Insulin-like growth factor-1 (IGF-1) decreases with age in many species and appears to have an important role in the age-related decline in capacity for protein synthesis with age. The goals of these studies were to determine whether (a) ad libitum fed mice demonstrate age-related decreases in IGF-1, (b) the relationship between IGF-1 and age-related changes in protein synthetic capacity in ad libitum fed animals, and (c) whether moderate dietary restriction (which increases both life span and protein synthetic capacity) delays age-related changes in protein synthesis and plasma IGF-1. These studies indicate that (a) in ad libitum fed animals, plasma IGF-1 decreases with age between 10 and 15 months and moderate dietary restriction decreases plasma IGF-1 in young but not older animals, and (b) the temporal changes in protein synthesis are tissue specific; moderate dietary restriction either increases or prevents the age-related decline in tissue protein synthesis. Results suggest that in normal aging, decreases in IGF-1 are associated with the decline in protein synthesis but that other regulatory mechanisms appear to have an important role in this process. Dietary restriction decreases plasma IGF-1 in young animals and either increases protein synthesis or prevents the age-related decline in protein synthesis, suggesting that the effects of dietary restriction are not mediated via increases in plasma IGF-1.