Bedrest and Aging

卧床休息与衰老

• 批准号: 6944712
• 负责人: WIlliam J Evans
• 金额: $ 110.49万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6944712
• 关键词: clinical research; human old age (65+); human subject; muscle metabolism; restricted physical activity

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.

描述（由申请人提供）：Bedrest对生理储量减少（尤其是老年人）降低的个体的后果既没有很好地研究，也没有理解。长时间的卧铺通常与多种疾病，创伤或手术相关的床上具有代谢和功能后果，这些后果可能会在老年人中加剧。因此，我们提出对10天完全卧床的老年人的影响（许多老年人被送往医院的常见的一段时间）对身体成分，力量，功能能力，胰岛素作用以及全身和骨骼肌代谢。项目1将检查必需氨基酸（EAA）溶液对肌肉大小和肌肉蛋白合成速率的影响。该项目将直接与项目2相互作用，该项目将研究最小肌肉活动对保留肌肉大小，功能和力量的影响。通过这两个项目的相互作用，将评估少量运动和EAA的综合影响。项目3将确定在葡萄糖耐受性正常和受损的受试者中，床质诱导的胰岛素抵抗的程度，以及二甲双胍对胰岛素作用降低的预防作用，脂质氧化和肌肉蛋白质代谢。项目4将检查肌肉脂质（通过根据较高或低的室内细胞内脂质水平分层对象对床质诱导的胰岛素耐药性进行分层）的作用，并且还将检验以下假设：pParalpha激动剂（fenonofibrate）将通过增加长链链链脂肪酸酸氧化速率来减轻胰岛素的耐药性。核心将支持这些项目：一种行政核心，一种分析核心，提供稳定的同位素分析和统计支持，以及胰岛素信号传导核心提供骨骼肌中胰岛素信号级联的组件分析。该计划项目将首次提供详细而全面的探讨，并详细介绍床上对老年人的影响，并将提供临床上有用的策略，以防止其在这一脆弱人群中的潜在灾难性影响。