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.