Human aging and the GH-IGF-I axis.

The activity of the GH-IGF-I axis undergoes an age-related reduction and in the elderly both spontaneous GH secretion and IGF-I levels are frequently low overlapping with those usually recorded in GH deficient patients. Hypoactivity of the GH-IGF-I axis could explain age-related changes in body composition, function and metabolism, as also indicated by evidence that treatment with rhGH reverses these alterations. The mechanisms underlying the hypoactivity of the GH-IGF-I axis in the aged likely include changes in nutrition and lifestyle, e.g. reduction of physical exercise. However, alterations of neurohormonal hypothalamic control of GH secretion, including reduced activity of GHRH-secreting neurons and somatostatinergic hyper-activity, seem to play a major role. The exaggerated somatostatinergic hyperactivity could be due, in turn, to the impairment of cholinergic activity found in the aging brain. Age-related variations in the activity of other neurotransmitters, such as catecholamines, amino acids, e.g. arginine, neuropeptides, e.g. galanin and/or a putative natural GHRP-like ligand, could play a key role in causing the reduced activity of the GH-IGF-I axis. It is still unclear whether it is of benefit to restore GH secretion in aging. As the pituitary GH releasable pool is preserved in the elderly, it would be more appropriate to increase GH by GH secretagogues such as the new synthetic GH-releasing peptides (GHRPs) or non-peptidyl GHRP mimetics which are active even with oral administration.