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

Authors: Baur JA; Pearson KJ; Price NL; Jamieson HA; Lerin C; Kalra A; Prabhu VV; Allard JS; Lopez-Lluch G; Lewis K; Pistell PJ; Poosala S; Becker KG; Boss O; Gwinn D; Wang M; Ramaswamy S; Fishbein KW; Spencer RG; Lakatta EG; Le Couteur D; Shaw RJ; Navas P; Puigserver P; Ingram DK; de Cabo R; Sinclair DA

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-gamma coactivator 1alpha (PGC-1alpha) 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.

Keywords: Acetylation/drug effects; Adenylate Kinase/metabolism; Animals; Energy Intake/*physiology; *Health; Insulin/metabolism; Liver/cytology/drug effects/metabolism; Male; Mice; Mice, Inbred C57BL; Mitochondria, Liver/drug effects/metabolism; Obesity/drug therapy; Oligonucleotide Array Sequence Analysis; Stilbenes/*pharmacology; Survival Rate; Trans-Activators/metabolism
Journal: Nature
Volume: 444
Issue: 7117
Pages: 337-42
Date: Nov. 7, 2006
PMID: 17086191
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Citation:

Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444: 337-42.



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