Context: Low IGF-I signaling activity prolongs lifespan in certain animal models, but the precise role of IGF-I in human survival remains controversial. The IGF-I kinase receptor activation assay (IGF-I KIRA) is a novel method for measuring IGF-I bioactivity in human serum. We speculated that determination of circulating IGF-I bioactivity is more informative than levels of immunoreactive IGFI. Objective: To study IGF-I bioactivity in relation to human survival. Design: Prospective observational study. Setting: A clinical research center at a university hospital. Study participants: 376 healthy elderly men (aged 73 to 94 years). Main outcome Measures: IGF-I bioactivity was determined by the IGF-I KIRA. Total and free IGF-I were determined by IGF-I immunoassays. Mortality was registered during follow-up (mean 82 months). Results: During the follow-up period of 8.6 years 170 men (45%) died. Survival of subjects in the highest quartile of IGF-I bioactivity was significantly better than in the lowest quartile, both in the total study group (HR = 1.8, (95% CI: 1.2 − 2.8, p = 0.01) as well as in subgroups having a medical history of cardiovascular disease (HR = 2.4 (95% CI: 1.3 − 4.3, p = 0.003) or a high inflammatory risk profile (HR = 2.3 (95% CI: 1.2 − 4.5, p = 0.01). Significant relationships were not observed for total or free IGF-I. Conclusion: Our study suggests that a relatively high circulating IGF-I bioactivity in elderly men is associated with extended survival and with reduced cardiovascular risk.

CRP, GFBPs, IGF-I, IGF-I bioactivity, IGFBP-1, IGFBP-3, free IGF-I, ongevit, survival, total IGF-I,
Journal of Clinical Endocrinology and Metabolism
Erasmus MC: University Medical Center Rotterdam

Brugts, M.P, van den Beld, A.W, Hofland, L.J, van der Wansem, K, van Koetsveld, P.M, Frystyk, J, … Janssen, J.A.M.J.L. (2008). Low Circulating IGF-I Bioactivity in Elderly Men is associated with Increased Mortality. Journal of Clinical Endocrinology and Metabolism, 93(7), 2515–2522. doi:10.1210/jc.2007-1633