AGING AND SKELETAL MUSCLE FATTY ACID METABOLISM

衰老与骨骼肌脂肪酸代谢

• 批准号: 2769437
• 负责人: ANDREW R COGGAN
• 金额: $ 12.25万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2769437
• 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)

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）：骨骼肌是 血浆游离脂肪酸 (FFA) 的主要消耗者，占 (50% 吸收后状态下的全身 FFA 处理。 然而， 与年龄相关的肌肉质量和/或呼吸能力的变化可能会损害 老年人氧化通过脂肪分解释放的 FFA 的能力。 这样一个 损伤可能导致中心性肥胖患病率增加， 老年人群中发现血脂异常和相关并发症。 因此，该项目的总体目标是确定 衰老对人类肌肉 FFA 利用率的影响。 具体如下 将测试假设： 1. 老年人肌肉 FFA 利用率降低，不仅仅是因为 肌肉质量减少，也是 FFA 使用量减少的结果 每公斤肌肉。 推测后者与下降有关 肌肉呼吸能力随年龄增长。 2. 随着年龄的增长，每公斤肌肉中 FFA 使用量的减少是由于 FFA 穿过线粒体内部的转运速率降低 膜。 3.耐力运动训练将改善肌肉FFA的缺陷 老年人的利用。 这些假设将通过结合使用示踪剂方法进行测试 通过动静脉平衡测量来量化 FFA 摄取和氧化 穿过健康的年轻和老年男性和女性的腿。 科目将是 在剧烈运动期间以及休息时进行研究，以放大任何 肌肉 FFA 代谢与年龄相关的差异，而 FFA 可用性 将通过给予阿昔莫司、肝素和英脱利匹特来控制。 中链和长链脂肪酸示踪剂（即 1-14C-辛酸 和 1-13C-油酸酯）将用于确定线粒体膜是否 交通限制了老年人对 FFA 的利用。 这些将是第一个 老年人肌肉 FFA 代谢的综合研究。