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. 2012 Sep;4(9):580-9.
doi: 10.18632/aging.100484.

Low circulating IGF-I bioactivity is associated with human longevity: findings in centenarians' offspring

Giovanni Vitale  1 , Michael P Brugts, Giulia Ogliari, Davide Castaldi, Letizia M Fatti, Aimee J Varewijck, Steven W Lamberts, Daniela Monti, Laura Bucci, Elisa Cevenini, Francesco Cavagnini, Claudio Franceschi, Leo J Hofland, Daniela Mari, Joseph Janssen
Affiliations

Low circulating IGF-I bioactivity is associated with human longevity: findings in centenarians' offspring

Giovanni Vitale et al. Aging (Albany NY). 2012 Sep.

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.

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Conflict of interest statement

The authors of this manuscript have no conflict of interests to declare.

Figures

Figure 1
Figure 1
Parent-offspring correlation for IGF-I bioactivity in a subpopulation of 76 centenarians and their corresponding 76 offspring. No such correlation was observed for other IGF-I/insulin system parameters.
Figure 2
Figure 2
Hypothetical relationships between caloric restriction, the mTOR pathway, insulin and IGF-I receptor sensitivity, circulating insulin levels and IGF-I bioactivity. (A) Overnutrition results in an increased activity of the mTOR pathway, which decreases the sensitivity of the insulin and IGF-I receptors. As a consequence there will be relatively high circulating insulin levels and IGF-I bioactivity. (B) Caloric restriction results in a reduced activity of the mTOR pathway, which increases the sensitivity of the insulin and IGF-I receptors. As a consequence there will be relatively low circulating insulin levels and IGF-I bioactivity.
See this image and copyright information in PMC

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