Human Growth Hormone and Human Aging

UNTIL recently, there has been little scientific inquiry into the physiological significance of, and possible therapy for, GH deficiency in adulthood. This was because the lack of efficacy in humans of animal-derived (e.g.1 bovine or porcine) GH and the limited supply of human cadaveric GH restricted use of exogenous GH to treatment of GHdeficient children. The availability of recombinant human GH (rhGH) has led to a renewal of scientific and clinical interest in investigating wider indications for GH administration. It is now recognized that GH deficiency may exert adverse metabolic effects in adults with panhypopituitarism, and that these effects can be reversed or attenuated by treatment with rhGH (1, 2). Recently, it has also become apparent that, with advancing age, an increasing proportion of men and women with no clinical evidence of pituitary pathology show decreases in GH secretion and serum levels of insulin-like growth factor-I (IGF-I) (3, 4). Because GH deficiency (1, 2) and normal aging (5) are both associated with decreases in protein synthesis and percent of lean body and bone mass, and with increases in percent of body fat, it is possible that reduced GH secretion and IGF-I levels might account, at least in part, for one or more of the above effects of aging, and that some older people might benefit from treatment with rhGH. In this regard, in several recent studies, administration of rhGH for periods varying from a few weeks to 6 months has resulted in improvements in nitrogen balance, an increase in lean body mass, and a decrease in percent body fat in older persons with low IGF-I levels (3, 4, 6, 7). We review herein the published work describing the alterations in GH and IGF-I production with increasing age, and the methods, benefits, and risks of GH treatment of older persons in the light of new knowledge regarding basic physiology of GH secretion and action. We also attempt to point out areas requiring further investigations.