Low circulating IGF-I bioactivity is associated with human longevity: Findings in centenarians’ offspring

Abstract

Centenarians’ offspring represent a suitable model to study age-dependent variables (e.g. IGF-I) potentially involved in the modulation of the lifespan. The aim of the present study was to investigate the role of the IGF-I in human longevity. We evaluated circulating IGF-I bioactivity measured by an innovative IGF-I Kinase Receptor Activation (KIRA) Assay, total IGF-I, IGFBP-3, total IGF-II, insulin, glucose, HOMA2-B% and HOMA2-S% in 192 centenarians’ offspring and 80 offspring-controls of which both parents died relatively young. Both groups were well-matched for age, gender and BMI with the centenarians’ offspring. IGF-I bioactivity (p<0.01), total IGF-I (p<0.01) and the IGF-I/IGFBP-3 molar ratio (p<0.001) were significantly lower in centenarians’ offspring compared to offspring matched-controls. Serum insulin, glucose, HOMA2-B% and HOMA2-S% values were similar between both groups. In centenarians’ offspring IGF-I bioactivity was inversely associated to insulin sensitivity. In conclusion: 1) centenarians’ offspring had relatively lower circulating IGF-I bioactivity compared to offspring matched-controls; 2) IGF-I bioactivity in centenarians’ offspring was inversely related to insulin sensitivity. These data support a role of the IGF-I/insulin system in the modulation of human aging process.

Dysregulation of the mTOR pathway in p53-deficient mice

“…4). Levels of IGF-1, a marker associated with accelerated aging, [73][74][75] tended to be increased in p53 −/− mice, reaching a statistical significance after radiation (Fig. 4F).…”

Effect of Cabergoline on Metabolism in Prolactinomas

“…Moreover, in healthy non-obese humans, activation of D 2 R has also been shown to affect circulating GH and consequently IGF-I levels [85]. Taking into account that IGF-I bioactivity has been found inversely associated to insulin sensitivity [86], the decrease in GH levels and/or in IGF-I bioactivity could represent another potential mechanism involved in insulin sensitivity amelioration. A significant improvement in glucose metabolism and insulin resistance after 6 months of treatment with BRC or CAB has been described in patients with prolactinomas [46,47].…”

Sleep and Insulin-Like Growth Factors in the Cardiovascular Health Study

“…[15][16][17][18][19][20][21] Fourth, emerging evidence suggests a positive influence of diminished GH/IGF-I axis on longevity (via improved cancer and diabetes related outcomes). [22][23][24] Whether this is partially mediated by the influence of sleep architecture and sleep disordered breathing on the GH/IGF-I axis is unknown.…”