CIRCULATING LEVELS OF INSULIN-LIKE-GROWTH-FACTOR (IGF) BINDING PROTEIN-1 AND PROTEIN-3 IN AGING MEN - RELATIONSHIPS TO INSULIN, GLUCOSE, IGF, AND DEHYDROEPIANDROSTERONE-SULFATE LEVELS AND ANTHROPOMETRIC MEASURES

Reduced secretion of GH and production of insulin-like growth factor I (IGF-I) contribute to altered body composition in human aging. IGF-bi nding proteins (IGFBPs) are important modulators of IGF action, yet li ttle is known regarding their role and regulation in aging. Accordingl y, we measured levels of IGFBP-1, an important short term modulator of IGF bioavailability that is suppressed by insulin, and levels of IGFB P-3, the major circulating IGF carrier protein, and examined their rel ationships to insulin, glucose, IGF, and dehydroepiandrosterone sulfat e levels and anthropometric measures in old (63-89 yr) and young (23-3 9 yr) men. Serum levers of IGFBP-1 were increased 3-fold in old cs. yo ung men despite high insulin levels in elders. Nevertheless, IGFBP-1 a nd insulin levels correlated in old and young men (r = -0.49; P < 0.00 2 and r = -0.42; P < 0.025), suggesting that insulin continues to play an important role in the regulation of IGFBP-1 in aging. Glucose leve l also were significantly inversely related to IGFBP-1 in old and youn g men (r = -0.37; P = 0.02 and r = -0.49; P < 0.01), and this relation ship was not accounted for by the effect of insulin. IGF-I levels mere reduced by 33% in elders (P < 0.001) and correlated with IGFBP-1 leve ls among old (r = -0.40; P < 0.01), but not young, men, indicating tha t low GH secretion and/or IGF-I production may contribute to the eleva tion of IGFBP-1 levels in aging. IGFBP-3 levels were reduced among eld ers, but not to the same extent as IGF-I, resulting in a relative exce ss of IGFBP-3 in elders (IGPBP-3/IGF-I ratio, 20.1 +/- 0.9 cs. 15.4 +/ - 1.0; P < 0.001). The IGFBP-3/IGF-I ratio correlated with IGF-I level s in young and old men (r = -0.79; P < 0.001 and r = -0.82: P < 0.001) , indicating that diminished GH secretion also may contribute to a rel ative excess of IGFBP-3 among elders. Dehydroepiandrosterone sulfate l evels were low in elders. but did not correlate with IGF, IGFBP, insul in, or glucose levels in either age group. Serum levels of IGFBP-1 (bu t not IGF-I or -II or IGFBP-3) correlated with body mass index and upp er arm fat and muscle areas in elders. These relationships were accoun ted for by the effects of insulin, suggesting that regulation of IGFBP -1 by insulin may play a role in determining body composition in aging . We conclude that insulin remains an important determinant of IGFBP-1 levels in elders, that the fasting glucose level is also a significan t determinant of IGFBP-1 in both old and young subjects, and that redu ced secretion of GH may contribute to impaired anabolism in aging thro ugh multiple mechanisms, including reduced production of IGF-1 and alt erations in circulating levels of both IGFBP-1 and -3. These findings are consistent with the concept that alterations in IGFBP levels may c ontribute to changes in TGF bioavailability and body composition in ag ing.