AGING AND SKELETAL MUSCLE FATTY ACID METABOLISM

衰老与骨骼肌脂肪酸代谢

• 批准号: 2387920
• 负责人: ANDREW R COGGAN
• 金额: $ 14.26万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 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 1998-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2387920
• 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 血浆传播游离脂肪酸（FFA）的主要消费者，占（50％） 在吸收后状态下全身FFA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 老年人通过脂解释放FFA的能力。 这样的 损害可能导致中央肥胖的患病率增加， 血脂血症以及老年人群中发现的相关合并症。 因此，该项目的总体目标是确定 人类肌肉FFA利用率的老化。 以下特定 假设将进行检验： 1。老年人的肌肉FFA利用率降低了，不仅是结果 肌肉质量减少，但由于FFA使用的下降 每公斤肌肉。 后者被认为与下降有关 随着年龄的增长，肌肉呼吸能力。 2。每公斤肌肉随着衰老而减少的FFA使用是a的结果 FFA转运率降低了内部线粒体的速度 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来检验 进行动静脉平衡测量，以量化FFA摄取和氧化 在健康的年轻男女健康的腿上。 受试者将是 在急性运动和休息期间进行了研究，以放大任何 肌肉FFA代谢与年龄有关的差异，而FFA的可用性 将通过施用Acipimox，肝素和脂质内施用来控制。 中链和长链脂肪酸示踪剂（即1-14c- octanoate） 和1-13c-olete）将用于确定线粒体膜是否 运输限制老年人的FFA利用率。 这些将是第一个 对老年人的肌肉FFA代谢的全面研究。