Association analysis of insulin-like growth factor-1 axis parameters with survival and functional status in nonagenarians of the Leiden Longevity Study

Reduced insulin/insulin-like growth factor 1 (IGF-1) signaling has been associated with longevity in various model organisms. However, the role of insulin/IGF-1 signaling in human survival remains controversial. The aim of this study was to test whether circulating IGF-1 axis parameters associate with old age survival and functional status in nonagenarians from the Leiden Longevity Study. This study examined 858 Dutch nonagenarian (males ≥89 years; females ≥91 years) siblings from 409 families, without selection on health or demographic characteristics. Nonagenarians were divided over sex-specific strata according to their levels of IGF-1, IGF binding protein 3 and IGF-1/IGFBP3 molar ratio. We found that lower IGF-1/IGFBP3 ratios were associated with improved survival: nonagenarians in the quartile of the lowest ratio had a lower estimated hazard ratio (95% confidence interval) of 0.73 (0.59 - 0.91) compared to the quartile with the highest ratio (p_trend = 0.002). Functional status was assessed by (Instrumental) Activities of Daily Living ((I)ADL) scales. Compared to those in the quartile with the highest IGF-1/IGFBP3 ratio, nonagenarians in the lowest quartile had higher scores for ADL (p_trend = 0.001) and IADL (p_trend = 0.003). These findings suggest that IGF-1 axis parameters are associated with increased old age survival and better functional status in nonagenarians from the Leiden Longevity Study.