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 LakattaDavid Le Couteur, Reuben J. Shaw, Placido Navas, Pere Puigserver, Donald K. Ingram, Rafael De Cabo, David A. Sinclair

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)337-342
Number of pages6
JournalNature
Volume444
Issue number7117
DOIs
StatePublished - Nov 16 2006
Externally publishedYes

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Diet
Health
Caloric Restriction
Peroxisome Proliferator-Activated Receptors
AMP-Activated Protein Kinases
Caenorhabditis elegans
Somatomedins
Drosophila melanogaster
Insulin-Like Growth Factor I
Saccharomyces cerevisiae
Insulin Resistance
Mammals
Obesity
resveratrol
Genes

ASJC Scopus subject areas

  • General

Cite this

Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., ... Sinclair, D. A. (2006). Resveratrol improves health and survival of mice on a high-calorie diet. Nature, 444(7117), 337-342. https://doi.org/10.1038/nature05354

Resveratrol improves health and survival of mice on a high-calorie diet. / Baur, Joseph A.; Pearson, Kevin J.; Price, Nathan L.; Jamieson, Hamish A.; Lerin, Carles; Kalra, Avash; Prabhu, Vinayakumar V.; Allard, Joanne S.; Lopez-Lluch, Guillermo; Lewis, Kaitlyn; Pistell, Paul J.; Poosala, Suresh; Becker, Kevin G.; Boss, Olivier; Gwinn, Dana; Wang, Mingyi; Ramaswamy, Sharan; Fishbein, Kenneth W.; Spencer, Richard G.; Lakatta, Edward; Le Couteur, David; Shaw, Reuben J.; Navas, Placido; Puigserver, Pere; Ingram, Donald K.; De Cabo, Rafael; Sinclair, David A.

In: Nature, Vol. 444, No. 7117, 16.11.2006, p. 337-342.

Research output: Contribution to journalArticle

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, E, 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, vol. 444, no. 7117, pp. 337-342. https://doi.org/10.1038/nature05354
Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature. 2006 Nov 16;444(7117):337-342. https://doi.org/10.1038/nature05354
Baur, Joseph A. ; Pearson, Kevin J. ; Price, Nathan L. ; Jamieson, Hamish A. ; Lerin, Carles ; Kalra, Avash ; Prabhu, Vinayakumar V. ; Allard, Joanne S. ; Lopez-Lluch, Guillermo ; Lewis, Kaitlyn ; Pistell, Paul J. ; Poosala, Suresh ; Becker, Kevin G. ; Boss, Olivier ; Gwinn, Dana ; Wang, Mingyi ; Ramaswamy, Sharan ; Fishbein, Kenneth W. ; Spencer, Richard G. ; Lakatta, Edward ; Le Couteur, David ; Shaw, Reuben J. ; Navas, Placido ; Puigserver, Pere ; Ingram, Donald K. ; De Cabo, Rafael ; Sinclair, David A. / Resveratrol improves health and survival of mice on a high-calorie diet. In: Nature. 2006 ; Vol. 444, No. 7117. pp. 337-342.
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