Serum Levels of Insulin-Like Growth Factor-I (IGF-I) and IGF-Binding Protein-3 in Healthy Centenarians: Relationship with Plasma Leptin and Lipid Concentrations, Insulin Action, and Cognitive Function

Abstract

It has been demonstrated that healthy centenarians have more favorableanthropometric characteristics and insulin-mediated glucose uptake thanaged subjects. The plasma insulin-like-growth factor I (IGF-I)concentration may account for such differences. Three groups of subjectswere studied: 1) adults (< 50 yr; n = 30), 2) aged subjects (75-99 yr; n= 30), 3) centenarians (> 100 yr; n = 19). In all subjects, fastingplasma IGF-I, IGF-binding protein-3 (IGFBP-3), leptin, and lipidconcentrations were determined; body composition was assessed bybioimpedance analysis; and insulin-mediated glucose uptake was evaluatedby euglycemic hyperinsulinemic glucose clamp. IGF-I declined withadvancing age, but no differences between aged subjects and centenarianswere found. IGFBP-3 showed a trend similar to IGF-I, but lower valueswere present in centenarians than in aged subjects. Nevertheless,centenarians had a plasma IGF-I/IGFBP-3 molar ratio greater than that inaged subjects. Centenarians had also a whole body glucose disposal(WBGD) greater than that in aged subjects, but similar to that inadults. Mini Mental State Examination (27 +/- 2.1 vs. 18.3 +/- 3.1; P < 0.001) scores were significantly different in aged subjects andcentenarians, respectively. In centenarians, the plasma IGF-I/IGFBP-3molar ratio correlated with the body mass index (r = -0.55; P < 0.009);the amount of body fat (r = 0.62; P < 0.003); fat-free mass (r = 0.56; P< 0.008); fasting pl asma leptin (r = -0.63; P < 0.004), triglycerides(r = -0.58; P < 0.01), free fatty acid (r = -0.64; P < 0.005), and lowdensity lipoprotein cholesterol (r = -0.59; P < 0.009) concentrations;Mini Mental State Examination (r = 0.53;P < 0.0.03); and WBGD (r = 0.64;P < 0.005). All correlations were independent of daily fat andcarbohydrate intake and WBGD (P < 0.05 for all). No significantcorrelations between the plasma IGF-I/IGFBP-3 molar ratio and plasmatotal(r = 0.31; P = NS) and high density lipoprotein cholesterol (r =0.34; P = NS) concentrations were present. The correlation between theplasma IGF-I/IGFBP-3 molar ratio and WBGD persisted after adjustment forbody fat, fasting plasma insulin concentration, daily carbohydrate andfat intake, and daily physical activity (r = 0.55; P < 0.009), but notafter further adjustment for plasma free fatty acid concentration (r =0.30; P = 0.17). IN conclusion, healthy centenarians have plasmaIGF-I/IGFBP-3 molar ratios greater than aged subjects. A more elevatedplasma IGF-I/IGFBP-3 molar ratio might improve insulin action and plasmalipid concentration in centenarians.