Tissue-specific regulation of SIRT1 by calorie restriction

2008/06/11 by Danica Chen, Joanne Bruno, Erin Easlon +4 · 3 citations
Medicine · #Sirtuins and Resveratrol in Medicine #Adipose Tissue and Metabolism #Biochemical effects in animals

paper · pdf · doi:10.1101/gad.1650608

openalex publication_date 2008/06/11 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/14

Abstract

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.

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