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Genther D.J.,Johns Hopkins University | Genther D.J.,Johns Hopkins Center on Aging and Health | Betz J.,Johns Hopkins Center on Aging and Health | Pratt S.,Geriatric Research Education and Clinical Center | And 14 more authors.
Journals of Gerontology - Series A Biological Sciences and Medical Sciences | Year: 2015

Background. Hearing impairment (HI) is highly prevalent in older adults and is associated with social isolation, depression, and risk of dementia. Whether HI is associated with broader downstream outcomes is unclear. We undertook this study to determine whether audiometric HI is associated with mortality in older adults. Methods. Prospective observational data from 1,958 adults70 years of age from the Health, Aging, and Body Composition Study were analyzed using Cox proportional hazards regression. Participants were followed for 8 years after audiometric examination. Mortality was adjudicated by obtaining death certificates. Hearing was defined as the pure-tone average of hearing thresholds in decibels re: hearing level (dB HL) at frequencies from 0.5 to 4kHz. HI was defined as pure-tone average >25 dB HL in the better ear. Results. Of the 1,146 participants with HI, 492 (42.9%) died compared with 255 (31.4%) of the 812 with normal hearing (odds ratio = 1.64, 95% CI: 1.36-1.98). After adjustment for demographics and cardiovascular risk factors, HI was associated with a 20% increased mortality risk compared with normal hearing (hazard ratio = 1.20, 95% CI: 1.03-1.41). Confirmatory analyses treating HI as a continuous predictor yielded similar results, demonstrating a nonlinear increase in mortality risk with increasing HI (hazard ratio = 1.14, 95% CI: 1.00-1.29 per 10 dB of threshold elevation up to 35 dB HL). Conclusions. HI in older adults is associated with increased mortality, independent of demographics and cardiovascular risk factors. Further research is necessary to understand the basis of this association and whether these pathways might be amenable to hearing rehabilitation. © 2014 © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. Source

Sanders J.L.,University of Pittsburgh | Iannaccone A.,University of Tennessee Health Science Center | Boudreau R.M.,University of Pittsburgh | Conley Y.P.,University of Pittsburgh | And 9 more authors.
Journals of Gerontology - Series A Biological Sciences and Medical Sciences | Year: 2011

Lens transparency, or the magnitude of cataract severity, is a potential in vivo marker of aging distinguishable from diagnosed cataract. To explore lens transparency as a marker of aging, we determined its association with leukocyte telomere length (LTL) measured with quantitative polymerase chain reaction. Cataract severity was directly measured in 259 participants, and prevalent cataract and incident cataract surgery were ascertained in 2,750 participants of the Health, Aging, and Body Composition Study. LTL was unassociated with clinical cataract outcomes. Six of 259 had successfully aged lenses and a mean LTL of 5,700 bp, whereas 253/259 with poorly aged lenses had a mean LTL of 4,770 bp. Participants with a 1,000 bp greater mean LTL had nearly half the odds of any cataract (odds ratio = 0.47, 95% confidence interval 0.22-1.02) after adjustment. Lens transparency might be associated with longer LTL in community-dwelling older adults and should be investigated further as a possible biomarker of aging. © 2011 The Author. Source

Taylor J.R.,ul Sticht Center on Aging | Ding J.,ul Sticht Center on Aging | Johnson C.,University of Washington | Siscovick D.,University of Washington | And 10 more authors.
Nature Communications | Year: 2014

Age-related variations in DNA methylation have been reported; however, the functional relevance of these differentially methylated sites (age-dMS) are unclear. Here we report potentially functional age-dMS, defined as age- and cis-gene expression-associated methylation sites (age-eMS), identified by integrating genome-wide CpG methylation and gene expression profiles collected ex vivo from circulating T cells (227 CD4+ samples) and monocytes (1,264 CD14+ samples, age range: 55-94 years). None of the age-eMS detected in 227 T-cell samples are detectable in 1,264 monocyte samples, in contrast to the majority of age-dMS detected in T cells that replicated in monocytes. Age-eMS tend to be hypomethylated with older age, located in predicted enhancers and preferentially linked to expression of antigen processing and presentation genes. These results identify and characterize potentially functional age-related methylation in human T cells and monocytes, and provide novel insights into the role age-dMS may have in the aging process. © 2014 Macmillan Publishers Limited. All rights reserved. Source

Zhang T.,Medical Center Boulevard | Choi S.J.,Medical Center Boulevard | Choi S.J.,Kyungsung University | Wang Z.-M.,Medical Center Boulevard | And 8 more authors.
Journals of Gerontology - Series A Biological Sciences and Medical Sciences | Year: 2014

Slow skeletal muscle troponin T (TnnT1) pre-messenger RNA alternative splicing (AS) provides transcript diversity and increases the variety of proteins the gene encodes. Here, we identified three major TnnT1 splicing patterns (AS1-3), quantified their expression in the vastus lateralis muscle of older adults, and demonstrated that resistance training modifies their relative abundance; specifically, upregulating AS1 and downregulating AS2 and AS3. In addition, abundance of TnnT1 AS2 correlated negatively with single muscle fiber-specific force after resistance training, while abundance of AS1 correlated negatively with Vmax. We propose that TnnT1 AS1, AS2 and the AS1/AS2 ratio are potential quantitative biomarkers of skeletal muscle adaptation to resistance training in older adults, and that their profile reflects enhanced single fiber muscle force in the absence of significant increases in fiber cross-sectional area. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. Source

Beavers K.M.,ul Sticht Center on Aging | Hsu F.-C.,Wake forest University | Isom S.,Wake forest University | Kritchevsky S.B.,ul Sticht Center on Aging | And 4 more authors.
Medicine and Science in Sports and Exercise | Year: 2010

Purpose: The purpose of this study was to determine the effects of a 12-month physical activity (PA) intervention on inflammatory biomarkers in elderly men and women. Methods: Four hundred and twenty-four elderly (age = 70-89 yr), nondisabled, community-dwelling men and women at risk for physical disability were enrolled in a multicenter, single-blind, randomized controlled trial. Participants were randomized to participate in either a 12-month moderate-intensity PA intervention or a successful aging health education intervention. Biomarkers of inflammation (interleukin (IL)-6sR, IL-1sRII, soluble tumor necrosis factor receptors 1 and 2 (sTNFRI, sTNFRII), IL-8, IL-15, adiponectin, IL-1ra, IL-2sRα, and TNFα) were measured at baseline, at 6 months, and at 12 months. Results: A baseline blood sample was successfully collected from 368 participants. After adjustment for gender, clinic site, diabetes status, and baseline outcome measure, IL-8 was the only inflammatory biomarker affected by the PA intervention (P = 0.03). The adjusted mean IL-8 at month 12 was 9.9% (0.87 pg•mL) lower in the PA compared with the successful aging group. Secondary interaction analyses between baseline biomarker status and treatment showed one significant interaction (P = 0.02) such that the PA intervention reduced IL-15 concentrations in participants with a baseline IL-15 above the median value of 1.67 pg.mL-1. However, these associations were no longer significant after consideration for multiple comparisons. Conclusions: Overall, this study does not provide definitive evidence for an effect of regular exercise for altering systemic concentrations of the measured inflammatory biomarkers in older adults. Copyright © 2010 by the American College of Sports Medicine. Source

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