Leucine supplementation mimics the effects of caloric restriction on yeast chronological lifespan

Leucine prototrophic yeast exhibits extended longevity and related phenotypes similar to yeast grown under calorie restriction (CR) condition. The extended longevity of leucine prototrophic yeast is thought to be a function of abundant cellular leucine level. To verify the similar effects of leucine-induced and CR-induced chronological life span (CLS), leucine prototrophic and auxotrophic yeast cells were grown in the presence or absence of exogenous leucine supplementation and CR condition, and their lifespan and various phenotypes were examined. Leucine supplementation induced CLS extension, increased cellular Cox2p levels, and decreased cell death. These phenotypes were similar to those of the cells grown under CR. Interestingly, simultaneous treatment with exogenous leucine supplementation and CR led to a synergistic effect. CLS and cellular Cox2p levels increased further by simultaneous treatment compared to the observations in cells treated with either leucine supplementation or CR. Similarly, the rate of cell death of simultaneously treated cells was significantly lower than that of cells undergoing only one treatment. Leucine-induced CLS extension and a decreased in the rate of cell death observed in this study verified the function of leucine in cell death prevention and CLS extension in yeast. Interestingly, leucine-induced changes were similar to CR-induced changes. The results in this study suggest that leucine can function as a CR mimetic.