GH is the most important protein anabolic agent in the body, and is essential for protein synthesis throughout the lifespan. We have shown that pulsatile GH secretion is reduced in old rats, and other have reported a GH decline in elderly human subjects. A decrease in protein synthesis in many aging body organs and tissues also has been demonstrated and may be associated with the decreases in function of these organs and tissues. Our objectives are to determine why GH secretion declines during aging, and the relation of this decline to reduced protein synthesis. The causes for the aging-related decrease in GH secretion will be studied by determining (a) the effects of GRF and somatostatin on GH release in vivo and in vitro in old (18-28 months), middle-aged (10-15 months) and young (2-4 months) rats (b) hypothalamic release in vitro of somatostatin?14? and?28? (and of GRF if antiserum can be obtained) in the 3 age groups (c) whether there are differences in size and biological activity of the GH release by the 3 age groups (d) the effects of GH on in vitro somatomedin-C release by liver fragments from the 3 age groups. The relation of GH secretion to protein synthesis will be studied by measuring amino acid in corporation into protein in diaphragm muscle, liver, and possibly other tissues in the 3 age groups. Attempts will be made to increase protein synthesis in these tissues of old rats by administering GH, GRF, and CNS active drugs that stimulate GH secretion (L-Dopa, clonidine, opiates, etc.) These studies will be performed both in male and female rats, since males continue to show a slow degree of body growth (in length as well as in weight) even late in life, whereas females show growth stasis beginning in middle age but respond readily to GH administration by weight and length increases. Our preliminary results show that the objectives and methods are feasible, and that solutions to the problems proposed are attainable.
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