Bedrest and Aging

描述(申请人提供)：卧床休息对生理储备减少的个人，特别是老年人的影响，既没有得到很好的研究，也没有得到很好的理解。延长卧床时间通常与各种疾病、创伤或手术有关，会导致代谢和功能方面的后果，在老年人中可能会加剧。因此，我们建议全面评估10天完全卧床(这段时间对于许多老年人来说是常见的住院时间)对身体成分、力量、机能、胰岛素作用以及全身和骨骼肌代谢的影响。项目1将研究必需氨基酸溶液(EaaS)对肌肉大小和肌肉蛋白质合成速度的影响。这个项目将直接与项目2互动，项目2将研究最少量的肌肉活动对保持肌肉大小、功能和力量的影响。通过这两个项目的相互作用，将评估少量锻炼和EAA的综合效果。项目3将确定卧床休息导致的胰岛素抵抗在糖耐量正常和受损的受试者中的程度，以及二甲双胍对胰岛素作用降低、脂肪氧化和肌肉蛋白质代谢的预防性影响。项目4将研究肌肉脂质(根据肌细胞内脂质水平的高低对受试者进行分层)在卧床诱导的胰岛素抵抗中的作用，并将测试PPARα激动剂非诺贝特将通过增加长链脂肪酸氧化率来改善胰岛素抵抗的假设。核心将支持这些项目：一个行政核心，一个分析核心，提供稳定的同位素分析和统计支持，以及一个胰岛素信号核心，提供对骨骼肌中胰岛素信号级联的组成部分的分析。该计划项目将首次详细和全面地了解卧床休息对老年人的影响，并将提供临床上有用的策略，以防止其在这一脆弱人群中产生潜在的灾难性影响。

DESCRIPTION (provided by applicant): The consequences of bedrest on individuals with a decreased physiological reserve, especially the elderly, are neither well studied nor understood. Extended periods of bedrest commonly associated with a wide variety of illnesses, trauma, or surgery have metabolic and functional consequences that are likely to be exacerbated in the elderly. Therefore, we propose a comprehensive assessment of the effects on elderly people of 10 days of complete bedrest (a period of time common for many elderly people to be admitted to a hospital) on body composition, strength, functional capacity, insulin action, and whole body and skeletal muscle metabolism. Project 1 will examine the effects of a solution of essential amino acids (EAAs) on muscle size and the rate of muscle protein synthesis. This project will interact directly with Project 2, which will examine the effects of minimal amounts of muscular activity on preservation of muscle size, function, and strength. Through the interaction of these two projects the combined effects of small amounts of exercise and EAAs will be assessed. Project 3 will determine the extent of bedrest-induced insulin resistance in subjects with normal and impaired glucose tolerance, and the prophylactic influence of metformin on decreased insulin action and lipid oxidation and muscle protein metabolism. Project 4 will examine the role of muscle lipid (by stratifying subjects according to high or low intramyocellular lipid levels) on bedrest-induced insulin resistance and will also test the hypothesis that a PPARalpha agonist, fenofibrate, will ameliorate insulin resistance by increasing the long-chain fatty acid oxidation rate. Cores will support these projects: an Administrative Core, an Analytical Core providing stable isotope analysis and statistical support, and an Insulin Signaling Core providing analyses of components of the insulin signaling cascade in skeletal muscle. This Program Project will, for the first time, provide a detailed and comprehensive look at the effects of bedrest in elderly people and will provide clinically useful strategies to prevent its potentially catastrophic effects in this vulnerable population.