The long-term goal of this project is to elucidate the mechanism of the muscle atrophy associated with aging, and to examine the effects of interventions that may reverse this process. The immediate goal is to test the following hypotheses: 1. that the rate of myofibrillar protein synthesis declines with aging in humans; 2. that progressive resistance exercise increases myofibrillar protein synthesis; 3. that growth hormone- treatment increases myofibrillar protein synthesis in older subjects; 4. that growth hormone and resistance exercise have an additive or synergistic effect on strength nd myofibrillar protein synthesis. Subjects will be untrained, but health, men and women, both young (18-30 years) and old (over 60 years). Before any interventions, they will undergo tests of dynamic muscle strength, muscle mass (creatinine excretion on a meat-free diet and magnetic resonance imaging of selected muscles), muscle fiber size (both type 1 and type 2) in tissue taken from quadriceps muscle (vastus lateralis), and myofibrillar protein synthesis in vastus lateralis muscle (determined by the rate of incorporation of leucine into myofibrillar protein using a stable isotope tracer). These studies will be repeated after a 3 month period of one of the following interventions: 1. No intervention or placebo injections (control groups); 2. Progressive strength training (weight lifting); 3. Human growth hormone injections (older subjects only); 4. Progressive strength training plus growth hormone (older subjects only). Older subjects will continue to be studied for 3 months after stopping the growth hormone (or placebo) treatment to determine if there is any long-term benefit of a temporary program of growth hormone treatment. These studies may provide significant new information about the mechanism of muscle atrophy in the elderly, and its treatment or prevention.
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