The study shows that as men get older, their bodies become less able to shut off growth hormone (GH) after a spike, which means the natural high‑amplitude GH bursts get weaker. In younger men, higher IGF‑I levels make this shut‑off stronger, leading to bigger GH pulses. The ghrelin‑mimic peptide GHRP‑2 can temporarily override this feedback, but its effect varies with age and IGF‑I levels.

Aging reduces the size (mass) of GH secretory bursts and thereby reduces total GH secretion. Experimental data indicate that high-amplitude GH pulses are evoked by reversible cycles of GH-induced negative feedback. Whether aging impairs autofeedback is unknown. The objective of this study is to assess whether age attenuates and IGF-I potentiates negative feedback by a near-physiological pulse of GH. In a university setting, 17 healthy men ages 19-71 yr each underwent four randomly ordered infusion studies on separate mornings fasting. Intravenous injection of a pulse of: 1) saline or 2) recombinant human (rh) GH to impose controlled negative feedback, followed in 2 h by a bolus of 3) saline or (iv) the ghrelin analog GHRP-2 to overcome feedback inhibition. The impact of age and IGF-I concentrations on GH autofeedback was assessed by regression analysis. Percentage feedback inhibition correlated negatively with: 1) age after consecutive rh GH/saline infusion (R(2) = 0.42, P = 0.005) at any IGF-I concentration; and 2) total IGF-I concentrations after rh GH/GHRP-2 infusion (R(2) = 0.40, P = 0.009) at any age. In contrast, sex-steroid concentrations and body mass index were unrelated to degree of autoinhibition. Increased age in healthy men predicts impaired GH autofeedback, which may contribute to attenuated renewal of high-amplitude GH pulses. Conversely, higher IGF-I concentrations in young men forecast accentuated GH autoinhibition, which may drive prominent GH pulses.