Sis2 regulates yeast replicative lifespan in a dose-dependent manner

Abstract

Application of microfluidic platforms facilitated high-precision measurements of yeast replicative lifespan (RLS);however, comparative quantification of lifespan across strain libraries has been missing. Here we microfluidically measure the RLS of 307 yeast strains, each deleted for a single gene. Despite previous reports of extended lifespan in these strains, we found that 56% of them did not actually live longer than the wild-type;while the remaining 44% showed extended lifespans, the degree of extension was often different from what was previously reported. Deletion of SIS2 gene led to the largest RLS increase observed. Sis2 regulated yeast lifespan in a dose-dependent manner, implying a role for the coenzyme A biosynthesis pathway in lifespan regulation. Introduction of the human PPCDC gene in the sis2 Delta background neutralized the lifespan extension. RNA-seq experiments revealed transcriptional increases in cell-cycle machinery components in sis2 Delta background. High-precision lifespan measurement will be essential to elucidate the gene network governing lifespan. Using a microfluidic single-cell aging platform, the authors report how single-cell lifespan varies across more than 300 yeast strains, each missing a single gene. Their top hit, Sis2, was found to regulate yeast lifespan in a dose-dependent fashion.