Age-Related Changes in Serum Insulin-Like Growth Factor-Binding Proteins in Women*

Abstract

Plasma insulin-like growth factor-I (IGF-I) concentrations are reported to decline with advancing age. Five IGF-binding proteins (IGF-BPs) have recently been characterized in human serum, although their biological role beyond circulatory transport of IGF-I is unknown. We studied plasma IGF-I (by RIA) and serum IGF-BPs (by Western ligand blotting) in healthy elderly (n = 21) and healthy young (n = 22) women to determine if aging alters IGF-I and its high affinity BPs. Plasma IGF-I was significantly lower in the elderly than in the young group (0.78 .+-. 0.08 vs. 1.22 .+-. 0.11 U/ml; P < 0.005). The number and size of IGF-BPs did not differ between age groups, but the IGF-BP binding ratios (binding of one BP fraction/binding of all fractions) for the BP-53 acid-stable complex (41.5K and 38.5K BPs), the 30K IGF-BP, and the 24K IGF-BP were all lower in the elderly than in the young group (P < 0.01 for each fraction, elderly vs. young). In contrast, the 34K IGF-BP binding ratio was significantly greater in the elderly than in the young (0.30 .+-. 0.03 vs. 0.12 .+-. 0.01; P < 0.001) and correlated closely with advancing age (r = 0.64; P < 0.01). The changes in IGF-BPs found in the elderly are quite similar to alterations in serum IGF-BPs previously reported in GH deficiency. Since several IGF-BPs in vitro have been shown to modulate the mitogenic activity of IGF-I, the serum IGF-BP changes noted above may be important for the growth and maintenance of connective tissue, muscle, and bone during the aging process.