GROWTH HORMONE AND/OR EXERCISE FOR THE FRAIL ELDERLY

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Progressive frailty in the elderly is a major cause of falls, associated fractures, social isolation, and ultimately institutionalization or death. Muscle weakness is one major cause of overall frailty. Contributing to this may be inactivity and decreased growth hormone secretion, known to occur with progressive aging. This study will test the hypothesis that GH administration and exercise training may synergize to improve muscle performance in the elderly; it will also test the sub-hypothesis that continued GH administration after discontinuation of a formal exercise program will prolong the benefits of that exercise training. The effects of recombinant human growth hormone (rhGH), an isotonic exercise program, or the two combined, will be determined in an elderly population preselected for below average physical performance. Male and female subjects (240) will be recruited in the neighborhoods of 3 senior citizen centers in Rhode Island and randomized to receive either rhGH, rhGH plus exercise training, placebo plus exercise or placebo alone. GH (0.015 mg/kg daily, s.c.) will be administered for one year; exercise training will be supervised in the 3 senior centers during 65 sessions over 6 months, followed by 6 months continued GH or placebo administration. Subjects will be evaluated with a standardized physical performance test; for muscle strength using isokinetic dynamometry; regional and whole body lean and adipose soft tissue mass and bone mineral content using dual X-ray densitometry; resting caloric expenditure; and biochemical and hormonal indices including IGF-I and its binding proteins. Ancillary studies will include muscle biopsies in a subset of subjects evaluating morphology and IGF-I and its receptor expression. Using a novel mechanically stimulated myocyte culture system, bioassay of muscle growth promoting effects of subjects' sera and muscle extract will be compared under static and stimulated conditions. Finally, using validated survey instruments of physical activity and health outcomes and utilization, this study may show that this combined intervention program has real efficacy in reducing the human and socioeconomic toll of progressive frailty in the elderly.