A. Raynaud-Simon1,2, L. Perin2, S. Meaume1, B. Ducos2,
M.C. Postel-Vinay3, Y. Le Bouc2

1Unité de Nutrition Gériatrique, Hôpital Charles Foix AP-HP, F-94205 Ivry sur Seine, France. 2Laboratoire d'Explorations Fonctionnelles Endocriniennes, Hôpital Armand Trousseau AP-HP, 75571 Paris Cedex 12 and INSERM U 515, Hôpital Saint-Antoine, F-75012 Paris, France. 3INSERM U344, Faculté de Médecine Necker, F-75014 Paris, France. Correspondence: Raynaud-Simon A, Unité de Nutrition Gériatrique, Hôpital Charles Foix AP-HP, F-94205 Ivry sur Seine, France. E-mail agathe.raynaud-simon@cfx.ap-hop-paris.fr

Abstract: Plasma samples from community-dwelling subjects aged 65 to 92 presenting no malnutrition and no inflammation (as assessed by albumin, transthyretin, CRP, and orosomucoid levels and BMI) were compared to those of healthy controls aged 20 to 65 to determine the effect of aging on the IGF system. Concentrations of IGF I, IGF II and IGFBP3 significantly decreased, and those of GHBP slightly increased with age from 20 to 92 years (n=327 r=-0.64 p<0.0001; n=45 r=-0.44 p<0.003; n=91 r=-0.23 p<0.03 and n=61 r=0.26; p<0.05 respectively). Western immunoblotting showed that the proteolysis of IGFBP3 was not significantly different in elderly and younger subjects. The affinity of the IGF type 1 receptor for IGF I was moderately lower (Ki=0.56±0.2 vs 0.33±0.1, nM respectively; p<0.005) and the number of binding sites was moderately higher (10.4±1.5 vs 8.1±1.9 binding sites/cell, respectively; p<0.03) in the elderly than in the younger adults. Our results suggest that the age-related decline in plasma levels of IGF I, IGF II and IGFBP3 occurs independently from malnutrition and inflammation processes. GHBP plasma levels, which reflect the number of GH receptors at the level of the liver, do not decline in our malnutrition-free elderly population, and thus are not involved in the decline of IGF I plasma levels with age. In the elderly, affinity and number of type 1 IGF receptor were close to those of younger subjects; the decline in IGF I plasma levels may account for the small rise in the number of type 1 IGF receptors binding sites per cell.

Key words: Insulin-like growth factors, insulin-like growth factors binding proteins, IGF type 1 receptor, malnutrition, inflammation, elderly, aging, nutrition.