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

Abstract

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 À1 ] compared with controls [238 (193-284) mU L À1 ]. 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.

Exceptional Human Longevity

“…76,77 To the extent that women tend to be shorter than men, a possible explanation for both greater longevity and lower height is diminished GH secretion. [78][79][80] Despite the greater longevity of women, functional status is better in older men compared with older women. 65,81 Resiliency There is growing evidence to suggest that resiliency, or the ability to adequately respond to or resist various stressors, plays a key role in conferring successful aging.…”

Emerging Molecular Pathways Governing Dietary Regulation of Neural Stem Cells during Aging

“…Conversely, people affected by acromegaly, characterized by increased GH release, experienced a 2–3 fold increase in death rate (Clayton, 2003 ; Suh et al, 2008 ; Verburgh, 2015 ). More recently, reduced growth hormone secretion, and thus indirectly IIS activity, was shown to correlate with human familial longevity (van der Spoel et al, 2016 ) and genomewide meta-analysis studies linked several gene loci to longevity and to levels of circulating IGF-related proteins (Teumer et al, 2016 ). These studies show that this pathway and its role in lifespan is conserved in more complex organisms.…”

Physiological and Metabolic Features of Mice with CRISPR/Cas9-Mediated Loss-of-Function in Growth Hormone-Releasing Hormone

“…Specifically, suppression of growth hormone (GH) signaling pathway has been linked to increased lifespan in mice [6, 8, 9]. A recent study involving human subjects showed that familial longevity is associated with lower GH secretion [10].…”