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

Abstract

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
DOIs
StatePublished - Feb 2011

Bibliographical note

Funding Information:
This study was supported by grants from the Israeli Academy of Sciences, Binational US-Israel Science Foundation, Israel Cancer Association, Koret Foundation, the Israel Cancer Research Fund, the Israel Health Ministry, and the ERC: European Research Council. O.R. is funded by the Council for Higher Education fellowship.

Funding

This study was supported by grants from the Israeli Academy of Sciences, Binational US-Israel Science Foundation, Israel Cancer Association, Koret Foundation, the Israel Cancer Research Fund, the Israel Health Ministry, and the ERC: European Research Council. O.R. is funded by the Council for Higher Education fellowship.

FundersFunder number
Israeli Academy of Sciences
Koret Foundation
Israel Cancer Research Fund
European Commission
Israel Cancer Association
Israel Science Foundation
Council for Higher Education
Ministry of Health, State of Israel

    Keywords

    • Calorie restriction
    • Respiration
    • Stress
    • Yeast

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