Multiple pathways regulating the calorie restriction response in yeast

Ofer Rahat, Noam Maoz, Haim Y. Cohen

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


In yeast, SIR2 overexpression or calorie restriction (CR) results in life-span extension. It was previously suggested that CR activates Sir2 by reducing the levels of Sir2 inhibitors, NADH, or nicotinamide. Whereas NADH reduction is associated with an increase in respiration, nicotinamide clearance is induced by the upregulation of PNC1. Here, we show that, consistent with the hormesis hypothesis, PNC1 is part of a transcriptional stress response module consisting of 39 genes that increases under various stresses. Under high CR (0.1% glucose), Pnc1 becomes activated and its levels increase. However, low CR (0.5% glucose) increases yeast life span without PNC1 induction or activation of any transcriptional stress response. Instead, microarray analysis of low CR shows that the messenger RNA levels of iron transport genes increase, suggesting that this mode of CR is regulated by a shift toward respiration and lowering NADH levels. Thus, at least two pathways regulate the CR response in yeast.

Original languageEnglish
Pages (from-to)163-169
Number of pages7
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume66 A
Issue number2
StatePublished - 1 Feb 2011
Externally publishedYes


  • Calorie restriction
  • Respiration
  • Stress
  • Yeast

ASJC Scopus subject areas

  • General Medicine


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