Low insulin-like growth factor-1 level predicts survival in humans with exceptional longevity

Abstract

Attenuated growth hormone and insulin-like growth factor-1 (GH/IGF-1) signaling is associated with extended lifespan in several animal models. However, the effect of diminished GH/IGF-1 activity on survival in humans has not been confirmed. We tested the hypothesis that IGF-1 levels in nonagenarians (n = 184), measured at study enrollment, predict the duration of their incremental survival. In the Kaplan-Meier analysis, females with IGF-1 levels below the median (≤ 96 ng mL(-1) ) had significantly longer survival compared with females with levels above the median, P < 0.01. However, this survival advantage was not observed in males (P = 0.83). On the other hand, in both males and females with a history of cancer, lower IGF-1 levels predicted longer survival (P < 0.01). IGF-1 level remained a significant predictor of survival duration in linear regression models after multivariable adjustment in females (P = 0.01) and individuals with a history of cancer (P < 0.01). We show for the first time that low IGF-1 levels predict life expectancy in exceptionally long-lived individuals.

Keywords: IGF-1; cancer; human; insulin-like growth factor 1; longevity; mortality.

Figure 1

Kaplan–Meier curves for groups with IGF-1 levels below (low IGF-1) and above (high IGF-1) the median (A–D). P-values for comparison between IGF-1 groups. (A) Females, P < 0.01. (B) Males, P = 0.83. (C) Negative history of malignancy, P = 0.42. (D) Positive history of malignancy, P < 0.01.