Attendant with the aging process there is a decline in the functional and metabolic capacity of the skeletal musculature. The general hypothesis of this proposal is that a significant contribution to the decline in the musculature observed concomitant with the aging process is insult without recovery. Two very common insults to the skeletal muscle will be studied alone and together. The first is disuse, which causes both a decline in muscle protein mass and a shift in the expressed characteristics of skeletal muscle. The second is the pharmacological stress caused by the medicinal use of glucocorticoids. Glucocorticoids cause a severe atrophy of skeletal muscle. Using a single hindlimb non-invasive immobilization procedure, disuse atrophy alone and in the context of pharmacological doses of glucocorticoids will be effected in muscles followed by remobilization and recovery. The type of insult to the muscle being studied in this project occurs with increasing frequency in humans as aging progresses. The experiments will involve populations of Fisher 344 rats of three ages so that the role of aging in the atrophic and recovery can be assessed. The second aspect of these studies is the analysis of the efficacy of recombinant growth hormone as a pharmacological agent to reduce atrophic processes and accelerate recovery of muscle following disuse- and glucocorticoid-induced insult. These studies will address directly both the observed changes in muscle that occur with aging and the mechanism that produces those changes. Evaluation of the changes in the muscles will involve an analysis of the functional changes, structural changes and changes in gene expression. Functional changes will involve the measurement of the contractile characteristics of the muscle. Structural changes will involve the measurement of both mRNA and the proteins for which they code. Understanding the physiological antagonism between rGH and glucocorticoids as a function of use/disuse will involve the measurement of the expression of selected aspects of both hormone cascade mechanisms at both the mRNA and protein level.