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 offspringcontrols 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.

Centenarians, Centenarians' offspring, IGF-I bioactivity, IGF-I receptors, Insulin receptors, Longevity
This work was funded by the European Commission 7th Framework Programme; grant id fp7/223576 - Understanding and combating human age-related muscle weakness (MYOAGE)
Department of Internal Medicine

Vitale, G, Brugts, M.P, Ogliari, G, Castaldi, D, Fatti, L.M, Varewijck, A.J, … Janssen, J.A.M.J.L. (2012). Low circulating IGF-I bioactivity is associated with human longevity: Findings in centenarians' offspring. Aging, 4(9), 580–589. Retrieved from http://hdl.handle.net/1765/85808