HUMAN AGING AND THE GH-IGF-I AXIS

The activity of the GH-IGF-I axis undergoes an age-related reduction a nd in the elderly both spontaneous GH secretion and IGF-I levels are f requently 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 indicate d by evidence that treatment with rhGH reverses these alterations, The mechanisms underlying the hypoactivity of the GH-IGF-I axis in the ag ed likely include changes in nutrition and lifestyle, e.g. reduction o f physical exercise, However, alterations of neurohormonal hypothalami c control of GH secretion, including reduced activity of GHRH-secretin g neurons and somatostatinergic hyperactivity, seem to play a major ro le, The exaggerated somatostatinergic hyperactivity could be due, in t urn, to the impairment of cholinergic activity found in the aging brai n, 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 stil l unclear whether it is of benefit to restore GH secretion in aging, A s the pituitary GH releasable pool is preserved in the elderly, it wou ld be more appropriate to increase GH by GH secretagogues such as the new synthetic GH-releasing peptides (GHRPs) or non-peptidyl GHRP mimet ics which are active even with oral administration.