Calorie restriction reduces rDNA recombination independently of rDNA silencing

Aging Cell. 2009 Dec;8(6):624-32. doi: 10.1111/j.1474-9726.2009.00514.x. Epub 2009 Sep 2.


Calorie restriction (CR) extends lifespan in yeast, worms, flies and mammals, suggesting that it acts via a conserved mechanism. In yeast, activation of the NAD-dependent histone deacetylase, Sir2, by CR is thought to increase silencing at the ribosomal DNA, thereby reducing the recombination-induced generation of extrachromosomal rDNA circles, hence increasing replicative lifespan. Although accumulation of extrachromosomal rDNA circles is specific to yeast aging, it is thought that Sirtuin activation represents a conserved longevity mechanism through which the beneficial effects of CR are mediated in various species. We show here that growing yeast on 0.05 or 0.5% glucose (severe and moderate CR, respectively) does not increase silencing at either sub-telomeric or rDNA loci compared with standard (2% glucose) media. Furthermore, rDNA silencing was unaffected in the hxk2Delta, sch9Delta and tor1Delta genetic mimics of CR, but inhibited by FOB1 deletion. All these interventions extend lifespan in multiple yeast backgrounds, revealing a poor correlation between rDNA silencing and longevity. In contrast, CR and deletion of the FOB1, HXK2, SCH9 and TOR1 genes, all significantly reduced rDNA recombination. This silencing-independent mechanism for suppressing rDNA recombination may therefore contribute to CR-mediated lifespan extension.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA, Fungal / genetics*
  • DNA, Ribosomal / genetics*
  • Gene Expression Regulation, Fungal*
  • Gene Silencing
  • Glucose / metabolism*
  • Mutation
  • Recombination, Genetic*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics


  • DNA, Fungal
  • DNA, Ribosomal
  • Saccharomyces cerevisiae Proteins
  • Glucose