ul Sticht Center on Aging

Wake Forest, NC, United States

ul Sticht Center on Aging

Wake Forest, NC, United States
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Justice J.,ul Sticht Center On Aging | Willard S.L.,University of Pennsylvania
Neuroscience and Biobehavioral Reviews | Year: 2017

Selective serotonin reuptake inhibitor (SSRI) use is ubiquitous because they are widely prescribed for a number of disorders in addition to depression. Depression increases the risk of coronary heart disease (CHD). Hence, treating depression with SSRIs could reduce CHD risk. However, the effects of long term antidepressant treatment on CHD risk, as well as other aspects of health, remain poorly understood. Thus, we undertook an investigation of multisystem effects of SSRI treatment with a physiologically relevant dose in middle-aged adult female cynomolgus monkeys, a primate species shown to be a useful model of both depression and coronary and carotid artery atherosclerosis. Sertraline had no effect on depressive behavior, reduced anxious behavior, increased affiliation, reduced aggression, changed serotonin neurotransmission and volumes of neural areas critical to mood disorders, and exacerbated coronary and carotid atherosclerosis. These data suggest that a conservative approach to prescribing SSRIs for cardiovascular or other disorders for long periods may be warranted, and that further study is critical given the widespread use of these medications. © 2016

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.

PubMed | ul Sticht Center on Aging and Wake forest University
Type: | Journal: Nutrition & diabetes | Year: 2016

Weight regain following intentional weight loss may negatively impact body composition, accelerating fat regain and increasing risk of physical disability. The purpose of this study was to compare long-term changes in whole body and thigh composition in obese older adults who intentionally lost and then partially regained weight to obese older adults who remained weight stable.This pilot study analyzed total body (dual-energy X-ray absorptiometry (DXA)) and thigh (computed tomography (CT)) composition data collected from 24 older (65-79 years) adults 18 months after completion of a 5-month randomized trial that compared resistance training alone (RT) with RT plus caloric restriction (RT+CR).Mean loss of body mass in the RT+CR group (n=13) was 7.12.4kg during the 5-month intervention (74% fat mass; 26% lean mass; all P<0.01), whereas RT (n=11) remained weight stable (+0.31.8kg; P=0.64). Differential group effects were observed for all DXA and CT body composition measures at 5 months (all P0.01); however, by 23 months, group differences persisted only for total body (RT+CR: 81.610.0kg vs RT: 88.514.9kg; P=0.03) and lean (RT+CR: 50.89.3kg vs RT: 54.412.0kg; P<0.01) mass. All RT+CR participants regained weight from 5 to 23 months (mean gain=+4.82.6kg; P<0.01). Total fat mass and all thigh fat volumes increased, whereas thigh muscle volume decreased, during the postintervention follow-up in RT+CR (all P0.01). In the RT group, body mass did not change from 5 to 23 months (-0.20.9kg; P=0.87). Decreased total thigh volume, driven by the loss of thigh muscle volume, were the only postintervention body composition changes observed in the RT group (both P<0.04).Short-term body composition benefits of an RT+CR intervention may be lost within 18 months after completion of the intervention.

PubMed | University of Maryland, Baltimore, Northwestern University, University of Florida, Stanford University and 6 more.
Type: Journal Article | Journal: Journal of the American Medical Directors Association | Year: 2015

The objective of this study was to evaluate cross-sectional and longitudinal associations between ankle-brachial index (ABI) and indicators of cognitive function.Randomized clinical trial (Lifestyle Interventions and Independence for Elders Trial).Eight US academic centers.A total of 1601 adults ages 70-89 years, sedentary, without dementia, and with functional limitations.Baseline ABI and interviewer- and computer-administered cognitive function assessments were obtained. These assessments were used to compare a physical activity intervention with a health education control. Cognitive function was reassessed 24 months later (interviewer-administered) and 18 or 30 months later (computer-administered) and central adjudication was used to classify individuals as having mild cognitive impairment, probable dementia, or neither.Lower ABI had a modest independent association with poorer cognitive functioning at baseline (partial r= 0.09; P < .001). Although lower baseline ABI was not associated with overall changes in cognitive function test scores, it was associated with higher odds for 2-year progression to a composite of either mild cognitive impairment or probable dementia (odds ratio 2.60 per unit lower ABI; 95% confidence interval 1.06-6.37). Across 2 years, changes in ABI were not associated with changes in cognitive function.In an older cohort sedentary individuals with dementia and with functional limitations, lower baseline ABI was independently correlated with cognitive function and associated with greater 2-year risk for progression to mild cognitive impairment or probable dementia.

PubMed | ul Sticht Center On Aging and Wake forest University
Type: | Journal: Aging clinical and experimental research | Year: 2016

Little is known about the comparative effect of aerobic training (AT) versus resistance training (RT) on gait speed, a strong predictor of disability.To compare the effect of AT versus RT on gait speed and other functional measures.Overweight and obese [body mass index (BMI) 27.0kg/mBoth AT and RT resulted in clinically significant improvements in usual-pace gait speed (0.080.14 and 0.080.17m/s, respectively, both p<0.05) and SPPB (0.531.40 and 0.531.20 points, both p<0.05) and chair rise time (-1.23.2 and -1.73.0s, p<0.05). Only AT improved fast-pace gait speed (0.110.10m/s, p<0.05). In the RT participants, lower baseline knee strength was associated with less improvement in usual-pace gait speed. In AT participants, lower baseline VOWhile both AT and RT improved usual-pace gait speed, only AT improved fast-pace gait speed. Lower baseline fitness was associated with less improvement with training.Research to directly compare which mode of training elicits the maximum improvement in older individuals with specific functional deficits could lead to better intervention targeting.

PubMed | University of Minnesota, University of Washington, CRS4 Bioinformatica, University of Vermont and 6 more.
Type: | Journal: BMC genomics | Year: 2015

Transcriptomic studies hold great potential towards understanding the human aging process. Previous transcriptomic studies have identified many genes with age-associated expression levels; however, small samples sizes and mixed cell types often make these results difficult to interpret.Using transcriptomic profiles in CD14+ monocytes from 1,264 participants of the Multi-Ethnic Study of Atherosclerosis (aged 55-94 years), we identified 2,704 genes differentially expressed with chronological age (false discovery rate, FDR0.001). We further identified six networks of co-expressed genes that included prominent genes from three pathways: protein synthesis (particularly mitochondrial ribosomal genes), oxidative phosphorylation, and autophagy, with expression patterns suggesting these pathways decline with age. Expression of several chromatin remodeler and transcriptional modifier genes strongly correlated with expression of oxidative phosphorylation and ribosomal protein synthesis genes. 17% of genes with age-associated expression harbored CpG sites whose degree of methylation significantly mediated the relationship between age and gene expression (p<0.05). Lastly, 15 genes with age-associated expression were also associated (FDR0.01) with pulse pressure independent of chronological age. Comparing transcriptomic profiles of CD14+ monocytes to CD4+ T cells from a subset (n=423) of the population, we identified 30 age-associated (FDR<0.01) genes in common, while larger sets of differentially expressed genes were unique to either T cells (188 genes) or monocytes (383 genes). At the pathway level, a decline in ribosomal protein synthesis machinery gene expression with age was detectable in both cell types.An overall decline in expression of ribosomal protein synthesis genes with age was detected in CD14+ monocytes and CD4+ T cells, demonstrating that some patterns of aging are likely shared between different cell types. Our findings also support cell-specific effects of age on gene expression, illustrating the importance of using purified cell samples for future transcriptomic studies. Longitudinal work is required to establish the relationship between identified age-associated genes/pathways and aging-related diseases.

You T.,University of Massachusetts Boston | Wang X.,University of South Carolina | Murphy K.M.,ul Sticht Center on Aging | Lyles M.F.,ul Sticht Center on Aging | And 5 more authors.
Obesity | Year: 2014

Objective To compare the regional differences in subcutaneous adipose tissue hormone/cytokine production in abdominally obese women during weight loss. Methods Forty-two abdominally obese, older women underwent a 20-week weight loss intervention composed of hypocaloric diet with or without aerobic exercise (total energy expenditure: 2800 kcal/week). Subcutaneous (gluteal and abdominal) adipose tissue biopsies were conducted before and after the intervention. Adipose tissue gene expression and release of leptin, adiponectin, and interleukin 6 (IL-6) were determined. Results The intervention resulted in significant weight loss (-10.1 ± 0.7 kg, P < 0.001). At baseline, gene expression of adiponectin were higher (P < 0.01), and gene expression and release of IL-6 were lower (both P < 0.05) in abdominal than in gluteal adipose tissue. After intervention, leptin gene expression and release were lower in both gluteal and abdominal adipose tissue compared to baseline (P < 0.05-0.01). Abdominal, but not gluteal, adipose tissue adiponectin gene expression and release increased after intervention (both P < 0.05). Conclusion A 20-week weight loss program decreased leptin production in both gluteal and abdominal adipose tissue, but only increased adiponectin production from abdominal adipose tissue in obese women. This depot-specific effect may be of importance for the treatment of health complications associated with abdominal adiposity. Copyright © 2014 The Obesity Society.

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.

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.

Beavers K.M.,ul Sticht Center on Aging | Lyles M.F.,ul Sticht Center on Aging | Davis C.C.,Wake forest University | Wang X.,University of Washington | And 2 more authors.
American Journal of Clinical Nutrition | Year: 2011

Background: Despite the well-known recidivism of obesity, surprisingly little is known about the composition of body weight during weight regain. Objective: The objective of this study was to determine whether the composition of body weight regained after intentional weight loss is similar to the composition of body weight lost. Design: The design was a follow-up to a randomized controlled trial of weight loss in which body composition was analyzed and compared in 78 postmenopausal women before the intervention, immediately after the intervention, and 6 and 12 mo after the intervention. Results: All body mass and composition variables were lower immediately after weight loss than at baseline (all P < 0.05). More fat than lean mass was lost with weight loss, which resulted in bodycomposition changes favoring a lower percentage of body fat and a higher lean-to-fat mass ratio (P < 0.001). Considerable interindividual variability in weight regain was noted (CV = 1.07). In women who regained ≥2 kg body weight, a decreasing trend in the lean-to-fat mass ratio was observed, which indicated greater fat mass accretion than lean mass accretion (P < 0.001). Specifically, for every 1 kg fat lost during the weight-loss intervention, 0.26 kg lean tissue was lost; for every 1 kg fat regained over the following year, only 0.12 kg lean tissue was regained. Conclusions: Although not all postmenopausal women who intentionally lose weight will regain it within 1 y, the data suggest that fat mass is regained to a greater degree than is lean mass in those who do experience some weight regain. The health ramifications of our findings remain to be seen. © 2011 American Society for Nutrition.

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