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AGING AND SKELETAL MUSCLE FATTY ACID METABOLISM

衰老与骨骼肌脂肪酸代谢

基本信息

批准号：
2832413
负责人：
ANDREW R COGGAN
金额：
$ 12.7万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-09-01 至 2001-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2832413
关键词：
aerobic exercise aerobiosis age difference aging cellular respiration fatty acid metabolism fatty acid transport free fatty acids human old age (65+) human subject mitochondrial membrane muscle metabolism oleate rest striated muscles young adult human (21-34)

项目摘要

DESCRIPTION (Adapted from the Applicant's Abstract): Skeletal muscle is a major consumer of plasma-borne free fatty acids (FFA), accounting for (50% of whole-body FFA disposal in the post-absorptive state. However, age-related changes in muscle mass and/or respiratory capacity may impair the ability of older persons to oxidize FFA released via lipolysis. Such an impairment could contribute to the increased prevalence of central obesity, dyslipidemia, and associated co-morbidities found in the elderly population. Thus, the overall goal of this project is to determine the influence of aging on muscle FFA utilization in humans. The following specific hypotheses will be tested: 1. Muscle FFA utilization is reduced in older persons, not only as a result of a decrease in muscle mass, but also as a result of a decline in FFA use per kg of muscle. The latter is hypothesized to be related to the decline in muscle respiratory capacity with age. 2. The decrease in FFA use per kg of muscle with aging is the result of a reduction in the rate of FFA transport across the inner mitochondrial membrane. 3. Endurance exercise training will ameliorate deficits in muscle FFA utilization in older individuals. These hypotheses will be tested by using tracer methodology in conjunction with arteriovenous balance measurements to quantify FFA uptake and oxidation across the legs of healthy young and older men and women. Subjects will be studied during acute exercise, as well as at rest, to magnify any age-related differences in muscle FFA metabolism, while FFA availability will be controlled via administration of acipimox, heparin, and Intralipid. Both medium-chain and long-chain fatty acid tracers (i.e., 1-14C-octanoate and 1-13C-oleate) will be used to determine whether mitochondrial membrane transport limits FFA utilization in older persons. These will be the first comprehensive studies of muscle FFA metabolism in older humans.

描述（改编自申请人的摘要）：Skeleton muscle是一种肌肉。血浆游离脂肪酸（FFA）的主要消费者，占（50% 在吸收后状态下的全身FFA处置。然而，在这方面，与年龄相关的肌肉质量和/或呼吸能力变化可能会损害老年人氧化通过脂解释放的FFA的能力。这样的损伤可能导致中心性肥胖的患病率增加，血脂异常和老年人群中发现的相关共病。因此，本项目的总体目标是确定衰老对人体肌肉FFA利用的影响。以下具体将检验假设： 1. 老年人肌肉FFA利用率下降，不仅是因为肌肉质量下降，但也是FFA使用减少的结果每公斤肌肉。后者被假设为与下降有关随着年龄的增长，肌肉的呼吸能力。 2. 随着年龄的增长，每公斤肌肉中FFA的使用量减少是由于 FFA通过线粒体内部转运的速率降低膜的 3. 耐力运动训练将改善肌肉FFA的缺陷在老年人中使用。这些假设将通过结合使用示踪方法进行测试通过动静脉平衡测量来量化FFA摄取和氧化在健康的年轻人和老年人的腿上。受试者将研究在急性运动，以及在休息，以放大任何与年龄相关的肌肉FFA代谢差异，而FFA可用性将通过给予阿昔莫司、肝素和Intraperoid进行控制。中链和长链脂肪酸示踪剂（即，1- 14 C-辛酸酯和1- 13 C-油酸酯）将用于确定线粒体膜是否交通限制了老年人对FFA的使用。这将是第一个老年人肌肉FFA代谢的综合研究。