Caloric restriction modulates insulin receptor signaling in liver and skeletal muscle of rat

Abstract Objective We investigated how the insulin/insulin-like growth factor-1 signaling pathway is involved in the robust antiaging effects produced by caloric restriction. Methods We subjected male rats to feeding ad libitum or calorie restriction, i.e., 60% of the ad libitum amount, for 2 and 25 mo and then assessed the effects of calorie restriction on insulin receptor (IR) signaling in liver and skeletal muscle. Results The results indicated that aging was accompanied by a significant decrease in IR tyrosine phosphorylation after insulin stimulation in live and skeletal muscle, which was associated with a significant increase in the activity of protein tyrosine phosphatase-1B. However, these age-related alterations were attenuated by long-term calorie restriction. Expression profile of mRNA showed an increased expression of mRNAs for IR and insulin-like growth factor-1 receptor in both tissues of calorie-restricted rats, but increased expression of IR mRNA was dissociated with the IR gene product in rats maintained on long-term calorie-restricted diet. Conclusion IR signaling may play an important role in aging and its retardation by calorie restriction, and normal function of IR in liver and skeletal muscle is required for healthy aging and extending lifespan in mammals.