Aging is associated with decreases in muscle and bone mass, an increased proportion of body fat, and a redistribution of adipose tissue from peripheral to central sites with marked increases in intra-abdominal visceral fat depots. These changes in body composition of older persons adversely affect functional capacity through declines in muscle strength, endurance, mobility, and increased fracture and cardiovascular risk. Both declining levels of growth hormone (GH) secretion and physical activity may be partially responsible for these changes In body composition. This suggests that physical training alone or GH therapy alone or the two in combination may reverse these changes. Aerobic exercise may enhance the lipolytic actions of GH and favorably modify body fat distribution while strength training may promote a greater anabolic response to GH in the muscle groups that are trained. Increased physical activity may also augment endogenous GH secretion towards levels observed in younger adults which may make exogenous GH administration unnecessary. Healthy older subjects will be randomized to one of six treatment groups in which they will receive either daily GH or placebo injections in a double-blind fashion and either aerobic training, strength training or no training for one year. The following endpoints, relevant to the functional capacity and cardiovascular risk factors of older persons will be assessed: 1) body composition including bone density; 2) regional fat distribution including intra-abdominal visceral fat; 3) exercise capacity; 4) isokinetic muscle strength; 5) carbohydrate metabolism; 6) serum lipoprotein profile; 7) resting metabolic rate; 8) 24-h profile of pulsable GH secretion; and 9) sleep duration and architecture.
Specific aims of this project are: 1) determine the specific effects of GH administration, physical training, and combined GH and physical training for one year on body composition, regional fat distribution (including intra-abdominal fat), exercise capacity, and muscle strength in older subjects; 2) determine whether physical training for one year will enhance endogenous GH secretion in older subjects; and 3) determine whether there are gender differences in the responses to GH administration and/or physical training. This project represents a unique collaboration between 3 established research groups at the University of Virginia and Laval University, Quebec, Canada, with expertise in the regulation of pulsatile GH secretion, the metabolic effects of GH, exercise physiology and training, and regional fat distribution. The results of this clinical trial will determine whether GH administration, in combination with exercise training, will improve the functional capacity (muscle strength, exercise capacity), fracture fisk (bone density), and cardiovascular risk factors (body fat distribution, serum lipoproteins, glucose tolerance) of older persons, and whether some (or all) of these effects may be achieved by enhancement of endogenous GH secretion by physical training.
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