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.
Section Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Evie
E
van der Spoel
Section Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Steffy W
SW
Jansen
Section Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Abimbola A
AA
Akintola
Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Bart E
BE
Ballieux
Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Christa M
CM
Cobbaert
Section Molecular Epidemiology, Department of Medical Statistics, Leiden University Medical Center, Leiden, The Netherlands.
P Eline
PE
Slagboom
Section Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Gerard Jan
GJ
Blauw
Section Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.|Department of Public Health and Center of Healthy Aging, University of Copenhagen, Copenhagen, Denmark.
Rudi G J
RGJ
Westendorp
Section Endocrinology, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Hanno
H
Pijl
Section Endocrinology, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Ferdinand
F
Roelfsema
Section Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Diana
D
van Heemst
IGF-1; approximate entropy; familial longevity; growth hormone; hormone secretion; human