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Sample records for assembly age-related increases

  1. 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.

  2. Lack of age-related increase in carotid artery wall viscosity in cardiorespiratory fit men.

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    Kawano, Hiroshi; Yamamoto, Kenta; Gando, Yuko; Tanimoto, Michiya; Murakami, Haruka; Ohmori, Yumi; Sanada, Kiyoshi; Tabata, Izumi; Higuchi, Mitsuru; Miyachi, Motohiko

    2013-12-01

    Age-related arterial stiffening and reduction of arterial elasticity are attenuated in individuals with high levels of cardiorespiratory fitness. Viscosity is another mechanical characteristic of the arterial wall; however, the effects of age and cardiorespiratory fitness have not been determined. We examined the associations among age, cardiorespiratory fitness and carotid arterial wall viscosity. A total of 111 healthy men, aged 25-39 years (young) and 40-64 years (middle-aged), were divided into either cardiorespiratory fit or unfit groups on the basis of peak oxygen uptake. The common carotid artery was measured noninvasively by tonometry and automatic tracking of B-mode images to obtain instantaneous pressure and diameter hysteresis loops, and we calculated the effective compliance, isobaric compliance and viscosity index. In the middle-aged men, the viscosity index was larger in the unfit group than in the fit group (2533 vs. 2018 mmHg·s/mm, respectively: Pviscosity index was increased with advancing age, but these parameters were unaffected by cardiorespiratory fitness level. These results suggest that the wall viscosity in the central artery is increased with advancing age and that the age-associated increase in wall viscosity may be attenuated in cardiorespiratory fit men.

  3. Increased expression of angiogenic growth factors in age-related maculopathy

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    M. Kliffen (Mike); H.S. Sharma (Hari); C.M. Mooy (Cornelia); S. Kerkvliet (Sonja); P.T.V.M. de Jong (Paulus)

    1997-01-01

    textabstractAIMS/BACKGROUND: The late stages of age-related maculopathy (ARM), especially neovascular macular degeneration (ARMD), can severely affect central vision and are the main cause of blindness in the elderly in the Western world. It has been shown that

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

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

    2015-01-01

    PURPOSE: We have recently identified homeostatic alterations in the circulating T cells of patients with age-related macular degeneration (AMD). In cultures of retinal pigment epithelial cells, we have demonstrated that T-cell-derived cytokines induced the upregulation of complement, chemokines...... 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...

  5. 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

  6. Absence of DJ-1 causes age-related retinal abnormalities in association with increased oxidative stress.

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    Bonilha, Vera L; Bell, Brent A; Rayborn, Mary E; Samuels, Ivy S; King, Anna; Hollyfield, Joe G; Xie, Chengsong; Cai, Huaibin

    2017-03-01

    Oxidative stress alters physiological function in most biological tissues and can lead to cell death. In the retina, oxidative stress initiates a cascade of events leading to focal loss of RPE and photoreceptors, which is thought to be a major contributing factor to geographic atrophy. Despite these implications, the molecular regulation of RPE oxidative stress under normal and pathological conditions remains largely unknown. A better understanding of the mechanisms involved in regulating RPE and photoreceptors oxidative stress response is greatly needed. To this end we evaluated photoreceptor and RPE changes in mice deficient in DJ-1, a protein that is thought to be important in protecting cells from oxidative stress. Young (3 months) and aged (18 months) DJ-1 knockout (DJ-1 KO) and age-matched wild-type mice were examined. In both group of aged mice, scanning laser ophthalmoscopy (SLO) showed the presence of a few autofluorescent foci. The 18 month-old DJ-1 KO retinas were also characterized by a noticeable increase in RPE fluorescence to wild-type. Optical coherence tomography (OCT) imaging demonstrated that all retinal layers were present in the eyes of both DJ-1 KO groups. ERG comparisons showed that older DJ-1 KO mice had reduced sensitivity under dark- and light-adapted conditions compared to age-matched control. Histologically, the RPE contained prominent vacuoles in young DJ-1 KO group with the appearance of enlarged irregularly shaped RPE cells in the older group. These were also evident in OCT and in whole mount RPE/choroid preparations labeled with phalloidin. Photoreceptors in the older DJ-1 KO mice displayed decreased immunoreactivity to rhodopsin and localized reduction in cone markers compared to the wild-type control group. Lower levels of activated Nrf2 were evident in retina/RPE lysates in both young and old DJ-1 KO mouse groups compared to wild-type control levels. Conversely, higher levels of protein carbonyl derivatives and i

  7. Age-related effects of increasing postural challenge on eye movement onset latencies to visual targets.

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    Jimenez, Sergio; Hollands, Mark; Palmisano, Stephen; Kim, Juno; Markoulli, Maria; McAndrew, Darryl; Stamenkovic, Alexander; Walsh, Joel; Bos, Sophie; Stapley, Paul J

    2016-06-01

    When a single light cue is given in the visual field, our eyes orient towards it with an average latency of 200 ms. If a second cue is presented at or around the time of the response to the first, a secondary eye movement occurs that represents a reorientation to the new target. While studies have shown that eye movement latencies to 'single-step' targets may or may not be lengthened with age, secondary eye movements (during 'double-step' displacements) are significantly delayed with increasing age. The aim of this study was to investigate whether the postural challenge posed simply by standing (as opposed to sitting) results in significantly longer eye movement latencies in older adults compared to the young. Ten young (older healthy adults (>65 years) participated in the study. They were required to fixate upon a central target and move their eyes in response to 2 types of stimuli: (1) a single-step perturbation of target position either 15° to the right or left and (2) a double-step target displacement incorporating an initial target jump to the right or left by 15°, followed after 200 ms, by a shift of target position to the opposite side (e.g. +15° then -15°). All target displacement conditions were executed in sit and stand positions with the participant at the same distance from the targets. Eye movements were recorded using electro-oculography. Older adults did not show significantly longer eye movement latencies than the younger adults for single-step target displacements, and postural configuration (stand compared to sit) had no effect upon latencies for either group. We categorised double-step trials into those during which the second light changed after or before the onset of the eye shift to the first light. For the former category, young participants showed faster secondary eye shifts to the second light in the standing position, while the older adults did not. For the latter category of double-step trial, young participants showed no

  8. 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.

    2015-01-01

    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 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. PMID:25627672

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

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    Faber, Carsten; Jehs, Tina; Juel, Helene Baek; Singh, Amardeep; Falk, Mads Krüger; Sørensen, Torben Lykke; Nissen, Mogens Holst

    2015-05-01

    We have recently identified homeostatic alterations in the circulating T cells of patients with age-related macular degeneration (AMD). In cultures of retinal pigment epithelial cells, we have demonstrated that T-cell-derived cytokines induced the upregulation of complement, chemokines 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. We conducted a case-control study. Age-related macular degeneration status was assessed using standardized multimodal imaging techniques. Plasma was isolated from freshly drawn peripheral venous blood samples and analysed for interleukin (IL)15, IL18, interferon (IFN)γ, soluble tumour necrosis factor (TNF) receptor II (sTNFRII) and complement factor H (CFH) Y402H genotype. We included 136 individuals with early or late 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. 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 with AMD. However, it remains to be determined whether increased levels of TNFα can be found, which directly reflects an increased activity of macrophages and T cells. © 2014 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  10. A common mutation of the MYH gene is associated with increased DNA oxidation and age-related diseases.

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    Sun, Caixia; Chen, Huimei; Guo, Wenwen; Zhang, Kui; Qi, Qiufeng; Gu, Xin; Zhu, Dalong; Wang, Yaping

    2010-02-01

    We describe a common mutation of the MYH gene, which is involved in the repair of oxidative damage to DNA, and its relationship to age, levels of 8-OHdG, and circulating levels of interleukin-1. We studied 1146 "healthy" and 562 unselected Chinese subjects. We observed a reverse insertion of the AluYb8 sequence (AluYb8MYH) to be homozygous in approximately 25.8% of the healthy Chinese population age 20-29 years, with the incidence of homozygosity decreasing to 15.7% by age 50-59 years. Because subjects were selected on the basis of absence of disease during medical screening, this suggests that homozygosity for this gene has a marked impact on the development of age-related or chronic diseases or mortality. Because the MYH gene is involved in DNA repair we assessed whether homozygous carriage of this gene was associated with increased levels of 8-OHdG in the leukocytic DNA of carriers. The level of 8-OHdG increased from 3.8 8-OHdG/10(6) dG in wild-type carriers to 10.8 8-OHdG/10(6) dG in homozygous carriers, suggesting that the presence of the mutation was associated with impaired DNA repair. Because this mutation might be associated with the increased development of age-related or chronic disease and inflammation, we also measured plasma concentrations of interleukin-1, which increases with aging and chronic disease. We observed a highly significant increase in plasma interleukin-1 in patients homozygous for the AluYb8 insertion in the MYH gene consistent with accelerated aging or development of undiagnosed disease in homozygous subjects. Screening for this genetic variation may have predictive value in assessing potential longevity of subjects in China, as well as in the Western world. Copyright 2009 Elsevier Inc. All rights reserved.

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

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

    2013-01-01

    PURPOSE: To examine the association between age-related changes in the T-cell compartment and prevalence of age-related macular degeneration (AMD). DESIGN: Case-control study. PARTICIPANTS: A total of 117 AMD cases and 106 controls were included prospectively. METHODS: Fresh-drawn peripheral bloo...

  12. Increased Th1/Th17 Responses Contribute to Low-Grade Inflammation in Age-Related Macular Degeneration.

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    Chen, Jiajia; Wang, Wenzhan; Li, Qiuming

    2017-01-01

    Age-related macular degeneration (AMD) is the primary cause of senior blindness in developed countries. Mechanisms underlying initiation and development of AMD remained known. We examined the CD4+ T cell compartments and their functions in AMD patients. AMD patients presented significantly higher frequencies of interferon (IFN)-γ-expressing and interleukin (IL)-17-expressing CD4+ T cells than healthy controls. The levels of IFN-γ and IL-17 expression by CD4+ T cells were significantly higher in AMD patients. These IFN-γ-expressing Th1 cells and IL-17-expressing Th17 cells could be selectively enriched by surface CCR3+ and CCR4+CCR6+ expression, respectively. Th1 and Th17 cells from AMD patients promoted the differentiation of monocytes toward M1 macrophages, which were previously associated with retinal damage. Th1 and Th17 cells also increased the level of MHC class I expression in human retinal pigment epithelial (RPE)-1 cells, while Th1 cells increased the frequency of MHC class II-expressing RPE-1 cells. These proinflammatory effects were partly, but not entirely, induced by the secretion of IFN-γ and IL-17. This study demonstrated an enrichment of Th1 cells and Th17 cells in AMD patients. These Th1 and Th17 cells possessed proinflammatory roles in an IFN-γ- and IL-17-dependent fashion, and could potentially serve as therapeutic targets. © 2017 The Author(s). Published by S. Karger AG, Basel.

  13. Increased Th1/Th17 Responses Contribute to Low-Grade Inflammation in Age-Related Macular Degeneration

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    Jiajia Chen

    2017-11-01

    Full Text Available Background/Aims: Age-related macular degeneration (AMD is the primary cause of senior blindness in developed countries. Mechanisms underlying initiation and development of AMD remained known. Methods: We examined the CD4+ T cell compartments and their functions in AMD patients. Results: AMD patients presented significantly higher frequencies of interferon (IFN-γ-expressing and interleukin (IL-17-expressing CD4+ T cells than healthy controls. The levels of IFN-γ and IL-17 expression by CD4+ T cells were significantly higher in AMD patients. These IFN-γ-expressing Th1 cells and IL-17-expressing Th17 cells could be selectively enriched by surface CCR3+ and CCR4+CCR6+ expression, respectively. Th1 and Th17 cells from AMD patients promoted the differentiation of monocytes toward M1 macrophages, which were previously associated with retinal damage. Th1 and Th17 cells also increased the level of MHC class I expression in human retinal pigment epithelial (RPE-1 cells, while Th1 cells increased the frequency of MHC class II-expressing RPE-1 cells. These proinflammatory effects were partly, but not entirely, induced by the secretion of IFN-γ and IL-17. Conclusions: This study demonstrated an enrichment of Th1 cells and Th17 cells in AMD patients. These Th1 and Th17 cells possessed proinflammatory roles in an IFN-γ- and IL-17-dependent fashion, and could potentially serve as therapeutic targets.

  14. ARMS2 increases the risk of early and late age-related macular degeneration in the European Eye Study.

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    Chakravarthy, Usha; McKay, Gareth J; de Jong, Paulus T V M; Rahu, Mati; Seland, Johan; Soubrane, Gisele; Tomazzoli, Laura; Topouzis, Fotis; Vingerling, Johannes R; Vioque, Jesus; Young, Ian S; Sofat, Reecha; Hingorani, Aroon D; Fletcher, Astrid E

    2013-02-01

    To study associations between severity stages of early and late age-related macular degeneration (AMD) and genetic variations in age-related maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH) and to investigate potential interactions between smoking and ARMS2. Population-based, cross-sectional European Eye Study in 7 countries in Europe. Four thousand seven hundred fifty participants, 65 years of age and older, recruited through random sampling. Participants were classified on the basis of the more severely affected eye into 5 mutually exclusive AMD severity stages ranging from no AMD, 3 categories of early AMD, and late AMD. History of cigarette smoking was available and allowed classification into never, former, and current smokers, with the latter 2 groups combined into a single category of ever smokers for analysis. Genotyping was performed for single nucleotide polymorphisms rs10490924 and rs4146894 in ARMS2 and rs1061170 in CFH. Associations were analyzed by logistic regression. Odds ratios (ORs) for stage of AMD associated with genetic variations in ARMS2 and CFH and interactions between ARMS2 and smoking status. Early AMD was present in 36.4% and late AMD was present in 3.3% of participants. Data on both genotype and AMD were available for 4276 people. The ORs for associations between AMD stage and ARMS2 increased monotonically with more severe stages of early AMD and were altered little by adjustment for potential confounders. Compared with persons with no AMD, carriers of the TT genotype for rs10490924 in ARMS2 had a 10-fold increase in risk of late AMD (Pearly AMD and late AMD. Interactions between rs10490924 in ARMS2 and smoking status were significant in both unadjusted and adjusted models (P = 0.001). The highest risk was observed in those doubly homozygous for rs10490924 and rs1061170 in CFH (OR, 62.3; 95% confidence interval, 16-242), with P values for trend ranging from 0.03 (early AMD, stage 1) to 1 × 10(-26) (late AMD). A strong

  15. Nutritional Supplementation Inhibits the Increase in Serum Malondialdehyde in Patients with Wet Age-Related Macular Degeneration.

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    Matsuura, Toshiyuki; Takayama, Kei; Kaneko, Hiroki; Ye, Fuxiang; Fukukita, Hiroshi; Tsunekawa, Taichi; Kataoka, Keiko; Hwang, Shiang-Jyi; Nagasaka, Yosuke; Ito, Yasuki; Terasaki, Hiroko

    2017-01-01

    Purpose. To compare serum levels of malondialdehyde (MDA) in patients with wet age-related macular degeneration (wAMD), patients with dry AMD (dAMD), and patients without AMD and to evaluate the efficacy of nutritional supplementation for treating elevated serum MDA in patients with wAMD. Methods. MDA levels were measured in sera from 20 patients with wAMD, 20 with dAMD, and 24 without AMD. Patients with wAMD were randomized to receive or not receive nutritional supplementation (10 patients in each group), and MDA levels were measured after 3 months of treatment. Results. MDA levels in patients with wAMD were significantly greater compared with patients without AMD. In eyes with wAMD, there was a significant correlation between MDA levels and choroidal neovascularization lesion area. Serum MDA levels decreased in most patients that received supplementation and significantly increased in those who did not. Conclusion. Baseline serum MDA levels were elevated in patients with wAMD, and MDA levels were directly correlated with choroidal neovascularization lesion area. In addition, nutritional supplementation appeared to exert a protective effect against oxidative stress in patients with wAMD.

  16. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Increased Expression of CD200 on Circulating CD11b+ Monocytes in Patients with Neovascular Age-related Macular Degeneration

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    Singh, Amardeep; Falk, Mads K; Hviid, Thomas V F

    2013-01-01

    OBJECTIVE: Dysregulation of retinal microglial activity has been implicated in the pathogenesis of neovascular age-related macular degeneration. Microglia activity can be regulated through the membrane protein CD200 and its corresponding receptor, the CD200 receptor (CD200R). Because both the lig...

  18. Age-related macular degeneration is associated with an increased risk of hip fractures in the Medicare database.

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    Anastasopoulos, Eleftherios; Yu, Fei; Coleman, Anne L

    2006-12-01

    To explore the relationship between age-related macular degeneration (AMD) and incident hip fractures in the Medicare population. Prospective cohort study. With a 5% random sample of Medicare beneficiaries in 1995, 8596 cases were coded with exudative AMD; 26,942 cases were coded with atrophic AMD, and 1,013,748 cases were coded without AMD. The Medicare claims from 1996 to 1999 were evaluated for hip fracture codes. The relationship between AMD and incident hip fractures was analyzed with multiple logistic regression models, with adjustment for baseline, ocular, and systemic covariates. In adjusted analyses, the risk of hip fractures was similar in cases that were coded with exudative AMD (odds ratio, 1.03; 95% confidence interval (CI), 0.95, 1.12) compared with cases with no AMD but was significantly higher in cases that were coded with atrophic AMD (odds ratio, 1.11; 95% CI, 1.06, 1.16). Medicare patients with a code for atrophic AMD had an 11% greater risk of hip fractures than did patients without a code for AMD over a four-year follow-up period.

  19. Glucose Transporter 1-Dependent Glycolysis Is Increased during Aging-Related Lung Fibrosis, and Phloretin Inhibits Lung Fibrosis.

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    Cho, Soo Jung; Moon, Jong-Seok; Lee, Chang-Min; Choi, Augustine M K; Stout-Delgado, Heather W

    2017-04-01

    Aging is associated with metabolic diseases such as type 2 diabetes mellitus, cardiovascular disease, cancer, and neurodegeneration. Aging contributes to common processes including metabolic dysfunction, DNA damage, and reactive oxygen species generation. Although glycolysis has been linked to cell growth and proliferation, the mechanisms by which the activation of glycolysis by aging regulates fibrogenesis in the lung remain unclear. The objective of this study was to determine if glucose transporter 1 (GLUT1)-induced glycolysis regulates age-dependent fibrogenesis of the lung. Mouse and human lung tissues were analyzed for GLUT1 and glycolytic markers using immunoblotting. Glycolytic function was measured using a Seahorse apparatus. To study the effect of GLUT1, genetic inhibition of GLUT1 was performed by short hairpin RNA transduction, and phloretin was used for pharmacologic inhibition of GLUT1. GLUT1-dependent glycolysis is activated in aged lung. Genetic and pharmacologic inhibition of GLUT1 suppressed the protein expression of α-smooth muscle actin, a key cytoskeletal component of activated fibroblasts, in mouse primary lung fibroblast cells. Moreover, we demonstrated that the activation of AMP-activated protein kinase, which is regulated by GLUT1-dependent glycolysis, represents a critical metabolic pathway for fibroblast activation. Furthermore, we demonstrated that phloretin, a potent inhibitor of GLUT1, significantly inhibited bleomycin-induced lung fibrosis in vivo. These results suggest that GLUT1-dependent glycolysis regulates fibrogenesis in aged lung and that inhibition of GLUT1 provides a potential target of therapy of age-related lung fibrosis.

  20. 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.

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

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    David Loeffler

    2016-07-01

    Full Text Available 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 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 in CSF samples from 34 healthy subjects ranging from 20 to 75 years of age. Age was negatively associated with HSPA8 (rho = -0.47; p = .005. An age-related increase in oxidative stress was indicated by a positive association between age and 8-OHdG (rho = 0.61; p = .0001. HSPA8 was moderately negatively associated with 8-OHdG (rho = -0.58; p = .0004. Age and HSPA8 were weakly associated with 8-isoprostane and total antioxidant capacity (range of rho values: -0.15 to 0.16. Our findings in this exploratory study suggest that during healthy aging, cerebrospinal fluid 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 cerebrospinal fluid. 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 cerebrospinal fluid is reflected by a similar change in the brain.

  2. Age-related increase in Wnt inhibitor causes a senescence-like phenotype in human cardiac stem cells.

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    Nakamura, Tamami; Hosoyama, Tohru; Murakami, Junichi; Samura, Makoto; Ueno, Koji; Kurazumi, Hiroshi; Suzuki, Ryo; Mikamo, Akihito; Hamano, Kimikazu

    2017-06-03

    Aging of cardiac stem/progenitor cells (CSCs) impairs heart regeneration and leads to unsatisfactory outcomes of cell-based therapies. As the precise mechanisms underlying CSC aging remain unclear, the use of therapeutic strategies for elderly patients with heart failure is severely delayed. In this study, we used human cardiosphere-derived cells (CDCs), a subtype of CSC found in the postnatal heart, to identify secreted factor(s) associated with CSC aging. Human CDCs were isolated from heart failure patients of various ages (2-83 years old). Gene expression of key soluble factors was compared between CDCs derived from young and elderly patients. Among these factors, SFRP1, a gene encoding a Wnt antagonist, was significantly up-regulated in CDCs from elderly patients (≥65 years old). sFRP1 levels was increased significantly also in CDCs, whose senescent phenotype was induced by anti-cancer drug treatment. These results suggest the participation of sFRP1 in CSC aging. We show that the administration of recombinant sFRP1 induced cellular senescence in CDCs derived from young patients, as indicated by increased levels of markers such as p16, and a senescence-associated secretory phenotype. In addition, co-administration of recombinant sFRP1 could abrogate the accelerated CDC proliferation induced by Wnt3A. Taken together, our results suggest that canonical Wnt signaling and its antagonist, sFRP1, regulate proliferation of human CSCs. Furthermore, excess sFRP1 in elderly patients causes CSC aging. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Age-related increases in long-range connectivity in fetal functional neural connectivity networks in utero

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    Moriah E. Thomason

    2015-02-01

    Full Text Available Formation of operational neural networks is one of the most significant accomplishments of human fetal brain growth. Recent advances in functional magnetic resonance imaging (fMRI have made it possible to obtain information about brain function during fetal development. Specifically, resting-state fMRI and novel signal covariation approaches have opened up a new avenue for non-invasive assessment of neural functional connectivity (FC before birth. Early studies in this area have unearthed new insights about principles of prenatal brain function. However, very little is known about the emergence and maturation of neural networks during fetal life. Here, we obtained cross-sectional rs-fMRI data from 39 fetuses between 24 and 38 weeks postconceptual age to examine patterns of connectivity across ten neural FC networks. We identified primitive forms of motor, visual, default mode, thalamic, and temporal networks in the human fetal brain. We discovered the first evidence of increased long-range, cerebral-cerebellar, cortical-subcortical, and intra-hemispheric FC with advancing fetal age. Continued aggregation of data about fundamental neural connectivity systems in utero is essential to establishing principles of connectomics at the beginning of human life. Normative data provides a vital context against which to compare instances of abnormal neurobiological development.

  4. Age-Related Increases in Tip-of-the-tongue are Distinct from Decreases in Remembering Names: A Functional MRI Study.

    Science.gov (United States)

    Huijbers, Willem; Papp, Kathryn V; LaPoint, Molly; Wigman, Sarah E; Dagley, Alex; Hedden, Trey; Rentz, Dorene M; Schultz, Aaron P; Sperling, Reisa A

    2017-09-01

    Tip-of-the-tongue (TOT) experiences increase with age and frequently heighten concerns about memory decline. We studied 73 clinically normal older adults participating in the Harvard Aging Brain Study. They completed a functional magnetic resonance imaging (fMRI) task that required remembering names associated with pictures of famous faces. Older age was associated with more self-reported TOT experiences and a decrease in the percentage of remembered names. However, the percentage of TOT experiences and the percentage of remembered names were not directly correlated. We mapped fMRI activity for recollection of famous names and TOT and examined activity in the hippocampal formation, retrosplenial cortex, and lateral prefrontal cortex. The hippocampal formation was similarly activated in recollection and TOT experiences. In contrast, the retrosplenial cortex was most active for recollection and lateral prefrontal cortex was most active for TOT experiences. Together, the results confirm that age-related increases in TOT experiences are not only solely the consequence of age-related decline in recollection, but also likely reflect functional alterations in the brain networks that support retrieval monitoring and cognitive control. These findings provide behavioral and neuroimaging evidence that age-related TOT experiences and memory failure are partially independent processes. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  5. Age-related infertility.

    Science.gov (United States)

    Crawford, Natalie M; Steiner, Anne Z

    2015-03-01

    Oocyte number and quality decrease with advancing age. Thus, fecundity decreases as age increases, with a more rapid decline after the mid-30s. Patients more than 35 years old should receive prompt evaluation for causes of infertility after no more than 6 months of attempted conception. Patients with abnormal tests of ovarian reserve have a poorer prognosis and may need more expedited and aggressive treatment. Although oocyte donation is the best method to overcome age-related infertility, other treatment options may help women proceed quicker toward pregnancy. Patients at an advanced age should be counseled and evaluated before undergoing infertility treatments. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Increased sensitivity to age-related differences in brain functional connectivity during continuous multiple object tracking compared to resting-state.

    Science.gov (United States)

    Dørum, Erlend S; Kaufmann, Tobias; Alnæs, Dag; Andreassen, Ole A; Richard, Geneviève; Kolskår, Knut K; Nordvik, Jan Egil; Westlye, Lars T

    2017-03-01

    Age-related differences in cognitive agility vary greatly between individuals and cognitive functions. This heterogeneity is partly mirrored in individual differences in brain network connectivity as revealed using resting-state functional magnetic resonance imaging (fMRI), suggesting potential imaging biomarkers for age-related cognitive decline. However, although convenient in its simplicity, the resting state is essentially an unconstrained paradigm with minimal experimental control. Here, based on the conception that the magnitude and characteristics of age-related differences in brain connectivity is dependent on cognitive context and effort, we tested the hypothesis that experimentally increasing cognitive load boosts the sensitivity to age and changes the discriminative network configurations. To this end, we obtained fMRI data from younger (n=25, mean age 24.16±5.11) and older (n=22, mean age 65.09±7.53) healthy adults during rest and two load levels of continuous multiple object tracking (MOT). Brain network nodes and their time-series were estimated using independent component analysis (ICA) and dual regression, and the edges in the brain networks were defined as the regularized partial temporal correlations between each of the node pairs at the individual level. Using machine learning based on a cross-validated regularized linear discriminant analysis (rLDA) we attempted to classify groups and cognitive load from the full set of edge-wise functional connectivity indices. While group classification using resting-state data was highly above chance (approx. 70% accuracy), functional connectivity (FC) obtained during MOT strongly increased classification performance, with 82% accuracy for the young and 95% accuracy for the old group at the highest load level. Further, machine learning revealed stronger differentiation between rest and task in young compared to older individuals, supporting the notion of network dedifferentiation in cognitive aging. Task

  7. Age-related toxicity of amyloid-beta associated with increased pERK and pCREB in primary hippocampal neurons: reversal by blueberry extract

    Science.gov (United States)

    Brewer, Gregory J.; Torricelli, John R.; Lindsey, Amanda L.; Kunz, Elizabeth Z.; Neuman, A.; Fisher, Derek R.; Joseph, James A.

    2009-01-01

    Further clarification is needed to address the paradox that memory formation, aging and neurodegeneration all involve calcium influx, oxyradical production (ROS) and activation of certain signaling pathways. In aged rats and in APP/PS-1 mice, cognitive and hippocampal Ca2+ dysregulation were reversed by food supplementation with a high antioxidant blueberry extract. Here, we studied whether neurons were an important target of blueberry extract and whether the mechanism involved altered ROS signaling through MAPK and CREB, pathways known to be activated in response to amyloid-beta. Primary hippocampal neurons were isolated and cultured from embryonic, middle-age or old-age (24 months) rats. Blueberry extract was found to be equally neuroprotective against amyloid-beta neurotoxicity at all ages. Increases in amyloid-beta toxicity with age were associated with age-related increases in immunoreactivity of neurons to pERK and an age-independent increase in pCREB. Treatment with blueberry extract strongly inhibited these increases in parallel with neuroprotection. Simultaneous labeling for ROS and for glutathione with dichlorofluorescein and monocholorobimane showed a mechanism of action of blueberry extract to involve transient ROS generation with an increase in the redox buffer, glutathione. We conclude that the increased age-related susceptibility of old-age neurons to amyloid-beta toxicity may be due to higher levels of activation of pERK and pCREB pathways that can be protected by blueberry extract through inhibition of both these pathways through an ROS stress response. These results suggest that the beneficial effects of blueberry extract may involve transient stress signaling and ROS protection that may translate into improved cognition in aging rats and APP/PS1 mice given blueberry extract. PMID:19954954

  8. Genetically heterogeneous mice show age-related vision deficits not related to increased rod cell L-type calcium channel function in vivo.

    Science.gov (United States)

    Berkowitz, Bruce A; Miller, Richard A; Roberts, Robin

    2017-01-01

    Visual performance declines over time in humans and 2-18 months outbred Long-Evans (LE) rats; vision is maintained in inbred 2-18 months C57BL/6 (B6) mice. Increased rod L-type calcium channel (LTCC) function predicts visual decline in LE rats but does not occur in B6 mice. Genetic diversity may contribute to rod LTCC function escalation time. To test this hypothesis, 4 and 18 months genetically heterogeneous UM-HET3 mice were studied. Rod LTCC function (manganese-enhanced magnetic resonance imaging [MRI]) and ocular anatomy (MRI, optical coherence tomography) were measured in vivo. Light-evoked subretinal space and choroid thickness changes were measured (diffusion-weighted MRI). Visual performance declined over time in the absence of (1) increased rod LTCC function; (2) changes in light-dependent expansion of the subretinal space and choroidal thickness; and (3) retinal thinning. Aging changed anterior and vitreous chambers' axial length and decreased light-stimulated choroidal expansion. Species differences appear to contribute to the LTCC function differences. Aging-related declines in vision in the UM-HET3 mice deserve more attention than they have received so far. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    Yanagi, Shigehisa; Tsubouchi, Hironobu; Miura, Ayako; Matsuo, Ayako; Matsumoto, Nobuhiro; Nakazato, Masamitsu

    2017-02-25

    Pneumonia generates considerable negative impacts on the elderly. Despite the widespread uses of vaccines and appropriate antibiotics, the morbidity and mortality of elderly pneumonia are significantly higher compared to the counterparts of young populations. The definitive mechanisms of high vulnerability in the elderly against pathogen threats are unclear. Age-associated, chronic low-grade inflammation augments the susceptibility and severity of pneumonia in the elderly. Cellular senescence, one of the hallmarks of aging, has its own characteristics, cell growth arrest and senescence-associated secretory phenotype (SASP). These properties are beneficial if the sequence of senescence-clearance-regeneration is transient in manner. However, persisting senescent cell accumulation and excessive SASP might induce sustained low-grade inflammation and disruption of normal tissue microenvironments in aged tissue. Emerging evidence indicates that cellular senescence is a key component in the pathogenesis of chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), which are known to be age-related and increase the risk of pneumonia. In addition to their structural collapses, COPD and IPF might increase the vulnerability to pathogen insults through SASP. Here, we discuss the current advances in understanding of the impacts of cellular senescence in elderly pneumonia and in these chronic lung disorders that heighten the risk of respiratory infections.

  10. A validated age-related normative model for male total testosterone shows increasing variance but no decline after age 40 years.

    Directory of Open Access Journals (Sweden)

    Thomas W Kelsey

    Full Text Available The diagnosis of hypogonadism in human males includes identification of low serum testosterone levels, and hence there is an underlying assumption that normal ranges of testosterone for the healthy population are known for all ages. However, to our knowledge, no such reference model exists in the literature, and hence the availability of an applicable biochemical reference range would be helpful for the clinical assessment of hypogonadal men. In this study, using model selection and validation analysis of data identified and extracted from thirteen studies, we derive and validate a normative model of total testosterone across the lifespan in healthy men. We show that total testosterone peaks [mean (2.5-97.5 percentile] at 15.4 (7.2-31.1 nmol/L at an average age of 19 years, and falls in the average case [mean (2.5-97.5 percentile] to 13.0 (6.6-25.3 nmol/L by age 40 years, but we find no evidence for a further fall in mean total testosterone with increasing age through to old age. However we do show that there is an increased variation in total testosterone levels with advancing age after age 40 years. This model provides the age related reference ranges needed to support research and clinical decision making in males who have symptoms that may be due to hypogonadism.

  11. Age-related effects of increased ambient pressure on discrimination reaction time: A study in 105 professional divers at 6.0 atm abs.

    Science.gov (United States)

    Tikkinen, Janne; Siimes, Martti A

    2015-01-01

    We investigated 105 professional divers using a computerized visual discrimination trial (Cognitrone) to measure the effects of ambient pressure on reaction times. The possible improvement in performance due to practice was anticipated, and the trials were carried out four times prior to pressurization in a hyperbaric chamber. The effect of increased ambient pressure was measured at 6.0 and 1.9 atm abs, and the potential for residual effects was tested after decompression. The results of our study indicate that repeated testing had a systematic influence on the measured time values. The effects of learning, which were independent of diver age, may have independently influenced response times. Exposure to 6.0 atm abs modified the systematic pattern of learning and was associated with increased reaction times. There were also age-related differences in response times associated with exposure to increased ambient pressures. Younger divers were more susceptible to elevated ambient pressure, evidenced by increased response times at 6 atm abs relative to their older colleagues. One out of every four of the younger divers could be considered susceptible to inert gas narcosis (ION) when an increase of one standard deviation/1SD (> 19%) or more in discrimination reaction time is used as an indicator. ION susceptibility appears independent of body composition and physical fitness. The slowed response speed experienced at 6.0 atm abs was of short duration and returned to baseline immediately with decompression. Our results suggest that IGN is demonstrated by an impaired learning process and decreased response speed and that some younger divers appear more susceptible.

  12. Age-Related Macular Degeneration.

    Science.gov (United States)

    Mehta, Sonia

    2015-09-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. AMD is diagnosed based on characteristic retinal findings in individuals older than 50. Early detection and treatment are critical in increasing the likelihood of retaining good and functional vision. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Prothrombin G20210A (rs1799963) polymorphism increases myocardial infarction risk in an age-related manner: A systematic review and meta-analysis.

    Science.gov (United States)

    Li, Changlong; Ren, Hui; Chen, Hong; Song, Junxian; Li, Sufang; Lee, Chongyou; Liu, Jun; Cui, Yuxia

    2017-10-19

    G20210A polymorphism (rs1799963) within the prothrombin gene is associated with a higher circulation level of prothrombin, thus increasing the likelihood of developing myocardial infarction (MI). Opinions differ regarding the correlation between prothrombin G20210A genotype and MI risk, which prompted us to conduct a meta-analysis to determine this association. PubMed, EMBASE, Web of Science and CNKI were searched for pertinent reports. A total of 34 studies involving 14 611 MI cases and 84 358 controls were analyzed in this quantitative analysis. We found a statistically significant association between prothrombin G20210A polymorphism and MI in the allele model (A vs. G, OR = 1.43, 95%CI: 1.18-1.72), heterozygote model (GA vs. GG, OR = 1.41, 95%CI: 1.16-1.72) and dominant model (GA + AA vs. GG, OR = 1.41, 95%CI: 1.15-1.72). The association remains significant in Caucasians but not in non-Caucasians. Moreover, prothrombin G20210A polymorphism increases MI risk in an age-related manner. A further significant association was found in a subpopulation younger than 55 years (allele model, OR = 1.76, 95%CI: 1.32-2.35; heterozygote model, OR = 1.70, 95%CI: 1.24-2.33; dominant model, OR = 1.70, 95%CI: 1.24-2.34). Sensitivity analysis and publication bias analysis revealed stable and statistically robust results. Our meta-analysis demonstrated that prothrombin G20210A polymorphism may represent a risk factor for MI.

  14. Increases in serum immunoglobulins to age-related normal levels in children with IgA and/or IgG subclass deficiency.

    Science.gov (United States)

    Kutukculer, Necil; Karaca, Neslihan Edeer; Demircioglu, Ozlem; Aksu, Guzide

    2007-03-01

    deficiency group and in 30% of patients in isolated IgG subclass deficiency group. The mean age for reaching age-related normal IgG subclass levels for these patients was 69.0 +/- 14.5 months. In conclusion, findings of this study suggest that IgA and/or IgG subclass deficiency may be either progressive or reversible disorders and emphasize the value of monitoring Ig levels in affected individuals.

  15. 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.

  16. Mitochondrial DNA variants of respiratory complex I that uniquely characterize haplogroup T2 are associated with increased risk of age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    John Paul SanGiovanni

    Full Text Available 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 reported in large prospective cohorts. METHODOLOGY/PRINICIPAL FINDINGS: We examined the relationship of inherited mtDNA variants with advanced AMD in 1168 people using a three-stage design on samples from 12-year and 10-year prospective studies on the natural history of age-related eye disease. In Stage I we resequenced the entire genome in 99 elderly AMD-free controls and 215 people with advanced AMD from the 12-year study. A consistent association with AMD in 14 of 17 SNPs characterizing the mtDNA T haplogroup emerged. Further analysis revealed these associations were driven entirely by the T2 haplogroup, and characterized by two variants in Complex I genes (A11812G of MT-ND4 and A14233G of MT-ND6. We genotyped T haplogroups in an independent sample of 490 cases and 61 controls from the same study (Stage II and in 56 cases and 246 controls from the 10-year study (Stage III. People in the T2 haplogroup were approximately 2.5 times more likely to have advanced AMD than their peers (odds ratio [OR] = 2.54, 95%CI 1.36-4.80, P

  17. Age-related increase in the fraction of CD27-CD4+ T cells and IL-4 production as a feature of CD4+ T cell differentiation in vivo

    NARCIS (Netherlands)

    Nijhuis, E. W.; Remarque, E. J.; Hinloopen, B.; van der Pouw-Kraan, T.; van Lier, R. A.; Ligthart, G. J.; Nagelkerken, L.

    1994-01-01

    The influence of ageing on phenotype and function of CD4+ T cells was studied by comparing young (19-28 years of age) and aged (75-84 years of age) donors that were selected using the SENIEUR protocol to exclude underlying disease. An age-related increase was observed in the relative number of

  18. 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.

  19. Dual sensory loss: A major age-related increase of comorbid hearing loss and hearing aid ownership in visually impaired adults

    NARCIS (Netherlands)

    Vreeken, H.L.; van Rens, G.H.M.B.; Knol, D.L.; van Reijen, N.A.; Kramer, S.E.; Festen, J.M.; van Nispen, R.M.A.

    2014-01-01

    Aim: Despite increasing interest in visual and hearing impairment in the older population, little attention has been paid to concurrent hearing and vision loss, also known as dual sensory loss. The aim of the present study was to investigate the prevalence of comorbid hearing disability and hearing

  20. 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

    AIMS: Endothelin-1 has potent constrictor and proliferative activity in vascular smooth muscle, and essential hypertension and aging are associated with increased endothelin-1-mediated vasoconstrictor tone. The aim of this study was to investigate the effect of physical activity, hypertension...... and 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...... 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...

  1. 1'-Acetoxychavicol acetate ameliorates age-related spatial memory deterioration by increasing serum ketone body production as a complementary energy source for neuronal cells.

    Science.gov (United States)

    Kojima-Yuasa, Akiko; Yamamoto, Tomiya; Yaku, Keisuke; Hirota, Shiori; Takenaka, Shigeo; Kawabe, Kouichi; Matsui-Yuasa, Isao

    2016-09-25

    1'-Acetoxychavicol acetate (ACA) is naturally obtained from the rhizomes and seeds of Alpinia galangal. Here, we examined the effect of ACA on learning and memory in senescence-accelerated mice prone 8 (SAMP8). In mice that were fed a control diet containing 0.02% ACA for 25 weeks, the learning ability in the Morris water maze test was significantly enhanced in comparison with mice that were fed the control diet alone. In the Y-maze test, SAMP8 mice showed decreased spontaneous alterations in comparison with senescence-accelerated resistant/1 (SAMR1) mice, a homologous control, which was improved by ACA pretreatment. Serum metabolite profiles were obtained by GC-MS analysis, and each metabolic profile was plotted on a 3D score plot. Based upon the diagram, it can be seen that the distribution areas for the three groups were completely separate. Furthermore, the contents of β-hydroxybutyric acid and palmitic acid in the serum of SAMP8-ACA mice were higher than those of SAMP8-control mice and SAMR1-control mice. We also found that SAMR1 mice did not show histological abnormalities, whereas histological damage in the CA1 region of the hippocampus in SAMP8-control mice was observed. However, SAMP8-ACA mice were observed in a similar manner as SAMR1 mice. These findings confirm that ACA increases the serum concentrations of β-hydroxybutyric acid and palmitic acid levels and thus these fuels might contribute to the maintenance of the cognitive performance of SAMP8 mice. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. 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

  3. 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.

  4. 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.

  5. Driving and Age-Related Macular Degeneration

    Science.gov (United States)

    Owsley, Cynthia; McGwin, Gerald, Jr.

    2008-01-01

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

  6. 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.

  7. [Age-related functional gastrointestinal disorders].

    Science.gov (United States)

    Frieling, T

    2011-01-01

    The demographic development will lead to a disproportionate increase of older people and to a significant increase of functional gastrointestinal disorders including dysphagia due to motility and reflux-related disorders, nausea and vomiting by gastrointestinal dysfunction and abdominal and pelvic pain caused by chronic obstipation, stool impaction and incontinence. This implies significant consequences with regard to the development of weight loss, anorexia, social disadvantages and increased mortality with serious socio-economic burden. Ageing processes are determined by differentiated neurogeneration of the myenteric plexus (cholinergic degeneration) through reactive oxygen and nitrogen species and alteration of protective and regenerative processes. Age-related gastrointestinal dysfunctions may be caused by the ageing gastrointestinal tract itself or by other age-related diseases such as tumour, neurological or inflammatory diseases, anatomic changes, therapeutic medication, polymorbidity or malnutrition. Because of the significant therapeutic options, differential diagnostic work-up is mandatory also in elderly patients. © Georg Thieme Verlag KG Stuttgart · New York.

  8. Interventions for age-related diseases

    DEFF Research Database (Denmark)

    Figueira, Inês; Fernandes, Adelaide; Mladenovic Djordjevic, Aleksandra

    2016-01-01

    Over 60% of people aged over 65 are affected by multiple morbidities, which are more difficult to treat, generate increased healthcare costs and lead to poor quality of life compared to individual diseases. With the number of older people steadily increasing this presents a societal challenge. Age...... is the major risk factor for age-related diseases and recent research developments have led to the proposal that pharmacological interventions targeting common mechanisms of ageing may be able to delay the onset of multimorbidity. Here we review the state of the knowledge of multimorbidity, appraise...... the available evidence supporting the role of mechanisms of ageing in the development of the most common age-related diseases and assess potential molecules that may successfully target those key mechanisms....

  9. Age-related macular degeneration

    DEFF Research Database (Denmark)

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

    2002-01-01

    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...... 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...

  10. Age-related decline in global form suppression

    DEFF Research Database (Denmark)

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

    2015-01-01

    . Selective attention, i.e., the ability to focus on relevant and ignore irrelevant information, declines with increasing age; however, how this deficit affects selection of global vs. local configurations remains unknown. On this background, the present study examined for age-related differences in a global...... to younger age. Our results suggest that the enhanced global-local asymmetry in the older age group originated from less effective suppression of global distracter forms on early processing stages – indicative of older observers having difficulties with disengaging from a global default selection mode......Visual selection of illusory ‘Kanizsa’ figures, an assembly of local elements that induce the percept of a whole object, is facilitated relative to configurations composed of the same local elements that do not induce a global form – an instance of ‘global precedence’ in visual processing...

  11. 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

  12. Age-related macular degeneration

    DEFF Research Database (Denmark)

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

    2002-01-01

    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 individ......, photodynamic therapy with verteporfin is the treatment of choice. Photodynamic therapy is also effective in eyes with pure occult CNV and evidence of recent disease progression. For new subfoveal CNV with poor vision and recurrent CNV, laser photocoagulation can be considered....... 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...... (exudative cases); the remainder has only geographic atrophy. In cross-sectional population-based studies about 45% of eyes with AMD have visual acuity reduced to 20/200 or worse. This is true both for exudative AMD and pure geographic atrophy. Age and genetic predisposition are known risk factors for AMD...

  13. Non-random food-web assembly at habitat edges increases connectivity and functional redundancy.

    Science.gov (United States)

    Peralta, Guadalupe; Frost, Carol M; Didham, Raphael K; Rand, Tatyana A; Tylianakis, Jason M

    2017-04-01

    Habitat fragmentation dramatically alters the spatial configuration of landscapes, with the creation of artificial edges affecting community structure and dynamics. Despite this, it is not known how the different food webs in adjacent habitats assemble at their boundaries. Here we demonstrate that the composition and structure of herbivore-parasitoid food webs across edges between native and plantation forests are not randomly assembled from those of the adjacent communities. Rather, elevated proportions of abundant, interaction-generalist parasitoid species at habitat edges allowed considerable interaction rewiring, which led to higher linkage density and less modular networks, with higher parasitoid functional redundancy. This was despite high overlap in host composition between edges and interiors. We also provide testable hypotheses for how food webs may assemble between habitats with lower species overlap. In an increasingly fragmented world, non-random assembly of food webs at edges may increasingly affect community dynamics at the landscape level. © 2016 by the Ecological Society of America.

  14. The proteasome maturation protein POMP increases proteasome assembly and activity in psoriatic lesional skin.

    Science.gov (United States)

    Zieba, Barbara A; Henry, Laurent; Lacroix, Matthieu; Jemaà, Mohamed; Lavabre-Bertrand, Thierry; Meunier, Laurent; Coux, Olivier; Stoebner, Pierre-Emmanuel

    2017-10-01

    The ubiquitin proteasome pathway is involved in the pathogenesis of psoriasis and proteasome subunits are increased in lesional psoriatic skin. Recent works have highlighted that proteasome levels can be regulated through modulation of proteasome assembly notably by the proteasome maturation protein POMP. To investigate whether proteasome assembly and POMP expression are modified in psoriatic skin. Proteasome assembly as well as expression of proteasome regulators were assessed in non-lesional and lesional psoriatic skin using native gel electrophoresis and western blots respectively. The protein and mRNA expression levels of POMP were compared by western blots, immunohistochemistry and quantitative polymerase chain reaction. The role of POMP in keratinocyte proliferation and differentiation was assessed by silencing POMP gene expression by RNA interference in human immortalized keratinocyte HaCaT cells. Both 20S and 26S proteasomes (and their respective proteolytic activities) as well as the main proteasome regulators are increased in lesional psoriatic skin. POMP binds to 20S precursor complexes and is overexpressed in lesional epidermal psoriatic skin, supporting that POMP-mediated proteasome assembly is increased in psoriatic skin. POMP silencing inhibited HaCaT cell proliferation and induced apoptosis through the inhibition of the proteasome assembly. Moreover POMP partial depletion decreased the expression of the differentiation markers keratin 10 and involucrin during the [Ca2+]-induced HaCaT cells differentiation. Altogether these results establish a potential role for POMP and proteasome assembly in psoriasis pathogenesis. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  15. Increasing Pizza Box Assembly Using Task Analysis and a Least-to-Most Prompting Hierarchy

    Science.gov (United States)

    Stabnow, Erin F.

    2015-01-01

    This study was designed to use a task analysis and a least-to-most prompting hierarchy to teach students with cognitive disabilities pizza box assembly skills. The purpose of this study was to determine whether a least-to-most prompting hierarchy was effective in teaching students with cognitive disabilities to increase the number of task-analyzed…

  16. The Age-Related Changes in Cartilage and Osteoarthritis

    Directory of Open Access Journals (Sweden)

    YongPing Li

    2013-01-01

    Full Text Available Osteoarthritis (OA is closely associated with aging, but its underlying mechanism is unclear. Recent publications were reviewed to elucidate the connection between aging and OA. With increasing OA incidence, more senior people are facing heavy financial and social burdens. Age-related OA pathogenesis is not well understood. Recently, it has been realized that age-related changes in other tissues besides articular cartilage may also contribute to OA development. Many factors including senescence-related secretory phenotypes, chondrocytes’ low reactivity to growth factors, mitochondrial dysfunction and oxidative stress, and abnormal accumulation of advanced glycation end products (AGEs may all play key roles in the pathogenesis of age-related OA. Lately, epigenetic regulation of gene expression was recognized for its impact on age-related OA pathogenesis. Up to now, few studies have been reported about the role of miRNA and long-noncoding RNA (lncRNA in age-related OA. Research focusing on this area may provide valuable insights into OA pathogenesis. OA-induced financial and social burdens have become an increasingly severe threat to older population. Age-related changes in noncartilage tissue should be incorporated in the understanding of OA development. Growing attention on oxidative stress and epigenetics will provide more important clues for the better understanding of the age-related OA.

  17. A ketogenic diet increases succinic dehydrogenase (SDH) activity and recovers age-related decrease in numeric density of SDH-positive mitochondria in cerebellar Purkinje cells of late-adult rats.

    Science.gov (United States)

    Balietti, Marta; Giorgetti, Belinda; Di Stefano, Giuseppina; Casoli, Tiziana; Platano, Daniela; Solazzi, Moreno; Bertoni-Freddari, Carlo; Aicardi, Giorgio; Lattanzio, Fabrizia; Fattoretti, Patrizia

    2010-02-01

    Ketogenic diets (KDs) have been applied in the therapy of paediatric epilepsy for nearly a century. Recently, beneficial results have also been reported on metabolic disorders and neurodegeneration, designating aged individuals as possible recipients. However, KDs efficacy decrease after the suckling period, and very little is known about their impact on the aging brain. In the present study, the effect on the neuronal energetic supply of a KD containing 20% of medium chain triglycerides (MCT) was investigated in Purkinje cells of the cerebellar vermis of late-adult (19-month-old) rats. The animals were fed with the KD for 8 weeks, and succinic dehydrogenase (SDH) activity was cytochemically determined. The following parameters of SDH-positive mitochondria were evaluated by the use of a computer-assisted image analysis system connected to a transmission electron microscope: numeric density (Nv), average volume (V), volume density (Vv), and cytochemical precipitate area/mitochondrial area (R). Young, age-matched, and old animals fed with a standard chow were used as controls. We found significantly higher Nv in MCT-KD-fed rats vs. all the control groups, in young vs. late-adult and old controls, and in late-adult vs. old controls. V and Vv showed no significant differences among the groups. R was significantly higher in MCT-KD-fed rats vs. all the control animals, and in old vs. young and late-adult controls. Present data indicate that the ketogenic treatment counteracted age-related decrease in numeric density of SDH-positive mitochondria, and enhanced their metabolic efficiency. Given the central role of mitochondrial impairment in age-related physio-pathological changes of the brain, these findings may represent a starting point to examine novel potentialities for KDs.

  18. Genes, inflammation, and age-related diseases

    NARCIS (Netherlands)

    Trompet, Stella

    2010-01-01

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

  19. What Is Age-Related Macular Degeneration?

    Science.gov (United States)

    ... Stories Español Eye Health / Eye Health A-Z Age-Related Macular Degeneration Sections What Is Macular Degeneration? Who is at ... Low Vision: Making the Most of Low Vision Age-Related Macular Degeneration Vision Simulator AMD Pictures and Videos: What Does ...

  20. [Depression in Patients with Age-Related Macular Degeneration].

    Science.gov (United States)

    Narváez, Yamile Reveiz; Gómez-Restrepo, Carlos

    2012-09-01

    Age-related macular degeneration is a cause for disability in the elderly since it greatly affects their quality of life and increases depression likelihood. This article discusses the negative effect depression has on patients with age-related macular degeneration and summarizes the interventions available for decreasing their depression index. Copyright © 2012 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

  1. Precursors of age-related macular degeneration

    DEFF Research Database (Denmark)

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

    2016-01-01

    PURPOSE: To investigate associations of very early age-related macular degeneration (AMD) with daily intake of vitamin A, beta-carotene, vitamin E, vitamin C, zinc and copper and interactions with AMD-associated polymorphisms in complement factor H (CFHY402H) and ARMS2/LOC387715. METHODS: Cross......-sectional study of 848 subjects aged 30-60 years from the Inter99 Eye Study. Daily intake of vitamins and minerals was estimated from a 198-item food frequency questionnaire. Digital fundus photographs were recorded in red-free illumination and graded for macular drusen >63 μm and numerous (>20) small hard...... for recruitment group, age and sex. There was a significant interaction with CFHY402H (p = 0.038). Among 504 participants with CFHY402H, the relative risk of having macular drusen >63 μm was increased in participants in the highest quartile of vitamin A intake (odds ratio = 2.58; CI95 1.16-5.73, p = 0...

  2. Age-related changes in mastication.

    Science.gov (United States)

    Peyron, M A; Woda, A; Bourdiol, P; Hennequin, M

    2017-04-01

    The paper reviews human mastication, focusing on its age-related changes. The first part describes mastication adaptation in young healthy individuals. Adaptation to obtain a food bolus ready to be swallowed relies on variations in number of cycles, muscle strength and volume of emitted saliva. As a result, the food bolus displays granulometric and rheological properties, the values of which are maintained within the adaptive range of deglutition. The second part concerns healthy ageing. Some mastication parameters are slightly modified by age, but ageing itself does not impair mastication, as the adaptation possibilities remain operant. The third part reports on very aged subjects, who display frequent systemic or local diseases. Local and/or general diseases such as tooth loss, salivary defect, or motor impairment are then indistinguishably superimposed on the effects of very old age. The resulting impaired function increases the risk of aspiration and choking. Lastly, the consequences for eating behaviour and nutrition are evoked. © 2016 John Wiley & Sons Ltd.

  3. Age related macular degeneration and visual disability.

    Science.gov (United States)

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

    2011-02-01

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

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

    Science.gov (United States)

    Turlea, C

    2012-01-01

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

  5. Age-related decline in global form suppression.

    Science.gov (United States)

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

    2015-12-01

    Visual selection of illusory 'Kanizsa' figures, an assembly of local elements that induce the percept of a whole object, is facilitated relative to configurations composed of the same local elements that do not induce a global form--an instance of 'global precedence' in visual processing. Selective attention, i.e., the ability to focus on relevant and ignore irrelevant information, declines with increasing age; however, how this deficit affects selection of global vs. local configurations remains unknown. On this background, the present study examined for age-related differences in a global-local task requiring selection of either a 'global' Kanizsa- or a 'local' non-Kanizsa configuration (in the presence of the respectively other configuration) by analyzing event-related lateralizations (ERLs). Behaviorally, older participants showed a more pronounced global-precedence effect. Electrophysiologically, this effect was accompanied by an early (150-225 ms) 'positivity posterior contralateral' (PPC), which was elicited for older, but not younger, participants, when the target was a non-Kanizsa configuration and the Kanizsa figure a distractor (rather than vice versa). In addition, timing differences in the subsequent (250-500 ms) posterior contralateral negativity (PCN) indicated that attentional resources were allocated faster to Kanizsa, as compared to non-Kanizsa, targets in both age groups, while the allocation of spatial attention seemed to be generally delayed in older relative to younger age. Our results suggest that the enhanced global-local asymmetry in the older age group originated from less effective suppression of global distracter forms on early processing stages--indicative of older observers having difficulties with disengaging from a global default selection mode and switching to the required local state of attentional resolution. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Aging-Related Hormone Changes in Men

    Science.gov (United States)

    ... over a period of many years and the consequences aren't necessarily clear. So what's the best way to refer to so-called male menopause? Many doctors use the term "andropause" to describe aging-related hormone changes in men. Other terms include ...

  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. CREB Overexpression Ameliorates Age-related Behavioral and Biophysical Deficits

    Science.gov (United States)

    Yu, Xiao-Wen

    Age-related cognitive deficits are observed in both humans and animals. Yet, the molecular mechanisms underlying these deficits are not yet fully elucidated. In aged animals, a decrease in intrinsic excitability of pyramidal neurons from the CA1 sub-region of hippocampus is believed to contribute to age-related cognitive impairments, but the molecular mechanism(s) that modulate both these factors has yet to be identified. Increasing activity of the transcription factor cAMP response element-binding protein (CREB) in young adult rodents has been shown to facilitate cognition, and increase intrinsic excitability of their neurons. However, how CREB changes with age, and how that impacts cognition in aged animals, is not clear. Therefore, we first systematically characterized age- and training-related changes in CREB levels in dorsal hippocampus. At a remote time point after undergoing behavioral training, levels of total CREB and activated CREB (phosphorylated at S133, pCREB) were measured in both young and aged rats. We found that pCREB, but not total CREB was significantly reduced in dorsal CA1 of aged rats. Importantly, levels of pCREB were found to be positively correlated with short-term spatial memory in both young and aged rats i.e. higher pCREB in dorsal CA1 was associated with better spatial memory. These findings indicate that an age-related deficit in CREB activity may contribute to the development of age-related cognitive deficits. However, it was still unclear if increasing CREB activity would be sufficient to ameliorate age-related cognitive, and biophysical deficits. To address this question, we virally overexpressed CREB in CA1, where we found the age-related deficit. Young and aged rats received control or CREB virus, and underwent water maze training. While control aged animals exhibited deficits in long-term spatial memory, aged animals with CREB overexpression performed at levels comparable to young animals. Concurrently, aged neurons

  9. Parainflammation, chronic inflammation, and age-related macular degeneration.

    Science.gov (United States)

    Chen, Mei; Xu, Heping

    2015-11-01

    Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune-privileged tissue as a result of its unique anatomic and physiologic properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate-immune system, particularly microglia and the complement system, undergoes low levels of activation (parainflammation). In many cases, this parainflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration, this parainflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal parainflammation include genetic predisposition, environmental risk factors, and old age. Dysregulated parainflammation (chronic inflammation) in age-related macular degeneration damages the blood retina barrier, resulting in the breach of retinal-immune privilege, leading to the development of retinal lesions. This review discusses the basic principles of retinal innate-immune responses to endogenous chronic insults in normal aging and in age-related macular degeneration and explores the difference between beneficial parainflammation and the detrimental chronic inflammation in the context of age-related macular degeneration. © Society for Leukocyte Biology.

  10. Reversal of age-related increase in brain protein oxidation, decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-tert-butyl-alpha-phenylnitrone

    Energy Technology Data Exchange (ETDEWEB)

    Carney, J.M.; Starke-Reed, P.E.; Oliver, C.N.; Landum, R.W.; Cheng, M.S.; Wu, J.F.; Floyd, R.A. (Univ. of Kentucky, Lexington (USA))

    1991-05-01

    Oxygen free radicals and oxidative events have been implicated as playing a role in bringing about the changes in cellular function that occur during aging. Brain readily undergoes oxidative damage, so it is important to determine if aging-induced changes in brain may be associated with oxidative events. Previously we demonstrated that brain damage caused by an ischemia/reperfusion insult involved oxidative events. In addition, pretreatment with the spin-trapping compound N-tert-butyl-alpha-phenylnitrone (PBN) diminished the increase in oxidized protein and the loss of glutamine synthetase (GS) activity that accompanied ischemia/reperfusion injury in brain. We report here that aged gerbils had a significantly higher level of oxidized protein as assessed by carbonyl residues and decreased GS and neutral protease activities as compared to young adult gerbils. We also found that chronic treatment with the spin-trapping compound PBN caused a decrease in the level of oxidized protein and an increase in both GS and neutral protease activity in aged Mongolian gerbil brain. In contrast to aged gerbils, PBN treatment of young adult gerbils had no significant effect on brain oxidized protein content or GS activity. Male gerbils, young adults (3 months of age) and retired breeders (15-18 months of age), were treated with PBN for 14 days with twice daily dosages of 32 mg/kg. If PBN administration was ceased after 2 weeks, the significantly decreased level of oxidized protein and increased GS and neutral protease activities in old gerbils changed in a monotonic fashion back to the levels observed in aged gerbils prior to PBN administration. We also report that old gerbils make more errors than young animals and that older gerbils treated with PBN made fewer errors in a radial arm maze test for temporal and spatial memory than the untreated aged controls.

  11. 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......Context: Age-related bone loss is associated with progressive changes in bone remodeling characterized by decreased bone formation relative to bone resorption. Both trabecular and periosteal bone formation decline with age in both sexes, which contributes to bone fragility and increased risk...... of fractures. Studies in rodents and humans revealed that, independent of sex hormone deficiency, the age-related decline in bone formation is characterized by decreased osteoblast number and lifespan and reduced bone-forming capacity of individual osteoblasts. An important clinical question is to identify...

  12. Prevention of Age-Related Macular Degeneration.

    Science.gov (United States)

    Singh, Niharika; Srinivasan, Sangeetha; Muralidharan, Vinata; Roy, Rupak; V, Jayprakash; Raman, Rajiv

    2017-01-01

    Age-related macular degeneration (AMD) compromises quality of life. However, the available therapeutic options are limited. This has led to the identification of modifiable risk factors to prevent the development or alter the natural course and prognosis of AMD. The identification and modification of risk factors has the potential for greater public health impact on reducing morbidity from AMD. Likewise, identifying the imaging clues and genetic clues could serve as a guide to recognizing the propensity for progression to severe and end stages of the disease. Several attempts, both successful and unsuccessful, have been made for interventions that could delay the progression of AMD. Of these, pharmacological interventions have shown promising results. The Age-Related Eye Disease Study 1 and 2 have shown the beneficial role of antioxidants in a selected group of patients. Copyright 2017 Asia-Pacific Academy of Ophthalmology.

  13. Age-related differences in work motivation

    OpenAIRE

    Inceoglu, I; Bartram, D; Segers, J.

    2012-01-01

    This paper examines age-related differences in work motivation in two samples of 9,388 and 2,512 individuals who completed a comprehensive motivation questionnaire for selection or development purposes. In the first sample, age differences were examined by controlling for gender and investigating whether relationships between age and motivation were non-linear. Statistically significant relationships between motivation and age were found for most motivation scales, explaining up to 12% of the...

  14. Long-term oil contamination increases deterministic assembly processes in soil microbes.

    Science.gov (United States)

    Liang, Yuting; Zhang, Xu; Zhou, Jizhong; Li, Guanghe

    2015-07-01

    The mechanisms that drive microbial turnover in time and space have received considerable attention but remain unclear, especially for situations with anthropogenic perturbation. To understand the impact of long-term oil contamination on microbial spatial turnover, 100 soil samples were taken from five oil exploration fields located in different geographic regions across China. The microbial functional diversity was analyzed with a high-throughput functional gene array, GeoChip. Our results indicated that soil microbial α-diversity (richness and Shannon diversity index) decreased significantly with contamination. All contaminated and uncontaminated samples exhibited significant spatial autocorrelation between microbial community similarity and spatial distance, as described by a distance-decay relationship (DDR). However, long-term oil exposure flattened the slopes of the DDRs of all of the functional genes and each functional group involved in C/N/P/S cycling, particularly of those involved in contaminant degradation. The relative importance of deterministic and stochastic processes in microbial assembly was determined. The decrease in microbial spatial turnover with long-term oil contamination was coupled with an increase in the proportion of deterministic processes that structured microbial assembly based on null model analysis. The results indicated long-term oil contamination significantly affects soil microbial community spatial structure by acting as an environmental filter to decrease the regional differences distinguishing soil microbial communities.

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

    Science.gov (United States)

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

    2015-09-23

    Aging is associated with performance decrements across multiple cognitive domains. The neural noise hypothesis, a dominant view of the basis of this decline, posits that aging is accompanied by an increase in spontaneous, noisy baseline neural activity. Here we analyze data from two different groups of human subjects: intracranial electrocorticography from 15 participants over a 38 year age range (15-53 years) and scalp EEG data from healthy younger (20-30 years) and older (60-70 years) adults to test the neural noise hypothesis from a 1/f noise perspective. Many natural phenomena, including electrophysiology, are characterized by 1/f noise. The defining characteristic of 1/f is that the power of the signal frequency content decreases rapidly as a function of the frequency (f) itself. The slope of this decay, the noise exponent (χ), is often noise (defined as χ = 0) with increasing task difficulty. We observed, in both electrophysiological datasets, that aging is associated with a flatter (more noisy) 1/f power spectral density, even at rest, and that visual cortical 1/f noise statistically mediates age-related impairments in visual working memory. These results provide electrophysiological support for the neural noise hypothesis of aging. Significance statement: Understanding the neurobiological origins of age-related cognitive decline is of critical scientific, medical, and public health importance, especially considering the rapid aging of the world's population. We find, in two separate human studies, that 1/f electrophysiological noise increases with aging. In addition, we observe that this age-related 1/f noise statistically mediates age-related working memory decline. These results significantly add to this understanding and contextualize a long-standing problem in cognition by encapsulating age-related cognitive decline within a neurocomputational model of 1/f noise-induced deficits in neural communication. Copyright © 2015 the authors 0270-6474/15/3513257-09$15.00/0.

  16. Pathophysiology of age-related diseases

    Science.gov (United States)

    Campisi, Giuseppina; Chiappelli, Martina; De Martinis, Massimo; Franco, Vito; Ginaldi, Lia; Guiglia, Rosario; Licastro, Federico; Lio, Domenico

    2009-01-01

    A Symposium regarding the Pathophysiology of Successful and Unsuccessful Ageing was held in Palermo, Italy on 7-8 April 2009. Three lectures from that Symposium by G. Campisi, L. Ginaldi and F. Licastro are here summarized. Ageing is a complex process which negatively impacts on the development of various bodily systems and its ability to function. A long life in a healthy, vigorous, youthful body has always been one of humanity's greatest dreams. Thus, a better understanding of the pathophysiology of age-related diseases is urgently required to improve our understanding of maintaining good health in the elderly and to program possible therapeutic intervention. PMID:19737378

  17. The NLRP3 Inflammasome Promotes Age-Related Thymic Demise and Immunosenescence

    Directory of Open Access Journals (Sweden)

    Yun-Hee Youm

    2012-01-01

    Full Text Available The collapse of thymic stromal cell microenvironment with age and resultant inability of the thymus to produce naive T cells contributes to lower immune-surveillance in the elderly. Here we show that age-related increase in ‘lipotoxic danger signals’ such as free cholesterol (FC and ceramides, leads to thymic caspase-1 activation via the Nlrp3 inflammasome. Elimination of Nlrp3 and Asc, a critical adaptor required for inflammasome assembly, reduces age-related thymic atrophy and results in an increase in cortical thymic epithelial cells, T cell progenitors and maintenance of T cell repertoire diversity. Using a mouse model of irradiation and hematopoietic stem cell transplantation (HSCT, we show that deletion of the Nlrp3 inflammasome accelerates T cell reconstitution and immune recovery in middle-aged animals. Collectively, these data demonstrate that lowering inflammasome-dependent caspase-1 activation increases thymic lymphopoiesis and suggest that Nlrp3 inflammasome inhibitors may aid the re-establishment of a diverse T cell repertoire in middle-aged or elderly patients undergoing HSCT.

  18. [Oxidation stress role in age-related cataractogenesis].

    Science.gov (United States)

    Zorić, Lepsa; Colak, Emina; Canadanović, Vladimir; Kosanović-Jaković, Natalija; Kisić, Bojana

    2010-01-01

    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 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 possess 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.

  19. Non-ionising UV light increases the optical density of hygroscopic self assembled DNA crystal films.

    Science.gov (United States)

    Gasperini, Alexandria E; Sanchez, Susy; Doiron, Amber L; Lyles, Mark; German, Guy K

    2017-07-26

    We report on ultraviolet (UV) light induced increases in the UV optical density of thin and optically transparent crystalline DNA films formed through self assembly. The films are comprised of closely packed, multi-faceted and sub micron sized crystals. UV-Vis spectrophotometry reveals that DNA films with surface densities up to 0.031 mg/mm(2) can reduce the transmittance of incident UVC and UVB light by up to 90%, and UVA transmittance by up to 20%. Subsequent and independent film irradiation with either UVA or UVB dosages upwards of 80 J/cm(2) both reduce UV transmittance, with reductions scaling monotonically with UV dosage. To date the induction of a hyperchromic effect has been demonstrated using heat, pH, high salt mediums, and high energy ionising radiation. Both hyperchromicity and increased light scattering could account for the increased film optical density after UV irradiation. Additional characterisation of the films reveal they are highly absorbent and hygroscopic. When coated on human skin, they are capable of slowing water evaporation and keeping the tissue hydrated for extended periods of time.

  20. Age-related percutaneous penetration part 1: skin factors.

    Science.gov (United States)

    Konda, S; Meier-Davis, S R; Cayme, B; Shudo, J; Maibach, H I

    2012-05-01

    Changes in the skin that occur in the elderly may put them at increased risk for altered percutaneous penetration from pharmacotherapy along with potential adverse effects. Skin factors that may have a role in age-related percutaneous penetration include blood flow, pH, skin thickness, hair and pore density, and the content and structure of proteins, glycosaminoglycans (GAGs), water, and lipids. Each factor is examined as a function of increasing age along with its potential impact on percutaneous penetration. Additionally, topical drugs that successfully overcome the barrier function of the skin can still fall victim to cutaneous metabolism, thereby producing metabolites that may have increased or decreased activity. This overview discusses the current data and highlights the importance of further studies to evaluate the impact of skin factors in age-related percutaneous penetration.

  1. 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. © 2015 S. Karger AG, Basel.

  2. 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.

  3. 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.

  4. Risk Factors for Age-Related Maculopathy

    Directory of Open Access Journals (Sweden)

    Paul P. Connell

    2009-01-01

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

  5. Age-Related Hyperkyphosis: Its Causes, Consequences, and Management

    OpenAIRE

    Katzman, Wendy B.; Wanek, Linda; Shepherd, John A.; Sellmeyer, Deborah E.

    2010-01-01

    Age-related postural hyperkyphosis is an exaggerated anterior curvature of the thoracic spine, sometimes referred to as Dowager’s hump or gibbous deformity. This condition impairs mobility,2,31 and increases the risk of falls33 and fractures.26 The natural history of hyperkyphosis is not firmly established. Hyperkyphosis may develop from either muscle weakness and degenerative disc disease, leading to vertebral fractures and worsening hyperkyphosis, or from initial vertebral fractures that pr...

  6. A data mining approach for classifying DNA repair genes into ageing-related or non-ageing-related.

    Science.gov (United States)

    Freitas, Alex A; Vasieva, Olga; de Magalhães, João Pedro

    2011-01-12

    The ageing of the worldwide population means there is a growing need for research on the biology of ageing. DNA damage is likely a key contributor to the ageing process and elucidating the role of different DNA repair systems in ageing is of great interest. In this paper we propose a data mining approach, based on classification methods (decision trees and Naive Bayes), for analysing data about human DNA repair genes. The goal is to build classification models that allow us to discriminate between ageing-related and non-ageing-related DNA repair genes, in order to better understand their different properties. The main patterns discovered by the classification methods are as follows: (a) the number of protein-protein interactions was a predictor of DNA repair proteins being ageing-related; (b) the use of predictor attributes based on protein-protein interactions considerably increased predictive accuracy of attributes based on Gene Ontology (GO) annotations; (c) GO terms related to "response to stimulus" seem reasonably good predictors of ageing-relatedness for DNA repair genes; (d) interaction with the XRCC5 (Ku80) protein is a strong predictor of ageing-relatedness for DNA repair genes; and (e) DNA repair genes with a high expression in T lymphocytes are more likely to be ageing-related. The above patterns are broadly integrated in an analysis discussing relations between Ku, the non-homologous end joining DNA repair pathway, ageing and lymphocyte development. These patterns and their analysis support non-homologous end joining double strand break repair as central to the ageing-relatedness of DNA repair genes. Our work also showcases the use of protein interaction partners to improve accuracy in data mining methods and our approach could be applied to other ageing-related pathways.

  7. A data mining approach for classifying DNA repair genes into ageing-related or non-ageing-related

    Directory of Open Access Journals (Sweden)

    Vasieva Olga

    2011-01-01

    Full Text Available Abstract Background The ageing of the worldwide population means there is a growing need for research on the biology of ageing. DNA damage is likely a key contributor to the ageing process and elucidating the role of different DNA repair systems in ageing is of great interest. In this paper we propose a data mining approach, based on classification methods (decision trees and Naive Bayes, for analysing data about human DNA repair genes. The goal is to build classification models that allow us to discriminate between ageing-related and non-ageing-related DNA repair genes, in order to better understand their different properties. Results The main patterns discovered by the classification methods are as follows: (a the number of protein-protein interactions was a predictor of DNA repair proteins being ageing-related; (b the use of predictor attributes based on protein-protein interactions considerably increased predictive accuracy of attributes based on Gene Ontology (GO annotations; (c GO terms related to "response to stimulus" seem reasonably good predictors of ageing-relatedness for DNA repair genes; (d interaction with the XRCC5 (Ku80 protein is a strong predictor of ageing-relatedness for DNA repair genes; and (e DNA repair genes with a high expression in T lymphocytes are more likely to be ageing-related. Conclusions The above patterns are broadly integrated in an analysis discussing relations between Ku, the non-homologous end joining DNA repair pathway, ageing and lymphocyte development. These patterns and their analysis support non-homologous end joining double strand break repair as central to the ageing-relatedness of DNA repair genes. Our work also showcases the use of protein interaction partners to improve accuracy in data mining methods and our approach could be applied to other ageing-related pathways.

  8. 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.

  9. Age-Related Neurodegeneration and Memory Loss in Down Syndrome

    Directory of Open Access Journals (Sweden)

    Jason P. Lockrow

    2012-01-01

    Full Text Available Down syndrome (DS is a condition where a complete or segmental chromosome 21 trisomy causes variable intellectual disability, and progressive memory loss and neurodegeneration with age. Many research groups have examined development of the brain in DS individuals, but studies on age-related changes should also be considered, with the increased lifespan observed in DS. DS leads to pathological hallmarks of Alzheimer's disease (AD by 40 or 50 years of age. Progressive age-related memory deficits occurring in both AD and in DS have been connected to degeneration of several neuronal populations, but mechanisms are not fully elucidated. Inflammation and oxidative stress are early events in DS pathology, and focusing on these pathways may lead to development of successful intervention strategies for AD associated with DS. Here we discuss recent findings and potential treatment avenues regarding development of AD neuropathology and memory loss in DS.

  10. Age-Related Loss of Cohesion: Causes and Effects.

    Science.gov (United States)

    Cheng, Jin-Mei; Liu, Yi-Xun

    2017-07-22

    Aneuploidy is a leading genetic cause of birth defects and lower implantation rates in humans. Most errors in chromosome number originate from oocytes. Aneuploidy in oocytes increases with advanced maternal age. Recent studies support the hypothesis that cohesion deterioration with advanced maternal age represents a leading cause of age-related aneuploidy. Cohesin generates cohesion, and is established only during the premeiotic S phase of fetal development without any replenishment throughout a female's period of fertility. Cohesion holds sister chromatids together until meiosis resumes at puberty, and then chromosome segregation requires the release of sister chromatid cohesion from chromosome arms and centromeres at anaphase I and anaphase II, respectively. The time of cohesion cleavage plays an important role in correct chromosome segregation. This review focuses specifically on the causes and effects of age-related cohesion deterioration in female meiosis.

  11. Genetic Biomarkers on Age-Related Cognitive Decline.

    Science.gov (United States)

    Lin, Chieh-Hsin; Lin, Eugene; Lane, Hsien-Yuan

    2017-01-01

    With ever-increasing elder populations, age-related cognitive decline, which is characterized as a gradual decline in cognitive capacity in the aging process, has turned out to be a mammoth public health concern. Since genetic information has become increasingly important to explore the biological mechanisms of cognitive decline, the search for genetic biomarkers of cognitive aging has received much attention. There is growing evidence that single-nucleotide polymorphisms (SNPs) within the ADAMTS9, BDNF, CASS4, COMT, CR1, DNMT3A, DTNBP1, REST, SRR, TOMM40, circadian clock, and Alzheimer's diseases-associated genes may contribute to susceptibility to cognitive aging. In this review, we first illustrated evidence of the genetic contribution to disease susceptibility to age-related cognitive decline in recent studies ranging from approaches of candidate genes to genome-wide association studies. We then surveyed a variety of association studies regarding age-related cognitive decline with consideration of gene-gene and gene-environment interactions. Finally, we highlighted their limitations and future directions. In light of advances in precision medicine and multi-omics technologies, future research in genomic medicine promises to lead to innovative ideas that are relevant to disease prevention and novel drugs for cognitive aging.

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

    Science.gov (United States)

    Chen, Huayue; Zhou, Xiangrong; Fujita, Hiroshi; Onozuka, Minoru; Kubo, Kin-Ya

    2013-01-01

    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. PMID:23573086

  13. 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.

  14. Animal models of age related macular degeneration

    Science.gov (United States)

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

    2013-01-01

    Age related macular degeneration (AMD) is the leading cause of vision loss of those over the age of 65 in the industrialized world. The prevalence and need to develop effective treatments for AMD has lead to the development of multiple animal models. AMD is a complex and heterogeneous disease that involves the interaction of both genetic and environmental factors with the unique anatomy of the human macula. Models in mice, rats, rabbits, pigs and non-human primates have recreated many of the histological features of AMD and provided much insight into the underlying pathological mechanisms of this disease. In spite of the large number of models developed, no one model yet recapitulates all of the features of human AMD. However, these models have helped reveal the roles of chronic oxidative damage, inflammation and immune dysregulation, and lipid metabolism in the development of AMD. Models for induced choroidal neovascularization have served as the backbone for testing new therapies. This article will review the diversity of animal models that exist for AMD as well as their strengths and limitations. PMID:22705444

  15. Age-related hearing loss or presbycusis.

    Science.gov (United States)

    Huang, Qi; Tang, Jianguo

    2010-08-01

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

  16. Senescent cells: SASPected drivers of age-related pathologies.

    Science.gov (United States)

    Ovadya, Yossi; Krizhanovsky, Valery

    2014-12-01

    The progression of physiological ageing is driven by intracellular aberrations including telomere attrition, genomic instability, epigenetic alterations and loss of proteostasis. These in turn damage cells and compromise their functionality. Cellular senescence, a stable irreversible cell-cycle arrest, is elicited in damaged cells and prevents their propagation in the organism. Under normal conditions, senescent cells recruit the immune system which facilitates their removal from tissues. Nevertheless, during ageing, tissue-residing senescent cells tend to accumulate, and might negatively impact their microenvironment via profound secretory phenotype with pro-inflammatory characteristics, termed senescence-associated secretory phenotype (SASP). Indeed, senescent cells are mostly abundant at sites of age-related pathologies, including degenerative disorders and malignancies. Interestingly, studies on progeroid mice indicate that selective elimination of senescent cells can delay age-related deterioration. This suggests that chronic inflammation induced by senescent cells might be a main driver of these pathologies. Importantly, senescent cells accumulate as a result of deficient immune surveillance, and their removal is increased upon the use of immune stimulatory agents. Insights into mechanisms of senescence surveillance could be combined with current approaches for cancer immunotherapy to propose new preventive and therapeutic strategies for age-related diseases.

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

    Science.gov (United States)

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

    2002-11-01

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

  18. Research status of conbercept treating age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Hai-Yan He

    2015-08-01

    Full Text Available Age-related macular degeneration(AMDis one of the major reasons of blindness among the elderly in the developed countries. As AMD patients are increasing year by year, AMD has become one of the important topics of ophthalmic research to prevent blindness. Its pathogenesis is not fully understood, but many studies have shown that vascular endothelial growth factor(VEGFplays an important role in the pathogenesis. With the development and application of anti-VEGF drugs, there are a variety of drugs applied to the disease. This article introduces conbercept for the treatment of AMD.

  19. Age-related deficits in auditory confrontation naming.

    Science.gov (United States)

    Hanna-Pladdy, Brenda; Choi, Hyun

    2010-09-01

    The naming of manipulable objects in older and younger adults was evaluated across auditory, visual, and multisensory conditions. Older adults were less accurate and slower in naming across conditions, and all subjects were more impaired and slower to name action sounds than pictures or audiovisual combinations. Moreover, there was a sensory by age group interaction, revealing lower accuracy and increased latencies in auditory naming for older adults unrelated to hearing insensitivity but modest improvement to multisensory cues. These findings support age-related deficits in object action naming and suggest that auditory confrontation naming may be more sensitive than visual naming. (c) 2010 APA, all rights reserved.

  20. Mitochondrial dysfunction and oxidative stress activate inflammasomes: impact on the aging process and age-related diseases.

    Science.gov (United States)

    Salminen, Antero; Ojala, Johanna; Kaarniranta, Kai; Kauppinen, Anu

    2012-09-01

    Oxidative stress and low-grade inflammation are the hallmarks of the aging process and are even more enhanced in many age-related degenerative diseases. Mitochondrial dysfunction and oxidative stress can provoke and potentiate inflammatory responses, but the mechanism has remained elusive. Recent studies indicate that oxidative stress can induce the assembly of multiprotein inflammatory complexes called the inflammasomes. Nod-like receptor protein 3 (NLRP3) is the major immune sensor for cellular stress signals, e.g., reactive oxygen species, ceramides, and cathepsin B. NLRP3 activation triggers the caspase-1-mediated maturation of the precursors of IL-1β and IL-18 cytokines. During aging, the autophagic clearance of mitochondria declines and dysfunctional mitochondria provoke chronic oxidative stress, which disturbs the cellular redox balance. Moreover, increased NF-κB signaling observed during aging could potentiate the expression of NLRP3 and cytokine proforms enhancing the priming of NLRP3 inflammasomes. Recent studies have demonstrated that NLRP3 activation is associated with several age-related diseases, e.g., the metabolic syndrome. We will review here the emerging field of inflammasomes in the appearance of the proinflammatory phenotype during the aging process and in age-related diseases.

  1. 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.

  2. Age-related changes in crowding and reading speed.

    Science.gov (United States)

    Liu, Rong; Patel, Bhavika N; Kwon, MiYoung

    2017-08-15

    Crowding, the inability to recognize objects in clutter, is known to play a role in developmental changes in reading speed. Here, we investigated whether crowding also plays a role in age-related changes in reading speed. We recruited 18 young (mean age: 22.6 ± 3.5; range: 18~31) and 21 older adults (mean age: 58.2 ± 7.0; range: 50~73) with normal vision. Reading speed was measured with short blocks of text. The degree of crowding was determined by measuring crowding zone (the distance between a target and flankers required to yield a criterion recognition accuracy) and the size of the visual span (an uncrowded window in the visual field within which letters can be recognizable reliably). Measurements were made across the central 16-degree visual field using letter-recognition tasks. Our results showed that, compared to young adults, older adults exhibited significantly slower reading speed (a decrease by 30%) and larger crowding: an enlargement of crowding zone (an increase by 31%) and shrinkage of the visual span (a decrease by 6.25 bits). We also observed significant correlations between reading speed and each of the crowding measures. Our results suggest that crowding increases with age. Age-related changes in crowding may in part explain slower reading in older adults.

  3. Associations between Rs4244285 and Rs762551 gene polymorphisms and age-related macular degeneration.

    Science.gov (United States)

    Stasiukonyte, Neringa; Liutkeviciene, Rasa; Vilkeviciute, Alvita; Banevicius, Mantas; Kriauciuniene, Loresa

    2017-01-01

    Age-related macular degeneration is the leading cause of blindness in elderly individuals in developed countries. The etiology and pathophysiology of age-related macular degeneration have not been elucidated yet. Knowing that the main pathological change of age-related macular degeneration is formation of drusen containing about 40% of lipids, there have been attempts to find associations between age-related macular degeneration and genes controlling lipid metabolism. To determine the frequency of CYP2C19 (G681A) Rs4244285 and CYP1A2 (-163C>A) Rs762551 genotypes in patients with age-related macular degeneration. The study enrolled 150 patients with early age-related macular degeneration and 296 age- and gender-matched healthy controls. The genotyping of Rs4244285 and Rs762551 was carried out by using the real-time polymerase chain reaction method. The CYP1A2 (-163C>A) Rs762551 C/C genotype was more frequently detected in patients with age-related macular degeneration than in the control group (32.7% vs. 21.6%, p = 0.011) and was associated with an increased risk of developing early age-related macular degeneration (OR = 1.759, 95% CI: 1.133-2.729; p = 0.012). The CYP1A2 (-163C>A) Rs762551 C/A genotype was more frequently documented in the control group compared with patients with age-related macular degeneration (46.3% vs. 30.7%, p = 0.002) and was associated with a decreased risk of having age-related macular degeneration (OR = 0.580. 95% CI: 0.362-0.929, p = 0.023) in the co-dominant model. The study showed that the CYP1A2 (-163C>A) Rs762551 C/C genotype was associated with an increased risk of age-related macular degeneration.

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

    Science.gov (United States)

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

    2016-09-06

    Fall prevention technologies have the potential to improve the lives of older adults. Because of the multisensory nature of human balance control, sensory therapies, including some involving tactile and auditory noise, are being explored that might reduce increased balance variability due to typical age-related sensory declines. Auditory white noise has previously been shown to reduce postural sway variability in healthy young adults. In the present experiment, we examined this treatment in young adults and typically aging older adults. We measured postural sway of healthy young adults and adults over the age of 65 years during silence and auditory white noise, with and without vision. Our results show reduced postural sway variability in young and older adults with auditory noise, even in the absence of vision. We show that vision and noise can reduce sway variability for both feedback-based and exploratory balance processes. In addition, we show changes with auditory noise in nonlinear patterns of sway in older adults that reflect what is more typical of young adults, and these changes did not interfere with the typical random walk behavior of sway. Our results suggest that auditory noise might be valuable for therapeutic and rehabilitative purposes in older adults with typical age-related balance variability. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. Melatonin: Protection against age-related cardiac pathology.

    Science.gov (United States)

    Favero, Gaia; Franceschetti, Lorenzo; Buffoli, Barbara; Moghadasian, Mohammed H; Reiter, Russel J; Rodella, Luigi F; Rezzani, Rita

    2017-05-01

    Aging is a complex and progressive process that involves physiological and metabolic deterioration in every organ and system. Cardiovascular diseases are one of the most common causes of mortality and morbidity among elderly subjects worldwide. Most age-related cardiovascular disorders can be influenced by modifiable behaviours such as a healthy diet rich in fruit and vegetables, avoidance of smoking, increased physical activity and reduced stress. The role of diet in prevention of various disorders is a well-established factor, which has an even more important role in the geriatric population. Melatonin, an indoleamine with multiple actions including antioxidant properties, has been identified in a very large number of plant species, including edible plant products and medical herbs. Among products where melatonin has been identified include wine, olive oil, tomato, beer, and others. Interestingly, consumed melatonin in plant foods or melatonin supplementation may promote health benefits by virtue of its multiple properties and it may counteract pathological conditions also related to cardiovascular disorders, carcinogenesis, neurological diseases and aging. In the present review, we summarized melatonin effects against age-related cardiac alterations and abnormalities with a special focus on heart ischemia/reperfusion (IR) injury and myocardial infarction. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Zhenyang Zhao

    2011-04-01

    Full Text Available 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.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.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.

  7. Autophagy and ageing: implications for age-related neurodegenerative diseases.

    Science.gov (United States)

    Carroll, Bernadette; Hewitt, Graeme; Korolchuk, Viktor I

    2013-01-01

    Autophagy is a process of lysosome-dependent intracellular degradation that participates in the liberation of resources including amino acids and energy to maintain homoeostasis. Autophagy is particularly important in stress conditions such as nutrient starvation and any perturbation in the ability of the cell to activate or regulate autophagy can lead to cellular dysfunction and disease. An area of intense research interest is the role and indeed the fate of autophagy during cellular and organismal ageing. Age-related disorders are associated with increased cellular stress and assault including DNA damage, reduced energy availability, protein aggregation and accumulation of damaged organelles. A reduction in autophagy activity has been observed in a number of ageing models and its up-regulation via pharmacological and genetic methods can alleviate age-related pathologies. In particular, autophagy induction can enhance clearance of toxic intracellular waste associated with neurodegenerative diseases and has been comprehensively demonstrated to improve lifespan in yeast, worms, flies, rodents and primates. The situation, however, has been complicated by the identification that autophagy up-regulation can also occur during ageing. Indeed, in certain situations, reduced autophagosome induction may actually provide benefits to ageing cells. Future studies will undoubtedly improve our understanding of exactly how the multiple signals that are integrated to control appropriate autophagy activity change during ageing, what affect this has on autophagy and to what extent autophagy contributes to age-associated pathologies. Identification of mechanisms that influence a healthy lifespan is of economic, medical and social importance in our 'ageing' world.

  8. Antioxidant Capacity of Lenses with Age-Related Cataract

    Directory of Open Access Journals (Sweden)

    Bojana Kisic

    2012-01-01

    Full Text Available The immediate cause of the occurrence of cataract is unknown, but oxidative damage and effects of reactive oxygen species are considered important in its etiopathogenesis. Our research was aimed at testing the nonenzyme antioxidant power of corticonuclear lens blocks, with different types and different maturity of age-related cataract. Clinical and biochemical researches were carried out in 101 patients with age-related cataract. In corticonuclear lens blocks of the patient, the concentration of nonprotein and total-SH groups and the concentration of total vitamin C and dehydroascorbic acid (DHA were determined; the current redox balance of dehydroascorbate/ascorbate and total antioxidant power measured by ferric-reducing ability were examined. In corticonuclear lens blocks with incipient cataract a significantly higher concentration of GSH, total SH groups, concentration of total vitamin C and ascorbic acid (AA, and ferric-reducing ability were measured. The measured concentration of DHA is higher than the concentration of AA in the lenses with the incipient and mature cataract. The concentration ratio of redox couple DHA/AA is higher in lenses with mature cataract, where the measured concentration of AA was lower than in the incipient cataract. Timely removal of DHA from the lens is important because of its potential toxicity as an oxidant. An increase of the current concentration of DHA/AA redox balance can be an indicator of oxidative stress.

  9. Age-related aspects of addiction

    Science.gov (United States)

    Koechl, Birgit; Unger, Annemarie; Fischer, Gabriele

    2013-01-01

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

  10. Rapid Assessment of Age-Related Differences in Standing Balance

    Directory of Open Access Journals (Sweden)

    Tobias Kalisch

    2011-01-01

    Full Text Available As life expectancy continues to rise, in the future there will be an increasing number of older people prone to falling. Accordingly, there is an urgent need for comprehensive testing of older individuals to collect data and to identify possible risk factors for falling. Here we use a low-cost force platform to rapidly assess deficits in balance under various conditions. We tested 21 healthy older adults and 24 young adults during static stance, unidirectional and rotational displacement of their centre of pressure (COP. We found an age-related increase in postural sway during quiet standing and a reduction of maximal COP displacement in unidirectional and rotational displacement tests. Our data show that even low-cost computerized assessment tools allow for the comprehensive testing of balance performance in older subjects.

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

    National Research Council Canada - National Science Library

    Muller, N.C; Genzel, L.K.E; Konrad, B.N; Pawlowski, M; Neville, D; Fernandez, G.S.E; Steiger, A; sler, M

    2016-01-01

    .... 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...

  12. [Melatonin as a molecular marker of age-related pathologies].

    Science.gov (United States)

    Zuev, V A; Trifonov, N I; Linkova, N S; Kvetnaia, T V

    2017-01-01

    The review has described melatonin as a prognostic marker of invasive and non-invasive diagnostic of organism aging time and age-related pathology. Decreasing of melatonin level in buccal cells has correlated with patient age. Melatonin level in patients with Alzheimer disease has decreased. Melatonin level in blood plasma has correlated with severity of menopausal syndrome. Melatonin secretion in enterocytes increased during gastric ulcer. In oncology patients was described changes of 6-COMT - metabolite of melatonin in urine in dependent of histology type and stage of disease. Thus, melatonin is the molecular marker, which characterized integral processes in neuro-immuno-endocrine system and can be verified by non-invasive methods in peripheral tissues and biological fluids of organism.

  13. Age-Related Macular Degeneration: Insights into Inflammatory Genes

    Directory of Open Access Journals (Sweden)

    Raffaella Cascella

    2014-01-01

    Full Text Available Age-related macular degeneration (AMD is a progressive neurodegenerative disease that affects approximately 8.7% of elderly people worldwide (>55 years old. AMD is characterized by a multifactorial aetiology that involves several genetic and environmental risk factors (genes, ageing, smoking, family history, dietary habits, oxidative stress, and hypertension. In particular, ageing and cigarette smoking (including oxidative compounds and reactive oxygen species have been shown to significantly increase susceptibility to the disease. Furthermore, different genes (CFH, CFI, C2, C3, IL-6, IL-8, and ARMS2 that play a crucial role in the inflammatory pathway have been associated with AMD risk. Several genetic and molecular studies have indicated the participation of inflammatory molecules (cytokines and chemokines, immune cells (macrophages, and complement proteins in the development and progression of the disease. Taking into consideration the genetic and molecular background, this review highlights the genetic role of inflammatory genes involved in AMD pathogenesis and progression.

  14. Overview of radiation trials for age-related macular degeneration.

    Science.gov (United States)

    Kaiser, Peter K

    2009-06-01

    Radiotherapy is a promising adjunctive tool to antiangiogenesis therapies for control of the choroidal neovascularization that characterizes exudative (wet) age-related macular degeneration. Historically, radiation monotherapy sufficient to effectively eradicate choroidal neovascularization has been associated with mixed results; however, newer techniques and delivery platforms have been developed to improve efficacy. The most significant improvements are technical advances that improve the precision of energy delivery, so that tissue destruction remains confined to the target. In addition, several combination therapies are showing promise for enhanced effect. Other strategies, such as pretreating neovascular tissue to increase its sensitivity to radiation, thereby reducing the energy dose, may also be viable. However, even though the modern delivery systems permit relatively low dosages, there are risks of radiotherapy to ocular tissue, and its role remains speculative, pending results of ongoing trials.

  15. Age-related and non-age-related changes in 100 surveyed horse brains.

    Science.gov (United States)

    Jahns, H; Callanan, J J; McElroy, M C; Sammin, D J; Bassett, H F

    2006-09-01

    Brains from 100 horses, aged 2-25 years, were systematically examined by histopathology at 46 different neuroanatomical sites. The horses were sourced from a slaughterhouse (group A, n = 57), from a kennel that collected dead animals, and from 2 diagnostic laboratories (group B, n = 43). All horses from group A and 26 horses from group B were examined by a veterinarian in the period before death. None of the horses were known to exhibit clinical signs suggestive of neurologic disease. Among the main changes identified were vacuolation in the neuropil (n = 73), neurons (n = 32), white matter (n = 31), and focal perivascular lymphoid cell infiltrates (n = 35). Spheroids were frequently seen (n = 91), and 10 horses each had more than 10 spheroids in the cuneate or gracile nucleus. Statistically significant age-related changes noted included intraneuronal (n = 97) and glial or extracellular lipofuscin deposition (n = 41), hemosiderin deposition around blood vessels (n = 60), and calcium depositions (n = 24). One horse had low-grade nonsuppurative meningoencephalitis; Alzheimer type II cells were detected in the brains of 2 horses. Hyalinized vessel walls in the cerebellum were observed in 1 horse. It was concluded that some histopathologic changes are a frequent feature in equine brains, which has implications for the pathologists involved in equine neurology and disease surveillance.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  17. Genetics Home Reference: age-related hearing loss

    Science.gov (United States)

    ... links) Age-related hearing impairment 1 Age-related hearing impairment 2 Sources for This Page Atcherson SR, Nagaraj NK, Kennett SE, Levisee M. Overview of Central Auditory Processing Deficits in Older Adults. Semin Hear. 2015 Aug;36(3):150-61. ...

  18. Serum 25-hydroxyvitamin D and Age-Related Cataract.

    Science.gov (United States)

    Park, Sangshin; Choi, Nam-Kyong

    2017-10-01

    Cataract and insufficient vitamin D intake are both increasing worldwide concerns, yet little is known about the relationship between serum 25-hydroxyvitamin D (25(OH)D) levels and age-related cataract. We performed this study to determine the association between serum 25(OH)D levels and age-related cataract in adults. Study participants comprised 16,086 adults aged 40 years or older who had never been diagnosed with or undergone surgery for cataract using Korean National Health and Nutrition Examination Survey data from 2008 to 2012. Participants were assessed to have cataract when diagnosed with cortical, nuclear, anterior subcapsular, posterior subcapsular, or mixed cataract. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the magnitude and significance of the association between serum 25(OH)D levels and cataract in multivariable logistic regression models. The OR for nuclear cataract with the highest quintile of serum 25(OH)D levels was 0.86 (95% CI 0.75-0.99) compared to the lowest quintile. A linear trend across quintiles was significant. Natural log-transformed serum 25(OH)D levels were also significantly associated with nuclear cataract (OR 0.84, 95% CI 0.75-0.95). The opulation-attributable fraction of nuclear cataract due to serum 25(OH)D insufficiency (D levels were inversely associated with the risk of nuclear cataract. Prospective studies investigating the effects of serum 25(OH)D levels on the development of nuclear cataract are needed to confirm our findings.

  19. Future living arrangements of Singaporeans with age-related dementia.

    Science.gov (United States)

    Thompson, James P; Riley, Crystal M; Eberlein, Robert L; Matchar, David B

    2012-10-01

    With rapid aging, Singapore faces an increasing proportion of the population with age-related dementia. We used system dynamics methodology to estimate the number and proportion of people with mild, moderate, and severe dementia in future years and to examine the impact of changing family composition on their likely living arrangements. A system dynamics model was constructed to estimate resident population, drawing birth and mortality rates from census data. We simulate future mild, moderate, and severe dementia prevalence matched with estimates of total dementia prevalence for the Asian region that includes Singapore. Then, integrating a submodel in which family size trends were projected based on fertility rates with tendencies for dependent elderly adults with dementia to live with family members, we estimate likely living arrangements of the future population of individuals with dementia. Though lower than other previous estimates, our simulation results indicate an increase in the number and proportion of people in Singapore with severe dementia. This and the concurrent decrease in family size point to an increasing number of individuals with dementia unlikely to live at home. The momenta of demographic and illness trends portend a higher number of individuals with dementia less likely to be cared for at home by family members. Traditions of care for frail elderly found in the diverse cultures of Singapore will be increasingly difficult to sustain, and care options that accommodate these demographic shifts are urgently needed.

  20. Proinflammatory cytokines, aging, and age-related diseases.

    Science.gov (United States)

    Michaud, Martin; Balardy, Laurent; Moulis, Guillaume; Gaudin, Clement; Peyrot, Caroline; Vellas, Bruno; Cesari, Matteo; Nourhashemi, Fati

    2013-12-01

    Inflammation is a physiological process that repairs tissues in response to endogenous or exogenous aggressions. Nevertheless, a chronic state of inflammation may have detrimental consequences. Aging is associated with increased levels of circulating cytokines and proinflammatory markers. Aged-related changes in the immune system, known as immunosenescence, and increased secretion of cytokines by adipose tissue, represent the major causes of chronic inflammation. This phenomenon is known as "inflamm-aging." High levels of interleukin (IL)-6, IL-1, tumor necrosis factor-α, and C-reactive protein are associated in the older subject with increased risk of morbidity and mortality. In particular, cohort studies have indicated TNF-α and IL-6 levels as markers of frailty. The low-grade inflammation characterizing the aging process notably concurs at the pathophysiological mechanisms underlying sarcopenia. In addition, proinflammatory cytokines (through a variety of mechanisms, such as platelet activation and endothelial activation) may play a major role in the risk of cardiovascular events. Dysregulation of the inflammatory pathway may also affect the central nervous system and be involved in the pathophysiological mechanisms of neurodegenerative disorders (eg, Alzheimer disease).The aim of the present review was to summarize different targets of the activity of proinflammatory cytokines implicated in the risk of pathological aging. Copyright © 2013 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.

  1. Intraocular Lenses for the Treatment of Age-Related Cataracts

    Science.gov (United States)

    2009-01-01

    Executive Summary Objective The objective of the report is to examine the comparative effectiveness and cost-effectiveness of various intraocular lenses (IOLs) for the treatment of age-related cataracts. Clinical Need: Target Population and Condition A cataract is a hardening and clouding of the normally transparent crystalline lens that may result in a progressive loss of vision depending on its size, location and density. The condition is typically bilateral, seriously compromises visual acuity and contrast sensitivity and increases glare. Cataracts can also affect people at any age, however, they usually occur as a part of the natural aging process. The occurrence of cataracts increases with age from about 12% at age 50 years, to 60% at age 70. In general, approximately 50% of people 65 year of age or older have cataracts. Mild cataracts can be treated with a change in prescription glasses, while more serious symptoms are treated by surgical removal of the cataract and implantation of an IOL. In Ontario, the estimated prevalence of cataracts increased from 697,000 in 1992 to 947,000 in 2004 (35.9% increase, 2.4% annual increase). The number of cataract surgeries per 1,000 individuals at risk of cataract increased from 64.6 in 1992 to 140.4 in 1997 (61.9% increase, 10.1% annual increase) and continued to steadily increase to 115.7 in 2004 (10.7% increase, 5.2% increase per year). Description of Technology/Therapy IOLs are classified either as monofocal, multifocal, or accommodative. Traditionally, monofocal (i.e.. fixed focusing power) IOLs are available as replacement lenses but their implantation can cause a loss of the eye’s accommodative capability (which allows variable focusing). Patients thus usually require eyeglasses after surgery for reading and near vision tasks. Multifocal IOLs aim to improve near and distant vision and obviate the need for glasses. Potential disadvantages include reduced contrast sensitivity, halos around lights and glare

  2. Sequence assembly

    DEFF Research Database (Denmark)

    Scheibye-Alsing, Karsten; Hoffmann, S.; Frankel, Annett Maria

    2009-01-01

    Despite the rapidly increasing number of sequenced and re-sequenced genomes, many issues regarding the computational assembly of large-scale sequencing data have remain unresolved. Computational assembly is crucial in large genome projects as well for the evolving high-throughput technologies...... and plays an important role in processing the information generated by these methods. Here, we provide a comprehensive overview of the current publicly available sequence assembly programs. We describe the basic principles of computational assembly along with the main concerns, such as repetitive sequences...... in genomic DNA, highly expressed genes and alternative transcripts in EST sequences. We summarize existing comparisons of different assemblers and provide a detailed descriptions and directions for download of assembly programs at: http://genome.ku.dk/resources/assembly/methods.html....

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

    Directory of Open Access Journals (Sweden)

    Marina A Lynch

    2010-01-01

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

  4. Aging, Obesity, and Inflammatory Age-Related Diseases

    Directory of Open Access Journals (Sweden)

    Daniela Frasca

    2017-12-01

    Full Text Available The increase in the prevalence of obesity represents a worldwide phenomenon in all age groups and is pathologically and genetically correlated with several metabolic and cardiovascular diseases, representing the most frequent age-related diseases. Obesity superimposed on aging drastically increases chronic low-grade inflammation (inflammaging, which is an important link between obesity, insulin resistance, and age-associated diseases. Immune cells of both the innate and the adaptive immune systems infiltrate the adipose tissue (AT and during obesity induce inflammatory responses associated with metabolic switches and changes in phenotypes and function of immune cell subsets. Obesity poses new health problems especially when it occurs in the context of other diseases, many of them frequently affect elderly subjects. An emerging problem is the decreased proportion of patients with obesity achieving clinical response to therapy. In this review, we will discuss the reciprocal influences of immune cell and AT inflammation in aging and age-associated diseases and the complex relationship of nutrient and energy-sensing homeostatic checkpoints, which contribute to shape the phenotype of the AT. We will specifically examine type-2 diabetes, rheumatoid arthritis, osteoarthritis, cognitive impairment, and dementia, where obesity plays a significant role, also in shaping some clinical aspects.

  5. Bioactive Nutrients and Nutrigenomics in Age-Related Diseases.

    Science.gov (United States)

    Rescigno, Tania; Micolucci, Luigina; Tecce, Mario F; Capasso, Anna

    2017-01-08

    The increased life expectancy and the expansion of the elderly population are stimulating research into aging. Aging may be viewed as a multifactorial process that results from the interaction of genetic and environmental factors, which include lifestyle. Human molecular processes are influenced by physiological pathways as well as exogenous factors, which include the diet. Dietary components have substantive effects on metabolic health; for instance, bioactive molecules capable of selectively modulating specific metabolic pathways affect the development/progression of cardiovascular and neoplastic disease. As bioactive nutrients are increasingly identified, their clinical and molecular chemopreventive effects are being characterized and systematic analyses encompassing the "omics" technologies (transcriptomics, proteomics and metabolomics) are being conducted to explore their action. The evolving field of molecular pathological epidemiology has unique strength to investigate the effects of dietary and lifestyle exposure on clinical outcomes. The mounting body of knowledge regarding diet-related health status and disease risk is expected to lead in the near future to the development of improved diagnostic procedures and therapeutic strategies targeting processes relevant to nutrition. The state of the art of aging and nutrigenomics research and the molecular mechanisms underlying the beneficial effects of bioactive nutrients on the main aging-related disorders are reviewed herein.

  6. Cardiorespiratory fitness and age-related arterial stiffness in lupus.

    Science.gov (United States)

    Montalbán-Méndez, Cristina; Soriano-Maldonado, Alberto; Vargas-Hitos, José Antonio; Sáez-Urán, Luis Manuel; Rosales-Castillo, Antonio; Morillas-de-Laguno, Pablo; Gavilán-Carrera, Blanca; Jiménez-Alonso, Juan

    2018-01-10

    The aim of the present study was twofold: 1) to examine the association of cardiorespiratory fitness with arterial stiffness in women with systemic lupus erythematosus; 2) to assess the potential interaction of cardiorespiratory fitness with age on arterial stiffness in this population. A total of 49 women with systemic lupus erythematosus (mean age 41.3 [Standard deviation 13.8] years) and clinical stability during the previous 6 months were included in the study. Arterial stiffness was assessed through pulse wave velocity (Mobil-O-Graph® 24h pulse wave velocity monitor). Cardiorespiratory fitness was estimated with the Siconolfi step test and the six-minute walk test. Cardiorespiratory fitness was inversely associated with pulse wave velocity in crude analyses (Pfitness×age interaction effect on pulse wave velocity, regardless of the test used to estimate cardiorespiratory fitness (Pfitness was associated with a lower increase in pulse wave velocity per each year increase in age. The results of the present study suggest that cardiorespiratory fitness attenuates the age-related arterial stiffening in women with systemic lupus erythematosus and might thus contribute to the primary prevention of cardiovascular disease in this population. Since the cross-sectional design precludes establishing causal relationships, future clinical trials should confirm or contrast these findings. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Bioactive Nutrients and Nutrigenomics in Age-Related Diseases

    Directory of Open Access Journals (Sweden)

    Tania Rescigno

    2017-01-01

    Full Text Available The increased life expectancy and the expansion of the elderly population are stimulating research into aging. Aging may be viewed as a multifactorial process that results from the interaction of genetic and environmental factors, which include lifestyle. Human molecular processes are influenced by physiological pathways as well as exogenous factors, which include the diet. Dietary components have substantive effects on metabolic health; for instance, bioactive molecules capable of selectively modulating specific metabolic pathways affect the development/progression of cardiovascular and neoplastic disease. As bioactive nutrients are increasingly identified, their clinical and molecular chemopreventive effects are being characterized and systematic analyses encompassing the “omics” technologies (transcriptomics, proteomics and metabolomics are being conducted to explore their action. The evolving field of molecular pathological epidemiology has unique strength to investigate the effects of dietary and lifestyle exposure on clinical outcomes. The mounting body of knowledge regarding diet-related health status and disease risk is expected to lead in the near future to the development of improved diagnostic procedures and therapeutic strategies targeting processes relevant to nutrition. The state of the art of aging and nutrigenomics research and the molecular mechanisms underlying the beneficial effects of bioactive nutrients on the main aging-related disorders are reviewed herein.

  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. 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.

  10. Age-related Impairment of Vascular Structure and Functions.

    Science.gov (United States)

    Xu, Xianglai; Wang, Brian; Ren, Changhong; Hu, Jiangnan; Greenberg, David A; Chen, Tianxiang; Xie, Liping; Jin, Kunlin

    2017-10-01

    Among age-related diseases, cardiovascular and cerebrovascular diseases are major causes of death. Vascular dysfunction is a key characteristic of these diseases wherein age is an independent and essential risk factor. The present work will review morphological alterations of aging vessels in-depth, which includes the discussion of age-related microvessel loss and changes to vasculature involving the capillary basement membrane, intima, media, and adventitia as well as the accompanying vascular dysfunctions arising from these alterations.

  11. Age-related alterations in female obturator internus muscle.

    Science.gov (United States)

    Cook, Mark S; Bou-Malham, Laura; Esparza, Mary C; Alperin, Marianna

    2017-05-01

    Pelvic floor muscle rehabilitation is a widely utilized, but often challenging therapy for pelvic floor disorders, which are prevalent in older women. Regimens involving the use of appendicular muscles, such as the obturator internus (OI), have been developed for strengthening of the levator ani muscle (LAM). However, changes that lead to potential dysfunction of these alternative targets in older women are not well known. We hypothesized that aging negatively impacts OI architecture, the main determinant of muscle function, and intramuscular extracellular matrix (ECM), paralleling age-related alterations in LAM. OI and LAM were procured from three groups of female cadaveric donors (five per group): younger (20 - 40 years), middle-aged (41 - 60 years), and older (≥60 years). Architectural predictors of the excursional (fiber length, L f), force-generating (physiological cross-sectional area, PCSA) and sarcomere length (L s) capacity of the muscles, and ECM collagen content (measure of fibrosis) were determined using validated methods. The data were analyzed using one-way ANOVA and Tukey's post-hoc test with a significance level of 0.05, and linear regression. The mean ages of the donors in the three groups were 31.2 ± 2.3 years, 47.6 ± 1.2 years, and 74.6 ± 4.2 years (P  0.5). OI L f and L s were not affected by aging. Age >60 years was associated with a substantial decrease in OI PCSA and increased collagen content (P < 0.05). Reductions in OI and LAM force-generating capacities with age were highly correlated (r 2 = 0.9). Our findings of age-related decreases in predicted OI force production and fibrosis suggest that these alterations should be taken into consideration, when designing pelvic floor fitness programs for older women.

  12. Tremor in the elderly: Essential and aging-related tremor.

    Science.gov (United States)

    Deuschl, Günther; Petersen, Inge; Lorenz, Delia; Christensen, Kaare

    2015-09-01

    Isolated tremor in the elderly is commonly diagnosed as essential tremor (ET). The prevalence of tremor increases steeply with increasing age, whereas hereditary tremor is becoming less common. Moreover, late-manifesting tremor seems to be associated with dementia and earlier mortality. We hypothesize that different entities underlie tremor in the elderly. Two thousand four hundred forty-eight subjects from the Longitudinal Study of Aging Danish Twins older than 70 y answered screening questions for ET in 2001. Two thousand fifty-six (84%) participants drew Archimedes spirals to measure their tremor severity, and classical aging phenotypes were assessed. A subgroup of 276 individuals fulfilling either screening criteria for ET or being controls were personally assessed. Medications and mortality data are available. The spiral score increased with age. The spiral score correlated with tremor severity. For the whole cohort, mortality was significantly correlated with the spiral score, and higher spiral scores were associated with lower physical and cognitive functioning. Multivariate analysis identified higher spiral scores as an independent risk factor for mortality. In contrast, the ET patients did not show an increased but rather a lower mortality rate although it was not statistically significant. Consistent with a slower than normal aging, they were also physically and cognitively better functioning than controls. Because incident tremors beyond 70 y of age show worse aging parameters and mortality than controls and ET, we propose to label it 'aging-related tremor' (ART). This tremor starts later in life and is accompanied by subtle signs of aging both cognitively and physically. More detailed clinical features and pathogenesis warrant further assessment. © 2015 International Parkinson and Movement Disorder Society.

  13. Tremor in the Elderly: Essential and Aging-Related Tremor

    Science.gov (United States)

    Deuschl, Günthe; Petersen, Inge; Lorenz, Delia; Christensen, Kaare

    2016-01-01

    Isolated tremor in the elderly is commonly diagnosed as essential tremor (ET). The prevalence of tremor increases steeply with increasing age, whereas hereditary tremor is becoming less common. Moreover, late-manifesting tremor seems to be associated with dementia and earlier mortality. We hypothesize that different entities underlie tremor in the elderly. Two thousand four hundred forty-eight subjects from the Longitudinal Study of Aging Danish Twins older than 70 y answered screening questions for ET in 2001. Two thousan fifty-six (84%) participants drew Archimedes spirals to measure their tremor severity, and classical aging phenotypes were assessed. A subgroup of 276 individuals fulfilling either screening criteria for ET or being controls were personally assessed. Medications and mortality data are available. The spiral score increased with age. The spiral score correlated with tremor severity. For the whole cohort, mortality was significantly correlated with the spiral score, and higher spiral scores were associated with lower physical and cognitive functioning. Multivariate analysis identified higher spiral scores as an independent risk factor for mortality. In contrast, the ET patients did not show an increased but rather a lower mortality rate although it was not statistically significant. Consistent with a slower than normal aging, they were also physically and cognitively better functioning than controls. Because incident tremors beyond 70 y of age show worse aging parameters and mortality than controls and ET, we propose to label it ‘aging-related tremor’ (ART). This tremor starts later in life and is accompanied by subtle signs of aging both cognitively and physically. More detailed clinical features and pathogenesis warrant further assessment. PMID:26095699

  14. 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.

  15. Imaging Polarimetry in Age-Related Macular Degeneration

    Science.gov (United States)

    Miura, Masahiro; Yamanari, Masahiro; Iwasaki, Takuya; Elsner, Ann E.; Makita, Shuichi; Yatagai, Toyohiko; Yasuno, Yoshiaki

    2010-01-01

    PURPOSE To evaluate the birefringence properties of eyes with age-related macular degeneration (AMD). To compare the information from two techniques—scanning laser polarimetry (GDx) and polarization-sensitive spectral-domain optical coherence tomography (OCT)—and investigate how they complement each other. METHODS The authors prospectively examined the eyes of two healthy subjects and 13 patients with exudative AMD. Using scanning laser polarimetry, they computed phase-retardation maps, average reflectance images, and depolarized light images. To obtain polarimetry information with improved axial resolution, they developed a fiber-based, polarization-sensitive, spectral-domain OCT system and measured the phase retardation associated with birefringence in the same eyes. RESULTS Both GDx and polarization-sensitive spectral-domain optical coherence tomography detected abnormal birefringence at the locus of exudative lesions. Polarization-sensitive, spectral-domain OCT showed that in the old lesions with fibrosis, phase-retardation values were significantly larger than in the new lesions (P = 0.020). Increased scattered light and altered polarization scramble were associated with portions of the lesions. CONCLUSIONS GDx and polarization-sensitive spectral-domain OCT are complementary in probing birefringence properties in exudative AMD. Polarimetry findings in exudative AMD emphasized different features and were related to the progression of the disease, potentially providing a noninvasive tool for microstructure in exudative AMD. PMID:18515594

  16. Is Alzheimer disease related to age-related macular degeneration?

    Science.gov (United States)

    Seden, Demirci; Alime, Güneş; Kadir, Demirci; Serpil, Demirci; Levent, Tök; Özlem, Tök

    2015-01-01

    To compare the cognitive functions and define the frequency of Alzheimer disease (AD) between participants with and without age-related macular degeneration (AMD). Fifty-nine patients with late-stage AMD (74.3 ± 7.3 years) and 49 age-, sex-, and education-matched control subjects were compared for the presence of AD according to the guidelines of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA). Detailed neuropsychological tests were performed for all subjects. Neuropsychiatric tests scores were lower in the AMD group than the control group. The frequency of AD was higher in patients with AMD (40.7% in AMD and 20.4% in control group, P = 0.03), and particularly higher in late dry (nonvascular) AMD (d-AMD) patients (71.4% in d-AMD and 31.1% in late wet (vascular) AMD, P = 0.007). d-AMD patients performed worse than controls on all tests. There was also an association between age, sex, and low education and neuropsychiatric tests scores (P < 0.01). However, there was no association between visual acuity and neuropsychiatric tests scores. The increased frequency of AD in patients with AMD is significant. This study demonstrated the importance of cognitive assessment in patients with AMD, particularly in the d-AMD type.

  17. 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.

  18. The age-related positivity effect in electronic gambling.

    Science.gov (United States)

    Bailey, Phoebe E; Gonsalvez, Craig J; Maiuolo, Michelle; Leon, Tarren; Benedek, Gülten

    2018-01-01

    Older adults are increasingly spending time and money playing electronic gambling machines (EGMs). The current study assessed whether the age-related positivity effect influences responding to various EGM outcomes, including wins and losses of equivalent magnitude and frequency. We also explored cognitive mechanisms potentially underpinning the positivity effect. We recorded the skin conductance response (SCR) of healthy older and younger adults while they played for wins, losses, and fake wins (losses disguised as wins). After every win and fake win, participants were forced to choose red or black to either double their win or lose it. They also provided ratings of enjoyment and excitement, estimated number of wins and losses, and completed measures of cognitive function. Young and older adults demonstrated larger SCRs to wins relative to losses. When these wins and losses were of equivalent magnitude and frequency following a double-or-nothing scenario, only older adults responded more to a win than a loss. There were no age group differences in excitement and enjoyment, but older adults were more accurate than young adults in their recall of wins and losses. During EGM play, young and older adults demonstrate similar patterns on autonomic arousal. However, young adults' responding suggests generalized excitement, whereas older adults respond more to the prospect of financial gain.

  19. Solar radiation and age-related macular degeneration.

    Science.gov (United States)

    Young, R W

    1988-01-01

    Age-related macular degeneration (AMD) involves a progressive impairment of the outer layers in the center of the retina. Experimental studies have demonstrated that bright light preferentially damages precisely the region that degenerates in AMD. The evidence that solar radiation is responsible for some of the deteriorative changes that lead to AMD is examined in this review. In the primate eye, the high-energy portion of the solar spectrum is most hazardous to retinal molecules, with damaging effects increasing as photon energy rises. This action spectrum is explicable by the quantum laws which describe the interaction of radiation with matter. High-energy visible and ultraviolet photons can produce molecular damage by a photochemical mechanism. The lesion is exacerbated by oxygen, which initiates free-radical chain reactions (photodynamic effects). Melanin exerts a protective effect against damage from sunlight. In the human retina, documented lesions from solar radiation range from the acute effects of sun-gazing to injuries resulting from prolonged periods of exposure in brightly illuminated environments. The damage occurs in the same region that degenerates in AMD. A cataractous lens and ocular melanin both protect the retina against AMD, as predicted by the radiation hypothesis. Identification of an environmental factor that evidently plays a role in the etiology of AMD provides the basis for a program of preventive medicine.

  20. Mechanism of Inflammation in Age-Related Macular Degeneration

    Science.gov (United States)

    Parmeggiani, Francesco; Romano, Mario R.; Costagliola, Ciro; Semeraro, Francesco; Incorvaia, Carlo; D'Angelo, Sergio; Perri, Paolo; De Palma, Paolo; De Nadai, Katia; Sebastiani, Adolfo

    2012-01-01

    Age-related macular degeneration (AMD) is a multifactorial disease that represents the most common cause of irreversible visual impairment among people over the age of 50 in Europe, the United States, and Australia, accounting for up to 50% of all cases of central blindness. Risk factors of AMD are heterogeneous, mainly including increasing age and different genetic predispositions, together with several environmental/epigenetic factors, that is, cigarette smoking, dietary habits, and phototoxic exposure. In the aging retina, free radicals and oxidized lipoproteins are considered to be major causes of tissue stress resulting in local triggers for parainflammation, a chronic status which contributes to initiation and/or progression of many human neurodegenerative diseases such as AMD. Experimental and clinical evidences strongly indicate the pathogenetic role of immunologic processes in AMD occurrence, consisting of production of inflammatory related molecules, recruitment of macrophages, complement activation, microglial activation and accumulation within those structures that compose an essential area of the retina known as macula lutea. This paper reviews some attractive aspects of the literature about the mechanisms of inflammation in AMD, especially focusing on those findings or arguments more directly translatable to improve the clinical management of patients with AMD and to prevent the severe vision loss caused by this disease. PMID:23209345

  1. Adiponectin deficiency exacerbates age-related hearing impairment

    Science.gov (United States)

    Tanigawa, T; Shibata, R; Ouchi, N; Kondo, K; Ishii, M; Katahira, N; Kambara, T; Inoue, Y; Takahashi, R; Ikeda, N; Kihara, S; Ueda, H; Murohara, T

    2014-01-01

    Obesity-related disorders are closely associated with the development of age-related hearing impairment (ARHI). Adiponectin (APN) exerts protective effects against obesity-related conditions including endothelial dysfunction and atherosclerosis. Here, we investigated the impact of APN on ARHI. APN-knockout (APN-KO) mice developed exacerbation of hearing impairment, particularly in the high frequency range, compared with wild-type (WT) mice. Supplementation with APN prevented the hearing impairment in APN-KO mice. At 2 months of age, the cochlear blood flow and capillary density of the stria vascularis (SV) were significantly reduced in APN-KO mice as compared with WT mice. APN-KO mice also showed a significant increase in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells in the organ of Corti in the cochlea at 2 months of age. At the age of 6 months, hair cells were lost at the organ of Corti in APN-KO mice. In cultured auditory HEI-OC1 cells, APN reduced apoptotic activity under hypoxic conditions. Clinically, plasma APN levels were significantly lower in humans with ARHI. Multiple logistic regression analysis identified APN as a significant and independent predictor of ARHI. Our observations indicate that APN has an important role in preventing ARHI. PMID:24763046

  2. Recent developments in age-related macular degeneration: a review

    Science.gov (United States)

    Al-Zamil, Waseem M; Yassin, Sanaa A

    2017-01-01

    Background Visual impairment in elderly people is a considerable health problem that significantly affects quality of life of millions worldwide. The magnitude of this issue is becoming more evident with an aging population and an increasing number of older individuals. Objective The objective of this article was to review the clinical and pathological aspects of age-related macular degeneration (AMD), diagnostic tools, and therapeutic modalities presently available or underway for both atrophic and wet forms of the disease. Methods An online review of the PubMed database was performed, searching for the key words. The search was limited to articles published since 1980 to date. Results Several risk factors have been linked to AMD, such as age (>60 years), lifestyle (smoking and diet), and family history. Although the pathogenesis of AMD remains unclear, genetic factors have been implicated in the condition. Treatment for atrophic AMD is mainly close observation, coupled with nutritional supplements such as zinc and antioxidants, whereas treatment of wet AMD is based on targeting choroidal neovascular membranes. Conclusion Identification of modifiable risk factors would improve the possibilities of preventing the progression of AMD. The role of anti-vascular endothelial growth factor (anti-VEGF) agents has transformed the therapeutic approach of the potentially blinding disease “wet AMD” into a more favorable outcome. PMID:28860733

  3. Antagonistic pleiotropy and mutation accumulation contribute to age-related decline in stress response.

    Science.gov (United States)

    Everman, Elizabeth R; Morgan, Theodore J

    2017-12-07

    As organisms age, the effectiveness of natural selection weakens, leading to age-related decline in fitness-related traits. The evolution of age-related changes associated with senescence is likely influenced by mutation accumulation (MA) and antagonistic pleiotropy (AP). MA predicts that age-related decline in fitness components is driven by age-specific sets of alleles, non-negative genetic correlations within trait across age, and an increase in the coefficient of genetic variance. AP predicts that age-related decline in a trait is driven by alleles with positive effects on fitness in young individuals and negative effects in old individuals, and is expected to lead to negative genetic correlations within traits across age. We build on these predictions using an association mapping approach to investigate the change in additive effects of SNPs across age and among traits for multiple stress-response fitness-related traits, including cold stress with and without acclimation and starvation resistance. We found support for both MA and AP theories of aging in the age-related decline in stress tolerance. Our study demonstrates that the evolution of age-related decline in stress tolerance is driven by a combination of alleles that have age-specific additive effects, consistent with MA, as well as non-independent and antagonistic genetic architectures characteristic of AP. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  4. Association of age-related macular degeneration and reticular macular disease with cardiovascular disease.

    Science.gov (United States)

    Rastogi, Neelesh; Smith, R Theodore

    2016-01-01

    Age-related macular degeneration is the leading cause of adult blindness in the developed world. Thus, major endeavors to understand the risk factors and pathogenesis of this disease have been undertaken. Reticular macular disease is a proposed subtype of age-related macular degeneration correlating histologically with subretinal drusenoid deposits located between the retinal pigment epithelium and the inner segment ellipsoid zone. Reticular lesions are more prevalent in females and in older age groups and are associated with a higher mortality rate. Risk factors for developing age-related macular degeneration include hypertension, smoking, and angina. Several genes related to increased risk for age-related macular degeneration and reticular macular disease are also associated with cardiovascular disease. Better understanding of the clinical and genetic risk factors for age-related macular degeneration and reticular macular disease has led to the hypothesis that these eye diseases are systemic. A systemic origin may help to explain why reticular disease is diagnosed more frequently in females as males suffer cardiovascular mortality at an earlier age, before the age of diagnosis of reticular macular disease and age-related macular degeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Nitrotoga is selected over Nitrospira in newly assembled biofilm communities from a tap water source community at increased nitrite loading

    DEFF Research Database (Denmark)

    Kinnunen, Marta; Gülay, Arda; Albrechtsen, Hans-Jørgen

    2017-01-01

    a source community, present in the tap water, to determine the extent of selection and neutral processes in newly assembled biofilm communities at both the community and the functional guild (of nitrite-oxidizing bacteria, NOB) levels. The community composition of biofilms assembled under low and high...... that can only be interrogated by observing multiple assemblies under controlled conditions. This article is protected by copyright. All rights reserved....

  6. 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

  7. Time series analysis of age related cataract hospitalizations and phacoemulsification

    Directory of Open Access Journals (Sweden)

    Moineddin Rahim

    2006-01-01

    Full Text Available Abstract Background Cataract surgery remains a commonly performed elective surgical procedure in the aging and the elderly. The purpose of this study was to utilize time series methodology to determine the temporal and seasonal variations and the strength of the seasonality in age-related (senile cataract hospitalizations and phacoemulsification surgeries. Methods A retrospective, cross-sectional time series analysis was used to assess the presence and strength of seasonal and temporal patterns of age-related cataract hospitalizations and phacoemulsification surgeries from April 1, 1991 to March 31, 2002. Hospital admission rates for senile cataract (n = 70,281 and phacoemulsification (n = 556,431 were examined to determine monthly rates of hospitalization per 100,000 population. Time series methodology was then applied to the monthly aggregates. Results During the study period, age-related cataract hospitalizations in Ontario have declined from approximately 40 per 100,000 to only one per 100,000. Meanwhile, the use of phacoemulsification procedures has risen dramatically. The study found evidence of biannual peaks in both procedures during the spring and autumn months, and summer and winter troughs. Statistical analysis revealed significant overall seasonal patterns for both age-related cataract hospitalizations and phacoemulsifications (p Conclusion This study illustrates the decline in age-related cataract hospitalizations in Ontario resulting from the shift to outpatient phacoemulsification surgery, and demonstrates the presence of biannual peaks (a characteristic indicative of seasonality, in hospitalization and phacoemulsification during the spring and autumn throughout the study period.

  8. The ERCC6 gene and age-related macular degeneration.

    Directory of Open Access Journals (Sweden)

    Dominique C Baas

    2010-11-01

    Full Text Available Age-related macular degeneration (AMD is the leading cause of irreversible visual loss in the developed countries and is caused by both environmental and genetic factors. A recent study (Tuo et al., PNAS reported an association between AMD and a single nucleotide polymorphism (SNP (rs3793784 in the ERCC6 (NM_000124 gene. The risk allele also increased ERCC6 expression. ERCC6 is involved in DNA repair and mutations in ERCC6 cause Cockayne syndrome (CS. Amongst others, photosensitivity and pigmentary retinopathy are hallmarks of CS.Separate and combined data from three large AMD case-control studies and a prospective population-based study (The Rotterdam Study were used to analyse the genetic association between ERCC6 and AMD (2682 AMD cases and 3152 controls. We also measured ERCC6 mRNA levels in retinal pigment epithelium (RPE cells of healthy and early AMD affected human donor eyes. Rs3793784 conferred a small increase in risk for late AMD in the Dutch population (The Rotterdam and AMRO-NL study, but this was not replicated in two non-European studies (AREDS, Columbia University. In addition, the AMRO-NL study revealed no significant association for 9 other variants spanning ERCC6. Finally, we determined that ERCC6 expression in the human RPE did not depend on rs3793784 genotype, but, interestingly, on AMD status: Early AMD-affected donor eyes had a 50% lower ERCC6 expression than healthy donor eyes (P = 0.018.Our meta-analysis of four Caucasian cohorts does not replicate the reported association between SNPs in ERCC6 and AMD. Nevertheless, our findings on ERCC6 expression in the RPE suggest that ERCC6 may be functionally involved in AMD. Combining our data with those of the literature, we hypothesize that the AMD-related reduced transcriptional activity of ERCC6 may be caused by diverse, small and heterogeneous genetic and/or environmental determinants.

  9. Parathyroid hormone: Data mining for age-related reference intervals in adults.

    Science.gov (United States)

    Farrell, Christopher-John L; Nguyen, Lan; Carter, Andrew C

    2018-02-01

    Age-related changes in parathyroid hormone (PTH) have been previously documented in adults. However, because of the limitations of traditional approaches to establishing reference intervals, age-related reference intervals have not been defined. We sought to use a data mining approach to derive age-related PTH reference intervals. Results from patients undergoing PTH testing over a 4-year period were extracted from the database of a private pathology laboratory in New South Wales, Australia. Patients were included in the study if they were 18 years or older and had simultaneous determination of PTH, serum calcium, estimated glomerular filtration rate and 25-hydroxyvitamin D (25-OHD). Patients with abnormalities of serum calcium or renal function were excluded. Bhattacharya analysis of log-transformed data was used to derive age-related PTH reference intervals across adulthood. Results were available for 33 652 subjects. Among patients with optimal 25-OHD status, older age was associated with higher PTH concentrations. Age-related reference intervals were derived and showed a 63% increase in the upper and lower reference limits between the youngest (18-29 years of age) and the oldest (80 years of age or older) age partitions. The appropriateness of using a single reference interval for patients of all ages was evaluated against objective criteria and was found to be unsatisfactory. Data mining was demonstrated to be a useful tool for establishing age-related PTH reference intervals. The technique demonstrated that increasing age is associated with higher PTH concentrations and that age-related reference intervals are important for accurate result interpretation. © 2017 John Wiley & Sons Ltd.

  10. Age-Related Changes in Bone Remodelling and Structure in Men: Histomorphometric Studies

    Directory of Open Access Journals (Sweden)

    Juliet Compston

    2011-01-01

    Full Text Available Histomorphometric studies of the age-related changes in bone remodelling and structure in men are relatively sparse and mainly limited to the iliac crest. The available data indicate that loss of trabecular bone is predominantly due to decreased formation at the level of individual bone remodelling units and that an increase in remodelling rate does not play a major role. The main structural consequence of the changes in bone remodelling is trabecular thinning. In cortical bone, an age-related reduction in cortical width and increase in porosity have been demonstrated at several skeletal sites. However, the alterations in bone remodelling responsible for these changes remain to be established.

  11. Age-related changes in oscillatory power affect motor action.

    Directory of Open Access Journals (Sweden)

    Liqing Liu

    Full Text Available With increasing age cognitive performance slows down. This includes cognitive processes essential for motor performance. Additionally, performance of motor tasks becomes less accurate. The objective of the present study was to identify general neural correlates underlying age-related behavioral slowing and the reduction in motor task accuracy. To this end, we continuously recorded EEG activity from 18 younger and 24 older right-handed healthy participants while they were performing a simple finger tapping task. We analyzed the EEG records with respect to local changes in amplitude (power spectrum as well as phase locking between the two age groups. We found differences between younger and older subjects in the amplitude of post-movement synchronization in the β band of the sensory-motor and medial prefrontal cortex (mPFC. This post-movement β amplitude was significantly reduced in older subjects. Moreover, it positively correlated with the accuracy with which subjects performed the motor task at the electrode FCz, which detects activity of the mPFC and the supplementary motor area. In contrast, we found no correlation between the accurate timing of local neural activity, i.e. phase locking in the δ-θ frequency band, with the reaction and movement time or the accuracy with which the motor task was performed. Our results show that only post-movement β amplitude and not δ-θ phase locking is involved in the control of movement accuracy. The decreased post-movement β amplitude in the mPFC of older subjects hints at an impaired deactivation of this area, which may affect the cognitive control of stimulus-induced motor tasks and thereby motor output.

  12. Age-Related Difference in Functional Brain Connectivity of Mastication

    Science.gov (United States)

    Lin, Chia-shu; Wu, Ching-yi; Wu, Shih-yun; Lin, Hsiao-Han; Cheng, Dong-hui; Lo, Wen-liang

    2017-01-01

    The age-related decline in motor function is associated with changes in intrinsic brain signatures. Here, we investigated the functional connectivity (FC) associated with masticatory performance, a clinical index evaluating general masticatory function. Twenty-six older adults (OA) and 26 younger (YA) healthy adults were recruited and assessed using the masticatory performance index (MPI) and resting-state functional magnetic resonance imaging (rs-fMRI). We analyzed the rs-fMRI FC network related to mastication, which was constructed based on 12 bilateral mastication-related brain regions according to the literature. For the OA and the YA group, we identified the mastication-related hubs, i.e., the nodes for which the degree centrality (DC) was positively correlated with the MPI. For each pair of nodes, we identified the inter-nodal link for which the FC was positively correlated with the MPI. The network analysis revealed that, in the YA group, the FC between the sensorimotor cortex, the thalamus (THA) and the cerebellum was positively correlated with the MPI. Consistently, the cerebellum nodes were defined as the mastication-related hubs. In contrast, in the OA group, we found a sparser connection within the sensorimotor regions and cerebellum and a denser connection across distributed regions, including the FC between the superior parietal lobe (SPL), the anterior insula (aINS) and the dorsal anterior cingulate cortex (dACC). Compared to the YA group, the network of the OA group also comprised more mastication-related hubs, which were spatially distributed outside the sensorimotor regions, including the right SPL, the right aINS, and the bilateral dACC. In general, the findings supported the hypothesis that in OA, higher masticatory performance is associated with a widespread pattern of mastication-related hubs. Such a widespread engagement of multiple brain regions associated with the MPI may reflect an increased demand in sensorimotor integration, attentional

  13. 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

  14. [Impact of thymic function in age-related immune deterioration].

    Science.gov (United States)

    Ferrando-Martínez, Sara; de la Fuente, Mónica; Guerrero, Juan Miguel; Leal, Manuel; Muñoz-Fernández, M Ángeles

    2013-01-01

    Age-related biological deterioration also includes immune system deterioration and, in consequence, a rise in the incidence and prevalence of infections and cancers, as well as low responses to vaccination strategies. Out of all immune cell subsets, T-lymphocytes seem to be involved in most of the age-related defects. Since T-lymphocytes mature during their passage through the thymus, and the thymus shows an age-related process of atrophy, thymic regression has been proposed as the triggering event of this immune deterioration in elderly people. Historically, it has been accepted that the young thymus sets the T-lymphocyte repertoire during the childhood, whereupon atrophy begins until the elderly thymus is a non-functional evolutionary trace. However, a rising body of knowledge points toward the thymus functioning during adulthood. In the elderly, higher thymic function is associated with a younger immune system, while thymic function failure is associated with all-cause mortality. Therefore, any new strategy focused on the improvement of the elderly quality of life, especially those trying to influence the immune system, should take into account, together with peripheral homeostasis, thymus function as a key element in slowing down age-related decline. Copyright © 2012 SEGG. Published by Elsevier Espana. All rights reserved.

  15. Age-Related Differences in Moral Identity across Adulthood

    Science.gov (United States)

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

    2016-01-01

    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…

  16. Do sleep complaints contribute to age-related cognitive decline?

    NARCIS (Netherlands)

    Altena, E.; Ramautar, J.R.; van der Werf, Y.D.; van Someren, E.J.W.

    2010-01-01

    The cognitive changes that occur with ageing are usually referred to as 'age-related cognitive decline'. The most pronounced changes may be found in the executive functions that require integrity of the prefrontal cortical circuitry. With age, sleep also changes profoundly, with more sleep

  17. Age-Related Changes in Binaural Interaction at Brainstem Level

    NARCIS (Netherlands)

    Yper, L.N. Van; Vermeire, K.; Vel, E.F. De; Beynon, A.J.; Dhooge, I.J.

    2016-01-01

    OBJECTIVES: Age-related hearing loss hampers the ability to understand speech in adverse listening conditions. This is attributed to a complex interaction of changes in the peripheral and central auditory system. One aspect that may deteriorate across the lifespan is binaural interaction. The

  18. Complement factor d in age-related macular degeneration

    NARCIS (Netherlands)

    Stanton, C.M.; Yates, J.R.W.; Hollander, A.I. den; Seddon, J.M.; Swaroop, A.; Stambolian, D.; Fauser, S.; Hoyng, C.B.; Yu, Y.; Atsuhiro, K.; Branham, K.; Othman, M.; Chen, W.; Kortvely, E.; Chalmers, K.; Hayward, C.; Moore, A.T.; Dhillon, B.; Ueffing, M.; Wright, A.F.

    2011-01-01

    Purpose. To examine the role of complement factor D (CFD) in age-related macular degeneration (AMD) by analysis of genetic association, copy number variation, and plasma CFD concentrations. Methods. Single nucleotide polymorphisms (SNPs) in the CFD gene were genotyped and the results analyzed by

  19. Age-Related Differences in Idiom Production in Adulthood

    Science.gov (United States)

    Conner, Peggy S.; Hyun, Jungmoon; O'Connor Wells, Barbara; Anema, Inge; Goral, Mira; Monereau-Merry, Marie-Michelle; Rubino, Daniel; Kuckuk, Raija; Obler, Loraine K.

    2011-01-01

    To investigate whether idiom production was vulnerable to age-related difficulties, we asked 40 younger (ages 18-30) and 40 older healthy adults (ages 60-85) to produce idiomatic expressions in a story-completion task. Younger adults produced significantly more correct idiom responses (73%) than did older adults (60%). When older adults generated…

  20. Age-Related Factors in Second Language Acquisition.

    Science.gov (United States)

    Twyford, Charles William

    The convergence of several lines of psycholinguistic and sociolinguistic research suggests possible explanations for age-related influences on language acquisition. These factors, which include cognitive development, sociocultural context, affective factors, and language input, can be helpful to language educators. By being alert to the cognitive…

  1. Prevalence of Age-Related Macular Degeneration in Europe

    NARCIS (Netherlands)

    Colijn, Johanna M.; Buitendijk, Gabriëlle H. S.; Prokofyeva, Elena; Alves, Dalila; Cachulo, Maria L.; Khawaja, Anthony P.; Cougnard-Gregoire, Audrey; Merle, Bénédicte M. J.; Korb, Christina; Erke, Maja G.; Bron, Alain; Anastasopoulos, Eleftherios; Meester-Smoor, Magda A.; Segato, Tatiana; Piermarocchi, Stefano; de Jong, Paulus T. V. M.; Vingerling, Johannes R.; Topouzis, Fotis; Creuzot-Garcher, Catherine; Bertelsen, Geir; Pfeiffer, Norbert; Fletcher, Astrid E.; Foster, Paul J.; Silva, Rufino; Korobelnik, Jean-François; Delcourt, Cécile; Klaver, Caroline C. W.; Ajana, Soufiane; Arango-Gonzalez, Blanca; Arndt, Verena; Bhatia, Vaibhav; Bhattacharya, Shomi S.; Biarnés, Marc; Borrell, Anna; Bühren, Sebastian; Calado, Sofia M.; Cougnard-Grégoire, Audrey; Dammeier, Sascha; de Jong, Eiko K.; de la Cerda, Berta; den Hollander, Anneke I.; Diaz-Corrales, Francisco J.; Diether, Sigrid; Emri, Eszter; Endermann, Tanja; Ferraro, Lucia L.; Garcia, Míriam; Heesterbeek, Thomas J.; Honisch, Sabina; Hoyng, Carel B.; Kersten, Eveline; Kilger, Ellen; Langen, Hanno; Lengyel, Imre; Luthert, Phil; Maugeais, Cyrille; Meester-Smoor, Magda; Monés, Jordi; Nogoceke, Everson; Peto, Tunde; Pool, Frances M.; Rodríguez, Eduardo; Ueffing, Marius; Ulrich Bartz-Schmidt, Karl U.; van Leeuwen, Elisabeth M.; Verzijden, Timo; Zumbansen, Markus; Acar, Niyazi; Anastosopoulos, Eleftherios; Azuara-Blanco, Augusto; Bergen, Arthur; Binquet, Christine; Bird, Alan; Brétillon, Lionel; Buitendijk, Gabrielle; Cachulo, Maria Luz; Chakravarthy, Usha; Chan, Michelle; Chang, Petrus; Colijn, Johanna; Cumberland, Philippa; Cunha-Vaz, José; Daien, Vincent; Deak, Gabor; Delyfer, Marie-Noëlle; den Hollander, Anneke; Dietzel, Martha; Erke, Maja Gran; Fauser, Sascha; Finger, Robert; Fletcher, Astrid; Foster, Paul; Founti, Panayiota; Göbel, Arno; Gorgels, Theo; Grauslund, Jakob; Grus, Franz; Hammond, Christopher; Helmer, Catherine; Hense, Hans-Werner; Hermann, Manuel; Hoehn, René; Hogg, Ruth; Holz, Frank; Hoyng, Carel; Jansonius, Nomdo; Janssen, Sarah; Khawaja, Anthony; Klaver, Caroline; Lamparter, Julia; Le Goff, Mélanie; Leal, Sergio; Lechanteur, Yara; Lehtimäki, Terho; Lotery, Andrew; Leung, Irene; Mauschitz, Matthias; Merle, Bénédicte; Meyer Zu Westrup, Verena; Midena, Edoardo; Miotto, Stefania; Mirshahi, Alireza; Mohan-Saïd, Sadek; Mueller, Michael; Muldrew, Alyson; Nunes, Sandrina; Oexle, Konrad; Rahi, Jugnoo; Raitakari, Olli; Ribeiro, Luisa; Rougier, Marie-Bénédicte; Sahel, José; Salonikiou, Aggeliki; Sanchez, Clarisa; Schmitz-Valckenberg, Steffen; Schweitzer, Cédric; Shehata, Jasmin; Silvestri, Giuliana; Simader, Christian; Souied, Eric; Springelkamp, Henriet; Tapp, Robyn; Verhoeven, Virginie; Von Hanno, Therese; Vujosevic, Stela; Williams, Katie; Wolfram, Christian; Yip, Jennifer; Zerbib, Jennyfer; Zwiener, Isabella

    2017-01-01

    Purpose: Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in

  2. Age-related Macular Degeneration: Current concepts in ...

    African Journals Online (AJOL)

    This paper reviews current concepts in the pathogenesis and management of agerelated macular degeneration as found in Pubmed journals over the past ten years with a view to recommending optimal treatment regimes for African populations. Keywords: age-related macular degeneration, pathogenesis, genetics ...

  3. Age Related Variations in The Architecture of Caprine Haemal Nodes

    African Journals Online (AJOL)

    Age related variations in the architecture of caprine haemal nodes were studied in West African dwarf goats aged between 1-24 months. Variations were observed in the thickness of the capsule, the content and organization of the cortical and medullary parenchyma as well as the stroma. In young goats age between 1-4 ...

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

    NARCIS (Netherlands)

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

    2016-01-01

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

  5. on visual acuity in age related macular degeneration

    African Journals Online (AJOL)

    marine origin) in the treatment of age related macular degeneration (AMD). In a randomized double blind clinical trial 280 eyes of 280 (157 F, 123 M) patients with wet and dry AMD were randomly assigned in treatment or placebo groups. Patients in ...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    OBJECTIVE: Although a reduced aflibercept (2.0 mg) injection frequency relative to the approved dosing posology is included in national treatment guidelines for wet age-related macular degeneration (AMD), there is limited evidence of its comparative efficacy. The objective was to compare...

  7. 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…

  8. Review Article Therapeutic Potential of Statins in Age-related ...

    African Journals Online (AJOL)

    2011-08-09

    Aug 9, 2011 ... The objective of this review is therefore to evaluate the evidence and discuss the rationale behind the recent suggestions that statins may be useful in the prevention and the treatment of age-related macular degeneration. This review recognised that there are potentially multiple biological bases for the.

  9. Therapeutic Potential of Statins in Age-related Macular Degeneration

    African Journals Online (AJOL)

    Age-related macular degeneration (ARMD) is the leading cause of irreversible vision loss, affecting one in three people aged 75 and above. Although exciting new pharmaceuticals to treat ARMD such as endothelial growth factor (VEGF) inhibitors, are now available, they are effective only in selected group of patients, and ...

  10. Age-related macular degeneration in Onitsha, Nigeria | Nwosu ...

    African Journals Online (AJOL)

    Objectives: To determine the incidence, pattern and ocular morbidity associated with age-related macular degeneration (AMD) at the Guinness Eye Center Onitsha Nigeria. Materials and Methods: The case files of all new patients aged 50 years and above seen between January 1997 and December 2004 were reviewed.

  11. Pathophysiology of Age-Related Hearing Loss (Peripheral and Central)

    OpenAIRE

    Lee, Kyu-Yup

    2013-01-01

    Age-related hearing loss (presbycusis) refers to bilaterally symmetrical hearing loss resulting from aging process. Presbycusis is a complex phenomenon characterized by audiometric threshold shift, deterioration in speech-understanding and speech-perception difficulties in noisy environments. Factors contributing to presbycusis include mitochondria DNA mutation, genetic disorders including Ahl, hypertension, diabetes, metabolic disease and other systemic diseases in the intrinsic aspects. Ext...

  12. An epigenetic hypothesis of aging-related cognitive dysfunction

    Directory of Open Access Journals (Sweden)

    Marsha R Penner

    2010-03-01

    Full Text Available This brief review will focus on a new hypothesis for the role of epigenetic mechanisms in aging-related disruptions of synaptic plasticity and memory. Epigenetics refers to a set of potentially self-perpetuating, covalent modifications of DNA and post-translational modifications of nuclear proteins that produce lasting alterations in chromatin structure. These mechanisms, in turn, result in alterations in specific patterns of gene expression. Aging-related memory decline is manifest prominently in declarative/episodic memory and working memory, memory modalities anatomically based largely in the hippocampus and prefrontal cortex, respectively. The neurobiological underpinnings of age-related memory deficits include aberrant changes in gene transcription that ultimately affect the ability of the aged brain to be “plastic”. The molecular mechanisms underlying these changes in gene transcription are not currently known, but recent work points toward a potential novel mechanism, dysregulation of epigenetic mechanisms. This has led us to hypothesize that dysregulation of epigenetic control mechanisms and aberrant epigenetic “marks” drive aging-related cognitive dysfunction. Here we focus on this theme, reviewing current knowledge concerning epigenetic molecular mechanisms, as well as recent results suggesting disruption of plasticity and memory formation during aging. Finally, several open questions will be discussed that we believe will fuel experimental discovery.

  13. 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…

  14. 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...

  15. Nutritional risk factors for age-related macular degeneration

    NARCIS (Netherlands)

    Ersoy, L.; Ristau, T.; Lechanteur, Y.T.E.; Hahn, M.; Hoyng, C.B.; Kirchhof, B.; Hollander, A.I. den; Fauser, S.

    2014-01-01

    Purpose. To evaluate the role of nutritional factors, serum lipids, and lipoproteins in late age-related macular degeneration (late AMD). Methods. Intake of red meat, fruit, fish, vegetables, and alcohol, smoking status, and body mass index (BMI) were ascertained questionnaire-based in 1147 late AMD

  16. Gene-diet interactions in age-related macular degeneration

    Science.gov (United States)

    Age-related macular degeneration (AMD) is a prevalent blinding disease, accounting for roughly 50% of blindness in developed nations. Very significant advances have been made in terms of discovering genetic susceptibilities to AMD as well as dietary risk factors. To date, nutritional supplementation...

  17. Nutritional modulation of age-related macular degeneration

    Science.gov (United States)

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. It affects 30-50 million individuals and clinical hallmarks of AMD are observed in at least one third of persons over the age of 75 in industrialized countries (Gehrs et al., 2006). Costs associated wi...

  18. Epidemiology of age-related maculopathy: a review

    NARCIS (Netherlands)

    van Leeuwen, Redmer; Klaver, Caroline C. W.; Vingerling, Johannes R.; Hofman, Albert; de Jong, Paulus T. V. M.

    2003-01-01

    Age-related maculopathy (ARM) is a degenerative disease of the retina and the leading cause of incurable blindness and visual impairment in industrialized countries. By definition, ARM is confined to the age-category above 50 years. The aetiology of ARM is still unknown, despite intensive research

  19. Assessment of Head Displacement and Disassembly Force With Increasing Assembly Load at the Head/Trunnion Junction of a Total Hip Arthroplasty Prosthesis.

    Science.gov (United States)

    Ramoutar, Darryl N; Crosnier, Emilie A; Shivji, Faiz; Miles, Anthony W; Gill, Harinderjit S

    2017-05-01

    Most femoral components used now for total hip arthroplasty are modular, requiring a strong connection at assembly. The aim of this study was to assess the effect of assembly force on the strength of head-trunnion interface and to measure the initial displacement of the head on the trunnion with different assembly forces. Three assembly load levels were assessed (A: 2 kN, B: 4 kN, C: 6 kN) with 4 implants in each group. The stems were mounted in a custom rig and the respective assembly loads were applied to the head at a constant rate of 0.05 kN/s (ISO7260-10:2003). Load levels were recorded during assembly. Head displacement was measured with a laser sensor. The disassembly force was determined by a standard pull-off test. The maximum head displacement on the trunnion was significantly different between the 2 kN group and the other 2 groups (4 kN, 6 kN, P = .029), but not between the 4 kN and 6 kN groups (P = .89). The disassembly forces between the 3 groups were significantly different (mean ± standard deviation, A: 1316 ± 223 kN; B: 2224 ± 151 kN; C: 3965 ± 344 kN; P = .007), with increasing assembly load leading to a higher pull-off force. For the 4 kN and 6 kN groups, a first peak of approximately 2.5 kN was observed on the load recordings during assembly before the required assembly load was eventually reached corresponding to sudden increase in head displacement to approximately 150 μm. An assembly force of 2 kN may be too low to overcome the frictional forces needed to engage the head and achieve maximum displacement on the trunnion and thus an assembly load of greater than 2.5 kN is recommended. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Interleukin-13 and age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Bo Fu

    2017-04-01

    Full Text Available AIM: To identify the effects of interleukin (IL-13 on retinal pigment epithelial (RPE cells and the IL-13 level in aqueous humor of age-related macular degeneration (AMD patients. METHODS: IL-13 levels in aqueous humor specimens from AMD patients were detected with enzyme-linked immunosorbent assay (ELISA. ARPE-19 cells were treated with 10 ng/mL IL-13 for 12, 24, and 48h. The cell proliferaton was evaluated by the MTS method. The mRNA and protein levels of α-SMA and ZO-1 were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR and Western blot respectively. The expression of tumor necrosis factor-α (TNF-α, transforming growth factor-β (TGF-β and vascular endothelial growth factor (VEGF were assessed by ELISA. RESULTS: IL-13 levels in the aqueous humor of patients with AMD were significantly higher than those in the control (167.33±17.64 vs 27.12±5.65 pg/mL; P<0.01. In vitro, IL-13 of high concentrations (10, 15, and 20 ng/mL inhibited ARPE-19 cell proliferation. α-SMA mRNA in ARPE-19 cell were increased (1.017±0.112 vs 1.476±0.168; P<0.001 and ZO-1 decreased (1.051±0.136 vs 0.702±0.069; P<0.001 after treated with 10 ng/mL IL-13 for 48h. The protein expression of α-SMA and ZO-1 also showed the same tendency (α-SMA: P=0.038; ZO-1: P=0.008. IL-13 significantly reduced the level of TNF-α (44.70±1.67 vs 31.79±3.53 pg/mL; P=0.005 at 48h, but the level of TGF-β2 was significantly increased from 34.44±2.92 to 57.61±6.31 pg/mL at 24h (P=0.004 and from 61.26±1.11 to 86.91±3.59 pg/mL at 48h (P<0.001. While expressions of VEGF didn’t change after IL-13 treatment. CONCLUSION: IL-13 in vitro inhibit ARPE-19 cell proliferation and expression in the aqueous may be associated with AMD.

  1. Vision Rehabilitation in Patients with Age-related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Filippo M. Amore

    2014-03-01

    Full Text Available Background The aim of this study was to investigate the rehabilitative process and visual rehabilitation outcomes in patients with central vision loss due to age-related macular degeneration (AMD. Methods Ninety-five subjects with AMD selected from the attendees of the National Centre of Services and Research for the Prevention of Blindness and Rehabilitation of Low Vision Patients—International Agency for Prevention of Blindness—IAPB Italia Onlus, were evaluated for this retrospective study. Low vision examination included psychological counseling, best corrected visual acuity (BCVA, near visual acuity, Pelli-Robson contrast sensitivity, and fixation stability analysis. Once the clinical assessment was completed, patients attended a low-vision rehabilitative pathway based on visual stimulation, devices training and, if needed, psychological support. Required magnification and reading speed were also evaluated. Results For the whole sample, the mean BCVA of the better eye was 0.7 (±0.2 LogMAR and of the worse eye was 1 (±0.2 LogMAR. Restoring reading ability was the most important focus for the patients examined as it was requested by 85% of the whole sample. Mean power of optical magnifying aids for near activities was 10.6 (±9.1 positive spherical diopters. Mean reading speed for the whole sample was 33.1 (±18.2 words per minute (wpm before visual rehabilitation sessions and increased to 55.2 (±33.1 wpm after visual rehabilitation path. To cope with distance difficulties, 78 distance refractive correction, 10 Galilean telescopes, and 7 Keplerian telescopes were prescribed. For intermediate distance activities, 22 compensation lenses and 10 Galilean telescopes were suggested. Moreover, PC magnifier softwares were prescribed to nine patients. Sixty-five polarized medical filters were prescribed to reduce glare of sunlight. Because of unstable fixation in their better eye (32.3% (±19.7 within 2° circle and 54.8% (±22.9 within 4

  2. The Potential of Chitosan and Its Derivatives in Prevention and Treatment of Age-Related Diseases

    Directory of Open Access Journals (Sweden)

    Garry Kerch

    2015-04-01

    Full Text Available Age-related, diet-related and protein conformational diseases, such as atherosclerosis, diabetes mellitus, cancer, hypercholesterolemia, cardiovascular and neurodegenerative diseases are common in the elderly population. The potential of chitosan, chitooligosaccharides and their derivatives in prevention and treatment of age-related dysfunctions is reviewed and discussed in this paper. The influence of oxidative stress, low density lipoprotein oxidation, increase of tissue stiffness, protein conformational changes, aging-associated chronic inflammation and their pathobiological significance have been considered. The chitosan-based functional food also has been reviewed.

  3.  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.

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

    NARCIS (Netherlands)

    Lever, A.G.; Geurts, H.M.

    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

  5. Improvement in age-related cognitive functions and life expectancy by ketogenic diets

    DEFF Research Database (Denmark)

    Astrup, Arne; Hjorth, Mads Fiil

    2017-01-01

    Rodent studies have indicated that low-carbohydrate diets prevent age-related cognitive decline and extend lifespan due to increased circulating levels of ketone bodies. A possible physiological mechanism for how ketone bodies exert this effect might be by improving central nervous system insulin...

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  7. 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...

  8. 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

    ObjectiveThe 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

  9. 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; Picavet, H. Susan J; van der Schouw, Yvonne T|info:eu-repo/dai/nl/073449253; Bakker, Stephan J L; Gansevoort, Ron T; Dollé, Martijn E T; Smit, Henriette A|info:eu-repo/dai/nl/067730043; Monique Verschuren, W M|info:eu-repo/dai/nl/071858849

    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

  10. Age and muscle strength mediate the age-related biomechanical plasticity of gait

    NARCIS (Netherlands)

    Hortobagyi, Tibor; Rider, Patrick; Gruber, Allison H.; DeVita, Paul

    Old compared with young adults walk with reduced ankle and increased hip mechanical output. We examined the idea that age, leg strength, or both are related to the age-related changes in mechanical output during gait. Healthy young (n = 32, age 21.5 years) and old adults (n = 32, age 76.8 years)

  11. Complement inhibitors for age-related macular degeneration.

    Science.gov (United States)

    Williams, Michael A; McKay, Gareth J; Chakravarthy, Usha

    2014-01-15

    Given the relatively high prevalence of age-related macular degeneration (AMD) and the increased incidence of AMD as populations age, the results of trials of novel treatments are awaited with much anticipation. The complement cascade describes a series of proteolytic reactions occurring throughout the body that generate proteins with a variety of roles including the initiation and promotion of immune reactions against foreign materials or micro-organisms. The complement cascade is normally tightly regulated, but much evidence implicates complement overactivity in AMD and so it is a logical therapeutic target in the treatment of AMD. To assess the effects and safety of complement inhibitors in the prevention or treatment of advanced AMD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 11), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to November 2013), EMBASE (January 1980 to November 2013), Allied and Complementary Medicine Database (AMED) (January 1985 to November 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to November 2013), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), Web of Science Conference Proceedings Citation Index - Science (CPCI-S) (January 1990 to November 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 21 November 2013. We also performed handsearching of proceedings, from 2012 onwards, of meetings and conferences of specific professional organisations. We planned to include randomised controlled trials (RCTs) with

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

    Science.gov (United States)

    Shaw, Peter X.; Stiles, Travis; Douglas, Christopher; Ho, Daisy; Fan, Wei; Du, Hongjun; Xiao, Xu

    2016-01-01

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

  13. 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

  14. Age-related macular degeneration: update for primary care.

    Science.gov (United States)

    Fong, D S

    2000-05-15

    Age-related macular degeneration is the leading cause of severe vision loss among the elderly. In this condition, central vision is lost, but peripheral vision almost always remains intact. Affected persons rarely require canes or guide dogs. The diagnosis of age-related macular degeneration is based on symptoms and ophthalmoscopic findings, and the disease can be classified into atrophic and exudative forms. The two currently proven treatments are laser photocoagulation and photodynamic therapy, but these measures are effective in only a small fraction of eyes with the exudative form of macular degeneration. Vision rehabilitation can help patients maximize their remaining vision and adapt so that they can perform activities of daily living. Families need encouragement in providing support and helping patients adjust to being partially sighted.

  15. Heart Failure as an Aging-Related Phenotype.

    Science.gov (United States)

    Morita, Hiroyuki; Komuro, Issei

    2018-01-27

    The molecular pathophysiology of heart failure, which is one of the leading causes of mortality, is not yet fully understood. Heart failure can be regarded as a systemic syndrome of aging-related phenotypes. Wnt/β-catenin signaling and the p53 pathway, both of which are key regulators of aging, have been demonstrated to play a critical role in the pathogenesis of heart failure. Circulating C1q was identified as a novel activator of Wnt/β-catenin signaling, promoting systemic aging-related phenotypes including sarcopenia and heart failure. On the other hand, p53 induces the apoptosis of cardiomyocytes in the failing heart. In these molecular mechanisms, the cross-talk between cardiomyocytes and non-cardiomyocytes (e,g,. endothelial cells, fibroblasts, smooth muscle cells, macrophages) deserves mentioning. In this review, we summarize recent advances in the understanding of the molecular pathophysiology underlying heart failure, focusing on Wnt/β-catenin signaling and the p53 pathway.

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

    Science.gov (United States)

    Hung, Pei-Fang; Nippold, Marilyn A

    2014-03-01

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

  17. 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 white matter over the adult lifespan. However, these previous studies were limited with a small sample of chimpanzees of the most advanced ages. In the present study, we sought to further test for potential age-related decline in cortical organization in chimpanzees by expanding the sample size of aged...... chimpanzees. We used the BrainVisa software to measure total brain volume, gray and white matter volumes, gray matter thickness, and gyrification index in a cross-sectional sample of 219 captive chimpanzees (8-53 years old), with 38 subjects being 40 or more years of age. Mean depth and cortical fold opening...

  18. Shared age-related influences on cognitive and noncognitive variables.

    Science.gov (United States)

    Salthouse, T A; Hambrick, D Z; McGuthry, K E

    1998-09-01

    Analyses of new data and of previously published data were conducted to examine the degree to which age-related variance was shared across cognitive and noncognitive variables and to investigate possible alterations in the composition of a factor common to all variables as a function of age. The results indicated that measures of visual acuity, grip strength, and blood pressure shared age-related variance with measures of perceptual speed, episodic memory, spatial visualization, and inductive reasoning. However, although the cognitive variables shared similar amounts of variance in age-restricted and age-partialed analyses, the variance shared between cognitive and noncognitive variables was substantially reduced after controlling the influence of age.

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

    Directory of Open Access Journals (Sweden)

    Zhenwei eGong

    2014-12-01

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

  20. Radiation treatment for age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Taniguchi, Tomoko; Mandai, Michiko; Honjo, Megumi; Matsuda, Naoko; Miyamoto, Hideki; Takahashi, Masayo; Ogura, Yuichiro; Sasai, Keisuke [Kyoto Univ. (Japan). Faculty of Medicine

    1996-11-01

    Fifteen eyes of age-related macular degeneration were treated by low-dose radiation. All the affected eyes had subfoveal neovascular membrane. Seventeen nontreated eyes with similar macular lesion served as control. Radiation was performed using photon beam at 6MV. Each eye received daily dose of 2 Gy for 5 consecutive days. When evaluated 9 to 12 months after treatment, the size of neovascular membrane had decreased in 47% of treated eyes and 7% of control eyes. The visual acuity improved by 2 lines or more in 13% of treated eyes and in none of control eyes. When the initial neovascular membrane was less than 1.5 disc diameter in size, the visual acuity had improved or remained stationary in 90% of treated eyes and in 36% of control eyes. The findings show the potential beneficial effect of radiation for age-related macular degeneration. (author)

  1. 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.

  2. Age-Related Neurochemical Changes in the Vestibular Nuclei

    OpenAIRE

    Paul eSmith

    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 ...

  3. Complement pathway biomarkers and age-related macular degeneration

    Science.gov (United States)

    Gemenetzi, M; Lotery, A J

    2016-01-01

    In the age-related macular degeneration (AMD) ‘inflammation model', local inflammation plus complement activation contributes to the pathogenesis and progression of the disease. Multiple genetic associations have now been established correlating the risk of development or progression of AMD. Stratifying patients by their AMD genetic profile may facilitate future AMD therapeutic trials resulting in meaningful clinical trial end points with smaller sample sizes and study duration. PMID:26493033

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

    Directory of Open Access Journals (Sweden)

    Sara Velilla

    2013-01-01

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

  5. Age-related epigenetic drift and phenotypic plasticity loss: implications in prevention of age-related human diseases.

    Science.gov (United States)

    Li, Yuanyuan; Tollefsbol, Trygve O

    2016-12-01

    Aging is considered as one of the most important developmental processes in organisms and is closely associated with global deteriorations of epigenetic markers such as aberrant methylomic patterns. This altered epigenomic state, referred to 'epigenetic drift', reflects deficient maintenance of epigenetic marks and contributes to impaired cellular and molecular functions in aged cells. Epigenetic drift-induced abnormal changes during aging are scantily repaired by epigenetic modulators. This inflexibility in the aged epigenome may lead to an age-related decline in phenotypic plasticity at the cellular and molecular levels due to epigenetic drift. This perspective aims to provide novel concepts for understanding epigenetic effects on the aging process and to provide insights into epigenetic prevention and therapeutic strategies for age-related human disease.

  6. Alcohol consumption, smoking and development of visible age-related signs: a prospective cohort study.

    Science.gov (United States)

    Schou, Anne L; Mølbak, Marie-Louise; Schnor, Peter; Grønbæk, Morten; Tolstrup, Janne S

    2017-12-01

    Visible age-related signs indicate biological age, as individuals that appear old for their age are more likely to be at poor health, compared with people that appear their actual age. The aim of this study was to investigate whether alcohol and smoking are associated with four visible age-related signs (arcus corneae, xanthelasmata, earlobe crease and male pattern baldness). We used information from 11 613 individuals in the Copenhagen City Heart Study (1976-2003). Alcohol intake, smoking habits and other lifestyle factors were assessed prospectively and visible age-related signs were inspected during subsequent examinations. The risk of developing arcus corneae, earlobe crease and xanthelasmata increased stepwise with increased smoking as measured by pack-years. For alcohol consumption, a high intake was associated with the risk of developing arcus corneae and earlobe crease, but not xanthelasmata. High alcohol consumption and smoking predict development of visible age-related signs. This is the first prospective study to show that heavy alcohol use and smoking are associated with generally looking older than one's actual age. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. Prevalence of age-related cataract in high-selenium areas of China.

    Science.gov (United States)

    Li, Tuo; He, Tao; Tan, Xiaodong; Yang, Shurong; Li, Jiazhang; Peng, Zuoquan; Li, Hongyan; Song, Xiusheng; Wu, Qingsong; Yang, Fanglie; Xing, Yiqiao

    2009-04-01

    The objective of this study was to determine the prevalence of age-related cataract in high-selenium areas of China. This is a cross-sectional study of 1,522 persons aged 50 years and more who were selected as a representative sample from the Enshi prefecture in Hubei province. All lenses were graded and classified for opacities by slit lamp after papillary dilation, using the Lens Opacification Classification System II. The age-related cataract patients were 418 cases (33.28%). The prevalence of age-related cataract was 37.2% in women and 26.0% in men. The prevalence of nuclear cataract was 23.7%; cortical cataract was 22.4% and posterior subcapsule cataract was 5.2%. The prevalence of cataract of the 50-59 group was 13.41%; 60-69 group was 42.15%; 70 and over group was 61.9%. The prevalence of age-related cataract in high-selenium areas has not significantly increased; to some extent, the high selenium intake will not become a risk factor for the increase of cataract incidence.

  8. Maternal Weight after Childbirth versus Aging-Related Weight Changes.

    Science.gov (United States)

    Yakusheva, Olga; Kapinos, Kandice; Weiss, Marianne

    Pregnancy weight gain is believed to contribute to female overweight and obesity. However, most studies do not account for the changes in body weight expected to occur as women age. We examined the long-term weight trajectory of childbearing women relative to weight progression that could be expected in the absence of pregnancy. From the hospital records of 32,187 women with two births in Wisconsin during 2006 to 2013, we extracted the maternal weight at pregravid, delivery, and subsequent pregravid. We predicted the corresponding aging-progressed weights using a weight-for-age equation adjusted for sociodemographic variables. Nonparametric mixed effects models estimated the average maternal weight trajectory and the corresponding aging-related progression through 5 years after birth. The estimated aging-related progression predicted a gradual annual weight increase of 1.94 pounds (95% confidence interval 1.90-1.98), from 152.79 pounds at pregravid to 163.76 pounds by 5 years after birth. Actual maternal weight followed a sinusoidal pattern: increasing during gestation, decreasing during the first postbirth year, converging with the aging-related progression during the second postbirth year, and then increasing at 2.89 pounds (95% confidence interval 2.23-3.55) annually and diverging upward from the aging-related progression to 168.03 pounds by 5 years after birth. Pregnancy weight gain did not contribute to the aging-related trend, but lifestyle changes of parenthood may later exacerbate the long-term trend. Copyright © 2016 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

  9. Age related shift in the mutation spectra of germline and somatic NF2 mutations: hypothetical role of DNA repair mechanisms

    National Research Council Canada - National Science Library

    Evans, D G R; Maher, E R; Baser, M E

    2005-01-01

    It has been suggested that somatic mutations that accumulate due to an age related decline in the efficiency of DNA repair mechanisms might contribute to the increased incidence of cancer in older people...

  10. Stem cell treatment for age-related neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Nurković J.

    2015-01-01

    Full Text Available The belief in the inability of neurogenesis, that is the inability to create new neurons after embryonic and early postnatal development of the central nervous system, was rejected in the mid-nineties, when the existence of neurogenesis in restricted areas of CNS adult mammals, including humans, was discovered.Transplantation of stem cells or their derivatives into respective tissues or organs is considered as one of the most promising remedies for many incurable diseases.In this review, we summarized current knowledge and present and future perspectives andchallenges regarding stem cells treatment for Parkinson's and Alzheimer's disease, as the most common age-related neurodegenerative diseases.

  11. Investigating the genetic and molecular basis of age-related macular degeneration

    OpenAIRE

    Stanton, Chloe May

    2012-01-01

    Age-related macular degeneration (AMD) is the leading cause of blindness worldwide, affecting an estimated 50 million individuals aged over 65 years. Environmental and genetic risk-factors contribute to the development of AMD. An AMD-risk locus on chromosome 10q26 spans two genes, ARMS2 and HTRA1, and controversy exists as to which variants are responsible for increased risk of disease. Recent work suggests that HTRA1 expression levels are significantly increased in carriers...

  12. Ginkgo biloba extract for age-related macular degeneration.

    Science.gov (United States)

    Evans, Jennifer R

    2013-01-31

    Ginkgo is used in the treatment of peripheral vascular disease and 'cerebral insufficiency'. It is thought to have several potential mechanisms of action including increased blood flow, platelet activating factor antagonism, and prevention of membrane damage caused by free radicals. Vascular factors and oxidative damage are thought to be two potential mechanisms in the pathology of age-related macular degeneration (AMD). The objective of this review was to determine the effect of Ginkgo biloba extract on the progression of AMD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 10), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to October 2012), EMBASE (January 1980 to October 2012), Allied and Complementary Medicine Database (AMED) (January 1985 to October 2012), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 October 2012. We searched the reference lists of identified reports and the Science Citation Index. We also contacted investigators of included studies for additional information. All randomised trials in people with AMD where Ginkgo biloba extract had been compared to control were included. The review author extracted data using a standardised form. The data were verified with the trial investigators. Trial quality was assessed. Two published trials were identified that randomised a total of 119 people. In one study conducted in France, 20 people were randomly allocated to Gingko biloba extract EGb 761 80 mg twice daily or placebo. In

  13. 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.

  14. 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.

  15. 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

  16. 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. © 2013 New York Academy of Sciences.

  17. SOCIETAL COSTS ASSOCIATED WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION IN THE UNITED STATES.

    Science.gov (United States)

    Brown, Melissa M; Brown, Gary C; Lieske, Heidi B; Tran, Irwin; Turpcu, Adam; Colman, Shoshana

    2016-02-01

    The purpose of this study was to use a cross-sectional prevalence-based health care economic survey to ascertain the annual, incremental, societal ophthalmic costs associated with neovascular age-related macular degeneration. Consecutive patients (n = 200) with neovascular age-related macular degeneration were studied. A Control Cohort included patients with good (20/20-20/25) vision, while Study Cohort vision levels included Subcohort 1: 20/30 to 20/50, Subcohort 2: 20/60 to 20/100, Subcohort 3: 20/200 to 20/400, and Subcohort 4: 20/800 to no light perception. An interviewer-administered, standardized, written survey assessed 1) direct ophthalmic medical, 2) direct nonophthalmic medical, 3) direct nonmedical, and 4) indirect medical costs accrued due solely to neovascular age-related macular degeneration. The mean annual societal cost for the Control Cohort was $6,116 and for the Study Cohort averaged $39,910 (P age-related macular degeneration dramatically increase as vision in the better-seeing eye decreases.

  18. Amniotic epithelial cells: a new tool to combat aging and age-related diseases?

    Directory of Open Access Journals (Sweden)

    Clara Di Germanio

    2016-11-01

    Full Text Available The number of elderly people is growing at an unprecedented rate and this increase of the aging population is expected to have a direct impact on the incidence of age-related diseases and healthcare-associated costs. Thus, it is imperative that new tools are developed to fight and slow age-related diseases. Regenerative medicine is a promising strategy for the maintenance of health and function late in life; however, stem cell-based therapies face several challenges including rejection and tumor transformation. As an alternative, the placenta offers an extraordinary source of fetal stem cells, including the amniotic epithelial cells (AECs, which retain some of the characteristics of embryonic stem cells, but show low immunogenicity, together with immunomodulatory and anti-inflammatory activities. Because of these characteristics, AECs have been widely utilized in regenerative medicine. This perspective highlights different mechanisms triggered by transplanted AECs that could be potentially useful for anti-aging therapies, which include: Graft and differentiation for tissue regeneration in age-related settings, anti-inflammatory behavior to combat inflammaging, anti-tumor activity, direct lifespan and healthspan extension properties, and possibly rejuvenation in a manner reminiscent of heterochronic parabiosis.Here, we critically discuss benefits and limitation of AECs-based therapies in age-related diseases.

  19. Protein Oxidative Damage at the Crossroads of Cellular Senescence, Aging, and Age-Related Diseases

    Directory of Open Access Journals (Sweden)

    Martin A. Baraibar

    2012-01-01

    Full Text Available Protein damage mediated by oxidation, protein adducts formation with advanced glycated end products and with products of lipid peroxidation, has been implicated during aging and age-related diseases, such as neurodegenerative diseases. Increased protein modification has also been described upon replicative senescence of human fibroblasts, a valid model for studying aging in vitro. However, the mechanisms by which these modified proteins could impact on the development of the senescent phenotype and the pathogenesis of age-related diseases remain elusive. In this study, we performed in silico approaches to evidence molecular actors and cellular pathways affected by these damaged proteins. A database of proteins modified by carbonylation, glycation, and lipid peroxidation products during aging and age-related diseases was built and compared to those proteins identified during cellular replicative senescence in vitro. Common cellular pathways evidenced by enzymes involved in intermediate metabolism were found to be targeted by these modifications, although different tissues have been examined. These results underscore the potential effect of protein modification in the impairment of cellular metabolism during aging and age-related diseases.

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

    Science.gov (United States)

    Luders, Eileen

    2014-01-01

    A growing body of research suggests that meditation practices are associated with substantial psychological as well as physiological benefits. In searching for the biological mechanisms underlying the beneficial impact of meditation, studies have revealed practice-induced alterations of neurotransmitters, brain activity, and cognitive abilities, just to name a few. These findings not only imply a close link between meditation and brain structure, but also suggest possible modulating effects of meditation on age-related brain atrophy. Given that normal aging is associated with significant loss of brain tissue, meditation-induced growth and/or preservation might manifest as a seemingly reduced brain age in meditators (i.e., cerebral measures characteristic of younger brains). Surprisingly, there are only three published studies that have addressed the question of whether meditation diminishes age-related brain degeneration. This paper reviews these three studies with respect to the brain attributes studied, the analytical strategies applied, and the findings revealed. The review concludes with an elaborate discussion on the significance of existing studies, implications and directions for future studies, as well as the overall relevance of this field of research. © 2013 New York Academy of Sciences.

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

    Science.gov (United States)

    Barnes, Daniel R.

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

  2. 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.

  3. KCNQ channels regulate age-related memory impairment.

    Science.gov (United States)

    Cavaliere, Sonia; Malik, Bilal R; Hodge, James J L

    2013-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Jacob A. Zarling

    2015-11-01

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

  5. KCNQ Channels Regulate Age-Related Memory Impairment

    Science.gov (United States)

    Cavaliere, Sonia; Malik, Bilal R.; Hodge, James J. L.

    2013-01-01

    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. PMID:23638087

  6. Radiation therapy for age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Takagi, Chikako; Mori, Hideo; Akuta, Keizou [Otsu Red Cross Hospital, Shiga (Japan); Yoshimura, Nagahisa

    1998-04-01

    We evaluated the effect of low-dose radiation on age-related macular degeneration in 8 affected eyes. Radiation was applied using photons at 4 MV. Each eye received 10 fractions of 2 Gy per day over 2 weeks. At 6 months after treatment, funduscopic or angiographic findings had either improved or remained unchanged in all the eyes. The visual acuity improved by 2 lines or more in 2 eyes (25%), remained unchanged in 5 eyes (63%) and deteriorated in 1 eye (13%). At the last examination, fundus findings had improved in 2 eyes (25%), remained unchanged in 1 eye (13%) and deteriorated in 5 eyes (63%). The visual acuity had improved or unchanged in 2 eyes each (25%) and deteriorated in 4 eyes (50%). There has been no negative side effects of radiation. Above findings show that low-dose radiation is potentially beneficial for subfoveal or juxtafoveal choroidal neovascularizations in age-related macular degeneration on a short term basis. (author)

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

    Science.gov (United States)

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

    2016-07-01

    Previous work investigating respiratory system mechanics in mice has reported an aging-related increase in compliance and mean linear intercept (Lm). However, these changes were assessed using only a young (2-mo-old) and old (20- and 26-mo-old) group yet were interpreted to reflect a linear evolution across the life span. Therefore, to investigate respiratory system mechanics and lung morphometry across a more complete spectrum of ages, we utilized 2 (100% survival, n = 6)-, 6 (100% survival, n = 12)-, 18 (90% survival, n = 12)-, 24 (75% survival, n = 12)-, and 30 (25% survival, n = 12)-mo-old C57BL/6 mice. We found a nonlinear aging-related decrease in respiratory system resistance and increase in dynamic compliance and hysteresis between 2- and 24-mo-old mice. However, in 30-mo-old mice, respiratory system resistance increased, and dynamic compliance and hysteresis decreased relative to 24-mo-old mice. Respiratory system impedance spectra were measured between 1-20.5 Hz at positive end-expiratory pressures (PEEP) of 1, 3, 5, and 7 cmH2O. Respiratory system resistance and reactance at each level of PEEP were increased and decreased, respectively, only in 2-mo-old animals. No differences in the respiratory system impedance spectra were observed in 6-, 18-, 24-, and 30-mo-old mice. Additionally, lungs were fixed following tracheal instillation of 4% paraformaldehyde at 25 cmH2O and processed for Lm and airway collagen deposition. There was an aging-related increase in Lm consistent with emphysematous-like changes and no evidence of increased airway collagen deposition. Accordingly, we demonstrate nonlinear aging-related changes in lung mechanics and morphometry in C57BL/6 mice. Copyright © 2016 the American Physiological Society.

  8. 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...

  9. 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...

  10. Prevalence of age-related maculopathy and age-related macular degeneration among the inuit in Greenland. The Greenland Inuit Eye Study

    DEFF Research Database (Denmark)

    Andersen, Mads Varis Nis; Rosenberg, Thomas; la Cour, Morten

    2008-01-01

    To examine the age- and gender-specific prevalence and describe the common phenotype of early age-related maculopathy (ARM) and late-stage age-related macular degeneration (AMD) among the Inuit in Greenland....

  11. Superior cervical gangliectomy induces non-exudative age-related macular degeneration in mice.

    Science.gov (United States)

    Dieguez, Hernán H; Romeo, Horacio E; Fleitas, María F González; Aranda, Marcos L; Milne, Georgia; Rosenstein, Ruth E; Dorfman, Damián

    2017-12-28

    Non-exudative age-related macular degeneration, a prevalent cause of blindness, is a progressive and degenerative disease, characterized by alterations in Bruch's membrane, retinal pigment epithelium, and photoreceptors exclusively localized in the macula. Despite there are experimental murine models, the vast majority take too long to develop retinal alterations, which in general are ubiquitous, many result from non-eye specific genetic manipulations, and most do not always reproduce the hallmarks of human age-related macular degeneration. Choroid vessels receive sympathetic innervation from the superior cervical ganglion, which together with the parasympathetic system, regulate the blood flow. Choroid blood flow changes have been involved in age-related macular degeneration development and progression. At present no experimental models take this factor into account. The aim of this work was to analyze the effect of superior cervical gangliectomy on the choroid, Bruch's membrane, retinal pigment epithelium, and retina. Adult male C57BL/6J mice were submitted to unilateral superior cervical gangliectomy and a contralateral sham procedure. Although superior cervical gangliectomy induced ubiquitous choroid and choriocapillaris changes, it induced Bruch's membrane thickening, retinal pigment epithelium melanin content and retinoid isomerohydrolase loss, drusen-like deposit occurrence, and retinal pigment epithelium and photoreceptors atrophy, exclusively localized in the temporal side. Moreover, superior cervical gangliectomy provoked a localized increase in retinal pigment epithelium and photoreceptors apoptosis, and photoreceptors electroretinographic function decline. Therefore, superior cervical gangliectomy recapitulated the main features of human non-exudative age-related macular degeneration, and could become a new experimental model of dry age-related macular degeneration, and a useful platform for developing new therapies. © 2017. Published by The Company of

  12. A multivariate analysis of age-related differences in functional networks supporting conflict resolution.

    Science.gov (United States)

    Salami, Alireza; Rieckmann, Anna; Fischer, Håkan; Bäckman, Lars

    2014-02-01

    Functional neuroimaging studies demonstrate age-related differences in recruitment of a large-scale attentional network during interference resolution, especially within dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). These alterations in functional responses have been frequently observed despite equivalent task performance, suggesting age-related reallocation of neural resources, although direct evidence for a facilitating effect in aging is sparse. We used the multi-source interference task and multivariate partial-least-squares to investigate age-related differences in the neuronal signature of conflict resolution, and their behavioral implications in younger and older adults. There were interference-related increases in activity, involving fronto-parietal and basal ganglia networks that generalized across age. In addition an age-by-task interaction was observed within a distributed network, including DLPFC and ACC, with greater activity during interference in the old. Next, we combined brain-behavior and functional connectivity analyses to investigate whether compensatory brain changes were present in older adults, using DLPFC and ACC as regions of interest (i.e. seed regions). This analysis revealed two networks differentially related to performance across age groups. A structural analysis revealed age-related gray-matter losses in regions facilitating performance in the young, suggesting that functional reorganization may partly reflect structural alterations in aging. Collectively, these findings suggest that age-related structural changes contribute to reductions in the efficient recruitment of a youth-like interference network, which cascades into instantiation of a different network facilitating conflict resolution in elderly people. © 2013. Published by Elsevier Inc. All rights reserved.

  13. Prevalence of age-related maculopathy and age-related macular degeneration among the inuit in Greenland. The Greenland Inuit Eye Study

    DEFF Research Database (Denmark)

    Andersen, Mads Varis Nis; Rosenberg, Thomas; la Cour, Morten

    2008-01-01

    To examine the age- and gender-specific prevalence and describe the common phenotype of early age-related maculopathy (ARM) and late-stage age-related macular degeneration (AMD) among the Inuit in Greenland.......To examine the age- and gender-specific prevalence and describe the common phenotype of early age-related maculopathy (ARM) and late-stage age-related macular degeneration (AMD) among the Inuit in Greenland....

  14. The impact of age-related cataract on measures of frailty in an aging global population.

    Science.gov (United States)

    Fukuoka, Hideki; Afshari, Natalie A

    2017-01-01

    To review the associations among age-related cataract, frailty, and frailty outcomes (e.g., disabilities). It is predicted that the proportion of the population aged 65 and older, in developed and developing nations alike, will rise until at least 2050. The proportion of patients suffering from cataracts and frailty is expected to increase, as are age-related diseases. Although there are many papers reporting on the association between frailty outcomes, cataract, and visual impairment, there is a relative paucity of papers describing associations between frailty markers, cataract, and visual impairment. Reports regarding the relationship between frailty, visual impairment, cataract, and cataract surgery are limited, but gradually increasing. Further research is expected to clarify the mechanism of visual function or the impact of restored vision on frailty. Evidence for the effect of cataract on frailty and frailty outcomes after restoring vision by cataract surgery remains limited.

  15. Redox control of senescence and age-related disease

    Directory of Open Access Journals (Sweden)

    Akshaya Chandrasekaran

    2017-04-01

    Full Text Available The signaling networks that drive the aging process, associated functional deterioration, and pathologies has captured the scientific community's attention for decades. While many theories exist to explain the aging process, the production of reactive oxygen species (ROS provides a signaling link between engagement of cellular senescence and several age-associated pathologies. Cellular senescence has evolved to restrict tumor progression but the accompanying senescence-associated secretory phenotype (SASP promotes pathogenic pathways. Here, we review known biological theories of aging and how ROS mechanistically control senescence and the aging process. We also describe the redox-regulated signaling networks controlling the SASP and its important role in driving age-related diseases. Finally, we discuss progress in designing therapeutic strategies that manipulate the cellular redox environment to restrict age-associated pathology.

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

    Science.gov (United States)

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

    2014-01-01

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

  17. [Age-related white matter lesions (leukoaraiosis): an update].

    Science.gov (United States)

    Miki, Yukio; Sakamoto, Shinichi

    2013-07-01

    Leukoaraiosis (age-related white matter hyperintensities) is the most frequently seen lesion on brain magnetic resonance (MR) images. This lesion is a subject of much current interest, because a number of multicenter studies have revealed that it is associated with various disturbances and poor prognoses. Leukoaraiosis corresponds to various pathologies, including demyelination, apoptosis, edema, dilated perivascular spaces, axonal damage, gliosis, and infarcts. Also noted in leukoaraiosis are changes in small vessels, such as fibrohyalinosis and venous collagenosis. The main cause of leukoaraiosis is thought to be chronic ischemia; other causes include edema and breakdown of the blood-brain barrier. Major risk factors for leukoaraiosis are age and hypertension. Disturbances that are related to leukoaraiosis include stroke, dementia, cognitive impairment, gait disturbance, fall, and depression. Leukoaraiosis is also a risk factor for death. Technologies, such as automatic volumetry, tissue segmentation, diffusion tensor imaging, magnetization tensor imaging, diffusion kurtosis imaging, and ultra-high field MR imaging may provide further insights into leukoaraiosis.

  18. Prevalence of Age-Related Macular Degeneration in Europe

    DEFF Research Database (Denmark)

    Colijn, Johanna M; Buitendijk, Gabriëlle H S; Prokofyeva, Elena

    2017-01-01

    PURPOSE: Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD...... in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. DESIGN: Meta-analysis of prevalence data. PARTICIPANTS: A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe....... METHODS: AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA...

  19. Radiation Therapy for Neovascular Age-related Macular Degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Kishan, Amar U. [Harvard Medical School, Boston, Massachusetts (United States); Modjtahedi, Bobeck S.; Morse, Lawrence S. [Department of Ophthalmology and Vision Sciences, University of California, Davis, Sacramento, California (United States); Lee, Percy, E-mail: percylee@mednet.ucla.edu [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, California (United States)

    2013-03-01

    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.

  20. Risk Factors and Biomarkers of Age-Related Macular Degeneration

    Science.gov (United States)

    Lambert, Nathan G.; Singh, Malkit K.; ElShelmani, Hanan; Mansergh, Fiona C.; Wride, Michael A.; Padilla, Maximilian; Keegan, David; Hogg, Ruth E.; Ambati, Balamurali K.

    2016-01-01

    A biomarker can be a substance or structure measured in body parts, fluids or products that can affect or predict disease incidence. As age-related macular degeneration (AMD) is the leading cause of blindness in the developed world, much research and effort has been invested in the identification of different biomarkers to predict disease incidence, identify at risk individuals, elucidate causative pathophysiological etiologies, guide screening, monitoring and treatment parameters, and predict disease outcomes. To date, a host of genetic, environmental, proteomic, and cellular targets have been identified as both risk factors and potential biomarkers for AMD. Despite this, their use has been confined to research settings and has not yet crossed into the clinical arena. A greater understanding of these factors and their use as potential biomarkers for AMD can guide future research and clinical practice. This article will discuss known risk factors and novel, potential biomarkers of AMD in addition to their application in both academic and clinical settings. PMID:27156982

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

    DEFF Research Database (Denmark)

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

    2002-01-01

    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...... 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...

  2. Age-related differences in multiple task monitoring.

    Directory of Open Access Journals (Sweden)

    Ivo Todorov

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

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

    Science.gov (United States)

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

    2016-08-01

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

  4. Redox control of senescence and age-related disease.

    Science.gov (United States)

    Chandrasekaran, Akshaya; Idelchik, Maria Del Pilar Sosa; Melendez, J Andrés

    2017-04-01

    The signaling networks that drive the aging process, associated functional deterioration, and pathologies has captured the scientific community's attention for decades. While many theories exist to explain the aging process, the production of reactive oxygen species (ROS) provides a signaling link between engagement of cellular senescence and several age-associated pathologies. Cellular senescence has evolved to restrict tumor progression but the accompanying senescence-associated secretory phenotype (SASP) promotes pathogenic pathways. Here, we review known biological theories of aging and how ROS mechanistically control senescence and the aging process. We also describe the redox-regulated signaling networks controlling the SASP and its important role in driving age-related diseases. Finally, we discuss progress in designing therapeutic strategies that manipulate the cellular redox environment to restrict age-associated pathology. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  5. Color vision deficits in intermediate age-related macular degeneration.

    Science.gov (United States)

    Downie, Laura E; Cheng, Ada S; Vingrys, Algis J

    2014-08-01

    To assess the effect of intermediate age-related macular degeneration (AMD) on foveal cone-contrast thresholds. We measured L-M and S-cone-contrast thresholds in subjects with intermediate AMD (n = 10) and age-matched control subjects (n = 10). Monocular, foveal 3-degree Gaussian blobs (600-millisecond raised cosine) were presented at 16 cone ratios throughout L-, M-, and S-cone space, and threshold contours were modeled with probability summation between two independent detection mechanisms. The role that preretinal absorption plays in aging was also evaluated by simulation with FG15 and neutral-density filters. Aging results in loss of neural sensitivity, not explained by lens changes. On average, intermediate AMD was associated with reduced sensitivity in both color and luminance channels (p Eyes with the same phenotype of intermediate AMD can have varying degrees of color threshold loss. Functional markers enhance the clinical definition of disease expression in AMD.

  6. Age-related hyperkyphosis: its causes, consequences, and management.

    Science.gov (United States)

    Katzman, Wendy B; Wanek, Linda; Shepherd, John A; Sellmeyer, Deborah E

    2010-06-01

    Age-related hyperkyphosis is an exaggerated anterior curvature in the thoracic spine that occurs commonly with advanced age. This condition is associated with low bone mass, vertebral compression fractures, and degenerative disc disease, and contributes to difficulty performing activities of daily living and decline in physical performance. While there are effective treatments, currently there are no public health approaches to prevent hyperkyphosis among older adults. Our objective is to review the prevalence and natural history of hyperkyphosis, associated health implications, measurement tools, and treatments to prevent this debilitating condition. Diagnosis/prognosis/therapy, level 5.J Orthop Sports Phys Ther 2010;40(6):352-360, Epub 15 April 2010. doi:10.2519/jospt.2010.3099.

  7. 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...

  8. Age-related stigma and the golden section hypothesis.

    Science.gov (United States)

    Widrick, Rebekah M; Raskin, Jonathan D

    2010-05-01

    The present study used the golden section hypothesis, which predicts that people organize information in a ratio of 61.8% positive to 38.2% negative, to examine age-related identities. It was predicted that people would rate identities of the aging population in accordance with a reverse golden section hypothesis. That is, people would assign negative ratings 61.8% of the time and positive ratings 38.2% of the time. A golden section survey was completed online by 148 participants. Along the top of the survey were 15 identities: child, elderly person, grandparent, middle-aged adult, nurse, musician, adolescent, senior citizen, business person, lawyer, secretary, mental patient, homeless person, retired person, and self. On the left side of the survey were 12 adjective pairs with well-established positive and negative poles: generous-stingy, pleasant-unpleasant, true-false, fair-unfair, active-passive, energetic-lethargic, sharp-dull, excitable-calm, strong-weak, bold-timid, hard-soft, and rugged-delicate. Elderly person and senior citizen were rated in a manner consistent with the reverse golden section hypothesis. In keeping with previous findings, the self was rated positively precisely 71% of the time. Combined ratings of the remaining identities were consistent with the traditional golden section hypothesis. A prior finding that mental patient and homeless person would produce a reverse golden section pattern was not replicated. Certain elderly identities evoke a reverse golden section rating pattern. This suggests that such identities have stigma associated with them. Because American society has coupled aging to stigma, people have come to associate negative connotations with certain age-related terms.

  9. Age-Related Neurochemical Changes in the Vestibular Nuclei

    Directory of Open Access Journals (Sweden)

    Paul eSmith

    2016-03-01

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

  10. 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.

  11. Effects of Age-Related Macular Degeneration on Driving Performance

    Science.gov (United States)

    Wood, Joanne M.; Black, Alex A.; Mallon, Kerry; Kwan, Anthony S.; Owsley, Cynthia

    2018-01-01

    Purpose To explore differences in driving performance of older adults with age-related macular degeneration (AMD) and age-matched controls, and to identify the visual determinants of driving performance in this population. Methods Participants included 33 older drivers with AMD (mean age [M] = 76.6 ± 6.1 years; better eye Age-Related Eye Disease Study grades: early [61%] and intermediate [39%]) and 50 age-matched controls (M = 74.6 ± 5.0 years). Visual tests included visual acuity, contrast sensitivity, visual fields, and motion sensitivity. On-road driving performance was assessed in a dual-brake vehicle by an occupational therapist (masked to drivers' visual status). Outcome measures included driving safety ratings (scale of 1–10, where higher values represented safer driving), types of driving behavior errors, locations at which errors were made, and number of critical errors (CE) requiring an instructor intervention. Results Drivers with AMD were rated as less safe than controls (4.8 vs. 6.2; P = 0.012); safety ratings were associated with AMD severity (early: 5.5 versus intermediate: 3.7), even after adjusting for age. Drivers with AMD had higher CE rates than controls (1.42 vs. 0.36, respectively; rate ratio 3.05, 95% confidence interval 1.47–6.36, P = 0.003) and exhibited more observation, lane keeping, and gap selection errors and made more errors at traffic light–controlled intersections (P < 0.05). Only motion sensitivity was significantly associated with driving safety in the AMD drivers (P = 0.005). Conclusions Drivers with early and intermediate AMD can exhibit impairments in their driving performance, particularly during complex driving situations; motion sensitivity was most strongly associated with driving performance. These findings have important implications for assessing the driving ability of older drivers with visual impairment. PMID:29340641

  12. Exercise boosts hippocampal volume by preventing early age-related gray matter loss.

    Science.gov (United States)

    Fuss, Johannes; Biedermann, Sarah V; Falfán-Melgoza, Claudia; Auer, Matthias K; Zheng, Lei; Steinle, Jörg; Hörner, Felix; Sartorius, Alexander; Ende, Gabriele; Weber-Fahr, Wolfgang; Gass, Peter

    2014-02-01

    Recently, a larger hippocampus was found in exercising mice and men. Here we studied the morphological underpinnings in wheel running mice by longitudinal magnetic resonance imaging. Voxel-based morphometry revealed that running increases hippocampal volume by inhibiting an early age-related gray matter loss. Disruption of neurogenesis-related neuroplasticity by focalized irradiation is sufficient to block positive effects of exercise on macroscopic brain morphology. Copyright © 2013 Wiley Periodicals, Inc.

  13. Age-related macular degeneration: what can a family physician do?

    OpenAIRE

    Latowsky, M L

    1988-01-01

    Age-related macular degeneration (ARMD) is the most common cause of blindness in Canada, and, as the name suggests, its incidence increases rapidly with age. Atrophic maculopathy, one of the forms of ARMD, is associated with only mild to moderate visual loss but is not treatable. On the other hand, exudative maculopathy, another form, is characterized by the formation of neovascular membranes and causes acute visual disturbances; however, it is potentially treatable by means of laser photocoa...

  14. Age-related decline in endurance running performance - an example of a multiple World records holder.

    Science.gov (United States)

    Lepers, Romuald; Cattagni, Thomas

    2018-01-01

    This study examined the age-related decline in endurance running performance of one of the greatest master runners ever, Ed Whitlock, who died recently. His running performances from 1500 m to marathon were analyzed for 5 periods of 5 years from 65-69 years to 85-89 years. Despite exceptional running performances for his advanced age, the rate of decline in his performances increased after 80 years and was drastically amplified after 85 years.

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

    Directory of Open Access Journals (Sweden)

    Kenji Watanabe

    2014-01-01

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

  16. Tryptophan metabolism: entering the field of aging and age-related pathologies.

    Science.gov (United States)

    van der Goot, Annemieke T; Nollen, Ellen A A

    2013-06-01

    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 and increase lifespan. Recent studies in multiple organisms have implicated tryptophan metabolism as a powerful regulator of age-related diseases and lifespan. Its high conservation throughout evolution has enabled studies that begin to dissect the contribution of individual enzymes and metabolites. Here, we focus on the emerging view of tryptophan metabolism as a pathway that integrates environmental and metabolic signals to regulate animal biology and health. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Exercise training as a preventive tool for age-related disorders: a brief review

    Directory of Open Access Journals (Sweden)

    Emmanuel Gomes Ciolac

    2013-05-01

    Full Text Available Aging populations are a worldwide phenomenon affecting both developed and developing countries. This issue raises serious concerns for both governments and the general population. Regular participation in physical activity and/or exercise training programs can minimize the physiological alterations that occur during aging and may contribute to improvements in health and well-being. The present review will discuss the role of regular exercise training in preventing age-related physiological decline and, consequently, associated chronic diseases. Compelling evidence that regular exercise and/or physical activity can improve quality of life, prevent or control the development of chronic disease and increase life expectancy is shown. In summary, regular exercise training and/or physical activity has an important influence on aging and may help to prevent age-related disorders.

  18. Role of Age-Related Shifts in Rumen Bacteria and Methanogens in Methane Production in Cattle

    Directory of Open Access Journals (Sweden)

    Chong Liu

    2017-08-01

    Full Text Available Rumen microbiota are essential for maintaining digestive and metabolic functions, producing methane as a byproduct. Dairy heifers produce large amounts of methane based on fermentation of digested organic matter, with adverse consequences for feed efficiency and the environment. It is therefore important to understand the influence of host age on the relationship between microbiota and methane production. This study explored the age effect on the relationship between microbial communities and enteric methane production in dairy cows and heifers using high-throughput sequencing. Methane production and volatile fatty acid concentrations were age-related. Heifers (9–10 months had lower methane production but higher methane production per dry matter intake (DMI. The acetate:propionate ratio decreased significantly with increasing age. Age-related microbiota changes in the rumen were reflected by a significant shift in bacterial taxa, but relatively stable archaeal taxa. Prevotella, Ruminococcus, Flavonifractor, Succinivibrio, and Methanobrevibacter were affected by age. This study revealed different associations between predominant bacterial phylotypes and Methanobrevibacter with increasing age. Prevotella was strongly correlated with Methanobrevibacter in heifers; howerver, in older cows (96–120 months this association was replaced by a correlation between Succinivibrio and Methanobrevibacter. This shift may account for the age-related difference in rumen fermentation and methane production per DMI.

  19. Role of Age-Related Shifts in Rumen Bacteria and Methanogens in Methane Production in Cattle

    Science.gov (United States)

    Liu, Chong; Meng, Qinghui; Chen, Yongxing; Xu, Mengsi; Shen, Min; Gao, Rui; Gan, Shangquan

    2017-01-01

    Rumen microbiota are essential for maintaining digestive and metabolic functions, producing methane as a byproduct. Dairy heifers produce large amounts of methane based on fermentation of digested organic matter, with adverse consequences for feed efficiency and the environment. It is therefore important to understand the influence of host age on the relationship between microbiota and methane production. This study explored the age effect on the relationship between microbial communities and enteric methane production in dairy cows and heifers using high-throughput sequencing. Methane production and volatile fatty acid concentrations were age-related. Heifers (9–10 months) had lower methane production but higher methane production per dry matter intake (DMI). The acetate:propionate ratio decreased significantly with increasing age. Age-related microbiota changes in the rumen were reflected by a significant shift in bacterial taxa, but relatively stable archaeal taxa. Prevotella, Ruminococcus, Flavonifractor, Succinivibrio, and Methanobrevibacter were affected by age. This study revealed different associations between predominant bacterial phylotypes and Methanobrevibacter with increasing age. Prevotella was strongly correlated with Methanobrevibacter in heifers; howerver, in older cows (96–120 months) this association was replaced by a correlation between Succinivibrio and Methanobrevibacter. This shift may account for the age-related difference in rumen fermentation and methane production per DMI. PMID:28855896

  20. Age-Related Decline of Precision and Binding in Visual Working Memory

    Science.gov (United States)

    2013-01-01

    Working memory declines with normal aging, but the nature of this impairment is debated. Studies based on detecting changes to arrays of visual objects have identified two possible components to age-related decline: a reduction in the number of items that can be stored, or a deficit in maintaining the associations (bindings) between individual object features. However, some investigations have reported intact binding with aging, and specific deficits arising only in Alzheimer’s disease. Here, using a recently developed continuous measure of recall fidelity, we tested the precision with which adults of different ages could reproduce from memory the orientation and color of a probed array item. The results reveal a further component of cognitive decline: an age-related decrease in the resolution with which visual information can be maintained in working memory. This increase in recall variability with age was strongest under conditions of greater memory load. Moreover, analysis of the distribution of errors revealed that older participants were more likely to incorrectly report one of the unprobed items in memory, consistent with an age-related increase in misbinding. These results indicate a systematic decline with age in working memory resources that can be recruited to store visual information. The paradigm presented here provides a sensitive index of both memory resolution and feature binding, with the potential for assessing their modulation by interventions. The findings have implications for understanding the mechanisms underpinning working memory deficits in both health and disease. PMID:23978008

  1. [Impact of cellular senescence on organismal aging and age-related diseases].

    Science.gov (United States)

    Bielak-Zmijewska, Anna; Grabowska, Wioleta; Przybylska, Dorota

    2014-01-01

    Development of the civilization and medicine enables an even longer lifespan of people. To modulate the aging process it is necessary to discover its molecular mechanism and its causes. It has been known for almost 60 years that cells undergo senescence. A lot of markers of senescence have been described to distinguish senescent cells. Every year we can observe an increase in the number of data, supporting the thesis that the reason for aging of the whole organism is cellular senescence. We age because cells building tissues and organs undergo senescence. It is also believed that cellular senescence can increase the frequency of age-related diseases. The role of cellular senescence strictly depends on the age of the individual. In young ones it is essential for: protection against cancer and tissue regeneration. In old ones it causes tissues and organs dysfunctions and leads to age-related diseases. Slowing down aging could prevent age-related diseases and this seems to be more promising than curing them. To enrich our knowledge concerning aging it is important to understand signaling pathways leading to senescence. Recently a new role of cellular senescence has been discovered, namely during embryogenesis. This observation is very surprising and shows a new face of cellular senescence. It is possible that, similarly to the previously described role of apoptosis in embryogenesis, senescence is indispensable for proper organogenesis. Cellular senescence seems to be the universal and fundamental process, the role of which changes during the lifespan.

  2. Physical Activity and Telomere Biology: Exploring the Link with Aging-Related Disease Prevention

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    Andrew T. Ludlow

    2011-01-01

    Full Text Available Physical activity is associated with reduced risk of several age-related diseases as well as with increased longevity in both rodents and humans. Though these associations are well established, evidence of the molecular and cellular factors associated with reduced disease risk and increased longevity resulting from physical activity is sparse. A long-standing hypothesis of aging is the telomere hypothesis: as a cell divides, telomeres shorten resulting eventually in replicative senescence and an aged phenotype. Several reports have recently associated telomeres and telomere-related proteins to diseases associated with physical inactivity and aging including cardiovascular disease, insulin resistance, and hypertension. Interestingly several reports have also shown that longer telomeres are associated with higher physical activity levels, indicating a potential mechanistic link between physical activity, reduced age-related disease risk, and longevity. The primary purpose of this review is to discuss the potential importance of physical activity in telomere biology in the context of inactivity- and age-related diseases. A secondary purpose is to explore potential mechanisms and important avenues for future research in the field of telomeres and diseases associated with physical inactivity and aging.

  3. The application of information theory for the research of aging and aging-related diseases.

    Science.gov (United States)

    Blokh, David; Stambler, Ilia

    2017-10-01

    This article reviews the application of information-theoretical analysis, employing measures of entropy and mutual information, for the study of aging and aging-related diseases. The research of aging and aging-related diseases is particularly suitable for the application of information theory methods, as aging processes and related diseases are multi-parametric, with continuous parameters coexisting alongside discrete parameters, and with the relations between the parameters being as a rule non-linear. Information theory provides unique analytical capabilities for the solution of such problems, with unique advantages over common linear biostatistics. Among the age-related diseases, information theory has been used in the study of neurodegenerative diseases (particularly using EEG time series for diagnosis and prediction), cancer (particularly for establishing individual and combined cancer biomarkers), diabetes (mainly utilizing mutual information to characterize the diseased and aging states), and heart disease (mainly for the analysis of heart rate variability). Few works have employed information theory for the analysis of general aging processes and frailty, as underlying determinants and possible early preclinical diagnostic measures for aging-related diseases. Generally, the use of information-theoretical analysis permits not only establishing the (non-linear) correlations between diagnostic or therapeutic parameters of interest, but may also provide a theoretical insight into the nature of aging and related diseases by establishing the measures of variability, adaptation, regulation or homeostasis, within a system of interest. It may be hoped that the increased use of such measures in research may considerably increase diagnostic and therapeutic capabilities and the fundamental theoretical mathematical understanding of aging and disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. The theory behind the age-related positivity effect

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    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.

  5. AGE RELATED CHANGES OF GFR IN A POPULATION OF KERALA

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    Chitra

    2015-08-01

    Full Text Available BACKGROUND: Glomerular Filtration Rate (GFR is the best index for assessing kidney function. Ethnicity has a potential influence on GFR. Anatomic and physiological changes of ageing kidney influences GFR. AIMS AND OBJECTIVES: To find age related variations of GFR in a population of Kerala. SUBJECTS AND METHODS : A total of 519 subjects of all ages from the community were screened. Blood pressure, diabetes, mellitus, proteinuria, serum creatinine being checked. Estimated GFR (e GFR assessed using modification of diet in renal disease [MDRD formula]. RESULTS: The mean e GFR of the population was found to be 61.2±18.2ml/min. and the e GFR of normal subjects excluding diabetes, mellitus, blood pressure and proteinuria was found to be 64.49±20.5ml/min. e - GFR was more for males compared to females, 67.5± 20ml/min and 55.4±14ml/min respectively. e GFR showed a steady decline as the age advanced and it was statistically significant(p < 0.05 . CONCLUSION: The age adjusted e GFR of kerali te population is much less compared to western standards. A more detailed study in general population is needed

  6. Ocular Surface Temperature in Age-Related Macular Degeneration

    Science.gov (United States)

    Sodi, Andrea; Giacomelli, Giovanni; Corvi, Andrea; Menchini, Ugo

    2014-01-01

    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. PMID:25436140

  7. Multisite Assessment of Aging-Related Tau Astrogliopathy (ARTAG).

    Science.gov (United States)

    Kovacs, Gabor G; Xie, Sharon X; Lee, Edward B; Robinson, John L; Caswell, Carrie; Irwin, David J; Toledo, Jon B; Johnson, Victoria E; Smith, Douglas H; Alafuzoff, Irina; Attems, Johannes; Bencze, Janos; Bieniek, Kevin F; Bigio, Eileen H; Bodi, Istvan; Budka, Herbert; Dickson, Dennis W; Dugger, Brittany N; Duyckaerts, Charles; Ferrer, Isidro; Forrest, Shelley L; Gelpi, Ellen; Gentleman, Stephen M; Giaccone, Giorgio; Grinberg, Lea T; Halliday, Glenda M; Hatanpaa, Kimmo J; Hof, Patrick R; Hofer, Monika; Hortobágyi, Tibor; Ironside, James W; King, Andrew; Kofler, Julia; Kövari, Enikö; Kril, Jillian J; Love, Seth; Mackenzie, Ian R; Mao, Qinwen; Matej, Radoslav; McLean, Catriona; Munoz, David G; Murray, Melissa E; Neltner, Janna; Nelson, Peter T; Ritchie, Diane; Rodriguez, Roberta D; Rohan, Zdenek; Rozemuller, Annemieke; Sakai, Kenji; Schultz, Christian; Seilhean, Danielle; Smith, Vanessa; Tacik, Pawel; Takahashi, Hitoshi; Takao, Masaki; Rudolf Thal, Dietmar; Weis, Serge; Wharton, Stephen B; White, Charles L; Woulfe, John M; Yamada, Masahito; Trojanowski, John Q

    2017-07-01

    Aging-related tau astrogliopathy (ARTAG) is a recently introduced terminology. To facilitate the consistent identification of ARTAG and to distinguish it from astroglial tau pathologies observed in the primary frontotemporal lobar degeneration tauopathies we evaluated how consistently neuropathologists recognize (1) different astroglial tau immunoreactivities, including those of ARTAG and those associated with primary tauopathies (Study 1); (2) ARTAG types (Study 2A); and (3) ARTAG severity (Study 2B). Microphotographs and scanned sections immunostained for phosphorylated tau (AT8) were made available for download and preview. Percentage of agreement and kappa values with 95% confidence interval (CI) were calculated for each evaluation. The overall agreement for Study 1 was >60% with a kappa value of 0.55 (95% CI 0.433-0.645). Moderate agreement (>90%, kappa 0.48, 95% CI 0.457-0.900) was reached in Study 2A for the identification of ARTAG pathology for each ARTAG subtype (kappa 0.37-0.72), whereas fair agreement (kappa 0.40, 95% CI 0.341-0.445) was reached for the evaluation of ARTAG severity. The overall assessment of ARTAG showed moderate agreement (kappa 0.60, 95% CI 0.534-0.653) among raters. Our study supports the application of the current harmonized evaluation strategy for ARTAG with a slight modification of the evaluation of its severity. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

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

    Science.gov (United States)

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

    2015-01-01

    Nitroxide small molecule agents are in development as preventative or therapeutic pharmaceutical drugs for age-related macular degeneration (AMD) and cardiovascular disease, which are two major diseases of aging. These aging diseases are associated with patient genetics, smoking, diet, oxidative stress, and chronic inflammation. Nitroxide drugs preventing aging-, smoking-, high sugar or high fat diet-, or radiation- and other environmental-induced pathophysiological conditions in aging disease are reviewed. Tempol (TP), Tempol Hydroxylamine (TP-H), and TP-H prodrug (OT-551) are evaluated in (1) non-smokers versus smokers with cutaneous microvascular dysfunction, rapidly reversed by cutaneous TP; (2) elderly cancer patients at risk for radiation-induced skin burns or hair loss, prevented by topical TP; and (3) elderly smoker or non-smoker AMD patients at risk for vision loss, prevented by daily eye drops of OT-551. The human data indicates safety and efficacy for these nitroxide drugs. Both TP and TP-H topically penetrate and function in skin or mucosa, protecting and treating radiation burns and hair loss or smoking-induced cutaneous vascular dysfunction. TP and TP-H do not penetrate the cornea, while OT-551 does effectively penetrate and travels to the back of the eye, preserving visual acuity and preserving normal and low light luminance in dry AMD smokers and non-smoker patients. Topical, oral, or injectable drug formulations are discussed. PMID:26594225

  9. Hospitalized cardiovascular diseases in neovascular age-related macular degeneration.

    Science.gov (United States)

    Nguyen-Khoa, Bao-Anh; Goehring, Earl L; Werther, Winifred; Gower, Emily W; Do, Diana V; Jones, Judith K

    2008-09-01

    To compare the incidence rate of hospitalized myocardial infarctions (MIs) and cerebrovascular accidents (CVAs) in subjects with and without neovascular age-related macular degeneration (AMD). A retrospective database cohort study was performed in subjects with neovascular AMD and controls matched for age, sex, geography, and enrollment duration. Healthcare claims for the study period from January 1, 2002, to June 30, 2005, were used to identify subjects and outcomes. Incidence of hospitalized MI and CVA events and rate ratios adjusted for 11 risk factors were calculated. In 7203 subjects with neovascular AMD and 20,208 controls, the rate of MI was 16.2 events per 1000 subjects with neovascular AMD and 23.1 events per 1000 controls. The adjusted rate ratio for MI was 0.58 (95% confidence interval, 0.48-0.72; P < .001) for subjects with neovascular AMD vs controls. The rate of CVA was 14.3 events per 1000 subjects with neovascular AMD and 22.1 events per 1000 controls. The adjusted rate ratio for CVA was 0.56 (95% confidence interval, 0.45-0.70; P < .001). Rates of MI or CVA were significantly lower in subjects with neovascular AMD than in controls. These findings could not be explained by systematic differences in case selection, health care use, or comorbidities, although other possible biases cannot be ruled out.

  10. Automatic age-related macular degeneration detection and staging

    Science.gov (United States)

    van Grinsven, Mark J. J. P.; Lechanteur, Yara T. E.; van de Ven, Johannes P. H.; van Ginneken, Bram; Theelen, Thomas; Sánchez, Clara I.

    2013-03-01

    Age-related macular degeneration (AMD) is a degenerative disorder of the central part of the retina, which mainly affects older people and leads to permanent loss of vision in advanced stages of the disease. AMD grading of non-advanced AMD patients allows risk assessment for the development of advanced AMD and enables timely treatment of patients, to prevent vision loss. AMD grading is currently performed manually on color fundus images, which is time consuming and expensive. In this paper, we propose a supervised classification method to distinguish patients at high risk to develop advanced AMD from low risk patients and provide an exact AMD stage determination. The method is based on the analysis of the number and size of drusen on color fundus images, as drusen are the early characteristics of AMD. An automatic drusen detection algorithm is used to detect all drusen. A weighted histogram of the detected drusen is constructed to summarize the drusen extension and size and fed into a random forest classifier in order to separate low risk from high risk patients and to allow exact AMD stage determination. Experiments showed that the proposed method achieved similar performance as human observers in distinguishing low risk from high risk AMD patients, obtaining areas under the Receiver Operating Characteristic curve of 0.929 and 0.934. A weighted kappa agreement of 0.641 and 0.622 versus two observers were obtained for AMD stage evaluation. Our method allows for quick and reliable AMD staging at low costs.

  11. Radiation therapy for age-related macular degeneration

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Ayako; Honda, Kaoru; Ishibashi, Tatsuro; Shioyama, Yoshiyuki [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1998-11-01

    We evaluated the effects of low-dose radiation on choroidal neovascular membrane (CNV) in age-related macular degeneration (AMD). Since Chakravarthy reported the benefits from administration of low-dose external-beam irradiation for CNV, many studies have demonstrated that irradiation could have a beneficial treatment effect, whereas several reports have not. In our hospital, 12 eyes with AMD received 10 Gy of 4 MV photons and the other 9 eyes received 20 Gy. Another 4 eyes were untreated as control. After 6 months of treatment, visual acuity was maintained in 11 eyes, improved in 5 eyes, and deteriorated in 5 eyes of treated patients. In control group, visual acuity was maintained in 1 eye and deteriorated in 3 eyes. The size of CNV regressed in 10 eyes, remained stationary in 2 eyes and progressed in 2 eyes of treated patients, while in control group CNV regressed in 2 eyes and remained stationary in 1 eye. After 12 months some CNV progressed. Although the present result seems to be better than those in previous reports, whether or not the treatment is beneficial has to be awaited. (author)

  12. 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.

  13. Mood, memory and movement: an age-related neurodegenerative complex?

    Science.gov (United States)

    Granholm, Ann-Charlotte; Boger, Heather; Emborg, Marina E

    2008-07-01

    The following review was constructed as a concept paper based on a recent workshop on neurodegenerative disease sponsored by the National Institute on Aging (NIA), the American Geriatric Society (AGS), and the John A. Hartford Foundation. The meeting was entitled "Thinking, moving and feeling: Common underlying mechanisms? 4(th) Annual Bedside-to-Bench Conference" and had the purpose to connect current basic and clinical findings on common brain-related alterations occurring with aging such as depression, movement disorders, and cognitive decline. Many prominent researchers expressed their opinion on aging and it was revealed that age-related brain dysfunction of any kind seems to share several risk factors and/or pathways. But can something be done to actively achieve "successful aging"? In this review, based largely on the workshop and current literature, we have summarized some of the current theories for depression, movement and cognitive impairment with aging, as well as potential preventive measures. We have also summarized the emerging need for relevant animal models and how these could be developed and utilized.

  14. Assessment of Age-Related Changes in Pediatric Gastrointestinal Solubility.

    Science.gov (United States)

    Maharaj, Anil R; Edginton, Andrea N; Fotaki, Nikoletta

    2016-01-01

    Compound solubility serves as a surrogate indicator of oral biopharmaceutical performance. Between infancy and adulthood, marked compositional changes in gastrointestinal (GI) fluids occur. This study serves to assess how developmental changes in GI fluid composition affects compound solubility. Solubility assessments were conducted in vitro using biorelevant media reflective of age-specific pediatric cohorts (i.e., neonates and infants). Previously published adult media (i.e., FaSSGF, FeSSGF, FaSSIF.v2, and FeSSIF.v2) were employed as references for pediatric media development. Investigations assessing age-specific changes in GI fluid parameters (i.e., pepsin, bile acids, pH, osmolality, etc.) were collected from the literature and served to define the composition of neonatal and infant media. Solubility assessments at 37 °C were conducted for seven BCS Class II compounds within the developed pediatric and reference adult media. For six of the seven compounds investigated, solubility fell outside an 80-125% range from adult values in at least one of the developed pediatric media. This result indicates a potential for age-related alterations in oral drug performance, especially for compounds whose absorption is delimited by solubility (i.e., BCS Class II). Developmental changes in GI fluid composition can result in relevant discrepancies in luminal compound solubility between children and adults.

  15. Cumulative lead exposure and age-related hearing loss: the VA Normative Aging Study.

    Science.gov (United States)

    Park, Sung Kyun; Elmarsafawy, Sahar; Mukherjee, Bhramar; Spiro, Avron; Vokonas, Pantel S; Nie, Huiling; Weisskopf, Marc G; Schwartz, Joel; Hu, Howard

    2010-10-01

    Although lead has been associated with hearing loss in occupational settings and in children, little epidemiologic research has been conducted on the impact of cumulative lead exposure on age-related hearing loss in the general population. We determined whether bone lead levels, a marker of cumulative lead exposure, are associated with decreased hearing ability in 448 men from the Normative Aging Study, seen between 1962 and 1996 (2264 total observations). Air conduction hearing thresholds were measured at 0.25-8 kHz and pure-tone averages (PTA) (mean of 0.5, 1, 2 and 4 kHz) were computed. Tibia and patella lead levels were measured using K X-ray fluorescence between 1991 and 1996. In cross-sectional analyses, after adjusting for potential confounders including occupational noise, patella lead levels were significantly associated with poorer hearing thresholds at 2, 3, 4, 6 and 8 kHz and PTA. The odds of hearing loss significantly increased with patella lead levels. We also found significant positive associations between tibia lead and the rate change in hearing thresholds at 1, 2, and 8 kHz and PTA in longitudinal analyses. Our results suggest that chronic low-level lead exposure may be an important risk factor for age-related hearing loss and reduction of lead exposure could help prevent or delay development of age-related hearing loss.

  16. Therapeutic potential of eccentric exercises for age-related muscle atrophy

    Directory of Open Access Journals (Sweden)

    Jae-Young Lim

    2016-09-01

    Full Text Available Recent studies have focused on evidence-based interventions to prevent mobility decline and enhance physical performance in older adults. Several modalities, in addition to traditional strengthening programs, have been designed to manage age-related functional decline more effectively. In this study, we reviewed the current relevant literatures to assess the therapeutic potential of eccentric exercises for age-related muscle atrophy (sarcopenia. Age-related changes in human skeletal muscle, and their relationship with physical performance, are discussed with reference to in vitro physiologic and human biomechanics studies. An overview of issues relevant to sarcopenia is provided in the context of the recent consensus on the diagnosis and management of the condition. A decline in mobility among the aging population is closely linked with changes in the muscle force–velocity relationship. Interventions based specifically on increasing velocity and eccentric strength can improve function more effectively compared with traditional strengthening programs. Eccentric strengthening programs are introduced as a specific method for improving both muscle force and velocity. To be more effective, exercise interventions for older adults should focus on enhancing the muscle force–velocity relationship. Exercises that can be performed easily, and that utilize eccentric strength (which is relatively spared during the aging process, are needed to improve both muscle force and velocity.

  17. Impact of age-related neuroglial cell responses on hippocampal deterioration

    Directory of Open Access Journals (Sweden)

    Joseph O Ojo

    2015-04-01

    Full Text Available Aging is one of the greatest risk factors for the development of sporadic age-related neurodegenerative diseases and neuroinflammation is a common feature of this disease phenotype. In the immunoprivileged brain, neuroglial cells, which mediate neuroinflammatory responses, are influenced by the physiological factors in the microenvironment of the central nervous system (CNS. These physiological factors include but are not limited to cell-to-cell communication involving cell adhesion molecules, neuronal electrical activity and neurotransmitter and neuromodulator action. However, despite this dynamic control of neuroglial activity, in the healthy aged brain there is an alteration in the underlying neuroinflammatory response notably seen in the hippocampus, typified by astrocyte/microglia activation and increased pro-inflammatory cytokine production and signalling. Normally, these changes occur without any concurrent pathology, however, they can correlate with deteriorations in hippocampal or cognitive function. In this review we examine two important phenomenons, firstly the relationship between age-related brain deterioration (focusing on hippocampal function and underlying neuroglial response(s, and secondly how the latter affects molecular and cellular processes within the hippocampus that makes it vulnerable to age-related cognitive decline.

  18. Gadd45 proteins: relevance to aging, longevity and age-related pathologies.

    Science.gov (United States)

    Moskalev, Alexey A; Smit-McBride, Zeljka; Shaposhnikov, Mikhail V; Plyusnina, Ekaterina N; Zhavoronkov, Alex; Budovsky, Arie; Tacutu, Robi; Fraifeld, Vadim E

    2012-01-01

    The Gadd45 proteins have been intensively studied, in view of their important role in key cellular processes. Indeed, the Gadd45 proteins stand at the crossroad of the cell fates by controlling the balance between cell (DNA) repair, eliminating (apoptosis) or preventing the expansion of potentially dangerous cells (cell cycle arrest, cellular senescence), and maintaining the stem cell pool. However, the biogerontological aspects have not thus far received sufficient attention. Here we analyzed the pathways and modes of action by which Gadd45 members are involved in aging, longevity and age-related diseases. Because of their pleiotropic action, a decreased inducibility of Gadd45 members may have far-reaching consequences including genome instability, accumulation of DNA damage, and disorders in cellular homeostasis - all of which may eventually contribute to the aging process and age-related disorders (promotion of tumorigenesis, immune disorders, insulin resistance and reduced responsiveness to stress). Most recently, the dGadd45 gene has been identified as a longevity regulator in Drosophila. Although further wide-scale research is warranted, it is becoming increasingly clear that Gadd45s are highly relevant to aging, age-related diseases (ARDs) and to the control of life span, suggesting them as potential therapeutic targets in ARDs and pro-longevity interventions. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Age-related relative volume preservation of the dominant hand cortical region.

    Science.gov (United States)

    Bonilha, Leonardo; Eckert, Mark A; Fridriksson, Julius; Hirth, Victor A; Moser, Dana; Morgan, Paul S; Rorden, Chris

    2009-12-11

    Aging is usually associated with a progressive difficulty in learning new skills. Similarly, the dexterity in the non-dominant hand is usually decreased with age, while the dominant hand maintains a relative preservation in agility. We investigated if age-related volume loss affects the hand areas asymmetrically by comparing structural measures of the dominant hand area versus the non-dominant area. We performed a region of interest analysis of T1-weighted images focusing on the sensorimotor cortex corresponding to the hand area. We evaluated images from young subjects (younger than 65 years of age, n=38, mean age=24+/-7 years) and senior subjects (65 years or older, n=61, mean age =73+/-6 years). We observed that older adults exhibited greater leftward gray matter asymmetry of sensorimotor cortex, due in large part to more pronounced age-related loss of gray matter in the right hemisphere. These results are consistent with evidence that disuse leads to atrophy and suggest that age-related declines in gray matter, and perhaps function, may be limited by increasing the use of the non-dominant hand.

  20. High Cognitive Reserve is associated with a reduced age-related deficit in spatial conflict resolution.

    Directory of Open Access Journals (Sweden)

    Olga ePuccioni

    2012-12-01

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

  1. Effects of Caloric Restriction on Age-Related Hearing Loss in Rodents and Rhesus Monkeys

    Science.gov (United States)

    Someya, Shinichi; Tanokura, Masaru; Weindruch, Richard; Prolla, Tomas A.; Yamasoba, Tatsuya

    2014-01-01

    Age-related hearing loss (AHL), also known as presbycusis, is a universal feature of mammalian aging and is the most frequently occurring sensory disorder in the elderly population. AHL is characterized by a decline of auditory function and loss of hair cells and spiral ganglion neurons in the cochlea of the inner ear. It has been postulated that AHL occurs gradually as a result of the cumulative effect with aging of exposure to noise, diet, oxidative damage, and mitochondrial DNA mutations. However, the molecular mechanisms of AHL remain unclear and no preventative or therapeutic interventions have been developed. A growing body of evidence suggests increased oxidative damage with aging to macromolecules such as DNA, proteins, and lipids may play a causal role in aging and age-related diseases. Caloric restriction (CR) extends the lifespan of most mammalian species, delays the onset of multiple age-related diseases, and attenuates both the degree of oxidative damage and the associated decline in physiological function. Here, we review studies on CR’s ability to prevent cochlear pathology and AHL in laboratory animals and discuss potential molecular mechanisms of CR’s actions. PMID:20298166

  2. Ageing of the bony orbit is a major cause of age-related intraorbital fat herniation.

    Science.gov (United States)

    Kim, Junhyung; Park, Sang Woo; Choi, Jaehoon; Jeong, Woonhyeok; Lee, Seongwon

    2017-11-28

    We evaluated the relationship between infraorbital fat herniation and age-related changes in the bony orbit and orbital fat density using computed tomography. Two hundred and sixty-five patients were enrolled (60 patients were evaluated for changes in the bony orbit and 205 for changes in orbital fat density). Five measurements using parasagittal sections and one measurement using three-dimensional images were obtained. Intraorbital fat herniation length was positively correlated with orbital rim inclination. Lowering of the inferior orbital rim, which is connected to the orbicularis retaining ligament, tear trough ligament and orbital septum, can cause mechanical stretching of the lower eyelid and may contribute to infraorbital fat herniation. A strong and significant negative correlation was observed between orbital fat density and age, indicating that existing orbital fat can accommodate an enlargement in bony orbit volume without orbital fat hyperplasia/hypertrophy. In other words, an increased orbital fat volume may be a by-product of the adaptation of orbital fat to changes in bony orbit volume. Mechanical stretching of the lower eyelid due to ageing of the bony orbit and weakening of the lower eyelid due to age-related factors such as dermal/fat/muscle atrophy and loss of muscle tone can together result in anterior drooping of the lower eyelid. Therefore, age-related changes in the bony orbit contribute to intraorbital fat herniation. Copyright © 2017 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  3. Ignorance is bliss: women's knowledge regarding age-related pregnancy risks.

    Science.gov (United States)

    Sheinis, Michal; Carpe, Nicole; Gold, Shira; Selk, Amanda

    2017-10-12

    Pregnancy risks rise with age and the average age of first time mothers is rising. This study aimed to assess women's actual knowledge and their perceived knowledge of pregnancy complications relating to advanced maternal age. A cross-sectional survey was administered to primiparous women measuring demographics, knowledge of age-related pregnancy risks, previous counselling and health literacy. Of the 218 women surveyed, the mean knowledge score was not significantly different for women difference in knowledge between the two groups, women ≥35 years of age perceived themselves to be more knowledgeable than those under 35 (p informing them of their increased risk of complications if they begin childbearing at older ages. Impact statement What is already known on this subject: The average age of first time mothers is rising worldwide. Pregnancy risks rise with age, especially in first time mothers. Previous studies have shown that knowledge of age-related pregnancy risks correlate with educational level and health literacy. What the results of this study add: This study supports those findings and also demonstrates that perceived knowledge does not correlate with measured knowledge of age-related pregnancy risks. Women ≥35 years of age (higher-risk women) are no more knowledgeable than their younger counterparts though they perceive themselves to be better informed. Greater education regarding these risks may allow women to mitigate some of these risks through lifestyle and diet alteration and will prepare women for what to expect if these risks and complications occur. The majority of women in this study seek pregnancy information on the internet, but desire further counselling from their doctors regarding age-related pregnancy risks. What the implications are of these findings for clinical practice and/or further research: Given these results, physicians must consider making greater efforts to counsel women about pregnancy risks in advanced maternal age and

  4. 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.

  5. Evaluation of curriculum to improve health professionals' ability to manage age-related driving impairments.

    Science.gov (United States)

    Hill, Linda L; Rybar, Jill; Styer, Tara

    2013-12-01

    As our elderly population increases in proportion with respect to the rest of society, age-related driving impairments are increasing in importance as a public health concern. In this context, health professionals play an important role in identifying impaired drivers. This situation is complicated for two reasons: discussion of driving cessation is a sensitive topic for both health professionals and the elderly, and physicians have limited familiarity with the current American Medical Association (AMA) screening guidelines or mandated reporting laws. To assess curriculum that trains health professionals to increase their awareness, screening, management, and reporting of age-related driving impairments. Between 2009 and September 2011, 47 trainings were delivered to 1202 health professionals. The majority of trainings were seminars or lectures lasting 1h; all were conducted in southern California. The training curriculum was divided into four sections: introduction and background; screening and interpretation; managing outcomes and reporting; and referrals and resources. Videos addressed broaching the topic with patients and counseling on driving cessation. The curriculum was delivered by physicians with the support of public health-trained program staff. Pre- and post-testing was done with 641 of the participants; the majority were physicians. Post-training, participants' confidence in ability to screen increased to 72% and intent to screen increased to 55%. Fully 92% stated they had developed a better understanding of California's mandated reporting laws. Similarly, 92% said they had developed a better understanding of the medical conditions and medications that may impair older adults' ability to drive safely. Furthermore, 91% said mandated-reporting laws helped protect the safety of patients and others, and 59% said it was easier to discuss and justify driving cessation with patients. In-person training of health professionals on age-related driving

  6. Aflibercept in exudative age related macular degeneration refractory to ranibizumab.

    Science.gov (United States)

    Ruiz Ramos, J; Pascual-Camps, I; Cuéllar-Monreal, M J; Dolz-Marco, R; Fenoll, M A; Font-Noguera, I; Poveda-Andrés, J L; Gallego-Pinazo, R

    2015-12-01

    The aim of this study is to determine the effectiveness, safety and cost of aflibercept in the treatment of wet age-related macular degeneration (ARMD) refractory to ranibizumab. Retrospective observational study was conducted on patients diagnosed with wet ARMD, and previously treated with ranibizumab. Efficacy variables assessed were changes in visual acuity (BCVA) and anatomical improvements in the most affected eye. Factors associated with improvement of BCVA with aflibercept were also studied. Adverse events related to the aflibercept administration were recorded. Cost analysis data were collected from the hospital perspective, and only taking the direct medical costs into account. Cost-effectiveness analysis was calculated using the aflibercept treatment cost, and effectiveness calculated as BCVA gained. A total of 50 eyes corresponding to 46 patients were included. The median follow-up period was 4.6 months (range: 1.0-6.0). Improvement in visual acuity after the first 2 doses and at the end of the follow-up period was observed in 32.0 and 28.0% of treated eyes, respectively. None of the variables studied was associated with an improvement in the BCVA after treatment. No significant differences were found in the average monthly cost between treatments. Aflibercept is shown to be an effective treatment in a significant number of patients resistant to treatment with ranibizumab, presenting a cost similar to that generated during the final stages of treatment with ranibizumab. Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  7. Age-related distance esotropia: Clinical features and therapeutic outcomes.

    Science.gov (United States)

    Gómez de Liaño Sánchez, P; Olavarri González, G; Merino Sanz, P; Escribano Villafruela, J C

    2016-12-01

    To describe the clinical characteristics and surgical outcomes of a group of patients with age-related distance esotropia (ARDE). A retrospective study was conducted on a consecutive case series of 16 adult patients diagnosed with ARDE between 2008 and 2015. The clinical features evaluated included mean age and gender, primary position deviations at distance and near, measured in prism dioptres (pd), treatment offered in each case, and post-surgical deviations. Ductions and versions were full, with no evidence of lateral rectus paresis. None of these patients had any obvious underlying neurological disorder, such as, high myopia or thyroid disease. A good result is considered to be the disappearance of diplopia in all positions of gaze. A total of 16 patients (11 females [68.8%]) were identified. The mean age at diagnosis was 78.19±6.77 years. The mean initial esodeviation was 2.25±3.08 pd at near (-4 to +8 pd) and 9.5±4.18 pd at distance (2 to 18 pd). Treatment was not necessary in 5 cases because the symptoms were intermittent or well-tolerated. Of the 11 patients with symptoms, one was corrected with an external base therapeutic prism. Botulinum toxin was administered in another patient, without satisfactory results. Unilateral medial rectus muscle recession was performed on one patient, and unilateral lateral rectus plication on 7 patients, indicating prisms before surgery. One patient refused surgery despite continuous diplopia in far vision. After a mean follow-up of 16.5 months, all operated patients were asymptomatic. Not all patients with ARDE require treatment, as the tolerance to diplopia varies from one subject to another. Both medial rectus weakening and lateral rectus strengthening provides excellent results. Crown Copyright © 2016. Publicado por Elsevier España, S.L.U. All rights reserved.

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

    Science.gov (United States)

    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

    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

  9. 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

  10. Chlamydia infection status, genotype, and age-related macular degeneration

    Science.gov (United States)

    Khandhadia, Sam; Foster, Sebastian; Cree, Angela; Griffiths, Helen; Osmond, Clive; Goverdhan, Srinivas

    2012-01-01

    Purpose To evaluate whether Chlamydia (C.) infections are associated with age-related macular degeneration (AMD) and to assess if this association is influenced by the complement factor H (CFH) Y402H or the high temperature requirement A serine peptidase 1 (HTRA1) rs11200638 risk genotypes. Methods One hundred ninety-nine AMD patients with early and late forms of the disease and 100 unaffected controls, at least 50 years old were included in the study. Patients in the AMD and control groups were selected based on known CFH Y402H variant genotype status (one third homozygous CC, one third heterozygous CT, and one third wild-type TT). Plasma from all patients and controls was tested for C. pneumoniae, C. trachomatis, and C. psittaci IgG seropositivity using a micro-immunofluorescent assay to establish previous infection status. Assays were conducted blind to risk genotypes and the results analyzed using univariate and multivariate (logistic regression) analysis. Results IgG seropositivity to C. pneumoniae was most prevalent (69.2%, n=207), followed by C. trachomatis (7.4%, n=22) and C. psittaci (3.3%, n=10). No association was found between each of the three Chlamydia species IgG seropositivity and AMD status or severity (early/late). There was also no significant association between Chlamydia species IgG seropositivity and AMD status or severity, in patients carrying at least one CFH Y402H risk allele (C) or HTRA1 rs11200638 risk allele (A), with univariate or logistic regression analysis. Conclusions Chlamydia infection status does not appear to be associated with AMD status or severity. The presence of CFH Y402H and HTRA1 rs11200638 risk genotypes does not alter this negative association. PMID:22259222

  11. Gluten intolerance: gender- and age-related differences in symptoms.

    Science.gov (United States)

    Bardella, Maria Teresa; Fredella, Clara; Saladino, Valeria; Trovato, Cristina; Cesana, Bruno Mario; Quatrini, Maurizio; Prampolini, Luigia

    2005-01-01

    Gluten intolerance is a common, immunologically mediated disorder with a widely variable clinical presentation that affects genetically predisposed subjects. Women seem to be more frequently affected although data on sex differences are poor. In this study the prevalence of different clinical pictures according to sex and age is analysed in a large series of patients. A total of 1436 patients with gluten intolerance were retrospectively considered, diagnosed from January 1975 to August 2001 based on compatible small-bowel biopsy and response to a gluten-free diet, plus immunofluorescent detection of granular IgA in papillary derma for dermatitis herpetiformis. The clinical picture at onset (classic, non-classic, silent) and age at diagnosis ( 2 and 14 years) was recorded; 362 parents of coeliac probands undergoing a familial screening were also studied. The relations among sex, age class and symptoms were analysed using the chi2 test with Yates's correction. The overall female/male ratio was 2.3:1 but the inter-sex difference was significant only when the diagnosis was made in adulthood where a significant association between iron-deficiency anaemia as manifestation at onset in adult women (34% versus 7%) was found. Low weight, dyspepsia and hypertransaminasaemia were more common in adult men than women (20%, 14% and 7% versus 13%, 3% and 2%, respectively). Dermatitis herpetiformis was present more frequently in men (16% versus 9%). The prevalence of silent cases was 6% in men and 3% in women. Familial screening showed the same prevalence (9.3%) of current coeliac disease in fathers and mothers. Diagnosis of coeliac disease is more frequent in women but physicians' awareness of sex- and age-related differences in clinical presentation could improve diagnostic performances in men.

  12. 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

  13. 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.

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

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    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.

  15. Age-related differences in perceptuomotor procedural learning in children.

    Science.gov (United States)

    Lejeune, Caroline; Catale, Corinne; Schmitz, Xavier; Quertemont, Etienne; Meulemans, Thierry

    2013-10-01

    Procedural learning is generally considered to proceed in a series of phases, with cognitive resources playing an important role during the initial step. From a developmental perspective, little is known about the development of procedural learning or the role played by explicit cognitive processes during learning. The main objectives of this study were (a) to determine whether procedural learning performance improves with age by comparing groups of 7-year-old children, 10-year-old children, and adults and (b) to investigate the role played by executive functions during the acquisition in these three age groups. The 76 participants were assessed on a computerized adaptation of the mirror tracing paradigm. Results revealed that the youngest children had more difficulty in adapting to the task (they were slower and committed more errors at the beginning of the learning process) than 10-year-olds, but despite this age effect observed at the outset, all children improved performance across trials and transferred their skill to a different figure as well as adults. Correlational analyses showed that inhibition abilities play a key role in the performance of 10-year-olds and adults at the beginning of the learning but not in that of 7-year-olds. Overall, our results suggest that the age-related differences observed in our procedural learning task are at least partly due to the differential involvement of inhibition abilities, which may facilitate learning (so long as they are sufficiently developed) during the initial steps of the learning process; however, they would not be a necessary condition for skill learning to occur. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Static and flicker perimetry in age-related macular degeneration.

    Science.gov (United States)

    Luu, Chi D; Dimitrov, Peter N; Wu, Zhichao; Ayton, Lauren N; Makeyeva, Galina; Aung, Khin-Zaw; Varsamidis, Mary; Robman, Luba; Vingrys, Algis J; Guymer, Robyn H

    2013-05-01

    The relationship between clinical severity of age-related macular degeneration (AMD) and macular function has not been well established. In this study, we investigated the correlation between clinical severity and functional deficits as detected by static and flicker perimetry. This cross-sectional study consisted of 279 AMD subjects and 24 control participants. AMD subjects were allocated into 1 of 10 AMD severity groups depending on the status of the designated study eye and the fellow eye, as assessed by color fundus photographs. Visual acuity, and static and flicker perimetry were tested on one eye during the same session. The geometric means, SDs, and percentage of abnormal eyes of static and flicker sensitivity of each AMD severity group were determined and compared. The pattern of change in sensitivity and percentage of abnormal eyes for static perimetry across all AMD severity groups were similar to flicker perimetry. Eyes with drusen > 125 μm (P[static] = 0.018, P[flicker] = 0.024), drusenoid epithelial detachment (P[static and flicker] static and flicker] static and flicker sensitivities compared to normal eyes. Static (β-coefficient -1.59, 95% confidence interval [CI] -4.78-1.60) and flicker (β-coefficient -1.29, 95% CI -4.66-2.08) sensitivities declined at a similar rate in eyes that showed clinical signs of progression. Static and flicker perimetry were affected similarly across the spectrum of AMD severity, and methods appeared to be valid techniques for assessing retinal sensitivity in AMD once drusen > 125 μm are present, but before the development of late AMD.

  17. Systemic and Ocular Long Pentraxin 3 in Patients with Age-Related Macular Degeneration

    DEFF Research Database (Denmark)

    Juel, Helene Bæk; Faber, Carsten; Fog, Lea Munthe

    2015-01-01

    Age-related macular degeneration (AMD) has been associated with both systemic and ocular alterations of the immune system. In particular dysfunction of complement factor H (CFH), a soluble regulator of the alternative pathway of the complement system, has been implicated in AMD pathogenesis. One......CRP or CFH genotype. The gene expression of PTX3 increased in RPE/choroid with age (P=0.0098 macular; P=0.003 extramacular), but did not differ between aged controls and AMD patients. In vitro, ARPE-19 cells increased expression of the PTX3 gene as well PTX3 apical secretions after stimulation with TNF...

  18. Computational explorations of the influence of structured knowledge on age-related cognitive decline.

    Science.gov (United States)

    Mireles, David E; Charness, Neil

    2002-06-01

    Experience in a domain can sometimes offset cognitive declines that occur with aging. Using a series of neural network simulations of learning chess opening positions, the authors investigated how structured knowledge in a distributed representation may influence age-related declines. Aging manipulations implemented as modulations of neural noise showed increased knowledge as being protective of performance on a chess memory span task, whereas changes in neural plasticity and neural loss lead to main effects without interactions and steeper declines for the initially more able. The models could also simulate the increase in variability in older groups.

  19. Hypothyroidism: age-related influence on cardiovascular nitric oxide system in rats.

    Science.gov (United States)

    Sarati, Lorena I; Martinez, Carla R; Artés, Nicolás; Arreche, Noelia; López-Costa, Juan J; Balaszczuk, Ana M; Fellet, Andrea L

    2012-09-01

    This study investigates whether changes in nitric oxide (NO) production participate in the cardiovascular manifestations of hypothyroidism and whether these changes are age-related. Sprague-Dawley rats aged 2 and 18 months old were treated with 0.02% methimazole (wt/vol) during 28 days. Left ventricular function was evaluated by echocardiography. Measurements of arterial blood pressure, heart rate, nitric oxide synthase (NOS) activity and NOS/caveolin-1 and -3 protein levels were performed. Hypothyroidism enhanced the age-related changes in heart function. Hypothyroid state decreased atrial NOS activity in both young and adult rats, associated with a reduction in protein levels of the three NOS isoforms in young animals and increased caveolin (cav) 1 expression in adult rats. Ventricle and aorta NOS activity increased in young and adult hypothyroid animals. In ventricle, changes in NOS activity were accompanied by an increase in inducible NOS isoform in young rats and by an increase in caveolins expression in adult rats. Greater aorta NOS activity level in young and in adult Hypo rats would derive from the inducible and the endothelial NOS isoform, respectively. Thyroid hormones would be one of the factors involved in the modulation of cardiovascular NO production and caveolin-1 and -3 tissue-specific abundance, regardless of age. Hypothyroidism appears to contribute in a differential way to aging-induced changes in the myocardium and aorta tissues. Low thyroid hormones levels would enhance the aging effect on the heart. Age-related changes in NO production participate in the cardiovascular manifestations of hypothyroidism. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Age-related changes in the fracture resistance of male Fischer F344 rat bone.

    Science.gov (United States)

    Uppuganti, Sasidhar; Granke, Mathilde; Makowski, Alexander J; Does, Mark D; Nyman, Jeffry S

    2016-02-01

    In addition to the loss in bone volume that occurs with age, there is a decline in material properties. To test new therapies or diagnostic tools that target such properties as material strength and toughness, a pre-clinical model of aging would be useful in which changes in bone are similar to those that occur with aging in humans. Toward that end, we hypothesized that similar to human bone, the estimated toughness and material strength of cortical bone at the apparent-level decreases with age in the male Fischer F344 rat. In addition, we tested whether the known decline in trabecular architecture in rats translated to an age-related decrease in vertebra (VB) strength and whether non-X-ray techniques could quantify tissue changes at micron and sub-micron length scales. Bones were harvested from 6-, 12-, and 24-month (mo.) old rats (n=12 per age). Despite a loss in trabecular bone with age, VB compressive strength was similar among the age groups. Similarly, whole-bone strength (peak force) in bending was maintained (femur) or increased (radius) with aging. There was though an age-related decrease in post-yield toughness (radius) and bending strength (femur). The ability to resist crack initiation was actually higher for the 12-mo. and 24-mo. than for 6-mo. rats (notch femur), but the estimated work to propagate the crack was less for the aged bone. For the femur diaphysis region, porosity increased while bound water decreased with age. For the radius diaphysis, there was an age-related increase in non-enzymatic and mature enzymatic collagen crosslinks. Raman spectroscopy analysis of embedded cross-sections of the tibia mid-shaft detected an increase in carbonate subsitution with advanced aging for both inner and outer tissue. Published by Elsevier Inc.

  1. Deficiency of circadian protein CLOCK reduces lifespan and increases age-related cataract development in mice

    OpenAIRE

    Dubrovsky, Yuliya V.; Samsa, William E.; Kondratov, Roman V.

    2010-01-01

    Circadian clock is implicated in the regulation of aging. The transcription factor CLOCK, a core component of the circadian system, operates in complex with another circadian clock protein BMAL1. Recently it was demonstrated that BMAL1 deficiency results in premature aging in mice. Here we investigate the aging of mice deficient for CLOCK protein. Deficiency of the CLOCK protein significantly affects longevity: the average lifespan of Clock−/− mice is reduced by 15% compared with wild type mi...

  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

  3. Wistar rats: A forgotten model of age-related hearing loss

    Directory of Open Access Journals (Sweden)

    Juan Carlos eAlvarado

    2014-03-01

    Full Text Available Age-related hearing loss (ARHL is one of the most frequent sensory impairments in senescence and is a source of important socio-economic consequences. Understanding the pathological responses that occur in the central auditory pathway of patients who suffer from this disability is vital to improve its diagnosis and treatment. Therefore, the goal of this study was to characterize age-related modifications in auditory brainstem responses (ABR and to determine whether these functional responses might be accompanied by an imbalance between excitation and inhibition in the cochlear nucleus of Wistar rats. To do so, ABR recordings at different frequencies and immunohistochemistry for the vesicular glutamate transporter 1 (VGLUT1 and the vesicular GABA transporter (VGAT in the ventral cochlear nucleus (VCN were performed in young, middle-aged and old male Wistar rats. The results demonstrate that there was a significant increase in the auditory thresholds, a significant decrease in the amplitudes and an increase in the latencies of the ABR waves as the age of the rat increased. Additionally, there were decreases in VGLUT1 and VGAT immunostaining in the VCN of older rats compared to younger rats. Therefore, the observed age-related decline in the magnitude of auditory evoked responses might be due in part to a reduction in markers of excitatory function; meanwhile, the concomitant reduction in both excitatory and inhibitory markers might reflect a common central alteration in animal models of ARLH. Together, these findings highlight the suitability of the Wistar rat as an excellent model to study ARHL.

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

    Directory of Open Access Journals (Sweden)

    Nicholas O. Thomas

    2016-12-01

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

  5. 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.

  6. 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

    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...... 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

  7. N-acetylcarnosine (NAC) drops for age-related cataract.

    Science.gov (United States)

    Dubois, Vincent Dj-P; Bastawrous, Andrew

    2017-02-28

    any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 28 June 2016. We handsearched the American Society of Cataract and Refractive Surgery (ASCRS) and the European Society of Cataract and Refractive Surgeons (ESCRS) meetings from 2005 until September 2015. We planned to include randomized or quasi-randomised controlled trials where NAC was compared to control in people with age-related cataract. We used standard methodological procedures expected by Cochrane. We identified two potentially eligible studies from Russia and the United States. One study was split into two arms: the first arm ran for six months, with two-monthly follow-up; the second arm ran for two years with six-monthly follow-up. The other study ran for four months with a data collection point at the start and end of the study only. A total of 114 people were enrolled in these studies. The ages ranged from 55 to 80 years.We were unable to obtain sufficient information to reliably determine how both these studies were designed and conducted. We have contacted the author of these studies, but have not yet received a reply. Therefore, these studies are assigned as 'awaiting classification' in the review until sufficient information can be obtained from the authors. There is currently no convincing evidence that NAC reverses cataract, nor prevents progression of cataract (defined as a change in cataract appearance either for the better or for the worse). Future studies should be randomized, double-masked, placebo-controlled trials with standardised quality of life outcomes and validated outcome measures in terms of visual acuity, contrast sensitivity and glare, and large enough to detect adverse effects.

  8. Risk factors for age-related maculopathy in a 14-year follow-up study

    DEFF Research Database (Denmark)

    Hesgaard, Helena; Vinding, Troels; la Cour, Morten

    2005-01-01

    To examine the association between potential risk factors and the 14-year incidence of age-related maculopathy (ARM).......To examine the association between potential risk factors and the 14-year incidence of age-related maculopathy (ARM)....

  9. 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....

  10. 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

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

    Science.gov (United States)

    Chong, Elaine W; Wang, Yuanyuan; Robman, Liubov D; Aung, Khin Zaw; Makeyeva, Galina A; Giles, Graham G; Graves, Stephen; Cicuttini, Flavia M; Guymer, Robyn H

    2015-01-01

    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 neck of femur may be

  12. Visual acuity outcomes after cataract surgery in patients with age-related macular degeneration: age-related eye disease study report no. 27.

    Science.gov (United States)

    Forooghian, Farzin; Agrón, Elvira; Clemons, Traci E; Ferris, Frederick L; Chew, Emily Y

    2009-11-01

    To evaluate visual acuity outcomes after cataract surgery in patients with varying degrees of age-related macular degeneration (AMD). Cohort study. A total of 4757 participants enrolled in the Age-Related Eye Disease Study (AREDS), a prospective, multicenter, epidemiological study of the clinical course of cataract and AMD and a randomized controlled trial of antioxidants and minerals. Standardized lens and fundus photographs, performed at baseline and annual visits, were graded by a centralized reading center using standardized protocols for severity of AMD and lens opacities. History of cataract surgery was obtained every 6 months. Analyses were conducted using multivariate logistic regression. The change in best-corrected visual acuity (BCVA) after cataract surgery compared with preoperative BCVA. Visual acuity results were analyzed for 1939 eyes that had cataract surgery during AREDS. The mean time from cataract surgery to measurement of postoperative BCVA was 6.9 months. After adjustment for age at surgery, gender, type, and severity of cataract, the mean change in visual acuity at the next study visit after the cataract surgery was as follows: Eyes without AMD gained 8.4 letters of acuity (P<0.0001), eyes with mild AMD gained 6.1 letters of visual acuity (P<0.0001), eyes with moderate AMD gained 3.9 letters (P<0.0001), and eyes with advanced AMD gained 1.9 letters (P = 0.04). The statistically significant gain in visual acuity after cataract surgery was maintained an average of 1.4 years after cataract surgery. On average, participants with varying severity of AMD benefited from cataract surgery with an increase in visual acuity postoperatively. This average gain in visual acuity persisted for at least 18 months.

  13. 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.......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....

  14. Crataegus special extract WS(®)1442 prevents aging-related endothelial dysfunction.

    Science.gov (United States)

    Idris-Khodja, N; Auger, C; Koch, E; Schini-Kerth, V B

    2012-06-15

    Aging is associated with a markedly increased incidence of cardiovascular diseases due, in part, to the development of vascular endothelial dysfunction. The present study has evaluated whether the Crataegus special extract WS(®)1442 prevents the development of aging-related endothelial dysfunction in rats, and, if so, to determine the underlying mechanisms. Wistar rats received either a control diet or the same diet containing 100 or 300 mg/kg/day of WS(®)1442 from week 25 until week 65. Vascular reactivity was assessed in mesenteric artery rings using organ chambers, oxidative stress by dihydroethidine staining and cyclooxygenase-1 (COX-1) and -2 (COX-2) expression by immunohistochemistry. Acetylcholine-induced endothelium-dependent relaxations in mesenteric artery rings were blunted in 65-week-old rats compared to 16-week-old rats. This effect was associated with a marked reduction of the endothelium-derived hyperpolarizing factor (EDHF) component whereas the nitric oxide (NO) component was not affected. Aging was also associated with the induction of endothelium-dependent contractile responses to acetylcholine. Both aging-related impairment of endothelium-dependent relaxations and the induction of endothelium-dependent contractile responses were improved by the Crataegus treatment and by COX inhibitors. An excessive vascular oxidative stress and an upregulation of COX-1 and COX-2 were observed in the mesenteric artery of old rats compared to young rats, and these effects were improved by the Crataegus treatment. In conclusion, chronic intake of Crataegus prevented aging-related endothelial dysfunction by reducing the prostanoid-mediated contractile responses, most likely by improving the increased oxidative stress and the overexpression of COX-1 and COX-2. Copyright © 2012 Elsevier GmbH. All rights reserved.

  15. Targeting cellular senescence prevents age-related bone loss in mice.

    Science.gov (United States)

    Farr, Joshua N; Xu, Ming; Weivoda, Megan M; Monroe, David G; Fraser, Daniel G; Onken, Jennifer L; Negley, Brittany A; Sfeir, Jad G; Ogrodnik, Mikolaj B; Hachfeld, Christine M; LeBrasseur, Nathan K; Drake, Matthew T; Pignolo, Robert J; Pirtskhalava, Tamar; Tchkonia, Tamara; Oursler, Merry Jo; Kirkland, James L; Khosla, Sundeep

    2017-09-01

    Aging is associated with increased cellular senescence, which is hypothesized to drive the eventual development of multiple comorbidities. Here we investigate a role for senescent cells in age-related bone loss through multiple approaches. In particular, we used either genetic (i.e., the INK-ATTAC 'suicide' transgene encoding an inducible caspase 8 expressed specifically in senescent cells) or pharmacological (i.e., 'senolytic' compounds) means to eliminate senescent cells. We also inhibited the production of the proinflammatory secretome of senescent cells using a JAK inhibitor (JAKi). In aged (20- to 22-month-old) mice with established bone loss, activation of the INK-ATTAC caspase 8 in senescent cells or treatment with senolytics or the JAKi for 2-4 months resulted in higher bone mass and strength and better bone microarchitecture than in vehicle-treated mice. The beneficial effects of targeting senescent cells were due to lower bone resorption with either maintained (trabecular) or higher (cortical) bone formation as compared to vehicle-treated mice. In vitro studies demonstrated that senescent-cell conditioned medium impaired osteoblast mineralization and enhanced osteoclast-progenitor survival, leading to increased osteoclastogenesis. Collectively, these data establish a causal role for senescent cells in bone loss with aging, and demonstrate that targeting these cells has both anti-resorptive and anabolic effects on bone. Given that eliminating senescent cells and/or inhibiting their proinflammatory secretome also improves cardiovascular function, enhances insulin sensitivity, and reduces frailty, targeting this fundamental mechanism to prevent age-related bone loss suggests a novel treatment strategy not only for osteoporosis, but also for multiple age-related comorbidities.

  16. Role of macrophages in age-related oxidative stress and lipofuscin accumulation in mice

    Directory of Open Access Journals (Sweden)

    Carmen Vida

    2017-08-01

    Full Text Available The age-related changes in the immune functions (immunosenescence may be mediated by an increase of oxidative stress and damage affecting leukocytes. Although the “oxidation-inflammation” theory of aging proposes that phagocytes are the main immune cells contributing to “oxi-inflamm-aging”, this idea has not been corroborated. The aim of this work was to characterize the age-related changes in several parameters of oxidative stress and immune function, as well as in lipofuscin accumulation (“a hallmark of aging”, in both total peritoneal leukocyte population and isolated peritoneal macrophages. Adult, mature, old and long-lived mice (7, 13, 18 and 30 months of age, respectively were used. The xanthine oxidase (XO activity-expression, basal levels of superoxide anion and ROS, catalase activity, oxidized (GSSG and reduced (GSH glutathione content and lipofuscin levels, as well as both phagocytosis and digestion capacity were evaluated. The results showed an age-related increase of oxidative stress and lipofuscin accumulation in murine peritoneal leukocytes, but especially in macrophages. Macrophages from old mice showed lower antioxidant defenses (catalase activity and GSH levels, higher oxidizing compounds (XO activity/expression and superoxide, ROS and GSSG levels and lipofuscin levels, together with an impaired macrophage functions, in comparison to adults. In contrast, long-lived mice showed in their peritoneal leukocytes, and especially in macrophages, a well-preserved redox state and maintenance of their immune functions, all which could account for their high longevity. Interestingly, macrophages showed higher XO activity and lipofuscin accumulation than lymphocytes in all the ages analyzed. Our results support that macrophages play a central role in the chronic oxidative stress associated with aging, and the fact that phagocytes are key cells contributing to immunosenescence and “oxi-inflamm-aging”. Moreover, the

  17. Associations of Common Genetic Variants With Age-Related Changes in Fasting and Postload Glucose

    Science.gov (United States)

    Jensen, Anders C.; Barker, Adam; Kumari, Meena; Brunner, Eric J.; Kivimäki, Mika; Hingorani, Aroon D.; Wareham, Nicholas J.; Tabák, Adam G.; Witte, Daniel R.; Langenberg, Claudia

    2011-01-01

    OBJECTIVE In the general, nondiabetic population, fasting glucose increases only slightly over time, whereas 2-h postload glucose shows a much steeper age-related rise. The reasons underlying these different age trajectories are unknown. We investigated whether common genetic variants associated with fasting and 2-h glucose contribute to age-related changes of these traits. RESEARCH DESIGN AND METHODS We studied 5,196 nondiabetic participants of the Whitehall II cohort (aged 40–78 years) attending up to four 5-yearly oral glucose tolerance tests. A genetic score was calculated separately for fasting and 2-h glucose, including 16 and 5 single nucleotide polymorphisms, respectively. Longitudinal modeling with age centered at 55 years was used to study the effects of each genotype and genetic score on fasting and 2-h glucose and their interactions with age, adjusting for sex and time-varying BMI. RESULTS The fasting glucose genetic score was significantly associated with fasting glucose with a 0.029 mmol/L (95% CI 0.023–0.034) difference (P = 2.76 × 10−21) per genetic score point, an association that remained constant over time (age interaction P = 0.17). Two-hour glucose levels differed by 0.076 mmol/L (0.047–0.105) per genetic score point (P = 3.1 × 10−7); notably, this effect became stronger with increasing age by 0.006 mmol/L (0.003–0.009) per genetic score point per year (age interaction P = 3.0 × 10−5), resulting in diverging age trajectories by genetic score. CONCLUSIONS Common genetic variants contribute to the age-related rise of 2-h glucose levels, whereas associations of variants for fasting glucose are constant over time, in line with stable age trajectories of fasting glucose. PMID:21441441

  18. 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

  19. Age-related declines in anaerobic muscular performance: weightlifting and powerlifting.

    Science.gov (United States)

    Anton, Maria M; Spirduso, Waneen W; Tanaka, Hirofumi

    2004-01-01

    One approach to studying the effects of aging on physiological functional capacity (PFC) in humans is to analyze the peak physical performance of trained athletes with increasing age. The primary aim of the present study was to determine weightlifting and powerlifting performance with increasing age in both men and women. We performed a retrospective analysis of top age-group weightlifting and powerlifting records compiled from the U.S. Weightlifting and U.S. Powerlifting Organizations. Regression analyses showed that in both men and women weightlifting and powerlifting performance declined curvilinearly and linearly, respectively. The rate and the overall magnitude of declines in performance with age were markedly greater (P powerlifting. The rates of age-related decline in muscular power were not different between upper body (bench press) and lower body (squat). Similarly, the age-related declines were not different between snatch and clean and jerk in weightlifting events. The magnitude of the declines with age was greater (P powerlifting performance. The findings in this cross-sectional study indicate that 1) peak anaerobic muscular power, as assessed by peak lifting performance, decreases progressively even from earlier ages than previously thought; 2) the overall magnitude of decline in peak muscular power appears to be greater in tasks requiring more complex and powerful movements; 3) the age-related rates of decline are greater in women than in men only in the events that require more complex and explosive power; and 4) upper- and lower-body muscular power demonstrate similar rate of decline with age.

  20. 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.

  1. Age-related changes in murine bladder structure and sensory innervation: a multiphoton microscopy quantitative analysis.

    Science.gov (United States)

    Schueth, Anna; Spronck, Bart; van Zandvoort, Marc A M J; van Koeveringe, Gommert A

    2016-02-01

    Our study aimed to examine and quantify age-related structural alterations in the healthy mouse bladder using ex vivo two-photon laser scanning microscopy (TPLSM). Freshly dissected bladders from 25-, 52-, and 85-week-old C57bl/6J mice were examined, and morphological analyses and quantification of cell layers and nerves were performed. The numbers of stretched, curled, branched, and total number of nerves in volume units of the stained muscle layer were quantified. We observed differences in the bladder wall architecture and innervation with age. Especially in 85-week-old mice, age-related changes were found, including detachment of urothelial cells and an increase in connective tissue, intermingled with the smooth muscle fibers in the muscle layer (collagen-smooth muscle ratio of 1.15 ± 0.29). In 25- and 52-week-old mice, the collagen-smooth muscle ratios were 0.20 ± 0.04 and 0.31 ± 0.11, respectively, and a clear separation of collagen and muscle was observed. The overall number of nerves and the number of curled nerves were significantly higher in the 85-week-old mice (74.0 ± 13.0 and 25.9 ± 4.8, respectively), when comparing to 25-week-old mice (26.0 ± 2.7 and 6.7 ± 1.2, respectively) and 52-week-old mice (43.8 ± 4.3 and 22.1 ± 3.3, respectively). Significant age-related alterations in bladder morphology and innervation were found, when comparing freshly dissected bladder tissue from 25-, 52-, and 85-week-old mice. The higher number of curled nerves might be an indication of an increased neurotransmitter release, resulting in a higher nerve activity, with a part of the nerves being possibly mechanically impaired. This study shows that two-photon laser scanning microscopy of healthy aging male mice is a useful method to investigate and quantify the age-related changes in the bladder wall.

  2. Age-related changes of gustatory function depend on alteration of neuronal circuits.

    Science.gov (United States)

    Iannilli, Emilia; Broy, Franziska; Kunz, Severine; Hummel, Thomas

    2017-10-01

    Studies on age-related gustatory function report a reduction of the taste function, but the degeneration of the peripheral papillae alone cannot explain this reduction. In the present study, we apply psychophysics and gustatory event-related potentials (gERPs) to explore age-related differences in the processing of gustatory information as indicated by the cerebral sources of the gERP. A total of 96 subjects (47 female), subdivided into four groups with increasing age, participated in the study. After olfactory and gustatory screening for normal function, the subjects were invited to two sessions of gERP acquisition. They received a randomized combination of five isointense basic tastants that were presented at a medium level. At the same time, we recorded scalp electroencephalography (EEG) from 128 scalp locations. Psychophysical testing for smell and taste function exhibited a significant decrease with age. Topographical analyses of the EEG delineated four basic topographical maps that explained the processing of taste in the pre-decline age range, with sources inside the relevant gustatory areas. The age-related change of gustatory processing was associated with the absence of a specific map with sources inside the cerebellum and posterior insula, and the temporal broadening of a map with sources in the bilateral inferior frontal gyrus. These results confirm the hypothesis that the reduction of taste function with aging is not only due to degradation of gustatory peripheral tissues but is also related to different neural signatures in the central nervous system. © 2017 Wiley Periodicals, Inc.

  3. Three-dimensional anatomy of equine incisors: tooth length, enamel cover and age related changes.

    Science.gov (United States)

    Schrock, Patricia; Lüpke, Matthias; Seifert, Hermann; Staszyk, Carsten

    2013-12-09

    Equine incisors are subjected to continuous occlusal wear causing multiple, age related changes of the extragingival crown. It is assumed that the occlusal wear is compensated by continued tooth elongation at the apical ends of the teeth. In this study, μCT-datasets offered the opportunity to analyze the three-dimensional appearance of the extra- and intraalveolar parts of the enamel containing dental crown as well as of the enamel-free dental root. Multiple morphometric measurements elucidated age related, morphological changes within the intraalveolar part of the incisors. Equine incisors possess a unique enamel cover displaying large indentations on the mesial and distal sides. After eruption tooth elongation at the apical end outbalances occlusal wear for two to four years resulting in increasing incisor length in this period of time. Remarkably, this maximum length is maintained for about ten years, up to a tooth age of 13 to 15 years post eruption. Variances in the total length of individual teeth are related to different Triadan positions (central-, middle- and corner incisors) as well as to the upper and lower arcades. Equine incisors are able to fully compensate occlusal wear for a limited period of time. However, after this ability ceases, it is expected that a diminished intraalveolar tooth length will cause massive changes in periodontal biomechanics. The time point of these morphodynamic and biomechanical changes (13 to 15 years post eruption) occurs in coincidence with the onset of a recently described destructive disease of equine incisor (equine odontoclastic tooth resorption and hypercementosis) in aged horses. However, further biomechanical, cell biological and microbiological investigations are needed to elucidate a correlation between age related changes of incisor morphology and this disease.

  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. Age-related differences in working memory performance in a 2-back task

    Directory of Open Access Journals (Sweden)

    Nele eWild-Wall

    2011-08-01

    Full Text Available The present study aimed to elucidate the neuro-cognitive processes underlying age-related differences in working memory. Young and middle-aged participants performed a two-choice task with low and a 2-back task with high working memory load. The P300, an event-related potential reflecting controlled stimulus-response processing in working memory, and the underlying neuronal sources of expected age-related differences were analyzed using sLORETA. Response speed was generally slower for the middle-aged than the young group. Under low working memory load the middle-aged participants traded speed for accuracy. The middle-aged were less efficient in the 2-back task as they responded slower while the error rates did not differ for groups. An age-related decline of the P300 amplitude and characteristic topographical differences were especially evident in the 2-back task. A more detailed analysis of the P300 in non-target trials revealed that amplitudes in the young but not middle-aged group differentiate between correctly detected vs. missed targets in the following trial. For these trials, source analysis revealed higher activation for the young vs. middle-aged group in brain areas which support working memory processes. The relationship between P300 and overt performance was validated by significant correlations. To sum up, under high working memory load the young group showed an increased neuronal activity before a successful detected target, while the middle-aged group showed the same neuronal pattern regardless of whether a subsequent target will be detected or missed. This stable memory trace before detected targets was reflected by a specific activation enhancement in brain areas which orchestrate maintenance, update, storage and retrieval of information in working memory.

  6. Nicotinamide phosphoribosyltransferase may be involved in age-related brain diseases.

    Directory of Open Access Journals (Sweden)

    Li-Ying Liu

    Full Text Available Nicotinamide phosphoribosyltransferase (NAMPT is a key enzyme for nicotinamide adenine dinucleotide (NAD biosynthesis, and can be found either intracellularly (iNAMPT or extracellularly (eNAMPT. Studies have shown that both iNAMPT and eNAMPT are implicated in aging and age-related diseases/disorders in the peripheral system. However, their functional roles in aged brain remain to be established. Here we showed that upon aging, NAMPT level increased in serum but decreased in brain, decreased in cortex and hippocampus but remained unchanged in cerebellum and striatum in brain, and increased in microglia but likely decreased in neuron. Accordingly, total NAD (tNAD level significantly decreased in hippocampus, cerebellum and striatum in aged brain. Application of recombinant NAMPT, mimicking the elevated serum NAMPT level, enhanced the susceptibility of cerebral endothelial cells to ischemic injury, while inhibition of iNAMPT by FK866, a specific inhibitor, reduced intracellular NAD level and induced neuronal death. Taken together, we have revealed a region- and cell-specific change of NAMPT level in brain and serum upon aging, deduced its potential consequences, which suggests that NAMPT is a regulatory factor in aging and age-related brain diseases.

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

    Science.gov (United States)

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

    2015-03-01

    Accurate memory retrieval from partial or degraded input requires the reactivation of memory traces, a hippocampal mechanism termed pattern completion. Age-related changes in hippocampal integrity have been hypothesized to shift the balance of memory processes in favor of the retrieval of already stored information (pattern completion), to the detriment of encoding new events (pattern separation). Using a novel behavioral paradigm, we investigated the impact of cognitive aging (1) on recognition performance across different levels of stimulus completeness, and (2) on potential response biases. Participants were required to identify previously learned scenes among new ones. Additionally, all stimuli were presented in gradually masked versions to alter stimulus completeness. Both young and older adults performed increasingly poorly as the scenes became less complete, and this decline in performance was more pronounced in elderly participants indicative of a pattern completion deficit. Intriguingly, when novel scenes were shown, only the older adults showed an increased tendency to identify these as familiar scenes. In line with theoretical models, we argue that this reflects an age-related bias towards pattern completion. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Perceptions of oocyte banking from women intending to circumvent age-related fertility decline.

    Science.gov (United States)

    de Groot, Marije; Dancet, Eline; Repping, Sjoerd; Goddijn, Mariette; Stoop, Dominic; van der Veen, Fulco; Gerrits, Trudie

    2016-12-01

    Women can now opt to bank their oocytes with the intention of increasing their chances of achieving a pregnancy after their fertility has declined. This exploratory study aimed to gain insight into how women, considering oocyte banking to circumvent age-related fertility decline, perceive this intervention. We conducted a qualitative study in a Dutch university medical center and held in-depth interviews with women on the waiting list for oocyte banking. We recorded the interviews, transcribed them verbatim and used thematic analysis. All women were financially independent and lived in single-person urban households. They opted for oocyte banking because they wished to share parenthood with a future partner rather than becoming a single parent. This strong desire was key in their interpretation of all aspects of the intervention. Women set aside information about the limited success rates and potential risks, as they were optimistic about their own prognosis, thought that the chances for success were equally likely as the chances it would fail, and because of "anticipatory regret". They perceived oocyte banking as a "helping hand" to achieve shared parenthood. Although women found the costs of the intervention high, they were willing to invest their money to increase their chances for shared parenthood. Oocyte banking allows women to circumvent age-related fertility decline. The prospect of potential shared parenthood overrules the perceived health risks and burden. Health professionals should take this into account when informing potential users of oocyte banking. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

  9. 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.

  10. Aging Is Not a Disease: Distinguishing Age-Related Macular Degeneration from Aging

    Science.gov (United States)

    Ardeljan, Daniel; Chan, Chi-Chao

    2013-01-01

    Age-related macular degeneration (AMD) is a disease of the outer retina, characterized most significantly by atrophy of photoreceptors and retinal pigment epithelium accompanied with or without choroidal neovascularization. Development of AMD has been recognized as contingent on environmental and genetic risk factors, the strongest being advanced age. In this review, we highlight pathogenic changes that destabilize ocular homeostasis and promote AMD development. With normal aging, photoreceptors are steadily lost, Bruch's membrane thickens, the choroid thins, and hard drusen may form in the periphery. In AMD, many of these changes are exacerbated in addition to the development of disease-specific factors such as soft macular drusen. Para-inflammation, which can be thought of as an intermediate between basal and robust levels of inflammation, develops within the retina in an attempt to maintain ocular homeostasis, reflected by increased expression of the anti-inflammatory cytokine IL-10 coupled with shifts in macrophage plasticity from the pro-inflammatory M1 to the anti-inflammatory M2 polarization. In AMD, imbalances in the M1 and M2 populations together with activation of retinal microglia are observed and potentially contribute to tissue degeneration. Nonetheless, the retina persists in a state of chronic inflammation and increased expression of certain cytokines and inflammasomes is observed. Since not everyone develops AMD, the vital question to ask is how the body establishes a balance between normal age-related changes and the pathological phenotypes in AMD. PMID:23933169

  11. Assessing social cognition: age-related changes in moral reasoning in childhood and adolescence.

    Science.gov (United States)

    Chiasson, V; Vera-Estay, E; Lalonde, G; Dooley, J J; Beauchamp, M H

    2017-04-01

    There is increasing recognition that socio-cognitive skills, such as moral reasoning (MR), are affected in a wide range of developmental and neuropsychological conditions. However, the lack of appropriate measures available to neuropsychologists poses a challenge for the direct assessment of these skills. This study sought to explore age-related changes in MR using an innovative visual tool and examine the developmental sensitivity of the task. To address some of the methodological limitations of traditional measures of MR, a novel, visual task, the Socio-Moral Reasoning Aptitude Level (So-Moral), was used to evaluate MR in 216 healthy participants aged 6-20 years. The findings show a linear increase in MR from childhood to late adolescence with significant group differences between childhood (6-8 years) and preadolescence (9-11 years), and between early adolescence (12-14 years) and middle adolescence (15-17 years). Interpreted in light of current brain development research, the results highlight age-related changes in MR that offer insight into typical MR development and opportunities for comparisons with clinical populations. The findings also provide evidence of the potential of the So-Moral as a developmentally appropriate measure of MR throughout childhood and adolescence.

  12. Age-related changes in vertebral and iliac crest 3D bone microstructure-differences and similarities

    DEFF Research Database (Denmark)

    Thomsen, Jesper Skovhus; Jensen, Michael Vinkel; Niklassen, Andreas Steenholt

    2015-01-01

    Summary Age-related changes of vertebra and iliac crest 3D microstructure were investigated, and we showed that they were in general similar. The 95th percentile of vertebral trabecular thickness distribution increased with age for women. Surprisingly, vertebral and iliac crest bone microstructure...... was only weakly correlated (r = 0.38 to 0.75), despite the overall similar age-related changes.Introduction The purposes of the study were to determine the age-related changes in iliac and vertebral bone microstructure for women and men over a large age range and to investigate the relationship between...... the bone microstructure at these skeletal sites.Methods Matched sets of transiliac crest bone biopsies and lumbar vertebral body (L2) specimens from 41 women (19–96 years) and 39 men (23–95 years) were micro-computed tomography (μCT) scanned, and the 3D microstructure was quantified.Results For both women...

  13. Counteracting age-related loss of skeletal muscle mass

    DEFF Research Database (Denmark)

    Bechshøft, Rasmus; Reitelseder, Søren; Højfeldt, Grith

    2016-01-01

    Background Aging is associated with decreased muscle mass and functional capacity, which in turn decrease quality of life. The number of citizens over the age of 65 years in the Western world will increase by 50 % over the next four decades, and this demographic shift brings forth new challenges ...

  14. The current pattern of gestational age-related anthropometric ...

    African Journals Online (AJOL)

    for gestational age, and to have an increased risk of complications such ... Methods. Consecutive term singleton mother-baby pairs were surveyed in the first 24 hours after birth. Weight, length, occipitofrontal circumference (OFC) and ponderal index were ..... circumference ratio in the assessment of growth restriction.

  15. Age-related variations in corneal biomechanical properties

    Directory of Open Access Journals (Sweden)

    Farideh Sharifipour

    2016-09-01

    Conclusions: In this study, there was a decrease in CH and CRF with an increase in age. Hyperopia and female gender are associated with higher CH and CRF. CCT is higher toward the extremes of life and is significantly correlated with CH and CRF.

  16. Age-related decrements in cycling and running performance ...

    African Journals Online (AJOL)

    Results. The rate of decline in running speed occurred at an earlier age (~ 32 years) during the running race compared with the cycling tour (~ 55 years). Conclusions. These findings establish a trend that there is 'accelerated' aging during running which can perhaps be attributed to the increased weight-bearing stress on ...

  17. 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…

  18. The effects of blueberry and strawberry serum metabolites on age-related oxidative and inflammatory signaling in vitro

    Science.gov (United States)

    Age-related decrements in cognition are thought to result from the increased susceptibility to and accumulating effects of oxidative stress and inflammation. Berry fruits contain a variety of bioactive polyphenolic compounds, such as anthocyanins, that exhibit potent antioxidant and anti-inflammator...

  19. 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…

  20. Resveratrol and pinostilbene confer neuroprotection against aging-related deficits through an ERK1/2 dependent-mechanism

    Science.gov (United States)

    Age-related declines in motor function may be due, in part, to an increase in oxidative stress in the aging brain leading to death of brain cells that transmit dopamine (DA), one of the brain chemicals responsible for transmitting signals between brain nerve cells. We examined the neuroprotective ef...

  1. Age-Related Psychophysical Changes and Low Vision

    Science.gov (United States)

    Dagnelie, Gislin

    2013-01-01

    When considering the burden of visual impairment on aging individuals and society at large, it is important to bear in mind that vision changes are a natural aspect of aging. In this article, we consider vision changes that are part of normal aging, the prevalence of abnormal vision changes caused by disorders of the visual system, and the anticipated incidence and impact of visual impairment as the US population ages. We then discuss the services available to reduce the impact of vision loss, and the extent to which those services can and should be improved, not only to be better prepared for the anticipated increase in low vision over the coming decades, but also to increase the awareness of interactions between visual impairment and comorbidities that are common among the elderly. Finally, we consider how to promote improved quality, availability, and acceptance of low vision care to lessen the impact of visual impairment on individuals, and its burden on society. PMID:24335074

  2. 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. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  3. Age-related neuronal loss in the rat brain starts at the end of adolescence

    Science.gov (United States)

    Morterá, Priscilla; Herculano-Houzel, Suzana

    2012-01-01

    Aging-related changes in the brain have been mostly studied through the comparison of young adult and very old animals. However, aging must be considered a lifelong process of cumulative changes that ultimately become evident at old age. To determine when this process of decline begins, we studied how the cellular composition of the rat brain changes from infancy to adolescence, early adulthood, and old age. Using the isotropic fractionator to determine total numbers of neuronal and non-neuronal cells in different brain areas, we find that a major increase in number of neurons occurs during adolescence, between 1 and 2–3 months of age, followed by a significant trend of widespread and progressive neuronal loss that begins as early as 3 months of age, when neuronal numbers are maximal in all structures, until decreases in numbers of neurons become evident at 12 or 22 months of age. Our findings indicate that age-related decline in the brain begins as soon as the end of adolescence, a novel finding has important clinical and social implications for public health and welfare. PMID:23112765

  4. 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. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  5. Management of significant reactivation of old disciform scars in wet age-related macular degeneration.

    Science.gov (United States)

    Coco, Rosa M; Sala-Puigdollers, Anna

    2014-06-25

    Fibrotic disciform scars represent the end-stage of wet age-related macular degeneration (AMD) and ophthalmologists tend not to treat them. However, reactivation can occur resulting in further worsening of patients. The aim of this study is to describe the clinical outcomes of 10 patients with disciform scars from age-related macular degeneration (AMD) that have subsequently reactivated. Indocyanine green angiography (ICG) was used to identify the active areas and these "hot spots" (HS) that were subsequently treated with focal laser photocoagulation. In 10 out of 11 patients with potential reactivation of an AMD scar, a treatable HS was found on the ICG at the border of the disciform scar. The identified HS was treated with focal laser photocoagulation. Post treatment these areas became inactive. However in 2 cases, reactivation occurred requiring retreatment a few months later. AMD patients who are noted to have disciform scars that are increasing in size and signs of activation such as lipid exudation and subretinal haemorrhage should undergo ICG imaging to look for HS. These patients could benefit from focal laser to stabilize the disease and avoid complications and further peripheral visual loss. It is suspected that these patients may have the polypoidal subtype of AMD.

  6. 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.

  7. Longitudinal mediation of processing speed on age-related change in memory and fluid intelligence.

    Science.gov (United States)

    Robitaille, Annie; Piccinin, Andrea M; Muniz-Terrera, Graciela; Hoffman, Lesa; Johansson, Boo; Deeg, Dorly J H; Aartsen, Marja J; Comijs, Hannie C; Hofer, Scott M

    2013-12-01

    Age-related decline in processing speed has long been considered a key driver of cognitive aging. While the majority of empirical evidence for the processing speed hypothesis has been obtained from analyses of between-person age differences, longitudinal studies provide a direct test of within-person change. Using recent developments in longitudinal mediation analysis, we examine the speed-mediation hypothesis at both the within-and between-person levels in two longitudinal studies, Longitudinal Aging Study Amsterdam (LASA) and Origins of Variance in the Oldest-Old (OCTO-Twin). We found significant within-person indirect effects of change in age, such that increasing age was related to lower speed, which in turn relates to lower performance across repeated measures on other cognitive outcomes. Although between-person indirect effects were also significant in LASA, they were not in OCTO-Twin which is not unexpected given the age homogeneous nature of the OCTO-Twin data. A more in-depth examination through measures of effect size suggests that, for the LASA study, the within-person indirect effects were small and between-person indirect effects were consistently larger. These differing magnitudes of direct and indirect effects across levels demonstrate the importance of separating between- and within-person effects in evaluating theoretical models of age-related change. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  8. 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.

  9. Age and muscle strength mediate the age-related biomechanical plasticity of gait.

    Science.gov (United States)

    Hortobágyi, Tibor; Rider, Patrick; Gruber, Allison H; DeVita, Paul

    2016-04-01

    Old compared with young adults walk with reduced ankle and increased hip mechanical output. We examined the idea that age, leg strength, or both are related to the age-related changes in mechanical output during gait. Healthy young (n = 32, age 21.5 years) and old adults (n = 32, age 76.8 years) participated in biomechanical gait analyses at 1.5 m/s and were also measured for maximal leg strength. Analysis 1 confirmed previous data as old compared with young adults walked with 50 % more hip positive work and 18 % less ankle positive work. Analysis 2 showed that leg strength did not affect gait kinetics in groups of subjects with similar ages. In a weak young and a strong old group, Analysis 3 showed that old adults still walked with 23 % greater hip positive work. The group by joint interaction in Analysis 4 was suggestive of an even greater reliance on hip and less reliance on ankle work in weak compared with strong old adults. Age and leg strength both contribute to the age-related changes in mechanical output during gait. Exercise prescription, normally targeting the knee extensors, should also involve ankle and hip muscles.

  10. Neuropsychological Impairments and Age-Related Differences in Children and Adolescents with Fetal Alcohol Spectrum Disorders.

    Science.gov (United States)

    Tamana, Sukhpreet; Pei, Jacqueline; Massey, Donald; Massey, Valerie; Rasmussen, Carmen

    2014-01-01

    BackgroundChildren and adolescents with Fetal Alcohol Spectrum Disorders (FASD) exhibit a range of physical, cognitive, behavioral, and/or learning deficits, as wells as poor executive functioning (EF). Children and adolescents with FASD often show greater impairments on complex neuropsychological tasks. However, little is known about age-related differences among children and adolescents with FASD.ObjectivesThe goals of this cross-sectional study were to explore the overall profile of neuropsychological impairments and extended previous reports on age-related differences among children and adolescents with FASD. MethodWe compared 117 children and adolescents diagnosed with an FASD (aged 5-17 years), clinically assessed on a broad range of tests covering 6 neurobehavioral domains. Data from a clinical database was used to generate profiles of neuropsychological impairments for clinically referred children and adolescents evaluated for FASD between 2001 and 2005. ResultsChildren and adolescents were impaired (relative to the norm) on a number of domains that include academic achievement, language, verbal memory, EF, visual-motor integration, and motor abilities. Older participants with FASD (relative to the norm) showed greater difficulty in areas involving EF or processing of complex information than younger participants. ConclusionsThese results suggest that for children and adolescents with FASD impairments in those areas important for independent functioning may become more pronounced with increasing age. However, further longitudinal research is needed to ascertain age changes over time.

  11. Age-related expansion of Tim-3 expressing T cells in vertically HIV-1 infected children.

    Directory of Open Access Journals (Sweden)

    Ravi Tandon

    Full Text Available As perinatally HIV-1-infected children grow into adolescents and young adults, they are increasingly burdened with the long-term consequences of chronic HIV-1 infection, with long-term morbidity due to inadequate immunity. In progressive HIV-1 infection in horizontally infected adults, inflammation, T cell activation, and perturbed T cell differentiation lead to an "immune exhaustion", with decline in T cell effector functions. T effector cells develop an increased expression of CD57 and loss of CD28, with an increase in co-inhibitory receptors such as PD-1 and Tim-3. Very little is known about HIV-1 induced T cell dysfunction in vertical infection. In two perinatally antiretroviral drug treated HIV-1-infected groups with median ages of 11.2 yr and 18.5 yr, matched for viral load, we found no difference in the proportion of senescent CD28(-CD57(+CD8(+ T cells between the groups. However, the frequency of Tim-3(+CD8(+ and Tim-3(+CD4(+ exhausted T cells, but not PD-1(+ T cells, was significantly increased in the adolescents with longer duration of infection compared to the children with shorter duration of HIV-1 infection. PD-1(+CD8(+ T cells were directly associated with T cell immune activation in children. The frequency of Tim-3(+CD8(+ T cells positively correlated with HIV-1 plasma viral load in the adolescents but not in the children. These data suggest that Tim-3 upregulation was driven by both HIV-1 viral replication and increased age, whereas PD-1 expression is associated with immune activation. These findings also suggest that the Tim-3 immune exhaustion phenotype rather than PD-1 or senescent cells plays an important role in age-related T cell dysfunction in perinatal HIV-1 infection. Targeting Tim-3 may serve as a novel therapeutic approach to improve immune control of virus replication and mitigate age related T cell exhaustion.

  12. Telomere in Aging and Age-Related Diseases

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2017-12-01

    Full Text Available BACKGROUND: The number of elderly population in the world keep increasing. In their advanced ages, many elderly face years of disability because of multiple chronic diseases, frailty, making them lost their independence. Consequently, this could have impacts on social and economic stability. A huge challenge has been sent for biomedical researchers to compress or at least eliminate this period of disability and increase the health span. CONTENT: Over the past decades, many studies of telomere biology have demonstrated that telomeres and telomere-associated proteins are implicated in human diseases. Accelerated telomere erosion was clearly correlated with a pack of metabolic and inflammatory diseases. Critically short telomeres or the unprotected end, are likely to form telomeric fusion, generating genomic instability, the cornerstone for carcinogenesis. Enlightening how telomeres involved in the mechanisms underlying the diseases’ pathogenesis was expected to uncover new molecular targets for any important diagnosis or therapeutic implications. SUMMARY: Telomere shortening was foreseen as an imporant mechanism to supress tumor by limiting cellular proliferative capacity by regulating senescence check point activation. Many human diseases and carcinogenesis are causally related to defective telomeres, asserting the importance of telomeres sustainment. Thus, telomere length assessment might serve as an important tool for clinical prognostic, diagnostic, monitoring and management. KEYWORDS: telomerase, cellular senescence, aging, cancer

  13. [Non-pharmacologic therapy of age-related macular degeneration, based on the etiopathogenesis of the disease].

    Science.gov (United States)

    Fischer, Tamás

    2015-07-12

    It has a great therapeutic significance that the disorder of the vascular endothelium, which supplies the affected ocular structures, plays a major role in the development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfuncition and age-related macular degeneration is accompanied by a general inflammatory response. The vascular wall including those in chorioids may be activated by several repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic and genetic factors causing a protracted host defence response with a consequent vascular damage, which leads to age-related macular degeneration. Based on this concept, age-related macular degeneration is a local manifestation of the systemic vascular disease. This recognition should have therapeutic implications because restoration of endothelial dysfunction can stabilize the condition of chronic vascular disease including age-related macular degeneration, as well. Restoration of endothelial dysfunction by non-pharmacological or pharmacological interventions may prevent the development or improve endothelial dysfunction resulting in prevention or improvement of age-related macular degeneration. Non-pharmacological interventions which may have beneficial effect in endothelial dysfunction include (1) smoking cessation; (2) reduction of increased body weight; (3) adequate physical activity; (4) appropriate diet (a) proper dose of flavonoids, polyphenols and kurcumin; (b) omega-3 long-chain polyunsaturated fatty acids: docosahexaenoic acid and eicosapentaenoic acid; (c) carotenoids, lutein and zeaxanthins), (d) management of dietary glycemic index, (e) caloric restriction, and (5) elimination of stressful lifestyle. Non-pharmacological interventions should be preferable even if medicaments are also used for the treatment of endothelial dysfunction.

  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

    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...

  15. Age-Related Changes in the Musculoskeletal System and the Development of Osteoarthritis

    Science.gov (United States)

    Loeser, Richard F.

    2010-01-01

    Synopsis Osteoarthritis (OA) is the most common cause of chronic disability in older adults. Although classically considered a “wear and tear” degenerative condition of articular joints, recent studies have demonstrated an inflammatory component to OA that includes increased activity of a number of cytokines and chemokines in joint tissues which drive production of matrix degrading enzymes. Rather than directly causing OA, aging changes in the musculoskeletal system contribute to the development of OA by making the joint more susceptible to the effects of other OA risk factors that include abnormal biomechanics, joint injury, genetics, and obesity. Age-related sarcopenia and increased bone turnover may also contribute to the development of OA. Understanding the basic mechanisms by which aging affects joint tissues should provide new targets for slowing or preventing the development of OA. PMID:20699160

  16. Age-related differences in acoustical aspects of contrastive stress in women.

    Science.gov (United States)

    Scukanec, G P; Petrosino, L; Colcord, R D

    1996-01-01

    The purpose of this investigation was to compare the fundamental frequency (F0), durational, and sound pressure characteristics of speech during production of contrastive stress, a suprasegmental component of speech, in young adult and elderly women. Results indicate that, while both groups significantly increased F0, duration, and sound pressure level during production of contrastive stress, elderly women increased F0 to a significantly greater extent than young women and, for all acoustic parameters, the groups were dissimilar in position effects. In spite of the age related differences, such differences did not appear to limit the ability of elderly women to provide linguistic information through prosody. However, they may do so differently from young women. These findings may have implications in terms of treatment of speech disorders in the elderly.

  17. Age-Related Macular Degeneration in Patients With Chronic Myeloproliferative Neoplasms

    DEFF Research Database (Denmark)

    Bak, Marie; Sorensen, Torben Lykke; Flachs, Esben Meulengracht

    2017-01-01

    Importance: It has been suggested that systemic inflammation increases the risk of age-related macular degeneration (AMD). Given that chronic immune modulation is present in patients with myeloproliferative neoplasms (MPNs), the risk of AMD in these patients may be increased. Objective: To compare......, and December 31, 2013, of essential thrombocythemia, polycythemia vera, myelofibrosis, or unclassifiable MPNs. For each patient, 10 age- and sex-matched controls were included. All patients without prior AMD were followed up from the date of diagnosis (or corresponding entry date for the controls) until...... thereafter. Results: A total of 7958 patients with MPNs (4279 women [53.8%] and 3679 men [46.2%]; mean [SD] age at diagnosis, 66.4 [14.3] years) were included in the study. The rate of AMD per 1000 person-years at risk was 5.2 (95% CI, 4.6-5.9) for patients with MPNs (2628 with essential thrombocythemia...

  18. [Age-related dynamics of the main extracellular matrix components in residents of the Russian Arctic].

    Science.gov (United States)

    Kim, L B; Belisheva, N K; Putyatina, A N; Russkih, G S; Kozhin, P M; Tsypysheva, O B

    2017-01-01

    The main extracellular matrix components in Arctic residents were studied. Northerners had increased levels of total glycosaminoglycans, hyaluronan, and collagen IV in plasma and both general and peptide-bound hydroxyproline in urine, which indicates an accelerated metabolism of the main extracellular matrix components compared with comparison group (residents of Siberia). Age-related remodeling of extracellular matrix in northerners manifested in changing ratio and quantity of its main components. Levels of total glycosaminoglycans, hyaluronan, fibronectin, hydroxyproline and its fractions increased with age while the level of collagen IV changed insignificantly. Average positive correlation between extracellular matrix components and biological aging indicators is suggestive of relationship between these two processes: aging - which is accelerated in the Arctic and pathological remodeling of extracellular matrix as it is associated with accelerated aging. Changes in local regulation system including those related to matrix metalloproteinases and their tissue inhibitors may be one of the reasons for pathological remodeling of extracellular matrix.

  19. Distinct cellular and molecular environments support aging-related DNA methylation changes in the substantia nigra.

    Science.gov (United States)

    Fasolino, Maria; Liu, Shuo; Wang, Yinsheng; Zhou, Zhaolan

    2017-01-01

    We aimed to couple brain region-specific changes in global DNA methylation over aging to underlying cellular and molecular environments. We measured two major forms of DNA methylation and analyzed Dnmt, Tet and metabolite levels in the striatum and substantia nigra (SN) over aging in healthy male mice. The ratio of 5-hydroxymethylcytosine to 5-methylcytosine increases over aging in the SN, and 5-hydroxymethylcytosine increases preferentially in dopaminergic neurons. Additionally, this age-dependent alteration in methylation correlates with a reduction in the ratio of α-ketoglutarate to succinate in the SN. Distinct cellular and molecular environments correlate with aging-associated methylation changes in the SN, implicating this epigenetic mechanism in the susceptibility of this brain region to age-related cell loss.

  20. Age related issues in reperfusion of myocardial infarction.

    Science.gov (United States)

    Carro, Amelia; Bastiaenen, Rachel; Kaski, Juan Carlos

    2011-04-01

    Advances in pharmacological treatment and effective early myocardial revascularization have led to improved clinical outcomes in patients with acute myocardial infarction (AMI). However, it has been suggested that compared to younger subjects, elderly AMI patients are less likely to receive evidence-based treatment. Several reasons have been postulated to explain this trend, including uncertainty regarding the benefits of the commonly used interventions in the older age group as well as increased risk associated with comorbidities. The diagnosis, management, and post-hospitalization care of elderly patients presenting with an acute coronary syndrome (ACS) pose many difficulties at present due, at least in part, to the fact that trial data are scanty as elderly patients have been poorly represented in most clinical trials. Thus it appears that these high-risk individuals are often managed with more conservative strategies, compared to younger patients. This article reviews current evidence regarding management of AMI in the elderly.

  1. Age-related changes of the nitric oxide system in the rat brain.

    Science.gov (United States)

    Siles, Eva; Martínez-Lara, Esther; Cañuelo, Ana; Sánchez, Marta; Hernández, Raquel; López-Ramos, Juan Carlos; Del Moral, María Luisa; Esteban, Francisco José; Blanco, Santos; Pedrosa, Juan Angel; Rodrigo, José; Peinado, María Angeles

    2002-11-29

    This work examines the age-related changes of the NO pathway in the central nervous system (CNS), analyzing nitric oxide synthase (NOS) isoform expression, the level of nitrotyrosine-modified proteins, and the NOS activity in the cerebral cortex, decorticated brain (basal ganglia, thalamus, hypothalamus, tegtum and tegmentum) and cerebellum of young, adult and aged rats. Our data demonstrate that the different NOS isoforms are not uniformly expressed across the CNS. In this sense, the nNOS and eNOS isoenzymes are expressed mainly in the cerebellum and decorticated brain, respectively, while the iNOS isoenzyme shows the highest level in cerebellum. Concerning age, in the cerebral cortex nNOS significantly increased its expression only in adult animals; meanwhile, in the cerebellum the eNOS expression decreased whereas iNOS increased in adult and aged rats. No age-related changes in any isoform were found in decorticated brain. NOS activity, determined by nitrate plus nitrite quantification, registered the highest levels in the cerebellum, where the significant increase detected with aging was probably related to iNOS activity. The number of nitrotyrosine-modified immunoreactive bands differed among regions; thus, the highest number was detected in the decorticated brain while the cerebellum showed the least number of bands. Finally, bulk protein nitration increased in cerebral cortex only in adult animal. No changes were found in the decorticated brain, and the decrease detected in the cerebellum of aged animals was not significant. According to these results, the NO pathway is differently modified with age in the three CNS regions analyzed. Copyright 2002 Elsevier Science B.V.

  2. Characterization of age-related variation in corneal biomechanical properties.

    Science.gov (United States)

    Elsheikh, Ahmed; Geraghty, Brendan; Rama, Paolo; Campanelli, Marino; Meek, Keith M

    2010-10-06

    An experimental study has been conducted to determine the stress-strain behaviour of human corneal tissue and how the behaviour varies with age. Fifty-seven well-preserved ex vivo donor corneas aged between 30 and 99 years were subjected to cycles of posterior pressure up to 60 mm Hg while monitoring their behaviour. The corneas were mechanically clamped along their ring of scleral tissue and kept in physiological conditions of temperature and hydration. The tissue demonstrated hyper-elastic pressure-deformation and stress-strain behaviour that closely matched an exponential trend. Clear stiffening (increased resistance to deformation) with age was observed in all loading cycles, and the rate of stiffness growth was nonlinear with bias towards older specimens. With a strong statistical association between stiffness and age (p ages between 30 and 99 years. These equations, which closely matched the experimental results, depicted corneal stiffening with age in a form suitable for implementation in numerical simulations of ocular biomechanical behaviour.

  3. Age-related changes in peripheral blood counts in humans.

    Science.gov (United States)

    Mahlknecht, Ulrich; Kaiser, Simone

    2010-11-01

    Anaemia has become a common concern in geriatric health. Since its prevalence varies quite significantly among different groups depending on factors such as ethnicity, lifestyle or fitness, the appropriateness of the current WHO definition of anaemia in the elderly may be questioned. We evaluated peripheral blood parameters from 1,724 individuals (908 women aged 18-101 years and 816 men aged 18-96 years), who were treated at the University of Heidelberg Medical Center with no known haematological history. Patients with a known malignant haematological or oncological disease or with chronic infection or inflammation were excluded. Patients with disorders affecting the kidneys, thyroid or stomach, as well as patients with a bleeding history, haemolysis or who had been previously diagnosed with anaemia were excluded from the study. Average haemoglobin levels for men beyond the age of 70 and for women beyond the age of 80 were found to fulfill the WHO criteria for the diagnosis of anaemia. While in our cohort ∼20% of men and women between 60-69 years of age were by definition anaemic, these numbers steadily increased to 63% in females and 76% in males beyond the age of 90. Based on the results of our study and in accordance with the literature on this topic, we suggest age-adjusted criteria for the diagnosis of anaemia in the elderly in conjunction with a geriatric assessment.

  4. Molecular Diagnostics of Ageing and Tackling Age-related Disease.

    Science.gov (United States)

    Timmons, James A

    2017-01-01

    As average life expectancy increases there is a greater focus on health-span and, in particular, how to treat or prevent chronic age-associated diseases. Therapies which were able to control 'biological age' with the aim of postponing chronic and costly diseases of old age require an entirely new approach to drug development. Molecular technologies and machine-learning methods have already yielded diagnostics that help guide cancer treatment and cardiovascular procedures. Discovery of valid and clinically informative diagnostics of human biological age (combined with disease-specific biomarkers) has the potential to alter current drug-discovery strategies, aid clinical trial recruitment and maximize healthy ageing. I will review some basic principles that govern the development of 'ageing' diagnostics, how such assays could be used during the drug-discovery or development process. Important logistical and statistical considerations are illustrated by reviewing recent biomarker activity in the field of Alzheimer's disease, as dementia represents the most pressing of priorities for the pharmaceutical industry, as well as the chronic disease in humans most associated with age. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Age-related impact of neuropathic pain on animal behaviour.

    Science.gov (United States)

    Pickering, Gisèle; Jourdan, Didier; Millecamps, Magali; Chapuy, Eric; Alliot, Josette; Eschalier, Alain

    2006-11-01

    The number of old and very old persons is increasing and there is evidence that aging coincides with chronic painful conditions. Pain induces behavioural disorders that have been so far poorly identified in old and even less in very old animals. The aim of this study was to: (1) compare the evolution of pain in senescent animals (37-39 months) to old (20-22 months) and young (4-6 months) Lou/cjall rats after a chronic constriction of the sciatic nerve; (2) evaluate pain during four weeks after surgery with an experimental and an observational approach to determine how the response to noxious stimuli correlates with recorded spontaneous behaviour. Results showed that senescent animals are less sensitive to neuropathic pain than old or young rats while senescent/old rats are more sensitive to acute pain. The correlation between observational and experimental pain scores stresses the reliability of non-invasive measures for pain evaluation in senescent populations. The dichotomy between neuropathic and acute pain perceptions with age needs to be further investigated and would help to better understand the reasons of this uneven pain perception and expression with age.

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

    Science.gov (United States)

    2016-10-20

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

  7. Age-related changes in phosphorylation of endothelial nitric oxide synthase in the rat penis.

    Science.gov (United States)

    Musicki, Biljana; Kramer, Melissa F; Becker, Robyn E; Burnett, Arthur L

    2005-05-01

    Aging is associated with erectile dysfunction (ED) attributed to reduced nitric oxide synthase (NOS) activity and nitric oxide bioavailability. However, the mechanism for this effect has not been fully investigated. We evaluated (i) whether age-related ED involves dysregulation of endothelial NOS (eNOS) phosphorylation; and (ii) whether vascular endothelial growth factor (VEGF) exerts erectile effects and operates via eNOS phosphorylation in aged rats. Male Fischer 344 "young" (4-month-old) and "aged" (19-month-old) rats were used. Electrical stimulation of the cavernous nerve (CNS) was performed to generate penile erection. Erectile response in the presence of rhVEGF165 was evaluated by intracavernosal pressure monitoring 25 minutes after intracavernosal injection of VEGF. Penes were excised at baseline, with or without rhVEGF treatment, and after CNS for Western immunoblot of phospho-eNOS (Ser-1177 and Thr-495), phospho-Akt, and eNOS. Erectile response was significantly reduced in aged rats compared with young rats. Phospho-eNOS (Ser-1177) and phospho-Akt were significantly reduced, while phospho-eNOS (Thr-495) was significantly increased, in the aged penis at baseline and after CNS. rhVEGF significantly improved erection and reversed downregulated Ser-1177, but not upregulated Thr-495 phosphorylation, on eNOS in aged penes. eNOS protein was significantly increased in aged penes. Age-related ED is associated with eNOS inactivation through a decrease in phosphorylation of its positive regulatory site (Ser-1177) and an increase in phosphorylation of its negative regulatory site (Thr-495) in the penis. Altered phosphorylation/constitutive activation of eNOS by fluid shear stress may be a major determinant of compromised vascular homeostasis of the aged penis. The finding that VEGF rapidly induces erection and partly corrects alterations in eNOS phosphorylation in the aged rat penis suggests impaired eNOS activation by deficient endogenous VEGF and supports the

  8. Age-related variation in health status after age 60.

    Science.gov (United States)

    Santoni, Giola; Angleman, Sara; Welmer, Anna-Karin; Mangialasche, Francesca; Marengoni, Alessandra; Fratiglioni, Laura

    2015-01-01

    Disability, functionality, and morbidity are often used to describe the health of the elderly. Although particularly important when planning health and social services, knowledge about their distribution and aggregation at different ages is limited. We aim to characterize the variation of health status in a 60+ old population using five indicators of health separately and in combination. 3080 adults 60+ living in Sweden between 2001 and 2004 and participating at the SNAC-K population-based cohort study. Health indicators: number of chronic diseases, gait speed, Mini Mental State Examination (MMSE), disability in instrumental-activities of daily living (I-ADL), and in personal-ADL (P-ADL). Probability of multimorbidity and probability of slow gait speed were already above 60% and 20% among sexagenarians. Median MMSE and median I-ADL showed good performance range until age 84; median P-ADL was close to zero up to age 90. Thirty% of sexagenarians and 11% of septuagenarians had no morbidity and no impairment, 92% and 80% of them had no disability. Twenty-eight% of octogenarians had multimorbidity but only 27% had some I-ADL disability. Among nonagenarians, 13% had severe disability and impaired functioning while 12% had multimorbidity and slow gait speed. Age 80-85 is a transitional period when major health changes take place. Until age 80, most people do not have functional impairment or disability, despite the presence of chronic disorders. Disability becomes common only after age 90. This implies an increasing need of medical care after age 70, whereas social care, including institutionalization, becomes a necessity only in nonagenarians.

  9. Age-related variation in health status after age 60.

    Directory of Open Access Journals (Sweden)

    Giola Santoni

    Full Text Available Disability, functionality, and morbidity are often used to describe the health of the elderly. Although particularly important when planning health and social services, knowledge about their distribution and aggregation at different ages is limited. We aim to characterize the variation of health status in a 60+ old population using five indicators of health separately and in combination.3080 adults 60+ living in Sweden between 2001 and 2004 and participating at the SNAC-K population-based cohort study. Health indicators: number of chronic diseases, gait speed, Mini Mental State Examination (MMSE, disability in instrumental-activities of daily living (I-ADL, and in personal-ADL (P-ADL.Probability of multimorbidity and probability of slow gait speed were already above 60% and 20% among sexagenarians. Median MMSE and median I-ADL showed good performance range until age 84; median P-ADL was close to zero up to age 90. Thirty% of sexagenarians and 11% of septuagenarians had no morbidity and no impairment, 92% and 80% of them had no disability. Twenty-eight% of octogenarians had multimorbidity but only 27% had some I-ADL disability. Among nonagenarians, 13% had severe disability and impaired functioning while 12% had multimorbidity and slow gait speed.Age 80-85 is a transitional period when major health changes take place. Until age 80, most people do not have functional impairment or disability, despite the presence of chronic disorders. Disability becomes common only after age 90. This implies an increasing need of medical care after age 70, whereas social care, including institutionalization, becomes a necessity only in nonagenarians.

  10. Gluten intolerance: Sex-and age-related features

    Science.gov (United States)

    Llorente-Alonso, MJ; Fernández-Aceñero, MJ; Sebastián, M

    2006-01-01

    OBJECTIVE: Gluten intolerance is an immune-mediated enteropathy associated with gluten-containing foods in genetically susceptible patients. The typical form mainly affecting children shows failure to thrive and/or gastrointestinal symptoms. The adult form is less typical, presenting vague gastrointestinal symptoms, iron deficiency (with or without anemia) or nonspecific serum chemistry abnormalities. The present study aims to analyze clinical and biochemical differences of celiac disease (CD) according to sex and age. PATIENTS AND METHODS: The present study reviewed clinical and biochemical features of patients with suspected CD admitted to the Hospital General of Móstoles (Madrid, Spain) between July 2001 and June 2005. Two hundred fifty-two patients were analyzed, in whom intestinal biopsy was performed due to clinical and/or biochemical abnormalities suggestive of CD. One hundred seventy-eight asymptomatic relatives of the affected patients were also included. Overall, 125 patients showed diagnostic features of CD in the intestinal biopsy. RESULTS: The results confirmed higher prevalence of typical forms of CD in children (67% in children compared with only 14.3% in adults). CD seemed to be more frequent in adult women than in men (ratio of women to men 4:1), but it is worth noting that men diagnosed were most often referred with a typical clinical picture, so atypical forms of the disease in men may have been underdiagnosed. CONCLUSIONS: CD shows atypical features in adults, and physicians must include this disorder in the differential diagnosis of adults with iron deficiency or slight hypertransaminasemia. Increased awareness of the disease and extensive availability of accurate serological tests will lead to improved diagnosis of this disorder, both in children and adults. PMID:17111054

  11. Gluten intolerance: sex and age-related features.

    Science.gov (United States)

    Llorente-Alonso, M J; Fernández-Acenero, M J; Sebastián, M

    2006-11-01

    Gluten intolerance is an immune-mediated enteropathy associated with gluten-containing foods in genetically susceptible patients. The typical form mainly affecting children shows failure to thrive and/or gastrointestinal symptoms. The adult form is less typical, presenting vague gastrointestinal symptoms, iron deficiency (with or without anemia) or nonspecific serum chemistry abnormalities. The present study aims to analyze clinical and biochemical differences of celiac disease (CD) according to sex and age. The present study reviewed clinical and biochemical features of patients with suspected CD admitted to the Hospital General of Móstoles (Madrid, Spain) between July 2001 and June 2005. Two hundred fifty-two patients were analyzed, in whom intestinal biopsy was performed due to clinical and/or biochemical abnormalities suggestive of CD. One hundred seventy-eight asymptomatic relatives of the affected patients were also included. Overall, 125 patients showed diagnostic features of CD in the intestinal biopsy. The results confirmed higher prevalence of typical forms of CD in children (67% in children compared with only 14.3% in adults). CD seemed to be more frequent in adult women than in men (ratio of women to men 4:1), but it is worth noting that men diagnosed were most often referred with a typical clinical picture, so atypical forms of the disease in men may have been underdiagnosed. CD shows atypical features in adults, and physicians must include this disorder in the differential diagnosis of adults with iron deficiency or slight hypertransaminasemia. Increased awareness of the disease and extensive availability of accurate sero-logical tests will lead to improved diagnosis of this disorder, both in children and adults.

  12. Age-related external anal sphincter muscle dysfunction and fibrosis: possible role of Wnt/β-catenin signaling pathways.

    Science.gov (United States)

    Rajasekaran, M Raj; Kanoo, Sadhana; Fu, Johnny; Nguyen, My-Uyen Lilly; Bhargava, Valmik; Mittal, Ravinder K

    2017-12-01

    Studies show an age-related increase in the prevalence of anal incontinence and sphincter muscle atrophy. The Wnt/β-catenin signaling pathway has been recently recognized as the major molecular pathway involved in age-related skeletal muscle atrophy and fibrosis. The goals of our study were to 1) evaluate the impact of normal aging on external anal sphincter (EAS) muscle length-tension (L-T) function and morphology and 2) specifically examine the role of Wnt signaling pathways in anal sphincter muscle fibrosis. New Zealand White female rabbits [6 young (6 mo of age) and 6 old (36 mo of age)] were anesthetized, and anal canal pressure was measured to determine the L-T function of EAS. Animals were killed at the end of the study, and the anal canal was harvested and processed for histochemical studies (Masson trichrome stain for muscle/connective tissue) as well as for molecular markers for fibrosis and atrophy [collagen I, β-catenin, transforming growth factor-β (TGF-β), atrogin-1, and muscle-specific RING finger protein-1 (MuRF-1)]. The L-T was significantly impaired in older animals compared with young animals. Anal canal sections stained with trichrome showed a significant decrease in the muscle content (52% in old compared with 70% in young) and an increase in the connective tissue/collagen content in the old animals. An increased protein and mRNA expression of all the fibrosis markers was seen in the older animals. Aging EAS muscle exhibits impairment of function and increase in connective tissue. Upregulation of atrophy and profibrogenic proteins with aging may be the reason for the age-related decrease in anal sphincter muscle thickness and function.NEW & NOTEWORTHY Our studies using a female rabbit model show age-related alterations in the structure and function of the external anal sphincter (EAS) muscle. We used endoluminal ultrasound to measure age-related changes in EAS muscle thickness. We employed Western blot and quantitative PCR to demonstrate

  13. Ageing-related corpora veno-occlusive dysfunction in the rat is ameliorated by pioglitazone.

    Science.gov (United States)

    Kovanecz, Istvan; Ferrini, Monica G; Vernet, Dolores; Nolazco, Gaby; Rajfer, Jacob; Gonzalez-Cadavid, Nestor F

    2007-10-01

    To determine whether ageing-related changes in the penile corpora cavernosa, namely corporal veno-occlusive dysfunction (CVOD), loss of smooth muscle cells (SMCs), and excessive collagen deposition, can be ameliorated by the peroxisome proliferator-activated receptor gamma (PPARgamma) agonist pioglitazone, in a rat model of ageing as we have shown in a rat model of type 2 diabetes. Male Fischer 344 rats (16-18 months old) were fed chow containing 0%, 0.001% or 0.02% pioglitazone for 2 or 4.5 months, using 5 month old rats as 'young' controls. Functional changes were determined by dynamic-infusion cavernosometry (DIC). Histological changes were assessed by histochemistry and immunohistochemistry followed by quantitative image analysis and/or quantitative Western blot. Reactive oxygen species were estimated in blood. Pioglitazone at both doses reduced the high DIC 'drop rate' present in the untreated aged groups to the level seen in the young rats. The papaverine response was increased to young control levels by short-term high-dose pioglitazone and the long-term low-dose treatment, but not by the short-term low-dose treatment. Pioglitazone at all doses and durations of treatment failed to reverse the decreased corporal SMC/collagen ratio and SMC content, oxidative stress, or the elevated contents of collagen, or transforming growth factor beta1, seen in the aged penis, but did reduce the collagen III/I ratio, and at a high dose increased apoptosis. Both treatments inhibited the Rho-kinase system, by increasing Src homology region 2-containing protein tyrosine phosphatase and reducing Vav. PPARgamma were detected in corporal SMCs. Pioglitazone ameliorated ageing-related CVOD, possibly by a PPARgamma-mediated inhibition of Rho-kinase and not by a protective effect on the corporal smooth muscle.

  14. 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

  15. Myopia, axial length, and age-related cataract: the Singapore Malay eye study.

    Science.gov (United States)

    Pan, Chen-Wei; Boey, Pui Yi; Cheng, Ching-Yu; Saw, Seang-Mei; Tay, Wan Ting; Wang, Jie Jin; Tan, Ava Grace; Mitchell, Paul; Wong, Tien Yin

    2013-07-02

    To describe the associations of myopia and axial length (AL) with age-related cataract in an Asian population in Singapore. A population-based cross-sectional study that examined 3280 (78.7% response) adults of Malay ethnicity aged 40 to 80 years. Refractive error was determined by subjective refraction and AL was measured using the Zeiss IOL-Master. Digital slit lamp and retroillumination lens photographs were taken and graded for age-related nuclear, cortical, and posterior subcapsular (PSC) cataract following the Wisconsin system. After excluding eyes with prior refractive or cataract surgery, 5474 eyes with gradable lens photographs were analyzed. In multivariate analyses adjusting for age, sex, body mass index, systolic blood pressure, glycosylated hemoglobin, smoking status, and education, myopia (spherical equivalent less than -0.5 diopter [D]) was associated with an increased prevalence of nuclear (OR: 4.99, 95% CI: 3.72–6.69) and PSC cataract (OR: 1.34, 95% CI: 1.30-1.39) but not with cortical cataract (OR: 0.85, 95% CI: 0.68-1.08) compared with emmetropia. Per-millimeter increase in AL was not associated with any of the three cataract subtypes. When myopia was defined as spherical equivalent of less than -5.0 D to -6.0 D, the OR of myopia for PSC cataract increased dramatically. Our study shows that myopia, but not AL, was associated with nuclear cataract, supporting the concept of index myopia with aging. Myopia, especially high myopia, may predispose to PSC cataract formation. Clinically, ophthalmologists should be aware that risk of PSC cataract appears to vary by refractive status.

  16. Therapeutic potential of eccentric exercises for age-related muscle atrophy

    OpenAIRE

    Lim, Jae-Young

    2016-01-01

    Recent studies have focused on evidence-based interventions to prevent mobility decline and enhance physical performance in older adults. Several modalities, in addition to traditional strengthening programs, have been designed to manage age-related functional decline more effectively. In this study, we reviewed the current relevant literatures to assess the therapeutic potential of eccentric exercises for age-related muscle atrophy (sarcopenia). Age-related changes in human skeletal muscle, ...

  17. Age-related Differences in Tongue-Palate Pressures for Strength and Swallowing Tasks

    OpenAIRE

    Fei, Tiffany; Polacco, Rebecca Cliffe; Hori, Sarah E.; Molfenter, Sonja M.; Peladeau-Pigeon, Melanie; Tsang, Clemence; Steele, Catriona M.

    2013-01-01

    The tongue plays a key role in the generation of pressures for transporting liquids and foods through the mouth in swallowing. Recent studies suggest that there is an age-related decline in tongue strength in healthy adults. However, whether age-related changes occur in tongue pressures generated for the purpose of swallowing remains unclear. Prior literature in this regard does not clearly explore the influence of task on apparent age-related differences in tongue pressure amplitudes. Furthe...

  18. Age-related variation in reproductive traits in the wandering albatross: evidence for terminal improvement following senescence.

    Science.gov (United States)

    Froy, Hannah; Phillips, Richard A; Wood, Andrew G; Nussey, Daniel H; Lewis, Sue

    2013-05-01

    The processes driving age-related variation in demographic rates are central to understanding population and evolutionary ecology. An increasing number of studies in wild vertebrates find evidence for improvements in reproductive performance traits in early adulthood, followed by senescent declines in later life. However, life history theory predicts that reproductive investment should increase with age as future survival prospects diminish, and that raised reproductive investment may have associated survival costs. These non-mutually exclusive processes both predict an increase in breeding performance at the terminal breeding attempt. Here, we use a 30-year study of wandering albatrosses (Diomedea exulans) to disentangle the processes underpinning age-related variation in reproduction. Whilst highlighting the importance of breeding experience, we reveal senescent declines in performance are followed by a striking increase in breeding success and a key parental investment trait at the final breeding attempt. © 2013 Blackwell Publishing Ltd/CNRS.

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

    Directory of Open Access Journals (Sweden)

    Schrader Angela

    2010-11-01

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

  20. Role of macrophages in age-related oxidative stress and lipofuscin accumulation in mice.

    Science.gov (United States)

    Vida, Carmen; de Toda, Irene Martínez; Cruces, Julia; Garrido, Antonio; Gonzalez-Sanchez, Mónica; De la Fuente, Mónica

    2017-08-01

    The age-related changes in the immune functions (immunosenescence) may be mediated by an increase of oxidative stress and damage affecting leukocytes. Although the "oxidation-inflammation" theory of aging proposes that phagocytes are the main immune cells contributing to "oxi-inflamm-aging", this idea has not been corroborated. The aim of this work was to characterize the age-related changes in several parameters of oxidative stress and immune function, as well as in lipofuscin accumulation ("a hallmark of aging"), in both total peritoneal leukocyte population and isolated peritoneal macrophages. Adult, mature, old and long-lived mice (7, 13, 18 and 30 months of age, respectively) were used. The xanthine oxidase (XO) activity-expression, basal levels of superoxide anion and ROS, catalase activity, oxidized (GSSG) and reduced (GSH) glutathione content and lipofuscin levels, as well as both phagocytosis and digestion capacity were evaluated. The results showed an age-related increase of oxidative stress and lipofuscin accumulation in murine peritoneal leukocytes, but especially in macrophages. Macrophages from old mice showed lower antioxidant defenses (catalase activity and GSH levels), higher oxidizing compounds (XO activity/expression and superoxide, ROS and GSSG levels) and lipofuscin levels, together with an impaired macrophage functions, in comparison to adults. In contrast, long-lived mice showed in their peritoneal leukocytes, and especially in macrophages, a well-preserved redox state and maintenance of their immune functions, all which could account for their high longevity. Interestingly, macrophages showed higher XO activity and lipofuscin accumulation than lymphocytes in all the ages analyzed. Our results support that macrophages play a central role in the chronic oxidative stress associated with aging, and the fact that phagocytes are key cells contributing to immunosenescence and "oxi-inflamm-aging". Moreover, the determination of oxidative stress and

  1. Age-related maculopathy and the impact of blue light hazard.

    Science.gov (United States)

    Algvere, Peep V; Marshall, John; Seregard, Stefan

    2006-02-01

    The pathogenesis of age-related maculopathy (ARM), the most common cause of visual loss after the age of 60 years, is indeed a complicated scenario that involves a variety of hereditary and environmental factors. The pathological cellular and molecular events underlying retinal photochemical light damage, including photoreceptor apoptosis, have been analysed in experimental animal models. Studies of age-related alterations of the retina and photoreceptors, the accumulation of lipofuscin in retinal pigment epithelium (RPE) cells, and the formation of drusen have greatly contributed to our knowledge. A new concept of an inflammatory response to drusen has emerged, suggesting immunogenic and systemic reactions in Bruch's membrane and the subretinal space. Oxidative stress and free radical damage also impact on the photoreceptors and RPE cells in the ageing eye. Based on the photoelectric effect, a fundamental concept in quantum physics, the consequences of high-energy irradiation have been analysed in animal models and cell culture. Short-wavelength radiation (rhodopsin spectrum), and the blue light hazard (excitation peak 440 nm), have been shown to have a major impact on photoreceptor and RPE function, inducing photochemical damage and apoptotic cell death. Following cataract surgery, there is a dramatic change in ocular transmittance. In aphakic or pseudophakic eyes (with clear intraocular lenses), high-energy (blue) and ultraviolet-A radiation strikes the retina. Epidemiological data indicate a significantly increased 5-year incidence of late ARM in non-phakic eyes compared with phakic eyes. In recent years, putative prophylactic measures against ARM have emerged. The implantation of 'yellow' intraocular lenses (IOLs) that absorb high-energy blue radiation is, from a theoretical point of view, the most rational approach, and, from a practical point of view, is easy to accomplish. With increasing age, RPE cells accumulate lipofuscin (chromophore A2E). It is

  2. 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

    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...... 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...

  3. LIFE HISTORY. Age-related mortality explains life history strategies of tropical and temperate songbirds.

    Science.gov (United States)

    Martin, Thomas E

    2015-08-28

    Life history theory attempts to explain why species differ in offspring number and quality, growth rate, and parental effort. I show that unappreciated interactions of these traits in response to age-related mortality risk challenge traditional perspectives and explain life history evolution in songbirds. Counter to a long-standing paradigm, tropical songbirds grow at similar overall rates to temperate species but grow wings relatively faster. These growth tactics are favored by predation risk, both in and after leaving the nest, and are facilitated by greater provisioning of individual offspring by parents. Increased provisioning of individual offspring depends on partitioning effort among fewer young because of constraints on effort from adult and nest mortality. These growth and provisioning responses to mortality risk finally explain the conundrum of small clutch sizes of tropical birds. Copyright © 2015, American Association for the Advancement of Science.

  4. 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.

  5. Normal age-related changes in left ventricular function: Role of afterload and subendocardial dysfunction.

    Science.gov (United States)

    Parikh, Jehill D; Hollingsworth, Kieren G; Wallace, Dorothy; Blamire, Andrew M; MacGowan, Guy A

    2016-11-15

    In normal ageing, both vascular and ventricular properties change, and how these affect left ventricular function is not clear. 96 subjects (ages 20-79) without cardiovascular disease underwent cardiac magnetic resonance (MR) imaging for measurement of global function, diastolic function (E/A ratio), MR tagging for measurement of torsion to shortening ratio (TSR, ratio of epicardial torsion to endocardial circumferential shortening, with increase in TSR suggesting subendocardial dysfunction relative to the subepicardium), and phase contrast MR imaging measurement of central aortic pulse wave velocity (PWV). The Vicorder device was used to measure carotid to femoral PWV. Univariate correlations established that the 4 principal age-related changes in the left ventricular function were: 1) diastolic function: E/A ratio (r: -0.61, psubendocardial dysfunction, has a significant role in reductions of cardiac output and end-diastolic volume index. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  6. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Does chronic exercise attenuate age-related physiological decline in males?

    Science.gov (United States)

    Hayes, Lawrence D; Grace, Fergal M; Sculthorpe, Nick; Herbert, Peter; Kilduff, Liam P; Baker, Julien S

    2013-01-01

    Alteration in body composition, physical function, and substrate metabolism occur with advancing age. These changes can be attenuated by exercise. This study evaluated whether master athletes (MA [n = 20]) would have improved exercise capabilities, anthropometry, and hormone profiles when compared with age-matched sedentary counterparts (S [n = 28]). The MA group was predominantly aerobically trained with some resistance exercise incorporated in their routine. The VO(2max), peak power output, and salivary testosterone was significantly higher (p group, while diastolic blood pressure, systolic blood pressure, and body fat percentage were lower (p different between groups. Salivary testosterone correlated positively with VO(2max) (r² = .320), suggesting that increased aerobic capacity is linked with higher concentrations of testosterone. These results suggest that life-long exercise is associated with favorable body composition and attenuation of the age related decline in testosterone.

  8. Systems-level analysis of age-related macular degeneration reveals global biomarkers and phenotype-specific functional networks

    Science.gov (United States)

    2012-01-01

    Background Age-related macular degeneration (AMD) is a leading cause of blindness that affects the central region of the retinal pigmented epithelium (RPE), choroid, and neural retina. Initially characterized by an accumulation of sub-RPE deposits, AMD leads to progressive retinal degeneration, and in advanced cases, irreversible vision loss. Although genetic analysis, animal models, and cell culture systems have yielded important insights into AMD, the molecular pathways underlying AMD's onset and progression remain poorly delineated. We sought to better understand the molecular underpinnings of this devastating disease by performing the first comparative transcriptome analysis of AMD and normal human donor eyes. Methods RPE-choroid and retina tissue samples were obtained from a common cohort of 31 normal, 26 AMD, and 11 potential pre-AMD human donor eyes. Transcriptome profiles were generated for macular and extramacular regions, and statistical and bioinformatic methods were employed to identify disease-associated gene signatures and functionally enriched protein association networks. Selected genes of high significance were validated using an independent donor cohort. Results We identified over 50 annotated genes enriched in cell-mediated immune responses that are globally over-expressed in RPE-choroid AMD phenotypes. Using a machine learning model and a second donor cohort, we show that the top 20 global genes are predictive of AMD clinical diagnosis. We also discovered functionally enriched gene sets in the RPE-choroid that delineate the advanced AMD phenotypes, neovascular AMD and geographic atrophy. Moreover, we identified a graded increase of transcript levels in the retina related to wound response, complement cascade, and neurogenesis that strongly correlates with decreased levels of phototransduction transcripts and increased AMD severity. Based on our findings, we assembled protein-protein interactomes that highlight functional networks likely to be

  9. Age-related skeletal muscle decline is similar in HIV-infected and uninfected individuals.

    Science.gov (United States)

    Yarasheski, Kevin E; Scherzer, Rebecca; Kotler, Donald P; Dobs, Adrian S; Tien, Phyllis C; Lewis, Cora E; Kronmal, Richard A; Heymsfield, Steven B; Bacchetti, Peter; Grunfeld, Carl

    2011-03-01

    Skeletal muscle (SM) mass decreases with advanced age and with disease in HIV infection. It is unknown whether age-related muscle loss is accelerated in the current era of antiretroviral therapy and which factors might contribute to muscle loss among HIV-infected adults. We hypothesized that muscle mass would be lower and decline faster in HIV-infected adults than in similar-aged controls. Whole-body (1)H-magnetic resonance imaging was used to quantify regional and total SM in 399 HIV-infected and 204 control men and women at baseline and 5 years later. Multivariable regression identified associated factors. At baseline and Year 5, total SM was lower in HIV-infected than control men. HIV-infected women were similar to control women at both time points. After adjusting for demographics, lifestyle factors, and total adipose tissue, HIV infection was associated with lower Year 5 SM in men and higher SM in women compared with controls. Average overall 5-year change in total SM was small and age related, but rate of change was similar in HIV-infected and control men and women. CD4 count and efavirenz use in HIV-infected participants were associated with increasing SM, whereas age and stavudine use were associated with decreasing SM. Muscle mass was lower in HIV-infected men compared with controls, whereas HIV-infected women had slightly higher SM than control women after multivariable adjustment. We found evidence against substantially faster SM decline in HIV infected versus similar-aged controls. SM gain was associated with increasing CD4 count, whereas stavudine use may contribute to SM loss.

  10. Risk Factors for Progression of Early Age-Related Macular Degeneration in Koreans.

    Science.gov (United States)

    Shim, Seong Hee; Kim, Soo-Geun; Bae, Jeong Hun; Yu, Hyeong Gon; Song, Su Jeong

    2016-01-01

    To identify risk factors for the progression of early age-related macular degeneration (AMD) in Koreans. This study was conducted at a health-screening center and followed a prospective cohort study design. Of 10,890 participants older than 50 years, 318 (2.92%) presented with early AMD. Among these 318 participants, we re-examined 172 participants after a mean duration of 4.4 years. Progression was defined by the Age-Related Eye Disease Study (AREDS) simplified AMD severity scale. Multivariable logistic regression was used to examine associations between AMD progression and baseline physical, demographic, behavioral, and ocular characteristics. Of the 172 participants with early AMD who were re-examined, 34 (19.8%) had progression. Multivariable analyses revealed that current smoking (odds ratio, OR, 7.0, 95% confidence interval, CI, 1.4-34.4, adjusted for age, alcohol consumption, body mass index, BMI, blood pressure, BP, total cholesterol, and high density lipoprotein, HDL, cholesterol) and hypertension (OR 10.3, 95% CI 1.9-55.7, adjusted for age, smoking status, alcohol consumption, BMI, total cholesterol, and HDL cholesterol) were independently associated with progression of early AMD. Additionally, the presence of a central drusen lesion within one-third disc diameter of the macula (age-adjusted OR 4.8, 95% CI 1.3-17.6) and 20 or more drusen (age adjusted OR 7.8, 95% CI 2.5-24.0) were independently associated with progression of early AMD. Current smoking, hypertension, central drusen location, and increasing number of drusen were associated with an increased risk of early AMD progression in Koreans.

  11. 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.)

  12. Age-related changes in muscle strength and spinal kyphosis angles in an elderly Japanese population

    Directory of Open Access Journals (Sweden)

    Kasukawa Y

    2017-02-01

    Full Text Available Yuji Kasukawa, Naohisa Miyakoshi, Michio Hongo, Yoshinori Ishikawa, Daisuke Kudo, Masazumi Suzuki, Takashi Mizutani, Ryouta Kimura, Yuichi Ono, Yoichi Shimada Department of Orthopedic Surgery, Akita University Graduate School of Medicine, Akita, Japan Abstract: Lumbar kyphosis and the decreased mobility of the lumbar spine increase the risk of falls and impair both the quality of life and the ability to perform activities of daily living. However, in the elderly Japanese population, little is known about the age-related changes and sex-related differences in muscle strength, including of the upper and lower extremities and back extensors. An adequate kyphotic or lordotic angle has also not been determined. In this study, we evaluated the age-related changes in muscle strength and spinal kyphosis in 252 males and 320 females ≥50 years of age. Grip, back extensor, hip flexor, and knee extensor strength; thoracic and lumbar kyphosis; and spinal inclination in the neutral standing position were assessed, together with the range of motion of the thoracic and lumbar spine and spinal inclination. Grip strength, back extensor strength, and the strength of the hip flexors and knee extensors decreased significantly with aging, both in males (P<0.0001 and in females (P=0.0015 to P<0.0001. The lumbar but not the thoracic kyphosis angle decreased significantly with aging, only in females (P<0.0001. Spinal inclination increased significantly with aging in both males (P=0.002 and females (P<0.0001. Back extensor strength and the thoracic kyphosis angle were significant variables influencing the lumbar kyphosis angle in both sexes. Spinal inclination correlated significantly with both the lumbar kyphosis angle and hip flexor strength in males, as well as with the lumbar kyphosis angle in females. Keywords: aging, gender, grip strength, back extensor strength, spinal curvature

  13. Characterization of age-related gene expression profiling in bone marrow and epididymal adipocytes

    Directory of Open Access Journals (Sweden)

    Ueno Masami

    2011-05-01

    Full Text Available Abstract Background While an increase in bone marrow adiposity is associated with age-related bone disease, the function of bone marrow adipocytes has not been studied. The aim of this study was to characterize and compare the age-related gene expression profiles in bone marrow adipocytes and epididymal adipocytes. Results A total of 3918 (13.7% genes were differentially expressed in bone marrow adipocytes compared to epididymal adipocytes. Bone marrow adipocytes revealed a distinct gene profile with low expression of adipocyte-specific genes peroxisome proliferator-activated receptor gamma (PPARγ, fatty acid binding protein 4 (FABP4, perilipin (Plin1, adipsin (CFD and high expression of genes associated with early adipocyte differentiation (CCAAT/enhancer binding protein beta (C/EBPβ, regulator of G-protein signaling 2 (RGS2. In addition, a number of genes including secreted frizzled related protein 4 (SFRP4, tumor necrosis factor α (TNFα, transforming growth factor beta 1(TGFβ1, G-protein coupled receptor 109A (GPR109A and interleukin 6 (IL-6, that could affect adipose-derived signaling to bone are markedly increased in bone marrow adipocytes. Age had a substantial effect on genes associated with mitochondria function and inflammation in bone marrow adipocytes. Twenty seven genes were significantly changed with age in both adipocyte depots. Among these genes, IL6 and GPR109A were significantly reduced with age in both adipocyte depots. Conclusions Overall, gene profiling reveals a unique phenotype for primary bone marrow adipocytes characterized by low adipose-specific gene expression and high expression of inflammatory response genes. Bone marrow and epididymal adipocytes share a common pathway in response to aging in mice, but age has a greater impact on global gene expression in epididymal than in bone marrow adipocytes. Genes that are differentially expressed at greater levels in the bone marrow are highly regulated with age.

  14. Age-related differences in oligodendrogenesis across the dorsal-ventral axis of the mouse hippocampus.

    Science.gov (United States)

    Yamada, Jun; Jinno, Shozo

    2014-08-01

    Oligodendrocyte precursor cells (OPCs) continue to divide and generate new oligodendrocytes (OLs) in the healthy adult brain. Although recent studies have indicated that adult oligodendrogenesis may be vital for the maintenance of normal brain function, the significance of adult oligodendrogenesis in brain aging remains unclear. In this study, we report a stereological estimation of age-related oligodendrogenesis changes in the mouse hippocampus: the dorsal subdivision is related to learning and memory, while the ventral subdivision is involved in emotional behaviors. To identify OPCs and OLs, we used a set of molecular markers, OL lineage transcription factor (Olig2) and platelet-derived growth factor receptor-alpha (PDGFαR). Intracellular dye injection shows that PDGFαR+/Olig2+ cells and PDGFαR-/Olig2+ cells can be defined as OPCs and OLs, respectively. In the dorsal Ammon's horn, the numbers of OPCs decreased with age, while those of OLs remained unchanged during aging. In the ventral Ammon's horn, the numbers of OPCs and OLs generally decreased with age. Bromodeoxyuridine (BrdU) fate-tracing analysis revealed that the numbers of BrdU+ mitotic OPCs in the Ammon's horn remained unchanged during aging in both the dorsal and ventral subdivisions. Unexpectedly, the numbers of BrdU+ newly generated OLs increased with age in the dorsal Ammon's horn, but remained unchanged in the ventral Ammon's horn. Together, the numbers of OLs in the dorsal Ammon's horn may be maintained during aging by increased survival of adult born OLs, while the numbers of OLs in the ventral Ammon's horn may be reduced with age due to the lack of such compensatory mechanisms. These observations provide new insight into the involvement of adult oligodendrogenesis in age-related changes in the structure and function of the hippocampus. © 2014 Wiley Periodicals, Inc.

  15. Normalisation against Circadian and Age-Related Disturbances Enables Robust Detection of Gene Expression Changes in Liver of Aged Mice

    Science.gov (United States)

    Fonseca Costa, Sara S.; Wegmann, Daniel; Ripperger, Jürgen A.

    2017-01-01

    The expression of some genes is affected by age. To detect such age-related changes, their expression levels are related to constant marker genes. However, transcriptional noise increasing with advancing age renders difficult the identification of real age-related changes because it may affect the marker genes as well. Here, we report a selection procedure for genes appropriate to normalise the mouse liver transcriptome under various conditions including age. These genes were chosen from an initial set of 16 candidate genes defined based on a RNA-sequencing experiment and published literature. A subset of genes was selected based on rigorous statistical assessment of their variability using both RNA-sequencing and Nanostring hybridization experiments. The robustness of these marker genes was then verified by the analysis of 130 publicly available data sets using the mouse liver transcriptome. Altogether, a set of three genes, Atp5h, Gsk3β, and Sirt2 fulfilled our strict selection criteria in all assessments, while four more genes, Nono, Tprkb, Tspo, and Ttr passed all but one assessment and were included into the final set of marker genes to enhance robustness of normalisation against outliers. Using the geometric mean of expression of the genes to normalise Nanostring hybridization experiments we reliably identified age-related increases in the expression of Casein kinase 1δ and 1ϵ, and Sfpq, while the expression of the glucose transporter Glut2 decreased. The age-related changes were verified by real-time PCR and Western blot analysis. As conclusion, proper normalisation enhances the robustness of quantitative methods addressing age-related changes of a transcriptome. PMID:28068403

  16. Age-related modifications of egr1 expression and ubiquitin-proteasome components in pet dog hippocampus.

    Science.gov (United States)

    Ghi, Piera; Di Brisco, Fabio; Dallorto, Dario; Osella, Maria Cristina; Orsetti, Marco

    2009-05-01

    In this paper we examined the impact of age on cognitive functions and the age-related modifications of egr1 expression, an inducible transcription factor with a confirmed role in synaptic plasticity and regulation of the proteasome activity, on pet dogs. Additionally, we examined the age-related changes of some elements of the ubiquitin-proteasome system, which is the apparatus that prevents the intracellular accumulation of abnormal proteins. The results of behavioral analysis revealed that old/senior dogs (9-16-year-old) had impaired cognitive performance compared to young/middle-aged dogs (2-8-year-old) in the Reversal Learning task. Taken togheter, the results (age-related decline of Psmd4, Psmb8, CHIP, and egr1 expression; increase of Psmb9 and Hsp90 expression) suggest that the activity of the ubiquitin-proteasome system in the dog hippocampus is a multi-step process, in which abnormal proteins destined for degradation are recognized and destroyed, and shows an age-related decline. The consequent failure of the "protein quality control system" might have detrimental effects on cell physiology and lead to a progressive impairment of cognitive functions.

  17. 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.

  18. Age-related disease association of endogenous γ-H2AX foci in mononuclear cells derived from leukapheresis.

    Directory of Open Access Journals (Sweden)

    Shepherd H Schurman

    Full Text Available The phosphorylated form of histone H2AX (γ-H2AX forms immunohistochemically detectable foci at DNA double strand breaks. In peripheral blood mononuclear cells (PBMCs derived from leukapheresis from patients enrolled in the Baltimore Longitudinal Study of Aging, γ-H2AX foci increased in a linear fashion with regards to age, peaking at ~57 years. The relationship between the frequency of γ-H2AX foci and age-related pathologies was assessed. We found a statistically significant (p = 0.023 50% increase in foci in PBMCs derived from patients with a known history of vitamin D deficiency. In addition, there were trends toward increased γ-H2AX foci in patients with cataracts (34% increase, p<0.10 and in sleep apnea patients (44%, p<0.10. Among patients ≥57 y/o, we found a significant (p = 0.037 36% increase in the number of γ-H2AX foci/cell for patients with hypertension compared to non-hypertensive patients. Our results support a role for increased DNA damage in the morbidity of age-related diseases. γ -H2AX may be a biomarker for human morbidity in age-related diseases.

  19. Age-related and historical changes in the clinical characteristics of sarcoidosis in Japan.

    Science.gov (United States)

    Sawahata, Michiru; Sugiyama, Yukihiko; Nakamura, Yosikazu; Nakayama, Masayuki; Mato, Naoko; Yamasawa, Hideaki; Bando, Masashi

    2015-02-01

    National surveys conducted in Japan between 1960 and 2004 suggest a gradually increasing incidence of sarcoidosis in women >50 years old with increased involvement of the eye, skin, and heart. However, whether this involvement is due to the increased age at diagnosis is still unclear. We aimed here to identify the age-related differences in organ involvement in sarcoidosis in Japan, as well as the historical changes in clinical characteristics and the age-specific distribution of cases at diagnosis. We reviewed 588 consecutive Japanese patients newly diagnosed with sarcoidosis between 1974 and 2012 at Jichi Medical University Hospital. We compared organ involvement between subgroups differentiated by sex and age (lymphatic extrathoracic organs such as the eye, heart, muscle, and kidney. The age at diagnosis has consistently increased over the past four decades. The monophasic distribution in men has tended to become biphasic, and the biphasic distribution in women monophasic. Increasing trends were apparent for hypercalcemia and involvement of the gastrointestinal tract, skin, nervous system, muscle, and kidney. Elderly patients at diagnosis had various extrathoracic involvement including eye, skin, and cardiac lesions. Moreover, the age at diagnosis of sarcoidosis has continued to increase in both sexes, influencing the recent trends in clinical characteristics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Effect of Age-Related Human Lens Sutures Growth on Its Fluid Dynamics.

    Science.gov (United States)

    Wu, Ho-Ting D; Howse, Louisa A; Vaghefi, Ehsan

    2017-12-01

    Age-related nuclear cataract is the opacification of the clear ocular lens due to oxidative damage as we age, and is the leading cause of blindness in the world. A lack of antioxidant supply to the core of ever-growing ocular lens could contribute to the cause of this condition. In this project, a computational model was developed to study the sutural fluid inflow of the aging human lens. Three different SOLIDWORKS computational fluid dynamics models of the human lens (7 years old; 28 years old; 46 years old) were created, based on available literature data. The fluid dynamics of the lens sutures were modelled using the Stokes flow equations, combined with realistic physiological boundary conditions and embedded in COMSOL Multiphysics. The flow rate, volume, and flow rate per volume of fluid entering the aging lens were examined, and all increased over the 40 years modelled. However, while the volume of the lens grew by ∼300% and the flow rate increased by ∼400%, the flow rate per volume increased only by very moderate ∼38%. Here, sutural information from humans of 7 to 46 years of age was obtained. In this modelled age range, an increase of flow rate per volume was observed, albeit at very slow rate. We hypothesize that with even further increasing age (60+ years old), the lens volume growth would outpace its flow rate increases, which would eventually lead to malnutrition of the lens nucleus and onset of cataracts.

  1. Age-Related Cataract, Cataract Surgery and Subsequent Mortality: A Systematic Review and Meta-Analysis

    Science.gov (United States)

    Song, E; Sun, Hongpeng; Xu, Yong; Ma, Yana; Zhu, Hong; Pan, Chen-Wei

    2014-01-01

    Purpose Changes in lens may reflect the status of systemic health of human beings but the supporting evidences are not well summarized yet. We aimed to determine the relationship of age-related cataract, cataract surgery and long-term mortality by pooling the results of published population-based studies. Methods We searched PubMed and Embase from their inception till March, 2014 for population-based studies reporting the associations of any subtypes of age-related cataract, cataract surgery with all-cause mortality. We pooled the effect estimates (hazards ratios [HRs]) under a random effects model. Results Totally, we identified 10 unique population-based studies including 39,659 individuals at baseline reporting the associations of any subtypes of cataract with all-cause mortality from 6 countries. The presence of any cataract including cataract surgery was significantly associated with a higher risk of death (pooled HR: 1.43, 95% CI, 1.21, 2.02; Pcataract were at higher risks of mortality (pooled HR: 1.55, 95% CI, 1.17, 2.05; P = 0.002; I2 = 89.2%). In the meta-analysis of 8 study findings, cortical cataract was associated with higher risks of mortality (pooled HR: 1.26, 95% CI, 1.12, 1.42; Pcataract was associated with higher risks of mortality (pooled HR: 1.37, 95% CI, 1.04, 1.80; P = 0.03; I2 = 67.3%). The association between cataract surgery and mortality was marginally non-significant by pooling 8 study findings (pooled HR: 1.27, 95% CI, 0.97, 1.66; P = 0.08; I2 = 76.6%). Conclusions All subtypes of age-related cataract were associated with an increased mortality with nuclear cataract having the strongest association among the 3 cataract subtypes. However, cataract surgery was not significantly related to mortality. These findings indicated that changes in lens may serve as markers for ageing and systemic health in general population. PMID:25369040

  2. Induced Pluripotent Stem Cell Derived Mesenchymal Stem Cells for Attenuating Age-Related Bone Loss

    Science.gov (United States)

    2012-07-01

    Mesenchymal stem cell (MSC) differentiation towards the bone forming osteoblastic lineage decreases as a function of age and may contribute to age-related...problem of age-related reduced availability of MSC we propose to examine the bone anabolic potential of induced pluripotent stem cell (iPS) derived MSC

  3. [Physical activity diminishes aging-related decline of physical and cognitive performance].

    Science.gov (United States)

    Apor, Péter; Babai, László

    2014-05-25

    Aging-related decline of muscle force, walking speed, locomotor coordination, aerobic capacity and endurance exert prognostic impact on life expectancy. Proper use of training may diminish the aging process and it may improve the quality of life of elderly persons. This paper provides a brief summary on the impact of training on aging-related decline of physical and cognitive functions.

  4. Assessment of age-related bone loss in normal South African ...

    African Journals Online (AJOL)

    Atr Med J. Assessment of age-related bone loss in normal South. African women by means of the Hologic QDR 1000 system. A. A. Kalla, A. B. Fataar, L. Bewerunge. The aim of this study was to evaluate age-related changes in cortical and trabecular bone mineral density (BMD) in. South African subjects, and to develop a ...

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

    Science.gov (United States)

    Dummer, Gail M.; And Others

    1985-01-01

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

  6. Is age-related maculopathy associated with Alzheimer's Disease? The Rotterdam Study

    NARCIS (Netherlands)

    Klaver, C. C.; Ott, A.; Hofman, A.; Assink, J. J.; Breteler, M. M.; de Jong, P. T.

    1999-01-01

    The authors examined the relation between age-related maculopathy and Alzheimer's disease in the Rotterdam Study, a prospective population-based study in the Netherlands. From 1990 to mid-1993, subjects aged 75 years or older (n = 1,438) were screened for the presence of age-related maculopathy and

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

    Science.gov (United States)

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

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

  8. 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...

  9. Vitamin D deficiency in neovascular versus nonneovascular age-related macular degeneration.

    Science.gov (United States)

    Itty, Sujit; Day, Shelley; Lyles, Kenneth W; Stinnett, Sandra S; Vajzovic, Lejla M; Mruthyunjaya, Prithvi

    2014-09-01

    To compare 25-hydroxyvitamin D (25OHD) levels in patients with neovascular age-related macular degeneration (NVAMD) with patients with nonneovascular age-related macular degeneration and control patients. Medical records of all patients diagnosed with age-related macular degeneration and tested for serum 25OHD level at a single medical center were reviewed. Control patients were selected from patients diagnosed with pseudophakia but without age-related macular degeneration. The lowest 25OHD level available for each patient was recorded. Two hundred sixteen patients with nonneovascular age-related macular degeneration, 146 with NVAMD, and 100 non-age-related macular degeneration control patients were included. The levels of 25OHD (mean ± SD) were significantly lower in NVAMD patients (26.1 ± 14.4 ng/mL) versus nonneovascular age-related macular degeneration (31.5 ± 18.2 ng/mL, P = 0.003) and control (29.4 ± 10.1 ng/mL, P = 0.049) patients. The prevalence of vitamin D insufficiency (age-related macular degeneration. Mean 25OHD levels were lower and vitamin D deficiency was more prevalent in NVAMD patients. These associations suggest that further research is necessary regarding vitamin D deficiency as a potentially modifiable risk factor for the development of NVAMD.

  10. Subfoveal fibrosis in eyes with neovascular age-related macular degeneration treated with intravitreal ranibizumab

    DEFF Research Database (Denmark)

    Bloch, Sara Brandi; Lund-Andersen, Henrik; Sander, Birgit

    2013-01-01

    To assess baseline and follow-up characteristics of choroidal neovascularization (CNV) lesions in age-related macular degeneration in relation to the development of subfoveal subretinal fibrosis.......To assess baseline and follow-up characteristics of choroidal neovascularization (CNV) lesions in age-related macular degeneration in relation to the development of subfoveal subretinal fibrosis....

  11. Three Studies Point to Same Risk Gene for Age-Related Macular Degeneration

    Science.gov (United States)

    ... Three studies point to same risk gene for age-related macular degeneration NIH-funded research helps unravel the biology of ... as a rare, but powerful risk factor for age-related macular degeneration (AMD), a common cause of vision loss in ...

  12. Cigarette smoking and age-related macular degeneration in the EUREYE Study

    NARCIS (Netherlands)

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

    2007-01-01

    To examine the association between cigarette smoking and age-related maculopathy (ARM) including age-related macular degeneration (AMD) in the European population. Cross-sectional study. Four thousand seven hundred fifty randomly sampled > or =65-year-olds from 7 study centers across Europe (Norway,

  13. New Treatment Greatly Improves Prognosis for Patients with AMD (Age-Related Macular Degeneration)

    Science.gov (United States)

    ... page please turn JavaScript on. Feature: Age-related Macular Degeneration New Treatment Greatly Improves Prognosis for Patients with ... study of nearly 650 people with age-related macular degeneration (AMD), half still had 20/40 vision or ...

  14. The relationship of major American dietary patterns to age-related macular degeneration

    Science.gov (United States)

    We hypothesized that major American dietary patterns are associated with age-related macular degeneration (AMD) risk. This was a cross-sectional study with 8,103 eyes from 4,088 eligible participants in the baseline Age-Related Eye Disease Study (AREDS) were classified into control (n=2,739), early ...

  15. Orexin restores aging-related brown adipose tissue dysfunction in male mice.

    Science.gov (United States)

    Sellayah, Dyan; Sikder, Devanjan

    2014-02-01

    The aging process causes an increase in percent body fat, but the mechanism remains unclear. In the present study we examined the impact of aging on brown adipose tissue (BAT) thermogenic activity as potential cause for the increase in adiposity. We show that aging is associated with interscapular BAT morphologic abnormalities and thermogenic dysfunction. In vitro experiments revealed that brown adipocyte differentiation is defective in aged mice. Interscapular brown tissue in aged mice is progressively populated by adipocytes bearing white morphologic characteristics. Aged mice fail to mobilize intracellular fuel reserves from brown adipocytes and exhibit deficiency in homeothermy. Our results suggest a role for orexin (OX) signaling in the regulation of thermogenesis during aging. Brown fat dysfunction and age-related assimilation of fat mass were accelerated in mice in which OX-producing neurons were ablated. Conversely, OX injections in old mice increased multilocular morphology, increased core body temperature, improved cold tolerance, and reduced adiposity. These results argue that BAT can be targeted for interventions to reverse age-associated increase in fat mass.

  16. Age-related differences in the automatic processing of single letters: implications for selective attention.

    Science.gov (United States)

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

    2014-01-22

    Older adults exhibit diminished ability to inhibit the processing of visual stimuli that are supposed to be ignored. The extent to which age-related changes in early visual processing contribute to impairments in selective attention remains to be determined. Here, 103 adults, 18-85 years of age, completed a color selective attention task in which they were asked to attend to a specified color and respond to designated target letters. An optimal approach would be to initially filter according to color and then process letter forms in the attend color to identify targets. An asymmetric N170 ERP component (larger amplitude over left posterior hemisphere sites) was used as a marker of the early automatic processing of letter forms. Young and middle-aged adults did not generate an asymmetric N170 component. In contrast, young-old and old-old adults produced a larger N170 over the left hemisphere. Furthermore, older adults generated a larger N170 to letter than nonletter stimuli over the left, but not right hemisphere. More asymmetric N170 responses predicted greater allocation of late selection resources to target letters in the ignore color, as indexed by P3b amplitude. These results suggest that unlike their younger counterparts, older adults automatically process stimuli as letters early in the selection process, when it would be more efficient to attend to color only. The inability to ignore letters early in the processing stream helps explain the age-related increase in subsequent processing of target letter forms presented in the ignore color.

  17. 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.

  18. The prevalence of age-related macular degeneration in Italy (PAMDI) study: report 1.

    Science.gov (United States)

    Piermarocchi, Stefano; Segato, Tatiana; Scopa, Pasquale; Masetto, Morena; Ceca, Stela; Cavarzeran, Fabiano; Peto, Tunde

    2011-06-01

    The present study aimed to estimate prevalence and risk factors associated with age-related macular degeneration (ARMD) in an Italian population and to analyze differences between urban and rural communities. We conducted a population-based cross-sectional study among elderly residents in Northeast Italy. Participants were divided into urban and rural groups based on whether they lived in the city of Padova or the villages of Teolo and Torreglia, respectively. Fundus photographs were graded according to the International Classification for Age-related Maculopathy. A total of 1162 randomly selected subjects aged 61 years or more were invited to participate in the study. We examined 885 subjects, and 845 were eligible for fundus photograph grading. ARMD was estimated to affect 62.7% of the whole population (drusen 63-124 μm = 48.3%; drusen ≥125 μm = 10.4%; advanced ARMD = 4.1%). Age was confirmed as a risk factor for drusen ≥125 μm and advanced ARMD (Odds Ratio [OR] = 1.47, 95% Confidence Interval [CI] 1.28-1.69 and OR = 1.62, 95% CI 1.28-2.05, respectively, for a 5-year increase in age). The rural group appeared to be at a higher risk of developing large drusen compared to the urban sample (OR = 1.61, 95% CI 1.01-2.63) when adjusting for age and gender. The results confirmed that ARMD affects a high percentage of the elderly population in Italy. This study does not support the hypothesis that living in a rural environment or belonging to a population of the Mediterranean basin may be protective against the intermediate stages of the disease.

  19. 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.

  20. Age-related decline in salivary dehydroepiandrosterone sulfate and associated health risks among African Americans.

    Science.gov (United States)

    Abraham, Preetha Anna; Kazman, Josh Ben; Zeno, Stacey Anne; Poth, Merrily; Deuster, Patricia Anne

    2013-01-01

    Dehydroepiandrosterone sulfate (DHEAS) declines with age and low endogenous DHEAS concentrations have been associated with obesity. In addition, DHEAS has been studied for its role in mood and wellbeing. However, limited data are available on salivary DHEAS concentrations in African Americans. Thus, we examined age-related changes in morning salivary DHEAS and the association between DHEAS and obesity risk factors among African Americans. Salivary DHEAS samples (n=170) were obtained from men and women divided into three age groups: 18 to 30 (young), 31 to 45 (middle) and 46 to 60 (older) years. Anthropometric, blood glucose, high sensitivity c-reactive protein (hsCRP), and blood pressure measures were obtained. Participants completed the Center for Epidemiologic Studies Depression (CESD), Beck Depression Inventory (BDI), Daily Hassles Scale (DHS), Perceived Stress Scale (PSS) and Pittsburgh Sleep Quality Index (PSQI) scales to assess depression, daily hassles, stress and quality of sleep, respectively. Mean salivary DHEAS concentrations decreased significantly with increasing age: mean values were 25.8 +/- 2.4, 21.9 +/- 1.9, and 14.4 +/- .9 nmol/L for young, middle, and older groups, respectively. Like DHEAS, PSQI, DHS, CESD, MAP, WC, BMI, systolic and diastolic BP and fasting blood glucose values differed significantly in the older compared to the young and middle groups. Women had significantly lower salivary DHEAS than men (P< or =.05). The age-related decline in salivary DHEAS in African Americans is associated with cardiovascular risk factors, sleep quality, hassles and mood. Whether supplementing DHEAS levels in aging African Americans will improve health remains to be determined.

  1. Genipin ameliorates age-related insulin resistance through inhibiting hepatic oxidative stress and mitochondrial dysfunction.

    Science.gov (United States)

    Guan, Lili; Feng, Haiyan; Gong, Dezheng; Zhao, Xu; Cai, Li; Wu, Qiong; Yuan, Bo; Yang, Mei; Zhao, Jie; Zou, Yuan

    2013-12-01

    Insulin resistance (IR) increases with age and plays a key role in the pathogenesis of type 2 diabetes mellitus. Oxidative stress and mitochondrial dysfunction are supposed to be major factors leading to age-related IR. Genipin, an extract from Gardenia jasminoides Ellis fruit, has been reported to stimulate insulin secretion in pancreatic islet cells by regulating mitochondrial function. In this study, we first investigated the effects of genipin on insulin sensitivity and the potential mitochondrial mechanisms in the liver of aging rats. The rats were randomly assigned to receive intraperitoneal injections of either 25mg/kg genipin or vehicle once daily for 12days. The aging rats showed hyperinsulinemia and hyperlipidemia, and insulin resistance as examined by the decreased glucose decay constant rate during insulin tolerance test (kITT). The hepatic tissues showed steatosis and reduced glycogen content. Hepatic malondialdehyde level and mitochondrial reactive oxygen species (ROS) were higher, and levels of mitochondrial membrane potential (MMP) and ATP were lower as compared with the normal control rats. Administration of genipin ameliorated systemic and hepatic insulin resistance, alleviated hyperinsulinemia, hyperglyceridemia and hepatic steatosis, relieved hepatic oxidative stress and mitochondrial dysfunction in aging rats. Furthermore, genipin not only improved insulin sensitivity by promoting insulin-stimulated glucose consumption and glycogen synthesis, inhibited cellular ROS overproduction and alleviated the reduction of levels of MMP and ATP, but also reversed oxidative stress-associated JNK hyperactivation and reduced Akt phosphorylation in palmitate-treated L02 hepatocytes. In conclusion, genipin ameliorates age-related insulin resistance through inhibiting hepatic oxidative stress and mitochondrial dysfunction. © 2013.

  2. Retinal vascular caliber and age-related macular degeneration in an Indian population from Singapore.

    Science.gov (United States)

    Chin, You Chuen; Wong, Tien Yin; Cheung, Chui Ming Gemmy; Cheung, Carol Yim-Lui; Zheng, Yingfeng; Mitchell, Paul; Huang, HuiQi; Wang, Jie Jin; Ikram, Mohammad Kamran

    2014-08-01

    To examine the association between retinal vascular caliber and early age-related macular degeneration (AMD) in an Indian population. A total of 3112 Indian participants aged ≥40 years from the population-based Singapore Indian Eye Study who had data available on retinal vascular caliber measurements and AMD status were included. Retinal arteriolar and venular calibers were measured from digital photographs using computer-assisted software according to a standardized protocol. Images of the macular region were graded according to the modified Wisconsin age-related maculopathy grading system. Right eyes were selected for analyses. Binary logistic regression models were used to assess the association, adjusting for age, sex, systolic blood pressure, total cholesterol, random blood glucose, body mass index, and the companion retinal vascular caliber. A total of 107 participants (3.4%) were diagnosed with early AMD. Neither arteriolar nor venular caliber was related to AMD. For early AMD, the age-, sex-, and companion retinal vascular caliber-adjusted odds ratio (OR) per standard deviation (SD) decrease in arteriolar caliber was 0.95 (95% CI 0.84-1.31; p = 0.671), and per SD increase in venular caliber was OR: 0.96 (95% CI: 0.77-1.20); p = 0.714. No trend was found after categorizing retinal vascular calibers into quartiles. Multivariate adjustment and stratified analyses did not alter these results. Retinal vascular calibers were not related to early AMD among Indian participants. These findings differ from those of several previous studies performed in Caucasian and Asian populations.

  3. Heightened inflammasome activation is linked to age-related cognitive impairment in Fischer 344 rats

    Directory of Open Access Journals (Sweden)

    Mawhinney Lana J

    2011-12-01

    Full Text Available Abstract Background Members of the mammalian nucleotide binding domain, leucine-rich repeat (LRR-containing receptor (NLR family of proteins are key modulators of innate immunity regulating inflammation. Our previous work has shown that among the members of this family, NLRP1/NALP1, present in neurons, plays a crucial role in inflammasome formation and the production of the inflammatory cytokines interleukin (IL -1β and IL-18 after various types of central nervous system injury. Results We investigated whether age-related cognitive decline may involve a heightened inflammatory response associated with activation of the NLRP1 inflammasome in the hippocampus. Young (3 months and aged (18 months male Fischer 344 rats were tested in a spatial acquisition task via Morris water maze. Following behavioral testing, hippocampal lysates were assayed for expression of NLRP1 inflammasome components and inflammatory cytokines. Hippocampal lysates from aged rats showed significantly higher levels of NLRP1 inflammasome constituents, caspase-1, caspase-11, the purinergic receptor P2X7, pannexin-1 and X-linked inhibitor of apoptosis (XIAP than lysates from younger animals. Following treatment with probenecid, an inhibitor or pannexin-1, aged animals demonstrated reduction in inflammasome activation and improvement in spatial learning performance. Conclusions Our behavioral findings are consistent with increases in IL-1β and IL-18 that have been previously shown to correlate with spatial learning deficits. Probenecid reduced activated caspase-1 and ameliorated spatial learning deficits in aged rats. Thus, aging processes stimulate activation of the NLRP1 inflammasome and secretion of IL-1β and IL-18 that may contribute to age-related cognitive decline in the growing elderly population. Moreover, probenecid may be potentially useful as a therapy to improve cognitive outcomes in the aging population.

  4. 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

    2015-10-06

    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.

  5. Normal age-related conversion of bone marrow in the skull base. Assessment with MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Koki; Tomura, Noriaki; Takahashi, Satoshi; Izumi, Junichi; Kurosawa, Ryo; Sashi, Ryuji; Watarai, Jiro [Akita Univ. (Japan). School of Medicine

    2000-12-01

    The purpose of this study was to assess the normal age-related sequence of conversion from hematopoietic to fatty marrow in the skull base by means of MR imaging. We retrospectively reviewed T1-weighted MR images of the skull base for the distribution of hematopoietic and fatty marrow. The subjects consisted of 169 MR examinations that were performed with the spin-echo technique. The age of the subjects ranged from 0 months to 20 years old. Patients with known marrow abnormalities were excluded from this study. Marrow conversion was assessed in the presphenoid, postsphenoid, basiocciput, petrous apex, clivus, zygomatic bone, and condyle of the mandible. The signal intensity was visually graded, and the signal intensity ratio was determined on the basis of the intensities of the subcutaneous fat and air. The signal intensity of all observed regions was as low as that of muscles until 3 months of age. Conversion of hematopoietic to fatty marrow first occurred in the zygomatic bone until 6 months of age. The presphenoid increased in signal intensity from 5 months to 2 years of age, and the sphenoid sinus began to be pneumatic at this age. Marrow conversion of the postsphenoid and basiocciput was later than that of the presphenoid. Most of the bone marrow of the skull base appeared as fatty conversion until 3 years of age, although some mandibular condyles appeared hematopoietic at 3 years of age. The normal age-related conversion from hematopoietic to fatty marrow in the skull base followed a well-defined sequence. Knowledge of the normal bone marrow conversion by MR imaging is essential for the recognition of pathologic marrow processes. (author)

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

    Science.gov (United States)

    Gipson, Ilene K

    2013-12-13

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

  7. Changing from bevacizumab to ranibizumab in age-related macular degeneration. Is it safe?

    Directory of Open Access Journals (Sweden)

    Dimitrios A Karagiannis

    2009-11-01

    Full Text Available Dimitrios A Karagiannis1, Ioannis D Ladas2, Efstratios Parikakis1, Ilias Georgalas2, Athanasios Kotsolis2, Giorgos Amariotakis1, Vasileios Soumplis1, Panagiotis Mitropoulos11Ophthalmiatrio Eye Hospital of Athens, Athens, Greece; 2First Department of Ophthalmology, Medical School of Athens University, General Hospital of Athens, Athens, GreeceObjective: To report our experiences in changing from intravitreal bevacizumab to ranibizumab in age-related macular degeneration (AMD.Design: Retrospective case series.Participants and methods: We retrospectively reviewed the records of 34 patients (36 eyes who were treated with monthly injections of intravitreal bevacizumab for six months and then switched to monthly injections of ranibizumab for 12 months. Best-corrected visual acuity measurements (BCVA, contact lens biomicroscopy, optical coherence tomography (OCT, and fluorescein angiography were performed at the baseline examination and then monthly. Chi-square test was used for statistical analysis.Results: Following bevacizumab treatment, retinal thickness decreased (P = 0.033 while BCVA improved (P = 0.040. Changing from bevacizumab to ranibizumab resulted in a transient decrease in BCVA (P = 0.045 and an increase in retinal thickness (P = 0.042. In addition, three eyes presented with a large subretinal hemorrhage. However, final retinal thickness was better than the initial thickness and the value following the bevacizumab course. No major ocular or systemic side effects were noted.Conclusions: Ranibizumab was clinically effective in the long term but the change of treatment from bevacizumab to a half-size molecule with less half-life in the vitreous such as ranibizumab contributed to a transient “instability” in the eye which may have triggered the large subretinal hemorrhage. There is insufficient experience reported in the literature in switching from one agent to another. A prospective study with controls is necessary to determine whether

  8. [The age-related macular degeneration as a vascular disease/part of systemic vasculopathy: contributions to its pathogenesis].

    Science.gov (United States)

    Fischer, Tamás

    2015-03-01

    The wall of blood vessels including those in choroids may be harmed by several repeated and/or prolonged mechanical, physical, chemical, microbiological, immunologic, and genetic impacts (risk factors), which may trigger a protracted response, the so-called host defense response. As a consequence, pathological changes resulting in vascular injury (e. g. atherosclerosis, age-related macular degeneration) may be evolved. Risk factors can also act directly on the endothelium through an increased production of reactive oxygen species promoting an endothelial activation, which leads to endothelial dysfunction, the onset of vascular disease. Thus, endothelial dysfunction is a link between the harmful stimulus and vascular injury; any kind of harmful stimuli may trigger the defensive chain that results in inflammation that may lead to vascular injury. It has been shown that even early age-related macular degeneration is associated with the presence of diffuse arterial disease and patients with early age-related macular degeneration demonstrate signs of systemic and retinal vascular alterations. Chronic inflammation, a feature of AMD, is tightly linked to diseases associated with ED: AMD is accompanied by a general inflammatory response, in the form of complement system activation, similar to that observed in degenerative vascular diseases such as atherosclerosis. All these facts indicate that age-related macular degeneration may be a vascular disease (or part of a systemic vasculopathy). This recognition could have therapeutic implications because restoration of endothelial dysfunction may prevent the development or improve vascular disease resulting in prevention or improvement of age-related macular degeneration as well.

  9. Preparation of MIL-53(Fe)-Reduced Graphene Oxide Nanocomposites by a Simple Self-Assembly Strategy for Increasing Interfacial Contact: Efficient Visible-Light Photocatalysts.

    Science.gov (United States)

    Liang, Ruowen; Shen, Lijuan; Jing, Fenfen; Qin, Na; Wu, Ling

    2015-05-13

    In this work, MIL-53(Fe)-reduced graphene oxide (M53-RGO) nanocomposites have been successfully fabricated by a facile and efficient electrostatic self-assembly strategy for improving the interfacial contact between RGO and the MIL-53(Fe). Compared with D-M53-RGO (direct synthesis of MIL-53(Fe)-reduced graphene oxide nanocomposites via one-pot solvothermal approach), M53-RGO nanocomposites exhibit improved photocatalytic activity compared with the D-M53-RGO under identical experimental conditions. After 80 min of visible light illumination (λ ≥ 420 nm), the reduction ratio of Cr(VI) is rapidly increased to 100%, which is also higher than that of reference sample (N-doped TiO2). More significantly, the M53-RGO nanocomposites are proven to perform as bifunctional photocatalysts with considerable activity in the mixed systems (Cr(VI)/dyes) under visible light, which made it a potential candidate for industrial wastewater treatment. Combining with photoelectrochemical analyses, it could be revealed that the introduction of RGO would minimize the recombination of photogenerated electron-hole pairs. Additionally, the effective interfacial contact between MIL-53(Fe) and RGO surface would further accelerate the transfer of photogenerated electrons, leading to the enhancement of photocatalytic activity of M53-RGO toward photocatalytic reactions. Finally, a possible photocatalytic reaction mechanism is also investigated in detail.

  10. Age-Related Pseudocapillarization of the Liver Sinusoidal Endothelium Impairs the Hepatic Clearance of Acetaminophen in Rats

    Science.gov (United States)

    Huizer-Pajkos, Aniko; Cogger, Victoria C.; McLachlan, Andrew J.; Le Couteur, David G.; Jones, Brett; de Cabo, Rafael; Hilmer, Sarah N.

    2011-01-01

    We investigated the effect of age-related pseudocapillarization of the liver sinusoidal endothelium on the hepatic disposition of acetaminophen. The multiple indicator dilution technique assessed the hepatic disposition of tracer 14C-acetaminophen and reference markers in isolated perfused livers of young (n = 11) and old (n = 12) rats. Electron microscopy confirmed defenestration of the sinusoidal endothelium in old rats compared with young rats. Acetaminophen recovery following a single pass through the liver was significantly increased in old rats (0.64 ± 0.04, old; 0.59 ± 0.05, young; p acetaminophen across the sinusoidal endothelium (0.034 ± 0.006 mL/s/g, old; 0.048 ± 0.014 mL/s/g, young; p acetaminophen that reflects enzyme activity. Age-related pseudocapillarization of the liver sinusoid resulted in increased acetaminophen recovery and decreased transfer of acetaminophen into the liver. PMID:21300741

  11. [The genetic variability of complement system in pathogenesis of age-related macular degeneration].

    Science.gov (United States)

    Kubicka-Trząska, Agnieszka; Karska-Basta, Izabella; Dziedzina, Sylwia; Sanak, Marek

    2015-01-01

    Age-related macular degeneration is the leading cause of irreversible central vision impairment in people aged over 50 in developed countries. Age-related macular degeneration is a complex disease derived from environmental, immune and genetic factors. The complement pathway has been implicated in the pathogenesis of many diseases. Recently, variants in several genes, such as complement H (CFH), complement factor B (CFB), complement 2 (C2), and complement 3 (C3), encoding complement pathway proteins, have been identified as associated with age-related macular degeneration. However, the associations between these genes and age-related macular degeneration varied due to genetic variation within populations and various ethnics groups. The strongest association was found between the age-related macular degeneration and SNP Y402H rs 1061170 variant of CFH gene, which is present in 30% to 50% of age-related macular degeneration patients in Caucasian population and which is a risk factor for the development of age-related macular degeneration. Cohort studies showed that polymorphism Arg102Gly (SNP rs 2230199) of C3 protein could serve as a high-risk genetic marker for the development of age-related macular degeneration. Other rare variants of C3 (Lys155Gln, Lys65Gln, Arg735Trp, Ser1619Arg), may also be associated with a high incidence of age-related macular degeneration in some ethnic groups. A protective haplotype of variants E318D and IVS10 in the C2 gene as well as L9H and R320 in the BF were associated with age-related macular degeneration but only in Caucasians. The genetic findings in age-related macular degeneration patients stress the importance of detailed phenotyping to identify age-related macular degeneration subtypes, which may be associated with the presence of different polymorphisms and various environmental risk factors in any population. Further studies may be helpful to improve the effectiveness of prophylaxis and therapeutic options in age-related

  12. Age-related changes in dynamic postural control and attentional demands are minimally affected by local muscle fatigue.

    OpenAIRE

    Anthony eRemaud; Cecile eThuong-Cong; Martin eBilodeau

    2016-01-01

    Normal aging results in alterations in the visual, vestibular and somtaosensory systems, which in turn modify the control of balance. Muscle fatigue may exacerbate these age-related changes in sensory and motor functions, and also increase the attentional demands associated with dynamic postural control. The purpose of this study was to investigate the effect of aging on dynamic postural control and posture-related attentional demands before and after a plantar flexor fatigue protocol. Partic...

  13. Age-Related Changes in Dynamic Postural Control and Attentional Demands are Minimally Affected by Local Muscle Fatigue

    OpenAIRE

    Remaud, Anthony; Thuong-Cong, Cécile; Bilodeau, Martin

    2016-01-01

    Normal aging results in alterations in the visual, vestibular and somtaosensory systems, which in turn modify the control of balance. Muscle fatigue may exacerbate these age-related changes in sensory and motor functions, and also increase the attentional demands associated with dynamic postural control. The purpose of this study was to investigate the effect of aging on dynamic postural control and posture-related attentional demands before and after a plantar flexor fatigue protocol. Partic...

  14. 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.

  15. 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.

  16. Association of HTRA1 rs11200638 with age-related macular degeneration (AMD) in Brazilian patients.

    Science.gov (United States)

    Lana, Tamires Prates; da Silva Costa, Sueli Matilde; Ananina, Galina; Hirata, Fábio Endo; Rim, Priscila Hae Hyun; Medina, Flávio MacCord; de Vasconcellos, José Paulo Cabral; de Melo, Mônica Barbosa

    2018-01-01

    Age-related macular degeneration is a multifactorial disease that can lead to vision impairment in older individuals. Although the etiology of age-related macular degeneration remains unknown, risk factors include age, ethnicity, smoking, hypertension, obesity, and genetic factors. Two main loci have been identified through genome-wide association studies, on chromosomes 1 and 10. Among the variants located at the 10q26 region, rs11200638, located at the HTRA1 gene promoter, has been associated with age-related macular degeneration in several populations and is considered the main polymorphism. We conducted a replication case-control study to analyze the frequency and participation of rs11200638 in the etiology of age-related macular degeneration in a sample of patients and controls from the State of São Paulo, Brazil, through polymerase chain reaction and enzymatic digestion. The frequency of the A allele was 57.60% in patients with age-related macular degeneration and 36.45% in controls (p value age-related macular degeneration group compared to the control group (p = 1.21 e-07 and 0.0357, respectively). No statistically significant results were observed after stratification in dry versus wet types or advanced versus non-advanced forms. To our knowledge, this is the first time the association between rs11200638 and overall age-related macular degeneration has been reported in South America.

  17. Age-related changes in petal membranes from attached and detached rose flowers.

    Science.gov (United States)

    Itzhaki, H; Borochov, A; Mayak, S

    1990-11-01

    Changes in petal membrane properties during aging were studied in cut and in attached rose flowers (Rosa hybrida L., cv Mercedes). Both cut and attached flowers exhibited a growth phase characterized by an increase in fresh weight and an accumulation of membrane components. The growth phase, which was more pronounced in the attached than in the cut flowers, was followed by a senescence phase, characterized by a decrease in fresh weight and a decline in membrane components. In cut flowers, both the growth and the senescence phases were accompanied by a decrease in membrane fluidity and in the ratio of unsaturated to saturated fatty acids, but the ratio of sterol to phospholipid increased. In attached flowers, while both the membrane fluidity and the sterol-to-phospholipid ratio remained unchanged during the growth phase, the senescence phase was accompanied (as in cut flowers) by a decrease in membrane fluidity and an increase in the sterol-to-phospholipid ratio. Unlike in cut flowers, however, the age-related changes in the ratio of unsaturation of fatty acids were not correlated with those of fluidity. Changes in the saturation of phospholipid acyl chains are commonly thought to influence membrane fluidity. Our observations question this view and suggest instead that the ratio of sterol to phospholipid may play the major role in maintaining membrane lipid fluidity.

  18. Age-related differences in the elasticity of the human cornea.

    Science.gov (United States)

    Knox Cartwright, Nathaniel E; Tyrer, John R; Marshall, John

    2011-06-17

    The goal of this study was to determine age-related variation in the elasticity of the human cornea using nondestructive means. Organ cultured human corneoscleral buttons were studied. Changes in strain were measured with a radial shearing speckle pattern interferometer after an increase in intraocular pressure from 15.0 to 15.5 mm Hg. Changes in central corneal displacement were calculated by integration, and a bulk corneal Young's modulus was derived by mathematical analysis. Fifty corneas, including 17 pairs, were studied. Donors were aged between 24 and 102 years (mean, 73.1); 29 (58%) specimens were from male donors and 21 from female donors. Young's modulus of the cornea increased with age, with the line of best fit indicating an approximate doubling from 0.27 MPa at age 20 years (95% confidence interval, 0.22-0.31) to 0.52 (0.50-0.54) MPa at age 100 years (R² = 0.70). The stiffness of the human cornea increases by a factor of approximately two between the ages of 20 and 100 years. This variation is relevant to the algorithms used to predict the response to incisional and ablative refractive surgery and will also affect the formulas used to calculate intraocular pressure by applanation.

  19. [Age-related coronary risk factors in Chinese patients with acute myocardial infarction].

    Science.gov (United States)

    Gao, X J; Yang, J G; Yang, Y J; Li, W; Xu, H Y; Wu, Y; Yan, R H; Jin, C

    2016-11-01

    Objective: To determine the age-related coronary risk factors in Chinese patients with acute myocardial infarction (AMI). Methods: Among 31 provinces, municipalities or autonomous districts in China, from January 1st 2013 to September 30th 2014, 24 394 consecutive AMI patients who were admitted to 107 hospitals were divided into five groups according to age. Cardiovascular risk factors of groupⅠ (myocardial infarction (STEMI) was diagnosed in 18 209 (74.6%) patients. The ratios of female, hypertension and diabetes tended to increase with the increase of age. Young AMI patients were predisposed to smoking, overweight/obesity and hyperglycemia. Nearly 90% patients in group Ⅰ and group Ⅱ were male. The ratio of male patients (92.3% to 58.0%), overweight/obesity (63.9% to 37.4%), current smoking (68.7% to 19.8%), dyslipidemia (9.1% to 4.5%), family history of premature coronary artery disease (CAD) (6.2% to 1.2%) and eating greasy food (86.1% to 66.2%) decreased markedly from group Ⅰ to Ⅴ patients. Proportion of hypertension gradually increased from 34.3% in group Ⅰ patients to 57.9% in group Ⅴ patients. Diabetes was most common to group Ⅳ (65-74 years) patients. Conclusion: There were different risk factors for AMI patients in different age groups, and young AMI patients were predisposed to live an unhealthy lifestyle.

  20. Tretinoin prevents age-related renal changes and stimulates antioxidant defenses in cultured renal mesangial cells.

    Science.gov (United States)

    Manzano, V M; Puyol, M R; Puyol, D R; Cazaña, F J

    1999-04-01

    Age-related progressive glomerular sclerosis in the rat is associated with increased expression of tumor necrosis factor-beta1 and increased protein content in the renal cortex, enhanced production of H2O2, in both renal glomeruli and mesangial cells (MCs) cultured from them, as well as augmented glomerular oxidative damage. We have previously shown that tretinoin-treated old male Fischer 344 rats have 30% lower protein content in the renal cortex than control old rats. Here, we report that this effect may depend on the inhibition of the expression of tumor necrosis factor-beta1, a matrigenic cytokine, and osteopontin, a protein with cell adhesive and chemotactic properties. In addition, we show that tretinoin prevents the cytotoxicity of H2O2 in cultured human MCs by increasing both the catalase activity and the reduced glutathione content, which are dose- and time-dependent changes. These increases were not dependent on each other: when these effects were previously inhibited with 3-amino-1,2,4-atriazole or L-buthionine-(S, R)-sulfoximine, respectively, tretinoin still induced the increase of the other noninhibited antioxidant defense. An enhanced gene transcription is the most likely mechanism involved in the tretinoin-induced stimulation of MC antioxidant defense systems because 1) preincubation of MCs with actinomycin D or cycloheximide fully abolished it; 2) tretinoin-incubated MCs showed increased levels of catalase mRNA and gamma-glutamyl-cysteine synthetase (catalytic subunit) mRNA, the latter being the rate-limiting step in de novo reduced glutathione synthesis; and 3) the stability of both mRNA was unchanged by tretinoin. These results show one strategy of protecting renal cells from H2O2-mediated injury based on increasing their antioxidant defenses.

  1. Intraocular lenses for the treatment of age-related cataracts: an evidence-based analysis.

    Science.gov (United States)

    2009-01-01

    The objective of the report is to examine the comparative effectiveness and cost-effectiveness of various intraocular lenses (IOLs) for the treatment of age-related cataracts. TARGET POPULATION AND CONDITION A cataract is a hardening and clouding of the normally transparent crystalline lens that may result in a progressive loss of vision depending on its size, location and density. The condition is typically bilateral, seriously compromises visual acuity and contrast sensitivity and increases glare. Cataracts can also affect people at any age, however, they usually occur as a part of the natural aging process. The occurrence of cataracts increases with age from about 12% at age 50 years, to 60% at age 70. In general, approximately 50% of people 65 year of age or older have cataracts. Mild cataracts can be treated with a change in prescription glasses, while more serious symptoms are treated by surgical removal of the cataract and implantation of an IOL. In Ontario, the estimated prevalence of cataracts increased from 697,000 in 1992 to 947,000 in 2004 (35.9% increase, 2.4% annual increase). The number of cataract surgeries per 1,000 individuals at risk of cataract increased from 64.6 in 1992 to 140.4 in 1997 (61.9% increase, 10.1% annual increase) and continued to steadily increase to 115.7 in 2004 (10.7% increase, 5.2% increase per year). IOLs are classified either as monofocal, multifocal, or accommodative. Traditionally, monofocal (i.e.. fixed focusing power) IOLs are available as replacement lenses but their implantation can cause a loss of the eye's accommodative capability (which allows variable focusing). Patients thus usually require eyeglasses after surgery for reading and near vision tasks. Multifocal IOLs aim to improve near and distant vision and obviate the need for glasses. Potential disadvantages include reduced contrast sensitivity, halos around lights and glare. Accommodating IOLs are designed to move with ciliary body contraction during

  2. 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

    2016-09-20

    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.

  3. Dietary magnesium intake alters age-related changes in rat adipose tissue cellularity.

    Science.gov (United States)

    Devaux, Sylvie; Adrian, Markus; Laurant, Pascal; Berthelot, Alain; Quignard-Boulangé, Annie

    2016-04-01

    Obesity and related metabolic diseases are associated with increased risk of cardiovascular disease. We have previously shown the beneficial effects of dietary magnesium (Mg) supplementation on cardiovascular disease in rats. Therefore, we aimed to examine the effect of an Mg-deficient or supplemented diet on adipose tissue cellularity changes during aging, and on blood pressure (BP), in rats. Male rats received for one (young adult) or 22 months (old), an Mg-deficient (Def) (150 mg/kg), standard (Std) (800 mg/kg) or Mg-supplemented (Sup) (3200 mg/kg) diet. Adipose tissue development and cellularity, BP and leptinemia were evaluated. In rats fed a standard diet, the large increase in adipose tissue weight observed during aging was related to an increase in both size and number of adipocytes. In young adult rats, although adiposity was unchanged, Mg supplementation resulted in a shift of the frequency distribution of adipocytes toward greater sizes, adipose cell weight increasing by 62%. Mg deficiency did not modify adipocyte size, but increased their number (30% more than for the standard or Sup-diet). In old rats, the Def-diet led to relative adipocyte hypotrophy, which was counterbalanced by an increase in the number of adipocyte. Conversely, adipocyte size and number were similar in the Sup-diet and standard diet-fed rats. BP was modified in old rats according to dietary Mg, whereas it remained unchanged young adult rats regardless of the diet received. This study suggests that Mg intake may affect age-related changes in rat adipose tissue lipid storage capacity.

  4. The age related prevalence of aggression and self-injury in persons with an intellectual disability: a review.

    Science.gov (United States)

    Davies, Louise; Oliver, Chris

    2013-02-01

    The aim of this study was to analyse statistically published data regarding the age related prevalence of aggression and self-injury in persons with intellectual disability. Studies including prevalence data for aggression and/or self-injury broken down by age band were identified and relative risk analyses conducted to generate indices of age related change. Despite conflicting results, the analysis conducted on included studies considered to be the most methodologically robust indicated that the relative risk of self-injury, and to a lesser extent aggression, increased with age until mid-adulthood, with some indication of a curvilinear relationship for self-injury. These conclusions have implications for the understanding of the development of different forms of challenging behaviour and the importance of early intervention strategies. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2013-12-01

    Over the next fifty years, the number of older adults is set to reach record levels. Protecting older adults from the age-related effects of cognitive decline is one of the greatest challenges of the next few decades as it places increasing pressure on families, health systems, and economies on a global scale. The disease-state of age-related cognitive decline-Alzheimer's disease and other dementias-hijacks our consciousness and intellectual autonomy. However, there is evidence that cognitively stimulating activities protect against the adverse effects of cognitive decline. Similarly, bilingualism is also considered to be a safeguard. We propose that foreign language learning programs aimed at older populations are an optimal solution for building cognitive reserve because language learning engages an extensive brain network that is known to overlap with the regions negatively affected by the aging process. It is recommended that future research should test this potentially fruitful hypothesis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. The Impact of Cardiorespiratory Fitness on Age-Related Lipids and Lipoproteins

    Science.gov (United States)

    Park, Yong-Moon Mark; Sui, Xuemei; Liu, Junxiu; Zhou, Haiming; Kokkinos, Peter F.; Lavie, Carl J.; Hardin, James W.; Blair, Steven N.

    2015-01-01

    Background Evidence on the effect of cardiorespiratory fitness (CRF) on age-related longitudinal changes of lipids and lipoproteins is scarce. Objectives This study sought to assess the longitudinal, aging trajectory of lipids and lipoproteins for the life course in adults, and to determine whether CRF modifies the age-associated trajectory of lipids and lipoproteins. Methods Data came from 11,418 men, 20 to 90 years of age, without known high cholesterol, high triglycerides, cardiovascular disease, and cancer at baseline and during follow-up from the Aerobics Center Longitudinal Study. There were 43,821 observations spanning 2 to 25 (mean 3.5) health examinations between 1970 and 2006. CRF was quantified by a maximal treadmill exercise test. Marginal models using generalized estimating equations were applied. Results Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and non-high-density lipoprotein cholesterol (non-HDL-C) presented similar inverted U-shaped quadratic trajectories with aging: gradual increases were noted until the mid-40s to early 50s, with subsequent declines (all p lipoproteins in young to middle-aged men than in older men. Conclusions Our investigation reveals a differential trajectory of lipids and lipoproteins with aging according to CRF in healthy men, and suggests that promoting increased CRF levels may help delay the development of dyslipidemia. PMID:25975472

  7. The effect of cardiorespiratory fitness on age-related lipids and lipoproteins.

    Science.gov (United States)

    Park, Yong-Moon Mark; Sui, Xuemei; Liu, Junxiu; Zhou, Haiming; Kokkinos, Peter F; Lavie, Carl J; Hardin, James W; Blair, Steven N

    2015-05-19

    Evidence on the effect of cardiorespiratory fitness (CRF) on age-related longitudinal changes of lipids and lipoproteins is scarce. This study sought to assess the longitudinal aging trajectory of lipids and lipoproteins for the life course in adults and to determine whether CRF modifies the age-associated trajectory of lipids and lipoproteins. Data came from 11,418 men, 20 to 90 years of age, without known high cholesterol, high triglycerides, cardiovascular disease, and cancer at baseline and during follow-up from the Aerobics Center Longitudinal Study. There were 43,821 observations spanning 2 to 25 health examinations (mean 3.5 examinations) between 1970 and 2006. CRF was quantified by a maximal treadmill exercise test. Marginal models using generalized estimating equations were applied. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides, and non-high-density lipoprotein cholesterol (non-HDL-C) presented similar inverted U-shaped quadratic trajectories with aging: gradual increases were noted until age mid-40s to early 50s, with subsequent declines (all p lipoproteins in young to middle-age men than in older men. Our investigation reveals a differential trajectory of lipids and lipoproteins with aging according to CRF in healthy men and suggests that promoting increased CRF levels may help delay the development of dyslipidemia. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  8. Can changes in eye movement scanning alter the age-related deficit in recognition memory?

    Directory of Open Access Journals (Sweden)

    Jessica P.K. Chan

    2011-05-01

    Full Text Available Older adults typically exhibit poorer face recognition compared to younger adults. These recognition differences may be due to underlying age-related changes in eye movement scanning. We examined whether older adults’ recognition could be improved by yoking their eye movements to those of younger adults. Participants studied younger and older faces, under free viewing conditions (bases, through a gaze-contingent moving window (own, or a moving window which replayed the eye movements of a base participant (yoked. During the recognition test, participants freely viewed the faces with no viewing restrictions. Own-age recognition biases were observed for older adults in all viewing conditions, suggesting that this effect occurs independently of scanning. Participants in the bases condition had the highest recognition accuracy, and participants in the yoked condition were more accurate than participants in the own condition. Among yoked participants, recognition did not depend on age of the base participant. These results suggest that successful encoding for all participants requires the bottom-up contribution of peripheral information, regardless of the locus of control of the viewer. Although altering the pattern of eye movements did not increase recognition, the amount of sampling of the face during encoding predicted subsequent recognition accuracy for all participants. Increased sampling may confer some advantages for subsequent recognition, particularly for people who have declining memory abilities.

  9. The role of prediction and anticipation on age-related effects on smooth pursuit eye movements.

    Science.gov (United States)

    Sprenger, Andreas; Trillenberg, Peter; Pohlmann, Jonas; Herold, Kirsten; Lencer, Rebekka; Helmchen, Christoph

    2011-09-01

    Externally guided sensory-motor processes deteriorate with increasing age. Internally guided, for example, predictive, behavior usually helps to overcome sensory-motor delays. We studied whether predictive components of visuomotor transformation decline with age. We investigated smooth pursuit eye movements (SPEM) of 45 healthy subjects with paradigms of different degrees of predictability with respect to target motion onset, type (smoothed triangular, ramp stimulation), and direction by blanking the target at various intervals of the ramp stimulation. Using repetitive trials of SPEM stimulation, we could dissociate anticipatory and predictive components of extraretinal smooth pursuit behavior. The main results suggest that basic motor parameters decline with increasing age, whereas both anticipation and prediction of target motion did not change with age. We suggest that the elderly maintain their capability of using prediction in the immediate control of motor behavior, which might be a way to compensate for age-related delays in sensory-motor transformation, even in the absence of sensory signals. © 2011 New York Academy of Sciences.

  10. Early age-related macular degeneration in patients with myocardial infarction.

    Science.gov (United States)

    Liutkeviciene, Rasa; Lesauskaite, Vaiva; Zaliuniene, Dalia; Zaliaduonyte-Peksiene, Diana; Cimbalas, Andrius; Jasinskas, Vytautas; Gustiene, Olivija; Simonytė, Sandrita; Tamosiunas, Abdonas

    2012-02-01

    To investigate the prevalence of early age-related macular degeneration (AMD) in patients with acute myocardial infarction (MI). Enrolled in the study were 262 acute MI patients (MI group), aged 40-64 years, as well as 1,155 non-MI persons, aged 40-64 years, from a random sample (reference group) of the Kaunas population. The prevalence of early AMD in the random sample was 7.3%, while in MI patients, the prevalence was 54.5% (P age groups, the prevalence of early AMD was significantly (P early AMD increased significantly with age, whereas no such trend was observed in the MI group. At the 45- to 54-year-olds, the prevalence was significantly higher in males than in females (9.9% vs. 3.7%; P early AMD in the males and females of the much larger reference group was 8.6% versus 6.2%, respectively (P > 0.05). It increased more with age for females (3.7% and 10.8% at the age 45-54 and 55-64 years, P age groups (9.9% vs. 11.6%; P > 0.05). We conclude that the prevalence of early AMD is significantly higher in patients with MI than in a random sample of the population.

  11. The Association between the Lipids Levels in Blood and Risk of Age-Related Macular Degeneration

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    Yafeng Wang

    2016-10-01

    Full Text Available Lipid metabolism 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 blood lipids. We performed a meta-analysis including a total of 19 studies to evaluate associations between blood lipids and this disease. The result reported that the high level of high-density lipoprotein cholesterol (HDL-C obtained with an increment of 1 mmol/L could result in a significantly increase in the AMD risk of approximately 18% (relative risk (RR, 1.18; 95% confidence interval (CI, 1.01 to 1.35; I2 = 53.8%; p = 0.007. High levels of total cholesterol (TC, low-density lipoprotein cholesterol (LDL-C, and triglycerides (TG were significantly associated with a decreased risk of AMD (RRs ranging from 0.92 to 0.95; all p < 0.05. The stratified analysis based on AMD subtypes showed that these blood lipids were only significantly associated with the risk of early AMD (all p < 0.05. The association between the blood lipids and AMD risk did not differ substantially based on the other characteristics of the participants. A high HDL-C level was associated with an increased AMD risk, whereas participants with high TC, LDL-C, and TG concentrations may show a decreased risk for this disease. Further well-designed large studies are warranted to confirm the conclusions.

  12. Fundus Autofluorescence and RPE Lipofuscin in Age-Related Macular Degeneration

    Science.gov (United States)

    Sparrow, Janet R.; Duncker, Tobias

    2014-01-01

    Genes that increase susceptibility to age-related macular degeneration (AMD) have been identified; however, since many individuals carrying these risk alleles do not develop disease, other contributors are involved. One additional factor, long implicated in the pathogenesis of AMD, is the lipofuscin of retinal pigment epithelium (RPE). The fluorophores that constitute RPE lipofuscin also serve as a source of autofluorescence (AF) that can be imaged by confocal laser ophthalmoscopy. The AF originating from lipofuscin is excited by the delivery of short wavelength (SW) light. A second autofluorescence is emitted from the melanin of RPE (and choroid) upon near-infrared (NIR-AF) excitation. SW-AF imaging is currently used in the clinical management of retinal disorders and the advantages of NIR-AF are increasingly recognized. Here we visit the damaging properties of RPE lipofuscin that could be significant when expressed on a background of genetic susceptibility. To advance interpretations of disease-related patterns of fundus AF in AMD, we also consider the photochemical and spectrophotometric features of the lipofuscin compounds responsible for generating the fluorescence emission. PMID:25774313

  13. Fundus Autofluorescence and RPE Lipofuscin in Age-Related Macular Degeneration

    Directory of Open Access Journals (Sweden)

    Janet R. Sparrow

    2014-11-01

    Full Text Available Genes that increase susceptibility to age-related macular degeneration (AMD have been identified; however, since many individuals carrying these risk alleles do not develop disease, other contributors are involved. One additional factor, long implicated in the pathogenesis of AMD, is the lipofuscin of retinal pigment epithelium (RPE. The fluorophores that constitute RPE lipofuscin also serve as a source of autofluorescence (AF that can be imaged by confocal laser ophthalmoscopy. The AF originating from lipofuscin is excited by the delivery of short wavelength (SW light. A second autofluorescence is emitted from the melanin of RPE (and choroid upon near-infrared (NIR-AF excitation. SW-AF imaging is currently used in the clinical management of retinal disorders and the advantages of NIR-AF are increasingly recognized. Here we visit the damaging properties of RPE lipofuscin that could be significant when expressed on a background of genetic susceptibility. To advance interpretations of disease-related patterns of fundus AF in AMD, we also consider the photochemical and spectrophotometric features of the lipofuscin compounds responsible for generating the fluorescence emission.

  14. The missing link between sleep disorders and age-related dementia: recent evidence and plausible mechanisms.

    Science.gov (United States)

    Zhang, Feng; Zhong, Rujia; Li, Song; Chang, Raymond Chuen-Chung; Le, Weidong

    2017-05-01

    Sleep disorders are among the most common clinical problems and possess a significant concern for the geriatric population. More importantly, while around 40% of elderly adults have sleep-related complaints, sleep disorders are more frequently associated with co-morbidities including age-related neurodegenerative diseases and mild cognitive impairment. Recently, increasing evidence has indicated that disturbed sleep may not only serve as the consequence of brain atrophy, but also contribute to the pathogenesis of dementia and, therefore, significantly increase dementia risk. Since the current therapeutic interventions lack efficacies to prevent, delay or reverse the pathological progress of dementia, a better understanding of underlying mechanisms by which sleep disorders interact with the pathogenesis of dementia will provide possible targets for the prevention and treatment of dementia. In this review, we briefly describe the physiological roles of sleep in learning/memory, and specifically update the recent research evidence demonstrating the association between sleep disorders and dementia. Plausible mechanisms are further discussed. Moreover, we also evaluate the possibility of sleep therapy as a potential intervention for dementia.

  15. 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.

  16. Age-related changes in rat prostate tissue; perspective of protein oxidation.

    Science.gov (United States)

    Uzun, Duygu; Yanar, Karolin; Atukeren, Pınar; Cebe, Tamer; Mengi, Murat; Ozan, Tuna; Kunbaz, Ahmad; Kuruç, Aylin Irmak; Çakatay, Ufuk; Aydın, Seval

    2015-03-01

    Increased systemic oxidative stress is considered as an important risk factor for prostate cancer occurrence; however, the relationship between impaired redox homeostasis of prostate tissue and aging remains unclear. In our study, we hypothesized that age-related deterioration of redox homeostasis in prostate tissue may be considered as a predisposing factor for prostate cancer occurrence. Sprague-Dawley rats were divided into two groups as young control (5 months) and naturally aged (24 months). We investigated the levels of oxidant and antioxidant parameters in prostate tissue. Advanced oxidation protein products, protein carbonyl, non-protein thiol and lipid hydroperoxides levels of aged rats were significantly higher than in the young control rats (p aged rats may prevent further dissemination of oxidative protein damage. We also propose that the increased levels of oxidative protein damage markers and decreased Cu-Zn superoxide dismutase activity in aged prostate may be considered as a predisposing factor for prostate cancer. Further studies are warranted to clarify all these oxidative changes as initiation factors for prostate cancer in the association of aging with prostate cancer.

  17. Aging related changes of retina and optic nerve of Uromastyx aegyptia and Falco tinnunculus.

    Science.gov (United States)

    El-Sayyad, Hassan I H; Khalifa, Soad A; Al-Gebaly, Asma S; El-Mansy, Ahmed A

    2014-01-15

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

  18. Fundus Autofluorescence and RPE Lipofuscin in Age-Related Macular Degeneration.

    Science.gov (United States)

    Sparrow, Janet R; Duncker, Tobias

    2014-01-01

    Genes that increase susceptibility to age-related macular degeneration (AMD) have been identified; however, since many individuals carrying these risk alleles do not develop disease, other contributors are involved. One additional factor, long implicated in the pathogenesis of AMD, is the lipofuscin of retinal pigment epithelium (RPE). The fluorophores that constitute RPE lipofuscin also serve as a source of autofluorescence (AF) that can be imaged by confocal laser ophthalmoscopy. The AF originating from lipofuscin is excited by the delivery of short wavelength (SW) light. A second autofluorescence is emitted from the melanin of RPE (and choroid) upon near-infrared (NIR-AF) excitation. SW-AF imaging is currently used in the clinical management of retinal disorders and the advantages of NIR-AF are increasingly recognized. Here we visit the damaging properties of RPE lipofuscin that could be significant when expressed on a background of genetic susceptibility. To advance interpretations of disease-related patterns of fundus AF in AMD, we also consider the photochemical and spectrophotometric features of the lipofuscin compounds responsible for generating the fluorescence emission.

  19. Age-related differences in resolving semantic and phonological competition during receptive language tasks.

    Science.gov (United States)

    Zhuang, Jie; Johnson, Micah A; Madden, David J; Burke, Deborah M; Diaz, Michele T

    2016-12-01

    Receptive language (e.g., reading) is largely preserved in the aging brain, and semantic processes in particular may continue to develop throughout the lifespan. We investigated the neural underpinnings of phonological and semantic retrieval in older and younger adults during receptive language tasks (rhyme and semantic similarity judgments). In particular, we were interested in the role of competition on language retrieval and varied the similarities between a cue, target, and distractor that were hypothesized to affect the mental process of competition. Behaviorally, all participants responded faster and more accurately during the rhyme task compared to the semantic task. Moreover, older adults demonstrated higher response accuracy than younger adults during the semantic task. Although there were no overall age-related differences in the neuroimaging results, an Age×Task interaction was found in left inferior frontal gyrus (IFG), with older adults producing greater activation than younger adults during the semantic condition. These results suggest that at lower levels of task difficulty, older and younger adults engaged similar neural networks that benefited behavioral performance. As task difficulty increased during the semantic task, older adults relied more heavily on largely left hemisphere language regions, as well as regions involved in perception and internal monitoring. Our results are consistent with the stability of language comprehension across the adult lifespan and illustrate how the preservation of semantic representations with aging may influence performance under conditions of increased task difficulty. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Age-Related Changes in the Hepatic Pharmacology and Toxicology of Paracetamol

    Science.gov (United States)

    Mitchell, Sarah J.; Kane, Alice E.; Hilmer, Sarah N.

    2011-01-01

    Optimal pharmacotherapy is determined when the pharmacokinetics and pharmacodynamics of the drug are understood. However, the age-related changes in pharmacokinetics and pharmacodynamics, as well as the increased interindividual variation mean optimal dose selection are a challenge for prescribing in older adults. Poor understanding of how hepatic clearance and toxicity are different with age results in suboptimal dose selection, poor efficacy, and/or increased toxicity. Of particular concern is the analgesic paracetamol which has been in use for more than 50 years and is consumed by a large proportion of older adults. Paracetamol is considered to be a relatively safe drug; however, caution must be taken because of its potential for toxicity. Paracetamol-induced liver injury from accidental overdose accounts for up to 55% of cases in older adults. Better understanding of how age affects the hepatic clearance and toxicity of drugs will contribute to evidence-based prescribing for older people, leading to fewer adverse drug reactions without loss of benefit. PMID:21765826

  1. Age-Related Changes in the Hepatic Pharmacology and Toxicology of Paracetamol

    Directory of Open Access Journals (Sweden)

    Sarah J. Mitchell

    2011-01-01

    Full Text Available Optimal pharmacotherapy is determined when the pharmacokinetics and pharmacodynamics of the drug are understood. However, the age-related changes in pharmacokinetics and pharmacodynamics, as well as the increased interindividual variation mean optimal dose selection are a challenge for prescribing in older adults. Poor understanding of how hepatic clearance and toxicity are different with age results in suboptimal dose selection, poor efficacy, and/or increased toxicity. Of particular concern is the analgesic paracetamol which has been in use for more than 50 years and is consumed by a large proportion of older adults. Paracetamol is considered to be a relatively safe drug; however, caution must be taken because of its potential for toxicity. Paracetamol-induced liver injury from accidental overdose accounts for up to 55% of cases in older adults. Better understanding of how age affects the hepatic clearance and toxicity of drugs will contribute to evidence-based prescribing for older people, leading to fewer adverse drug reactions without loss of benefit.

  2. New loci and coding variants confer risk for age-related macular degeneration in East Asians.

    Science.gov (United States)

    Cheng, Ching-Yu; Yamashiro, Kenji; Chen, Li Jia; Ahn, Jeeyun; Huang, Lulin; Huang, Lvzhen; Cheung, Chui Ming G; Miyake, Masahiro; Cackett, Peter D; Yeo, Ian Y; Laude, Augustinus; Mathur, Ranjana; Pang, Junxiong; Sim, Kar Seng; Koh, Adrian H; Chen, Peng; Lee, Shu Yen; Wong, Doric; Chan, Choi Mun; Loh, Boon Kwang; Sun, Yaoyao; Davila, Sonia; Nakata, Isao; Nakanishi, Hideo; Akagi-Kurashige, Yumiko; Gotoh, Norimoto; Tsujikawa, Akitaka; Matsuda, Fumihiko; Mori, Keisuke; Yoneya, Shin; Sakurada, Yoichi; Iijima, Hiroyuki; Iida, Tomohiro; Honda, Shigeru; Lai, Timothy Yuk Yau; Tam, Pancy Oi Sin; Chen, Haoyu; Tang, Shibo; Ding, Xiaoyan; Wen, Feng; Lu, Fang; Zhang, Xiongze; Shi, Yi; Zhao, Peiquan; Zhao, Bowen; Sang, Jinghong; Gong, Bo; Dorajoo, Rajkumar; Yuan, Jian-Min; Koh, Woon-Puay; van Dam, Rob M; Friedlander, Yechiel; Lin, Ying; Hibberd, Martin L; Foo, Jia Nee; Wang, Ningli; Wong, Chang Hua; Tan, Gavin S; Park, Sang Jun; Bhargava, Mayuri; Gopal, Lingam; Naing, Thet; Liao, Jiemin; Ong, Peng Guan; Mitchell, Paul; Zhou, Peng; Xie, Xuefeng; Liang, Jinlong; Mei, Junpu; Jin, Xin; Saw, Seang-Mei; Ozaki, Mineo; Mizoguchi, Takanori; Kurimoto, Yasuo; Woo, Se Joon; Chung, Hum; Yu, Hyeong-Gon; Shin, Joo Young; Park, Dong Ho; Kim, In Taek; Chang, Woohyok; Sagong, Min; Lee, Sang-Joon; Kim, Hyun Woong; Lee, Ji Eun; Li, Yi; Liu, Jianjun; Teo, Yik Ying; Heng, Chew Kiat; Lim, Tock Han; Yang, Suk-Kyun; Song, Kyuyoung; Vithana, Eranga N; Aung, Tin; Bei, Jin Xin; Zeng, Yi Xin; Tai, E Shyong; Li, Xiao Xin; Yang, Zhenglin; Park, Kyu-Hyung; Pang, Chi Pui; Yoshimura, Nagahisa; Wong, Tien Yin; Khor, Chiea Chuen

    2015-01-28

    Age-related macular degeneration (AMD) is a major cause of blindness, but presents differently in Europeans and Asians. Here, we perform a genome-wide and exome-wide association study on 2,119 patients with exudative AMD and 5,691 controls, with independent replication in 4,226 patients and 10,289 controls, all of East Asian descent, as part of The Genetics of AMD in Asians (GAMA) Consortium. We find a strong association between CETP Asp442Gly (rs2303790), an East Asian-specific mutation, and increased risk of AMD (odds ratio (OR)=1.70, P=5.60 × 10(-22)). The AMD risk allele (442Gly), known to protect from coronary heart disease, increases HDL cholesterol levels by 0.17 mmol l(-1) (P=5.82 × 10(-21)) in East Asians (n=7,102). We also identify three novel AMD loci: C6orf223 Ala231Ala (OR=0.78, P=6.19 × 10(-18)), SLC44A4 Asp47Val (OR=1.27, P=1.08 × 10(-11)) and FGD6 Gln257Arg (OR=0.87, P=2.85 × 10(-8)). Our findings suggest that some of the genetic loci conferring AMD susceptibility in East Asians are shared with Europeans, yet AMD in East Asians may also have a distinct genetic signature.

  3. Dysfunctional autophagy in RPE, a contributing factor in age-related macular degeneration.

    Science.gov (United States)

    Golestaneh, Nady; Chu, Yi; Xiao, Yang-Yu; Stoleru, Gianna L; Theos, Alexander C

    2017-01-05

    Age-related macular degeneration (AMD) is a devastating neurodegenerative disease and a major cause of blindness in the developed world. Owing to its complexity and the lack of an adequate human model that recapitulates key aspects of the disease, the molecular mechanisms of AMD pathogenesis remain poorly understood. Here we show that cultured human retinal pigment epithelium (RPE) from AMD donors (AMD RPE) are functionally impaired and exhibit distinct phenotypes compared with RPE cultured from normal donors (normal RPE). Accumulation of lipid droplets and glycogen granules, disintegration of mitochondria, and an increase in autophagosomes were observed in AMD RPE cultures. Compared with normal RPE, AMD RPE exhibit increased susceptibility to oxidative stress, produce higher levels of reactive oxygen species (ROS) under stress conditions, and showed reduced mitochondrial activity. Measurement of the ratio of LC3-II/ LC3-I, revealed impaired autophagy in AMD RPE as compared with normal RPE. Autophagic flux was also reduced in AMD RPE as compared with normal RPE, as shown by inability of AMD RPE to downregulate p62 levels during starvation. Impaired autophagic pathways were further shown by analyzing late autophagic vesicles; immunostaining with lysosome-associated membrane protein 1 (LAMP-1) antibody revealed enlarged and annular LAMP-1-positive organelles in AMD RPE as opposed to smaller discrete puncta observed in normal RPE. Our study provides insights into AMD cellular and molecular mechanisms, proposes dysfunctional autophagy as an underlying mechanism contributing to the pathophysiology of the disease, and opens up new avenues for development of novel treatment strategies.

  4. Candesartan, angiotensin II type 1 receptor blocker is able to relieve age-related cognitive impairment.

    Science.gov (United States)

    Trofimiuk, Emil; Wielgat, Przemysław; Braszko, Jan J

    2017-07-21

    Candesartan is one of the standard antihypertensive drug belonging to AT1R angiotensin receptor blockers (ARBs) group. Beneficial effects of this drug in the treatment of hypertension are well recognized. In this study we tested a hypothesis that candesartan could alleviate age-related memory decline. Aged and young rats have been treated with candesartan (0.1 mg kg-1) for 21 days and then underwent a battery of behavioral tests: for assessment of long-term memory (Passive avoidance test - PA), recognition memory (Object recognition test - OR), locomotor functions (Open field - OF) and anxiety behavior (Elevated plus maze - EPM). Aged rats (2-years-old) displayed clear declining tendency in the retrieval of passive avoidance behavior showing thus increased forgetting. Prolonged administration of candesartan significantly (p candesartan significantly improved recognition memory (p candesartan potently abolishes some kinds of aging-induced memory impairments and cognitive declines in aged rats, but in some circumstances it may even could increase the damage of memory. It seems that the use of sartans in the treatment of hypertension for patients with associated cognitive impairment, or for people in risk groups for such disorders can be an interesting alternative. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  5. Visual function and performance with blue-light blocking filters in age-related macular degeneration.

    Science.gov (United States)

    Kiser, Ava K; Deschler, Emily K; Dagnelie, Gislin

    2008-08-01

    Some dispute has occurred over the use of blue-light-attenuating intraocular lenses in age-related macular degeneration (AMD), as they may reduce scotopic vision. This study aimed to determine if a blue blocking filter would affect performance during eye-hand coordination and mobility tasks in scotopic illumination, psychophysically measured scotopic sensitivity or colour discrimination in AMD patients. Scotopic measures performed with and without a blue-attenuating filter included a mobility obstacle course, manipulation of cylindrical blocks and a psychophysical dark-adapted full-field flash test. A navy and blue sock colour sorting task evaluated photopic colour discrimination. Subjects were 22 bilateral pseudophakes with early AMD and visual acuity >6/24. On average with the filter, there was a 13% increase in time during the block test. The differences in time and number of bumps with versus without the filter were not significant for the mobility course. Performance with and without the filter was well correlated for the blocks (r = 0.70), flash test (r = 0.83) and mobility (r = 0.66), and the regression slopes were not significantly different from unity. 77% of subjects misidentified at least one navy sock as black with the filter compared with 9% without, with a significant increase in such misidentifications with the filter. The difference in scotopic visual function or performance with versus without a blue-blocking filter most likely does not produce a clinically significant effect or risk; however, detection of navy colour may be impaired.

  6. Age-related eye diseases and visual impairment among U.S. adults.

    Science.gov (United States)

    Chou, Chiu-Fang; Cotch, Mary Frances; Vitale, Susan; Zhang, Xinzhi; Klein, Ronald; Friedman, David S; Klein, Barbara E K; Saaddine, Jinan B

    2013-07-01

    Visual impairment is a common health-related disability in the U.S. The association between clinical measurements of age-related eye diseases and visual impairment in data from a national survey has not been reported. To examine common eye conditions and other correlates associated with visual impairment in the U.S. Data from the 2005-2008 National Health and Nutrition Examination Survey of 5222 Americans aged ≥40 years were analyzed in 2012 for visual impairment (presenting distance visual acuity worse than 20/40 in the better-seeing eye), and visual impairment not due to refractive error (distance visual acuity worse than 20/40 after refraction). Diabetic retinopathy (DR) and age-related macular degeneration (AMD) were assessed from retinal fundus images; glaucoma was assessed from two successive frequency-doubling tests and a cup-to-disc ratio measurement. Prevalence of visual impairment and of visual impairment not due to refractive error was 7.5% (95% CI=6.9%, 8.1%) and 2.0% (1.7%, 2.3%), respectively. The prevalence of visual impairment not due to refractive error was significantly higher among people with AMD (2.2%) compared to those without AMD (0.8%), or with DR (3.5%) compared to those without DR (1.2%). Independent predictive factors of visual impairment not due to refractive error were AMD (OR=4.52, 95% CI=2.50, 8.17); increasing age (OR=1.09 per year, 95% CI=1.06, 1.13); and less than a high school education (OR=2.99, 95% CI=1.18, 7.55). Visual impairment is a public health problem in the U.S. Visual impairment in two thirds of adults could be eliminated with refractive correction. Screening of the older population may identify adults at increased risk of visual impairment due to eye diseases. Copyright © 2013 American Journal of Preventive Medicine. All rights reserved.

  7. 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

  8. Age-related temporal and parietal cortical thinning in autism spectrum disorders.

    Science.gov (United States)

    Wallace, Gregory L; Dankner, Nathan; Kenworthy, Lauren; Giedd, Jay N; Martin, Alex

    2010-12-01

    age-related thinning in the autism spectrum disorders group but not in the typically developing group. Both thinner temporal and parietal cortices during adolescence and young adulthood and discrepantly accelerated age-related cortical thinning in autism spectrum disorders suggest that a second period of abnormal cortical growth (i.e. greater thinning) may be characteristic of these disorders.

  9. Age-Related Eye Diseases and Visual Impairment Among U.S. Adults

    Science.gov (United States)

    Chou, Chiu-Fang; Cotch, Mary Frances; Vitale, Susan; Zhang, Xinzhi; Klein, Ronald; Friedman, David S.; Klein, Barbara E.K.; Saaddine, Jinan B.

    2014-01-01

    Background Visual impairment is a common health-related disability in the U.S. The association between clinical measurements of age-related eye diseases and visual impairment in data from a national survey has not been reported. Purpose To examine common eye conditions and other correlates associated with visual impairment in the U.S. Methods Data from the 2005–2008 National Health and Nutrition Examination Survey of 5222 Americans aged ≥40 years were analyzed in 2012 for visual impairment (presenting distance visual acuity worse than 20/40 in the better-seeing eye), and visual impairment not due to refractive error (distance visual acuity worse than 20/40 after refraction). Diabetic retinopathy (DR) and age-related macular degeneration (AMD) were assessed from retinal fundus images; glaucoma was assessed from two successive frequency-doubling tests and a cup-to-disc ratio measurement. Results Prevalence of visual impairment and of visual impairment not due to refractive error was 7.5% (95% CI=6.9%, 8.1%) and 2.0% (1.7%, 2.3%), respectively. The prevalence of visual impairment not due to refractive error was significantly higher among people with AMD (2.2%) compared to those without AMD (0.8%), or with DR (3.5%) compared to those without DR (1.2%). Independent predictive factors of visual impairment not due to refractive error were AMD (OR=4.52, 95% CI=2.50, 8.17); increasing age (OR=1.09 per year, 95% CI=1.06, 1.13); and less than a high school education (OR=2.99, 95% CI=1.18, 7.55). Conclusions Visual impairment is a public health problem in the U.S. Visual impairment in two thirds of adults could be eliminated with refractive correction. Screening of the older population may identify adults at increased risk of visual impairment due to eye diseases. PMID:23790986

  10. 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

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

    National Research Council Canada - National Science Library

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

    2014-01-01

    ...), 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...

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  13. 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

  14. Serum APOE, leptin, CFH and HTRA1 levels in Pakistani age related macular degeneration patients.

    Science.gov (United States)

    Qureshi, Irfan Zia; Ambreen, Fareeha

    2017-06-01

    To determine the association between serum levels of apolipoprotein E, leptin, complimentary factor H and high temperature requirement A-1 in patients with age-related macular degeneration. This case-control study was conducted at the Quaid-i-Azam University, Islamabad, Pakistan, from May to October 2013, and comprised patients with age-related macular degeneration and matching controls. The confirmation of age-related macular degeneration was carried out through slit lamp examination, fundoscopy and ocular coherence tomography. The selected subjects were not suffering with any other systemic or ophthalmic complication(s). Serum apolipoprotein E, leptin, complimentary factor H and high temperature requirement A-1 were estimated in serum samples of all subjects. SPSS 18 was used for data analysis. Of the 190 participants, 90(47.4%) were patients with age-related macular degeneration and 100(52.6%) were controls. Significantly elevated serum apolipoprotein E (page-related macular degeneration patients.

  15. Cataract surgery in patients with neovascular age-related macular degeneration

    DEFF Research Database (Denmark)

    Kessel, Line; Theil, Pernille Koefoed; Sørensen, Torben Lykke

    2016-01-01

    Purpose To examine the outcome after cataract surgery in patients with neovascular age-related macular degeneration (AMD) treated with intravitreal anti-vascular endothelial growth factor (VEGF) injections in routine clinical practice. Methods We extracted information about patients recorded...

  16. Age-related eye diseases and visual impairment among U.S. adults

    National Research Council Canada - National Science Library

    Chou, Chiu-Fang; Cotch, Mary Frances; Vitale, Susan; Zhang, Xinzhi; Klein, Ronald; Friedman, David S; Klein, Barbara E K; Saaddine, Jinan B

    2013-01-01

    Visual impairment is a common health-related disability in the U.S. The association between clinical measurements of age-related eye diseases and visual impairment in data from a national survey has not been...

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

    Science.gov (United States)

    Blagosklonny, Mikhail V

    2009-03-28

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

  18. Aging Changes in Retinal Microglia and their Relevance to Age-related Retinal Disease.

    Science.gov (United States)

    Ma, Wenxin; Wong, Wai T

    2016-01-01

    Age-related retinal diseases, such as age-related macular degeneration (AMD) and glaucoma, contain features of chronic retinal inflammation that may promote disease progression. However, the relationship between aging and neuroinflammation is unclear. Microglia are long-lived, resident immune cells of the retina, and mediate local neuroinflammatory reactions. We hypothesize that aging changes in microglia may be causally linked to neuroinflammatory changes underlying age-dependent retinal diseases. Here, we review the evidence for (1) how the retinal microglial phenotype changes with aging, (2) the factors that drive microglial aging in the retina, and (3) aging-related changes in microglial gene expression. We examine how these aspects of microglial aging changes may relate to pathogenic mechanisms of immune dysregulation driving the progression of age-related retinal disease. These relationships can highlight microglial aging as a novel target for the prevention and treatment of retinal disease.

  19. 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

    2014-04-01

    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 between age and the self-reported wish to be rich. Ecological concerns, a form of contributing to the public good, were positively related to age. Study 2 investigated whether these values are expressed behaviorally when participants solved a complex problem that allowed striving for monetary gains or contributing to a public good. Confirming hypotheses, young adults' strategies were consistent with the aim of optimizing personal financial gain, and older adults' strategies with the aim to contribute to the public good. Studies 3 and 4 showed that older adults were more likely than younger and middle-aged adults to donate money to a good cause than to keep it for themselves. Study 4 manipulated participants' future time perspective as a factor potentially contributing to age-related differences. Partly confirming hypotheses, a longer time perspective reduced donations by older adults, but a shorter time perspective did not increase donations by younger adults. These studies suggest that older adults not only report valuing contributions to the public good more highly but also are more likely to behave altruistically than younger adults. All studies used cross-sectional designs that prevent a strict test of developmental trajectories but rather provide age-related differences at 1 point in time, representing a 1st step in investigating adult age-related differences in altruism. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  20. The chronic care for age-related macular degeneration study (CHARMED: Study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Held Ulrike

    2011-10-01

    Full Text Available Abstract Background Neovascular age-related macular degeneration is the leading cause of irreversible blindness in people 50 years of age or older in the developed world. As in other chronic diseases, several effective treatments are available, but in clinical daily practice there is an evidence performance gap. The Chronic Care Model represents an evidence-based framework for the care of chronically ill patients and aims at closing that gap. However, no data are available regarding patients with neovascular age-related macular degeneration. Methods/Design CHARMED is a multicenter randomized controlled trial. The study challenges the hypothesis that the implementation of core elements of the Chronic Care Model (patient empowerment, delivering evidence based information, clinical information system, reminder system with structured follow up and frequent monitoring via a specially trained Chronic Care Coach in Swiss centres for neovascular age-related macular degeneration results in better visual acuity (primary outcome and an increased disease specific quality of life (secondary outcome in patients with neovascular age-related macular degeneration. According to the power calculation, a total sample size of 352 patients is needed (drop out rate of 25%. 14 specialised medical doctors from leading ophtalmologic centres in Switzerland will include 25 patients. In each centre, a Chronic Care Coach will provide disease specific care according to the Chronic Care Model for intervention group. Patients from the control group will be treated as usual. Baseline measurements will be taken in month III - XII, starting in March 2011. Follow-up data will be collected after 6 months and 1 year. Discussion Multiple studies have shown that implementing Chronic Care Model elements improve clinical outcomes as well as process parameters in different chronic diseases as osteoarthritis, depression or e.g. the cardiovascular risk profile of diabetes patients. This

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

    OpenAIRE

    Reinisalo, Mika; K?rlund, Anna; Koskela, Ali; Kaarniranta, Kai; Karjalainen, Reijo O.

    2015-01-01

    Numerous studies have highlighted the key roles of oxidative stress and inflammation in aging-related diseases such as obesity, type 2 diabetes, age-related macular degeneration (AMD), and Alzheimer’s disease (AD). In aging cells, the natural antioxidant capacity decreases and the overall efficiency of reparative systems against cell damage becomes impaired. There is convincing data that stilbene compounds, a diverse group of natural defence phenolics, abundant in grapes, berries, and conifer...

  2. Aging of marrow stromal (skeletal) stem cells and their contribution to age-related bone loss

    OpenAIRE

    Bellantuono, Ilaria; Aldahmash, Abdullah; Kassem, Moustapha

    2009-01-01

    Abstract 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 in vivo, leading to decreased ability to form and maintain bone homeostasis with age. In this review we summarize evidence of MSC involvement in age related bone loss and sugges...

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  4. Self-reported optometric practise patterns in age-related macular degeneration.

    Science.gov (United States)

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

    2017-11-01

    The use of advanced imaging in clinical practice is emerging and the use of this technology by optometrists in assessing patients with age-related macular degeneration is of interest. Therefore, this study explored contemporary, self-reported patterns of practice regarding age-related macular degeneration diagnosis and management using a cross-sectional survey of optometrists in Australia and New Zealand. Practising optometrists were surveyed on four key areas, namely, demographics, clinical skills and experience, assessment and management of age-related macular degeneration. Questions pertaining to self-rated competency, knowledge and attitudes used a five-point Likert scale. Completed responses were received from 127 and 87 practising optometrists in Australia and New Zealand, respectively. Advanced imaging showed greater variation in service delivery than traditional techniques (such as slitlamp funduscopy) and trended toward optical coherence tomography, which was routinely performed in age-related macular degeneration by 49 per cent of respondents. Optical coherence tomography was also associated with higher self-rated competency, knowledge and perceived relevance to practice than other modalities. Most respondents (93 per cent) indicated that they regularly applied patient symptoms, case history, visual function results and signs from traditional testing, when queried about their management of patients with age-related macular degeneration. Over half (63 per cent) also considered advanced imaging, while 31 per cent additionally considered all of these as well as the disease stage and clinical guidelines. Contrary to the evidence base, 68 and 34 per cent rated nutritional supplements as highly relevant or relevant in early age-related macular degeneration and normal aging changes, respectively. These results highlight the emergence of multimodal and advanced imaging (especially optical coherence tomography) in the assessment of age-related macular degeneration

  5. Age-related hyperkyphosis: update of its potential causes and clinical impacts—narrative review

    OpenAIRE

    Roghani, T; Zavieh, MK; Manshadi, FD; King, N; Katzman, W.

    2017-01-01

    © 2016, Springer International Publishing Switzerland. The present study aims to qualitatively review the contributing factors and health implications of age-related hyperkyphosis. We conducted a narrative review of observational and cohort studies describing the risk factors and epidemiology of hyperkyphosis from 1955 to 2016 using the following key words: kyphosis, hyperkyphosis, posture, age-related hyperkyphosis, kyphotic posture, aetiology and causes. This review included 77 studies. App...

  6. Multiple morbidities in companion dogs: a novel model for investigating age-related disease

    Directory of Open Access Journals (Sweden)

    Kelly Jin

    2016-11-01

    Full Text Available The proportion of men and women surviving over 65 years has been steadily increasing over the last century. In their later years, many of these individuals are afflicted with multiple chronic conditions, placing increasing pressure on healthcare systems. The accumulation of multiple health problems with advanced age is well documented, yet the causes are poorly understood. Animal models have long been employed in attempts to elucidate these complex mechanisms with limited success. Recently, the domestic dog has been proposed as a promising model of human aging for several reasons. Mean lifespan shows twofold variation across dog breeds. In addition, dogs closely share the environments of their owners, and substantial veterinary resources are dedicated to comprehensive diagnosis of conditions in dogs. However, while dogs are therefore useful for studying multimorbidity, little is known about how aging influences the accumulation of multiple concurrent disease conditions across dog breeds. The current study examines how age, body weight, and breed contribute to variation in multimorbidity in over 2,000 companion dogs visiting private veterinary clinics in England. In common with humans, we find that the number of diagnoses increases significantly with age in dogs. However, we find no significant weight or breed effects on morbidity number. This surprising result reveals that while breeds may vary in their average longevity and causes of death, their age-related trajectories of morbidities differ little, suggesting that age of onset of disease may be the source of variation in lifespan across breeds. Future studies with increased sample sizes and longitudinal monitoring may help us discern more breed-specific patterns in morbidity. Overall, the large increase in multimorbidity seen with age in dogs mirrors that seen in humans and lends even more credence to the value of companion dogs as models for human morbidity and mortality.

  7. 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.

  8. Age-related differences in brain activity in the subsequent memory paradigm: a meta-analysis.

    Science.gov (United States)

    Maillet, David; Rajah, M Natasha

    2014-09-01

    Healthy aging is associated with declines in episodic memory. This reduction is thought to be due in part to age-related differences in encoding-related processes. In the current study, we performed an activation likelihood estimation meta-analysis of functional magnetic resonance imaging (fMRI) studies assessing age-related differences in the neural correlates of episodic encoding. Only studies using the subsequent memory paradigm were included. We found age-related under-recruitment of occipital and fusiform cortex, but over-recruitment in a set of regions including bilateral middle/superior frontal gyri, anterior medial frontal gyrus, precuneus and left inferior parietal lobe. We demonstrate that all of the regions consistently over-recruited by older adults during successful encoding exhibit either direct overlap, or occur in close vicinity to regions consistently involved in unsuccessful encoding in young adults. We discuss the possibility that this overall pattern of age-related differences represents an age-related shift in focus: away from perceptual details, and toward evaluative and personal thoughts and feelings during memory tasks. We discuss whether these age-related differences in brain activation benefit performance in older adults, and additional considerations. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Age-related changes in processing speed: unique contributions of cerebellar and prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Mark A Eckert

    2010-03-01

    Full Text Available Age-related declines in processing speed are hypothesized to underlie the widespread changes in cognition experienced by older adults. We used a structural covariance approach to identify putative neural networks that underlie age-related structural changes associated with processing speed for 42 adults ranging in age from 19-79 years. To characterize a mechanism by which age-related gray matter changes lead to slower processing speed, we examined the extent to which cerebral small vessel disease influenced the association between age-related gray matter changes and processing speed. A frontal pattern of gray matter and white matter variation that was related to cerebral small vessel disease, as well as a cerebellar pattern of gray matter and white matter variation were uniquely related to age-related declines in processing speed. These results demonstrate that at least 2 distinct factors affect age-related changes in processing speed, which might be slowed by mitigating cerebral small vessel disease and factors affecting declines in cerebellar morphology.

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

    Science.gov (United States)

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

    2016-01-01

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

  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 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.

  13. Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration.

    Science.gov (United States)

    Evans, Jennifer R; Lawrenson, John G

    2012-06-13

    There is inconclusive evidence from observational studies to suggest that people who eat a diet rich in antioxidant vitamins (carotenoids, vitamins C and E) or minerals (selenium and zinc) may be less likely to develop age-related macular degeneration (AMD). To examine the evidence as to whether or not taking antioxidant vitamin or mineral supplements prevents the development of AMD. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2011, Issue 12), MEDLINE (January 1950 to January 2012), EMBASE (January 1980 to January 2012), Open Grey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 26 January 2012. We included all randomised controlled trials (RCTs) comparing an antioxidant vitamin and/or mineral supplement (alone or in combination) to control. Both review authors independently assessed risk of bias in the included studies and extracted data. One author entered data into RevMan 5 and the other author checked the data entry. We pooled data using a fixed-effect model. We included four RCTs in this review; 62,520 people were included in the analyses. The trials were conducted in Australia, Finland and the USA and investigated vitamin E and beta-carotene supplements. Overall the quality of the evidence was high. People who took these supplements were not at decreased (or increased) risk of developing AMD. The pooled risk ratio for any antioxidant supplement in the prevention of any AMD was 0.98 (95% confidence interval 0.89 to 1.08) and for advanced AMD was 1.05 (95% CI 0.80 to 1.39). Similar results were seen when the analyses were

  14. 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.

  15. Discrepant expression of cytokines in inflammation- and age-related cataract patients.

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    Wan Chen

    Full Text Available PURPOSE: Inflammatory cataracts secondary to Behcet's disease (BD or Vogt-Koyanagi-Harada disease (VKH are thought to result from a pathological dysregulation of cytokines that is different from that of age-related (AR cataracts. However, little is known about the function of cytokines in the development of inflammatory cataracts. The purpose of this study was to identify possible differences in cytokine expression in inflammation- and age-related cataract patients. METHODS: Analysis techniques involving the concomitant use of a cocktail of antibody-coated non-magnetic beads were used to determine the cytokine expression profiles of BD, VKH and AR cataract patients. Furthermore, anterior chamber aqueous flares and inflammatory cells were quantitatively measured with a laser flare cell meter (LFCM. RESULTS: The expressions of interleukin-2 (IL-2, IL-4, IL-6, IL-10, IL-17A, and interferon-γ (IFN-γ were analyzed in aqueous humor (AqH, phytohemagglutinin (PHA-stimulated and non-PHA-stimulated cultures of peripheral blood mononuclear cells (PBMCs from the three types of cataract patients. IL-6 and IFN-γ were identified above the detection limits, but, among the BD and VKH cataract patients, only the levels of IL-6 were significantly higher in both the AqH and PBMC non-PHA cultures compared with the levels observed in the AR cataract patients. In contrast, IFN-γ was significantly elevated in the AqH of the BD cataract patients compared with the VKH and AR cataract patients. In the PHA-stimulated PBMC cultures, IL-2, IFN-γ, IL-6, and IL-17A were significantly increased, and the IL-6 level was significantly higher in the VKH patients than in the BD and AR cataract patients. The correlation analyses of the cytokines and inflammation indexes of the AqH obtained with the LFCM revealed that only IL-6 was significantly correlated with the inflammation index. CONCLUSION: Distinct expression profiles of cytokines and the correlations of these profiles

  16. Glaucomatous and age-related changes in corneal pulsation shape. The ocular dicrotism.

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    Monika E Danielewska

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

  17. Aging-related alterations in the distribution of Ca(2+)-dependent PKC isoforms in rabbit hippocampus.

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    Van der Zee, E A; Palm, I F; O'Connor, M; Maizels, E T; Hunzicker-Dunn, M; Disterhoft, J F

    2004-01-01

    The immunocytochemical and subcellular localization of the Ca(2+)-dependent protein kinase C (cPKC) isoforms (PKCalpha, beta1, beta2, and gamma) was examined in rabbit hippocampus of young (3 months of age; n = 11) and aging (36 months of age; n = 14) subjects. Detailed immunocytochemical analyses revealed a significant increase in PKCbeta1, beta2, and gamma immunoreactivity in principal cell bodies and associated dendrites, and interneurons of the hilar region in the aging rabbits. The number of PKCalpha- and gamma-positive interneurons in the aging stratum oriens declined significantly. PKCalpha was least affected in principal cells, showing an increase in immunostaining in granule cells only. Weakly PKC-positive principal cells intermingled between densely stained ones were seen in parts of the hippocampus in most of the aging rabbits, showing that the degree of aging-related alterations in PKC-immunoreactivity varies between neurons. Changes in PKC expression in the molecular and subgranular layer of the aging dentate gyrus suggested a reorganization of PKC-positive afferents to this region. Western blot analysis revealed a significant loss of PKC in the pellet fraction for all isoforms, and a tendency for increased levels of cytosolic PKC. However, no significant changes were found in total PKC content for any PKC isoform. A concurrent dramatic loss of the PKC anchoring protein receptor for activated C kinase (RACK1) in the pellet fraction was shown by Western blotting. These findings suggest that the loss of RACK1 contributes to the dysregulation of the PKC system in the aging rabbit hippocampus. The enhanced PKC-immunoreactivity might relate to reduced protein-protein interactions of PKC with the anchoring protein RACK1 leading to increased access of the antibodies to the antigenic site. In conclusion, the results suggest that memory deficits in aging rabbits are (in part) caused by dysregulation of subcellular PKC localization in hippocampal neurons

  18. Age-Related Trajectories of Memory Function in Middle-Aged and Older Adults with and without Hearing Impairment.

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    Wu, Shang-Te; Chiu, Ching-Ju

    2016-01-01

    To examine age-related trajectories of memory function associated with hearing status and to explore potential confounding by sociodemographic, physiological, and behavioral factors in that link. A national representative sample of Taiwanese adults ≥50 years with and without hearing impairment in 1996 (n = 4,707) were interviewed every 3-4 years until 2007. Cross-sectional and prospective associations between hearing impairment and memory function were determined using multilevel modeling. In bivariate analyses, hearing impairment was associated not only with poor memory function but also with sociodemographic, behavioral and self-rated health status and chronic conditions. These factors, however, did not confound the relationship of hearing impairment with the level or rate of change in the modified Rey Auditory Verbal Learning Test (m-RAVLT) score - hearing impairment increased the age-related differences in the intercept of the memory function by 25.6%, and that the association was significantly greater in older people than in younger people, but hearing impairment was not associated with the slope of the cognitive trajectory over time. Hearing impairment and the m-RAVLT score at any point in time may have partially combined pathologic mechanisms with age. The vascular risk covariates we considered might also share the etiological pathways and be part of important prevention strategies for guarding against age-related memory decline in the future. © 2016 S. Karger AG, Basel.

  19. Age-related functional changes and susceptibility to eccentric contraction-induced damage in skeletal muscle cell

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    Seung-Jun Choi

    2016-09-01

    Full Text Available Depending upon external loading conditions, skeletal muscles can either shorten, lengthen, or remain at a fixed length as they produce force. Fixed-end or isometric contractions stabilize joints and allow muscles to act as active struts during locomotion. Active muscles dissipate energy when they are lengthened by an external force that exceeds their current force producing capacity. These unaccustomed eccentric activities often lead to muscle weakness, soreness, and inflammation. During aging, the ability to produce force under these conditions is reduced and appears to be due to not only reductions in muscle mass but also to alterations in the basic mechanisms of contraction. These alterations include impairments in the excitation–contraction process, and the action of the cross-bridges. Also, it is well known that age-related skeletal muscle atrophy is characterized by a preferential atrophy of fast fibers, and increased susceptibility to fast muscle fiber when aged muscles are exposed to eccentric contraction followed by the impaired recovery process has been reported. Taken together, the selective loss of fast muscle fiber in aged muscle could be affected by eccentric-induced muscle damage, which has significant implication to identify the etiology of the age-related functional changes. Therefore, in this review the alteration of age-related muscle function and its impact to/of eccentric induced muscle damage and recovery will be addressed in detail.

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

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    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.