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This version published online on April 15, 2008
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2007-1633
A more recent version of this article appeared on July 1, 2008
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Submitted on July 23, 2007
Accepted on April 7, 2008

Low Circulating IGF-I Bioactivity in Elderly Men is associated with Increased Mortality

M P Brugts*, A W Van den Beld, L J Hofland, K van der Wansem, P M van Koetsveld, J Frystyk, S WJ Lamberts, and J AMJL Janssen

Division of Endocrinology, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands; Medical Research Laboratories, Clinical Institute and Medical Department M, Aarhus University Hospital, Aarhus C, Denmark

* To whom correspondence should be addressed. E-mail: m.brugts{at}erasmusmc.nl.

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 IGF-I.

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.
Key words: IGF-I • total IGF-I • Free IGF-I • IGF-I bioactivity • IGFBPs • IGFBP-1 • IGFBP-3 • survival • longevity • CRP






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