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

Abstract

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 (ptrend=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 (ptrend=0.001) and IADL (ptrend=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.

The Somatotropic Axis in Human Aging: Framework for the Current State of Knowledge and Future Research

“…Our group demonstrated that lower IGF-1 levels can predict extended survival in Ashkenazi Jewish female nonagenarians and nonagenarians of both sexes with a history of cancer (Milman et al, 2014). In Dutch nonagenarians of both sexes, the hazard of death was 27% lower among those with IGF-1/IGFBP-3 ratios in the first quartile compared to those in the fourth quartile (van der Spoel et al, 2015). Furthermore, those with the lowest IGF-1/IGFBP-3 demonstrated higher scores on performance of activities of daily living (ADL) (van der Spoel et al, 2015).…”

“…In Dutch nonagenarians of both sexes, the hazard of death was 27% lower among those with IGF-1/IGFBP-3 ratios in the first quartile compared to those in the fourth quartile (van der Spoel et al, 2015). Furthermore, those with the lowest IGF-1/IGFBP-3 demonstrated higher scores on performance of activities of daily living (ADL) (van der Spoel et al, 2015). Such evidence suggests that diminished function of the GH/IGF-1 axis may be beneficial to human aging and promotes longevity by conferring protection against age-related diseases and dysfunction.…”

“…Although the beneficial effects of attenuated GH/IGF-1 signaling on lifespan and some aspects of healthspan in invertebrates (Kenyon et al, 1993) and rodents (Brown-Borg et al, 1996; Ikeno et al, 2003) have long been recognized, only recently have similar benefits been observed in humans (Guevara-Aguirre et al, 2011; Milman et al, 2014; Suh et al, 2008; van der Spoel et al, 2015). GH and IGF-1 levels change throughout the human lifespan.…”

“…Data is accumulating from dwarf humans (Guevara-Aguirre et al, 2011) and individuals with exceptional longevity (Milman et al, 2014; Suh et al, 2008; van der Spoel et al, 2015) about the potential beneficial effects of attenuated somatotropic signaling on human lifespan and healthspan, yet results of epidemiological studies remain inconclusive. This ambiguity stems from several shortcomings of epidemiological studies, such as failure to account for sex, age, organ-specific effects and function, rather than levels of GH/IGF-1.…”

Pulmonary function tests in Egyptian schoolchildren in rural and urban areas

“…Air pollution in Cairo is considered one of the greatest challenges to health in Egypt because of its multiple sources, including industrial waste, burning of agricultural residues, vehicle emissions and pollutants resulting from open burning of municipal solid waste (9). The study compared respiratory function between schoolchildren in an urban area (Cairo) and a rural area (Shibin El-Kom) of Egypt and also explored the relative importance of an urban-rural setting and other known risk factors in relation to respiratory function.…”