Growth hormone secretion is diminished and tightly controlled in humans enriched for familial longevity

Reduced growth hormone (GH) signaling has been consistently associated with increased health and lifespan in various mouse models. Here, we assessed GH secretion and its control in relation with human familial longevity. We frequently sampled blood over 24 h in 19 middle-aged offspring of long-living families from the Leiden Longevity Study together with 18 of their partners as controls. Circulating GH concentrations were measured every 10 min and insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP3) every 4 h. Using deconvolution analysis, we found that 24-h total GH secretion was 28% lower (P = 0.04) in offspring [172 (128-216) mU L-1] compared with controls [238 (193-284) mU L-1]. We used approximate entropy (ApEn) to quantify the strength of feedback/feedforward control of GH secretion. ApEn was lower (P = 0.001) in offspring [0.45 (0.39-0.53)] compared with controls [0.66 (0.56-0.77)], indicating tighter control of GH secretion. No significant differences were observed in circulating levels of IGF-1 and IGFBP3 between offspring and controls. In conclusion, GH secretion in human familial longevity is characterized by diminished secretion rate and more tight control. These data imply that the highly conserved GH signaling pathway, which has been linked to longevity in animal models, is also associated with human longevity.