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.