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REVIVE - Resveratrol to enhance vitality and vigor in elders

REVIVE - 白藜芦醇增强老年人的活力和活力

基本信息

批准号：
8724341
负责人：
Stephen D Anton
金额：
$ 34.54万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-09-01 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8724341
关键词：
5&apos -AMP-activated protein kinase Adverse event Affect Age Aging Attenuated Award Biochemical Biogenesis Biological Blood Blood Chemical Analysis Blood Pressure Cell Respiration Cells Clinic Visits Clinical Trials Cognitive Collaborations Complex Cross-Over Studies Data Diastolic blood pressure Disease Dose Elderly Energy-Generating Resources Enzymes Etiology Gait Genes Genetic Crossing Over Glucose Goals Grapes Health Human Impairment Individual Insulin Intervention Link Literature Lower Extremity Measures Metabolic Metabolism Mitochondria Mitochondrial DNA Monitor Muscle Muscle Fatigue Muscle Fibers Near-Infrared Spectroscopy Non obese Obesity Overweight Oxidative Phosphorylation PPAR gamma Participant Performance Physical Function Physical activity Pilot Projects Placebos Play Ploidies Population Qualifying Randomized Recording of previous events Research Research Personnel Resistance Respiration Rest Resveratrol Risk Risk Factors Sampling Sirtuins Skeletal Muscle Skin Specimen Speed Staging Supplementation Testing Translating Walking Work age related cognitive function disability enzyme activity experience functional decline high risk improved men meter middle age older men older women primary outcome red wine vastus lateralis

项目摘要

A large and growing number of older adults experience progressive declines in physical function, culminating in age-related physical disability with no clear connection to a single disease. Although the etiology of age-related physical disability is complex and multi-factorial, emerging evidence implicates the mitochondria as playing a key role in the initial onset and progression of functional decline in many older adults. Additionally, our pilot data strongly suggest functional declines are associated with reductions in mitochondrial respiration, as well as decreases in oxidative mitochondrial enzyme activities and enzyme content. These changes were linked to a large decline in peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and specific Sirtuins (i.e., SIRT3) in skeletal muscle, both of which are regulators of mitochondria biogenesis. The natural compound resveratrol appears to oppose the reductions in mitochondrial function associated with aging by affecting the expression of key genes, such as PGC-1α, which support oxidative phosphorylation and mitochondrial biogenesis. In another recently completed pilot study, we found resveratrol, at a dose of 1000 mg/day, significantly enhanced resting muscle oxidative metabolism (measured using near infrared spectroscopy), as well as cognitive and physical function, in older adults (age > 65 years). Despite promising findings from one recent clinical trial involving obese, middle-age men, no study to date has examined the effects of resveratrol supplementation on mitochondrial function in older adults, or whether the hypothesized changes in mitochondrial function translate to improvements in physical functioning. Thus, the proposed randomized, parallel study will determine, in older men and women (> 70 years), whether 90 days of resveratrol supplementation is associated with (i) increases in muscle mitochondrial function (State 3 & 4 respiration), (ii) increases in levels of PGC-1α, AMP-activated protein kinase (AMPK), and Sirtuins (i.e. SIRT1 and SIRT3), and (iii) improvements in functional performance, as well as metabolic risk factors. To achieve these aims, 60 moderate to low functioning participants will be randomized to receive a placebo (n=20), 1000 mg/day of resveratrol (n=20), or 1500 mg/day of resveratrol (n=20) for a 90-day period. We will collect muscle specimens from the vastus lateralis and blood at baseline and 90 days for biochemical analyses, as well as monitor blood chemistries and adverse events at monthly clinic visits. If our hypotheses are supported, this study will be the first to show that resveratrol improves mitochondrial function in muscle, and that these changes are associated with increased levels of physical function in moderate to low functioning older adults ¿ the population who is at greatest risk of functional decline and physical disability.