Bedrest and Aging

卧床休息与衰老

• 批准号: 7236152
• 负责人: WIlliam J Evans
• 金额: $ 112.45万
• 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/7236152
• 关键词: Bedrest; Aging

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）：卧床休息对生理储备减少的个体（尤其是老年人）的影响尚未得到充分研究和了解。长时间卧床通常与多种疾病、创伤或手术相关，会对代谢和功能产生影响，而这种影响在老年人中可能会加剧。因此，我们建议全面评估老年人完全卧床10天（许多老年人入院时常见的一段时间）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的影响。项目 1 将研究必需氨基酸 (EAA) 溶液对肌肉大小和肌肉蛋白质合成速率的影响。该项目将与项目 2 直接互动，项目 2 将检查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，将评估少量运动和 EAA 的综合效果。项目 3 将确定糖耐量正常和受损受试者卧床诱导的胰岛素抵抗的程度，以及二甲双胍对胰岛素作用下降、脂质氧化和肌肉蛋白代谢的预防性影响。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）对卧床诱导的胰岛素抵抗的作用，还将检验 PPARα 激动剂非诺贝特通过增加长链脂肪酸氧化速率来改善胰岛素抵抗的假设。核心将支持这些项目：管理核心、提供稳定同位素分析和统计支持的分析核心，以及提供骨骼肌中胰岛素信号级联成分分析的胰岛素信号核心。该计划项目将首次详细、全面地研究卧床休息对老年人的影响，并将提供临床上有用的策略，以防止卧床休息对这一弱势群体产生潜在的灾难性影响。