In:
Science Advances, American Association for the Advancement of Science (AAAS), Vol. 3, No. 6 ( 2017-06-02)
Kurzfassung:
Although both growth hormone (GH) and insulin-like growth factor 1 (IGF-1) signaling were shown to regulate life span in lower organisms, the role of GH signaling in human longevity remains unclear. Because a GH receptor exon 3 deletion ( d3-GHR ) appears to modulate GH sensitivity in humans, we hypothesized that this polymorphism could play a role in human longevity. We report a linear increased prevalence of d3-GHR homozygosity with age in four independent cohorts of long-lived individuals: 841 participants [567 of the Longevity Genes Project (LGP) (8% increase; P = 0.01), 152 of the Old Order Amish (16% increase; P = 0.02), 61 of the Cardiovascular Health Study (14.2% increase; P = 0.14), and 61 of the French Long-Lived Study (23.5% increase; P = 0.02)]. In addition, mega analysis of males in all cohorts resulted in a significant positive trend with age (26% increase; P = 0.007), suggesting sexual dimorphism for GH action in longevity. Further, on average, LGP d3 / d3 homozygotes were 1 inch taller than the wild-type (WT) allele carriers ( P = 0.05) and also showed lower serum IGF-1 levels ( P = 0.003). Multivariate regression analysis indicated that the presence of d3 / d3 genotype adds approximately 10 years to life span. The LGP d3/ d3-GHR transformed lymphocytes exhibited superior growth and extracellular signal–regulated kinase activation, to GH treatment relative to WT GHR lymphocytes ( P 〈 0.01), indicating a GH dose response. The d3-GHR variant is a common genetic polymorphism that modulates GH responsiveness throughout the life span and positively affects male longevity.
Materialart:
Online-Ressource
ISSN:
2375-2548
DOI:
10.1126/sciadv.1602025
Sprache:
Englisch
Verlag:
American Association for the Advancement of Science (AAAS)
Publikationsdatum:
2017
ZDB Id:
2810933-8
