Identification of a new gene that is critical in yeast life span determination by metabolic and genetic studies

초록

Caloric restriction (CR) has been known to extend life span of many species. In yeast, CR extends both replicative life span and chronological life span. Although many years of researches revealed mechanisms responsible for CR-associated life span extension, specific metabolic effector molecules that act on the mechanisms and how their levels are modulated by metabolic enzymes are largely unknown. Using metabolomics and genetic approaches, we identified metabolites affecting CR-induced chronological life span in yeast. Among 23 metabolites with altered profile by CR, alanine level was inversely correlated with yeast chronological life span. Later analysis revealed that alanine transaminase is an important factor for life span maintenance. Life span modulation by alanine and ALT1 was TOR1-independent. This study shows the importance of small molecule metabolism and relevance of metabolomics combined with genetic approach in the mechanistic studies in life span.