Changes in the growth hormone (GH)–IGF-1 axis with aging
Aging is associated with a significant decline in the GH area under the curve, as well as the number and amplitude of night-time GH peaks. These changes in GH secretion (approximately 15% decline for every decade after age 30 years) are also associated with a steady decline in IGF-1 production. By age 65 years, most individuals have a serum IGF-1 concentration that is near or below the lower limit of normal for young healthy individuals. The observed decline in the GH–IGF-1 axis appears to occur above the level of the pituitary because chronic treatment with growth hormone–releasing hormone (GHRH) and/or other GH secretagogues (GHS) mitigates much of the decline. The cause of the fall-off in GH–IGF-1 axis activity is not clear but could be explained by age-related decreases in GHRH or ghrelin secretion, increased inhibition by somatostatin, increased sensitivity of somatotrophs to negative feedback inhibition by IGF-1, and/or a decline in pituitary responsiveness to GHRH or ghrelin. Ghrelin appears to be the natural ligand for the GHS receptor. Although there is a close physiologic relationship between GH secretion and slow-wave sleep, it is unclear if the altered GH–IGF-1 axis is the consequence or cause of profound age-related changes in sleep architecture.