Resveratrol improves health and survival of mice on a high-calorie diet

Joseph A. Baur, Kevin J. Pearson, Nathan L. Price, Hamish A. Jamieson, Carles Lerin, Avash Kalra, Vinayakumar V. Prabhu, Joanne S. Allard, Guillermo Lopez-Lluch, Kaitlyn Lewis, Paul J. Pistell, Suresh Poosala, Kevin G. Becker, Olivier Boss, Dana Gwinn, Mingyi Wang, Sharan Ramaswamy, Kenneth W. Fishbein, Richard G. Spencer, Edward G. Lakatta, David Le Couteur, Reuben J. Shaw, Placido Navas, Pere Puigserver, Donald K. Ingram, Rafael de Cabo () and David A. Sinclair ()
Additional contact information
Joseph A. Baur: Harvard Medical School
Kevin J. Pearson: Laboratory of Experimental Gerontology
Nathan L. Price: Laboratory of Experimental Gerontology
Hamish A. Jamieson: Centre for Education and Research on Ageing, and the ANZAC Research Institute University of Sydney
Carles Lerin: Johns Hopkins University School of Medicine
Avash Kalra: Laboratory of Experimental Gerontology
Vinayakumar V. Prabhu: Gene Expression and Genomics Unit
Joanne S. Allard: Laboratory of Experimental Gerontology
Guillermo Lopez-Lluch: Universidad Pablo de Olavide-CSIC
Kaitlyn Lewis: Laboratory of Experimental Gerontology
Paul J. Pistell: Laboratory of Experimental Gerontology
Suresh Poosala: Research Resources Branch
Kevin G. Becker: Gene Expression and Genomics Unit
Olivier Boss: Sirtris Pharmaceuticals, Inc.
Dana Gwinn: The Salk Institute
Mingyi Wang: Laboratory of Cardiovascular Science
Sharan Ramaswamy: National Institute on Aging, National Institutes of Health
Kenneth W. Fishbein: National Institute on Aging, National Institutes of Health
Richard G. Spencer: National Institute on Aging, National Institutes of Health
Edward G. Lakatta: Laboratory of Cardiovascular Science
David Le Couteur: Centre for Education and Research on Ageing, and the ANZAC Research Institute University of Sydney
Reuben J. Shaw: The Salk Institute
Placido Navas: Universidad Pablo de Olavide-CSIC
Pere Puigserver: Johns Hopkins University School of Medicine
Donald K. Ingram: Laboratory of Experimental Gerontology
Rafael de Cabo: Laboratory of Experimental Gerontology
David A. Sinclair: Harvard Medical School

Nature, 2006, vol. 444, issue 7117, 337-342

Abstract: Abstract Resveratrol (3,5,4′-trihydroxystilbene) extends the lifespan of diverse species including Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. In these organisms, lifespan extension is dependent on Sir2, a conserved deacetylase proposed to underlie the beneficial effects of caloric restriction. Here we show that resveratrol shifts the physiology of middle-aged mice on a high-calorie diet towards that of mice on a standard diet and significantly increases their survival. Resveratrol produces changes associated with longer lifespan, including increased insulin sensitivity, reduced insulin-like growth factor-1 (IGF-I) levels, increased AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) activity, increased mitochondrial number, and improved motor function. Parametric analysis of gene set enrichment revealed that resveratrol opposed the effects of the high-calorie diet in 144 out of 153 significantly altered pathways. These data show that improving general health in mammals using small molecules is an attainable goal, and point to new approaches for treating obesity-related disorders and diseases of ageing.

Date: 2006
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DOI: 10.1038/nature05354

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