title: Cellular senescence in yeast is regulated by rDNA noncoding transcription.
abstract: Genomic instability is a conserved factor in lifespan reduction, although the molecular mechanism is not known. Studies in the yeast Saccharomyces cerevisiae over the past 20 years have found a connection between the ribosomal RNA gene cluster (rDNA) and lifespan. The highly repetitive rDNA exhibits genomic instability, and the antiaging histone deacetylase gene SIR2 regulates this instability. We previously proposed that SIR2 governs lifespan by repressing rDNA noncoding transcription and rDNA instability, but the extent to which lifespan is affected by SIR2 acting at the rDNA versus other genomic regions, and the relationship between rDNA noncoding transcription/rDNA stability and lifespan have remained controversial. To control rDNA noncoding transcription and rDNA instability, we use a strain in which the rDNA noncoding promoter is replaced with an inducible promoter. Here, we show that repression of noncoding transcription extends lifespan and makes SIR2 dispensable for lifespan extension. These results indicate that Sir2 maintains lifespan through repression of E-pro noncoding transcription in the rDNA cluster, rather than pleiotropically at other loci. The observation of rDNA instability in other organisms, including humans, suggests that this may be a conserved aging pathway.
authors.affiliation: Division of Cytogenetics, National Institute of Genetics, The Graduate University for Advanced Studies, Sokendai, 1111 Yata, Mishima, Shizuoka 411-8540, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Saka
authors.forename: Satoru
authors.initials: S
authors.lastname: Ide
authors.forename: Austen R D
authors.initials: AR
authors.lastname: Ganley
authors.forename: Takehiko
authors.initials: T
authors.lastname: Kobayashi
mesh_terms: D016922:Cellular Senescence / Q000235:genetics*; D004275:DNA, Ribosomal / Q000502:physiology*; D042822:Genomic Instability; D008136:Longevity / Q000235:genetics; D008957:Models, Genetic; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D004275:DNA, Ribosomal