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The GH receptor exon 3 deletion is a marker of male-specific exceptional longevity associated with increased GH sensitivity and taller stature.
Tuesday,2018-01-16 16:58 America/Los_Angeles — ecterry
| Title | The GH receptor exon 3 deletion is a marker of male-specific exceptional longevity associated with increased GH sensitivity and taller stature. |
| Publication Type | Journal Article |
| Year of Publication | 2017 |
| Authors | Ben-Avraham, D, Govindaraju, DR, Budagov, T, Fradin, D, Durda, P, Liu, B, Ott, S, Gutman, D, Sharvit, L, Kaplan, R, Bougnères, P, Reiner, A, Shuldiner, AR, Cohen, P, Barzilai, N, Atzmon, G |
| Journal | Sci Adv |
| Volume | 3 |
| Issue | 6 |
| Pagination | e1602025 |
| Date Published | 2017 Jun |
| ISSN | 2375-2548 |
| Abstract | <p>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.</p> |
| DOI | 10.1126/sciadv.1602025 |
| Alternate Journal | Sci Adv |
| PubMed ID | 28630896 |
| PubMed Central ID | PMC5473676 |
ePub date:
17/06