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

By Joseph A. Baur, K. Pearson, Nathan L. Price, H. Jamieson, C. Lerin, Avash Kalra, V. Prabhu, Joanne S. Allard, G. López-Lluch, Kaitlyn N. Lewis and 17 more. Nature, 2006

4,383 citations recorded by the source corpus.

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.

View Paper: https://www.semanticscholar.org/paper/5f4d510a19644d15e0f671f6f7f5b41908df50e6

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

1. C. Cantó
2. D. Hardie
3. R. Houtkooper
4. G. Steinberg
5. Johan Auwerx
6. Antero Salminen
7. S. Hawley
8. Nir Barzilai

Citations in the corpus

• Repeat Dose Study of the Cancer Chemopreventive Agent Resveratrol in Healthy Volunteers: Safety, Pharmacokinetics and Effect on the Insulin-like Growth Factor Axis (2010, unknown): “Resveratrol can also retard parameters linked to aging and acts as a calorie restriction-mimetic in mice (3,4), important findings in the light of emerging evidence of a possible association between calorie restriction and anticarcinogenesis (5).”
• Butyrate Improves Insulin Sensitivity and Increases Energy Expenditure in Mice (2009, background): “These activities of butyrate are similar to those of resveratrol (1,2).”
• Antioxidants reduce endoplasmic reticulum stress and improve protein secretion (2008, background): “In particular, antioxidants can reduce insulin resistance in animal models (47, 48).”
• DNA damage-induced alterations in chromatin contribute to genomic integrity and age-related changes in gene expression (2008, unknown): “Resveratrol was fed at 2.4 mg/kg food as previously described (Baur et al., 2006).”
• Novel insights of dietary polyphenols and obesity. (2014, background): “[113] Male C57BL/6NIA mice (1 year old).”
• AMPK in Health and Disease. (2009, background): “port (384) and mitochondrial biogenesis (36), while in”
• AMPK Phosphorylates and Inhibits SREBP Activity to Attenuate Hepatic Steatosis and Atherosclerosis in Diet-induced Insulin Resistant Mice (2011, unknown): “Other studies have also shown that resveratrol activates hepatic AMPK and ameliorates insulin sensitivity in high fat-fed mice (Baur et al., 2006) and that the metabolic effects of resveratrol are abrogated in AMPKa1- or a2-deficientmice (Umet al.”
• A Low Dose of Dietary Resveratrol Partially Mimics Caloric Restriction and Retards Aging Parameters in Mice (2008, background): “Thus, our microarray results suggest that a low dose of dietary resveratrol induces a transcriptional program similar to CR in multiple tissues and retards aging parameters, but these effects may be largely independent of the increase in SIRT1 activity and activation of Pgc-1a transcriptional target”
• The pros and cons of phytoestrogens (2010, unknown): “One notable study using mice fed a high fat diet found that high dose resveratrol (22 mg/kg) could effectively stave off many of the adverse health effects of obesity, resulting in significantly improved survival rates [23].”
• Calorie restriction-like effects of 30 days of Resveratrol (resVida™) supplementation on energy metabolism and metabolic profile in obese humans (2011, background): “These beneficial effects of resveratrol on metabolism are in concordance with several findings of resveratrol supplementation in animals (Baur et al., 2006; Cantó et al., 2009; Lagouge et al., 2006; Pearson et al., 2008; Sun et al., 2007).”
• Hepatocyte-specific Deletion of SIRT1 Alters Fatty Acid Metabolism and Results in Hepatic Steatosis and Inflammation (2009, background): “For example, activation of SIRT1 by the polyphenol resveratrol and several synthetic pharmacologic activators has been shown to protect against high-fat induced obesity and metabolic derangements (Baur et al., 2006; Lagouge et al., 2006; Milne et al., 2007).”