ERYTHROCYTE INSULIN-LIKE GROWTH-FACTOR-I BINDING IN YOUNGER AND OLDERMALES

OBJECTIVE Insulin-like growth factor-I (IGF-I) levels are lower in old er compared with younger subjects. We tested the hypothesis that the r eduction in circulating IGF-I would be accompanied by upregulation in tissue IGF-I binding in at least some tissues. We tested erythrocyte I GF-I binding since blood is an accessible tissue in humans, and there is growing evidence to suggest that erythrocyte IGF-I binding is influ enced by circulating IGF-I. DESIGN AND PATIENTS We compared 9 healthy older males (61-68 years old) with 9 healthy younger males (15-19 year s old), MEASUREMENTS Standard techniques were used to assay circulatin g IGF-I and IGF binding proteins 1-5 (IGFBPs 1-5), Erythrocyte IGF-I b inding was first measured by studies in which native [I-125]-IGF-I was displaced with unlabelled native IGF-I, In order to determine a possi ble role for IGF binding proteins (IGFBP), native [I-125]-IGF-I was di splaced with des-(1-3)IGF-I, which binds with IGF receptors but not IG FBPs, RESULTS As expected, circulating IGF-I was significantly lower i n the older compared with the younger subjects, In addition, IGFBP-3 a nd 5 were significantly lower, and IGFBP-4 higher, in older compared w ith younger subjects. When native [I-125]-IGF-I was displaced with unl abelled native IGF-I, the number of IGF-I binding sites per erythrocyt e was higher in the older subjects (43 +/- 5 vs. 18 +/- 2, older vs. y ounger, respectively; P < 0.05). In contrast, when native [I-125]-IGF- I was displaced with des-(1-3), IGF-I binding capacity was not differe nt between the two age groups. CONCLUSIONS Erythrocyte IGF binding was increased in older compared with younger subjects. Surprisingly, the mechanism of the increase may not be a simple up regulation of IGF-I r eceptors in response to reduced circulating IGF-I, but possibly by an increase in the levels of as yet unidentified erythrocyte membrane-ass ociated IGF binding proteins.