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

Authors:Baur, Joseph A.
Pearson, Kevin J.
Price, Nathan L.
Jamieson, Hamish A.
Lerin, Carles
Kalra, Avash
Prabhu, Vinayakumar V.
Allard, Joanne S.
López-Lluch, Guillermo
Lewis, Kaitlyn N.
Pistell, Paul J.
Poosala, Suresh
Becker, Kevin G.
Boss, Olivier
Gwinn, Dana
Wang, Mingyi
Ramaswamy, Sharan
Fishbein, Kenneth W.
Spencer, Richard G.
Lakatta, Edward G.
Couteur, David le
Shaw, Reuben J.
Navas, Plácido
Puigserver, Pere
Ingram, Donald K.
Cabo, Rafael de
Sinclair, David A.
Keywords:Resveratrol, Drosophila melanogaster, Caloric restriction, Insulin, Mitochondrial, Obesity, Aging
Issue Date:1-Nov-2006
Publisher:Nature Publishing Group
Citation:Nature 444 (7117): 337-342 (2006)
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- coactivator 1(PGC-1) 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.
Description:6 páginas, 4 figuras, 1 tabla.
Publisher version (URL):http://dx.doi.org/10.1038/nature05354
E-ISSNmetadata.dc.identifier.doi = DOI:1476-4687
Appears in Collections:(CABD) Artículos

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