Tissue-specific regulation of SIRT1 by calorie restriction

Danica Chen, Joanne Bruno, Erin Easlon, Su Ju Lin, Hwei Ling Cheng, Frederick W. Alt, Leonard Guarente

Research output: Contribution to journalArticlepeer-review

456 Scopus citations


Calorie restriction (CR) has been reported to increase SIRT1 protein levels in mice, rats, and humans, and elevated activity of SIRT1 orthologs extends life span in yeast, worms, and flies. In this study, we challenge the paradigm that CR induces SIRT1 activity in all tissues by showing that activity of this sirtuin in the liver is, in fact, reduced by CR and activated by a high-caloric diet. We demonstrate this change both by assaying levels of SIRT1 and its small molecule regulators, NAD and NADH, as well as assessing phenotypes of a liver-specific SIRT1 knockout mouse on various diets. Our findings suggest that designing CR mimetics that target SIRT1 to provide uniform systemic benefits may be more complex than currently imagined.

Original languageEnglish (US)
Pages (from-to)1753-1757
Number of pages5
JournalGenes and Development
Issue number13
StatePublished - Jul 1 2008


  • Aging
  • Calorie restriction
  • SIRT1

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology


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