science.gov (United States)

    Frisina, Robert D; Walton, Joseph P

    2006-01-01

    Presbycusis - age-related hearing loss - is a key communication disorder and chronic medical condition of our aged population. The cochlear nucleus is the major site of projections from the auditory portion of the inner ear. Relative to other levels of the peripheral and central auditory systems, relatively few studies have been conducted examining age-related changes in the cochlear nucleus. The neurophysiological investigations suggest declines in glycine-mediated inhibition, reflected in increased firing rates in cochlear nucleus neurons from old animals relative to young adults. Biochemical investigations of glycine inhibition in the cochlear nucleus are consistent with the functional aging declines of this inhibitory neurotransmitter system that affect complex sound processing. Anatomical reductions in neurons of the cochlear nucleus and their output pathways can occur due to aging changes in the brain, as well as due to age-dependent plasticity of the cochlear nucleus in response to the age-related loss of inputs from the cochlea, particularly from the basal, high-frequency regions. Novel preventative and curative biomedical interventions in the future aimed at alleviating the hearing loss that comes with age, will likely emanate from increasing our knowledge and understanding of its neural and molecular bases. To the extent that this sensory deficit resides in the central auditory system, including the cochlear nucleus, future neural therapies will be able to improve hearing in the elderly.

  7. Early-age-related changes in proteostasis augment immunopathogenesis of sepsis and acute lung injury.

    Directory of Open Access Journals (Sweden)

    Manish Bodas

    Full Text Available BACKGROUND: The decline of proteasomal activity is known to be associated with the age-related disorders but the early events involved in this process are not apparent. To address this, we investigated the early-age-related (pediatric vs. adult mechanisms that augment immunopathogenesis of sepsis and acute lung injury. METHODOLOGY/PRINCIPAL FINDINGS: The 3-weeks (pediatric and 6-months (adult old C57BL/6 mice were selected as the study groups. Mice were subjected to 1×20 cecal ligation and puncture (CLP mediated sepsis or intratracheal Psuedomonas aeruginosa (Pa-LPS induced acute lung injury (ALI.We observed a significant increase in basal levels of pro-inflammatory cytokine, IL-6 and neutrophil activity marker, myeloperoxidase (MPO in the adult mice compared to the pediatric indicating the age-related constitutive increase in inflammatory response. Next, we found that age-related decrease in PSMB6 (proteasomal subunit expression in adult mice results in accumulation of ubiquitinated proteins that triggers the unfolded protein response (UPR. We identified that Pa-LPS induced activation of UPR modifier, p97/VCP (valosin-containing protein in the adult mice lungs correlates with increase in Pa-LPS induced NFκB levels. Moreover, we observed a constitutive increase in p-eIF2α indicating a protective ER stress response to accumulation of ubiquitinated-proteins. We used MG-132 treatment of HBE cells as an in vitro model to standardize the efficacy of salubrinal (inhibitor of eIF2α de-phosphorylation in controlling the accumulation of ubiquitinated proteins and the NFκB levels. Finally, we evaluated the therapeutic efficacy of salubrinal to correct proteostasis-imbalance in the adult mice based on its ability to control CLP induced IL-6 secretion or recruitment of pro-inflammatory cells. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate the critical role of early-age-related proteostasis-imbalance as a novel mechanism that augments the NFκB mediated

  8. Adsorption and self-assembly of bio-organic molecules at model surfaces: A route towards increased complexity

    Science.gov (United States)

    Costa, Dominique; Pradier, Claire-Marie; Tielens, Frederik; Savio, Letizia

    2015-12-01

    Understanding the bio-physical-chemical interactions at nanostructured biointerfaces and the assembly mechanisms of so-called hybrid nano-composites is nowadays a key issue for nanoscience in view of the many possible applications foreseen. The contribution of surface science in this field is noteworthy since, using a bottom-up approach, it allows the investigation of the fundamental processes at the basis of complex interfacial phenomena and thus it helps to unravel the elementary mechanisms governing them. Nowadays it is well demonstrated that a wide variety of different molecular assemblies can form upon adsorption of small biomolecules at surfaces. The geometry of such self-organized structures can often be tuned by a careful control of the experimental conditions during the deposition process. Indeed an impressive number of studies exists (both experimental and - to a lesser extent - theoretical), which demonstrates the ability of molecular self-assembly to create different structural motifs in a more or less predictable manner, by tuning the molecular building blocks as well as the metallic substrate. In this frame, amino acids and small peptides at surfaces are key, basic, systems to be studied. The amino acids structure is simple enough to serve as a model for the chemisorption of biofunctional molecules, but their adsorption at surfaces has applications in surface functionalization, in enantiospecific catalysis, biosensing, shape control of nanoparticles or in emerging fields such as "green" corrosion inhibition. In this paper we review the most recent advances in this field. We shall start from the adsorption of amino acids at metal surfaces and we will evolve then in the direction of more complex systems, in the light of the latest improvements of surface science techniques and of computational methods. On one side, we will focus on amino acids adsorption at oxide surfaces, on the other on peptide adsorption both at metal and oxide substrates. Particular

  9. Age-related shifts in brain activity dynamics during task switching.

    Science.gov (United States)

    Jimura, Koji; Braver, Todd S

    2010-06-01

    Cognitive aging studies have suggested that older adults show declines in both sustained and transient cognitive control processes. However, previous neuroimaging studies have primarily focused on age-related change in the magnitude, but not temporal dynamics, of brain activity. The present study compared brain activity dynamics in healthy old and young adults during task switching. A mixed blocked/event-related functional magnetic resonance imaging design enabled separation of transient and sustained neural activity associated with cognitive control. Relative to young adults, older adults exhibited not only decreased sustained activity in the anterior prefrontal cortex (aPFC) during task-switching blocks but also increased transient activity on task-switch trials. Another pattern of age-related shift in dynamics was present in the lateral PFC (lPFC) and posterior parietal cortex (PPC), with younger adults showing a cue-related response during task-switch trials in lPFC and PPC, whereas older adults exhibited switch-related activation during the cue period in PPC only. In all 3 regions, these qualitatively distinct patterns of brain activity predicted qualitatively distinct patterns of behavioral performance across the 2 age groups. Together, these results suggest that older adults may shift from a proactive to reactive cognitive control strategy as a means of retaining relatively preserved behavioral performance in the face of age-related neurocognitive changes. PMID:19805420

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

    Science.gov (United States)

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

    2015-10-01

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

  11. What determines age-related disease: do we know all the right questions?

    Science.gov (United States)

    Juckett, David A

    2010-06-01

    The average human lifespan has increased throughout the last century due to the mitigation of many infectious diseases. More people now die of age-related diseases than ever before, but these diseases have been resistant to elimination. Progress has been made in treatments and preventative measures to delay the onsets of these diseases, but most cancers and vascular diseases are still with us and they kill about the same fraction of the population year after year. For example, US Caucasian female deaths from breast plus genital cancers have remained a fairly constant approximately 7% of the age-related disease deaths from 1938 to 1998 and have been consistently approximately 2-fold greater than female colon plus rectal cancer deaths over that span. This type of stability pattern pervades the age-related diseases and suggests that intrinsic properties within populations determine these fractions. Recognizing this pattern and deciphering its origin will be necessary for the complete understanding of these major causes of death. It would appear that more than the random processes of aging drive this effect. The question is how to meaningfully approach this problem. This commentary discusses the epidemiological and aging perspectives and their current limitations in providing an explanation. The age of bioinformatics offers hope, but only if creative systems approaches are forthcoming. PMID:19904627

  12. Age-related reduction of chromatin fractal dimension in toluidine blue - stained hepatocytes.

    Science.gov (United States)

    Pantic, Igor; Petrovic, Danica; Paunovic, Jovana; Vucevic, Danijela; Radosavljevic, Tatjana; Pantic, Senka

    2016-07-01

    In this study, we proposed a hypothesis that chromatin of mouse hepatocytes exhibits age-related reduction of fractal dimension. This hypothesis was based on previously published works demonstrating that complexity of biological systems such as tissues, decreases during the process of physiological aging. Liver tissue was obtained from 24 male mice divided into 3 age groups: 10-days-old (young, juvenile), 210-days-old (adult) and 390-days-old. The tissue was stained using a modification of toluidine blue (nucleic acid - specific) staining method. A total of 480 chromatin structures (20 for each animal) were analyzed. For each structure, the values of fractal dimension, lacunarity, textural angular second moment and inverse difference moment were calculated using ImageJ software and its plugins. The results indicated the age-related reduction in fractal dimension and increase in lacunarity (p<0.01). Fractal dimension is a potentially good indicator of age associated changes in chromatin structure. To our knowledge, this is the first study to show that fractal complexity of hepatocyte chromatin decreases during the process of physiological aging. Fractal analysis as a method could be useful in detection of small age-related changes in chromatin distribution not otherwise visible with naked eye on conventional tissue micrographs. PMID:27412950

  13. Overview of the age-related degradation of nuclear power plant structures

    International Nuclear Information System (INIS)

    License renewal of nuclear power plants is an issue of increasing interest to the U.S. nuclear industry and the U.S. NRC. This paper presents and evaluates the plausible age-related degradation mechanisms that may affect the concrete and steel containment structures and other Class I structures to continue to perform their safety functions. Preventive and/or mitigative options are outlined for managing degradation mechanisms that could significantly affect plant performance during the license renewal period. The provided technical information and the degradation management options may be used as references for comparison with plant specific conditions to ensure that age-related degradation is controlled during the license renewal term. Plausible degradation mechanisms described and analyzed as they may affect the concrete, reinforcing steel, containment steel shell, prestressed-tendon, steel liner and other structural components typically used in Class I structures. The significance of these age-related degradation mechanisms to the structural components are evaluated, giving consideration to the design basis and quality of construction; typical service conditions; operating and maintenance history; and current test, inspection and refurbishment practices for containment and Class I structures. Degradation mechanisms which cannot be generically dispositioned on the basis of the two-step approach: (1) they will not cause significant degradation, or (2) any potential degradation will be bounded by current test, inspection, analytical evaluation, and/or refurbishment programs are identified. Aging degradation management measures are recommended to address the remaining age-related degradation mechanisms. A three-phase approach for the management of the containment and Class I structures is introduced. Various techniques, testing tools and the acceptable criteria for each step of the evaluation of the structures status are provided. The preventive and mitigative

  14. Effects of chronic estrogen treatment on modulating age-related bone loss in female mice.

    Science.gov (United States)

    Syed, Farhan A; Mödder, Ulrike Il; Roforth, Matthew; Hensen, Ira; Fraser, Daniel G; Peterson, James M; Oursler, Merry Jo; Khosla, Sundeep

    2010-11-01

    While female mice do not have the equivalent of a menopause, they do undergo reproductive senescence. Thus, to dissociate the effects of aging versus estrogen deficiency on age-related bone loss, we sham-operated, ovariectomized, or ovariectomized and estrogen-replaced female C57/BL6 mice at 6 months of age and followed them to age 18 to 22 months. Lumbar spines and femurs were excised for analysis, and bone marrow hematopoietic lineage negative (lin-) cells (enriched for osteoprogenitor cells) were isolated for gene expression studies. Six-month-old intact control mice were euthanized to define baseline parameters. Compared with young mice, aged/sham-operated mice had a 42% reduction in lumbar spine bone volume/total volume (BV/TV), and maintaining constant estrogen levels over life in ovariectomized/estrogen-treated mice did not prevent age-related trabecular bone loss at this site. By contrast, lifelong estrogen treatment of ovariectomized mice completely prevented the age-related reduction in cortical volumetric bone mineral density (vBMD) and thickness at the tibial diaphysis present in the aged/sham-operated mice. As compared with cells from young mice, lin- cells from aged/sham-operated mice expressed significantly higher mRNA levels for osteoblast differentiation and proliferation marker genes. These data thus demonstrate that, in mice, age-related loss of cortical bone in the appendicular skeleton, but not loss of trabecular bone in the spine, can be prevented by maintaining constant estrogen levels over life. The observed increase in osteoblastic differentiation and proliferation marker gene expression in progenitor bone marrow cells from aged versus young mice may represent a compensatory mechanism in response to ongoing bone loss. PMID:20499336

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

    Directory of Open Access Journals (Sweden)

    Ramya eVajapey

    2014-11-01

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

  16. Age-related differences in memory-encoding fMRI responses after accounting for decline in vascular reactivity.

    Science.gov (United States)

    Liu, Peiying; Hebrank, Andrew C; Rodrigue, Karen M; Kennedy, Kristen M; Section, Jarren; Park, Denise C; Lu, Hanzhang

    2013-09-01

    BOLD fMRI has provided a wealth of information about the aging brain. A common finding is that posterior regions of the brain manifest an age-related decrease in activation while the anterior regions show an age-related increase. Several neurocognitive models have been proposed to interpret these findings. However, one issue that has not been sufficiently considered to date is that the BOLD signal is based on vascular responses secondary to neural activity. Thus the above findings could be in part due to a vascular change, especially in view of the expected decline of vascular health with age. In the present study, we aim to examine age-related differences in memory-encoding fMRI response in the context of vascular aging. One hundred and thirty healthy subjects ranging from 20 to 89 years old underwent a scene-viewing fMRI task and, in the same session, cerebrovascular reactivity (CVR) was measured in each subject using a CO2-inhalation task. Without accounting for the influence of vascular changes, the task-activated fMRI signal showed the typical age-related decrease in visual cortex and medial temporal lobe (MTL), but manifested an increase in the right inferior frontal gyrus (IFG). In the same individuals, an age-related CVR reduction was observed in all of these regions. We then used a previously proposed normalization approach to calculate a CVR-corrected fMRI signal, which was defined as the uncorrected signal divided by CVR. Based on the CVR-corrected fMRI signal, an age-related increase is now seen in both the left and right sides of IFG; and no brain regions showed a signal decrease with age. We additionally used a model-based approach to examine the fMRI data in the context of CVR, which again suggested an age-related change in the two frontal regions, but not in the visual and MTL regions.

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

    Science.gov (United States)

    Johnson, M A; Choy, D

    1987-04-15

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

  18. The theory behind the age-related positivity effect

    Directory of Open Access Journals (Sweden)

    Andrew E Reed

    2012-09-01

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

  19. Ocular Surface Temperature in Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Andrea Sodi

    2014-01-01

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

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

    Science.gov (United States)

    Chakravarti, Bulbul; Chakravarti, Deb N

    2007-01-01

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

  1. Eye Conditions in Older Adults: Age-Related Macular Degeneration.

    Science.gov (United States)

    Iroku-Malize, Tochi; Kirsch, Scott

    2016-06-01

    Age-related macular degeneration (AMD) causes a progressive loss of photoreceptors in the macula. It is the most common cause of legal blindness in the United States, and some form of AMD is thought to affect more than 9 million individuals. Risk factors include older age, smoking, dyslipidemia, obesity, white race, female sex, and a family history of AMD. There are two types of advanced AMD: nonexudative (dry or geographic atrophy) and exudative (wet or neovascular). Both cause progressive central vision loss with intact peripheral vision. Nonexudative AMD accounts for 80% to 90% of all advanced cases, and more than 90% of patients with severe vision loss have exudative AMD. On ophthalmoscopic examination, early findings include drusen (ie, yellow deposits in the retina). Prominent choroidal vessels, subretinal edema, and/or hemorrhage are seen in wet AMD. Regular eye examinations, visual field testing, fluorescein angiography, and optical coherence tomography are used for diagnosis and to guide management. There is no specific therapy for dry AMD, but antioxidant supplementation may be helpful. Intravitreal injection of a vascular endothelial growth factor inhibitor is the treatment of choice for wet AMD. Optical aids and devices can help to maximize function for patients with AMD. PMID:27348529

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

    Science.gov (United States)

    Scheerer, Nichole; Marrone, Diano F.

    2014-01-01

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

  3. Cellular models and therapies for age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    David L. Forest

    2015-05-01

    Full Text Available Age-related macular degeneration (AMD is a complex neurodegenerative visual disorder that causes profound physical and psychosocial effects. Visual impairment in AMD is caused by the loss of retinal pigmented epithelium (RPE cells and the light-sensitive photoreceptor cells that they support. There is currently no effective treatment for the most common form of this disease (dry AMD. A new approach to treating AMD involves the transplantation of RPE cells derived from either human embryonic or induced pluripotent stem cells. Multiple clinical trials are being initiated using a variety of cell therapies. Although many animal models are available for AMD research, most do not recapitulate all aspects of the disease, hampering progress. However, the use of cultured RPE cells in AMD research is well established and, indeed, some of the more recently described RPE-based models show promise for investigating the molecular mechanisms of AMD and for screening drug candidates. Here, we discuss innovative cell-culture models of AMD and emerging stem-cell-based therapies for the treatment of this vision-robbing disease.

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

    Science.gov (United States)

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

    2016-04-01

    Triple-negative breast cancer is a type of breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER-2). It is an important and clinically relevant condition as it has a poor prognosis and is difficult to treat. Basal-like triple-negative cancer is highly prevalent in both African-Americans and adolescents. We therefore examined whether such a cancer likewise occurs in specific breeds and age groups in dogs, focusing on basal-like triple-negative cancer in particular. In this study, 181 samples from dogs with malignant mammary carcinoma from the 5 most common breeds and 2 age groups in Korea were analyzed. Histological classification and molecular subtyping, including assessment of immunohistochemical findings, were carried out. Twenty-five of 28 (89.3%) triple-negative carcinomas were identified as basal-like triple-negative carcinomas. Analysis of associations of classified factors revealed that the shih tzu breed (9/25, 36.0%) and advanced-age (19/25, 76.0%) groups were characterized by higher prevalence of basal-like triple-negative tumors with diverse histological types and of a higher grade. These results suggest that breed- and age-related differences can be identified in canine mammary carcinoma and, notably, in the shih tzu breed and at older ages. Further investigation of these distinguishing characteristics of the shih tzu breed is warranted. PMID:27127342

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

    Science.gov (United States)

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

    2000-12-01

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

  6. Age-related cerebral white matter changes on computed tomography

    International Nuclear Information System (INIS)

    Changes of cerebral white matter on computed cranial tomography related to aging were studied in 70 subjects aged 30 to 94 years. The subjects had no histories of cerebrovascular accidents and no abnormalities in the central nervous system were shown by physical examinations and CT scans. We measured the average attenuation values (CT numbers) of each elliptical region (165 pixels, 0.39cm2) in the bilateral thalamus and twelve areas of deep white matter. Multiple regression analysis was used to assess the effects of age, cranial size and cranial bone CT numbers on the brain CT numbers. We also studied the association between brain CT numbers and brain atrophy, hypertension, diabetes mellitus. CT numbers of frontal white matter surrounding anterior horns decreased with aging in 70 subjects aged 30 to 94 years. No significant correlation between age and brain CT numbers was found in any other region by multivariate analysis, because of the prominent effect of cranial bone CT numbers on brain CT numbers. Although no age-related changes of white matter CT numbers was found in 41 subjects aged 30 to 65 years, there were significant negative correlations between age and white matter CT numbers at all regions in 29 subjects aged 66 to 94 years. Brain atrophy was associated with brain CT numbers. No association was found for hypertension or diabetes mellitus. Brain CT numbers decreased with aging even in neurologically healthy persons in older age. Brain CT numbers also decreased as cerebral atrophy advanced. (author)

  7. Age-related cerebral white matter changes on computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Fukuda, Hitoshi; Kobayashi, Shotai; Koide, Hiromi; Yamaguchi, Shuhei; Okada, Kazunori; Shimote, Kouichi; Tsunematsu, Tokugoro

    1989-01-01

    Changes of cerebral white matter on computed cranial tomography related to aging were studied in 70 subjects aged 30 to 94 years. The subjects had no histories of cerebrovascular accidents and no abnormalities in the central nervous system were shown by physical examinations and CT scans. We measured the average attenuation values (CT numbers) of each elliptical region (165 pixels, 0.39cm/sup 2/) in the bilateral thalamus and twelve areas of deep white matter. Multiple regression analysis was used to assess the effects of age, cranial size and cranial bone CT numbers on the brain CT numbers. We also studied the association between brain CT numbers and brain atrophy, hypertension, diabetes mellitus. CT numbers of frontal white matter surrounding anterior horns decreased with aging in 70 subjects aged 30 to 94 years. No significant correlation between age and brain CT numbers was found in any other region by multivariate analysis, because of the prominent effect of cranial bone CT numbers on brain CT numbers. Although no age-related changes of white matter CT numbers was found in 41 subjects aged 30 to 65 years, there were significant negative correlations between age and white matter CT numbers at all regions in 29 subjects aged 66 to 94 years. Brain atrophy was associated with brain CT numbers. No association was found for hypertension or diabetes mellitus. Brain CT numbers decreased with aging even in neurologically healthy persons in older age. Brain CT numbers also decreased as cerebral atrophy advanced. (author).

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

    Directory of Open Access Journals (Sweden)

    K. A. Mirzabekova

    2014-01-01

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

  9. DNA damage and repair in age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Szaflik, Jacek P. [Department of Ophthalmology, Medical University of Warsaw and Samodzielny Publiczny Szpital Okulistyczny, Sierakowskiego 13, 03-710 Warsaw (Poland); Janik-Papis, Katarzyna; Synowiec, Ewelina; Ksiazek, Dominika [Department of Molecular Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland); Zaras, Magdalena [Department of Ophthalmology, Medical University of Warsaw and Samodzielny Publiczny Szpital Okulistyczny, Sierakowskiego 13, 03-710 Warsaw (Poland); Wozniak, Katarzyna [Department of Molecular Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland); Szaflik, Jerzy [Department of Ophthalmology, Medical University of Warsaw and Samodzielny Publiczny Szpital Okulistyczny, Sierakowskiego 13, 03-710 Warsaw (Poland); Blasiak, Janusz, E-mail: januszb@biol.uni.lodz.pl [Department of Molecular Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz (Poland)

    2009-10-02

    Age-related macular degeneration (AMD) is a retinal degenerative disease that is the main cause of vision loss in individuals over the age of 55 in the Western world. Clinically relevant AMD results from damage to the retinal pigment epithelial (RPE) cells thought to be mainly caused by oxidative stress. The stress also affects the DNA of RPE cells, which promotes genome instability in these cells. These effects may coincide with the decrease in the efficacy of DNA repair with age. Therefore individuals with DNA repair impaired more than average for a given age may be more susceptible to AMD if oxidative stress affects their RPE cells. This may be helpful in AMD risk assessment. In the present work we determined the level of basal (measured in the alkaline comet assay) endogenous and endogenous oxidative DNA damage, the susceptibility to exogenous mutagens and the efficacy of DNA repair in lymphocytes of 100 AMD patients and 110 age-matched individuals without visual disturbances. The cells taken from AMD patients displayed a higher extent of basal endogenous DNA damage without differences between patients of dry and wet forms of the disease. DNA double-strand breaks did not contribute to the observed DNA damage as checked by the neutral comet assay and pulsed field gel electrophoresis. The extent of oxidative modification to DNA bases was grater in AMD patients than in the controls, as probed by DNA repair enzymes NTH1 and Fpg. Lymphocytes from AMD patients displayed a higher sensitivity to hydrogen peroxide and UV radiation and repaired lesions induced by these factors less effectively than the cells from the control individuals. We postulate that the impaired efficacy of DNA repair may combine with enhanced sensitivity of RPE cells to blue and UV lights, contributing to the pathogenesis of AMD.

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

    Directory of Open Access Journals (Sweden)

    K. A. Mirzabekova

    2014-07-01

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

  11. Age-related distribution of vertebral bone-marrow diffusivity

    International Nuclear Information System (INIS)

    Purpose: To determine age-related diffusivity changes of the lumbar bone marrow by measurement of apparent diffusion coefficient (ADC) values. Materials and methods: The local ethics committee approved this study and written informed consent was obtained. The study group comprised 88 individuals including 75 healthy volunteers and 13 patients (48 female, 40 male; mean age 36 years, range 0–84 years). The pediatric cases were recruited from patients. Echo-planar diffusion weighted imaging (DWI) was performed with b-values of 50, 400 and 800 s/mm2. ADC-values were calculated and measured in the 1st and 2nd vertebral body of the lumbar spine. Correlation between age and ADC-values was analyzed with Spearman's rho test. Results: The ADC values of the vertebral bone marrow of the lumbar spine showed a significant negative correlation with age (rho = −0.398, p = 0.001). The mean ADC values (×10−3 mm2/s) in the age groups 0–29 years (mean age 18.0 years, n = 42) and 30–88 years (mean age 51.6 years, n = 46) were 0.54 ± 0.07 and 0.47 ± 0.08, respectively (p < 0.001, T-test). No significant differences were found between children and young adults. Conclusion: Bone marrow ADC values of the lumbar spine show a linear decrease with growing age and thereby reflect the gradual changes of cell composition occurring during marrow conversion.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Hendrik P N Scholl

    Full Text Available Dysregulation of the alternative pathway (AP of complement cascade has been implicated in the pathogenesis of age-related macular degeneration (AMD, the leading cause of blindness in the elderly. To further test the hypothesis that defective control of complement activation underlies AMD, parameters of complement activation in blood plasma were determined together with disease-associated genetic markers in AMD patients. Plasma concentrations of activation products C3d, Ba, C3a, C5a, SC5b-9, substrate proteins C3, C4, factor B and regulators factor H and factor D were quantified in patients (n = 112 and controls (n = 67. Subjects were analyzed for single nucleotide polymorphisms in factor H (CFH, factor B-C2 (BF-C2 and complement C3 (C3 genes which were previously found to be associated with AMD. All activation products, especially markers of chronic complement activation Ba and C3d (p<0.001, were significantly elevated in AMD patients compared to controls. Similar alterations were observed in factor D, but not in C3, C4 or factor H. Logistic regression analysis revealed better discriminative accuracy of a model that is based only on complement activation markers Ba, C3d and factor D compared to a model based on genetic markers of the complement system within our study population. In both the controls' and AMD patients' group, the protein markers of complement activation were correlated with CFH haplotypes.This study is the first to show systemic complement activation in AMD patients. This suggests that AMD is a systemic disease with local disease manifestation at the ageing macula. Furthermore, the data provide evidence for an association of systemic activation of the alternative complement pathway with genetic variants of CFH that were previously linked to AMD susceptibility.

  14. Age-related changes in brain structural covariance networks

    Directory of Open Access Journals (Sweden)

    Xinwei eLi

    2013-03-01

    Full Text Available Previous neuroimaging studies have suggested that cerebral changes over normal aging are not simply characterized by regional alterations, but rather by the reorganization of cortical connectivity patterns. The investigation of structural covariance networks (SCNs using voxel-based morphometry is an advanced approach to examining the pattern of covariance in gray matter volumes among different regions of the human cortex. To date, how the organization of critical SCNs change during normal aging remains largely unknown. In this study, we used an SCN mapping approach to investigate eight large-scale networks in 240 healthy participants aged 18–89 years. These participants were subdivided into young (18–23 years, middle aged (30–58 years, and older (61–89 years subjects. Eight seed regions were chosen from widely reported functional intrinsic connectivity networks. The voxels showing significant positive associations with these seed regions were used to describe the topological organization of an SCN. All of these networks exhibited non-linear patterns in their spatial extent that were associated with normal aging. These networks, except the primary motor network, had a distributed topology in young participants, a sharply localized topology in middle aged participants, and were relatively stable in older participants. The structural covariance derived using the primary motor cortex was limited to the ipsilateral motor regions in the young and older participants, but included contralateral homologous regions in the middle aged participants. In addition, there were significant between-group differences in the structural networks associated with language-related speech and semantics processing, executive control, and the default-mode network. Taken together, the results of this study demonstrate age-related changes in the topological organization of SCNs, and provide insights into normal aging of the human brain.

  15. Age-Related Macular Degeneration: Genetics and Biology.

    Science.gov (United States)

    Kumaramanickavel, Govindasamy

    2016-01-01

    Age-related macular degeneration (AMD), widely prevalent across the globe, is a major stakeholder among adult visual morbidity and blindness, not only in the Western world but also in Asia. Several risk factors have been identified, including critical genetic factors, which were never imagined 2 decades ago. The etiopathogenesis is emerging to demonstrate that immune and complement-related inflammation pathway members chronically exposed to environmental insults could justifiably influence disease morbidity and treatment outcomes. Approximately half a dozen physiological and biochemical cascades are disrupted in the AMD disease genesis, eventually leading to the distortion and disruption of the subretinal space, subretinal pigment epithelium, and Bruch membrane, thus setting off chaos and disorder for signs and symptoms to manifest. Approximately 3 dozen genetic factors have so far been identified, including the recent ones, through powerful genomic technologies and large robust sample sizes. The noteworthy genetic variants (common and rare) are complement factor H, complement factor H-related genes 1 to 5, C3, C9, ARMS2/HTRA1, vascular endothelial growth factor A, vascular endothelial growth factor receptor 2/KDR, and rare variants (show causal link) such as TIMP3, fibrillin, COL4A3, MMP19, and MMP9. Despite the enormous amount of scientific information generated over the years, diagnostic genetic or biomarker tests are still not available for clinicians to understand the natural course of the disease and its management in a patient. However, further research in the field should reduce this gap not only by aiding the clinician but also through the possibilities of clinical intervention with complement pathway-related inhibitors entering preclinical and clinical trials in the near future. PMID:27488064

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

    Directory of Open Access Journals (Sweden)

    Felix Grassmann

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

  17. Age Related Macular Degeneration and Total Hip Replacement Due to Osteoarthritis or Fracture: Melbourne Collaborative Cohort Study.

    Directory of Open Access Journals (Sweden)

    Elaine W Chong

    Full Text Available Osteoarthritis is the leading cause of total hip replacement, accounting for more than 80% of all total hip replacements. Emerging evidence suggests that osteoarthritis has a chronic inflammatory component to its pathogenesis similar to age-related macular degeneration. We evaluated the association between age-related macular degeneration and total hip replacement as proxy for severe osteoarthritis or fractured neck of femur in the Melbourne Collaborative Cohort Study. 20,744 participants had complete data on both age-related macular degeneration assessed from colour fundus photographs taken during 2003-2007 and total hip replacement. Total hip replacements due to hip osteoarthritis and fractured neck of femur during 2001-2011 were identified by linking the cohort records to the Australian Orthopedic Association National Joint Replacement Registry. Logistic regression was used to examine the association between age-related macular degeneration and risk of total hip replacement due to osteoarthritis and fracture separately, adjusted for confounders. There were 791 cases of total hip replacement for osteoarthritis and 102 cases of total hip replacement due to fractured neck of femur. After adjustment for age, sex, body mass index, smoking, and grouped country of birth, intermediate age-related macular degeneration was directly associated with total hip replacement for osteoarthritis (odds ratio 1.22, 95% CI 1.00-1.49. Late age-related macular degeneration was directly associated with total hip replacement due to fractured neck of femur (odds ratio 5.21, 95% CI2.25-12.02. The association between intermediate age-related macular degeneration and an increased 10-year incidence of total hip replacement due to osteoarthritis suggests the possibility of similar inflammatory processes underlying both chronic diseases. The association of late age-related macular degeneration with an increased 10-year incidence of total hip replacement due to fractured

  18. Functional behavior of bio-electrochemical treatment system with increasing azo dye concentrations: Synergistic interactions of biocatalyst and electrode assembly.

    Science.gov (United States)

    Sreelatha, S; Velvizhi, G; Naresh Kumar, A; Venkata Mohan, S

    2016-08-01

    Treatment of dye bearing wastewater through biological machinery is particularly challenging due to its recalcitrant and inhibitory nature. In this study, functional behavior and treatment efficiency of bio-electrochemical treatment (BET) system was evaluated with increasing azo dye concentrations (100, 200, 300 and 500mg dye/l). Maximum dye removal was observed at 300mg dye/l (75%) followed by 200mg dye/l (65%), 100mg dye/l (62%) and 500mg dye/l (58%). Concurrent increment in dye load resulted in enhanced azo reductase and dehydrogenase activities respectively (300mg dye/l: 39.6U; 4.96μg/ml). Derivatives of cyclic voltammograms also supported the involvement of various membrane bound redox shuttlers, viz., cytochrome-c, cytochrome-bc1 and flavoproteins during the electron transfer. Bacterial respiration during BET operation utilized various electron acceptors such as electrodes and dye intermediates with simultaneous bioelectricity generation. This study illustrates the synergistic interaction of biocatalyst with electrode assembly for efficient treatment of azo dye wastewater. PMID:27067459

  19. Age-related decline in functional connectivity of the vestibular cortical network.

    Science.gov (United States)

    Cyran, Carolin Anna Maria; Boegle, Rainer; Stephan, Thomas; Dieterich, Marianne; Glasauer, Stefan

    2016-04-01

    In the elderly, major complaints include dizziness and an increasing number of falls, possibly related to an altered processing of vestibular sensory input. In this study, we therefore investigate age-related changes induced by processing of vestibular sensory stimulation. While previous functional imaging studies of healthy aging have investigated brain function during task performance or at rest, we used galvanic vestibular stimulation during functional MRI in a task-free sensory stimulation paradigm to study the effect of healthy aging on central vestibular processing, which might only become apparent during stimulation processing. Since aging may affect signatures of brain function beyond the BOLD-signal amplitude-such as functional connectivity or temporal signal variability-we employed independent component analysis and partial least squares analysis of temporal signal variability. We tested for age-associated changes unrelated to vestibular processing, using a motor paradigm, voxel-based morphometry and diffusion tensor imaging. This allows us to control for general age-related modifications, possibly originating from vascular, atrophic or structural connectivity changes. Age-correlated decreases of functional connectivity and increases of BOLD-signal variability were associated with multisensory vestibular networks. In contrast, no age-related functional connectivity changes were detected in somatosensory networks or during the motor paradigm. The functional connectivity decrease was not due to structural changes but to a decrease in response amplitude. In synopsis, our data suggest that both the age-dependent functional connectivity decrease and the variability increase may be due to deteriorating reciprocal cortico-cortical inhibition with age and related to multimodal vestibular integration of sensory inputs. PMID:25567421

  20. The Association between Plasma 25-Hydroxyvitamin D and Subgroups in Age-Related Macular Degeneration

    DEFF Research Database (Denmark)

    Singh, Amardeep; Falk, Mads Krüger; Subhi, Yousif;

    2013-01-01

    To evaluate potential differences in plasma 25-hydroxyvitamin in subtypes of age-related macular degeneration (AMD), and in patients in Clinical Age-Related Maculopathy Staging (CARMS) group 5 with or without subretinal fibrosis....

  1. 14-year incidence, progression, and visual morbidity of age-related maculopathy

    DEFF Research Database (Denmark)

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

    2005-01-01

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

  2. Brain protein oxidation in age-related neurodegenerative disorders that are associated with aggregated proteins.

    Science.gov (United States)

    Butterfield, D A; Kanski, J

    2001-07-15

    Protein oxidation, one of a number of brain biomarkers of oxidative stress, is increased in several age-related neurodegenerative disorders or animal models thereof, including Alzheimer's disease, Huntington's disease, prion disorders, such as Creutzfeld-Jakob disease, and alpha-synuclein disorders, such as Parkinson's disease and frontotemporal dementia. Each of these neurodegenerative disorders is associated with aggregated proteins in brain. However, the relationship among protein oxidation, protein aggregation, and neurodegeneration remain unclear. The current rapid progress in elucidation of mechanisms of protein oxidation in neuronal loss should provide further insight into the importance of free radical oxidative stress in these neurodegenerative disorders.

  3. Visual outcomes in relation to time to treatment in neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Rasmussen, Annette; Bloch, Sara Brandi; Fuchs, Josefine;

    2015-01-01

    within the range 0.23-0.24 Snellen and the median patient age within 79-80 years, whereas BCVA at first visit after the third injection increased from 0.24 to 0.31 (p ...PURPOSE: To study the relation between the interval from diagnosis to initiation of intravitreal injection therapy and visual outcome in neovascular age-related macular degeneration (nAMD) and to report changes over time in fellow-eye status. METHODS: Retrospective chart review. The study included...

  4. Age-related differences in recall for words using semantics and prosody.

    Science.gov (United States)

    Sober, Jonathan D; VanWormer, Lisa A; Arruda, James E

    2016-01-01

    The positivity effect is a developmental shift seen in older adults to be increasingly influenced by positive information in areas such as memory, attention, and decision-making. This study is the first to examine the age-related differences of the positivity effect for emotional prosody. Participants heard a factorial combination of words that were semantically positive or negative said with either positive or negative intonation. Results showed a semantic positivity effect for older adults, and a prosody positivity effect for younger adults. Additionally, older adults showed a significant decrease in recall for semantically negative words said in an incongruent prosodically positive tone.

  5. Female CREBαδ- deficient mice show earlier age-related cognitive deficits than males

    OpenAIRE

    Hebda-Bauer, Elaine K.; Luo, Jie; Watson, Stanley J.; Akil, Huda

    2007-01-01

    Age-related changes in the hippocampus increase vulnerability to impaired learning and memory. Our goal is to understand how a genetic vulnerability to cognitive impairment can be modified by aging and sex. Mice with a mutation in the cAMP response element binding (CREB) protein gene (CREBαδ- deficient mice) have a mild cognitive impairment and show test condition-dependent learning and memory deficits. We tested 3 ages of CREBαδ- deficient and wild-type (WT) mice in 2 Morris water maze (MWM)...

  6. Age-related differences in recall for words using semantics and prosody.

    Science.gov (United States)

    Sober, Jonathan D; VanWormer, Lisa A; Arruda, James E

    2016-01-01

    The positivity effect is a developmental shift seen in older adults to be increasingly influenced by positive information in areas such as memory, attention, and decision-making. This study is the first to examine the age-related differences of the positivity effect for emotional prosody. Participants heard a factorial combination of words that were semantically positive or negative said with either positive or negative intonation. Results showed a semantic positivity effect for older adults, and a prosody positivity effect for younger adults. Additionally, older adults showed a significant decrease in recall for semantically negative words said in an incongruent prosodically positive tone. PMID:26786734

  7. Age relations of cardiovascular risk factors in a traditional Melanesian society: the Kitava Study.

    Science.gov (United States)

    Lindeberg, S; Berntorp, E; Nilsson-Ehle, P; Terént, A; Vessby, B

    1997-10-01

    This study examined cross-sectional age relations of blood pressure, anthropometric indexes, serum lipids, and hemostatic variables in 203 subsistence horticulturists aged 20-86 y in Kitava, Trobriand Islands, Papua New Guinea. The population is characterized by extreme leanness (despite food abundance), low blood pressure, low plasma plasminogen activator inhibitor 1 activity, and rarity of cardiovascular disease. Tubers, fruit, fish, and coconut are dietary staples whereas dairy products, refined fat and sugar, cereals, and alcohol are absent and salt intake is low. Although diastolic blood pressure was not associated with age in Kitavans, systolic blood pressure increased linearly after 50 y of age in both sexes. Body mass index decreased with age in both sexes. Serum total cholesterol, triacylglycerol, low-density-lipoprotein cholesterol, and apolipoprotein B increased in males between 20 and 50 y of age, whereas high-density-lipoprotein cholesterol and apolipoprotein A-I decreased. There were no significant differences in these indexes with age in the few females studied. A slight linear age-related increase of lipoprotein(a) was present in males. Plasma fibrinogen, factor VII clotting activity, factor VIII clotting activity, and von Willebrand factor antigen increased with age in both sexes but plasminogen activator inhibitor 1 activity did not. The modest or absent relations between the indexes measured and age are apparently important explanations of the virtual nonexistence of stroke and ischemic heart disease in Kitava.

  8. Dynamical network model for age-related health deficits and mortality

    Science.gov (United States)

    Taneja, Swadhin; Mitnitski, Arnold B.; Rockwood, Kenneth; Rutenberg, Andrew D.

    2016-02-01

    How long people live depends on their health, and how it changes with age. Individual health can be tracked by the accumulation of age-related health deficits. The fraction of age-related deficits is a simple quantitative measure of human aging. This quantitative frailty index (F ) is as good as chronological age in predicting mortality. In this paper, we use a dynamical network model of deficits to explore the effects of interactions between deficits, deficit damage and repair processes, and the connection between the F and mortality. With our model, we qualitatively reproduce Gompertz's law of increasing human mortality with age, the broadening of the F distribution with age, the characteristic nonlinear increase of the F with age, and the increased mortality of high-frailty individuals. No explicit time-dependence in damage or repair rates is needed in our model. Instead, implicit time-dependence arises through deficit interactions—so that the average deficit damage rates increase, and deficit repair rates decrease, with age. We use a simple mortality criterion, where mortality occurs when the most connected node is damaged.

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

    OpenAIRE

    Blagosklonny, Mikhail V.

    2009-01-01

    Humans die from age-related diseases, which are deadly manifestations of the aging process. In order to extend life span, an anti-aging drug must delay age-related diseases. All together age-related diseases are the best biomarker of aging. Once a drug is used for treatment of any one chronic disease, its effect against other diseases (atherosclerosis, cancer, prostate enlargement, osteoporosis, insulin resistance, Alzheimer's and Parkinson's diseases, age-related macular degeneration) may be...

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

  12. The age-related deficit in LTP is associated with changes in perfusion and blood-brain barrier permeability.

    Science.gov (United States)

    Blau, Christoph W; Cowley, Thelma R; O'Sullivan, Joan; Grehan, Belinda; Browne, Tara C; Kelly, Laura; Birch, Amy; Murphy, Niamh; Kelly, Aine M; Kerskens, Christian M; Lynch, Marina A

    2012-05-01

    In view of the increase in the aging population and the unavoidable parallel increase in the incidence of age-related neurodegenerative diseases, a key challenge in neuroscience is the identification of clinical signatures which change with age and impact on neuronal and cognitive function. Early diagnosis offers the possibility of early therapeutic intervention, thus magnetic resonance imaging (MRI) is potentially a powerful diagnostic tool. We evaluated age-related changes in relaxometry, blood flow, and blood-brain barrier (BBB) permeability in the rat by magnetic resonance imaging and assessed these changes in the context of the age-related decrease in synaptic plasticity. We report that T2 relaxation time was decreased with age; this was coupled with a decrease in gray matter perfusion, suggesting that the observed microglial activation, as identified by increased expression of CD11b, MHCII, and CD68 by immunohistochemistry, flow cytometry, or polymerase chain reaction (PCR), might be a downstream consequence of these changes. Increased permeability of the blood-brain barrier was observed in the perivascular area and the hippocampus of aged, compared with young, rats. Similarly there was an age-related increase in CD45-positive cells by flow cytometry, which are most likely infiltrating macrophages, with a parallel increase in the messenger mRNA expression of chemokines IP-10 and MCP-1. These combined changes may contribute to the deficit in long-term potentiation (LTP) in perforant path-granule cell synapses of aged animals.

  13. Lipids, Lipid Genes and Incident Age-Related Macular Degeneration: The Three Continent Age-Related Macular Degeneration Consortium

    Science.gov (United States)

    Klein, Ronald; Myers, Chelsea E.; Buitendijk, Gabriëlle H. S.; Rochtchina, Elena; Gao, Xiaoyi; de Jong, Paulus T. V. M.; Sivakumaran, Theru A.; Burlutsky, George; McKean-Cowdin, Roberta; Hofman, Albert; Iyengar, Sudha K.; Lee, Kristine E.; Stricker, Bruno H.; Vingerling, Johannes R.; Mitchell, Paul; Klein, Barbara E. K.; Klaver, Caroline C. W.; Wang, Jie Jin

    2014-01-01

    Purpose To describe associations of serum lipid levels and lipid pathway genes to the incidence of age-related macular degeneration (AMD). Design Meta-analysis. Methods Setting Three population-based cohorts. Population 6950 participants from the Beaver Dam Eye Study (BDES), Blue Mountains Eye Study (BMES) and Rotterdam Study (RS). Observation Procedures Participants were followed over 20 years and examined at 5-year intervals. Hazard ratios (HRs) associated with lipid levels per standard deviation above the mean or associated with each additional risk allele for each lipid pathway gene were calculated using random-effects inverse-weighted meta-analysis models, adjusting for known AMD risk factors. Main Outcome Measures Incidence of AMD. Results The average 5-year incidences of early AMD were 8.1%, 15.1%, and 13.0% in the BDES, BMES, and RS, respectively. Substantial heterogeneity in the effect of cholesterol and lipid pathway genes on the incidence and progression of AMD was evident when the data from the three studies were combined in meta-analysis. After correction for multiple comparisons, we did not find a statistically significant association between any of the cholesterol measures, statin use, or serum lipid genes and any of the AMD outcomes in the meta-analysis. Conclusion In a meta-analysis, there were no associations of cholesterol measures, history of statin use, or lipid pathway genes to the incidence and progression of AMD. These findings add to inconsistencies in earlier reports from our studies and others showing weak associations, no associations, or inverse associations of high-density lipoprotein cholesterol and total cholesterol with AMD. PMID:24879949

  14. Ayurvedic Drugs in Prevention and Management of Age Related Cognitive Decline: A Review

    Directory of Open Access Journals (Sweden)

    Satyendra Kumar Tiwari

    2012-07-01

    Full Text Available Age related cognitive decline is a term reserved for abnormal cognitive function less severe than dementia in person older than 50. It is considered as a prior condition to senile dementia. The term dementia signifies cognitive deterioration so severe that social and occupational functioning of an individual is markedly impaired to such an extent that he can no longer remain a fully independent and productive citizen. As the disease progresses, the personality of an individual also changes and subsequently, social withdrawal take a hold. Advanced dementia is characterized by progressive loss of personality and increasing disability to perform even a simplest task. According to World Health Organization, it is estimated that 5% of men and 6% of women of above 60 years of age affected with Alzheimer’s type of dementia worldwide. According to Alzheimer’s Disease International there are 35.6 million people living with dementia worldwide in 2010, increasing to 65.7 million by 2030 and 115.4 million by 2050. Degeneration of the cerebral neurons is one of the commonest and important causes of dementia with advancing age which leads to deterioration of quality of life in elderly. Therefore it is of prime importance to curb this progress of cognitive decline before it crosses the threshold to dementia. Ayuveda is full of evidences regarding use of single drugs or formulations in age related cognitive decline. The drugs either mentioned as Medhya rasayanas specifically or other having Medhya activity can be potentially used for prevention and management of age related cognitive decline.

  15. Innate immunity and inflammation in ageing: a key for understanding age-related diseases

    Directory of Open Access Journals (Sweden)

    Colonna-Romano Giuseppina

    2005-05-01

    Full Text Available Abstract The process of maintaining life for the individual is a constant struggle to preserve his/her integrity. This can come at a price when immunity is involved, namely systemic inflammation. Inflammation is not per se a negative phenomenon: it is the response of the immune system to the invasion of viruses or bacteria and other pathogens. During evolution the human organism was set to live 40 or 50 years; today, however, the immune system must remain active for much a longer time. This very long activity leads to a chronic inflammation that slowly but inexorably damages one or several organs: this is a typical phenomenon linked to ageing and it is considered the major risk factor for age-related chronic diseases. Alzheimer's disease, atherosclerosis, diabetes and even sarcopenia and cancer, just to mention a few – have an important inflammatory component, though disease progression seems also dependent on the genetic background of individuals. Emerging evidence suggests that pro-inflammatory genotypes are related to unsuccessful ageing, and, reciprocally, controlling inflammatory status may allow a better chance of successful ageing. In other words, age-related diseases are "the price we pay" for a life-long active immune system: this system has also the potential to harm us later, as its fine tuning becomes compromised. Our immune system has evolved to control pathogens, so pro-inflammatory responses are likely to be evolutionarily programmed to resist fatal infections with pathogens aggressively. Thus, inflammatory genotypes are an important and necessary part of the normal host responses to pathogens in early life, but the overproduction of inflammatory molecules might also cause immune-related inflammatory diseases and eventually death later. Therefore, low responder genotypes involved in regulation of innate defence mechanisms, might better control inflammatory responses and age-related disease development, resulting in an increased

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

    Science.gov (United States)

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

    2015-12-01

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

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

    Science.gov (United States)

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

    2006-06-01

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

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

    Science.gov (United States)

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

    2015-12-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2013-01-01

    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.

  1. Enriched Childhood Experiences Moderate Age-related Motor and Cognitive Decline

    Directory of Open Access Journals (Sweden)

    Megan J. Metzler

    2013-02-01

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

  2. Age-Related Increase in Inferior Frontal Gyrus Activity and Social Functioning in Autism Spectrum Disorder

    NARCIS (Netherlands)

    Bastiaansen, Jojanneke A.; Thioux, Marc; Nanetti, Luca; van der Gaag, Christiaan; Ketelaars, Cees; Minderaa, Ruud; Keysers, Christian

    2011-01-01

    Background: Hypoactivation of the inferior frontal gyrus during the perception of facial expressions has been interpreted as evidence for a deficit of the mirror neuron system in children with autism. We examined whether this dysfunction persists in adulthood, and how brain activity in the mirror ne

  3. Age-related decline in metabolic competence of small and medium-sized synaptic mitochondria

    Science.gov (United States)

    Bertoni-Freddari, Carlo; Fattoretti, Patrizia; Giorgetti, Belinda; Spazzafumo, Liana; Solazzi, Moreno; Balietti, Marta

    2005-02-01

    A computer-assisted morphometric investigation of cytochrome oxidase (COX) activity, selectively evidenced by preferential diaminobenzidine cytochemistry, has been carried out on synaptic mitochondria in the cerebellar cortex of adult and old rats. The ratio (R) of the area of the cytochemical precipitate (CPA) to the overall area of each mitochondrion (MA) was calculated. R refers to the fraction of the inner mitochondrial membrane actively involved in cellular respiration, thus its quantitative estimation constitutes a reliable index of the mitochondrial metabolic competence (MMC). In adult rats a significant negative correlation between MA and R values was found, while in old animals there was just a positive trend. Paired-quartile comparisons of R values showed a significant age-related decrease in small and medium-sized mitochondria, whereas the lowest and not significant age-related reduction was found in oversized organelles. A paired decrease in number and increase in size is reported to be a general trend for mitochondria during aging, but oversized organelles, according to their low R value, constitute a scanty, though functional, compensating reaction. Thus, the present findings support the argument that the currently reported age-related cellular metabolic decay appears to rely both on the decline in MMC of the small and medium-sized mitochondria, and on their specific reduction in number. This novel result is of biological relevance since it is largely the small and medium-sized mitochondria that are required for the provision of adequate amounts of ATP for actual cellular performance, while the significantly enlarged organelles are thought to represent an intermediate ultrastructural feature in mitochondrial genesis and/or remodelling.

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

    Directory of Open Access Journals (Sweden)

    Yunfei Pu

    2013-11-01

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

  5. Absence of collagen XVIII in mice causes age-related insufficiency in retinal pigment epithelium proteostasis.

    Science.gov (United States)

    Kivinen, Niko; Felszeghy, Szabolcs; Kinnunen, Aino I; Setälä, Niko; Aikio, Mari; Kinnunen, Kati; Sironen, Reijo; Pihlajaniemi, Taina; Kauppinen, Anu; Kaarniranta, Kai

    2016-08-01

    Collagen XVIII has the structural properties of both collagen and proteoglycan. It has been found at the basement membrane/stromal interface where it is thought to mediate their attachment. Endostatin, a proteolytic fragment from collagen XVIII C-terminal end has been reported to possess anti-angiogenic properties. Age-related vision loss in collagen XVIII mutant mice has been accompanied with a pathological accumulation of deposits under the retinal pigment epithelium (RPE). We have recently demonstrated that impaired proteasomal and autophagy clearance are associated with the pathogenesis of age-related macular degeneration. This study examined the staining levels of proteasomal and autophagy markers in the RPE of different ages of the Col18a1 (-/-) mice. Eyes from 3, 6-7, 10-13 and 18 months old mice were enucleated and embedded in paraffin according to the routine protocol. Sequential 5 μm-thick parasagittal samples were immunostained for proteasome and autophagy markers ubiquitin (ub), SQSTM1/p62 and beclin-1. The levels of immunopositivity in the RPE cells were evaluated by confocal microscopy. Collagen XVIII knock-out mice had undergone age-related RPE degeneration accompanied by an accumulation of drusen-like deposits. Ub protein conjugate staining was prominent in both RPE cytoplasm and extracellular space whereas SQSTM1/p62 and beclin-1 stainings were clearly present in the basal part of RPE cell cytoplasm in the Col18a1 (-/-) mice. SQSTM1/p62 displayed mild extracellular space staining. Disturbed proteostasis regulated by collagen XVIII might be responsible for the RPE degeneration, increased protein aggregation, ultimately leading to choroidal neovascularization. PMID:27125427

  6. Age-Related Effects of Study Time Allocation on Memory Performance in a Verbal and a Spatial Task

    Science.gov (United States)

    Krueger, Lacy E.

    2012-01-01

    Past studies have suggested that study time allocation partially mediates age relations on memory performance in a verbal task. To identify whether this applied to a different material modality, participants ages 20-87 completed a spatial task in addition to a traditional verbal task. In both the verbal and the spatial task, increased age was…

  7. The "Open-Earedness" Hypothesis and the Development of Age-Related Aesthetic Reactions to Music in Elementary School Children

    Science.gov (United States)

    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…

  8. Age-Related Differences in Altruism across Adulthood: Making Personal Financial Gain versus Contributing to the Public Good

    Science.gov (United States)

    Freund, Alexandra M.; Blanchard-Fields, Fredda

    2014-01-01

    Four studies utilizing different methodological approaches investigated adult age-related differences in altruism (i.e., contributions to the public good) and the self-centered value of increasing personal wealth. In Study 1, data from the World Values Survey (World Values Survey Association, 2009) provided 1st evidence of a negative association…

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-10-15

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

  10. Highway crash rates and age-related driver limitations: Literature review and evaluation of data bases

    Energy Technology Data Exchange (ETDEWEB)

    Hu, P.S. [Oak Ridge National Lab., TN (United States); Young, J.R. [Tennessee Univ., Knoxville, TN (United States); Lu, An [Oak Ridge Associated Universities, Inc., TN (United States)

    1993-08-01

    American society is undergoing a major demographic transformation that is resulting in a larger proportion of older individuals in the population. Moreover, recent travel surveys show that an increasing number of older individuals are licensed to drive and that they drive more than their same age cohort a decade ago. However, they continue to take shorter trips than younger drivers and they avoid driving during congested hours. This recent demographic transformation in our society, the graying of America, coupled with the increasing mobility of the older population impose a serious highway safety issue that cannot be overlooked. Some of the major concerns are the identification of ``high-risk`` older drivers and the establishment of licensing guidelines and procedures that are based on conclusive scientific evidence. Oak Ridge National Laboratory`s (ORNL) objectives in this project can be characterized by the following tasks: Review and evaluate the 1980 American Association of Motor Vehicle Administrators (AAMVA) and National Highway Traffic Safety Administration (NHTSA) licensing guidelines. Determine whether the license restriction recommended in the 1980 AAMVA and NHTSA guidelines was based on scientific evidence or on judgement of medical advisors. Identify in the scientific literature any medical conditions which are found to be highly associated with highway crashes, and which are not mentioned in the 1980 guidelines. Summarize States` current licensing practices for drivers with age-related physical and mental limitations. Identify potential data sources to establish conclusive evidence on age-related functional impairments and highway crashes.

  11. Protective effect of myostatin gene deletion on aging-related muscle metabolic decline.

    Science.gov (United States)

    Chabi, B; Pauly, M; Carillon, J; Carnac, G; Favier, F B; Fouret, G; Bonafos, B; Vanterpool, F; Vernus, B; Coudray, C; Feillet-Coudray, C; Bonnieu, A; Lacan, D; Koechlin-Ramonatxo, C

    2016-06-01

    While myostatin gene deletion is a promising therapy to fight muscle loss during aging, this approach induces also skeletal muscle metabolic changes such as mitochondrial deficits, redox alteration and increased fatigability. In the present study, we evaluated the effects of aging on these features in aged wild-type (WT) and mstn knockout (KO) mice. Moreover, to determine whether an enriched-antioxidant diet may be useful to prevent age-related disorders, we orally administered to the two genotypes a melon concentrate rich in superoxide dismutase for 12 weeks. We reported that mitochondrial functional abnormalities persisted (decreased state 3 and 4 of respiration; p<0.05) in skeletal muscle from aged KO mice; however, differences with WT mice were attenuated at old age in line with reduced difference on running endurance between the two genotypes. Interestingly, we showed an increase in glutathione levels, associated with lower lipid peroxidation levels in KO muscle. Enriched antioxidant diet reduced the aging-related negative effects on maximal aerobic velocity and running limit time (p<0.05) in both groups, with systemic adaptations on body weight. The redox status and the hypertrophic phenotype appeared to be beneficial to KO mice, mitigating the effect of aging on the skeletal muscle metabolic remodeling. PMID:26944368

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

    Science.gov (United States)

    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

  13. Safety and Tolerability Study of AAV2-sFLT01 in Patients With Neovascular Age-Related Macular Degeneration (AMD)

    Science.gov (United States)

    2016-01-05

    Macular Degeneration; Age-Related Maculopathies; Age-Related Maculopathy; Maculopathies, Age-Related; Maculopathy, Age-Related; Retinal Degeneration; Retinal Neovascularization; Gene Therapy; Therapy, Gene; Eye Diseases

  14. Perceptual and Social Attributes Underlining Age-Related Preferences for Faces.

    Science.gov (United States)

    Kiiski, Hanni S M; Cullen, Brendan; Clavin, Sarah L; Newell, Fiona N

    2016-01-01

    Although aesthetic preferences are known to be important in person perception and can play a significant role in everyday social decisions, the effect of the age of the observer on aesthetic preferences for faces of different ages has not yet been fully investigated. In the present study we investigated whether aesthetic preferences change with aging, with an age-related bias in favoring faces from one's own age group. In addition, we examined the role of age on both the perceptual qualities and the social attributes of faces that may influence these aesthetic judgements. Both younger and older adult observers provided ratings to images of younger, middle-aged and older unfamiliar faces. As well as attractiveness, the rating dimensions included other perceptual (distinctiveness, familiarity) and social (competence, trustworthiness and dominance) factors. The results suggested a consistent aesthetic preference for youthful faces across all ages of the observers but, surprisingly, no evidence for an age-related bias in attractiveness ratings. Older adults tended to provide higher ratings of attractiveness, competence and trustworthiness to the unfamiliar faces, consistent with the positivity effect previously reported. We also tested whether perceptual factors such as face familiarity or distinctiveness affected aesthetic ratings. Only ratings of familiarity, but not distinctiveness, were positively associated with the attractiveness of the faces. Moreover, ratings of familiarity decreased with increasing age of the face. With regard to the social characteristics of the faces, we found that the age of the face negatively correlated with ratings of trustworthiness provided by all observers, but with the competence ratings of older observers only. Interestingly, older adults provided higher ratings of perceived competence and trustworthiness to younger than older faces. However, our results also suggest that higher attractiveness ratings, together with older aged faces

  15. Perceptual and Social Attributes Underlining Age-Related Preferences for Faces

    Science.gov (United States)

    Kiiski, Hanni S. M.; Cullen, Brendan; Clavin, Sarah L.; Newell, Fiona N.

    2016-01-01

    Although aesthetic preferences are known to be important in person perception and can play a significant role in everyday social decisions, the effect of the age of the observer on aesthetic preferences for faces of different ages has not yet been fully investigated. In the present study we investigated whether aesthetic preferences change with aging, with an age-related bias in favoring faces from one’s own age group. In addition, we examined the role of age on both the perceptual qualities and the social attributes of faces that may influence these aesthetic judgements. Both younger and older adult observers provided ratings to images of younger, middle-aged and older unfamiliar faces. As well as attractiveness, the rating dimensions included other perceptual (distinctiveness, familiarity) and social (competence, trustworthiness and dominance) factors. The results suggested a consistent aesthetic preference for youthful faces across all ages of the observers but, surprisingly, no evidence for an age-related bias in attractiveness ratings. Older adults tended to provide higher ratings of attractiveness, competence and trustworthiness to the unfamiliar faces, consistent with the positivity effect previously reported. We also tested whether perceptual factors such as face familiarity or distinctiveness affected aesthetic ratings. Only ratings of familiarity, but not distinctiveness, were positively associated with the attractiveness of the faces. Moreover, ratings of familiarity decreased with increasing age of the face. With regard to the social characteristics of the faces, we found that the age of the face negatively correlated with ratings of trustworthiness provided by all observers, but with the competence ratings of older observers only. Interestingly, older adults provided higher ratings of perceived competence and trustworthiness to younger than older faces. However, our results also suggest that higher attractiveness ratings, together with older aged

  16. Perceptual and Social Attributes Underlining Age-Related Preferences for Faces.

    Science.gov (United States)

    Kiiski, Hanni S M; Cullen, Brendan; Clavin, Sarah L; Newell, Fiona N

    2016-01-01

    Although aesthetic preferences are known to be important in person perception and can play a significant role in everyday social decisions, the effect of the age of the observer on aesthetic preferences for faces of different ages has not yet been fully investigated. In the present study we investigated whether aesthetic preferences change with aging, with an age-related bias in favoring faces from one's own age group. In addition, we examined the role of age on both the perceptual qualities and the social attributes of faces that may influence these aesthetic judgements. Both younger and older adult observers provided ratings to images of younger, middle-aged and older unfamiliar faces. As well as attractiveness, the rating dimensions included other perceptual (distinctiveness, familiarity) and social (competence, trustworthiness and dominance) factors. The results suggested a consistent aesthetic preference for youthful faces across all ages of the observers but, surprisingly, no evidence for an age-related bias in attractiveness ratings. Older adults tended to provide higher ratings of attractiveness, competence and trustworthiness to the unfamiliar faces, consistent with the positivity effect previously reported. We also tested whether perceptual factors such as face familiarity or distinctiveness affected aesthetic ratings. Only ratings of familiarity, but not distinctiveness, were positively associated with the attractiveness of the faces. Moreover, ratings of familiarity decreased with increasing age of the face. With regard to the social characteristics of the faces, we found that the age of the face negatively correlated with ratings of trustworthiness provided by all observers, but with the competence ratings of older observers only. Interestingly, older adults provided higher ratings of perceived competence and trustworthiness to younger than older faces. However, our results also suggest that higher attractiveness ratings, together with older aged faces

  17. Perceptual and social attributes underlining age-related preferences for faces

    Directory of Open Access Journals (Sweden)

    Hanni SM Kiiski

    2016-08-01

    Full Text Available Although aesthetic preferences are known to be important in person perception and can play a significant role in everyday social decisions, the effect of the age of the observer on aesthetic preferences for faces of different ages has not yet been fully investigated. In the present study we investigated whether aesthetic preferences change with ageing, with an age-related bias in favouring faces from one’s own age group. In addition, we examined the role of age on both the perceptual qualities and the social attributes of faces that may influence these aesthetic judgements. Both younger and older adult observers provided ratings to images of younger, middle-aged and older unfamiliar faces. As well as attractiveness, the rating dimensions included other perceptual (distinctiveness, familiarity and social (competence, trustworthiness and dominance factors. The results suggested a consistent aesthetic preference for youthful faces across all ages of the observers but, surprisingly, no evidence for an age-related bias in attractiveness ratings. Older adults tended to provide higher ratings of attractiveness, competence and trustworthiness to the unfamiliar faces, consistent with the positivity effect previously reported. We also tested whether perceptual factors such as face familiarity or distinctiveness affected aesthetic ratings. Only ratings of familiarity, but not distinctiveness, were positively associated with the attractiveness of the faces. Moreover, ratings of familiarity decreased with increasing age of the face. With regard to the social characteristics of the faces, we found that the age of the face negatively correlated with ratings of trustworthiness provided by all observers, but with the competence ratings of older observers only. Interestingly, older adults provided higher ratings of perceived competence and trustworthiness to younger than older faces. However, our results also suggest that higher attractiveness ratings, together

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

    Science.gov (United States)

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

    2013-01-01

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

  19. A BOLD perspective on age-related flow-metabolism coupling and neural efficiency changes in human visual cortex

    Directory of Open Access Journals (Sweden)

    Joanna Lynn Hutchison

    2013-05-01

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

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

    Science.gov (United States)

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

    2013-11-01

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

  1. An overview on age related macular degeneration and recent advances in its management

    Directory of Open Access Journals (Sweden)

    SOBIA N.

    2014-03-01

    Full Text Available Age-related macular degeneration (AMD is a condition characterized, in the early stages, by slow development and progression, absence of symptoms over a number of years, and extensive retinal deposits called drusen, often associated with pigmentary abnormalities (early AMD.There is strong and consistent evidence that increasing age, family history, obesity/high body mass index, and cataract surgery are associated with late AMD. Smoking is the strongest and most consistently found modifiable risk factor for late AMD.Age-related macular degeneration remains one of the most severe and profound disabilities encountered in medicine, particularly due to the loss of the central vision and the high economic burden it places on patients and societies.Recent advances in management of AMD is anti-angiogenic drugs. The identification of the crucial role played by vascular endothelial growth factor (VEGF in the pathogenesis of wet AMD hasallowed the development of VEGF-blocking agents such as bevacizumab, pegaptanib and ranibizumab.

  2. Age-Related Impairment of Quality of Joint Motion in Vibroarthrographic Signal Analysis

    Directory of Open Access Journals (Sweden)

    Dawid Bączkowicz

    2015-01-01

    Full Text Available Aging is associated with degenerative changes in articular surfaces leading to quantitative and qualitative impairment of joint motion. Therefore, the aim of this study is to evaluate an age-related quality of the patellofemoral joint (PFJ motion in the vibroarthrographic (VAG signal analysis. Two hundred and twenty individuals were enrolled in this study and divided into five groups according to age. The VAG signals were collected during flexion/extension knee motion using an acceleration sensor and described using four parameters (VMS, P1, P2, and H. We observed that values of parameters VMS, P1, and P2 increase in accordance with the age, but H level decreases. The most significant differences were achieved between the youngest and the oldest participants’ groups. Moreover, we show that parameters VMS, P1, and P2 positively correlate with age, contrary to negatively associated H parameter. Our results suggest that the impairment of joint motion is a result of age-related osteoarticular degenerative changes.

  3. Nutrient-rich meat proteins in offsetting age-related muscle loss.

    Science.gov (United States)

    Phillips, Stuart M

    2012-11-01

    From a health perspective, an underappreciated consequence of the normal aging process is the impacts that the gradual loss of skeletal muscle mass, termed sarcopenia, has on health beyond an effect on locomotion. Sarcopenia, refers to the loss of muscle mass, and associated muscle weakness, which occurs in aging and is thought to proceed at a rate of approximately 1% loss per year. However, periods of inactivity due to illness or recovery from orthopedic procedures such as hip or knee replacement are times of accelerated sarcopenic muscle loss from which it may be more difficult for older persons to recover. Some of the consequences of age-related sarcopenia are easy to appreciate such as weakness and, eventually, reduced mobility; however, other lesser recognized consequences include, due to the metabolic role the skeletal muscle plays, an increased risk for poor glucose control and a predisposition toward weight gain. What we currently know is that two stimuli can counter this age related muscle loss and these are physical activity, specifically resistance exercise (weightlifting), and nutrition. The focus of this paper is on the types of dietary protein that people might reasonably consume to offset sarcopenic muscle loss. PMID:22632883

  4. Age-related differences in the rhythmic structure of the golf swing.

    Science.gov (United States)

    Kim, Tae Hoon; Jagacinski, Richard J; Lavender, Steven A

    2011-01-01

    Participants were 20 younger golfers (M age=19.8 years, SD=1.84 years) and 20 older golfers (M age=63.0 years, SD=2.55 years) who attempted 40- and 80-yard eight-iron shots requiring an adjustment of their force and timing. No age-related differences were found in the tempo or speed of the shot; however, there were differences in the rhythmic relationship between the clubhead force and the weight shift. Whereas younger golfers primarily exhibited a 3 versus 2 polyrhythmic pattern between the peak forces of the clubhead and weight shift, older golfers primarily exhibited a simpler 3 versus 3 rhythmic force pattern by adding a forward weight shift at the beginning of the shot. Additionally, older golfers exhibited less independence between the timing of the clubhead force and weight shift, which indicated greater use of a single integrated coordinative unit rather than 2 units. These findings are interpreted as compensations for age-related slowing and increased temporal variability that help to preserve tempo at a speed comparable to younger adults. PMID:22004259

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

    Directory of Open Access Journals (Sweden)

    Chatchada Sutalangka

    2013-01-01

    Full Text Available To date, the preventive strategy against dementia is still essential due to the rapid growth of its prevalence and the limited therapeutic efficacy. Based on the crucial role of oxidative stress in age-related dementia and the antioxidant and nootropic activities of Moringa oleifera, the enhancement of spatial memory and neuroprotection of M. oleifera leaves extract in animal model of age-related dementia was determined. The possible underlying mechanism was also investigated. Male Wistar rats, weighing 180–220 g, were orally given M. oleifera leaves extract at doses of 100, 200, and 400 mg/kg at a period of 7 days before and 7 days after the intracerebroventricular administration of AF64A bilaterally. Then, they were assessed memory, neuron density, MDA level, and the activities of SOD, CAT, GSH-Px, and AChE in hippocampus. The results showed that the extract improved spatial memory and neurodegeneration in CA1, CA2, CA3, and dentate gyrus of hippocampus together with the decreased MDA level and AChE activity but increased SOD and CAT activities. Therefore, our data suggest that M. oleifera leaves extract is the potential cognitive enhancer and neuroprotectant. The possible mechanism might occur partly via the decreased oxidative stress and the enhanced cholinergic function. However, further explorations concerning active ingredient(s are still required.

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

    Directory of Open Access Journals (Sweden)

    Sara Sepe

    2016-05-01

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

  7. Obesity and medicare expenditure: accounting for age-related height loss.

    Science.gov (United States)

    Onwudiwe, Nneka C; Stuart, Bruce; Zuckerman, Ilene H; Sorkin, John D

    2011-01-01

    To determine the relationship between BMI and Medicare expenditure for adults 65-years and older and determine whether this relationship changes after accounting for misclassification due to age-related height loss. Using a cross sectional study design, the relationship between BMI and fee-for-service Medicare expenditure was examined among beneficiaries who completed the Medicare Current Beneficiary Survey (MCBS) in 2002, were not enrolled in Medicare Health Maintenance Organization, had a self-reported height and weight, and were 65 and older (n = 7,706). Subjects were classified as underweight, normal weight, overweight, obese (obese I), and severely obese (obese II/III). To adjust BMI for the artifactual increase associated with age-related height loss, the reported height was transformed by adding the sex-specific age-associated height loss to the reported height in MCBS. The main outcome variable was total Medicare expenditure. There was a significant U-shaped pattern between unadjusted BMI and Medicare expenditure: underweight $4,581 (P accounting for height loss: underweight $4,640 (P cost is not found at "normal" BMI, but rather in overweight subjects with higher spending in the obese and underweight categories. Adjusting for loss-of-height with aging had little affect on cost estimates.

  8. Modulation of age-related insulin sensitivity by VEGF-dependent vascular plasticity in adipose tissues.

    Science.gov (United States)

    Honek, Jennifer; Seki, Takahiro; Iwamoto, Hideki; Fischer, Carina; Li, Jingrong; Lim, Sharon; Samani, Nilesh J; Zang, Jingwu; Cao, Yihai

    2014-10-14

    Mechanisms underlying age-related obesity and insulin resistance are generally unknown. Here, we report age-related adipose vascular changes markedly modulated fat mass, adipocyte functions, blood lipid composition, and insulin sensitivity. Notably, VEGF expression levels in various white adipose tissues (WATs) underwent changes uninterruptedly in different age populations. Anti-VEGF and anti- VEGF receptor 2 treatment in different age populations showed marked variations of vascular regression, with midaged mice exhibiting modest sensitivity. Interestingly, anti-VEGF treatment produced opposing effects on WAT adipocyte sizes in different age populations and affected vascular density and adipocyte sizes in brown adipose tissue. Consistent with changes of vasculatures and adipocyte sizes, anti-VEGF treatment increased insulin sensitivity in young and old mice but had no effects in the midaged group. Surprisingly, anti-VEGF treatment significantly improved insulin sensitivity in midaged obese mice fed a high-fat diet. Our findings demonstrate that adipose vasculatures show differential responses to anti-VEGF treatment in various age populations and have therapeutic implications for treatment of obesity and diabetes with anti-VEGF-based antiangiogenic drugs.

  9. Age-related differences in emotion regulation strategies: Examining the role of contextual factors.

    Science.gov (United States)

    Schirda, Brittney; Valentine, Thomas R; Aldao, Amelia; Prakash, Ruchika Shaurya

    2016-09-01

    Increasing age is characterized by greater positive affective states. However, there is mixed evidence on the implementation of emotion regulation strategies across the life span. To clarify the discrepancies in the literature, we examined the modulating influence of contextual factors in understanding emotion regulation strategy use in older and young adults. Forty-eight older adults and forty-nine young adults completed a retrospective survey inquiring about the use of emotion regulation strategies in emotion-eliciting situations experienced over the preceding 2 weeks. We used factor analysis to establish clusters of emotion regulation strategies, resulting in cognitive strategies, acceptance, and maladaptive strategies. Overall, we found context-dependent age-related differences in emotion regulation strategy use. Specifically, older adults reported greater use of acceptance than young adults in situations of moderate intensity and in situations that evoke anxiety and sadness. In addition, older adults reported using maladaptive strategies to a lesser extent in high- and moderate-intensity situations and in situations that elicit anxiety and sadness when compared with young adults. There were no age-related differences in the use of cognitive strategies across contexts. Older adults, compared to young adults, reported less use of maladaptive strategies and greater use of acceptance than young adults, which suggests that the enhanced emotional functioning observed later in life may be due to a shift in strategy implementation. (PsycINFO Database Record PMID:27570980

  10. Accelerated Apoptosis Contributes to Aging-Related Hyperinflammation in Endotoxemia

    OpenAIRE

    Zhou, Mian; Wu, Rongqian; Dong, Weifeng; Leong, Jennifer; Ping WANG

    2010-01-01

    Sepsis is associated with an increase in circulating levels of bacterial endotoxin. Sepsis is a particularly serious problem in the geriatric population due to the high mortality associated with it. However, it remains unknown whether this phenomenon is related to an increase of apoptosis in splenic cells. To study this, male Fischer-344 rats (young: 3-months old; aged: 24-months old) were subjected to endotoxemia by injection of LPS. Splenic samples were collected 4 h thereafter. Apoptosis w...

  11. Age-related alterations in the neural coding of envelope periodicities.

    Science.gov (United States)

    Walton, Joseph P; Simon, Henry; Frisina, Robert D

    2002-08-01

    This research was guided by the working hypothesis that the aging auditory system progressively loses its ability to process rapid acoustic transients efficiently, and in elderly listeners, this results in difficulties in speech perception. Neural correlates of age-related deficits in temporal processing were investigated by recording from inferior colliculus (IC) neurons from young adult and old CBA mice. Single-unit responses were recorded to sinusoidally amplitude-modulated (SAM) noise carriers, presented at 65-80 dB SPL, having modulation frequencies (MFs) that ranged from 10 to 800 Hz. Because phasic-type temporal response patterns dominate responses to tone and noise in mammalian IC, we limited our analyses to only phasic units. Modulation transfer functions (MTF) for both rate (rMTF) and synchronization (sMTF) measures were used to derive respective best modulation frequencies (rBMF and sBMF). The main age-related finding was that there was an overall increase in response rate to SAM noise carriers and a decrease in the median upper cutoff frequency in units from old mice. At rBMF, the median spike count from units from old animals was 1.63 times greater, and at the sBMF, the median spike count was 2.29 times greater than the young adult sample. We explored whether the increase in driven activity was due to a change in the transient (first cycle response) or periodic (remaining response) component of the response to SAM noise. Median spike counts of the transient component decreased with increasing MF for both young adult and old units, with median counts consistently greater in the old sample as compared with young. Median spike counts for the periodic response remained relatively constant as a function of MF; however, there was a significantly greater (3 times) response for older units in a restricted range of MFs. The greater median spike counts found for the transient and periodic response was also evident when we analyzed the cycle-by-cycle response

  12. Nutritional Supplements in Support of Resistance Exercise to Counter Age-Related Sarcopenia12

    Science.gov (United States)

    Phillips, Stuart M

    2015-01-01

    Age-related sarcopenia, composed of myopenia (a decline in muscle mass) and dynapenia (a decline in muscle strength), can compromise physical function, increase risk of disability, and lower quality of life in older adults. There are no available pharmaceutical treatments for this condition, but evidence shows resistance training (RT) is a viable and relatively low-cost treatment with an exceptionally positive side effect profile. Further evidence suggests that RT-induced increases in muscle mass, strength, and function can be enhanced by certain foods, nutrients, or nutritional supplements. This brief review focuses on adjunctive nutritional strategies, which have a reasonable evidence base, to enhance RT-induced gains in outcomes relevant to sarcopenia and to reducing risk of functional declines. PMID:26178029

  13. Age-related differences in mechanism, cause, and location of trauma deaths

    DEFF Research Database (Denmark)

    Meisler, Rikke; Thomsen, Annemarie Bondegaard; Theilade, Peter;

    2011-01-01

    BACKGROUND: Trauma death has traditionally been described as primarily occurring in young men exposed to penetrating trauma or road traffic accidents. The epidemiology of trauma fatalities in Europe may change as a result of the increasing proportion of elderly patients. The goal of this study...... was to describe age-related differences in trauma type, mechanism, cause and location of death in a well-defined European region. METHODS: We prospectively registered all trauma patients and severe burn patients in eastern Denmark over 12 consecutive months. We analyzed all trauma fatalities in our region...... regarding the trauma type, mechanism, cause and location of death. RESULTS: A total of 2923 patients were registered, of which 292 (9.9%) died within 30 days. Mortality increased with age, with a mortality of 46.1% in patients older than 80 years old. Blunt trauma was the most frequent trauma type at all...

  14. Age-related differences in mechanism, cause, and location of trauma deaths

    DEFF Research Database (Denmark)

    Meisler, Rikke; Thomsen, Annemarie Bondegaard; Theilade, Peter;

    2011-01-01

    was to describe age-related differences in trauma type, mechanism, cause and location of death in a well-defined European region. METHODS: We prospectively registered all trauma patients and severe burn patients in eastern Denmark over 12 consecutive months. We analyzed all trauma fatalities in our region......BACKGROUND: Trauma death has traditionally been described as primarily occurring in young men exposed to penetrating trauma or road traffic accidents. The epidemiology of trauma fatalities in Europe may change as a result of the increasing proportion of elderly patients. The goal of this study...... regarding the trauma type, mechanism, cause and location of death. RESULTS: A total of 2923 patients were registered, of which 292 (9.9%) died within 30 days. Mortality increased with age, with a mortality of 46.1% in patients older than 80 years old. Blunt trauma was the most frequent trauma type at all...

  15. The Critical Need to Promote Research of Aging and Aging-related Diseases to Improve Health and Longevity of the Elderly Population

    OpenAIRE

    Jin, Kunlin; Simpkins, James W.; Ji, Xunming; Leis, Miriam; Stambler, Ilia

    2014-01-01

    Due to the aging of the global population and the derivative increase in aging-related non-communicable diseases and their economic burden, there is an urgent need to promote research on aging and aging-related diseases as a way to improve healthy and productive longevity for the elderly population. To accomplish this goal, we advocate the following policies: 1) Increasing funding for research and development specifically directed to ameliorate degenerative aging processes and to extend healt...

  16. Self-assembly into spheres of a hybrid diphenylalanine-porphyrin: increased fluorescence lifetime and conserved electronic properties.

    Science.gov (United States)

    Charalambidis, Georgios; Kasotakis, Emmanouil; Lazarides, Theodore; Mitraki, Anna; Coutsolelos, Athanassios G

    2011-06-20

    A series of protected phenylalanine and diphenylalanine derivatives have been coupled through a peptide bond to a monoaminoporphyrin to form new materials. A comparative study in solution and in the solid state has been performed and confirmed new and interesting properties for the self-assembled hybrid materials while conserving the electronic properties of the chromophore. Thus, they are powerful candidates for use in dye-sensitized solar cells. PMID:21618629

  17. The Role of Vitamins in the Treatment of Age Related Macular Degeneration

    OpenAIRE

    Mandić, Zdravko; Benčić, Goran; Vatavuk, Zoran

    2004-01-01

    The role of vitamins in the treatment of age related macular degeneration was reviewed. The following studies were selected for review: Eye Disease Case Control Study (EDCCS), Beaver Dam Eye Study, Blue Mountains Eye Study, Pathologies Oculaires Liees a l'Age Study (studija POLA) and Age Related Eye Disease Study (AREDS). These studies showed that antioxidant intake could be recommended in patients with certain forms of age related macular degeneration. A definite answer concerning the role o...

  18. Growth factors, aging and age-related diseases.

    Science.gov (United States)

    Balasubramanian, Priya; Longo, Valter D

    2016-06-01

    Simple organisms including yeast and flies with mutations in the IGF-1 and Tor-S6K pathways are dwarfs, are highly protected from toxins, and survive up to 3 times longer. Similarly, dwarf mice with deficiencies in the growth hormone-IGF-I axis are also long lived and protected from diseases. We recently reported that humans with Growth Hormone Receptor Deficiency (GHRD) rarely develop cancer or diabetes. These findings are in agreement with the effect of defects in the Tor-S6K pathways in causing dwarfism and protection of DNA. Because protein restriction reduces both GHR-IGF-1 axis and Tor-S6K activity, we examined links between protein intake, disease, and mortality in over 6000 US subjects in the NHANES CDC database. Respondents aged 50-65 reporting a high protein intake displayed an increase in IGF-I levels, a 75% increased risk of overall mortality and a 3-4 fold increased risk of cancer mortality in agreement with findings in mouse experiments. These studies point to a conserved link between proteins and amino acids, GHR-IGF-1/insulin, Tor-S6k signaling, aging, and diseases. PMID:26883276

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

    Science.gov (United States)

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

    2015-09-01

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

  20. Auditory sensitivity and the outer hair cell system in the CBA mouse model of age-related hearing loss.

    Science.gov (United States)

    Frisina, Robert D; Zhu, Xiaoxia

    2010-06-01

    Age-related hearing loss is a highly prevalent sensory disorder, from both the clinical and animal model perspectives. Understanding of the neurophysiologic, structural, and molecular biologic bases of age-related hearing loss will facilitate development of biomedical therapeutic interventions to prevent, slow, or reverse its progression. Thus, increased understanding of relationships between aging of the cochlear (auditory portion of the inner ear) hair cell system and decline in overall hearing ability is necessary. The goal of the present investigation was to test the hypothesis that there would be correlations between physiologic measures of outer hair cell function (otoacoustic emission levels) and hearing sensitivity (auditory brainstem response thresholds), starting in middle age. For the CBA mouse, a useful animal model of age-related hearing loss, it was found that correlations between these two hearing measures occurred only for high sound frequencies in middle age. However, in old age, a correlation was observed across the entire mouse range of hearing. These findings have implications for improved early detection of progression of age-related hearing loss in middle-aged mammals, including mice and humans, and distinguishing peripheral etiologies from central auditory system decline.

  1. Age related changes in histomorphology of medium sized muscular artery

    International Nuclear Information System (INIS)

    The aim of this study was to contribute to the knowledge of histomorphometric changes which are associated with increasing age in local population, with the experience obtained in the dissection on cadavers. Study Design: Cross-sectional comparative study Place and Duration of Study: The study was carried out at the department of Anatomy, Army Medical College Rawalpindi in collaboration with Forensic departments of various medical institutes where cadavers were brought for autopsy, spanning from 15 Feb 2010 to 15 Aug 2010. Material and Methods: A total of forty cadavers from local population (Punjab and Khyber Pakhtunkhwa) were dissected and specimen (Common hepatic artery) (CHA) were obtained. Two age groups, one below the age of forty years (1 to 39 years) and the other above the age of forty years (40 to 70 years) were made. The specimen were processed and stained with Hematoxylin and Eosin. Using a microscope with 10 X objective, micrometry was done and data of intima thickness (IT), media thickness (MT) and intima media thickness (IMT) was noted. Results: After comparing the two age groups, statistically significant difference was found between the IT (p value <0.01). The mean values of media failed to attain any statistical difference. No statistically significant difference was found in the IMT of the two age groups. Conclusion: Increase in intima thickness was found while MT and IMT did not show any statistical difference. (author)

  2. Age related flow rate nomograms in a normal pediatric population.

    Science.gov (United States)

    Gaum, L D; Wese, F X; Liu, T P; Wong, A K; Hardy, B E; Churchill, B M

    1989-01-01

    Uroflow studies in a normal pediatric population were analysed statistically. Single studies for 511 subjects (272 boys and 239 girls) were reviewed. Nomograms relating peak flow to volume voided and age were established. An acceptable lower limit for peak flow was obtained from the data and a volume voided range was calculated so that both criteria could be used with 90% probability to define the normal voiding situation. The mean values of peak flow rate increased with volume voided in both sexes and also with age in the male population. Different sets of nomograms, which are necessary for daily clinical evaluation, are given. They define the normal values in the normal population. PMID:2763925

  3. Benign prostatic hyperplasia: age-related tissue-remodeling.

    Science.gov (United States)

    Untergasser, Gerold; Madersbacher, Stephan; Berger, Peter

    2005-03-01

    Aging and androgens are the two established risk factors for the development of benign prostatic hyperplasia (BPH) and benign prostatic enlargement (BPE), which can lead to lower urinary tract symptoms (LUTS) in elderly men. BPH, consisting of a nodular overgrowth of the epithelium and fibromuscular tissue within transition zone and periurethral areas, is first detectable around the fourth decade of life and affects nearly all men by the ninth decade. The pathogenesis of BPH is still largely unresolved, but multiple partially overlapping and complementary theories have been proposed, all of which seem to be operative at least to some extent. In addition to nerve-, endocrine- and immune system, local para- and luminocrine pleiotrope mechanisms/factors are implicated in the prostatic tissue-remodeling process. Prostate tissue-remodeling in the transition zone is characterized by: (i) hypertrophic basal cells, (ii) altered secretions of luminal cells leading to calcification, clogged ducts and inflammation, (iii) lymphocytic infiltration with production of proinflammatory cytokines, (iv) increased radical oxygen species (ROS) production that damages epithelial and stromal cells, (v) increased basic fibroblast (bFGF) and transforming growth factor beta (TGF-beta 1) production leading to stromal proliferation, transdifferentiation and extracellular matrix production, (vi) altered autonomous innervation that decreases relaxation and leads to a high adrenergic tonus, (vii) and altered neuroendocine cell function and release of neuroendocrine peptides (NEP). This review summarizes the multifactorial nature of prostate tissue remodeling in elderly men with symptomatic BPH with a particular focus on changes of cell-cell interactions and cell functions in the human aging prostate.

  4. Student journals: a means of assessing transformative learning in aging related courses.

    Science.gov (United States)

    Cohen, Adrienne L; Pitman Brown, Pamela; Morales, Justin P

    2015-01-01

    In courses where topics are sensitive or even considered taboo for discussion, it can be difficult to assess students' deeper learning. In addition, incorporating a wide variety of students' values and beliefs, designing instructional strategies and including varied assessments adds to the difficulty. Journal entries or response notebooks can highlight reflection upon others' viewpoints, class readings, and additional materials. These are useful across all educational levels in deep learning and comprehension strategies assessments. Journaling meshes with transformative learning constructs, allowing for critical self-reflection essential to transformation. Qualitative analysis of journals in a death and dying class reveals three transformative themes: awareness of others, questioning, and comfort. Students' journal entries demonstrate transformative learning via communication with others through increased knowledge/exposure to others' experiences and comparing/contrasting others' personal beliefs with their own. Using transformative learning within gerontology and geriatrics education, as well as other disciplined aging-related courses is discussed. PMID:25386895

  5. Genetic and functional dissection of HTRA1 and LOC387715 in age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Zhenglin Yang

    2010-02-01

    Full Text Available A common haplotype on 10q26 influences the risk of age-related macular degeneration (AMD and encompasses two genes, LOC387715 and HTRA1. Recent data have suggested that loss of LOC387715, mediated by an insertion/deletion (in/del that destabilizes its message, is causally related with the disorder. Here we show that loss of LOC387715 is insufficient to explain AMD susceptibility, since a nonsense mutation (R38X in this gene that leads to loss of its message resides in a protective haplotype. At the same time, the common disease haplotype tagged by the in/del and rs11200638 has an effect on the transcriptional upregulation of the adjacent gene, HTRA1. These data implicate increased HTRA1 expression in the pathogenesis of AMD and highlight the importance of exploring multiple functional consequences of alleles in haplotypes that confer susceptibility to complex traits.

  6. Targeting the age-related occurrence, removal, and accumulation of molecular damage by hormesis.

    Science.gov (United States)

    Rattan, Suresh I S

    2010-06-01

    Strategies for testing and developing effective means of intervention, prevention, and modulation of aging incorporate means to minimize the occurrence and accumulation of molecular damage, to reduce molecular heterogeneity, and to evaluate the relevance of the type and extent of damage with respect to its role in aging and age-related diseases. One such approach is that of mild stress-induced hormesis, which stimulates maintenance and repair systems and strengthens the homeodynamic space of cells and organisms. Hormesis through mild heat shock, natural and synthetic hormetins, and other stressors brings about several antiaging effects in human fibroblasts, keratinocytes, and telomerase-immortalized bone marrow stem cells. Depending on the cell type, these antiaging hormetic effects include extension of replicative life span, enhanced proteasomal activities, increased chaperone levels, and improved wound healing, angiogenesis, and differentiation. The main molecular pathways for achieving such hormetic effects are through targeting the processes for the repair and removal of molecular damage, which can slow aging.

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

    Science.gov (United States)

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

    2016-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Nadège Minois

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

  9. Relationship between the complement system, risk factors and prediction models in age-related macular degeneration.

    Science.gov (United States)

    Bora, Nalini S; Matta, Bharati; Lyzogubov, Valeriy V; Bora, Puran S

    2015-02-01

    Studies performed over the past decade in humans and experimental animals have been a major source of information and improved our understanding of how dysregulation of the complement system contributes to age-related macular degeneration (AMD) pathology. Drusen, the hall-mark of dry-type AMD are reported to be the by-product of complement mediated inflammatory processes. In wet AMD, unregulated complement activation results in increased production of angiogenic growth factors leading to choroidal neovascularization both in humans and in animal models. In this review article we have linked the complement system with modifiable and non-modifiable AMD risk factors as well as with prediction models of AMD. Understanding the association between the complement system, risk factors and prediction models will help improve our understanding of AMD pathology and management of this disease.

  10. Cataract surgery and age-related macular degeneration. An evidence-based update

    DEFF Research Database (Denmark)

    Kessel, Line; Erngaard, Ditte; Flesner, Per;

    2015-01-01

    PURPOSE: Age-related macular degeneration (AMD) and cataract often coexist in patients and concerns that cataract surgery is associated with an increased risk of incidence or progression of existing AMD has been raised. This systematic review and meta-analysis is focused on presenting the evidence...... concerning progression of AMD in patients undergoing cataract surgery. METHODS: We performed a systematic literature search in the PubMed, Medline, Cochrane Library and CINAHL databases. Two randomized trials and two case-control trials were identified. Quality of the studies was assessed using the Cochrane...... risk of bias tool, data were extracted, and meta-analyses were performed. Quality of the available evidence was evaluated using the GRADE system. RESULTS: We found that visual acuity at 6-12 months follow-up was significantly better (6.5-7.5 letters) in eyes that had undergone cataract surgery than...

  11. The impact of major transformations of a production process on age-related accident risks

    DEFF Research Database (Denmark)

    Blank, V L; Laflamme, L; Diderichsen, Finn

    1996-01-01

    and consequent changes in job content. It was hypothesized that the combined effect of these factors might lead accident risks, both non-specific (aggregated) and specific (by kind), to increase with age. Accident risk ratios (ARRs), however, proved to be higher for younger workers than older ones, in both...... the non-specific and the specific cases. However, two accident patterns (specific risks) also show relatively high ARRs among workers in their 40s (and even 30s), results that might be explained by particular exposures and/or age-related performance problems. The findings suggest that technological......This paper describes a study of whether accident risks were equally distributed across age categories among a population of mining workers whose work activities were suspected to be age-impaired. The impairment factors in focus are the transformation of production technology during the 80s...

  12. Individual variability in human blood metabolites identifies age-related differences

    Science.gov (United States)

    Murakami, Itsuo; Takada, Junko; Kondoh, Hiroshi; Yanagida, Mitsuhiro

    2016-01-01

    Metabolites present in human blood document individual physiological states influenced by genetic, epigenetic, and lifestyle factors. Using high-resolution liquid chromatography-mass spectrometry (LC-MS), we performed nontargeted, quantitative metabolomics analysis in blood of 15 young (29 ± 4 y of age) and 15 elderly (81 ± 7 y of age) individuals. Coefficients of variation (CV = SD/mean) were obtained for 126 blood metabolites of all 30 donors. Fifty-five RBC-enriched metabolites, for which metabolomics studies have been scarce, are highlighted here. We found 14 blood compounds that show remarkable age-related increases or decreases; they include 1,5-anhydroglucitol, dimethyl-guanosine, acetyl-carnosine, carnosine, ophthalmic acid, UDP-acetyl-glucosamine, N-acetyl-arginine, N6-acetyl-lysine, pantothenate, citrulline, leucine, isoleucine, NAD+, and NADP+. Six of them are RBC-enriched, suggesting that RBC metabolomics is highly valuable for human aging research. Age differences are partly explained by a decrease in antioxidant production or increasing inefficiency of urea metabolism among the elderly. Pearson’s coefficients demonstrated that some age-related compounds are correlated, suggesting that aging affects them concomitantly. Although our CV values are mostly consistent with those CVs previously published, we here report previously unidentified CVs of 51 blood compounds. Compounds having moderate to high CV values (0.4–2.5) are often modified. Compounds having low CV values, such as ATP and glutathione, may be related to various diseases because their concentrations are strictly controlled, and changes in them would compromise health. Thus, human blood is a rich source of information about individual metabolic differences. PMID:27036001

  13. Individual variability in human blood metabolites identifies age-related differences.

    Science.gov (United States)

    Chaleckis, Romanas; Murakami, Itsuo; Takada, Junko; Kondoh, Hiroshi; Yanagida, Mitsuhiro

    2016-04-19

    Metabolites present in human blood document individual physiological states influenced by genetic, epigenetic, and lifestyle factors. Using high-resolution liquid chromatography-mass spectrometry (LC-MS), we performed nontargeted, quantitative metabolomics analysis in blood of 15 young (29 ± 4 y of age) and 15 elderly (81 ± 7 y of age) individuals. Coefficients of variation (CV = SD/mean) were obtained for 126 blood metabolites of all 30 donors. Fifty-five RBC-enriched metabolites, for which metabolomics studies have been scarce, are highlighted here. We found 14 blood compounds that show remarkable age-related increases or decreases; they include 1,5-anhydroglucitol, dimethyl-guanosine, acetyl-carnosine, carnosine, ophthalmic acid, UDP-acetyl-glucosamine,N-acetyl-arginine,N6-acetyl-lysine, pantothenate, citrulline, leucine, isoleucine, NAD(+), and NADP(+) Six of them are RBC-enriched, suggesting that RBC metabolomics is highly valuable for human aging research. Age differences are partly explained by a decrease in antioxidant production or increasing inefficiency of urea metabolism among the elderly. Pearson's coefficients demonstrated that some age-related compounds are correlated, suggesting that aging affects them concomitantly. Although our CV values are mostly consistent with those CVs previously published, we here report previously unidentified CVs of 51 blood compounds. Compounds having moderate to high CV values (0.4-2.5) are often modified. Compounds having low CV values, such as ATP and glutathione, may be related to various diseases because their concentrations are strictly controlled, and changes in them would compromise health. Thus, human blood is a rich source of information about individual metabolic differences. PMID:27036001

  14. Size, shape and age-related changes of the mandibular condyle during childhood

    Energy Technology Data Exchange (ETDEWEB)

    Karlo, Christoph A. [University Children' s Hospital Zurich, Department of Diagnostic Imaging, Zurich (Switzerland); University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland); Stolzmann, Paul [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland); Habernig, Sandra; Kellenberger, Christian J. [University Children' s Hospital Zurich, Department of Diagnostic Imaging, Zurich (Switzerland); Mueller, Lukas [University of Zurich, Clinics for Orthodontics and Paediatric Dentistry, Zurich (Switzerland); Saurenmann, Traudel [University Children' s Hospital Zurich, Department of Rheumatology, Zurich (Switzerland)

    2010-10-15

    To determine age-related differences in the size and shape of the mandibular condyle in children to establish anatomical reference values. A total of 420 mandibular condyles in 210 children (mean age, 7 years) were retrospectively analysed by using computed tomography (CT) imaging. The greatest left-right (LRD) and anterior-posterior (APD) diameters and the anteversion angles (AA) were measured by two readers. An APD/LRD ratio was calculated. The shape of the condyles was graded into three types on sagittal images. Correlations of parameters with the children's age were assessed by using Pearson's correlation analyses. The LRD (mean, 14.1 {+-} 2.4 mm), APD (mean, 7.3 {+-} 1.0 mm) and LRD/APD ratio (mean, 1.9 {+-} 0.3) increased (r{sub LRD} = 0.70, p < 0.01; r{sub APD} = 0.56, p < 0.01; r{sub rat} = 0.28, p < 0.01) while the AA (mean, 27 {+-} 7 ) decreased significantly (r{sub antang} = -0.26, p < 0.001) with age. The condylar shape as determined on sagittal images correlated significantly with age (r = 0.69, p < 0.05). Boys had significantly higher anteversion angles (p < 0.01), greater LRDs (p < 0.05) and greater mean ratios (p < 0.05). The mandibular condyle is subject to significant age-related changes in size and shape during childhood. As the size of the condyles increases with age, the anteversion angles decrease and the shape of the condyle turns from round to oval. (orig.)

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

    Science.gov (United States)

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

    1987-06-01

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

  16. Age-related declines in distortion product otoacoustic emissions utilizing pure tone contralateral stimulation in CBA/CaJ mice.

    Science.gov (United States)

    Varghese, George I; Zhu, Xiaoxia; Frisina, Robert D

    2005-11-01

    One role of the medial olivocochlear (MOC) auditory efferent system is to suppress cochlear outer hair cell (OHC) responses when presented with a contralateral sound. Using distortion product otoacoustic emissions (DPOAEs), the effects of active changes in OHC responses due to the MOC as a function of age can be observed when contralateral stimulation with a pure tone is applied. Previous studies have shown that there are age-related declines of the MOC when broad band noise is presented to the contralateral ear. In this study, we measured age-related changes in CBA/CaJ mice by comparing DPOAE generation with and without a contralateral pure tone at three different frequencies (12, 22, and 37 kHz). Young (n = 16), middle (n = 10) and old-aged (n = 10) CBA mice were tested. DPOAE-grams were obtained using L1 = 65 and L2 = 50 dB SPL, F1/F2 = 1.25, using eight points per octave covering a frequency range from 5.6-44.8 kHz. The pure tone was presented contralaterally at 55 dB SPL. DPOAE-grams and ABR levels indicated age-related hearing loss in the old mice. In addition, there was an overall change in DPOAEs in the middle-aged and old groups relative to the young. Pure tone stimulation was not as effective as a suppressor compared to broadband noise. An increase in pure tone frequency from 12 to 22 kHz induced greater suppression of DPOAEs, but the 37 kHz was least effective. These results indicate that as the mouse ages, there are significant changes in the efficiency of the suppression mechanism as elicited by contralateral narrowband stimuli. These findings reinforce the idea that age-related changes in the MOC or the operating points of OHCs play a role in the progression of presbycusis - age-related hearing loss in mammals.

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

    Science.gov (United States)

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    BACKGROUND: Cardiovascular disease is 1 of the most common age-related diseases, and also 1 of the most common causes of death in the general population. We tested the hypothesis that visible age-related signs associate with risk of ischemic heart disease (IHD), myocardial infarction (MI), and de...

  19. Vitamin D mitigates age-related cognitive decline through the modulation of pro-inflammatory state and decrease in amyloid burden

    OpenAIRE

    Briones Teresita L; Darwish Hala

    2012-01-01

    Abstract Background Increasing evidence shows an association between the use of vitamin D and improvement in age-related cognitive decline. In this study, we investigated the possible mechanisms involved in the neuroprotective effects of vitamin D on age-related brain changes and cognitive function. Methods Male F344 rats aged 20 months (old) and 6 months (young) were used and randomly assigned to either vitamin D supplementation or no supplementation (control). A total of n = 39 rats were us...

  20. Adipocyte-derived factors in age-related dementia and their contribution to vascular and Alzheimer pathology.

    Science.gov (United States)

    Ishii, Makoto; Iadecola, Costantino

    2016-05-01

    Age-related dementia is increasingly recognized as having a mixed pathology, with contributions from both cerebrovascular factors and pathogenic factors associated with Alzheimer's disease (AD). Furthermore, there is accumulating evidence that vascular risk factors in midlife, e.g., obesity, diabetes, and hypertension, increase the risk of developing late-life dementia. Since obesity and changes in body weight/adiposity often drive diabetes and hypertension, understanding the relationship between adiposity and age-related dementia may reveal common underlying mechanisms. Here we offer a brief appraisal of how changes in body weight and adiposity are related to both AD and dementia on vascular basis, and examine the involvement of two key adipocyte-derived hormones: leptin and adiponectin. The evidence suggests that in midlife increased body weight/adiposity and subsequent changes in adipocyte-derived hormones may increase the long-term susceptibility to dementia. On the other hand, later in life, decreases in body weight/adiposity and related hormonal changes are early manifestations of disease that precede the onset of dementia and may promote AD and vascular pathology. Understanding the contribution of adiposity to age-related dementia may help identify the underlying pathological mechanisms common to both vascular dementia and AD, and provide new putative targets for early diagnosis and therapy. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock. PMID:26546479

  1. Age-related differences in susceptibility to cisplatin-induced renal toxicity.

    Science.gov (United States)

    Espandiari, P; Rosenzweig, B; Zhang, J; Zhou, Y; Schnackenberg, L; Vaidya, V S; Goering, P L; Brown, R P; Bonventre, J V; Mahjoob, K; Holland, R D; Beger, R D; Thompson, K; Hanig, J; Sadrieh, N

    2010-03-01

    Limited experimental models exist to assess drug toxicity in pediatric populations. We recently reported how a multi-age rat model could be used for pre-clinical studies of comparative drug toxicity in pediatric populations. The objective of this study was to expand the utility of this animal model, which previously demonstrated an age-dependent sensitivity to the classic nephrotoxic compound, gentamicin, to another nephrotoxicant, namely cisplatin (Cis). Sprague-Dawley rats (10, 25, 40 and 80 days old) were injected with a single dose of Cis (0, 1, 3 or 6 mg kg(-1) i.p.). Urine samples were collected prior and up to 72 h after treatment in animals that were >or= 25 days old. Several serum, urinary and 'omic' injury biomarkers as well as renal histopathology lesions were evaluated. Statistically significant changes were noted with different injury biomarkers in different age groups. The order of age-related Cis-induced nephrotoxicity was different than our previous study with gentamicin: 80 > 40 > 10 > 25 day-old vs 10 >or= 80 > 40 > 25-day-old rats, respectively. The increased levels of kidney injury molecule-1 (Kim-1: urinary protein/tissue mRNA) provided evidence of early Cis-induced nephrotoxicity in the most sensitive age group (80 days old). Levels of Kim-1 tissue mRNA and urinary protein were significantly correlated to each other and to the severity of renal histopathology lesions. These data indicate that the multi-age rat model can be used to demonstrate different age-related sensitivities to renal injury using mechanistically distinct nephrotoxicants, which is reflected in measurements of a variety of metabolite, gene transcript and protein biomarkers.

  2. Age-related differences in susceptibility to cisplatin-induced renal toxicity†

    Science.gov (United States)

    Espandiari, P.; Rosenzweig, B.; Zhang, J.; Zhou, Y.; Schnackenberg, L.; Vaidya, V. S.; Goering, P. L.; Brown, R. P.; Bonventre, J. V.; Mahjoob, K.; Holland, R. D.; Beger, R. D.; Thompson, K.; Hanig, J.; Sadrieh, N.

    2009-01-01

    Limited experimental models exist to assess drug toxicity in pediatric populations. We recently reported how a multi-age rat model could be used for pre-clinical studies of comparative drug toxicity in pediatric populations. The objective of this study was to expand the utility of this animal model, which previously demonstrated an age-dependent sensitivity to the classic nephrotoxic compound, gentamicin, to another nephrotoxicant, namely cisplatin (Cis). Sprague-Dawley rats (10, 25, 40 and 80 days old) were injected with a single dose of Cis (0, 1, 3 or 6 mg kg−1 i.p.). Urine samples were collected prior and up to 72 h after treatment in animals that were ≥25 days old. Several serum, urinary and `omic' injury biomarkers as well as renal histopathology lesions were evaluated. Statistically significant changes were noted with different injury biomarkers in different age groups. The order of age-related Cis-induced nephrotoxicity was different than our previous study with gentamicin: 80 > 40 > 10 > 25 day-old vs 10 ≥ 80 > 40 > 25-day-old rats, respectively. The increased levels of kidney injury molecule-1 (Kim-1: urinary protein/tissue mRNA) provided evidence of early Cis-induced nephrotoxicity in the most sensitive age group (80 days old). Levels of Kim-1 tissue mRNA and urinary protein were significantly correlated to each other and to the severity of renal histopathology lesions. These data indicate that the multi-age rat model can be used to demonstrate different age-related sensitivities to renal injury using mechanistically distinct nephrotoxicants, which is reflected in measurements of a variety of metabolite, gene transcript and protein biomarkers. PMID:19839026

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

    Directory of Open Access Journals (Sweden)

    Mu-En Liu

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

  4. Long-term treatment with aldosterone slows the progression of age-related hearing loss.

    Science.gov (United States)

    Halonen, Joshua; Hinton, Ashley S; Frisina, Robert D; Ding, Bo; Zhu, Xiaoxia; Walton, Joseph P

    2016-06-01

    Age-related hearing loss (ARHL), clinically referred to as presbycusis, is one of the three most prevalent chronic medical conditions of our elderly, with the majority of persons over the age of 60 suffering from some degree of ARHL. The progressive loss of auditory sensitivity and perceptual capability results in significant declines in workplace productivity, quality of life, cognition and abilities to communicate effectively. Aldosterone is a mineralocorticoid hormone produced in the adrenal glands and plays a role in the maintenance of key ion pumps, including the Na-K(+)-Cl co-transporter 1 or NKCC1, which is involved in homeostatic maintenance of the endocochlear potential. Previously we reported that aldosterone (1 μM) increases NKCC1 protein expression in vitro and that this up-regulation of NKCC1 was not dose-dependent (dosing range from 1 nM to 100 μM). In the current study we measured behavioral and electrophysiological hearing function in middle-aged mice following long-term systemic treatment with aldosterone. We also confirmed that blood pressure remained stable during treatment and that NKCC1 protein expression was upregulated. Pre-pulse inhibition of the acoustic startle response was used as a functional measure of hearing, and the auditory brainstem response was used as an objective measure of peripheral sensitivity. Long-term treatment with aldosterone improved both behavioral and physiological measures of hearing (ABR thresholds). These results are the first to demonstrate a protective effect of aldosterone on age-related hearing loss and pave the way for translational drug development, using aldosterone as a key component to prevent or slow down the progression of ARHL. PMID:27157488

  5. Understanding the Experience of Age-Related Vestibular Loss in Older Individuals: A Qualitative Study

    Science.gov (United States)

    Li, Carol; Bridges, John F. P.; Agrawal, Yuri

    2016-01-01

    Background Inner ear balance (or vestibular) function declines with age and is associated with decreased mobility and an increased risk of falls in older individuals. We sought to understand the lived experience of older adults with vestibular loss in order to improve care in this population. Methods Qualitative data were derived from semi-structured interviews of individuals aged 65 years or older presenting to the Balance and Falls Prevention Clinic from February 1, 2014 to March 30, 2015 for evaluation of age-related vestibular loss. Transcripts were analyzed using interpretive phenomenological analysis. We created a taxonomy of overarching superordinate themes based on the World Health Organization's International Classification of Functioning, Disability, and Health (ICF) Framework, and classified key dimensions within each of these themes. Results Sixteen interviews were conducted with individuals (mean age 76.0 years, 75 % female) with age-related vestibular loss. The three superordinate themes and associated key dimensions were (1) body impairment (including depression, fatigue, fear/anxiety, and problems with concentrating and memory); (2) activity limitation and participation restriction (isolation, needing to stop in the middle of activities, reduced participation relative to expectations, reduced ability to drive or travel, and problems with bending/looking up, standing, and walking); and (3) environmental influences (needing help with daily activities). All participants reported difficulty walking. Conclusions Older adults report that vestibular loss impacts their body functioning and restricts their participation in activities. The specific key dimensions uncovered by this qualitative study can be used to evaluate care from the patient's perspective. PMID:26739817

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

    Science.gov (United States)

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

    2015-10-01

    Despite numerous developed drugs based on glucose metabolism interventions for treatment of age-related diseases such as diabetes neuropathies (DNs), DNs are still increasing in patients with type 1 or type 2 diabetes (T1D, T2D). We aimed to identify novel candidates in adipose tissue (AT) and pancreas with T2D for targeting to develop new drugs for DNs therapy. AT-T2D displayed 15 (e.g. SYT4 up-regulated and VGF down-regulated) and pancreas-T2D showed 10 (e.g. BAG3 up-regulated, VAV3 and APOA1 down-regulated) highly differentially expressed genes with neuronal functions as compared to control tissues. ELISA was blindly performed to measure proteins of 5 most differentially expressed genes in 41 human subjects. SYT4 protein was upregulated, VAV3 and APOA1 were down-regulated, and BAG3 remained unchanged in 1- Obese and 2- Obese-T2D without insulin, VGF protein was higher in these two groups as well as in group 3- Obese-T2D receiving insulin than 4-lean subjects. Interaction networks analysis of these 5 genes showed several metabolic pathways (e.g. lipid metabolism and insulin signaling). Pancreas is a novel site for APOA1 synthesis. VGF is synthesized in AT and could be considered as good diagnostic, and even prognostic, marker for age-induced diseases obesity and T2D. This study provides new targets for rational drugs development for the therapy of age-related DNs.

  7. Age-related changes in the joint position sense of the human hand

    Directory of Open Access Journals (Sweden)

    Kowalewski R

    2012-11-01

    Full Text Available Tobias Kalisch,1,2,* Jan-Christoph Kattenstroth,2,* Rebecca Kowalewski,2 Martin Tegenthoff,1 Hubert R Dinse21Department of Neurology, BG-Kliniken Bergmannsheil, Ruhr-University Bochum, Bochum, Germany; 2Neural Plasticity Lab, Institute for Neuroinformatics, Ruhr-University Bochum, Bochum, Germany*These authors contributed equally to this workAbstract: Age-related changes in lower limb joint position sense and their contributions to postural stability are well documented. In contrast, only a few studies have investigated the effect of age on proprioceptive hand function. Here, we introduce a novel test for measuring joint position sense in the fingers of the human hand. In a concurrent matching task, subjects had to detect volume differences between polystyrene balls grasped with their dominant (seven test stimuli: 126–505 cm3 and their nondominant hand (three reference stimuli: 210, 294, and 505 cm3. A total of 21 comparisons were performed to assess the number of errors, the weight of errors (ie, the volume difference between test and reference stimuli, and the direction of errors (ie, over- or underestimation of test stimulus. The test was applied to 45 healthy subjects aged 21 to 79 years. Our results revealed that all variables changed significantly with age, with the number of errors showing the strongest increase. We also assessed tactile acuity (two-point discrimination thresholds and sensorimotor performance (pegboard performance in a subset of subjects, but these scores did not correlate with joint position sense performance, indicating that the test reveals specific information about joint position sense that is not captured with pure sensory or motor tests. The average test–retest reliability assessed on 3 consecutive days was 0.8 (Cronbach's alpha. Our results demonstrate that this novel test reveals age-related decline in joint position sense acuity that is independent from sensorimotor performance.Keywords: aging, hand

  8. Basis for the Age-related Decline in Intestinal Mucosal Immunity

    Directory of Open Access Journals (Sweden)

    Douglas L. Schmucker

    2003-01-01

    Full Text Available The elderly are characterized by mucosal immunosenescence and high rates of morbidity and mortality associated with infectious diseases of the intestinal tract. Little is known about how the differentiation of immunoglobulin A (IgA plasma cells in Peyer's patches (PPs and their subsequent homing to the small intestinal lamina propria (LP is affected by aging. Quantitative immunohistochemical analyses demonstrated a 2-fold increase in the number of IgA+ cells in the PPs, coupled with significant declines in the numbers of IgA+ and antibody-positive cells in the intestinal LP of senescent rats compared to young adult animals. These data suggest that aging diminishes the emigration of IgA immunoblasts from these lymphoid aggregates, as well as their migration to the intestinal LP. Flow cytometry and lymphocyte adoptive transfer studies showed 3- to 4-fold age-related declines in the homing of antibody-containing cells and mesenteric lymph node lymphocytes to the small intestines of rhesus macaques and rats, respectively. The number of peripheral blood IgA immunoblasts expressing the homing molecule α4β7 declined 30% in senescent rats. This was accompanied by a >17% decrease in the areal density of LP blood vessels staining positive for the cell adhesion molecule MAdCAM-1. Cumulatively, declines in expression of these homing molecules constitute a substantial age-related diminution of IgA immunoblast homing potential. In vitro antibody secretion by LP plasma cells, i.e. antibody secreted per antibody-positive cell, remains unchanged as a function of donor age. Intestinal mucosal immunosenescence is a consequence of reduced homing of IgA plasma cells to the intestinal LP as a result of declines in homing molecule expression.

  9. Long-term treatment with aldosterone slows the progression of age-related hearing loss.

    Science.gov (United States)

    Halonen, Joshua; Hinton, Ashley S; Frisina, Robert D; Ding, Bo; Zhu, Xiaoxia; Walton, Joseph P

    2016-06-01

    Age-related hearing loss (ARHL), clinically referred to as presbycusis, is one of the three most prevalent chronic medical conditions of our elderly, with the majority of persons over the age of 60 suffering from some degree of ARHL. The progressive loss of auditory sensitivity and perceptual capability results in significant declines in workplace productivity, quality of life, cognition and abilities to communicate effectively. Aldosterone is a mineralocorticoid hormone produced in the adrenal glands and plays a role in the maintenance of key ion pumps, including the Na-K(+)-Cl co-transporter 1 or NKCC1, which is involved in homeostatic maintenance of the endocochlear potential. Previously we reported that aldosterone (1 μM) increases NKCC1 protein expression in vitro and that this up-regulation of NKCC1 was not dose-dependent (dosing range from 1 nM to 100 μM). In the current study we measured behavioral and electrophysiological hearing function in middle-aged mice following long-term systemic treatment with aldosterone. We also confirmed that blood pressure remained stable during treatment and that NKCC1 protein expression was upregulated. Pre-pulse inhibition of the acoustic startle response was used as a functional measure of hearing, and the auditory brainstem response was used as an objective measure of peripheral sensitivity. Long-term treatment with aldosterone improved both behavioral and physiological measures of hearing (ABR thresholds). These results are the first to demonstrate a protective effect of aldosterone on age-related hearing loss and pave the way for translational drug development, using aldosterone as a key component to prevent or slow down the progression of ARHL.

  10. Risk factors for age-related maculopathy are associated with a relative lack of macular pigment.

    Science.gov (United States)

    Nolan, John M; Stack, Jim; O' Donovan, Orla; Loane, Edward; Beatty, Stephen

    2007-01-01

    Macular pigment (MP) is composed of the two dietary carotenoids lutein (L) and zeaxanthin (Z), and is believed to protect against age-related maculopathy (ARM). This study was undertaken to investigate MP optical density with respect to risk factors for ARM, in 828 healthy subjects from an Irish population. MP optical density was measured psychophysically using heterochromatic flicker photometry, serum L and Z were quantified by HPLC, and dietary intake of L and Z was assessed using a validated food-frequency questionnaire. Clinical and personal details were also recorded, with particular attention directed towards risk factors for ARM. We report a statistically significant age-related decline in MP optical density (r2=0.082, p<0.01). Current and past smokers had lower average MP optical density than never smokers and this difference was statistically significant (p<0.01). Subjects with a confirmed family history of ARM had significantly lower levels of MP optical density than subjects with no known family history of disease (p<0.01). For each of these established risk factors, their statistically significant negative association with MP persisted after controlling for the other two, and also after controlling for other potentially confounding variables such as sex, cholesterol, dietary and serum L (p<0.01). In the absence of retinal pathology, and in advance of disease onset, the relative lack of MP seen in association with increasing age, tobacco use and family history of ARM supports the hypothesis that the enhanced risk that these variables represent for ARM may be attributable, at least in part, to a parallel deficiency of macular carotenoids. PMID:17083932

  11. Emerging therapeutic roles for NAD(+) metabolism in mitochondrial and age-related disorders.

    Science.gov (United States)

    Srivastava, Sarika

    2016-12-01

    Nicotinamide adenine dinucleotide (NAD(+)) is a central metabolic cofactor in eukaryotic cells that plays a critical role in regulating cellular metabolism and energy homeostasis. NAD(+) in its reduced form (i.e. NADH) serves as the primary electron donor in mitochondrial respiratory chain, which involves adenosine triphosphate production by oxidative phosphorylation. The NAD(+)/NADH ratio also regulates the activity of various metabolic pathway enzymes such as those involved in glycolysis, Kreb's cycle, and fatty acid oxidation. Intracellular NAD(+) is synthesized de novo from L-tryptophan, although its main source of synthesis is through salvage pathways from dietary niacin as precursors. NAD(+) is utilized by various proteins including sirtuins, poly ADP-ribose polymerases (PARPs) and cyclic ADP-ribose synthases. The NAD(+) pool is thus set by a critical balance between NAD(+) biosynthetic and NAD(+) consuming pathways. Raising cellular NAD(+) content by inducing its biosynthesis or inhibiting the activity of PARP and cADP-ribose synthases via genetic or pharmacological means lead to sirtuins activation. Sirtuins modulate distinct metabolic, energetic and stress response pathways, and through their activation, NAD(+) directly links the cellular redox state with signaling and transcriptional events. NAD(+) levels decline with mitochondrial dysfunction and reduced NAD(+)/NADH ratio is implicated in mitochondrial disorders, various age-related pathologies as well as during aging. Here, I will provide an overview of the current knowledge on NAD(+) metabolism including its biosynthesis, utilization, compartmentalization and role in the regulation of metabolic homoeostasis. I will further discuss how augmenting intracellular NAD(+) content increases oxidative metabolism to prevent bioenergetic and functional decline in multiple models of mitochondrial diseases and age-related disorders, and how this knowledge could be translated to the clinic for human relevance. PMID

  12. Post-crystallization increases in the mechanical strength of self-assembled fibrillar networks is due to an increase in network supramolecular ordering

    International Nuclear Information System (INIS)

    Fibre-fibre interactions strongly influence the elastic properties of an organogel and are of critical importance to the ability of the network to entrain liquid oil. At 30 deg. C, there was a significant decrease in the storage modulus in time due to a decrease in the amount of crystalline material (i.e. a decrease in the free induction decay (FID) amplitude) and order of crystalline material (i.e. an increase in the FID T2 relaxation time (i.e. a measure of proton mobility)). Conversely, at 5 deg. C, there was an increase in G' in time but no changes were observed in both the amount of crystalline material and its order. This increase in G' was accompanied by a significant increase in the enthalpy of melt and the melting temperature, which translated to a significant increase in the entropy of melt of the system. This decrease in the absolute entropy of the system in time probably arose due to an increase in the number of van der Waals interactions between 12-hydroxystearic acid fibres. Hence the increased order of the system is due to the fibre-fibre interactions which results in a significant increase in G' in time at 5 deg. C.

  13. Association of Serum Ferritin and Kidney Function with Age-Related Macular Degeneration in the General Population

    OpenAIRE

    Oh, Il Hwan; Choi, Eun Young; Park, Joon-Sung; Lee, Chang Hwa

    2016-01-01

    Ferritin is considered to be a marker of the body’s iron stores and has a potential relationship with the systemic manifestations of inflammatory reactions. Data on the association between increased levels of serum ferritin and ocular problems are limited, particularly in relation to age-related macular degeneration (AMD). Serum ferritin levels, as a possible clinical parameter for predicting AMD, were analyzed in anthropometric, biochemical, and ophthalmologic data from a nation-wide, popula...

  14. Age-related changes in cerebellar and hypothalamic function accompany non-microglial immune gene expression, altered synapse organization, and excitatory amino acid neurotransmission deficits

    Science.gov (United States)

    Bonasera, Stephen J.; Arikkath, Jyothi; Boska, Michael D.; Chaudoin, Tammy R.; DeKorver, Nicholas W.; Goulding, Evan H.; Hoke, Traci A.; Mojtahedzedah, Vahid; Reyelts, Crystal D.; Sajja, Balasrinivasa; Schenk, A. Katrin; Tecott, Laurence H.; Volden, Tiffany A.

    2016-01-01

    We describe age-related molecular and neuronal changes that disrupt mobility or energy balance based on brain region and genetic background. Compared to young mice, aged C57BL/6 mice exhibit marked locomotor (but not energy balance) impairments. In contrast, aged BALB mice exhibit marked energy balance (but not locomotor) impairments. Age-related changes in cerebellar or hypothalamic gene expression accompany these phenotypes. Aging evokes upregulation of immune pattern recognition receptors and cell adhesion molecules. However, these changes do not localize to microglia, the major CNS immunocyte. Consistent with a neuronal role, there is a marked age-related increase in excitatory synapses over the cerebellum and hypothalamus. Functional imaging of these regions is consistent with age-related synaptic impairments. These studies suggest that aging reactivates a developmental program employed during embryogenesis where immune molecules guide synapse formation and pruning. Renewed activity in this program may disrupt excitatory neurotransmission, causing significant behavioral deficits. PMID:27689748

  15. Catechol-O-methyltransferase (COMT Genotype Affects Age-Related Changes in Plasticity in Working Memory: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Stephan Heinzel

    2014-01-01

    Full Text Available Objectives. Recent work suggests that a genetic variation associated with increased dopamine metabolism in the prefrontal cortex (catechol-O-methyltransferase Val158Met; COMT amplifies age-related changes in working memory performance. Research on younger adults indicates that the influence of dopamine-related genetic polymorphisms on working memory performance increases when testing the cognitive limits through training. To date, this has not been studied in older adults. Method. Here we investigate the effect of COMT genotype on plasticity in working memory in a sample of 14 younger (aged 24–30 years and 25 older (aged 60–75 years healthy adults. Participants underwent adaptive training in the n-back working memory task over 12 sessions under increasing difficulty conditions. Results. Both younger and older adults exhibited sizeable behavioral plasticity through training (P<.001, which was larger in younger as compared to older adults (P<.001. Age-related differences were qualified by an interaction with COMT genotype (P<.001, and this interaction was due to decreased behavioral plasticity in older adults carrying the Val/Val genotype, while there was no effect of genotype in younger adults. Discussion. Our findings indicate that age-related changes in plasticity in working memory are critically affected by genetic variation in prefrontal dopamine metabolism.

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

    Directory of Open Access Journals (Sweden)

    Herbert eHeuer

    2014-07-01

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

  17. Nutrition and physical activity for the prevention and treatment of age-related sarcopenia.

    Science.gov (United States)

    Bosaeus, Ingvar; Rothenberg, Elisabet

    2016-05-01

    Sarcopenia, defined as loss of skeletal muscle mass and function, is associated with adverse outcomes such as physical disability, impaired quality of life and increased mortality. Several mechanisms are involved in the development of sarcopenia. Potentially modifiable factors include nutrition and physical activity. Protein metabolism is central to the nutritional issues, along with other potentially modifying nutritional factors as energy balance and vitamin D status. An increasing but still incomplete knowledge base has generated recent recommendations on an increased protein intake in the elderly. Several factors beyond the total amount of protein consumed emerge as potentially important in this context. A recent summit examined three hypotheses: (1) A meal threshold; habitually consuming 25-30 g protein at breakfast, lunch and dinner provides sufficient protein to effectively stimulate muscle protein anabolism; (2) Protein quality; including high-quality protein at each meal improves postprandial muscle protein synthesis; and (3) performing physical activity in close temporal proximity to a high-quality protein meal enhances muscle anabolism. Optimising the potential for muscle protein anabolism by consuming an adequate amount of high-quality protein at each meal, in combination with physical activity, appears as a promising strategy to prevent or delay the onset of sarcopenia. However, results of interventions are inconsistent, and well-designed, standardised studies evaluating exercise or nutrition interventions are needed before guidelines can be developed for the prevention and treatment of age-related sarcopenia. PMID:26620911

  18. What is the role of assisted reproduction technology in the management of age-related infertility?

    Science.gov (United States)

    Marinakis, Gerasimos; Nikolaou, Dimitrios

    2011-03-01

    Although in the UK the upper age limit for National Health Service (NHS) provision of in vitro fertilisation (IVF) is 39 years of age there has been an increase in number of women having fertility treatment in their 40s. However, the success rates of IVF and intra-uterine insemination (IUI) in this group remain low. Human Fertilisation and Embryology Authority (HFEA) data from 2006 showed that the live-birth rate from IVF in the UK was 11% in the age group 40-42, 4.6% in the age group 43-44 and less than 4% in women over 44. We performed a literature search for studies using terms and combinations of terms in online databases and published meta-analyses reporting the outcome of interventions in older women. This review showed that assisted reproduction technologies (ARTs) continue to have low live-birth rates in women over 40. Trials showed that assisted hatching may increase the chance of pregnancy in women with poor history. Blastocyst transfer is associated with better outcome, whereas application of pre-implantation genetic screening (PGS) in older women has not increased the success rates. It appears that, with the exception of egg-donation, ART has no answer yet to age-related decline of female fertility. PMID:21329469

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

    Science.gov (United States)

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

    2014-10-01

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

  20. Increasing the dynamic control space of mammalian transcription devices by combinatorial assembly of homologous regulatory elements from different bacterial species.

    Science.gov (United States)

    Bacchus, William; Weber, Wilfried; Fussenegger, Martin

    2013-01-01

    Prokaryotic transcriptional regulatory elements are widely utilized building blocks for constructing regulatory genetic circuits adapted for mammalian cells and have found their way into a broad range of biotechnological applications. Prokaryotic transcriptional repressors, fused to eukaryotic transactivation or repression domains, compose the transcription factor, which binds and adjusts transcription from chimeric promoters containing the repressor-specific operator sequence. Escherichia coli and Chlamydia trachomatis share common features in the regulatory mechanism of the biosynthesis of l-tryptophan. The repressor protein TrpR of C. trachomatis regulates the trpRBA operon and the TrpR of E. coli regulates the trpEDCBA operon, both requiring l-tryptophan as a co-repressor. Fusion of these bacterial repressors to the VP16 transactivation domain of Herpes simplex virus creates synthetic transactivators that could bind and activate chimeric promoters, assembled by placing repressor-specific operator modules adjacent to a minimal promoter, in an l-tryptophan-adjustable manner. Combinations of different transactivator and promoter variants from the same or different bacterial species resulted in a multitude of regulatory systems where l-tryptophan regulation properties, background noise, and maximal gene expression levels were significantly diverse. Different l-tryptophan analogues showed diverse regulatory capacity depending on the promoter/transactivator combination. We believe the systems approach to rationally choose promoters, transactivators and inducer molecules, to obtain desired and predefined genetic expression dynamics and control profiles, will significantly advance the design of new regulatory circuits as well as improving already existing ones. PMID:23178502

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

    NARCIS (Netherlands)

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

    2003-01-01

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

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

    Science.gov (United States)

    Maillet, David; Schacter, Daniel L

    2016-01-01

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

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

    Science.gov (United States)

    Maillet, David; Schacter, Daniel L

    2016-01-01

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

  4. Diagnosis Of Age-Related Cardiovascular Disorders | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    The National Institute on Aging Cardiovascular Biology Unit-Vascular Group is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize novel methods for diagnosing age-related cardiovascular disorders.

  5. Elevated high-density lipoprotein cholesterol and age-related macular degeneration: the Alienor study.

    Directory of Open Access Journals (Sweden)

    Audrey Cougnard-Grégoire

    Full Text Available BACKGROUND: Lipid metabolism and particularly high-density lipoprotein (HDL may be involved in the pathogenic mechanism of age-related macular degeneration (AMD. However, conflicting results have been reported in the associations of AMD with plasma HDL and other lipids, which may be confounded by the recently reported associations of AMD with HDL-related genes. We explored the association of AMD with plasma lipid levels and lipid-lowering medication use, taking into account most of HDL-related genes associated with AMD. METHODS: The Alienor study is a population-based study on age-related eye diseases performed in 963 elderly residents of Bordeaux (France. AMD was graded from non mydriatic color retinal photographs in three exclusive stages: no AMD (n = 430 subjects, 938 eyes; large soft distinct drusen and/or large soft indistinct drusen and/or reticular drusen and/or pigmentary abnormalities (early AMD, n = 176, 247; late AMD (n = 40, 61. Associations of AMD with plasma lipids (HDL, total cholesterol (TC, Low-density lipoprotein (LDL, and triglycerides (TG were estimated using Generalized Estimating Equation logistic regressions. Statistical analyses included 646 subjects with complete data. RESULTS: After multivariate adjustment for age, sex, educational level, smoking, BMI, lipid-lowering medication use, cardiovascular disease and diabetes, and for all relevant genetic polymorphisms (ApoE2, ApoE4, CFH Y402H, ARMS2 A69S, LIPC rs10468017, LIPC rs493258, LPL rs12678919, ABCA1 rs1883025 and CETP rs3764261, higher HDL was significantly associated with an increased risk of early (OR = 2.45, 95%CI: 1.54-3.90; P = 0.0002 and any AMD (OR = 2.29, 95%CI: 1.46-3.59; P = 0.0003. Association with late AMD was far from statistical significance (OR = 1.58, 95%CI: 0.48-5.17; p = 0.45. No associations were found for any stage of AMD with TC, LDL and TG levels, statin or fibrate drug use. CONCLUSIONS: This study suggests that elderly patients with high HDL

  6. Evaluation of cardiovascular biomarkers in patients with age-related wet macular degeneration

    Directory of Open Access Journals (Sweden)

    Keles S

    2014-08-01

    Full Text Available Sadullah Keles,1 Orhan Ates,1 Baki Kartal,2 Hamit Hakan Alp,3 Metin Ekinci,4 Erdinc Ceylan,2 Osman Ondas,5 Eren Arpali,2 Semih Dogan,6 Kenan Yildirim,7 Mevlut Sait Keles8 1Department of Ophthalmology, School of Medicine, Ataturk University, Erzurum, Turkey; 2Department of Ophthalmology, Regional Training and Research Hospital, Erzurum, Turkey; 3Department of Biochemistry, School of Medicine, Yuzuncu Yil University, Van, Turkey; 4Department of Ophthalmology, School of Medicine, Kafkas University, Kars, Turkey; 5Department of Ophthalmology, Erbaa Government Hospital, Tokat, Turkey; 6Department of Ophthalmology, Kolan Hospital, Istanbul, Turkey; 7Department of Ophthalmology, Igdir Government Hospital, Igdir, Turkey; 8Department of Biochemistry, School of Medicine, Ataturk University, Erzurum, Turkey Aim: To evaluate levels of homocysteine, asymmetric dimethylarginine (ADMA, and nitric oxide (NO, as well as activity of endothelial NO synthase (eNOS, in patients with age-related macular degeneration (AMD.Methods: The levels of homocysteine, ADMA, and NO and activity of eNOS in patients who were diagnosed with wet AMD by fundus fluorescein angiography (n=30 were compared to a control group with no retinal pathology (n=30.Results: Levels of homocysteine and ADMA were found to be significantly higher in the wet AMD group than in the control group (P<0.001, whereas NO levels and eNOS activity were higher in the control group (P<0.001. In the wet AMD group, we detected a 2.64- and 0.33-fold increase in the levels of ADMA and homocysteine, respectively, and a 0.49- and 2.41-fold decrease in the eNOS activity and NO level, respectively.Conclusion: Elevated levels of homocysteine and ADMA were observed in patients with wet AMD. Increased ADMA may be responsible for the diminished eNOS activity found in these patients, which in turn contributes to the decrease in NO levels, which likely plays a role in the pathogenesis of AMD. Keywords: age-related macular

  7. Age-related alteration in the composition of immunocompetent blood cells in atomic bomb survivors

    International Nuclear Information System (INIS)

    1328 survivors of Hiroshima were studied for alterations in the number of blood lymphocytes belonging to T-cell subpopulations, CD19 antigen-positive B cells and Leu 7 and CD16 antigen-positive lymphocytes. With increasing age, significant decreasing trends in the numbers of some lymphocytes in T-cell subpopulations and of B-cells were seen. The number of blood lymphocytes positive for CD5 antigen was significantly lower in those exposed to radiation (> 1Gy) in the older age group (more than 30 years at the time of bombing) and a similar tendency for decreases in the numbers of CD4, CD8, and CD19 antigen-positive cells was observed, but differences were not significant. The results suggest aging of the T-cell related immune system is accelerated in the irradiated people of advanced age, explained by the age-related decrease in thymic function in those subjects. The number of Leu 7 or CD19 antigen-positive cells was found to be increased significantly in the older age group compared to the younger, although there was little dose dependence. (U.K.)

  8. Grip strength is potentially an early indicator of age-related decline in mice

    Directory of Open Access Journals (Sweden)

    Xuan Ge

    2016-09-01

    Full Text Available The hand grip test has been correlated with mobility and physical performance in older people and has been shown to be a long-term predictor of mortality. Implementation of new strategies for enhancing healthy aging and maintaining independent living are dependent on predictable preclinical studies. The mouse is used extensively as a model in these types of studies, and the paw grip strength test is similar to the hand grip test for people in that it assesses the ability to grip a device with the paw, is non-invasive and easy to perform, and provides reproducible information. However, little has been reported on how grip strength declines with increasing age in mice. This report shows that grip strength was decreased in C57BL/6 (B6 NIA and C57BL/6×BALB/c F1 (CB6F1 NIA male mice at 12 months of age compared to 8-month-old mice, and continued a robust decline to 20 months and then 28 months of age, when the study was terminated. The decline was not related to lean muscle mass, but extensive age-related carpal and digital exostosis could help explain the decreased grip strength times with increasing age. In conclusion, the grip strength test could be useful in mouse preclinical studies to help make translational predictions on treatment strategies to enhance healthy aging.

  9. Grip strength is potentially an early indicator of age-related decline in mice

    Science.gov (United States)

    Ge, Xuan; Cho, Anthony; Ciol, Marcia A.; Pettan-Brewer, Christina; Snyder, Jessica; Rabinovitch, Peter; Ladiges, Warren

    2016-01-01

    The hand grip test has been correlated with mobility and physical performance in older people and has been shown to be a long-term predictor of mortality. Implementation of new strategies for enhancing healthy aging and maintaining independent living are dependent on predictable preclinical studies. The mouse is used extensively as a model in these types of studies, and the paw grip strength test is similar to the hand grip test for people in that it assesses the ability to grip a device with the paw, is non-invasive and easy to perform, and provides reproducible information. However, little has been reported on how grip strength declines with increasing age in mice. This report shows that grip strength was decreased in C57BL/6 (B6) NIA and C57BL/6×BALB/c F1 (CB6F1) NIA male mice at 12 months of age compared to 8-month-old mice, and continued a robust decline to 20 months and then 28 months of age, when the study was terminated. The decline was not related to lean muscle mass, but extensive age-related carpal and digital exostosis could help explain the decreased grip strength times with increasing age. In conclusion, the grip strength test could be useful in mouse preclinical studies to help make translational predictions on treatment strategies to enhance healthy aging. PMID:27613499

  10. Promoter methylation and age-related downregulation of Klotho in rhesus monkey.

    Science.gov (United States)

    King, Gwendalyn D; Rosene, Douglas L; Abraham, Carmela R

    2012-12-01

    While overall DNA methylation decreases with age, CpG-rich areas of the genome can become hypermethylated. Hypermethylation near transcription start sites typically decreases gene expression. Klotho (KL) is important in numerous age-associated pathways including insulin/IGF1 and Wnt signaling and naturally decreases with age in brain, heart, and liver across species. Brain tissues from young and old rhesus monkeys were used to determine whether epigenetic modification of the KL promoter underlies age-related decreases in mRNA and protein levels of KL. The KL promoter in genomic DNA from brain white matter did not show evidence of oxidation in vivo but did exhibit an increase in methylation with age. Further analysis identified individual CpG motifs across the region of interest with increased methylation in old animals. In vitro methyl modification of these individual cytosine residues confirmed that methylation of the promoter can decrease gene transcription. These results provide evidence that changes in KL gene expression with age may, at least in part, be the result of epigenetic changes to the 5' regulatory region. PMID:21922250

  11. Grip strength is potentially an early indicator of age-related decline in mice.

    Science.gov (United States)

    Ge, Xuan; Cho, Anthony; Ciol, Marcia A; Pettan-Brewer, Christina; Snyder, Jessica; Rabinovitch, Peter; Ladiges, Warren

    2016-01-01

    The hand grip test has been correlated with mobility and physical performance in older people and has been shown to be a long-term predictor of mortality. Implementation of new strategies for enhancing healthy aging and maintaining independent living are dependent on predictable preclinical studies. The mouse is used extensively as a model in these types of studies, and the paw grip strength test is similar to the hand grip test for people in that it assesses the ability to grip a device with the paw, is non-invasive and easy to perform, and provides reproducible information. However, little has been reported on how grip strength declines with increasing age in mice. This report shows that grip strength was decreased in C57BL/6 (B6) NIA and C57BL/6×BALB/c F1 (CB6F1) NIA male mice at 12 months of age compared to 8-month-old mice, and continued a robust decline to 20 months and then 28 months of age, when the study was terminated. The decline was not related to lean muscle mass, but extensive age-related carpal and digital exostosis could help explain the decreased grip strength times with increasing age. In conclusion, the grip strength test could be useful in mouse preclinical studies to help make translational predictions on treatment strategies to enhance healthy aging. PMID:27613499

  12. Mitochondrial DNA polymorphism A4917G is independently associated with age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Jeffrey A Canter

    Full Text Available The objective of this study was to determine if MTND2*LHON4917G (4917G, a specific non-synonymous polymorphism in the mitochondrial genome previously associated with neurodegenerative phenotypes, is associated with increased risk for age-related macular degeneration (AMD. A preliminary study of 393 individuals (293 cases and 100 controls ascertained at Vanderbilt revealed an increased occurrence of 4917G in cases compared to controls (15.4% vs.9.0%, p = 0.11. Since there was a significant age difference between cases and controls in this initial analysis, we extended the study by selecting Caucasian pairs matched at the exact age at examination. From the 1547 individuals in the Vanderbilt/Duke AMD population association study (including 157 in the preliminary study, we were able to match 560 (280 cases and 280 unaffected on exact age at examination. This study population was genotyped for 4917G plus specific AMD-associated nuclear genome polymorphisms in CFH, LOC387715 and ApoE. Following adjustment for the listed nuclear genome polymorphisms, 4917G independently predicts the presence of AMD (OR = 2.16, 95%CI 1.20-3.91, p = 0.01. In conclusion, a specific mitochondrial polymorphism previously implicated in other neurodegenerative phenotypes (4917G appears to convey risk for AMD independent of recently discovered nuclear DNA polymorphisms.

  13. The past, present, and future of exudative age-related macular degeneration treatment

    Directory of Open Access Journals (Sweden)

    Yoreh Barak

    2012-01-01

    Full Text Available Treatment of exudative age-related macular degeneration has been revolutionized within the last 6 years with the introduction of vascular endothelial growth factor neutralizing agents. Previously popular "destructive treatments," such as laser photocoagulation and photodynamic treatment have either been abandoned or used as an adjunct to pharmacotherapy. Despite the increase in vision after antivascular endothelial growth factor (VEGF agents, they require repetitive and costly intravitreal injections that also carry the inherit risks of infection, retinal tears, and detachment. Several new and more potent VEGF inhibitors are at different stages of development. The goal of evolving pharmacotherapy is to preserve the therapeutic effect while reducing or eliminating the discomfort of intravitreal drug delivery, as well as identify new therapeutic targets. Complement inhibitors, immunomodulators, integrin inhibitors are a few of the new class of drugs that are expected to be in our armamentarium soon. Current medications act to decrease leakage through abnormal subretinal choroidal vasculature and promote involution. However, these medications are only effective in treating the active stage of the choroidal neovascular membrane. Restoration of vision of a large number of patients with involuted choroidal neovascular membranes is warranted. For this purpose, tissue engineering techniques have been employed to reconstruct the subretinal anatomy. Discovery of biomarkers, pharmacogenetics, and very specific targeting holds the promise of increased potency and safety in the future.

  14. In vivo imaging of retinal pigment epithelium cells in age related macular degeneration.

    Science.gov (United States)

    Rossi, Ethan A; Rangel-Fonseca, Piero; Parkins, Keith; Fischer, William; Latchney, Lisa R; Folwell, Margaret A; Williams, David R; Dubra, Alfredo; Chung, Mina M

    2013-01-01

    Morgan and colleagues demonstrated that the RPE cell mosaic can be resolved in the living human eye non-invasively by imaging the short-wavelength autofluorescence using an adaptive optics (AO) ophthalmoscope. This method, based on the assumption that all subjects have the same longitudinal chromatic aberration (LCA) correction, has proved difficult to use in diseased eyes, and in particular those affected by age-related macular degeneration (AMD). In this work, we improve Morgan's method by accounting for chromatic aberration variations by optimizing the confocal aperture axial and transverse placement through an automated iterative maximization of image intensity. The increase in image intensity after algorithmic aperture placement varied depending upon patient and aperture position prior to optimization but increases as large as a factor of 10 were observed. When using a confocal aperture of 3.4 Airy disks in diameter, images were obtained using retinal radiant exposures of less than 2.44 J/cm(2), which is ~22 times below the current ANSI maximum permissible exposure. RPE cell morphologies that were strikingly similar to those seen in postmortem histological studies were observed in AMD eyes, even in areas where the pattern of fluorescence appeared normal in commercial fundus autofluorescence (FAF) images. This new method can be used to study RPE morphology in AMD and other diseases, providing a powerful tool for understanding disease pathogenesis and progression, and offering a new means to assess the efficacy of treatments designed to restore RPE health.

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

    Institute of Scientific and Technical Information of China (English)

    H; P; Heidenkummer

    1991-01-01

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

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

    OpenAIRE

    Manard, Marine; Carabin, Delphine; Jaspar, Mathieu; Collette, Fabienne

    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 wer...

  17. Female-Specific Effects on Age-Related Spatial Learning Decline in Songbirds

    OpenAIRE

    Kosarussavadi, Saritha

    2015-01-01

    Spatial cognitive decline is a known hallmark for age-related deterioration in learning and memory, as neurobiological changes occur in the hippocampus with advancing age. Sexually dimorphic spatial abilities have also been consistently demonstrated in humans and other mammalian studies. Despite their extended lifespan and adaptations to aging, little is known about avian age-related cognition and physiology. In this experiment, we used zebra finches (Taeniopygia guttata) to investigate the e...

  18. Age-related differences in persistence with bisphosphonates in women with metastatic breast cancer

    OpenAIRE

    Jacob, L; Hadji, P.; Kostev, K

    2016-01-01

    Aims: To investigate age-related persistence with bisphosphonates (BIS) in women with breast cancer (BC) and bone metastases. Methods: We included a dataset of 1541 patients diagnosed with BC and bone metastases and initially treated with BIS between 1994 and 2013. The primary outcome measure was the age-related rate of BIS discontinuation within 12 months after treatment initiation. Therapy discontinuation was defined as a period of at least 90 days without treatment. A multivariate Cox r...

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

    OpenAIRE

    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 t...

  20. Research Highlights from the Purdue-UAB Botanicals Research Center for Age Related Diseases

    OpenAIRE

    Weaver, Connie M.; Barnes, Stephen; Wyss, J. Michael; Kim, Helen; Morré, Dorothy M.; Morré, D. James; Simon, James E.; Lila, Mary Ann; Janle, Elsa M; Ferruzzi, Mario G.

    2009-01-01

    The Purdue-UAB Botanicals Research Center for Age Related Disease uses multidisciplinary and innovative technologies to investigate the bioavailability of bioactive polyphenolic constituents from botanicals and their relationship to human health. Many age-related diseases are associated with oxidative stress and tissue damage. One of the research goals of the Purdue-UAB Center is to investigate the bioavailability of bioactive natural compounds from a complex botanical mixture to the organ af...

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Huiqiang eChen

    2014-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Biswas Jyotirmay

    2002-01-01

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

  4. Metformin inhibits age-related centrosome amplification in Drosophila midgut stem cells through AKT/TOR pathway.

    Science.gov (United States)

    Na, Hyun-Jin; Park, Joung-Sun; Pyo, Jung-Hoon; Jeon, Ho-Jun; Kim, Young-Shin; Arking, Robert; Yoo, Mi-Ae

    2015-07-01

    We delineated the mechanism regulating the inhibition of centrosome amplification by metformin in Drosophila intestinal stem cells (ISCs). Age-related changes in tissue-resident stem cells may be closely associated with tissue aging and age-related diseases, such as cancer. Centrosome amplification is a hallmark of cancers. Our recent work showed that Drosophila ISCs are an excellent model for stem cell studies evaluating age-related increase in centrosome amplification. Here, we showed that metformin, a recognized anti-cancer drug, inhibits age- and oxidative stress-induced centrosome amplification in ISCs. Furthermore, we revealed that this effect is mediated via down-regulation of AKT/target of rapamycin (TOR) activity, suggesting that metformin prevents centrosome amplification by inhibiting the TOR signaling pathway. Additionally, AKT/TOR signaling hyperactivation and metformin treatment indicated a strong correlation between DNA damage accumulation and centrosome amplification in ISCs, suggesting that DNA damage might mediate centrosome amplification. Our study reveals the beneficial and protective effects of metformin on centrosome amplification via AKT/TOR signaling modulation. We identified a new target for the inhibition of age- and oxidative stress-induced centrosome amplification. We propose that the Drosophila ISCs may be an excellent model system for in vivo studies evaluating the effects of anti-cancer drugs on tissue-resident stem cell aging.

  5. Age-related changes in the motricity of the inbred mice strains 129/sv and C57BL/6j.

    Science.gov (United States)

    Serradj, Najet; Jamon, Marc

    2007-02-12

    The development of motor skills was studied at different stages in the life of the mouse, focusing on three key aspects of motor development: early rhythmic motor activities prior to the acquisition of quadruped locomotion, motor skills in young adults, and the effect of aging on motor skills. The age-related development pattern was analysed and compared in two strains of major importance for genomic studies (C57Bl6/j and 129/sv). Early rhythmic air-stepping activities by l-dopa injected mice showed similar overall development in both strains; differences were observed with greater beating frequency and less inter-limb coordination in 129/sv, suggesting that 129/sv had a different maturation process. Performance on the rotarod by young adult C57Bl6/j gradually improved between 1 and 3 months, but then declined with age; performance on the treadmill also declined with an age-related increase in fatigability. Overall performance by 129/sv mice was lower than C57Bl6/j, and the age-related pattern of change was different, with 129/sv having relatively stable performance over time. Inter-strain differences and their possible causes, in particular the role of dopaminergic pathways, are discussed together with repercussions affecting mutant phenotyping procedures. PMID:17126421

  6. Gelotophobia and age: Do disposition towards ridicule and being laughed at predict coping with age-related vulnerabilities?

    Directory of Open Access Journals (Sweden)

    Willibald Ruch

    2010-06-01

    Full Text Available The present study examines how dispositions to ridicule and being laughed at (gelotophobic, gelotophilic or katagelasticistic assist, or hinder, coping with age-related problems or vulnerabilities. A sample of 131 adult participants completed the PhoPhiKat-30, the PPK-Vulnerability Statement Comparison (PPK-VSC, and the Third Age Vulnerabilities Anxiety Survey (TAVAS. Results showed that the PhoPhiKat-30 is a reliable self-report instrument in its English language form. The dispositions to ridicule and being laughed at (as measured by the PhoPhiKat-30 together with education level and amount of worry about actual or potential problems predicted the nature of the response to the age-related vulnerabilities. People of low education, who generally fear being laughed at but who also ridicule others, and have not experienced many age-related vulnerabilities but worry about them, indicate that they would act gelotophobicly when facing such problems. Gelotophilia, higher education and not experiencing worrying vulnerabilities are predictive of a tendency to make others laugh at ones problems. Katagelasticistism, increased age, no education above compulsory schooling, and a higher number of problems encountered but not worried about relates to laughing at the misfortunes of others. The implications of the results for those interacting with older people are discussed.

  7. Age-related changes of the diffusion tensor imaging parameters of the normal cervical spinal cord

    International Nuclear Information System (INIS)

    Highlights: • It is essential to determine the DTI parameters in the whole CSC. • To analyze DTI parameters in all intervertebral space levels of the CSC. • To study the impact of age on these parameters in healthy Chinese subjects. • Provide better insights in factors that could bias the diagnosis of CSC pathologies. - Abstract: Background: The diffusion tensor imaging (DTI) parameters of the cervical spinal cord (CSC) changes with age. However, previous studies only examined specific CSC areas. Objectives: To analyze the DTI parameters in all intervertebral space levels of the whole normal CSC and to study the impact of age on these parameters in a Chinese population. Methods: Thirty-six healthy subjects aged 20–77 years were recruited. DTI parameters were calculated for gray matter (GM) and white matter (WM) funiculi in all the CSC intervertebral spaces (C1/2-C6/7). Age-related changes of DTI parameters were analyzed for the GM and WM funiculi. Results: Fractional anisotropy (FA) and mean diffusivity (MD) were lower in GM than in WM. MD and FA values were lower in the WM in the lower CSC compared with the upper CSC (all P < 0.05), but no difference was observed in GM. In ventral funiculi, MD increased with age, while FA decreased (all P < 0.001). In lateral and dorsal funiculi, MD and FA decreased with age (all P < 0.001). In GM, MD and FA decreased with age (all P < 0.001). Significant age-related changes were observed in FA and MD from GM and WM funiculi. FA was correlated with age in all funiculi (ventral: r = −0.733; lateral: r = −0.468; dorsal: r = −0.607; GM: r = −0.724; all P < 0.01). Conclusion: Important changes in MD and FA were observed with advancing age at all levels of CSC in Chinese patients. DTI parameters may be useful to assess CSC pathology, but the influence of age and segments need to be taken into account in diagnosis

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

    Directory of Open Access Journals (Sweden)

    Fong AH

    2013-04-01

    Full Text Available Angie HC Fong,1 Timothy YY Lai1,2 1Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong Eye Hospital, Kowloon, Hong Kong; 22010 Retina and Macula Centre, Tsimshatsui, Kowloon, Hong Kong Abstract: Neovascular age-related macular degeneration (AMD and diabetic macular edema (DME are major causes of visual impairment in the elderly population worldwide. With the aging population, the prevalence of neovascular AMD and DME has increased substantially over the recent years. Vascular endothelial growth factor (VEGF has been implicated as playing an important role in the pathogenesis of both neovascular AMD and DME. Since its introduction in 2006, ranibizumab, a recombinant, humanized, monoclonal antibody fragment against all isoforms of VEGF-A, has revolutionized the treatment of neovascular AMD and DME. The efficacy and safety of ranibizumab in neovascular AMD has been demonstrated in the ANCHOR and MARINA trials. Further studies including the PIER, PrONTO, and SUSTAIN trials have also evaluated the optimal dosing regimen of ranibizumab in neovascular AMD. The CATT and IVAN trials compared the safety and efficacy of ranibizumab with off-label use of bevacizumab. Studies such as SUSTAIN and HORIZON have shown that ranibizumab has a good safety profile and is well tolerated for over 4 years with very few serious ocular and systemic adverse events. For DME, Phase II RESOLVE study and Phase III RISE and RIDE studies have demonstrated superiority of ranibizumab treatment in improving vision over placebo controls. Phase II READ and Phase III RESOLVE and REVEAL studies have shown that ranibizumab is more effective both as monotherapy and in combination with laser compared with laser monotherapy. The 3-year results from the DRCRnet protocol I study found that ranibizumab with deferred laser resulted in better long-term visual outcome compared with ranibizumab with prompt laser. This review summarizes various

  9. A circulating microrna profile is associated with late-stage neovascular age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Felix Grassmann

    Full Text Available Age-related macular degeneration (AMD is the leading cause of severe vision impairment in Western populations over 55 years. A growing number of gene variants have been identified which are strongly associated with an altered risk to develop AMD. Nevertheless, gene-based biomarkers which could be dysregulated at defined stages of AMD may point toward key processes in disease mechanism and thus may support efforts to design novel treatment regimens for this blinding disorder. Circulating microRNAs (cmiRNAs which are carried by nanosized exosomes or microvesicles in blood plasma or serum, have been recognized as valuable indicators for various age-related diseases. We therefore aimed to elucidate the role of cmiRNAs in AMD by genome-wide miRNA expression profiling and replication analyses in 147 controls and 129 neovascular AMD patients. We identified three microRNAs differentially secreted in neovascular (NV AMD (hsa-mir-301-3p, pcorrected = 5.6*10-5, hsa-mir-361-5p, pcorrected = 8.0*10-4 and hsa-mir-424-5p, pcorrected = 9.6*10-3. A combined profile of the three miRNAs revealed an area under the curve (AUC value of 0.727 and was highly associated with NV AMD (p = 1.2*10-8. To evaluate subtype-specificity, an additional 59 AMD cases with pure unilateral or bilateral geographic atrophy (GA were analyzed for microRNAs hsa-mir-301-3p, hsa-mir-361-5p, and hsa-mir-424-5p. While we found no significant differences between GA AMD and controls neither individually nor for a combined microRNAs profile, hsa-mir-424-5p levels remained significantly higher in GA AMD when compared to NV (pcorrected<0.005. Pathway enrichment analysis on genes predicted to be regulated by microRNAs hsa-mir-301-3p, hsa-mir-361-5p, and hsa-mir-424-5p, suggests canonical TGFβ, mTOR and related pathways to be involved in NV AMD. In addition, knockdown of hsa-mir-361-5p resulted in increased neovascularization in an in vitro angiogenesis assay.

  10. Age-related changes of the diffusion tensor imaging parameters of the normal cervical spinal cord

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Kun, E-mail: medsciwangkun@126.com [Orthopedics Department, Changhai Hospital Affiliated to Second Military Medical University, Shanghai (China); Song, Qingxin; Zhang, Fan; Chen, Zhi; Hou, Canglong; Tang, Yixing [Orthopedics Department, Changhai Hospital Affiliated to Second Military Medical University, Shanghai (China); Chen, Shiyue [Radiology Department, Changhai Hospital Affiliated to Second Military Medical University, Shanghai (China); Hao, Qiang, E-mail: haoqiang@189.cn [Radiology Department, Changhai Hospital Affiliated to Second Military Medical University, Shanghai (China); Shen, Hongxing, E-mail: shenhxgk@126.com [Orthopedics Department, Changhai Hospital Affiliated to Second Military Medical University, Shanghai (China)

    2014-12-15

    Highlights: • It is essential to determine the DTI parameters in the whole CSC. • To analyze DTI parameters in all intervertebral space levels of the CSC. • To study the impact of age on these parameters in healthy Chinese subjects. • Provide better insights in factors that could bias the diagnosis of CSC pathologies. - Abstract: Background: The diffusion tensor imaging (DTI) parameters of the cervical spinal cord (CSC) changes with age. However, previous studies only examined specific CSC areas. Objectives: To analyze the DTI parameters in all intervertebral space levels of the whole normal CSC and to study the impact of age on these parameters in a Chinese population. Methods: Thirty-six healthy subjects aged 20–77 years were recruited. DTI parameters were calculated for gray matter (GM) and white matter (WM) funiculi in all the CSC intervertebral spaces (C1/2-C6/7). Age-related changes of DTI parameters were analyzed for the GM and WM funiculi. Results: Fractional anisotropy (FA) and mean diffusivity (MD) were lower in GM than in WM. MD and FA values were lower in the WM in the lower CSC compared with the upper CSC (all P < 0.05), but no difference was observed in GM. In ventral funiculi, MD increased with age, while FA decreased (all P < 0.001). In lateral and dorsal funiculi, MD and FA decreased with age (all P < 0.001). In GM, MD and FA decreased with age (all P < 0.001). Significant age-related changes were observed in FA and MD from GM and WM funiculi. FA was correlated with age in all funiculi (ventral: r = −0.733; lateral: r = −0.468; dorsal: r = −0.607; GM: r = −0.724; all P < 0.01). Conclusion: Important changes in MD and FA were observed with advancing age at all levels of CSC in Chinese patients. DTI parameters may be useful to assess CSC pathology, but the influence of age and segments need to be taken into account in diagnosis.

  11. Age-related compaction of lens fibers affects the structure and optical properties of rabbit lenses

    Directory of Open Access Journals (Sweden)

    Al-Ghoul Walid M

    2007-12-01

    that inner cortical fibers undergo a greater degree of age-related compaction than nuclear fibers. Increased scatter appears to be only tentatively correlated with regions of fiber compaction, suggesting that it is simply one of an array of factors that contribute to the overall decreased transparency in aged rabbit lenses.

  12. Age-related disruption of autophagy in dermal fibroblasts modulates extracellular matrix components

    Energy Technology Data Exchange (ETDEWEB)

    Tashiro, Kanae [Skin Research Department, POLA Chemical Industries, Inc., Yokohama (Japan); Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka (Japan); Shishido, Mayumi [Skin Research Department, POLA Chemical Industries, Inc., Yokohama (Japan); Fujimoto, Keiko [Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka (Japan); Organelle Homeostasis Research Center, Kyushu University, Fukuoka (Japan); Hirota, Yuko [Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka (Japan); Yo, Kazuyuki; Gomi, Takamasa [Skin Research Department, POLA Chemical Industries, Inc., Yokohama (Japan); Tanaka, Yoshitaka, E-mail: tanakay@bioc.phar.kyushu-u.ac.jp [Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka (Japan); Organelle Homeostasis Research Center, Kyushu University, Fukuoka (Japan)

    2014-01-03

    Highlights: •Autophagosomes accumulate in aged dermal fibroblasts. •Autophagic degradation is impaired in aged dermal fibroblasts. •Autophagy disruption affects extracellular matrix components in dermal fibroblasts. -- Abstract: Autophagy is an intracellular degradative system that is believed to be involved in the aging process. The contribution of autophagy to age-related changes in the human skin is unclear. In this study, we examined the relationship between autophagy and skin aging. Transmission electron microscopy and immunofluorescence microscopy analyses of skin tissue and cultured dermal fibroblasts derived from women of different ages revealed an increase in the number of nascent double-membrane autophagosomes with age. Western blot analysis showed that the amount of LC3-II, a form associated with autophagic vacuolar membranes, was significantly increased in aged dermal fibroblasts compared with that in young dermal fibroblasts. Aged dermal fibroblasts were minimally affected by inhibition of autophagic activity. Although lipofuscin autofluorescence was elevated in aged dermal fibroblasts, the expression of Beclin-1 and Atg5—genes essential for autophagosome formation—was similar between young and aged dermal fibroblasts, suggesting that the increase of autophagosomes in aged dermal fibroblasts was due to impaired autophagic flux rather than an increase in autophagosome formation. Treatment of young dermal fibroblasts with lysosomal protease inhibitors, which mimic the condition of aged dermal fibroblasts with reduced autophagic activity, altered the fibroblast content of type I procollagen, hyaluronan and elastin, and caused a breakdown of collagen fibrils. Collectively, these findings suggest that the autophagy pathway is impaired in aged dermal fibroblasts, which leads to deterioration of dermal integrity and skin fragility.

  13. Age-related disruption of autophagy in dermal fibroblasts modulates extracellular matrix components

    International Nuclear Information System (INIS)

    Highlights: •Autophagosomes accumulate in aged dermal fibroblasts. •Autophagic degradation is impaired in aged dermal fibroblasts. •Autophagy disruption affects extracellular matrix components in dermal fibroblasts. -- Abstract: Autophagy is an intracellular degradative system that is believed to be involved in the aging process. The contribution of autophagy to age-related changes in the human skin is unclear. In this study, we examined the relationship between autophagy and skin aging. Transmission electron microscopy and immunofluorescence microscopy analyses of skin tissue and cultured dermal fibroblasts derived from women of different ages revealed an increase in the number of nascent double-membrane autophagosomes with age. Western blot analysis showed that the amount of LC3-II, a form associated with autophagic vacuolar membranes, was significantly increased in aged dermal fibroblasts compared with that in young dermal fibroblasts. Aged dermal fibroblasts were minimally affected by inhibition of autophagic activity. Although lipofuscin autofluorescence was elevated in aged dermal fibroblasts, the expression of Beclin-1 and Atg5—genes essential for autophagosome formation—was similar between young and aged dermal fibroblasts, suggesting that the increase of autophagosomes in aged dermal fibroblasts was due to impaired autophagic flux rather than an increase in autophagosome formation. Treatment of young dermal fibroblasts with lysosomal protease inhibitors, which mimic the condition of aged dermal fibroblasts with reduced autophagic activity, altered the fibroblast content of type I procollagen, hyaluronan and elastin, and caused a breakdown of collagen fibrils. Collectively, these findings suggest that the autophagy pathway is impaired in aged dermal fibroblasts, which leads to deterioration of dermal integrity and skin fragility

  14. Age-related differences in control of a visuomotor coordination task: a preliminary study.

    Science.gov (United States)

    Ryu, Young Uk; Lee, Kyu-Ho; Lee, Hocheol; Park, Jungsik

    2016-04-01

    [Purpose] The purpose of the current study was to examine age-related differences in control of a perception-action coordination skill. We adapted a visuomotor tracking experiment requiring various coordination patterns between a limb's motion and an external signal. [Subjects and Methods] A total of 12 subjects (6 elderly and 6 young) voluntarily participated in the study. The experimental session consisted of 3 trials for 3 different relative phase patterns: 0°, 90°, and 180°, defined by the relationship between the online visual feedback of the joystick motion and the white dot signal. [Results] The 0° and 180° tracking patterns were stable compared with the 90° tracking pattern for both age groups. The present results also showed that the elderly subjects were less stable than were young subjects for all tracking patterns. [Conclusion] The intrinsic coordination dynamics predicted by the Haken-Kelso-Bunz (HKB) mathematical model did not change with age, whereas utilization of visual feedback information declined overall. Further research is needed regarding methods for increasing utilization of visual feedback information from the perspective of rehabilitation. PMID:27190463

  15. Age-related degeneration of the fornix in the human brain: a diffusion tensor imaging study.

    Science.gov (United States)

    Jang, Sung Ho; Cho, Sang-Hyun; Chang, Min Cheol

    2011-02-01

    As a part of the Papez circuit, the fornix carries information on episodic memory. Several diffusion tensor imaging (DTI) studies have reported on changes in the fornix that occur with aging; however, these studies have been controversial. Using DTI, we attempted to investigate age-related changes of the fornix in the human brain. Sixty subjects (30 males, 30 females; mean age, 49.2 years; range, 20-78 years) were recruited. We categorized subjects into three groups, including young (20-39 years), middle-aged (40-59 years), and older (60-79 years) adults. DTIs were acquired using a sensitivity-encoding head coil on a 1.5 T. We divided the whole fornix into three parts (column, body, and crus) and constructed tractography for each part. We measured fractional anisotropy (FA), apparent diffusion coefficient (ADC), and tract number for each part of the fornix. In all three parts of the fornix, the FA value and tract number decreased, whereas ADC value increased with aging. In addition, a linear regression model was fitted to all three DTI parameters in each part of the fornix. Degenerative change of the fornix in the human brain appears to have occurred at a near constant rate from the 20s to the30s throughout the lifespan. PMID:21062216

  16. Aging Chart: a community resource for rapid exploratory pathway analysis of age-related processes.

    Science.gov (United States)

    Moskalev, Alexey; Zhikrivetskaya, Svetlana; Shaposhnikov, Mikhail; Dobrovolskaya, Evgenia; Gurinovich, Roman; Kuryan, Oleg; Pashuk, Aleksandr; Jellen, Leslie C; Aliper, Alex; Peregudov, Alex; Zhavoronkov, Alex

    2016-01-01

    Aging research is a multi-disciplinary field encompassing knowledge from many areas of basic, applied and clinical research. Age-related processes occur on molecular, cellular, tissue, organ, system, organismal and even psychological levels, trigger the onset of multiple debilitating diseases and lead to a loss of function, and there is a need for a unified knowledge repository designed to track, analyze and visualize the cause and effect relationships and interactions between the many elements and processes on all levels. Aging Chart (http://agingchart.org/) is a new, community-curated collection of aging pathways and knowledge that provides a platform for rapid exploratory analysis. Building on an initial content base constructed by a team of experts from peer-reviewed literature, users can integrate new data into biological pathway diagrams for a visible, intuitive, top-down framework of aging processes that fosters knowledge-building and collaboration. As the body of knowledge in aging research is rapidly increasing, an open visual encyclopedia of aging processes will be useful to both the new entrants and experts in the field. PMID:26602690

  17. Challenges in the Development of Therapy for Dry Age-Related Macular Degeneration.

    Science.gov (United States)

    Wei, Cynthia X; Sun, Aixu; Yu, Ying; Liu, Qianyong; Tan, Yue-Qing; Tachibana, Isamu; Zeng, Hong; Wei, Ji-Ye

    2016-01-01

    Dry age-related macular degeneration (AMD), a multifactorial progressive degenerative disease of the retinal photoreceptors, pigmented epithelium and Bruch's membrane/choroid in central retina, causes visual impairment in millions of elderly people worldwide. The only available therapy for this disease is the over-the-counter (OTC) multi-vitamins plus macular xanthophyll (lutein/zeaxanthin) which attempts to block the damages of oxidative stress and ionizing blue light. Therefore development of dry AMD prescribed treatment is a pressing unmet medical need. However, this effort is currently hindered by many challenges, including an incomplete understanding of the mechanism of pathogenesis that leads to uncertain targets, confounded by not yet validated preclinical models and the difficulty to deliver the drugs to the posterior segment of the eye. Additionally, with slow disease progression and a less than ideal endpoint measurement method, clinical trials are necessarily large, lengthy and expensive. Increased commitment to research and development is an essential foundation for dealing with these problems. Innovations in clinical trials with novel endpoints, nontraditional study designs and the use of surrogate diseases might shorten the study time, reduce the patient sample size and consequently lower the budget for the development of the new therapies for the dry AMD. PMID:26427400

  18. Hyperhomocysteinemia disrupts retinal pigment epithelial structure and function with features of age-related macular degeneration.

    Science.gov (United States)

    Ibrahim, Ahmed S; Mander, Suchreet; Hussein, Khaled A; Elsherbiny, Nehal M; Smith, Sylvia B; Al-Shabrawey, Mohamed; Tawfik, Amany

    2016-02-23

    The disruption of retinal pigment epithelial (RPE) function and the degeneration of photoreceptors are cardinal features of age related macular degeneration (AMD); however there are still gaps in our understanding of underlying biological processes. Excess homocysteine (Hcy) has been reported to be elevated in plasma of patients with AMD. This study aimed to evaluate the direct effect of hyperhomocysteinemia (HHcy) on structure and function of RPE. Initial studies in a mouse model of HHcy, in which cystathionine-β-synthase (cbs) was deficient, revealed abnormal RPE cell morphology with features similar to that of AMD upon optical coherence tomography (OCT), fluorescein angiography (FA), histological, and electron microscopic examinations. These features include atrophy, vacuolization, hypopigmentation, thickened basal laminar membrane, hyporeflective lucency, choroidal neovascularization (CNV), and disturbed RPE-photoreceptor relationship. Furthermore, intravitreal injection of Hcy per se in normal wild type (WT) mice resulted in diffuse hyper-fluorescence, albumin leakage, and CNV in the area of RPE. In vitro experiments on ARPE-19 showed that Hcy dose-dependently reduced tight junction protein expression, increased FITC dextran leakage, decreased transcellular electrical resistance, and impaired phagocytic activity. Collectively, our results demonstrated unreported effects of excess Hcy levels on RPE structure and function that lead to the development of AMD-like features.

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

    Directory of Open Access Journals (Sweden)

    Pierpaola Davalli

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Natalie Sampson

    2012-01-01

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

  1. Photo-damage, photo-protection and age-related macular degeneration.

    Science.gov (United States)

    Marquioni-Ramella, Melisa D; Suburo, Angela M

    2015-09-26

    Age-related macular degeneration (AMD) is a degenerative retinal disease that causes blindness in people 60-65 years and older, with the highest prevalence appearing in people 90 years-old or more. Epidemiological estimates indicate that the number of cases is increasing, and will almost double in the next 20 years. Preventive measures require precise etiological knowledge. This is quite difficult, since AMD is a multifactorial condition with intricate relationships between causes and risk factors. In this review, we describe the impact of light on the structure and physiology of the retina and the pigment epithelium, taking into account the continuous exposure to natural and artificial light sources along the life of an individual. A large body of experimental evidence demonstrates the toxic effects of some lighting conditions on the retina and the pigment epithelium, and consensus exists about the importance of photo-oxidation phenomena in the causality chain between light and retinal damage. Here, we analyzed the transmission of light to the retina, and compared the aging human macula in healthy and diseased retinas, as shown by histology and non-invasive imaging systems. Finally, we have compared the putative retinal photo-sensitive molecular structures that might be involved in the genesis of AMD. The relationship between these compounds and retinal damage supports the hypothesis of light as an important initiating cause of AMD.

  2. Exercise Counteracts Aging-Related Memory Impairment: A Potential Role for the Astrocytic Metabolic Shuttle.

    Science.gov (United States)

    Tsai, Sheng-Feng; Chen, Pei-Chun; Calkins, Marcus J; Wu, Shih-Ying; Kuo, Yu-Min

    2016-01-01

    Age-related cognitive impairment has become one of the most common health threats in many countries. The biological substrate of cognition is the interconnection of neurons to form complex information processing networks. Experience-based alterations in the activities of these information processing networks lead to neuroadaptation, which is physically represented at the cellular level as synaptic plasticity. Although synaptic plasticity is known to be affected by aging, the underlying molecular mechanisms are not well described. Astrocytes, a glial cell type that is infrequently investigated in cognitive science, have emerged as energy suppliers which are necessary for meeting the abundant energy demand resulting from glutamatergic synaptic activity. Moreover, the concerted action of an astrocyte-neuron metabolic shuttle is essential for cognitive function; whereas, energetic incoordination between astrocytes and neurons may contribute to cognitive impairment. Whether altered function of the astrocyte-neuron metabolic shuttle links aging to reduced synaptic plasticity is unexplored. However, accumulated evidence documents significant beneficial effects of long-term, regular exercise on cognition and synaptic plasticity. Furthermore, exercise increases the effectiveness of astrocyte-neuron metabolic shuttle by upregulation of astrocytic lactate transporter levels. This review summarizes previous findings related to the neuronal activity-dependent astrocyte-neuron metabolic shuttle. Moreover, we discuss how aging and exercise may shape the astrocyte-neuron metabolic shuttle in cognition-associated brain areas. PMID:27047373

  3. Improving function in age-related macular degeneration: design and methods of a randomized clinical trial.

    Science.gov (United States)

    Rovner, Barry W; Casten, Robin J; Hegel, Mark T; Massof, Robert W; Leiby, Benjamin E; Tasman, William S

    2011-03-01

    Age-Related Macular Degeneration (AMD) is the leading cause of severe vision loss in older adults and impairs the ability to read, drive, and live independently and increases the risk for depression, falls, and earlier mortality. Although new medical treatments have improved AMD's prognosis, vision-related disability remains a major public health problem. Improving Function in AMD (IF-AMD) is a two-group randomized, parallel design, controlled clinical trial that compares the efficacy of Problem-Solving Therapy (PST) with Supportive Therapy (ST) (an attention control treatment) to improve vision function in 240 patients with AMD. PST and ST therapists deliver 6 one-hour respective treatment sessions to subjects in their homes over 2 months. Outcomes are assessed masked to treatment assignment at 3 months (main trial endpoint) and 6 months (maintenance effects). The primary outcome is targeted vision function (TVF), which refers to specific vision-dependent functional goals that subjects highly value but find difficult to achieve. TVF is an innovative outcome measure in that it is targeted and tailored to individual subjects yet is measured in a standardized way. This paper describes the research methods, theoretical and clinical aspects of the study treatments, and the measures used to evaluate functional and psychiatric outcomes in this population.

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

    Directory of Open Access Journals (Sweden)

    Alessandro Ghezzo

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

  5. Age related differences in mechanical demands imposed on the lower back by manual material handling tasks.

    Science.gov (United States)

    Shojaei, Iman; Vazirian, Milad; Croft, Emily; Nussbaum, Maury A; Bazrgari, Babak

    2016-04-11

    The prevalence of low back pain (LBP) increases with age, yet the underlying mechanism(s) responsible for this remains unclear. To explore the role of biomechanical factors, we investigated age-related differences in lower-back biomechanics during sagittally-symmetric simulated manual material handling tasks. For each task, trunk kinematics and mechanical demand on the lower back were examined, from among 60 participants within five equal-sized and gender-balanced age groups spanning from 20 to 70 years old. The tasks involved lowering a 4.5kg load from an upright standing posture to both knee height and a fixed height and then lifting the load back to the initial upright posture. During these tasks, segmental body kinematics and ground reaction forces were collected using wireless inertial measurement units and a force platform. Overall, older participants completed the tasks with larger pelvic rotation and smaller lumbar flexion. Such adopted trunk kinematics resulted in larger peak shearing demand at the lower back in older vs. younger participants. These results suggest that older individuals may be at a higher risk for developing lower back pain when completing similar manual material handling tasks, consistent with epidemiological evidence for higher risks of occupational low back pain among this cohort. PMID:26556714

  6. Superoxide Dismutase1 Levels in North Indian Population with Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Akshay Anand

    2013-01-01

    Full Text Available Aim. The aim of the study was to estimate the levels of superoxide dismutase1 (SOD1 in patients of age-related macular degeneration (AMD and examine the role of oxidative stress, smoking, hypertension, and other factors involved in the pathogenesis of AMD. Methods. 115 AMD patients and 61 healthy controls were recruited for this study. Serum SOD1 levels were determined by ELISA and were correlated to various risk factors. Logistic regression model of authenticity, by considering SOD1 as independent variable, has been developed along with ROC curve. Results. The SOD1 levels were significantly higher in AMD patients as compared to those of the controls. The difference was not significant for wet and dry AMD. However, the difference was significant between wet AMD subtypes. Nonsignificance of the Hosmer-Lemeshow goodness of fit statistic (χ2=10.516, df=8, P=0.231 indicates the appropriateness of logistic regression model to predict AMD. Conclusion. Oxidative stress in AMD patients may mount compensatory response resulting in increased levels of SOD1 in AMD patients. To predict the risk of AMD on the basis of SOD1, a logistic regression model shows authenticity of 78%, and area under the ROC curve (0.827, P=.0001 with less standard error of 0.033 coupled with 95% confidence interval of 0.762–0.891 further validates the model.

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

    Science.gov (United States)

    Lemke, Ulrike; Besser, Jana

    2016-01-01

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

  8. Age-related changes of structures in cerebellar cortex of cat

    Indian Academy of Sciences (India)

    Changzheng Zhang; Tianmiao Hua; Zaiman Zhu; Xun Luo

    2006-03-01

    We studied the structures of the cerebellar cortex of young adult and old cats for age-related changes, which were statistically analysed. Nissl staining was used to visualize the cortical neurons. The immunohistochemical method was used to display glial fibrillary acidic protein (GFAP)-immunoreactive (IR) astrocytes and neurofilament-immunoreactive (NF-IR) neurons. Under the microscope, the thickness of the cerebellar cortex was measured; and the density of neurons in all the layers as well as that of GFAP-IR cells in the granular layer was analysed. Compared with young adult cats, the thickness of the molecular layer and total cerebellar cortex was significantly decreased in old cats, and that of the granular layer increased. The density of neurons in each layer was significantly lower in old cats than in young adult ones. Astrocytes in old cats were significantly denser than in young adult ones, and accompanied by evident hypertrophy of the cell bodies and enhanced immunoreaction of GFAP substance. Purkinje cells (PCs) in old cats showed much fewer NF-IR dendrites than those in young adults. The above findings indicate a loss of neurons and decrease in the number of dendrites of the PCs in the aged cerebellar cortex, which might underlie the functional decline of afferent efficacy and information integration in the senescent cerebellum. An age-dependent enhancement of activity of the astrocytes may exert a protective effect on neurons in the aged cerebellum.

  9. Age related changes in striatal resting state functional connectivity in autism

    Directory of Open Access Journals (Sweden)

    Aarthi ePadmanabhan

    2013-11-01

    Full Text Available Characterizing the nature of developmental change is critical to understanding the mechanisms that are impaired in complex neurodevelopment disorders such as autism spectrum disorder (ASD and, pragmatically, may allow us to pinpoint periods of plasticity when interventions are particularly useful. Although aberrant brain development has long been theorized as a characteristic feature of ASD, the neural substrates have been difficult to characterize, in part due to a lack of developmental data and to performance confounds. To address these issues, we examined the development of intrinsic functional connectivity with resting state fMRI from late childhood to early adulthood (8-36 years, using a seed based functional connectivity method with the striatum. Overall, we found that both groups show decreases in cortico-striatal circuits over age. However, when controlling for age, ASD participants showed increased connectivity with parietal cortex and decreased connectivity with prefrontal cortex relative to TD participants. In addition, ASD participants showed aberrant age-related changes in connectivity with anterior aspects of cerebellum, and posterior temporal regions (e.g. fusiform gyrus, inferior and superior temporal gyri. In sum, we found prominent differences in the development of striatal connectivity in ASD, most notably, atypical development of connectivity in striatal networks that may underlie cognitive and social reward processing. Our findings highlight the need to identify the biological mechanisms of perturbations in brain reorganization over development, which also may help clarify discrepant findings in the literature.

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

    Science.gov (United States)

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

    2016-08-15

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

  11. Age Related Bioenergetics Profiles in Isolated Rat Cardiomyocytes Using Extracellular Flux Analyses.

    Directory of Open Access Journals (Sweden)

    Kennedy S Mdaki

    Full Text Available Mitochondrial dysfunction is increasingly recognized and studied as a mediator of heart disease. Extracellular flux analysis (XF has emerged as a powerful tool to investigate cellular bioenergetics in the context of cardiac health and disease, however its use and interpretation requires improved understanding of the normal metabolic differences in cardiomyocytes (CM at various stages of maturation. This study standardized XF analyses methods (mitochondrial stress test, glycolytic stress test and palmitate oxidation test and established age related differences in bioenergetics profiles of healthy CMs at newborn (NB1, weaning (3WK, adult (10WK and aged (12-18MO time points. Findings show that immature CMs demonstrate a more robust and sustained glycolytic capacity and a relative inability to oxidize fatty acids when compared to older CMs. The study also highlights the need to recognize the contribution of CO2 from the Krebs cycle as well as lactate from anaerobic glycolysis to the proton production rate before interpreting glycolytic capacity in CMs. Overall, this study demonstrates that caution should be taken to assure that translatable developmental time points are used to investigate mitochondrial dysfunction as a cause of cardiac disease. Specifically, XF analysis of newborn CMs should be reserved to study fetal/neonatal disease and older CMs (≥10 weeks should be used to investigate adult disease pathogenesis. Knowledge gained will aid in improved investigation of developmentally programmed heart disease and stress the importance of discerning maturational differences in bioenergetics when developing mitochondrial targeted preventative and therapeutic strategies for cardiac disease.

  12. Age Related Bioenergetics Profiles in Isolated Rat Cardiomyocytes Using Extracellular Flux Analyses.

    Science.gov (United States)

    Mdaki, Kennedy S; Larsen, Tricia D; Weaver, Lucinda J; Baack, Michelle L

    2016-01-01

    Mitochondrial dysfunction is increasingly recognized and studied as a mediator of heart disease. Extracellular flux analysis (XF) has emerged as a powerful tool to investigate cellular bioenergetics in the context of cardiac health and disease, however its use and interpretation requires improved understanding of the normal metabolic differences in cardiomyocytes (CM) at various stages of maturation. This study standardized XF analyses methods (mitochondrial stress test, glycolytic stress test and palmitate oxidation test) and established age related differences in bioenergetics profiles of healthy CMs at newborn (NB1), weaning (3WK), adult (10WK) and aged (12-18MO) time points. Findings show that immature CMs demonstrate a more robust and sustained glycolytic capacity and a relative inability to oxidize fatty acids when compared to older CMs. The study also highlights the need to recognize the contribution of CO2 from the Krebs cycle as well as lactate from anaerobic glycolysis to the proton production rate before interpreting glycolytic capacity in CMs. Overall, this study demonstrates that caution should be taken to assure that translatable developmental time points are used to investigate mitochondrial dysfunction as a cause of cardiac disease. Specifically, XF analysis of newborn CMs should be reserved to study fetal/neonatal disease and older CMs (≥10 weeks) should be used to investigate adult disease pathogenesis. Knowledge gained will aid in improved investigation of developmentally programmed heart disease and stress the importance of discerning maturational differences in bioenergetics when developing mitochondrial targeted preventative and therapeutic strategies for cardiac disease. PMID:26872351

  13. Progress and Prospects in Human Genetic Research into Age-Related Hearing Impairment

    Directory of Open Access Journals (Sweden)

    Yasue Uchida

    2014-01-01

    Full Text Available Age-related hearing impairment (ARHI is a complex, multifactorial disorder that is attributable to confounding intrinsic and extrinsic factors. The degree of impairment shows substantial variation between individuals, as is also observed in the senescence of other functions. This individual variation would seem to refute the stereotypical view that hearing deterioration with age is inevitable and may indicate that there is ample scope for preventive intervention. Genetic predisposition could account for a sizable proportion of interindividual variation. Over the past decade or so, tremendous progress has been made through research into the genetics of various forms of hearing impairment, including ARHI and our knowledge of the complex mechanisms of auditory function has increased substantially. Here, we give an overview of recent investigations aimed at identifying the genetic risk factors involved in ARHI and of what we currently know about its pathophysiology. This review is divided into the following sections: (i genes causing monogenic hearing impairment with phenotypic similarities to ARHI; (ii genes involved in oxidative stress, biologic stress responses, and mitochondrial dysfunction; and (iii candidate genes for senescence, other geriatric diseases, and neurodegeneration. Progress and prospects in genetic research are discussed.

  14. Effects of physical training on age-related balance and postural control.

    Science.gov (United States)

    Lelard, T; Ahmaidi, S

    2015-11-01

    In this paper, we review the effects of physical activity on balance performance in the elderly. The increase in the incidence of falls with age reflects the disorders of balance-related to aging. We are particularly interested in age-related changes in the balance control system as reflected in different static and dynamic balance tests. We report the results of studies demonstrating the beneficial effects of physical activity on postural balance. By comparing groups of practitioners of different physical activities, it appears that these effects on postural control depend on the type of activity and the time of practice. Thus, we have focused in the present review on "proprioceptive" and "strength" activities. Training programs offering a combination of several activities have demonstrated beneficial effects on the incidence of falls, and we present and compare the effects of these two types of training activities. It emerges that there are differential effects of programs of activities: while all activities improve participants' confidence in their ability, the "proprioceptive" activities rather improve performance in static tasks, while "strength" activities tend to improve performance in dynamic tasks. These effects depend on the targeted population and will have a greater impact on the frailest subjects. The use of new technologies in the form of "exergames" may also be proposed in home-based exercises. PMID:26548366

  15. Effects of physical training on age-related balance and postural control.

    Science.gov (United States)

    Lelard, T; Ahmaidi, S

    2015-11-01

    In this paper, we review the effects of physical activity on balance performance in the elderly. The increase in the incidence of falls with age reflects the disorders of balance-related to aging. We are particularly interested in age-related changes in the balance control system as reflected in different static and dynamic balance tests. We report the results of studies demonstrating the beneficial effects of physical activity on postural balance. By comparing groups of practitioners of different physical activities, it appears that these effects on postural control depend on the type of activity and the time of practice. Thus, we have focused in the present review on "proprioceptive" and "strength" activities. Training programs offering a combination of several activities have demonstrated beneficial effects on the incidence of falls, and we present and compare the effects of these two types of training activities. It emerges that there are differential effects of programs of activities: while all activities improve participants' confidence in their ability, the "proprioceptive" activities rather improve performance in static tasks, while "strength" activities tend to improve performance in dynamic tasks. These effects depend on the targeted population and will have a greater impact on the frailest subjects. The use of new technologies in the form of "exergames" may also be proposed in home-based exercises.

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

    Science.gov (United States)

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

    2016-09-01

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

  17. Vascular endothelial growth factor gene polymorphisms in age-related macular degeneration in a Turkish population

    Institute of Scientific and Technical Information of China (English)

    Yunus; Bulgu; Gokhan; Ozan; Cetin; Vildan; Caner; Ebru; Nevin; Cetin; Volkan; Yaylali; Cem; Yildirim

    2014-01-01

    AIM:To assess the association between age-related macular degeneration(AMD) and three single nucleotide polymorphisms(SNPS) related to the vascular endothelial growth factor(VEGF) gene.METHODS:The patients who were diagnosed with AMD were included in this prospective study. Three SNPs(rs1413711, rs2146323, and rs3025033) of the VEGF gene were genotyped by real-time polymerase chain reaction in the genomic DNA isolated from peripheral blood samples of the 82 patients and 80 controls.RESULTS:The genotype frequencies of rs1413711 and rs2146323 were not significantly different between the study group and the control group(P =0.072 and P =0.058).However, there was a significant difference in the genotype frequencies of these SNPs between the wet type AMD and dry type AMD(P =0.005 and P =0.010,respectively). One of the SNPs(rs1413711) was also found to be associated with the severity of AMD(P =0.001)with significant genotype distribution between early,intermediate, and advanced stages of the disease. The ancestral alleles were protective for both SNPs while the polymorphic alleles increased the risk for dry AMD.CONCLUSION:VEGF SNPs rs1413711 and rs2146323 polymorphisms are significantly associated with AMD subtypes in our population.

  18. Age-related changes in kinematics of the knee joint during deep squat.

    Science.gov (United States)

    Fukagawa, Shingo; Leardini, Alberto; Callewaert, Barbara; Wong, Pius D; Labey, Luc; Desloovere, Kaat; Matsuda, Shuichi; Bellemans, Johan

    2012-06-01

    Researchers frequently use the deep knee squat as a motor task in order to evaluate the kinematic performance after total knee arthroplasty. Many authors reported about the kinematics of a normal squatting motion, however, little is known on what the influence of aging is. Twenty-two healthy volunteers in various age groups (range 21-75 years) performed a deep knee squat activity while undergoing motion analysis using an optical tracking system. The influence of aging was evaluated with respect to kinematics of the trunk, hip, knee and ankle joints. Older subjects required significantly more time to perform a deep squat, especially during the descending phase. They also had more knee abduction and delayed peak knee flexion. Older subjects were slower in descend than ascend during the squat. Although older subjects had a trend towards less maximal flexion and less internal rotation of the knee compared to younger subjects, this difference was not significant. Older subjects also showed a trend towards more forward leaning of the trunk, resulting in increased hip flexion and anterior thoracic tilt. This study confirmed that some aspects of squat kinematics vary significantly with age, and that the basic methodology employed here can successfully detect these age-related trends. Older subjects had more abduction of the knee joint, and this may indicate the load distribution of the medial and lateral condyles could be different amongst ages. Age-matched control data are therefore required whenever the performance of an implant is evaluated during a deep knee squat.

  19. NLRP3 Inflammasome: Activation and Regulation in Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Jiangyuan Gao

    2015-01-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of legal blindness in the elderly in industrialized countries. AMD is a multifactorial disease influenced by both genetic and environmental risk factors. Progression of AMD is characterized by an increase in the number and size of drusen, extracellular deposits, which accumulate between the retinal pigment epithelium (RPE and Bruch’s membrane (BM in outer retina. The major pathways associated with its pathogenesis include oxidative stress and inflammation in the early stages of AMD. Little is known about the interactions among these mechanisms that drive the transition from early to late stages of AMD, such as geographic atrophy (GA or choroidal neovascularization (CNV. As part of the innate immune system, inflammasome activation has been identified in RPE cells and proposed to be a causal factor for RPE dysfunction and degeneration. Here, we will first review the classic model of inflammasome activation, then discuss the potentials of AMD-related factors to activate the inflammasome in both nonocular immune cells and RPE cells, and finally introduce several novel mechanisms for regulating the inflammasome activity.

  20. Mechanical strain modulates age-related changes in the proliferation and differentiation of mouse adipose-derived stromal cells

    Directory of Open Access Journals (Sweden)

    Chiang Wen-Sheng

    2010-03-01

    Full Text Available Abstract Background Previous studies on the effects of aging in human and mouse mesenchymal stem cells suggest that a decline in the number and differentiation potential of stem cells may contribute to aging and aging-related diseases. In this report, we used stromal cells isolated from adipose tissue (ADSCs of young (8-10 weeks, adult (5 months, and old (21 months mice to test the hypothesis that mechanical loading modifies aging-related changes in the self-renewal and osteogenic and adipogenic differentiation potential of these cells. Results We show that aging significantly reduced the proliferation and increased the adipogenesis of ADSCs, while the osteogenic potential is not significantly reduced by aging. Mechanical loading (10% cyclic stretching, 0.5 Hz, 48 h increased the subsequent proliferation of ADSCs from mice of all ages. Although the number of osteogenic colonies with calcium deposition was increased in ADSCs subjected to pre-strain, it resulted from an increase in colony number rather than from an increase in osteogenic potential after strain. Pre-strain significantly reduced the number of oil droplets and the expression of adipogenic marker genes in adult and old ADSCs. Simultaneously subjecting ADSCs to mechanical loading and adipogenic induction resulted in a stronger inhibition of adipogenesis than that caused by pre-strain. The reduction of adipogenesis by mechanical strain was loading-magnitude dependent: loading with 2% strain only resulted in a partial inhibition, and loading with 0.5% strain could not inhibit adipogenesis in ADSCs. Conclusions We demonstrate that mechanical stretching counteracts the loss of self-renewal in aging ADSCs by enhancing their proliferation and, at the same time, reduces the heightened adipogenesis of old cells. These findings are important for the further study of stem cell control and treatment for a variety of aging related diseases.

  1. Age-related changes in the plasticity and toughness of human cortical bone at multiple length-scales

    Energy Technology Data Exchange (ETDEWEB)

    Zimmermann, Elizabeth A.; Schaible, Eric; Bale, Hrishikesh; Barth, Holly D.; Tang, Simon Y.; Reichert, Peter; Busse, Bjoern; Alliston, Tamara; Ager III, Joel W.; Ritchie, Robert O.

    2011-08-10

    The structure of human cortical bone evolves over multiple length-scales from its basic constituents of collagen and hydroxyapatite at the nanoscale to osteonal structures at nearmillimeter dimensions, which all provide the basis for its mechanical properties. To resist fracture, bone’s toughness is derived intrinsically through plasticity (e.g., fibrillar sliding) at structural-scales typically below a micron and extrinsically (i.e., during crack growth) through mechanisms (e.g., crack deflection/bridging) generated at larger structural-scales. Biological factors such as aging lead to a markedly increased fracture risk, which is often associated with an age-related loss in bone mass (bone quantity). However, we find that age-related structural changes can significantly degrade the fracture resistance (bone quality) over multiple lengthscales. Using in situ small-/wide-angle x-ray scattering/diffraction to characterize sub-micron structural changes and synchrotron x-ray computed tomography and in situ fracture-toughness measurements in the scanning electron microscope to characterize effects at micron-scales, we show how these age-related structural changes at differing size-scales degrade both the intrinsic and extrinsic toughness of bone. Specifically, we attribute the loss in toughness to increased non-enzymatic collagen cross-linking which suppresses plasticity at nanoscale dimensions and to an increased osteonal density which limits the potency of crack-bridging mechanisms at micron-scales. The link between these processes is that the increased stiffness of the cross-linked collagen requires energy to be absorbed by “plastic” deformation at higher structural levels, which occurs by the process of microcracking.

  2. Age-related changes in metabolism and disposition of salicylic acid (SAL) in male Fischer 344 rats

    International Nuclear Information System (INIS)

    SAL-induced nephrotoxicity has been reported to be greater in older rats. To examine age- and dose-related changes in disposition and metabolism, SAL was administered po at 5, 50 and 500 mg/kg to male Fischer 344 rats aged 3, 12, and 25 mo. At 5 mg 14C-SAL/kg, urinary excretion was complete by 24hr in 3 and 25 mo rats, but not until 48 hours in 12 mo rats. No age-related differences were observed in the percentage of administered 14C-SAL excreted as oxidative metabolites, unmetabolized SAL, or salicyl ester glucuronide. 25 mo rats excreted significantly less of a total dose of 14C-SAL as the ether glucuronide, while a significant age-related increase was noted in the percentage excreted as salicyluric acid (SUA). At 50 mg 14C-SAL/kg, urinary elimination shifted towards zero-order kinetics and excretion was not complete until 48 hr in all age groups. The percentage of an administered dose of 14C-SAL found in urine as oxidative metabolites and SAL ester glucuronide increased significantly in all age groups, while the percentage excreted as SUA decreased. In addition, 12 and 25 month rats excreted a significantly greater percentage of the total dose as 2,3 and 2,5-dihydroxybenzoic acid than 3 mo rats at ≥ 50 mg 14C-SAL/kg. These results indicate that increased production of oxidative metabolites in older rats at higher doses of SAL may be responsible in part for the age-related increase in acute SAL nephrotoxicity

  3. Sex- and age-related variations of the somatotype in a Chuvasha population.

    Science.gov (United States)

    Kalichman, L; Kobyliansky, E

    2006-01-01

    The aim of this large, cross-sectional study was to describe the age- and sex-related variations of the somatotype, employing Heath and Carter's method, in a Chuvasha population residing in a rural region in central Russia. The investigated sample included 802 males aged 18-89 years (mean 46.9) and 738 females aged 18-90 years (mean 48.6). We evaluated the age and sex differences by one-way ANOVA with somatotype components as dependent variables and sex or age groups as grouping variables. Sex differences of somatotypes appear to be the strongest for endomorphy, with generally higher values in women. Endomorphy in males remained virtually unchanged after 30 years of age, but endomorphy in females kept increasing up to the 6th decade, and then subsequently decreased. Virtually no differences were noted in mesomorphy and a very small difference in ectomorphy between males and females aged 18-30 years. A reduction of sexual dimorphism in all somatotype components after age 70 was also observed. The largest difference of all somatotype components appeared between age groups 18-30 and 31-40 years. Thereafter, somatotypes remained practically unchanged. Mesomorphy continued to increase until the 5th decade in both sexes, while in females, endomorphy continuously increased until their 6th decade. In the 7th and 8th decades, a decrease in mean values was observed. Mesomorphy and ectomorphy showed opposite age-related trends. Results of our study clearly suggest that in physique investigations, the somatotypes need to be studied in each sex separately, and in studies of young people, they need also to be adjusted to age. PMID:16574118

  4. Normal cranial bone marrow MR imaging pattern with age-related ADC value distribution

    Energy Technology Data Exchange (ETDEWEB)

    Li Qi [Department of Radiology, Shengjing Hospital of China Medical University, Sanhao Street No. 36, Heping District, Shenyang 110004 (China); Pan Shinong, E-mail: cjr.panshinong@vip.163.com [Department of Radiology, Shengjing Hospital of China Medical University, Sanhao Street No. 36, Heping District, Shenyang 110004 (China); Yin Yuming [Radiology Associates, LLP, Corpus Christi, TX 78411 (United States); Li Wei; Chen Zhian [Department of Radiology, Shengjing Hospital of China Medical University, Sanhao Street No. 36, Heping District, Shenyang 110004 (China); Liu Yunhui [Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004 (China); Wu Zhenhua; Guo Qiyong [Department of Radiology, Shengjing Hospital of China Medical University, Sanhao Street No. 36, Heping District, Shenyang 110004 (China)

    2011-11-15

    Objective: To determine MRI appearances of normal age-related cranial bone marrow and the relationship between MRI patterns and apparent diffusion coefficient (ADC) values. Methods: Five hundred subjects were divided into seven groups based on ages. Cranial bone marrow MRI patterns were performed based on different thickness of the diploe and signal intensity distribution characteristics. ADC values of the frontal, parietal, occipital and temporal bones on DWI were measured and calculated. Correlations between ages and ADC values, between patterns and ADC values, as well as the distribution of ADC values were analyzed. Results: Normal cranial bone marrow was divided into four types and six subtypes, Type I, II, III and IV, which had positive correlation with age increasing ({chi}{sup 2} = 266.36, P < 0.01). The ADC values of normal parietal and occipital bone marrow showed significant negative correlation with age growing (r = -0.561 and -0.622, P < 0.01), while there were no significant differences of that with age increasing in frontal and temporal bone marrow (P > 0.05). In addition, there was significant negative correlation between the ADC values and MRI patterns in the normal parietal and occipital bones (r = -0.691 and -0.750, P < 0.01). Conclusion: The combination of MRI features and ADC values changes in different cranial bones showed significant correlation with age increasing. Familiar with the MRI appearance of the normal bone marrow conversion pattern in different age group and their ADC value will aid the diagnosis and differential of the cranial bone pathology.

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

    Directory of Open Access Journals (Sweden)

    Johanna eHamel

    2013-06-01

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

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

    Science.gov (United States)

    Fischer, Tamás

    2015-11-15

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

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

    Directory of Open Access Journals (Sweden)

    Francisco Max Damico

    2012-02-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-07-01

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

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

    Science.gov (United States)

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

    2013-01-01

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

  10. Are age-related trends in suicide rates associated with life expectancy and socio-economic factors?

    Science.gov (United States)

    Shah, Ajit

    2009-01-01

    Background. A recent cross-national study reported that suicide rates increased, decreased or remained unchanged with increasing age in individual countries. The relationship between age-related trends in suicide rates and child mortality rates, life expectancy and socio-economic factors was examined. Methods. Countries with an increase, decrease and no change in suicide rates with increasing age were ascertained from an earlier study (Shah, 2007a, International Psychogeriatrics, 19, 1141), which analysed data from the World Health Organisation (WHO). The relationship between age-related trends in suicide rates and (i) child mortality rates, (ii) life expectancy and (iii) markers of socio-economic status (per capita gross national domestic product (GDP) and the Gini coeffcient) was examined using data from the WHO and the United Nations. Results. The main findings were: (i) child mortality rates were significantly lower in countries with an increase in suicide rates with increasing age when compared to countries without a change in suicide rates with increasing age in males; (ii) life expectancy was significantly higher in countries with an increase in suicide rates with increasing age when compared to countries without a change in suicide rates with increasing age in males; and (iii) the Gini coefficient was significantly lower in countries with an increase in suicide rates with increasing age when compared to countries without a change or a decline in suicide rates with increasing age in females. Conclusions. Potential explanations for these findings and the interaction of life expectancy and socio-economic factors with other factors that differentially influence suicide rates in different age and sex groups requires further examination.

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

    DEFF Research Database (Denmark)

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

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Kate E Sprecher

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

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-07-09

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

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

    Science.gov (United States)

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

    2016-01-01

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

  16. Role of homocysteine in age-related vascular and non-vascular diseases.

    Science.gov (United States)

    Parnetti, L; Bottiglieri, T; Lowenthal, D

    1997-08-01

    Homocysteine (Hcy) may represent a metabolic link in the pathogenesis of atherosclerotic vascular diseases and old-age dementias. Hyperhomocysteinemia is an independent risk factor for coronary artery disease and peripheral vascular disease, and is also associated with cerebrovascular disease; specifically, the risk of extracranial carotid atherosclerosis significantly increases in relation to Hcy levels. Hcy is a reliable marker of vitamin B12 deficiency, a common condition in the elderly which is known to induce neurological deficits including cognitive impairment; a high prevalence of folate deficiency has been reported in psychogeriatric patients suffering from depression and dementia. Both these vitamins occupy a key position in the remethylation and synthesis of S-adenosylmethionine (SAMe), a major methyl donor in CNS; therefore, deficiencies in either of these vitamins lead to a decrease in SAMe and increase in Hcy, which can be critical in the aging brain. Another pathogenetic mechanism linking high Hcy levels to reduced cognitive performances in the elderly might be represented by excitotoxicity, since hyperhomocysteinemia may lead to an excessive production of homocysteic acid and cysteine sulphinic acid, which act as endogenous agonists of NMDA receptors. Considering the reasonably high prevalence in the general population of a genetic predisposition to a thermolabile form of the enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR), hyperhomocysteinemia can be seen as the result of multiple genetic and environmental factors leading to vascular and/or neurodegenerative disorders where age-related involutive phenomena represent a common pathogenetic ground. Systematic studies in different psychogeriatric conditions monitoring Hcy levels and clinical features before and after vitamin supplementation are therefore highly recommended. PMID:9359935

  17. Dietary and lifestyle risk factors associated with age-related macular degeneration: A hospital based study

    Directory of Open Access Journals (Sweden)

    Bhatiwada Nidhi

    2013-01-01

    Full Text Available Aim : To establish the frequency, associations and risk factors for age-related macular degeneration (AMD in hospital population of South India. Materials and Methods : In this cross-sectional hospital based study, 3549 subjects (2090 men and 1459 women above 45 years of age were screened randomly for AMD. Participants underwent ocular evaluation and were interviewed for lifestyle variables and dietary intake of carotenoids by structured food frequency questionnaire. AMD was defined according to the international classifications and grading system. Results : Either form of AMD was detected in 77 (2.2% participants. Of which, early and late AMD was present in 63 (1.8% and 14 (0.4% subjects, respectively. Binary logistic analysis showed that the incidence of AMD was significantly higher with increasing age (Odds ratio [OR] 1.17; 95% CI 1.13-1.22 and diabetes (OR 3.97; 95% CI 2.11-7.46. However, AMD was significant among heavy cigarette smokers (OR 5.58; 95% CI 0.88-7.51 and alcoholics (OR 4.85; 95% CI 2.45-12.22. Dietary lutein/zeaxanthin (L/Z and β-carotene intake were associated (P < 0.001 with the reduction in risk for AMD, with an OR of 0.38 and 0.65, respectively. Conclusions : Higher dietary intake of carotenoids, especially L/Z, was associated with lower risk for AMD. Risk of AMD is higher with increasing age and was prevalent among subjects with diabetes. Cessation of smoking and alcohol may reduce the risk of AMD in this population.

  18. Age-Related, Sport-Specific Adaptions of the Shoulder Girdle in Elite Adolescent Tennis Players

    Science.gov (United States)

    Cools, Ann M.; Palmans, Tanneke; Johansson, Fredrik R.

    2014-01-01

    Context: Tennis requires repetitive overhead movements that can lead to upper extremity injury. The scapula and the shoulder play a vital role in injury-free playing. Scapular dysfunction and glenohumeral changes in strength and range of motion (ROM) have been associated with shoulder injury in the overhead athlete. Objective: To compare scapular position and strength and shoulder ROM and strength between Swedish elite tennis players of 3 age categories (16 years). Design: Cross-sectional study. Setting: Tennis training sports facilities. Patients or Other Participants: Fifty-nine adolescent Swedish elite tennis players (ages 10–20 years) selected based on their national ranking. Main Outcome Measure(s): We used a clinical screening protocol with a digital inclinometer and a handheld dynamometer to measure scapular upward rotation at several angles of arm elevation, isometric scapular muscle strength, glenohumeral ROM, and isometric rotator cuff strength. Results: Players older than 16 years showed less scapular upward rotation on the dominant side at 90° and 180° (P < .05). Although all absolute scapular muscle strength values increased with age, there was no change in the body-weight–normalized strength of the middle (P = .9) and lower (P = .81) trapezius or serratus anterior (P = .17). Glenohumeral internal-rotation ROM and total ROM tended to decrease, but this finding was not statistically significant (P = .052 and P = .06, respectively). Whereas normalized internal-rotator strength increased from 14 to 16 years to older than 16 years (P = .009), normalized external-rotator and supraspinatus strength remained unchanged. Conclusions: Age-related changes in shoulder and scapular strength and ROM were apparent in elite adolescent tennis players. Future authors should examine the association of these adaptations with performance data and injury incidence. PMID:25098662

  19. Phacoemulsification Surgery in Eyes with Neovascular Age-Related Macular Degeneration

    Science.gov (United States)

    Papavasileiou, Evangelia; Kumar, Balakrishna Vineeth; Prasad, Som

    2014-01-01

    Purpose. To evaluate the visual outcomes and effect of phacoemulsification surgery on the progression of neovascular age-related macular degeneration (AMD). Methods. Retrospective, noncomparative, and interventional case series. Thirty eyes from 29 subjects with neovascular AMD treated with intravitreal antivascular endothelial growth factor (VEGF) injections who underwent phacoemulsification and had a postsurgery follow-up of 6 months were included. LogMAR best corrected visual acuity (BCVA) was assessed preoperatively; 1 month, 3 months, and 6 months postoperatively; and finally at the last visit. The frequency of anti-VEGF therapy, calculated as the number of intravitreal injections per month, and central macular thickness (CMT) before and after cataract surgery were determined. Results. Median (range) logMAR BCVA was 0.69 (0.16 to 1.32) preoperatively; 0.55 (−0.04 to 1.32) at 1 month, 0.52 (−0.1 to 1.32) at 3 months, and 0.50 (0.0 to 1.32) at 6 months postoperatively; and 0.6 (0.0 to 1.4) at final visit (P = 0.0011). There was no difference in the frequency of anti-VEGF injections between the immediate 6 months before and after phacoemulsification, which was equal to 0.1667 injections per month (P = 0.6377). Median CMT measured 203 μm preoperatively, which temporarily increased to 238 μm at 1 month after surgery (P = 0.0093) and then spontaneously returned to baseline, measuring 212.5 μm at 3 months postoperatively (P = 0.3811). Conclusion. Phacoemulsification surgery significantly improved vision in patients with neovascular AMD, with no increased need for anti-VEGF injections to keep the macula dry postoperatively. PMID:24719771

  20. Understanding Age-Related Changes in Skeletal Muscle Metabolism: Differences Between Females and Males.

    Science.gov (United States)

    Gheller, Brandon J F; Riddle, Emily S; Lem, Melinda R; Thalacker-Mercer, Anna E

    2016-07-17

    Skeletal muscle is the largest metabolic organ system in the human body. As such, metabolic dysfunction occurring in skeletal muscle impacts whole-body nutrient homeostasis. Macronutrient metabolism changes within the skeletal muscle with aging, and these changes are associated in part with age-related skeletal muscle remodeling. Moreover, age-related changes in skeletal muscle metabolism are affected differentially between males and females and are likely driven by changes in sex hormones. Intrinsic and extrinsic factors impact observed age-related changes and sex-related differences in skeletal muscle metabolism. Despite some support for sex-specific differences in skeletal muscle metabolism with aging, more research is necessary to identify underlying differences in mechanisms. Understanding sex-specific aging skeletal muscle will assist with the development of therapies to attenuate adverse metabolic and functional outcomes. PMID:27431365

  1. Mitochondrial ROS regulate oxidative damage and mitophagy but not age-related muscle fiber atrophy

    Science.gov (United States)

    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

  2. Aging-related Changes of Microglia and Astrocytes in Hypothalamus after Intraperitoneal Injection of Hypertonic Saline in Rats

    Institute of Scientific and Technical Information of China (English)

    WANG Xiaoli; XU Yun; WANG Fang; TANG Lihua; LIU Zhilong; LI Honglian; LIU Shenghong

    2006-01-01

    To examine the aging-related changes of microglia and astrocytes in hypothalamus of rats after intraperitoneal injection of hypertonic saline in rats, old- and young-aged rats were injected with hypertonic saline solution into peritoneal cavity. Lectin histochemical techniques using Ricinus communis agglutinin-1 (RCA-1) and immunocytochemical method employing antibody against glial fibrillary acidic protein (GFAP) were used to demonstrate microglia and astrocytes in the hypothalamus of the rats, and the positively-stained cells were analyzed by computer-assisted image analysis system. Our results showed that the numbers of microglia and astrocytes were significantly increased in the hypothalamus of old-aged rats. After intraperitoneal injection of hypertonic saline,the number of microglia was significantly decreased in the hypothalamus of both young- and oldaged groups. After introperitoneal injection of hypertonic saline, the number of GFAP positive cells was significantly increased in the hypothalamus of young rats, but the number of GFAP positive cells did not show significant change in the hypothalamus of old rats. It is concluded that in the hypothalamus of old-aged rats, the increase of microglia may be related with the aging or degeneration of neurons, and the increase of astrocytes may provide more nourishment required by the aged neurons. The microglia and astrocytes in the hypothalamus of the two group rats may be affected by hypertonic saline, and the response of these cells to the stimuli is characterized by some aging-related changes.

  3. Dietary Polyphenols, Berries, and Age-Related Bone Loss: A Review Based on Human, Animal, and Cell Studies

    Directory of Open Access Journals (Sweden)

    Patrice A. Hubert

    2014-03-01

    Full Text Available Bone loss during aging has become an increasing public health concern as average life expectancy has increased. One of the most prevalent forms of age-related bone disease today is osteoporosis in which the body slows down bone formation and existing bone is increasingly being resorbed by the body to maintain the calcium balance. Some causes of this bone loss can be attributed to dysregulation of osteoblast and osteoclast activity mediated by increased oxidative stress through the aging process. Due to certain serious adverse effects of the currently available therapeutic agents that limit their efficacy, complementary and alternative medicine (CAM has garnered interest as a natural means for the prevention of this debilitating disease. Natural antioxidant supplementation, a type of CAM, has been researched to aid in reducing bone loss caused by oxidative stress. Naturally occurring polyphenols, such as anthocyanins rich in berries, are known to have anti-oxidative properties. Several studies have been reviewed to determine the impact polyphenol intake—particularly that of berries—has on bone health. Studies reveal a positive association of high berry intake and higher bone mass, implicating berries as possible inexpensive alternatives in reducing the risk of age related bone loss.

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

    Science.gov (United States)

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

    2013-01-01

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

  5. Reactive oxygen species production induced by ethanol in Saccharomyces cerevisiae increases because of a dysfunctional mitochondrial iron-sulfur cluster assembly system.

    Science.gov (United States)

    Pérez-Gallardo, Rocio V; Briones, Luis S; Díaz-Pérez, Alma L; Gutiérrez, Sergio; Rodríguez-Zavala, José S; Campos-García, Jesús

    2013-12-01

    Ethanol accumulation during fermentation contributes to the toxic effects in Saccharomyces cerevisiae, impairing its viability and fermentative capabilities. The iron-sulfur (Fe-S) cluster biogenesis is encoded by the ISC genes. Reactive oxygen species (ROS) generation is associated with iron release from Fe-S-containing enzymes. We evaluated ethanol toxicity, ROS generation, antioxidant response and mitochondrial integrity in S. cerevisiae ISC mutants. These mutants showed an impaired tolerance to ethanol. ROS generation increased substantially when ethanol accumulated at toxic concentrations under the fermentation process. At the cellular and mitochondrial levels, ROS were increased in yeast treated with ethanol and increased to a higher level in the ssq1∆, isa1∆, iba57∆ and grx5∆ mutants - hydrogen peroxide and superoxide were the main molecules detected. Additionally, ethanol treatment decreased GSH/GSSG ratio and increased catalase activity in the ISC mutants. Examination of cytochrome c integrity indicated that mitochondrial apoptosis was triggered following ethanol treatment. The findings indicate that the mechanism of ethanol toxicity occurs via ROS generation dependent on ISC assembly system functionality. In addition, mutations in the ISC genes in S. cerevisiae contribute to the increase in ROS concentration at the mitochondrial and cellular level, leading to depletion of the antioxidant responses and finally to mitochondrial apoptosis. PMID:24028658

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

    OpenAIRE

    Lepers, Romuald; Stapley, P.J.

    2011-01-01

    International audience 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 5 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 ru...

  7. Gender difference and age-related changes in performance at the long distance duathlon world championship

    OpenAIRE

    Rüst, Christoph Alexander; Knechtle, Beat; Knechtle, Patrizia; Pfeifer, Susanne; Rosemann, Thomas; Lepers, Romuald; Senn, Oliver

    2013-01-01

    The differences in gender and the age-related changes in triathlon (i.e. swimming, cycling, and running) performances have been previously investigated, but data are missing for duathlon (i.e. running, cycling, and running). We investigated the participation and performance trends, as well as the gender difference and the age-related decline in performance, at the 'Powerman Zofingen' long-distance duathlon (10km run, 150km cycle, and 30km run) from 2002 to 2011. During this period, there were...

  8. Fatty old hearts: role of cardiac lipotoxicity in age-related cardiomyopathy

    Science.gov (United States)

    Drosatos, Konstantinos

    2016-01-01

    Age-related cardiomyopathy accounts for a significant part of heart failure cases. Imbalance of the energetic equilibrium of the heart along with mitochondrial dysfunction and impaired β-adrenergic receptor signaling contributes in the aggravation of cardiac function in the elderly. In this review article, studies that correlate cardiac aging with lipotoxicity are summarized. The involvement of inhibition of peroxisome proliferator-activated receptor-α, β-adrenergic receptor desensitization, and mitochondrial dysfunction as underlying mechanisms for the lipid-driven age-related cardiomyopathy are presented with the aim to indicate potential therapeutic targets for cardiac aging. PMID:27558317

  9. Fatty old hearts: role of cardiac lipotoxicity in age-related cardiomyopathy

    Directory of Open Access Journals (Sweden)

    Konstantinos Drosatos

    2016-08-01

    Full Text Available Age-related cardiomyopathy accounts for a significant part of heart failure cases. Imbalance of the energetic equilibrium of the heart along with mitochondrial dysfunction and impaired β-adrenergic receptor signaling contributes in the aggravation of cardiac function in the elderly. In this review article, studies that correlate cardiac aging with lipotoxicity are summarized. The involvement of inhibition of peroxisome proliferator-activated receptor-α, β-adrenergic receptor desensitization, and mitochondrial dysfunction as underlying mechanisms for the lipid-driven age-related cardiomyopathy are presented with the aim to indicate potential therapeutic targets for cardiac aging.

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

    Science.gov (United States)

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

    2015-12-01

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

  11. Measurement of choroid plexus perfusion using dynamic susceptibility MR imaging: capillary permeability and age-related changes

    Energy Technology Data Exchange (ETDEWEB)

    Bouzerar, Roger; Chaarani, Bader; Baledent, Olivier [University Hospital, Image Processing Department, Amiens (France); Gondry-Jouet, Catherine [University Hospital, Radiology Department, Amiens (France); Zmudka, Jadwiga [University Hospital, Geriatric Unit, Amiens (France)

    2013-12-15

    The cerebrospinal fluid (CSF) plays a major role in the physiology of the central nervous system. The continuous turnover of CSF is mainly attributed to the highly vascularized choroid plexus (CP) located in the cerebral ventricles which represent a complex interface between blood and CSF. We propose a method for evaluating CP functionality in vivo using perfusion MR imaging and establish the age-related changes of associated parameters. Fifteen patients with small intracranial tumors were retrospectively studied. MR Imaging was performed on a 3T MR Scanner. Gradient-echo echo planar images were acquired after bolus injection of gadolinium-based contrast agent (CA). The software developed used the combined T1- and T2-effects. The decomposition of the relaxivity signals enables the calculation of the CP capillary permeability (K{sub 2}). The relative cerebral blood volume (rCBV), mean transit time (MTT), and signal slope decrease (SSD) were also calculated. The mean permeability K{sub 2} of the extracted CP was 0.033+/-0.18 s{sup -1}. K{sub 2} and SSD significantly decreased with subject's age whereas MTT significantly increased with subject's age. No significant correlation was found for age-related changes in rCBV and rCBF. The decrease in CP permeability is in line with the age-related changes in CSF secretion observed in animals. The MTT increase indicates significant structural changes corroborated by microscopy studies in animals or humans. Overall, DSC MR-perfusion enables an in vivo evaluation of the hemodynamic state of CP. Clinical applications such as neurodegenerative diseases could be considered thanks to specific functional studies of CP. (orig.)

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

    Science.gov (United States)

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

    2016-01-01

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

  13. Investigating Aging-Related Changes in the Coordination of Agonist and Antagonist Muscles Using Fuzzy Entropy and Mutual Information

    Directory of Open Access Journals (Sweden)

    Wenbo Sun

    2016-06-01

    Full Text Available Aging alters muscular coordination patterns. This study aimed to investigate aging-related changes in the coordination of agonist and antagonist muscles from two aspects, the activities of individual muscles and the inter-muscular coupling. Eighteen young subjects and 10 elderly subjects were recruited to modulate the agonist muscle activity to track a target during voluntary isometric elbow flexion and extension. Normalized muscle activation and fuzzy entropy (FuzzyEn were applied to depict the activities of biceps and triceps. Mutual information (MI was utilized to measure the inter-muscular coupling between biceps and triceps. The agonist activation decreased and the antagonist activation increased significantly during elbow flexion and extension with aging. FuzzyEn values of agonist electromyogram (EMG were similar between the two age groups. FuzzyEn values of antagonist EMG increased significantly with aging during elbow extension. MI decreased significantly with aging during elbow extension. These results indicated increased antagonist co-activation and decreased inter-muscular coupling with aging during elbow extension, which might result from the reduced reciprocal inhibition and the recruitment of additional cortical-spinal pathways connected to biceps. Based on FuzzyEn and MI, this study provided a comprehensive understanding of the mechanisms underlying the aging-related changes in the coordination of agonist and antagonist muscles.

  14. Individualized Treatment of Neovascular Age-Related Macular Degeneration: What are Patients Gaining? Or Losing?

    Directory of Open Access Journals (Sweden)

    Michael W. Stewart

    2015-05-01

    Full Text Available The widespread use of drugs that bind diffusible vascular endothelial growth factor (VEGF has revolutionized the treatment of neovascular age-related macular degeneration (AMD. The pivotal ranibizumab and aflibercept registration trials featured monthly intravitreal injections for 12 months, during which visual acuities and macular edema rapidly improved for the first 3 months and modest gains or stabilization continued until the primary endpoint. In many subsequent trials, patients were evaluated monthly and treated as-needed (PRN according to the results of visual acuity (VA testing, fundus examinations and optical coherence tomography scans. Compared to monthly-treated control groups, PRN treated patients require fewer injections during the first year but they also experience smaller VA gains (1–3 letters. A small number of prospective trials that directly compared monthly with PRN therapy showed that VA gains with discontinuous therapy lag slightly behind those achieved with monthly injections. Physicians recognize that monthly office visits with frequent intraocular injections challenge patients’ compliance, accrue high drug and professional service costs, and clog office schedules with frequently returning patients. To decrease the numbers of both office visits and anti-VEGF injections without sacrificing VA gains, physicians have embraced the treat-and-extend strategy. Treat-and-extend has not been studied as rigorously as PRN but it has become popular among both vitreoretinal specialists and patients. Despite the possible risks associated with discontinuous therapy (decreased VA and increased macular fluid, most physicians individualize treatment (PRN or treat-and-extend for the majority of their patients. This review chapter explores the many advantages of individualized therapy, while balancing these against suboptimal responses due to the decreased frequency of anti-VEGF injections.

  15. Age-related differences in susceptibility to toxic effects of valproic acid in rats.

    Science.gov (United States)

    Espandiari, Parvaneh; Zhang, Jun; Schnackenberg, Laura K; Miller, Terry J; Knapton, Alan; Herman, Eugene H; Beger, Richard D; Hanig, Joseph P

    2008-07-01

    A multi-age rat model was evaluated as a means to identify a potential age-related difference in liver injury following exposure to valproic acid (VPA), a known pediatric hepatotoxic agent. Different age groups of Sprague-Dawley (SD) rats (10-, 25-, 40-, 80-day-old) were administered VPA at doses of 160, 320, 500 or 650 mg kg(-1) (i.p.) for 4 days. Animals from all age groups developed toxicity after treatment with VPA; however, the patterns of toxicity were dissimilar within each age group. The high dose of VPA caused significant lethality in 10- and 25-day-old rats. All doses of VPA caused decrease in the platelet counts (10-, 25-day-old rats) and the rate of growth (40-day-old rats) and increases in the urine creatine concentration (high dose, 80-day-old rats). VPA induced hepatic and splenic alterations in all age groups. The most severe lesions were found mostly in 10- and 80-day-old rats. Significant changes in blood urea nitrogen, alanine aminotransferase and alkaline phosphatase were observed in 10-day-old pups after treatment with low doses of VPA. The highest VPA dose caused significant decreases in the levels of serum total protein (40- and 80-day-old rats). Principal component analysis of spectra derived from terminal urine samples of all age groups showed that each age group clusters separately. In conclusion, this study showed that the vulnerability profile of each age group was different indicating that a multi-age pediatric animal model is appropriate to assess more completely age-dependent changes in drug toxicity.

  16. Effect of yogic practices on age related changes in oxygen metabolism and antioxidant-redox status

    Directory of Open Access Journals (Sweden)

    Rameswar Pal

    2013-08-01

    Full Text Available Objective: The aim of the study was to evaluate the effect of yogic practice on age related changes in antioxidants and redox status, resting metabolism and energy expenditure. Methods: The study was conducted on 60 healthy male volunteers of three age groups viz 20-29 years, 30-39 years and 40-50 years. In addition to their routine activities, volunteers practiced yogasana, pranayama and meditation for a period of 3 months. Blood samples were collected in fasting condition before and after 3 months of yogic practice for the estimation of biochemical parameters. Results: Oxygen consumption and energy expenditure were decreased with the advancement of age and after yogic practice. Respiratory quotient was increased with the age and decreased after yogic practice. Advancement of age showed progressive shifting of redox status towards the oxidized state, which restored by yogic practice. Lowered levels of reduced glutathione, the ratio of reduced to oxidized glutathione, total antioxidant status, vitamin C and vitamin E as well as the activity of enzymes such as superoxide dismutase, catalase, glutathione reductase and glutathione S-transferase were associated with aging. The regular yogic practice helps to improve in these above mentioned parameters. Hydroperoxides, protein carbonyl, malondialdehyde and glutathione peroxidase levels were found to be higher due to progression of age. These have been decreased after yogic practice. Conclusion: Regular yogic practices have the ability to revert back with the changes in antioxidant and redox status due to advancement of age. [J Exp Integr Med 2013; 3(4.000: 305-312

  17. Intra-organ variation in age-related mutation accumulation in the mouse.

    Directory of Open Access Journals (Sweden)

    Rita A Busuttil

    Full Text Available Using a transgenic mouse model harboring chromosomally integrated lacZ mutational target genes, we previously demonstrated that mutations accumulate with age much more rapidly in the small intestine than in the brain. Here it is shown that in the small intestine point mutations preferentially accumulate in epithelial cells of the mucosa scraped off the underlying serosa. The mucosal cells are the differentiated villus cells that have undergone multiple cell divisions. A smaller age-related increase, also involving genome rearrangements, was observed in the serosa, which consists mainly of the remaining crypts and non-dividing smooth muscle cells. In the brain we observed an accumulation of only point mutations in no other areas than hypothalamus and hippocampus. To directly test for cell division as the determining factor in the generation of point mutations we compared mutation induction between mitotically active and quiescent embryonic fibroblasts from the same lacZ mice, treated with either UV (a point mutagen or hydrogen peroxide (a clastogen. The results indicate that while point mutations are highly replication-dependent, genome rearrangements are as easily induced in non-dividing cells as in mitotically active ones. This strongly suggests that the point mutations found to have accumulated in the mucosal part of the small intestine are the consequence of replication errors. The same is likely true for point mutations accumulating in hippocampus and hypothalamus of the brain since neurogenesis in these two areas continues throughout life. The observed intra-organ variation in mutation susceptibility as well as the variation in replication dependency of different types of mutations indicates the need to not only extend observations made on whole organs to their sub-structures but also take the type of mutations and mitotic activity of the cells into consideration. This should help elucidating the impact of genome instability and its

  18. Absence of age-related dopamine transporter loss in current cocaine abusers

    Energy Technology Data Exchange (ETDEWEB)

    Wang, G.J.; Volkow, N.D.; Fischman, M. [Brookhaven National Lab., Upton, NY (United States)] [and others

    1997-05-01

    The brain dopamine (DA) system appears to play a crucial role in the reinforcing properties of cocaine. Using PET we had previously shown significant decreases in DA D2 receptors but no changes in DA transporters (DAT) in detoxified cocaine abusers (>1 month after last cocaine use). This study evaluates DAT availability in current cocaine abusers (15 male and 5 female; age = 36.2{+-}5.3 years old) using PET and [C-11]cocaine, as a DAT ligand, and compares it to that in 18 male and 2 female age matched normal controls. Cocaine abusers had a history of abusing 4.2{+-}2.8 gm /week of cocaine for an average of 11.0{+-}4.9 years and their last use of cocaine was 5.4{+-}8 days prior to PET study. DAT availability was obtained using the ratio of the distribution volume in the region of interest (caudate, pulamen) to that in cerebellum which is a function of Bmax./Kd.+1. DAT availability in cocaine abusers did not differ to that in normals (N) (C= 1.78{+-}0.14, N= 1.77{+-}0.13). In addition, there were no differences between the groups in the distribution volume or the Kl (plasma to brain transfer constant) measures for [C-11]cocaine. However, in the normals but not in the abusers striatal DAT availability decreased with age (C: r = -0.07, p = 0.76; N: r = -0.55, p < 0.01). Though this study fails to show group differences in DAT availability between normals and current cocaine abusers it indicates a blunting of the age-related decline in DAT availability in the cocaine abusers. Future studies in older cocaine abusers at different time after detoxification arc required in order to assess if cocaine slows the loss of DAT with age or whether these changes reflect compensation to increased DAT blockade and recover with detoxification.

  19. Age-related dynamics of follicles and hormones during an induced ovulatory follicular wave in mares.

    Science.gov (United States)

    Ginther, O J; Gastal, M O; Gastal, E L; Jacob, J C; Beg, M A

    2009-03-15

    An ovulatory follicular wave was induced by ablation of follicles > or =6mm and treatment with prostaglandin F2alpha (PGF) on Day 10 (ovulation=Day 0). Follicle and hormone dynamics of the induced waves were compared among three age groups: young (5-6 y, n=14 waves), intermediate (10-14 y, n=16), and old (> or =18, n=15). During the common-growth phase of the induced wave (Days 12-17), diameter of the future ovulatory follicle was not different among ages, but the young group had more (P or =10mm. The number was correlated (r=+0.7; Pmares between consecutive interovulatory intervals, indicating repeatability. Concentrations of LH increased in all age groups during Days 12-17, but were greatest (P<0.002) in the young group and continued to be greater (P<0.0001) throughout the ovulatory LH surge. During several days before Day-1, there were no age-related effects on systemic estradiol concentrations, diameter of the preovulatory follicle, or B-mode echotexture or color-Doppler signals of blood flow in the follicle wall. Interpretations were: (1) greater number of follicles in the young group reflected a greater follicle reserve, (2) greater LH concentrations throughout the ovulatory surge in the young group reflected a more positive response to an extraovarian/environmental influence after removal of the negative effect of progesterone, and (3) lower LH concentrations in the older groups were adequate for the preovulatory changes in the follicle. PMID:19004489

  20. Age-related differences in the toxicity of ochratoxin A in female rats.

    Science.gov (United States)

    Dortant, P M; Peters-Volleberg, G W; Van Loveren, H; Marquardt, R R; Speijers, G J

    2001-01-01

    Ochratoxin A (OTA) is a mycotoxin found in food and feedstuffs of plant and animal origin. OTA exposure is related to nephropathy in humans. Age-related differences, especially in nephro- and immunotoxicity of OTA, were investigated in young adult (aged 12 weeks) and old (aged 27-30 months) female SPF Wag rats, treated by gavage with 0, 0.07, 0.34 or 1.68 mg OTA/kg body weight for 4 weeks. In both age groups, survival was significantly decreased in the highest dose group. Clinical condition, body weight, clinical chemistry parameters (ALAT, ASAT, creatinin and urea) and target organs (as identified by weight and pathology - kidney, liver, adrenals, forestomach and brain) were affected by age and dose, but often more severely in old than in young rats. OTA induced primarily nephropathy. Old rats were more sensitive to induction of tubular karyomegaly and vacuolation/necrosis. In young rats, OTA induced a dose-related thickening of the basement membrane and reduction in splenic T-cell fraction. Decreased IgG levels were seen at 0.34 mg/kg OTA (young and old rats) and 1.68 mg/kg OTA (young rats). Vacuolation of the white brain matter (cerebellar medulla and ventral parts of the brain stem) was significantly increased in young rats at 0.34 and 1.68 mg/kg OTA and in old rats at 0.07 and 0.34 mg/kg OTA. It was concluded that: (1) the profiles of OTA toxicity for both age groups are similar, with the kidney and possibly the brain being primary target organs; (2) based on clinical and pathological data old rats are more sensitive to OTA than young rats; and (3) the immune system is probably not the primary target of OTA toxicity.

  1. A novel source of methylglyoxal and glyoxal in retina: implications for age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Kee Dong Yoon

    Full Text Available Aging of retinal pigment epithelial (RPE cells of the eye is marked by accumulations of bisretinoid fluorophores; two of the compounds within this lipofuscin mixture are A2E and all-trans-retinal dimer. These pigments are implicated in pathological mechanisms involved in some vision-threatening disorders including age-related macular degeneration (AMD. Studies have shown that bisretinoids are photosensitive compounds that undergo photooxidation and photodegradation when irradiated with short wavelength visible light. Utilizing ultra performance liquid chromatography (UPLC with electrospray ionization mass spectrometry (ESI-MS we demonstrate that photodegradation of A2E and all-trans-retinal dimer generates the dicarbonyls glyoxal (GO and methylglyoxal (MG, that are known to modify proteins by advanced glycation endproduct (AGE formation. By extracellular trapping with aminoguanidine, we established that these oxo-aldehydes are released from irradiated A2E-containing RPE cells. Enzyme-linked immunosorbant assays (ELISA revealed that the substrate underlying A2E-containing RPE was AGE-modified after irradiation. This AGE deposition was suppressed by prior treatment of the cells with aminoguanidine. AGE-modification causes structural and functional impairment of proteins. In chronic diseases such as diabetes and atherosclerosis, MG and GO modify proteins by non-enzymatic glycation and oxidation reactions. AGE-modified proteins are also components of drusen, the sub-RPE deposits that confer increased risk of AMD onset. These results indicate that photodegraded RPE bisretinoid is likely to be a previously unknown source of MG and GO in the eye.

  2. Natural history of age-related lobular involution and impact on breast cancer risk.

    Science.gov (United States)

    Radisky, Derek C; Visscher, Daniel W; Frank, Ryan D; Vierkant, Robert A; Winham, Stacey; Stallings-Mann, Melody; Hoskin, Tanya L; Nassar, Aziza; Vachon, Celine M; Denison, Lori A; Hartmann, Lynn C; Frost, Marlene H; Degnim, Amy C

    2016-02-01

    Age-related lobular involution (LI) is a physiological process in which the terminal duct lobular units of the breast regress as a woman ages. Analyses of breast biopsies from women with benign breast disease (BBD) have found that extent of LI is negatively associated with subsequent breast cancer development. Here we assess the natural course of LI within individual women, and the impact of progressive LI on breast cancer risk. The Mayo Clinic BBD cohort consists of 13,455 women with BBD from 1967 to 2001. The BBD cohort includes 1115 women who had multiple benign biopsies, 106 of whom had developed breast cancer. Within this multiple biopsy cohort, the progression of the LI process was examined by age at initial biopsy and time between biopsies. The relationship between LI progression and breast cancer risk was assessed using standardized incidence ratios and by Cox proportional hazards analysis. Women who had multiple biopsies were younger age and had a slightly higher family history of breast cancer as compared with the overall BBD cohort. Extent of LI at subsequent biopsy was greater with increasing time between biopsies and for women age 55 + at initial biopsy. Among women with multiple biopsies, there was a significant association of higher breast cancer risk among those with involution stasis (lack of progression, HR 1.63) as compared with those with involution progression, p = 0.036. The multiple biopsy BBD cohort allows for a longitudinal study of the natural progression of LI. The majority of women in the multiple biopsy cohort showed progression of LI status between benign biopsies, and extent of progression was highest for women who were in the perimenopausal age range at initial biopsy. Progression of LI status between initial and subsequent biopsy was associated with decreased breast cancer risk.

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

    Science.gov (United States)

    Elenbaas, Laura; Killen, Melanie

    2016-01-01

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

  4. Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Evans Christopher

    2010-12-01

    Full Text Available Abstract Background Age-related macular degeneration (AMD is the leading cause of blindness in Western countries. Numerous risk factors have been reported but the evidence and strength of association is variable. We aimed to identify those risk factors with strong levels of evidence which could be easily assessed by physicians or ophthalmologists to implement preventive interventions or address current behaviours. Methods A systematic review identified 18 prospective and cross-sectional studies and 6 case control studies involving 113,780 persons with 17,236 cases of late AMD that included an estimate of the association between late AMD and at least one of 16 pre-selected risk factors. Fixed-effects meta-analyses were conducted for each factor to combine odds ratio (OR and/or relative risk (RR outcomes across studies by study design. Overall raw point estimates of each risk factor and associated 95% confidence intervals (CI were calculated. Results Increasing age, current cigarette smoking, previous cataract surgery, and a family history of AMD showed strong and consistent associations with late AMD. Risk factors with moderate and consistent associations were higher body mass index, history of cardiovascular disease, hypertension, and higher plasma fibrinogen. Risk factors with weaker and inconsistent associations were gender, ethnicity, diabetes, iris colour, history of cerebrovascular disease, and serum total and HDL cholesterol and triglyceride levels. Conclusions Smoking, previous cataract surgery and a family history of AMD are consistent risk factors for AMD. Cardiovascular risk factors are also associated with AMD. Knowledge of these risk factors that may be easily assessed by physicians and general ophthalmologists may assist in identification and appropriate referral of persons at risk of AMD.

  5. Ethnic and age-related fat free mass loss in older Americans: The Third National Health and Nutrition Examination Survey (NHANES III)

    OpenAIRE

    Akomolafe Abimbola; Adams Richard G; Bond Vernon; Aliyu Muktar H; Obisesan Thomas O; Rotimi Charles N

    2005-01-01

    Abstract Background Although age-related loss of fat free mass (FFM) is well known, there is paucity of data on national estimates, and on the differential influence of ethnicity on the decline in FFM with increasing age. We determined whether age-related loss in FFM and fat free mass index (FFMI) vary by gender and or ethnicity, using representative data from the Third National Health and Nutrition Examination Survey (NHANES III). Methods Analyses were limited to 5,803 non-institutionalized,...

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

    DEFF Research Database (Denmark)

    Bellantuono, Ilaria; Aldahmash, Abdullah; Kassem, Moustapha

    2009-01-01

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

  7. Prediction of age-related macular degeneration in the general population: The three continent AMD consortium

    NARCIS (Netherlands)

    G.H.S. Buitendijk (Gabrielle); E. Rochtchina (Elena); C.E. Myers (Chelsea); C.M. van Duijn (Cock); K.E. Lee (Kristine); B.E.K. Klein (Barbara); S.M. Meuer (Stacy); P.T.V.M. de Jong (Paulus); E.G. Holliday (Elizabeth); A.G. Tan (Ava); A.G. Uitterlinden (André); T.A. Sivakumaran (Theru); J. Attia (John); A. Hofman (Albert); P. Mitchell (Paul); J.R. Vingerling (Hans); S.K. Iyengar (Sudha); A.C.J.W. Janssens (Cécile); J.J. Wang (Jie Jin); B.E.K. Klein (Barbara); C.C.W. Klaver (Caroline)

    2013-01-01

    textabstractPurpose Prediction models for age-related macular degeneration (AMD) based on case-control studies have a tendency to overestimate risks. The aim of this study is to develop a prediction model for late AMD based on data from population-based studies. Design Three population-based studies

  8. Complement component C3 and risk of age-related macular degeneration

    NARCIS (Netherlands)

    D.D.G. Despriet; C.M. van Duijn; B.A. Oostra; A.G. Uitterlinden; A. Hofman; A.F. Wright; J.B. ten Brink; A. Bakker; P.T.V.M. de Jong; J.R. Vingerling; A.A.B. Bergen; C.C.W. Klaver

    2009-01-01

    OBJECTIVE: To explore the association between polymorphisms in the complement component 3 (C3) gene and age-related macular degeneration (AMD), and to investigate the modifying effect of complement factor H (CFH) Y402H, LOC387715 A69S and smoking. DESIGN: Pooled data from the prospective, population

  9. Lutein and Age-Related Ocular Disorders in the Older Adult: A Review

    Science.gov (United States)

    Lutein, a carotenoid found in dark green, leafy vegetables, has been implicated as being protective against the acquired ocular diseases, such as cataracts and age-related macular degeneration. In the eye, lutein may act as an antioxidant and as a blue light filter to protect the underlying tissues ...

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

    Science.gov (United States)

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

    2013-01-01

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

  11. Gray matters : Age-related differences in context-dependent idiom processing

    NARCIS (Netherlands)

    la Roi, Amélie; Sprenger, Simone; Hendriks, Petra

    2016-01-01

    Background How does age-related cognitive decline affect context-dependent idiom processing? When people grow older, their cognitive functions decline. Compared to younger adults, elderly adults show impaired cognitive inhibitory skills (Hasher, Stoltzfus, Zacks, & Rypma, 1991) and reduced working m

  12. A novel radial water tread maze tracks age-related cognitive decline in mice

    Directory of Open Access Journals (Sweden)

    Christina Pettan-Brewer

    2013-10-01

    Full Text Available There is currently no treatment and cure for age-related dementia and cognitive impairment in humans. Mice suffer from age-related cognitive decline just as people do, but assessment is challenging because of cumbersome and at times stressful performance tasks. We developed a novel radial water tread (RWT maze and tested male C57BL/6 (B6 and C57BL/6 x Balb/c F1 (CB6F1 mice at ages 4, 12, 20, and 28 months. B6 mice showed a consistent learning experience and memory retention that gradually decreased with age. CB6F1 mice showed a moderate learning experience in the 4 and 12 month groups, which was not evident in the 20 and 28 month groups. In conclusion, CB6F1 mice showed more severe age-related cognitive impairment compared to B6 mice and might be a suitable model for intervention studies. In addition, the RWT maze has a number of operational advantages compared to currently accepted tasks and can be used to assess age-related cognition impairment in B6 and CB6F1 mice as early as 12 months of age.

  13. Cortical complexity as a measure of age-related brain atrophy.

    Science.gov (United States)

    Madan, Christopher R; Kensinger, Elizabeth A

    2016-07-01

    The structure of the human brain changes in a variety of ways as we age. While a sizeable literature has examined age-related differences in cortical thickness, and to a lesser degree, gyrification, here we examined differences in cortical complexity, as indexed by fractal dimensionality in a sample of over 400 individuals across the adult lifespan. While prior studies have shown differences in fractal dimensionality between patient populations and age-matched, healthy controls, it is unclear how well this measure would relate to age-related cortical atrophy. Initially computing a single measure for the entire cortical ribbon, i.e., unparcellated gray matter, we found fractal dimensionality to be more sensitive to age-related differences than either cortical thickness or gyrification index. We additionally observed regional differences in age-related atrophy between the three measures, suggesting that they may index distinct differences in cortical structure. We also provide a freely available MATLAB toolbox for calculating fractal dimensionality. PMID:27103141

  14. Age-related decrease in motor cortical inhibition during standing under different sensory conditions

    NARCIS (Netherlands)

    Papegaaij, Selma; Taube, Wolfgang; Hogenhout, Margot; Baudry, Stephane; Hortobagyi, Tibor

    2014-01-01

    Background: Although recent studies point to the involvement of the primary motor cortex in postural control, it is unknown if age-related deterioration of postural control is associated with changes in motor cortical circuits. We examined the interaction between age and sensory condition in the exc

  15. Fragmentation of the rest-activity rhythm correlates with age-related cognitive deficits

    NARCIS (Netherlands)

    Oosterman, J.M.; Someren, E.J.W. van; Vogels, R.L.C.; Harten, B. van; Scherder, E.J.A.

    2009-01-01

    Aging affects both cognitive performance and the sleep-wake rhythm. The recent surge of studies that support a role of sleep for cognitive performance in healthy young adults suggests that disturbed sleep-wake rhythms may contribute to 'age-related' cognitive decline. This relationship has however n

  16. Tryptophan metabolism : entering the field of aging and age-related pathologies

    NARCIS (Netherlands)

    van der Goot, Annemieke T.; Nollen, Ellen A. A.

    2013-01-01

    Aging is an important risk factor for many debilitating diseases, including cancer and neurodegeneration. In model organisms, interfering with metabolic signaling pathways, including the insulin/insulin-like growth factor (IGF) 1 (IIS) and TOR pathways, can protect against age-related pathologies an

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

    Science.gov (United States)

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

    1998-11-01

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

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

    Science.gov (United States)

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

    2016-08-18

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

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

    NARCIS (Netherlands)

    Steegenga, W.T.; Boekschoten, M.V.; Lute, C.; Hooiveld, G.J.E.J.; Groot, de P.J.; Morris, T.J.; Teschendorff, A.E.; Butcher, L.M.; Beck, S.; Müller, M.R.

    2014-01-01

    Aging is a progressive process that results in the accumulation of intra- and extracellular alterations that in turn contribute to a reduction in health. Age-related changes in DNA methylation have been reported before and may be responsible for aging-induced changes in gene expression, although a c

  20. Segmentation of age-related white matter changes in a clinical multi-center study

    DEFF Research Database (Denmark)

    Dyrby, Tim B.; Rostrup, E.; Baare, W.F.C.;

    2008-01-01

    Age-related white matter changes (WMC) are thought to be a marker of vascular pathology, and have been associated with motor and cognitive deficits. In the present study, an optimized artificial neural network was used as an automatic segmentation method to produce probabilistic maps of WMC...

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

    DEFF Research Database (Denmark)

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2014-12-01

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

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

    Science.gov (United States)

    American Psychologist, 2012

    2012-01-01

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

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

    NARCIS (Netherlands)

    Wisse, L.E.M.

    2014-01-01

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

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Laurent Boyer

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

  7. Age-related behavioral effects of methomyI in Brown Norway rats.

    Science.gov (United States)

    Methomyl is a cholinesterase-inhibiting carbamate pesticide that is used in the field on cotton and a variety of fruits and vegetables. Concerns have been raised generally about age-related differences in susceptibility to cholinesterase-inhibiting pesticides, especially for chil...

  8. Through thick and thin: A circulating growth factor inhibits age-related cardiac hypertrophy

    OpenAIRE

    McPherron, Alexandra C

    2013-01-01

    In an intriguing new study, Loffredo et al., report that joining the circulation of old mice with that of young mice reduces age-related cardiac hypertrophy. They also found that the growth factor GDF11 is a circulating negative regulator of cardiac hypertrophy which suggests that raising GDF11 levels may be useful to treat cardiac hypertrophy associated with aging.

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  10. A systematic review on zinc for the prevention and treatment of age-related macular degeneration

    Science.gov (United States)

    Zinc is a potential candidate for the prevention and treatment of age-related macular degeneration (AMD) due to its high concentration in the retina and role as a cofactor for antioxidant enzymes. The objective of this work was to conduct a systematic review of studies that investigated dietary inta...

  11. Patients’ knowledge and perspectives on wet age-related macular degeneration and its treatment

    Directory of Open Access Journals (Sweden)

    Sushma Kandula

    2010-04-01

    Full Text Available Sushma Kandula1, Jeffrey C Lamkin1, Teresa Albanese2, Deepak P Edward11Department of Ophthalmology, 2Health Service Research and Education Institute, SUMMA Health System, Akron OH, USASummary: There have been no studies examining the level of understanding age-related macular degeneration (ARMD patients have about their disease, or their perceptions about intraocular injections as treatment. In this study, patient knowledge about ARMD risk factors was low but patients appeared more optimistic than fearful when confronted with intraocular antivascular endothelial growth factor (anti-VEGF injections as treatment.Purpose: In recent years there has been an increase in our understanding of wet ARMD, and a dramatic shift in the treatment paradigm. However, to our knowledge, no studies have examined how much ARMD patients understand their disease, or how they feel about receiving intraocular injections as treatment. The primary objectives of this study are to identify areas in which ARMD patients may be uninformed about their disease, and to recognize specific fears or expectations that patients may have regarding treatment with intraocular anti-VEGF injections.Design: Prospective, survey-based study.Methods: This is a prospective survey-based study. An anonymous 32-item questionnaire was compiled and distributed to patients with wet ARMD who underwent at least one intraocular anti-VEGF injection. Eighty-three patients from a retina practice in a suburban setting completed the questionnaire that gauged both their knowledge of ARMD and their perspectives on its treatment. Data was analyzed using chi-square testing.Results: Seventy-eight percent of patients received most of their knowledge of ARMD from their physician. Eighty-nine percent of patients prefer to receive more information on ARMD, if needed, directly from their physician. Only 21%, 48%, 37%, 48%, and 36%, respectively, correctly identified how diet, special vitamins, high blood pressure

  12. Age related changes in pancreatic beta cells: A putative extra-cerebral site of Alzheimer’s pathology

    Science.gov (United States)

    Maj, Magdalena; Ilhan, Aysegul; Neziri, Dashurie; Gartner, Wolfgang; Berggard, Tord; Attems, Johannes; Base, Wolfgang; Wagner, Ludwig

    2011-01-01

    Frequent concomitant manifestation of type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) has been recently demonstrated by epidemiological studies. This might be due to functional similarities between β-cells and neurons, such as secretion on demand of highly specific molecules in a tightly controlled fashion. An additional similarity represents the age-related alteration of hyperphosphorylated tau in AD patients. Similarly, alterations have been identified in β-cells of T2DM patients. The islet amyloid polypeptide has been associated with β-cell apoptosis. As a consequence of increasing age, the accumulation of highly modified proteins together with decreased regenerative potential might lead to increasing rates of apoptosis. Moreover, reduction of β-cell replication capabilities results in reduction of β-cell mass in mammals, simultaneously with impaired glucose tolerance. The new challenge is to learn much more about age-related protein modifications. This can lead to new treatment strategies for reducing the incidence of T2DM and AD. PMID:21537460

  13. Plasma and macular responses to lutein supplement in subjects with and without age-related maculopathy: a pilot study.

    Science.gov (United States)

    Koh, Hui-Hiang; Murray, Ian J; Nolan, Daniel; Carden, Dave; Feather, Jim; Beatty, Stephen

    2004-07-01

    There is a growing body of evidence which suggests that macular pigment (MP), which is entirely of dietary origin, protects against age-related maculopathy. We evaluated the effect of a daily 20 mg lutein ester (equivalent of 10 mg/day free lutein) supplement in patients with early age-related maculopathy (ARM), in terms of macular pigment optical density (MPOD) and plasma concentrations of lutein. MPOD was measured using a flicker photometric technique in seven ARM sufferers and six age-matched controls over a period of supplementation which lasted 18-20 weeks. Plasma lutein increased from a mean (SD) baseline concentration of 182 (127)ng ml(-1) to a peak of 1077 (165)ng ml(-1) in ARM patients, and from 152 (57) to 1110 (605)ng ml(-1) in control subjects. Mean MPOD had increased significantly from baseline of 0.24 to a peak of 0.31 in ARM sufferers. This mean increment of 0.07 was the same for the age-matched controls (baseline: 0.20; peak: 0.27). The augmentation of MP, and plasma concentrations of lutein, following supplementation in subjects with ARM provides the first evidence the disease is not associated with intestinal malabsorption of the relevant macular carotenoids, and that a diseased macula can accumulate and stabilise lutein and/or zeaxanthin. Furthermore, these results suggest that the beneficial effects of lutein supplementation, if any, may be extended to subjects with established ARM. PMID:15183097

  14. Age-related alteration of arginase activity impacts on severity of leishmaniasis.

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    Ingrid Müller

    Full Text Available BACKGROUND: The leishmaniases are a group of vector-borne parasitic diseases that represent a major international public health problem; they belong to the most neglected tropical diseases and have one of the highest rates of morbidity and mortality. The clinical outcome of infection with Leishmania parasites depends on a variety of factors such as parasite species, vector-derived products, genetics, behaviour, and nutrition. The age of the infected individuals also appears to be critical, as a significant proportion of clinical cases occur in children; this age-related higher prevalence of disease is most remarkable in visceral leishmaniasis. The mechanisms resulting in this higher incidence of clinical disease in children are poorly understood. We have recently revealed that sustained arginase activity promotes uncontrolled parasite growth and pathology in vivo. Here, we tested the hypothesis that arginase-mediated L-arginine metabolism differs with age. METHODOLOGY: The age distribution of patients with visceral or cutaneous leishmaniasis was determined in cohorts of patients in our clinics in endemic areas in Ethiopia. To exclude factors that are difficult to control in patients, we assessed the impact of ageing on the manifestations of experimental leishmaniasis. We determined parasite burden, T cell responses, and macrophage effector functions in young and aged mice during the course of infection. RESULTS: Our results show that younger mice develop exacerbated lesion pathology and higher parasite burdens than aged mice. This aggravated disease development in younger individuals does not correlate with a change in T helper cytokine profile. To address the underlying mechanisms responsible for the more severe infections in younger mice, we investigated macrophage effector functions. Our results show that macrophages from younger mice do not have an impaired capacity to kill parasites; however, they express significantly higher levels of

  15. Impaired cardiac SIRT1 activity by carbonyl stress contributes to aging-related ischemic intolerance.

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    Chunhu Gu

    Full Text Available Reactive aldehydes can initiate protein oxidative damage which may contribute to heart senescence. Sirtuin 1 (SIRT1 is considered to be a potential interventional target for I/R injury management in the elderly. We hypothesized that aldehyde mediated carbonyl stress increases susceptibility of aged hearts to ischemia/reperfusion (I/R injury, and elucidate the underlying mechanisms with a focus on SIRT1. Male C57BL/6 young (4-6 mo and aged (22-24 mo mice were subjected to myocardial I/R. Cardiac aldehyde dehydrogenase (ALDH2, SIRT1 activity and protein carbonyls were assessed. Our data revealed that aged heart exhibited increased endogenous aldehyde/carbonyl stress due to impaired ALDH2 activity concomitant with blunted SIRT1 activity (P<0.05. Exogenous toxic aldehydes (4-HNE exposure in isolated cardiomyocyte verified that aldehyde-induced carbonyl modification on SIRT1 impaired SIRT1 activity leading to worse hypoxia/reoxygenation (H/R injury, which could all be rescued by Alda-1 (ALDH2 activator (all P<0.05. However, SIRT1 inhibitor blocked the protective effect of Alda-1 on H/R cardiomyocyte. Interestingly, myocardial I/R leads to higher carbonylation but lower activity of SIRT1 in aged hearts than that seen in young hearts (P<0.05. The application of Alda-1 significantly reduced the carbonylation on SIRT1 and markedly improved the tolerance to in vivo I/R injury in aged hearts, but failed to protect Sirt1(+/- knockout mice against myocardial I/R injury. This was verified by Alda-1 treatment improved postischemic contractile function recovery in ex vivo perfused aged but not in Sirt1(+/- hearts. Thus, aldehyde/carbonyl stress is accelerated in aging heart. These results provide a new insight that impaired cardiac SIRT1 activity by carbonyl stress plays a critical role in the increased susceptibility of aged heart to I/R injury. ALDH2 activation can restore this aging-related myocardial ischemic intolerance.

  16. The Corneoscleral Shell of the Eye: an Age-Related Analysis of Structural Biomechanical Properties. Literature review

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    E. N. Iomdina

    2016-01-01

    Full Text Available Structural biomechanical properties of the ocular corneoscleral shell largely determine its anatomic and optical parameters and its supporting and protective function. Therefore, changes related to age restructuring processes may affect the state of the cornea and the sclera, which should be taken into account in diagnosing eye diseases, especially age-related. According to actual literary data, age-related changes of the corneoscleral shell affecting its biomechanical properties involve all connective tissue components of the extracellular matrix: fibrous proteins (collagen and elastin and intermediate substance components (proteoglycans and glycosaminoglycans. Aged patients have a larger diameter of elastic fiber fibrils in the external part of the sclera and a lower density of fibrils in the center as compared to young patients, which is an evidence of elastin damage at the molecular level and fibril degeneration. Age-related changes of proteoglycans are primarilymanifested in hydration loss, which leads to an increase in corneal and sclera density and regional thinning of tissues. Agerelated changes of collagen are less expressed than those of elastin and proteoglycans. Yet, the distance between collagen fibrils in the cornea becomes smaller with age; they are subject to destruction, and small spaces devoid of collagen tend to appear in the posterior stroma. The most pronounced age-related degenerative changes of collagen in the deeper layers of the corneal stroma occur in the limb, which accumulates more cross striated collagen fibrils. Recent years of research have shown that the formation of cross-linked chemical bonds, i.e. intra- and intermolecular cross links of collagen is the most important structural factor. It is this particular process that is responsible for structural stability of the corneal and scleral tissue, which tends to change with age or due to certain eye diseases, such as keratoconus or progressive myopia

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

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    Dae Woo Kim

    Full Text Available 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.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.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.Age-related decline in neutrophil inflammation may favorably affect postoperative results in elderly patients with NE-NP.

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

    Science.gov (United States)

    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

  19. Age-related Hearing Loss: GABA, Nicotinic Acetylcholine and NMDA Receptor Expression Changes in Spiral Ganglion Neurons of the Mouse

    Science.gov (United States)

    Tang, Xiaolan; Zhu, Xiaoxia; Ding, Bo; Walton, Joseph P.; Frisina, Robert D.; Su, Jiping

    2014-01-01

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

  20. Nucleosynthetic history of elements in the Galactic disk. [X/Fe]-age relations from high-precision spectroscopy

    Science.gov (United States)

    Spina, L.; Meléndez, J.; Karakas, A. I.; Ramírez, I.; Monroe, T. R.; Asplund, M.; Yong, D.

    2016-10-01

    Context. The chemical composition of stars is intimately linked to the formation and evolution of the Galaxy. Aims: We aim to trace the chemical evolution of the Galactic disk through the inspection of the [X/Fe]-age relations of 24 species from C to Eu. Methods: Using high-resolution and high signal-to-noise UVES spectra of nine solar twins, we obtained precise estimates of stellar ages and chemical abundances. These determinations have been integrated with additional accurate age and abundance determinations from recent spectroscopic studies of solar twins existing in the literature, comprising superb abundances with 0.01 dex precision. Based on this data set, we outlined the [X/Fe]-age relations over a time interval of 10 Gyr. Results: We present the [X/Fe] - age relations for 24 elements (C, O, Na, Mg, Al, Si, S, K, Ca, Sc, Ti, V, Cr, Mn, Co, Ni, Cu, Zn, Y, Ba, La, Ce, Nd, and Eu). Each different class of elements showed a distinct evolution with time that relies on the different characteristics, rates, and timescales of the nucleosynthesis sites from which they are produced. The α-elements are characterized by a [X/Fe] decrease with time. Strikingly, the opposite behavior is observed for Ca. The iron-peak elements show an early [X/Fe] increase followed by a decrease towards the youngest stars. The [X/Fe] for the n-capture elements decrease with age. We also found that both [Mg/Y] and [Al/Y] are precise stellar clocks, with [Al/Y] showing the steepest dependence on age. Conclusions: Knowledge of the [X/Fe]-age relations is a gold mine from which we can achieve a great understanding of the processes that governed the formation and evolution of the Milky Way. Through the reverse engineering of these relations we will be able to put strong constraints on the nature of the stellar formation history, the SNe rates, the stellar yields, and the variety of the SNe progenitors. Based on observations obtained at the ESO VLT at Paranal Observatory (Observing program 083

  1. Age-related changes in ac-impedance spectroscopy studies of normal human dentine: further investigations.

    Science.gov (United States)

    Eldarrat, A H; High, A S; Kale, G M

    2010-01-01

    One of the age-related changes occurring in dentine structure is the formation of peritubular dentine on the inner walls of dentinal tubules leading to complete closure of tubules. Ac-impedance is safe, fast and non-invasive technique. In the last decade, the popularity of the technique has increased in dental research. Several investigators have used the technique to detect tooth cracks and caries. The results of in vitro studies showed that ac-impedance technique was more advanced for caries detection than visual and radiographic methods. However, other studies demonstrated that the accuracy of impedance measurements can be affected by many factors such as remineralization after tooth eruption. A study has been published on effect of age on impedance measurements by the authors for two age groups by employing ac-impedance spectroscopy. Therefore, the aim of this study was to demonstrate the importance of this technique by conducting further investigations on dentine samples of wider age groups. Dentine samples were prepared from extracted sound third molars of known patient age. The ac-impedance measurements were carried out over a wide range of frequency. After performing all electrical measurements, dentine samples were examined under SEM to correlate the electrical measurements with their structure. Impedance measurements showed that there were differences in impedance between young and old dentine. One-way ANOVA of the means of resistance and capacitance for all age groups (20, 25, 30, 40 and 50 years old dentine) revealed a significant difference (ANOVA, P < 0.0001) as a function of age. Applying Tukey's post hoc test, to the same data showed that this difference was due to the 50 years old dentine for resistance and was due to the 40 and 50 years old dentine for capacitance which were statistically different to all other groups. SEM investigation of dentine samples showed that young dentine is characterized by open dentinal tubules distributed all over the

  2. Low Vision Depression Prevention Trial in Age-Related Macular Degeneration

    Science.gov (United States)

    Rovner, Barry W.; Casten, Robin J.; Hegel, Mark T.; Massof, Robert W.; Leiby, Benjamin E.; Ho, Allen C.; Tasman, William S.

    2014-01-01

    Purpose To compare the efficacy of behavior activation (BA) + low vision rehabilitation (LVR) with supportive therapy (ST) + LVR to prevent depressive disorders in patients with age-related macular degeneration (AMD). Design Single-masked, attention-controlled, randomized, clinical trial with outcome assessment at 4 months. Participants Patients with AMD and subsyndromal depressive symptoms attending retina practices (n = 188). Interventions Before randomization, all subjects had 2 outpatient LVR visits, and were then randomized to in-home BA+LVR or ST+LVR. Behavior activation is a structured behavioral treatment that aims to increase adaptive behaviors and achieve valued goals. Supportive therapy is a nondirective, psychological treatment that provides emotional support and controls for attention. Main Outcome Measures The Diagnostic and Statistical Manual IV defined depressive disorder based on the Patient Health Questionnaire-9 (primary outcome), Activities Inventory, National Eye Institute Vision Function Questionnaire–25 plus Supplement (NEI-VFQ), and NEI-VFQ quality of life (secondary outcomes). Results At 4 months, 11 BA+LVR subjects (12.6%) and 18 ST+LVR subjects (23.4%) developed a depressive disorder (relative risk [RR], 0.54; 95% CI, 0.27–1.06; P = 0.067). In planned adjusted analyses the RR was 0.51 (95% CI, 0.27–0.98; P = 0.04). A mediational analysis suggested that BA+LVR prevented depression to the extent that it enabled subjects to remain socially engaged. In addition, BA+LVR was associated with greater improvements in functional vision than ST+LVR, although there was no significant between-group difference. There was no significant change or between-group difference in quality of life. Conclusions An integrated mental health and low vision intervention halved the incidence of depressive disorders relative to standard outpatient LVR in patients with AMD. As the population ages, the number of persons with AMD and the adverse effects of comorbid

  3. Ranibizumab in neovascular age-related macular degeneration: a 5-year follow-up

    Directory of Open Access Journals (Sweden)

    Cvetkova NP

    2016-06-01

    Full Text Available Nadezhda P Cvetkova, Kristina Hölldobler, Philipp Prahs, Viola Radeck, Horst Helbig, David Märker Department of Ophthalmology, University of Regensburg, Regensburg, Germany Purpose: Our aim was to evaluate an optical coherence tomography (OCT and visual acuity (VA-guided, variable-dosing regimen with intravitreal ranibizumab injection for treating patients with neovascular age-related macular degeneration (AMD from 2007 to 2012. Design: This was a retrospective clinical study of 5 years follow-up in a tertiary eye center. Patients and methods: In this study, 66 patients with neovascular AMD (mean age of 74 years, SD 8.7 years were included. We investigated the development of best-corrected visual acuity (BCVA, the number of intravitreal injections, and the central retinal thickness measured with OCT (OCT Spectralis over 5 years of intravitreal treatment. Results: The mean number of intravitreal ranibizumab injections over 5 years was 8.8. The mean BCVA before therapy was 0.4 logarithm of the minimum angle of resolution (logMAR. After 5 years of therapy, the mean BCVA was 0.6 logMAR. In all, 16% of treated patients had stable VA over 5 years and 10% of study eyes approved their VA. The mean OCT-measured central retinal thickness at the beginning of this study was 295 µm; after 5 years of treatment, the mean central retinal thickness was 315 µm. There was an increase in central retinal thickness in 47.5% of examined eyes. Conclusion: Other studies showed VA improvement in OCT-guided variable-dosing regimens. Our study revealed a moderate decrease in VA after a total mean injection number as low as 8.8 injections over 5 years. In OCT, an increase in central retinal thickness over 5 years could be observed. Probably, this is due to deficient treatment when comparing the total injection number to other treatment regimens. Anti-VEGF therapy helps to keep the VA stable for a period of time, but cannot totally stop the progression of

  4. [Age-related macular degeneration – a challenge for public health care].

    Science.gov (United States)

    Mantel, Irmela

    2016-01-01

    Age-related macular degeneration (AMD) is the predominant cause of legal blindness in the population over 50 years of age. The disorder shows exponentially increasing prevalence with age, and the late forms with their vision threatening evolution are found in approximately one third of cases. The late AMD may be purely atrophic and so far untreatable. Or it may be neovascular and exudative, for which medical treatment is available, consisting of repetitive intravitreous injections of Anti-VEGF molecules. The treatment is highly effective in blocking the growth of the pathological vessels and allowing resolution of the accompanying edema. Visual improvement is variable but often very meaningful for the patients. However, the final visual level depends mostly on early intervention. Thus, screening for the first signs of neovascular AMD is crucial for the endresult. However, the repetitive intraocular injections are an important burden for the patients. Due to the high patient numbers, the chronic care management with steadily adding new patients is a major challenge for treating institutions. Limited resources may put patients at risk of undertreatment with resulting visual loss. Various strategies have been developed to cope with the burden. In addition, the financial cost is high for the health care system. On the other hand, timely and ongoing treatment is the best investment to achieve meaningful visual improvement, which is extremely important for the quality of life and autonomy of the patients. Side effects of the treatment are limited and mostly procedure related. Systemic side effects are possible but despite the large studies not conclusive. However, care must be taken in cases of high cardiovascular risk, as thromboembolic risk increase may rarely happen. So far unsolved problems include the long term visual results, the degree of reversibility of neovascularization, and the missing treatment options of atrophic AMD. Basic and clinical research on various

  5. Working memory in middle-aged males: age-related brain activation changes and cognitive fatigue effects.

    Science.gov (United States)

    Klaassen, Elissa B; Evers, Elisabeth A T; de Groot, Renate H M; Backes, Walter H; Veltman, Dick J; Jolles, Jelle

    2014-02-01

    We examined the effects of aging and cognitive fatigue on working memory (WM) related brain activation using functional magnetic resonance imaging. Age-related differences were investigated in 13 young and 16 middle-aged male school teachers. Cognitive fatigue was induced by sustained performance on cognitively demanding tasks (compared to a control condition). Results showed a main effect of age on left dorsolateral prefrontal and superior parietal cortex activation during WM encoding; greater activation was evident in middle-aged than young adults regardless of WM load or fatigue condition. An interaction effect was found in the dorsomedial prefrontal cortex (DMPFC); WM load-dependent activation was elevated in middle-aged compared to young in the control condition, but did not differ in the fatigue condition due to a reduction in activation in middle-aged in contrast to an increase in activation in the young group. These findings demonstrate age-related activation differences and differential effects of fatigue on activation in young and middle-aged adults.

  6. Age-related changes in the brain antioxidant status: modulation by dietary supplementation of Decalepis hamiltonii and physical exercise.

    Science.gov (United States)

    Ravikiran, Tekupalli; Sowbhagya, Ramachandregowda; Anupama, Sindhghatta Kariyappa; Anand, Santosh; Bhagyalakshmi, Dundaiah

    2016-08-01

    The synergistic effects of physical exercise and diet have profound benefits on brain function. The present study was aimed to determine the effects of exercise and Decalepis hamiltonii (Dh) on age-related responses on the antioxidant status in discrete regions of rat brain. Male Wistar albino rats of 4 and 18 months old were orally supplemented with Dh extract and swim trained at 3 % intensity for 30 min/day, 5 days/week, for a period of 30 days. Supplementation of 100 mg Dh aqueous extract/kg body weight and its combination with exercise significantly elevated the antioxidant enzyme activities irrespective of age. Age-related and region-specific changes were observed in superoxide levels, and protein carbonyl and malondialdehyde contents, and were found to be decreased in both trained and supplemented groups. Levels of total thiols, protein, and nonprotein thiols decreased with age and significantly increased in the SW-T(+100 mg) groups. Our results demonstrated that the interactive effects of two treatments enhanced the antioxidant status and decreased the risk of protein and lipid oxidation in the rat brain. PMID:27379504

  7. Guidelines for the management of neovascular age-related macular degeneration by the European Society of Retina Specialists (EURETINA)

    DEFF Research Database (Denmark)

    Schmidt-Erfurth, Ursula; Chong, Victor; Loewenstein, Anat;

    2014-01-01

    UNLABELLED: Age-related macular degeneration (AMD) is still referred to as the leading cause of severe and irreversible visual loss world-wide. The disease has a profound effect on quality of life of affected individuals and represents a major socioeconomic challenge for societies due to the expo......UNLABELLED: Age-related macular degeneration (AMD) is still referred to as the leading cause of severe and irreversible visual loss world-wide. The disease has a profound effect on quality of life of affected individuals and represents a major socioeconomic challenge for societies due...... to the exponential increase in life expectancy and environmental risks. Advances in medical research have identified vascular endothelial growth factor (VEGF) as an important pathophysiological player in neovascular AMD and intraocular inhibition of VEGF as one of the most efficient therapies in medicine. The wide......, unresolved medicolegal debates about the use of off-label substances and overwhelming problems in large population management. The burden of disease has turned into a burden of care with a dissociation of scientific advances and real-world clinical performance. Simultaneously, ground-breaking innovations...

  8. Using the gradient of human cortical bone properties to determine age-related bone changes via ultrasonic guided waves.

    Science.gov (United States)

    Baron, Cécile

    2012-06-01

    Bone fragility depends not only on bone mass but also on bone quality (structure and material). To accurately evaluate fracture risk or propose therapeutic treatment, clinicians need a criterion, which reflects the determinants of bone strength: geometry, structure and material. In human long bone, the changes due to aging, accentuated by osteoporosis are often revealed through the trabecularization of cortical bone, i.e., increased porosity of endosteal bone inducing a thinning of the cortex. Consequently, the intracortical porosity gradient corresponding to the spatial variation in porosity across the cortical thickness is representative of loss of mass, changes in geometry (thinning) and variations in structure (porosity). This article examines the gradient of material properties and its age-related evolution as a relevant parameter to assess bone geometry, structure and material. By applying a homogenization process, cortical bone can be considered as an anisotropic functionally graded material with variations in material properties. A semi-analytical method based on the sextic Stroh formalism is proposed to solve the wave equation in an anisotropic functionally graded waveguide for two geometries, a plate and a tube, without using a multilayered model to represent the structure. This method provides an analytical solution called the matricant and explicitly expressed under the Peano series expansion form. Our findings indicate that ultrasonic guided waves are sensitive to the age-related evolution of realistic gradients in human bone properties across the cortical thickness and have their place in a multimodal clinical protocol. PMID:22502890

  9. No late effect of ionizing radiation on the aging-related oxidative changes in the mouse brain

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Beom Su; Kim, Seol Wha; Jung, U Hee; Jo, Sung Kee [Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of)

    2010-09-15

    Radiation-induced late injury to normal tissue is a primary area of radiation biology research. The present study was undertaken to investigate whether the late effect of the ionizing radiation appears as an age-related oxidative status in the brain. Three groups of 4-month old C57BL/6 mice that were exposed to {sup 137}Cs {gamma}-rays at a single dose (5 Gy) or fractionated doses (1 Gy x 5 times, or 0,2 Gy x 25 times) at 2 months old were investigated for the oxidative status of their brains with both young (2-month) and old (24-month) mice. A significant (pincreased in the old mice brain. However, any significant difference in SOD activity and MDA contents of the irradiated brain was not observed compared to age-matched control group mice. SOD activity and MDA content were observed within good parameters of brain aging and there no late effects on the age-related oxidative level in the {gamma}-ray irradiated mice brains.

  10. Light treatment for sleep disorders: consensus report. V. Age-related disturbances.

    Science.gov (United States)

    Campbell, S S; Terman, M; Lewy, A J; Dijk, D J; Eastman, C I; Boulos, Z

    1995-06-01

    Sleep maintenance insomnia is a major complaint among the elderly. As a result, an inordinate proportion of sleeping pill prescriptions go to individuals over 65 y of age. Because of the substantial problems associated with use of hypnotics in older populations, efforts have been made to develop nondrug treatments for age-related sleep disturbance, including timed exposure to bright light. Such bright light treatments are based on the assumption that age-related sleep disturbance is the consequence of alterations in the usual temporal relationship between body temperature and sleep. Although studies are limited, results strongly suggest that evening bright light exposure is beneficial in alleviating sleep maintenance insomnia in healthy elderly subjects. Less consistent, but generally positive, findings have been reported with regard to bright light treatment of sleep and behavioral disturbance in demented patients. For both groups, it is likely that homeostatic factors also contribute to sleep disturbance, and these may be less influenced by bright light interventions. PMID:7632988

  11. Light treatment for sleep disorders: consensus report. V. Age-related disturbances.

    Science.gov (United States)

    Campbell, S S; Terman, M; Lewy, A J; Dijk, D J; Eastman, C I; Boulos, Z

    1995-06-01

    Sleep maintenance insomnia is a major complaint among the elderly. As a result, an inordinate proportion of sleeping pill prescriptions go to individuals over 65 y of age. Because of the substantial problems associated with use of hypnotics in older populations, efforts have been made to develop nondrug treatments for age-related sleep disturbance, including timed exposure to bright light. Such bright light treatments are based on the assumption that age-related sleep disturbance is the consequence of alterations in the usual temporal relationship between body temperature and sleep. Although studies are limited, results strongly suggest that evening bright light exposure is beneficial in alleviating sleep maintenance insomnia in healthy elderly subjects. Less consistent, but generally positive, findings have been reported with regard to bright light treatment of sleep and behavioral disturbance in demented patients. For both groups, it is likely that homeostatic factors also contribute to sleep disturbance, and these may be less influenced by bright light interventions.

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

    Science.gov (United States)

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

    2013-07-02

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Clinical hallmarks of AMD are observed in one third of the elderly in industrialized countries. Preventative interventions through dietary modification are attractive strategies, because they are more affordable than clinical therapies, do not require specialists for administration and many studies suggest a benefit of micro- and macro-nutrients with respect to AMD with few, if any, adverse effects. The goal of this review is to provide information from recent literature on the value of various nutrients, particularly omega-3 fatty acids, lower glycemic index diets and, perhaps, some carotenoids, with regard to diminishing risk for onset or progression of AMD. Results from the upcoming Age-Related Eye Disease Study (AREDS) II intervention trial should be particularly informative.

  13. Diminishing Risk for Age-Related Macular Degeneration with Nutrition: A Current View

    Directory of Open Access Journals (Sweden)

    Allen Taylor

    2013-07-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of blindness in the elderly. Clinical hallmarks of AMD are observed in one third of the elderly in industrialized countries. Preventative interventions through dietary modification are attractive strategies, because they are more affordable than clinical therapies, do not require specialists for administration and many studies suggest a benefit of micro- and macro-nutrients with respect to AMD with few, if any, adverse effects. The goal of this review is to provide information from recent literature on the value of various nutrients, particularly omega-3 fatty acids, lower glycemic index diets and, perhaps, some carotenoids, with regard to diminishing risk for onset or progression of AMD. Results from the upcoming Age-Related Eye Disease Study (AREDS II intervention trial should be particularly informative.

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

    Science.gov (United States)

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

    2015-11-01

    Nanoparticles combined with cells, drugs, and specially designed genes provide improved therapeutic efficacy in studies and clinical setting, demonstrating a new era of treatment strategy, especially in retinal diseases. Nanotechnology-based drugs can provide an essential platform for sustaining, releasing and a specific targeting design to treat retinal diseases. Poly-lactic-co-glycolic acid is the most widely used biocompatible and biodegradable polymer approved by the Food and Drug Administration. Many studies have attempted to develop special devices for delivering small-molecule drugs, proteins, and other macromolecules consistently and slowly. In this article, we first review current progress in the treatment of age-related macular degeneration. Then, we discuss the function of vascular endothelial growth factor (VEGF) and the pharmacological effects of anti-VEGF-A antibodies and soluble or modified VEGF receptors. Lastly, we summarize the combination of antiangiogenic therapy and nanomedicines, and review current potential targeting therapy in age-related macular degeneration.

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

    Science.gov (United States)

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

    2015-03-01

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

  16. Age-related changes in brain hemodynamics; A calibrated MRI study

    DEFF Research Database (Denmark)

    De Vis, J B; Hendrikse, J; Bhogal, A;

    2015-01-01

    INTRODUCTION: Blood oxygenation-level dependent (BOLD) magnetic resonance imaging signal changes in response to stimuli have been used to evaluate age-related changes in neuronal activity. Contradictory results from these types of experiments have been attributed to differences in cerebral blood....... A dual-echo pseudocontinuous arterial spin labeling (ASL) sequence was performed during normocapnic, hypercapnic, and hyperoxic breathing challenges. Whole brain and regional gray matter values of CBF, ASL cerebrovascular reactivity (CVR), BOLD CVR, oxygen extraction fraction (OEF), and CMRO2 were...... could potentially be explained by differences in EtCO2 . Regional CMRO2 was lower in older subjects. BOLD studies should take this into account when investigating age-related changes in neuronal activity....

  17. Carnosine and Related Peptides: Therapeutic Potential in Age-Related Disorders.

    Science.gov (United States)

    Cararo, José H; Streck, Emilio L; Schuck, Patricia F; Ferreira, Gustavo da C

    2015-09-01

    Imidazole dipeptides (ID), such as carnosine (β-alanyl-L-histidine), are compounds widely distributed in excitable tissues of vertebrates. ID are also endowed of several biochemical properties in biological tissues, including antioxidant, bivalent metal ion chelating, proton buffering, and carbonyl scavenger activities. Furthermore, remarkable biological effects have been assigned to such compounds in age-related human disorders and in patients whose activity of serum carnosinase is deficient or undetectable. Nevertheless, the precise biological role of ID is still to be unraveled. In the present review we shall discuss some evidences from clinical and basic studies for the utilization of ID as a drug therapy for age-related human disorders. PMID:26425391

  18. Age-Related Alterations in the Expression of Genes and Synaptic Plasticity Associated with Nitric Oxide Signaling in the Mouse Dorsal Striatum

    Directory of Open Access Journals (Sweden)

    Aisa N. Chepkova

    2015-01-01

    Full Text Available Age-related alterations in the expression of genes and corticostriatal synaptic plasticity were studied in the dorsal striatum of mice of four age groups from young (2-3 months old to old (18–24 months of age animals. A significant decrease in transcripts encoding neuronal nitric oxide (NO synthase and receptors involved in its activation (NR1 subunit of the glutamate NMDA receptor and D1 dopamine receptor was found in the striatum of old mice using gene array and real-time RT-PCR analysis. The old striatum showed also a significantly higher number of GFAP-expressing astrocytes and an increased expression of astroglial, inflammatory, and oxidative stress markers. Field potential recordings from striatal slices revealed age-related alterations in the magnitude and dynamics of electrically induced long-term depression (LTD and significant enhancement of electrically induced long-term potentiation in the middle-aged striatum (6-7 and 12-13 months of age. Corticostriatal NO-dependent LTD induced by pharmacological activation of group I metabotropic glutamate receptors underwent significant reduction with aging and could be restored by inhibition of cGMP hydrolysis indicating that its age-related deficit is caused by an altered NO-cGMP signaling cascade. It is suggested that age-related alterations in corticostriatal synaptic plasticity may result from functional alterations in receptor-activated signaling cascades associated with increasing neuroinflammation and a prooxidant state.

  19. Is the onset of influenza in the community age-related?

    Science.gov (United States)

    Fleming, D M; Durnall, H; Warburton, F; Ellis, J S; Zambon, M C

    2016-08-01

    We studied the spread of influenza in the community between 1993 and 2009 using primary-care surveillance data to investigate if the onset of influenza was age-related. Virus detections [A(H3N2), B, A(H1N1)] and clinical incidence of influenza-like illness (ILI) in 12·3 million person-years in the long-running Royal College of General Practitioners-linked clinical-virological surveillance programme in England & Wales were examined. The number of days between symptom onset and the all-age peak ILI incidence were compared by age group for each influenza type/subtype. We found that virus detection and ILI incidence increase, peak and decrease were in unison. The mean interval between symptom onset to peak ILI incidence in virus detections (all ages) was: A(H3N2) 20·5 [95% confidence interval (CI) 19·7-21·6] days; B, 18·8 (95% CI 15·8·0-21·7) days; and A(H1N1) 17·0 (95% CI 15·6-18·4) days. Differences by age group were examined using the Kruskal-Wallis test. For A(H3N2) and A(H1N1) viruses the interval was similar in each age group. For influenza B there were highly significant differences by age group (P = 0·0001). Clinical incidence rates of ILI reported in the 8 weeks preceding the period of influenza virus activity were used to estimate a baseline incidence and threshold value (upper 95% CI of estimate) which was used as a marker of epidemic progress. Differences between the age groups in the week in which the threshold was reached were small and not localized to any age group. In conclusion we found no evidence to suggest that influenza A(H3N2) and A(H1N1) occurs in the community in one age group before another. For influenza B, virus detection was earlier in children aged 5-14 years than in persons aged ⩾25 years. PMID:27350234

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

    OpenAIRE

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

    2014-01-01

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

  1. Aging Chart: a community resource for rapid exploratory pathway analysis of age-related processes

    OpenAIRE

    Moskalev, Alexey; Zhikrivetskaya, Svetlana; Shaposhnikov, Mikhail; Dobrovolskaya, Evgenia; Gurinovich, Roman; Kuryan, Oleg; Pashuk, Aleksandr; Jellen, Leslie C.; Aliper, Alex; Peregudov, Alex; Zhavoronkov, Alex

    2015-01-01

    Aging research is a multi-disciplinary field encompassing knowledge from many areas of basic, applied and clinical research. Age-related processes occur on molecular, cellular, tissue, organ, system, organismal and even psychological levels, trigger the onset of multiple debilitating diseases and lead to a loss of function, and there is a need for a unified knowledge repository designed to track, analyze and visualize the cause and effect relationships and interactions between the many elemen...

  2. Genetic Markers in Biological Fluids for Aging-Related Major Neurocognitive Disorder

    OpenAIRE

    Castro-Chavira, S.A.; Fernández, T.; Nicolini, H.; Diaz-Cintra, S.; Prado-Alcalá, R.A.

    2015-01-01

    Aging-related major neurocognitive disorder (NCD), formerly named dementia, comprises of the different acquired diseases whose primary deficit is impairment in cognitive functions such as complex attention, executive function, learning and memory, language, perceptual/motor skills, and social cognition, and that are related to specific brain regions and/or networks. According to its etiology, the most common subtypes of major NCDs are due to Alzheimer’s disease (AD), vascular disease (VaD), L...

  3. Age-related mitochondrial DNA depletion and the impact on pancreatic Beta cell function.

    Directory of Open Access Journals (Sweden)

    Donna L Nile

    Full Text Available Type 2 diabetes is characterised by an age-related decline in insulin secretion. We previously identified a 50% age-related decline in mitochondrial DNA (mtDNA copy number in isolated human islets. The purpose of this study was to mimic this degree of mtDNA depletion in MIN6 cells to determine whether there is a direct impact on insulin secretion. Transcriptional silencing of mitochondrial transcription factor A, TFAM, decreased mtDNA levels by 40% in MIN6 cells. This level of mtDNA depletion significantly decreased mtDNA gene transcription and translation, resulting in reduced mitochondrial respiratory capacity and ATP production. Glucose-stimulated insulin secretion was impaired following partial mtDNA depletion, but was normalised following treatment with glibenclamide. This confirms that the deficit in the insulin secretory pathway precedes K+ channel closure, indicating that the impact of mtDNA depletion is at the level of mitochondrial respiration. In conclusion, partial mtDNA depletion to a degree comparable to that seen in aged human islets impaired mitochondrial function and directly decreased insulin secretion. Using our model of partial mtDNA depletion following targeted gene silencing of TFAM, we have managed to mimic the degree of mtDNA depletion observed in aged human islets, and have shown how this correlates with impaired insulin secretion. We therefore predict that the age-related mtDNA depletion in human islets is not simply a biomarker of the aging process, but will contribute to the age-related risk of type 2 diabetes.

  4. Aging-related changes in calcium binding proteins in rat perirhinal cortex

    OpenAIRE

    Moyer, James R.; Furtak, Sharon C.; McGann, John P.; Brown, Thomas H.

    2009-01-01

    Dysregulation of intracellular calcium homeostasis has been linked to neuropathological symptoms observed in aging and age-related disease. Alterations in the distribution and relative frequency of calcium-binding proteins (CaBPs), which are important in regulating intracellular calcium levels, may contribute to disruption of calcium homeostasis. Here we examined the laminar distribution of three CaBPs in rat perirhinal cortex (PR) as a function of aging. Calbindin-D28k (CB), parvalbumin (PV)...

  5. Aging-related deficits in orexin/hypocretin modulation of the septo-hippocampal cholinergic system

    OpenAIRE

    Stanley, Emily M.; Fadel, Jim

    2012-01-01

    The medial septum (MS) of the basal forebrain contains cholinergic neurons that project to the hippocampus, support cognitive function, and are implicated in age-related cognitive decline. Hypothalamic orexin/hypocretin neurons innervate and modulate basal forebrain cholinergic neurons and provide direct inputs to the hippocampus. However, the precise role of orexin in modulating hippocampal cholinergic transmission—and how these interactions are altered in aging—is unknown. Here, orexin A wa...

  6. Age-related changes in glutathione and glutathione-related enzymes in rat brain

    OpenAIRE

    Zhu, Yuangui; Carvey, Paul M.; Ling, Zaodung

    2006-01-01

    The most reliable and robust risk factor for some neurodegenerative diseases is aging. It has been proposed that processes of aging are associated with the generation of reactive oxygen species and a disturbance of glutathione homeostasis in the brain. Yet, aged animals have rarely been used to model the diseases that are considered to be age-related such as Parkinson's or Alzheimer's disease. This suggests that the results from these studies would be more valuable if aged animals were used. ...

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

    Science.gov (United States)

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

    2014-06-01

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

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

    Directory of Open Access Journals (Sweden)

    O. M. Drapkina

    2015-01-01

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

  9. An Investigation of Age-Related Differences in Understanding of Empathy and Emotions

    OpenAIRE

    Kuske, Hannah

    2010-01-01

    The current study investigated age-related differences in social cognition, emotional understanding, Theory of Mind (ToM) and empathy. A new task assessing different aspects of social cognition (ToM, emotional understanding, knowledge/understanding of social rules) using cartoon-strip stories was applied in conjunction with established measures of emotion recognition (‘the faces task’, or FEEST), ToM (‘Reading the mind in the eyes task’), empathy (IRI) and executive functions (Bri...

  10. Less efficient pattern separation may contribute to age-related spatial memory deficits

    OpenAIRE

    Gilbert, Paul E.

    2012-01-01

    Spatial memory deficits have been well-documented in older adults and may serve as an early indicator of mild cognitive impairment (MCI) or Alzheimer's disease (AD) in some individuals. Pattern separation is a critical mechanism for reducing potential interference among similar memory representations to enhance memory accuracy. A small but growing literature indicates that spatial pattern separation may become less efficient as a result of normal aging, possibly due to age-related changes in ...

  11. Age-related incidence of pineal calcification detected by computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Zimmerman, R.A.; Bilaniuk, L.T.

    1982-03-01

    The age-related incidence of detectable pineal calcification in 725 patients (age range, newborn-20 yrs) suggests that there is a relationship between calcification and the hormonal role played by the pineal gland in the regulation of sexual development. Pineal calcification (demonstrated by computed tomography (CT) on 8-mm-thick sections) in patients less than 6 years old should be looked upon with suspicion, and follow-up CT should be considered to exclude the possible development of a pineal neoplasm.

  12. Age-related changes in midbrain dopaminergic regulation of the human reward system

    OpenAIRE

    Dreher, Jean-Claude; Meyer-Lindenberg, Andreas; Kohn, Philip; Berman, Karen Faith

    2008-01-01

    The dopamine system, which plays a crucial role in reward processing, is particularly vulnerable to aging. Significant losses over a normal lifespan have been reported for dopamine receptors and transporters, but very little is known about the neurofunctional consequences of this age-related dopaminergic decline. In animals, a substantial body of data indicates that dopamine activity in the midbrain is tightly associated with reward processing. In humans, although indirect evidence from pharm...

  13. Transcriptome Analysis on Monocytes from Patients with Neovascular Age-Related Macular Degeneration

    OpenAIRE

    Michelle Grunin; Shira- Hagbi-Levi; Batya Rinsky; Yoav Smith; Itay Chowers

    2016-01-01

    Mononuclear phagocytes (MPs), including monocytes/macrophages, play complex roles in age-related macular degeneration (AMD) pathogenesis. We reported altered gene-expression signature in peripheral blood mononuclear cells from AMD patients, and a chemokine receptor signature on AMD monocytes. To obtain comprehensive understanding of MP involvement, particularly in peripheral circulation in AMD, we performed global gene expression analysis in monocytes. We separated monocytes from treatment-na...

  14. A genome-wide association study for age-related hearing impairment in the Saami

    OpenAIRE

    Van Camp, Guy; Van Laer, Lut; Huyghe, Jeroen; Hannula, Samuli; Van Eyken, Els; Stephan, Dietrich; Mäki-Torkko, Elina; Aikio, Pekka; Lysholm-Bernacchi, Alana; Sorri, Martti; Huentelman, Matthew J; Fransen, Erik

    2010-01-01

    International audience This study aimed to contribute to the elucidation of the genetic basis of age-related hearing impairment (ARHI), a common multifactorial disease with an important genetic contribution as demonstrated by heritability studies. We conducted a genome-wide association study (GWAS) in the Finnish Saami, a small ancient genetically isolated population without evidence of demographic expansion. The choice of this study population was motivated by its anticipated higher exten...

  15. A genome-wide association study for age-related hearing impairment in the Saami

    OpenAIRE

    Van Laer, Lut; Huyghe, Jeroen R; Hannula, Samuli; Van Eyken, Els; Stephan, Dietrich A.; Mäki-Torkko, Elina; Aikio, Pekka; Fransen, Erik; Lysholm-Bernacchi, Alana; Sorri, Martti; Huentelman, Matthew J; Van Camp, Guy

    2010-01-01

    This study aimed at contributing to the elucidation of the genetic basis of age-related hearing impairment (ARHI), a common multifactorial disease with an important genetic contribution as demonstrated by heritability studies. We conducted a genome-wide association study (GWAS) in the Finnish Saami, a small, ancient, genetically isolated population without evidence of demographic expansion. The choice of this study population was motivated by its anticipated higher extent of LD, potentially o...

  16. Patients’ knowledge and perspectives on wet age-related macular degeneration and its treatment

    OpenAIRE

    Sushma Kandula; Jeffrey C Lamkin; Teresa Albanese; et al

    2010-01-01

    Sushma Kandula1, Jeffrey C Lamkin1, Teresa Albanese2, Deepak P Edward11Department of Ophthalmology, 2Health Service Research and Education Institute, SUMMA Health System, Akron OH, USASummary: There have been no studies examining the level of understanding age-related macular degeneration (ARMD) patients have about their disease, or their perceptions about intraocular injections as treatment. In this study, patient knowledge about ARMD risk factors was low but patients appeared more optimisti...

  17. P73 and age-related diseases: is there any link with Parkinson Disease?

    OpenAIRE

    Grespi, Francesca; Melino, Gerry

    2012-01-01

    P73 is a member of the p53 transcription factors family with a prominent role in neurobiology, affecting brain development as well as controlling neuronal survival. Accordingly, p73 has been identified as key player in many age-related neurodegenerative diseases, such as Alzheimer's disease, neuroAIDS and Niemann-Pick type C disease. Here we investigate possible correlations of p73 with Parkinson disease. Tyrosine hydroxylase is a crucial player in Parkinson disease being the enzyme necessary...

  18. Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson’s Disease

    OpenAIRE

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

    2016-01-01

    The underlying relation between Parkinson’s disease (PD) etiopathology and its major risk factor, aging, is largely unknown. In light of the causative link between genome stability and aging, we investigate a possible nexus between DNA damage accumulation, aging, and PD by assessing aging-related DNA repair pathways in laboratory animal models and humans. We demonstrate that dermal fibroblasts from PD patients display flawed nucleotide excision repair (NER) capacity and that Ercc1 mutant mice...

  19. Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson’s Disease

    OpenAIRE

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

    2016-01-01

    Summary The underlying relation between Parkinson’s disease (PD) etiopathology and its major risk factor, aging, is largely unknown. In light of the causative link between genome stability and aging, we investigate a possible nexus between DNA damage accumulation, aging, and PD by assessing aging-related DNA repair pathways in laboratory animal models and humans. We demonstrate that dermal fibroblasts from PD patients display flawed nucleotide excision repair (NER) capacity and that Ercc1 mut...

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

    Science.gov (United States)

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

    2014-06-01

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

  1. Attenuation of age-related changes in mouse neuromuscular synapses by caloric restriction and exercise

    OpenAIRE

    Valdez, G; Tapia, J; Kang, H; Clemenson, G.D.; Gage, F.H.; Lichtman, Jeff; Sanes, Joshua R.

    2010-01-01

    The cellular basis of age-related behavioral decline remains obscure but alterations in synapses are likely candidates. Accordingly, the beneficial effects on neural function of caloric restriction and exercise, which are among the most effective anti-aging treatments known, might also be mediated by synapses. As a starting point in testing these ideas, we studied the skeletal neuromuscular junction (NMJ), a large, accessible peripheral synapse. Comparison of NMJs in young adult and aged mice...

  2. Age-related reduction in the maximal capacity for sleep - implications for insomnia

    OpenAIRE

    Klerman, Elizabeth B.; Dijk, Derk-Jan

    2008-01-01

    Sleep changes markedly across the life span and complaints about insomnia are prevalent in older people [1]. Whether age-related alterations in sleep are due to modifications in social factors, circadian physiology, homeostatic drive or the ability to sleep remains unresolved. We assessed habitual sleep duration at home and then quantified daytime sleep propensity, sleep duration and sleep structure in an inpatient protocol that included extended sleep opportunities covering 2/3 of the circad...

  3. Age-related activation of mitochondrial caspase-independent apoptotic signaling in rat gastrocnemius muscle

    OpenAIRE

    Marzetti, Emanuele; Wohlgemuth, Stephanie Eva; Lees, Hazel Anne; Chung, Hae-young; Giovannini, Silvia; Leeuwenburgh, Christiaan

    2008-01-01

    Mitochondria-mediated apoptosis represents a central process driving age-related muscle loss. However, the temporal relation between mitochondrial apoptotic signaling and sarcopenia as well as the regulation of release of pro-apoptotic factors from the mitochondria has not been elucidated. In this study, we investigated mitochondrial apoptotic signaling in skeletal muscle of rats across a wide age range. We also investigated whether mitochondrial-driven apoptosis was accompanied by changes in...

  4. Effects of Age-related Differences in Empathy on Social Economic Decision-Making

    OpenAIRE

    Beadle, Janelle N.; Paradiso, Sergio; Kovach, Christopher; Polgreen, Linnea; Denburg, Natalie; Tranel, Daniel

    2012-01-01

    Background: The ways in which aging affects social economic decision-making is a central issue in the psychology of aging. To examine age-related differences in social economic decision-making as a function of empathy, 80 healthy volunteers participated in the Repeated Fixed Opponent Ultimatum Game (UG-R). Previous economic decision-making research has shown that in younger adults empathy is associated with prosocial behavior. The effects of empathy on older adult social economic decision-mak...

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

    Institute of Scientific and Technical Information of China (English)

    Sibel; Doguizi; Sengul; Ozdek; Selcen; Yuksel

    2015-01-01

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

  6. Low fluence rate photodynamic therapy combined with intravitreal bevacizumab for neovascular age related macular degeneration.

    OpenAIRE

    Costagliola, Ciro; Romano, Mario R.; Rinaldi, Michele; Dell'Omo, Robeto; Chiosi, Flavia; Menzione, Massimo; Semeraro, Francesco

    2010-01-01

    Abstract Aims: to report efficacy and safety of intravitreal bevacizumab (IVB) alone versus IVB plus low fluence PDT in age-related macular degeneration (AMD) patients and to verify the occurrence of a synergistic effect of the combined approach on visual acuity, size and morphology of lesion, as well as on the treatment rate. Method: prospective comparative interventional study on 85 patients with treatment naive classic, or predominantly classic, subfoveal choroid...

  7. Individual variability in human blood metabolites identifies age-related differences

    OpenAIRE

    Chaleckis, Romanas; MURAKAMI, Itsuo; Takada, Junko; Kondoh, Hiroshi; Yanagida, Mitsuhiro

    2016-01-01

    Human blood provides a rich source of information about metabolites that reflects individual differences in health, disease, diet, and lifestyle. The coefficient of variation for human blood metabolites enriched in red blood cells or plasma was quantified after careful preparation. We identified 14 age-related metabolites. Metabolites that decline strikingly in the elderly include antioxidants and compounds involved in high physical activity, including carnosine, UDP-acetyl-glucosamine, ophth...

  8. Classifying Human Audiometric Phenotypes of Age-Related Hearing Loss from Animal Models

    OpenAIRE

    Dubno, Judy R.; Eckert, Mark A.; Lee, Fu-Shing; Matthews, Lois J.; Schmiedt, Richard A.

    2013-01-01

    Age-related hearing loss (presbyacusis) has a complex etiology. Results from animal models detailing the effects of specific cochlear injuries on audiometric profiles may be used to understand the mechanisms underlying hearing loss in older humans and predict cochlear pathologies associated with certain audiometric configurations (“audiometric phenotypes”). Patterns of hearing loss associated with cochlear pathology in animal models were used to define schematic boundaries of human audiograms...

  9. Age-Related Shifts in Brain Activity Dynamics during Task Switching

    OpenAIRE

    Jimura, Koji; Braver, Todd S.

    2009-01-01

    Cognitive aging studies have suggested that older adults show declines in both sustained and transient cognitive control processes. However, previous neuroimaging studies have primarily focused on age-related change in the magnitude, but not temporal dynamics, of brain activity. The present study compared brain activity dynamics in healthy old and young adults during task switching. A mixed blocked/event-related functional magnetic resonance imaging design enabled separation of transient and ...

  10. Fatty old hearts: role of cardiac lipotoxicity in age-related cardiomyopathy

    OpenAIRE

    Drosatos, Konstantinos

    2016-01-01

    Age-related cardiomyopathy accounts for a significant part of heart failure cases. Imbalance of the energetic equilibrium of the heart along with mitochondrial dysfunction and impaired β-adrenergic receptor signaling contributes in the aggravation of cardiac function in the elderly. In this review article, studies that correlate cardiac aging with lipotoxicity are summarized. The involvement of inhibition of peroxisome proliferator-activated receptor-α, β-adrenergic receptor desensitization, ...

  11. Carotenoids and co-antioxidants in age-related maculopathy: design and methods.

    OpenAIRE

    Neelam, K.; Hogg, RE; Stevenson,, I.; Johnston, E.; Anderson, R; BEATTY, S; Chakravarthy, U

    2008-01-01

    Age-related macular degeneration (AMD), is the leading cause of blind registration in the Western World among individuals 65 years or older. Early AMD, a clinical state without overt functional loss, is said to be present clinically when yellowish deposits known as drusen and/or alterations of fundus pigmentation are seen in the macular retina. Although the etiopathogenesis of AMD remains uncertain, there is a growing body of evidence in support of the view that cumulative oxidative damage pl...

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

    Science.gov (United States)

    Lepers, Romuald; Stapley, Paul J

    2011-08-01

    The aims of this study were: (i) to analyze age-related declines in swimming, cycling, and running performances for road-based and off-road triathlons, and (ii) to compare age-related changes in these three disciplines between road-based and off-road triathlons. Swimming, cycling, running and total time performances of the top five males between 20 and 70 years of age (in 5-year intervals) were analyzed for short distance road-based (1.5 km swim, 40 km cycle, and 10 km run) and off-road (1.5 km swim, 30 km mountain bike, and 11 km trail run) triathlons at the 2009 World Championships. Independently of age, there was a lesser age-related decline in cycling performance (P 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 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.

  13. TCCR/WSX-1 is a novel angiogenic factor in age-related macular degeneration

    OpenAIRE

    Sung, Ho Jin; Han, Jung Il; Lee, Ji Won; Uhm, Ki Bang; Heo, Kyun

    2012-01-01

    Purpose Age-related macular degeneration (AMD) is the major cause of blindness among persons aged 60 years and older. The current approved therapies for AMD are exclusively limited to inhibiting vascular endothelial growth factor. However, substantial improvement in vision occurs in only one-third of patients treated with vascular endothelial growth factor antagonists, and one-sixth of treated patients still progress to legal blindness. Therefore, more specific targets are needed to treat AMD...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    , and were living in Denmark at the time of study inclusion. Data for study outcomes were obtained from the Danish National Hospital Registry and the Danish National Registry of Causes of Death and were cardiovascular diseases (myocardial infarction and stroke), cancers (virus associated, smoking related......, and other), severe neurocognitive disease, chronic kidney disease, chronic liver disease, and osteoporotic fractures. We calculated excess and age-standardised incidence rates and adjusted incidence rate ratios of outcomes for time after HIV diagnosis, highly active antiretroviral therapy (ART) initiation...... of cardiovascular diseases, cancers, and severe neurocognitive disease did not increase substantially with time after HIV diagnosis or ART initiation. Except for chronic kidney diseases, the age-standardised and relative risks of age-related diseases did not increase with calendar time. INTERPRETATIONS: Severe age...

  15. Age-Related Hypercholesterolemia and HMG-CoA Reductase Dysregulation: Sex Does Matter (A Gender Perspective

    Directory of Open Access Journals (Sweden)

    Laura Trapani

    2010-01-01

    Full Text Available Although cardiovascular diseases are less prevalent in premenopausal women than in men, their occurrence in women increases at the onset of menopause, and the loss of female sex hormones contributes to the striking increase in cardiovascular morbidity and mortality in postmenopausal women. We present here a description of age-related disruption of lipid homeostasis, which particularly affects 3-hydroxy 3-methylglutaryl Coenzyme A reductase, the key rate-limiting enzyme in the cholesterol biosynthetic pathway. We further discuss the age- and gender-related dysregulation of this enzyme, providing new evidence for the different mechanisms driving dyslipidemia in elderly men and women. In addition, we introduce pharmacological methods of regulating HMGR and maintaining cholesterol homeostasis.

  16. What effects has the cataract surgery on the development and progression of Age-Related Macular Degeneration (AMD?

    Directory of Open Access Journals (Sweden)

    Willich, Stefan N.

    2006-12-01

    Full Text Available Background: The cataract (Cataracta senilis is the most frequent eye disease of elderly people worldwide. In Germany, the cataract operation - with currently 450,000 interventions each year the most frequent operation in ophthalmology – can be seen as routine surgery. The age related macular degeneration (AMD is a further one of the most common, age-related eye diseases and the most frequent cause of blindness of elderly people in industrial nations. Due to demographic changes an increasing number of patients will suffer from cataract and AMD at the same time. This coincidence leads to a greater interest in the question of a mutual influence of both diseases, respectively their therapies, on each other. Objectives: The aim of this report was the evaluation of the medical and health economic effects of cataract operations on the development and progression of an age related macular degeneration (AMD. It was differentiated between first manifestations of AMD, progression of early stages of AMD and influence on further impairment in late stages of AMD. Methods: The relevant publications for this report were identified by DIMDI via structured database enquiry as well as common, self-made enquiry and were evaluated, based on the criteria of evidence based medicine. The present report included German and English literature published since 1983. Results: The database enquiry generated a record of 2769 issue-related publications. Eight medical publications were eligible for analysis in the course of the present HTA report. No relevant studies on health economical, ethical, social or legal issues could be included. Three epidemiological cohort studies provided some evidence for a promoting influence of cataract extractions on the progression of early types of AMD. Two of the epidemiological studies assessed the risk of first manifestation of AMD after cataract extraction. Both came up with up with increased incidences that did not reach statistical

  17. Middle ear impedance studies in elderly patients implications on age-related hearing loss

    Directory of Open Access Journals (Sweden)

    Olusola Ayodele Sogebi

    2015-04-01

    Full Text Available INTRODUCTION: Controversies arise with respect to functioning of the middle ear over time.OBJECTIVE: To assess changes in middle ear impedance that may be related to aging, and/or if there was an association of these changes with those of the inner ear in the elderly patients.METHODS: Cross-sectional, comparative study of elderly patients managed in ear, nose and throat clinics. A structured questionnaire was administered to obtain clinical information. Pure tone audiometry, tympanometry, and acoustic reflexes were performed. Comparative analyses were performed to detect intergroup differences between clinico-audiometric findings and middle ear measures, viz. tympanograms and acoustic reflexes.RESULTS: One hundred and three elderly patients participated in the study; 52.4% were male, averagely 70.0 ± 6.3 years old, age-related hearing loss in 59.2%, abnormal tympanograms in 39.3%, absent acoustic reflex in 37.9%. There was no association between age and gender in patients with abnormal tympanograms and absent acoustic reflex. Significantly more patients with different forms and grades of age-related hearing loss had abnormal tympanometry and absent acoustic reflex.CONCLUSION: Some abnormalities were observed in the impedance audiometric measures of elderly patients, which were significantly associated with parameters connected to age-related hearing loss.

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

    Institute of Scientific and Technical Information of China (English)

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

    2000-01-01

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

  19. Magnetic resonance fiber density mapping of age-related white matter changes

    International Nuclear Information System (INIS)

    Objectives: To introduce fiber density mapping (FDM) for investigation of age-related white matter (WM) changes and to compare its capabilities with conventional diffusion tensor imaging (DTI) post-processing. Methods: DTI data with 1.9 mm3 isotropic voxels were acquired from 44 healthy volunteers (18–88 years) at 3 T. FDM is a 3-step approach which includes diagonalization of the diffusion tensor, fiber reconstruction for the whole brain, and calculation of fiber density (FD) values. Maps of fractional anisotropy (FA) and mean diffusivity (MD) were additionally calculated. Voxel-based analyses were performed to determine volume clusters of significant correlation with age. Bivariate linear regression models and Hotelling–Williams tests were used to detect significant differences between correlations. Results: FDM detected a larger WM volume affected by age-related changes concomitant with fewer significant clusters compared to FA and MD. This indicates that WM alterations due to normal aging occur rather globally than locally. FD values showed a significant stronger correlation with age in frontal lobes (prefrontal and precentral gyrus), limbic lobes (cingulate and parahippocampal gyrus), the corpus callosum (genu) and temporal lobes. Conclusions: FDM shows higher sensitivity for detection of age-related WM changes because it includes all surrounding fiber structures into the evaluation of each DTI data voxel.

  20. Physiological antioxidative network of the bilirubin system in aging and age-related diseases

    Directory of Open Access Journals (Sweden)

    Sung Young eKim

    2012-03-01

    Full Text Available Oxidative stress is detrimental to life processes and is particularly responsible for aging and age-related diseases. Thus, most organisms are well equipped with a spectrum of biological defense mechanisms against oxidative stress. The major efficient antioxidative mechanism is the glutathione system, operating a redox cycling mechanism for glutathione utilization, which consists of glutathione and its peroxidase and reductase. However, this system is mainly effective for hydrophilic oxidants, while lipophilic oxidants require another scavenging system. Since many age-related pathological conditions are related to lipid peroxidation, especially in association with the aging process, the physiological role of the scavenging system for lipophilic oxidants should be considered. In this regard, the biliverdin to bilirubin conversion pathway, via biliverdin reductase, is suggested to be another major protective mechanism that scavenges lipophilic oxidants because of the lipophilic nature of bilirubin. The efficiency of this bilirubin system might be potentiated by operation of the intertwined bicyclic systems of the suggested redox metabolic cycle of biliverdin and bilirubin and the transcriptional control cycle of biliverdin reductase and heme oxygenase-1. In order to combat oxidative stress, both anti-oxidative systems, against hydrophilic and lipophilic oxidants, respectively, are required to work cooperatively. In this regard, the roles of the bilirubin system in aging and age-related diseases are reassessed in this review, and their interacting networks are evaluated.