Human Familial Longevity Is Characterized By Tight Control and Diminished Secretion of Growth Hormone

Presentation Number: OR40-4
Date of Presentation: April 4th, 2016

Evie van der Spoel1, Steffy Wilhelmina Jansen1, Abimbola Akintola1, Bart EPB Ballieux1, Christa M Cobbaert2, Petronella E. Slagboom1, Gerard Jan Blauw3, Rudi G J Westendorp1, Hanno Pijl2, Ferdinand Roelfsema2 and Diana van Heemst*1
1Leiden University Medical Center, Netherlands, 2Leiden University Medical Center, Leiden, Netherlands, 3Leiden University Medical Center

Abstract

Only few studies have included subjects with a propensity to reach old age in good health, aiming to disentangle mechanisms contributing to staying healthier for longer. Reduced GH signaling has been consistently associated with increased health and life span in various GH-deficient and GH-resistant mice, while pathological GH excess reduces life expectancy in both mice and men (1). It is unknown whether healthy human longevity is associated with differences in GH secretion. In this study, we assessed the control and magnitude of GH secretion in relation with human familial longevity.

We examined 37 participants from the Leiden Longevity Study, consisting of 19 offspring of nonagenarian siblings (mean age 66 years) together with 18 of their partners (age-matched controls) not originating from long-lived families. Blood was frequently sampled over 24 h, and circulating GH concentrations were measured every 10 min and concentrations of insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP3) every 4 h. Approximate entropy was used to quantify the regularity of 24 h GH concentration profiles, with lower values being indicative of greater regularity due to tighter (feedback and/or feedforward) control. We used deconvolution analysis to asses specific features of GH secretion, including basal secretion, pulsatile secretion and total secretion. Data are shown as mean and 95% CI.

Approximate entropy was lower (P=0.001) in offspring (0.45 (0.39–0.53) compared to controls (0.66 (0.56-0.77). Total GH secretion over 24 h was also lower (P=0.04) in offspring (171.7 (127.7-215.8) mU/L) compared to controls (238.1 (192.7-283.5) mU/L), which was predominantly attributable to diminished basal GH secretion over 24 h (P=0.03) in offspring (14.5 (9.8-21.5) mU/L) compared to controls (26.9 (17.9 -40.4) mU/L). In contrast, no significant differences were observed in pulsatile GH secretion, GH pulse frequency and mass, and GH half-life between offspring and controls. In line with our previous observations (2), circulating concentrations of IGF-1 and IGFBP3 were similar between groups.

In conclusion, GH secretion in human familial longevity is characterized by tight control and 28% diminished secretion rate, without differences in circulating levels of IGF-1 and IGFBP3. In line with recent observations of reduced GH signaling in long-lived mice (3), we hypothesize that pleiotropic and possibly tissue-specific effects of reduced GH secretion may also favor human longevity, independent of effects of GH on circulating IGF-1 concentrations. Our future research is focused on dissecting the mechanisms via which diminished GH secretion is associated with human longevity.

 

Nothing to Disclose: EV, SWJ, AA, BEB, CMC, PES, GJB, RGJW, HP, FR, DV