AGING AND SKELETAL MUSCLE FATTY ACID METABOLISM

描述(改编自申请者的摘要)：骨骼肌是一种 血浆中游离脂肪酸(FFA)的主要消费者，占(50%) 全身游离脂肪酸在吸收后状态下的处置。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 老年人氧化通过脂解释放的游离脂肪酸的能力。这样的一种 损伤可能导致中心性肥胖症患病率增加， 在老年人群中发现的血脂异常和相关的并存疾病。 因此，这个项目的总体目标是确定 衰老对人体肌肉游离脂肪酸利用的影响。以下是具体的 假设将得到检验： 1.老年人肌肉中游离脂肪酸的利用率降低，不仅是因为 肌肉质量的减少，但也是FFA使用量下降的结果 每公斤肌肉。后者被假定与下降有关 肌肉呼吸量随年龄增长。 2.随着年龄的增长，每公斤肌肉中FFA使用量的减少是由于 游离脂肪酸跨内线粒体转运速度的降低 薄膜。 3.耐力运动训练将改善肌肉FFA的缺陷 老年人的利用情况。 这些假设将通过结合使用示踪剂方法论进行检验 动静脉平衡测量来量化FFA的摄取和氧化 跨过健康的年轻和老年男性和女性的腿。主题将是 在剧烈运动和休息时进行研究，以放大任何 肌肉FFA代谢的年龄相关差异，而FFA的利用率 将通过服用阿昔莫司、肝素和Intralipid进行控制。 中链和长链脂肪酸示踪剂(即1-14C-辛酸酯 和1-13C-油酸)将用于确定线粒体膜 运输限制了老年人对FFA的使用。这将是第一次 老年人肌肉游离脂肪酸代谢的综合研究。

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.