Influence of Age and Long-term Dietary Restriction on Plasma Insulin-like Growth Factor-1 (IGF-1), IGF-1 Gene Expression, and IGF-1 Binding Proteins

The purpose of these studies was to determine more accurately the relationship between IGF-1 and life span, and to determine whether moderate dietary caloric restriction alters the age-related changes in IGF-1. Studies included an assessment of plasma IGF-1, hepatic IGF-1 mRNA, and plasma IGF-1 binding proteins (IGF-1-BP). Rats (6, 12, 22, and 28 months of age) were fed ad libitum or maintained on a diet 60% of ad libitum. In ad libitum fed animals, plasma IGF-1 decreased by 20% between 6 and 28 months of age. Similar age-related declines were observed in dietary restricted animals but levels were generally 14-25% lower at each age group. IGF-1 mRNA levels demonstrated similar decreases with age in ad libitum fed animals, but in dietary restricted animals, levels plateaued at 22 and 28 months. IGF-1 binding protein analysis revealed 3 bands at approximate molecular weights of 40k, 30k, and 24k. All bands demonstrated a decrease in relative IGF-1-BP concentration with age, as well as a decrease in the 40k and 30k binding proteins after dietary restriction. These results indicate that (a) aging in ad libitum fed animals is associated with decreases in plasma IGF-1, IGF-1-BP, and IGF-1 mRNA levels; and (b) long-term dietary restriction decreases plasma IGF-1 and IGF-1-BP levels in each age group although the age-associated decreases in IGF-1 mRNA levels are prevented by dietary restriction.(ABSTRACT TRUNCATED AT 250 WORDS)