title: Low circulating insulin-like growth factor I bioactivity in elderly men is associated with increased mortality.
abstract: BACKGROUND
  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 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
  Our objective was to study IGF-I bioactivity in relation to human survival. DESIGN, SETTING, AND STUDY PARTICIPANTS: We conducted a prospective observational study at a clinical research center at a university hospital of 376 healthy elderly men (aged 73-94 yr).
  
  
  METHODS
  IGF-I bioactivity was determined by the IGF-I kinase receptor activation assay. 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 yr, 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 [hazard ratio (HR) = 1.8; 95% confidence interval (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.
  
  
  CONCLUSIONS
  Our study suggests that a relatively high circulating IGF-I bioactivity in elderly men is associated with extended survival and with reduced cardiovascular risk.
authors.affiliation: Department of Internal Medicine, Erasmus Medical Center, Dr. Molewaterplein 50, Rotterdam, The Netherlands. m.brugts@erasmusmc.nl
authors.forename: M P
authors.initials: MP
authors.lastname: Brugts
authors.forename: A W
authors.initials: AW
authors.lastname: van den Beld
authors.forename: L J
authors.initials: LJ
authors.lastname: Hofland
authors.forename: K
authors.initials: K
authors.lastname: van der Wansem
authors.forename: P M
authors.initials: PM
authors.lastname: van Koetsveld
authors.forename: J
authors.initials: J
authors.lastname: Frystyk
authors.forename: S W J
authors.initials: SW
authors.lastname: Lamberts
authors.forename: J A M J L
authors.initials: JA
authors.lastname: Janssen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000401:mortality; D015331:Cohort Studies; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D008297:Male; D009026:Mortality; D016016:Proportional Hazards Models; D011446:Prospective Studies; D017526:Receptor, IGF Type 1 / Q000378:metabolism
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D002097:C-Reactive Protein; D017526:Receptor, IGF Type 1