Aging is associated with reductions in muscle mass, strength, and endurance, while fat mass (especially central adiposity) and the associated metabolic abnormalities are increased. These """"""""age related"""""""" changes may have profound effects on physical function and predispose to dependence. A recent study found significant improvements in fat free mass, fat mass, bone mass and skin thickness in older growth hormone (GH) deficient men following six months of subcutaneous recombinant GH administration. The interpretation of that study is limited by its failure to measure changes in strength, endurance, distribution of fat, and function status or to carefully document the metabolic side effects of therapy. Furthermore, the study was conducted in GH deficient males, a small subpopulation of those elders at risk for frailty. We propose to use a prospective, randomized, double blinded, partial factorial study design in a group of women who are not already frail to: (1) assess the positive and negative physiologic effects of a 6 month intervention with synthetic growth hormone releasing hormone (GHRH) alone or in combination with either endurance (ET) or strength (ST) training; (2) define any potential therapeutic relationships between GHRH administration and exercise, including additive effects or the ability of exercise to mitigate metabolic side effects; (3) determine whether ST alone can maintain any benefits attained in the initial 6 month use of GHRH alone or in combination with ST; (4) assess how any observed physiologic improvements translate into measurable gains in physical functional status. We have chosen to use GHRH instead of GH because its smaller size potentially make it cheaper to produce, and more likely to be administered orally or nasally. More importantly, there is evidence that subcutaneous administration of GHRH is associated with restoration of a more physiologic pulsatile GH response in young and older subjects. We hypothesize that: 1) both exercise (ET or ST) or GHRH administration will improve strength body composition and function, and that exercise plus GHRH will be additive; 2) ET will, to a greater extent, mitigate any insulin resistance observed associated with GHRH, while ST will produce greater gains in strength and fat free mass; 3) the improvements after 6 months of GHRH alone or GHRH plus ST will be maintainable with an additional 6 months of ST alone; 4) the physiologic gains following GHRH, exercise or the combination will translate into measurable improvement in functional performance.
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