Sis2 regulates yeast replicative lifespan in a dose-dependent manner

Nat Commun. 2023 Nov 27;14(1):7719. doi: 10.1038/s41467-023-43233-y.

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 sis2Δ background neutralized the lifespan extension. RNA-seq experiments revealed transcriptional increases in cell-cycle machinery components in sis2Δ background. High-precision lifespan measurement will be essential to elucidate the gene network governing lifespan.

MeSH terms

  • Cell Cycle
  • Cell Cycle Proteins* / genetics
  • Cell Cycle Proteins* / metabolism
  • DNA Replication / genetics
  • Longevity / genetics
  • Saccharomyces cerevisiae Proteins* / genetics
  • Saccharomyces cerevisiae Proteins* / metabolism
  • Saccharomyces cerevisiae* / metabolism

Substances

  • Saccharomyces cerevisiae Proteins
  • SIS2 protein, S cerevisiae
  • Cell Cycle Proteins