Age- and Tissue-Dependent Modulation of IGF-1/PI3K/Akt Protein Expression by Dietary Restriction in Mice

Insulin-like growth factor-1 (IGF-1), a key mediator of growth hormone action in mammals, plays an important role in the regulation of cellular and tissue functions. In the present investigation, the normal age-dependent and effect of dietary restriction on the expression levels of serum IGF-1, phosphotidylinositol 3-kinase (PI3K), and protein kinase B (PKB/Akt) in the liver, kidney and skeletal muscles of 1-, 9-, and 21-month-old female mice were ascertained using ELISA and Western blot analysis. Results showed that serum IGF-1 peaks at 9-month-old and decreases in older age. Dietary restriction (DR) decreases IGF-1 in both age groups. In liver, PI3K and relative amount of phosphorylated Akt (pAkt/Akt) showed an age-dependent correlated expression level as IGF-1 protein. In kidney and skeletal muscles, PI3K levels showed no changes with age. However, pAkt/Akt ratio increased in 9-month-old mice and decreased in 21-month-old mice. In liver, DR increased the level of PI3K and pAkt/Akt ratio in 9-month-old mice, but no significant change was seen in 21-month-old mice as compared to ad libitum-fed group. In kidney and skeletal muscles, DR mice showed an increase in PI3K level in both age groups while the pAkt/Akt ratio showed no change in 9-month-old mice, but exhibited a decrease in 21-month-old mice. These results indicate that there is a tissue-specific regulation of IGF-1/PI3K/Akt during normal aging and upon DR to help maintain the metabolic status of these tissues at those phases of animal's lifespan.