During childhood and early adult life, growth hormone (GH), secreted by the anterior pituitary, is involved in the growth of bones and muscles and other organs as well. Aging is characterized by a decrease in muscle mass and bone strength and an increase in adipose, similar to the effects of pathological hyposecretion of GH in the young. Aging is also accompanied by a gradual decrease in the output of GH, like the drying of an internal fountain, until in the eighth decade of life, it is secreted at less than one-fifth of the "youthful" level.The GH hypothesis of aging posits that with the availability of human recombinant growth hormone and human recombinant insulin-like growth factor-I, which mediates most of the effects of GH, the GH hypothesis has become testable. Initial experiments involving short term administration of GH in a group of elderly men did indeed show modest improvement in lean body mass and adipose tissue. These studies are sometimes—and incorrectly—taken as proof of the correctness of the growth hormone hypothesis of aging. Subsequent year-long studies have shown GH therapy causes significant adverse effects. Other concerns of long-term treatment include possible diabetogenic effects, potential for increased risk of cancer, and high costs (>$10,000/yr). IGF-I, which mediates most of the effects of GH, is also being explored experimentally, but its role as a growth factor raises fears about tumor induction.Methods being explored to raise GH levels more physiologically include: GHRH, the GH— releasing hormone produced by the hypothalamus; GH-releasing hexapeptides (GHRPs) which stimulate GH secretion via a novel receptor whose normal function is unknown; and orally active aromatic compounds, developed synthetically which mimic the effects of GHRPs. Because of the unknown long-term effects of elevated GH in the elderly, mimetics should be carefully restricted to clinical trials and temporary
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