Bedrest and Aging

卧床休息与衰老

• 批准号: 7090046
• 负责人: WIlliam J Evans
• 金额: $ 110.81万
• 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/7090046
• 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）：卧床休息对生理储备下降的个体（尤其是老年人）的影响既没有得到很好的研究，也没有得到很好的理解。通常与各种疾病、创伤或手术相关的长时间卧床休息具有代谢和功能后果，这些后果可能在老年人中加剧。因此，我们建议全面评估10天完全卧床休息（许多老年人住院的一段时间）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将研究最小量的肌肉活动对肌肉大小，功能和力量的保护的影响。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将确定葡萄糖耐量正常和受损受试者中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降低、脂质氧化和肌肉蛋白质代谢的预防作用。项目4将检查肌肉脂质（根据高或低肌细胞内脂质水平对受试者进行分层）在卧床诱导的胰岛素抵抗中的作用，并将检验PPARalpha激动剂非诺贝特通过增加长链脂肪酸氧化速率改善胰岛素抵抗的假设。核心将支持这些项目：一个管理核心、一个提供稳定同位素分析和统计支持的分析核心，以及一个提供骨骼肌中胰岛素信号级联组件分析的胰岛素信号核心。该计划项目将首次详细和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战略，以防止其对这一弱势群体的潜在灾难性影响。