UC Irvine

OBJECTIVE: Insulin-like growth factor-1 (IGF-l) levels are lower in older compared with younger subjects. We tested the hypothesis that the reduction in circulating IGF-l would be accompanied by upregulation in tissue IGF-l binding in at least some tissues. We tested erythrocyte IGF-l binding since blood is an accessible tissue in humans, and there is growing evidence to suggest that erythrocyte IGF-l binding is influenced by circulating IGF-l. DESIGN AND PATIENTS: We compared 9 healthy older males (61-68 years old) with 9 healthy younger males (15-19 years old). MEASUREMENTS: Standard techniques were used to assay circulating IGF-l and IGF binding proteins 1-5 (IGFBPs 1-5). Erythrocyte IGF-l binding was first measured by studies in which native [125l]-IGF-l was displaced with unlabelled native IGF-l. In order to determine a possible role for IGF binding proteins (IGFBP), native [125l]-IGF-l was displaced with des-(1-3)IGF-1, which binds with IGF receptors but not IGFBPs. RESULTS: As expected, circulating IGF-l was significantly lower in the older compared with the younger subjects. In addition, IGFBP-3 and 5 were significantly lower, and IGFBP-4 higher, in older compared with younger subjects. When native [125l]-IGF-l was displaced with unlabelled native IGF-l, the number of IGF-l binding sites per erythrocyte was higher in the older subjects (43 +/- 5 vs. 18 +/- 2, older vs. younger, respectively; P < 0.05). In contrast, when native [125l]-IGF-l was displaced with des-(1-3), IGF-l binding capacity was not different 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-l receptors in response to reduced circulating IGF-l, but possibly by an increase in the levels of as yet unidentified erythrocyte membrane-associated IGF binding proteins.