title: Low circulating IGF-I bioactivity is associated with human longevity: findings in centenarians' offspring.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vitale
authors.forename: Michael P
authors.initials: MP
authors.lastname: Brugts
authors.forename: Giulia
authors.initials: G
authors.lastname: Ogliari
authors.forename: Davide
authors.initials: D
authors.lastname: Castaldi
authors.forename: Letizia M
authors.initials: LM
authors.lastname: Fatti
authors.forename: Aimee J
authors.initials: AJ
authors.lastname: Varewijck
authors.forename: Steven W
authors.initials: SW
authors.lastname: Lamberts
authors.forename: Daniela
authors.initials: D
authors.lastname: Monti
authors.forename: Laura
authors.initials: L
authors.lastname: Bucci
authors.forename: Elisa
authors.initials: E
authors.lastname: Cevenini
authors.forename: Francesco
authors.initials: F
authors.lastname: Cavagnini
authors.forename: Claudio
authors.initials: C
authors.lastname: Franceschi
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Hofland
authors.forename: Daniela
authors.initials: D
authors.lastname: Mari
authors.forename: Joseph
authors.initials: J
authors.lastname: Janssen
mesh_terms: D032721:Adult Children; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006304:Health Status; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism*; D008136:Longevity / Q000502:physiology*; D008297:Male; D010375:Pedigree
chemical_list: D007334:Insulin-Like Growth Factor I