Insulin-like growth factor 1 receptor polymorphism rs2229765 and circulating interleukin-6 level affect male longevity in a population-based prospective study (Treviso Longeva− TRELONG)

Abstract

Insulin-like growth factor 1 (IGF-1) signaling modulation has been associated with increased lifespan in model organisms, while high levels of circulating interleukin-6 (IL-6) are a marker of disability and mortality. In the prospective, population-based “Treviso Longeva”− TRELONG Study from Italy (n = 668, age range 70–105.5 years at baseline, followed for seven years) we investigated the effects of survival on the IGF-1 receptor (IGF-1R) gene polymorphism rs2229765, the IL-6 gene promoter polymorphism rs1800795, and plasma concentrations of IGF-1 and IL-6, alone or in combination. We found a sex-dependent effect for the IGF-1R rs2229765 polymorphism, as male carriers of the homozygous A/A genotype survived longer, while the IL-6 rs1800795 genotype did not influence overall or sex-specific longevity. Higher IL-6 levels were more detrimental for survival among males than females, while IGF-1 had no dose–response effect. These findings sustain the hypothesis that sex-specific longevity relies on detectable differences in genetic and biochemical parameters between males and females.

Keywords::

• IGF-1
• IL-6
• aging
• longevity
• inflammation
• male genetics

Declaration of interest: This study was supported by grants from the Veneto Region, the Treviso Municipality, Treviso Province and Fondazione Veneto Banca. LP is recipient of a fellowship from “Golgi Cenci Foundation”, Abbiategrasso, Milan, Italy. We thank Judith Baggott for editing of the English language.