Genes determining yeast replicative life span in a long-lived genetic background.

Here we describe the replicative life spans of more than 50 congenic Saccharomyces cerevisiae strains, each carrying a mutation previously implicated in yeast aging. This analysis provides a direct comparison, in a single, long-lived strain background, of a majority of reported yeast aging genes. Of the eleven deletion mutations previously reported to increase yeast life span, we find that deletion of FOB1, deletion of SCH9, and deletion of GPA2, GPR1, or HXK2 (three genetic models of calorie restriction) significantly enhanced longevity. In addition, over-expression of SIR2 or growth on low glucose increased life span. These results define a limited number of genes likely to regulate replicative life span in a strain-independent manner, and create a basis for future epistasis analysis to determine genetic pathways of aging.