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; David A. Sinclair

doi:10.1038/nature05354

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

Research output: Contribution to journal › Article › peer-review

3888 Scopus citations

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 language	English
Pages (from-to)	337-342
Number of pages	6
Journal	Nature
Volume	444
Issue number	7117
DOIs	https://doi.org/10.1038/nature05354
State	Published - Nov 16 2006

Bibliographical note

Funding Information:
Acknowledgements We thank H. Rasnow for his donation towards purchasing the mice; V. Massari for help with electron microscopy; W. Matson for HPLC assays of resveratrol; M. Chachich and M. Tatar for help with statistical analysis; W. Wood for microarray assistance; D. Phillips for animal care; J. Egan’s group for insulin measurements; the Sinclair laboratory, N. Wolf, P. Elliott, C. Westphal, R. Weindruch, P. Lambert, J. Milne and M. Milburn for advice on experimental design; and S. Luikenhuis and M. Dipp for critical reading of the manuscript. D.A.S. was supported by The Ellison Medical Research Foundation, J.A.B. by The American Heart Foundation, H.J. and D.LeC. by an Australian NHMRC project grant and an NHMRC post-graduate scholarship, and C.L. and P.P. by the American Diabetes Association and NIH. This research was supported (in part) by the Intramural Research Program of the NIH, NIA, a Spanish MCyT grant to P.N., NIH grants to D.A.S., and by the support of P. F. Glenn and The Paul F. Glenn Laboratories for the Biological Mechanisms of Aging.

ASJC Scopus subject areas

General

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/nature05354

Cite this

Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., Prabhu, V. V., Allard, J. S., Lopez-Lluch, G., Lewis, K., Pistell, P. J., Poosala, S., Becker, K. G., Boss, O., Gwinn, D., Wang, M., Ramaswamy, S., Fishbein, K. W., Spencer, R. G., ... 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

@article{03a42ae7aeb74ba8a2a0544b563f4f86,

title = "Resveratrol improves health and survival of mice on a high-calorie diet",

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.",

author = "Baur, {Joseph A.} and Pearson, {Kevin J.} and Price, {Nathan L.} and Jamieson, {Hamish A.} and Carles Lerin and Avash Kalra and Prabhu, {Vinayakumar V.} and Allard, {Joanne S.} and Guillermo Lopez-Lluch and Kaitlyn Lewis and Pistell, {Paul J.} and Suresh Poosala and Becker, {Kevin G.} and Olivier Boss and Dana Gwinn and Mingyi Wang and Sharan Ramaswamy and Fishbein, {Kenneth W.} and Spencer, {Richard G.} and Lakatta, {Edward G.} and {Le Couteur}, David and Shaw, {Reuben J.} and Placido Navas and Pere Puigserver and Ingram, {Donald K.} and {De Cabo}, Rafael and Sinclair, {David A.}",

note = "Funding Information: Acknowledgements We thank H. Rasnow for his donation towards purchasing the mice; V. Massari for help with electron microscopy; W. Matson for HPLC assays of resveratrol; M. Chachich and M. Tatar for help with statistical analysis; W. Wood for microarray assistance; D. Phillips for animal care; J. Egan{\textquoteright}s group for insulin measurements; the Sinclair laboratory, N. Wolf, P. Elliott, C. Westphal, R. Weindruch, P. Lambert, J. Milne and M. Milburn for advice on experimental design; and S. Luikenhuis and M. Dipp for critical reading of the manuscript. D.A.S. was supported by The Ellison Medical Research Foundation, J.A.B. by The American Heart Foundation, H.J. and D.LeC. by an Australian NHMRC project grant and an NHMRC post-graduate scholarship, and C.L. and P.P. by the American Diabetes Association and NIH. This research was supported (in part) by the Intramural Research Program of the NIH, NIA, a Spanish MCyT grant to P.N., NIH grants to D.A.S., and by the support of P. F. Glenn and The Paul F. Glenn Laboratories for the Biological Mechanisms of Aging.",

year = "2006",

month = nov,

day = "16",

doi = "10.1038/nature05354",

language = "English",

volume = "444",

pages = "337--342",

number = "7117",

}

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, vol. 444, no. 7117, pp. 337-342. https://doi.org/10.1038/nature05354

TY - JOUR

T1 - Resveratrol improves health and survival of mice on a high-calorie diet

AU - Baur, Joseph A.

AU - Pearson, Kevin J.

AU - Price, Nathan L.

AU - Jamieson, Hamish A.

AU - Lerin, Carles

AU - Kalra, Avash

AU - Prabhu, Vinayakumar V.

AU - Allard, Joanne S.

AU - Lopez-Lluch, Guillermo

AU - Lewis, Kaitlyn

AU - Pistell, Paul J.

AU - Poosala, Suresh

AU - Becker, Kevin G.

AU - Boss, Olivier

AU - Gwinn, Dana

AU - Wang, Mingyi

AU - Ramaswamy, Sharan

AU - Fishbein, Kenneth W.

AU - Spencer, Richard G.

AU - Lakatta, Edward G.

AU - Le Couteur, David

AU - Shaw, Reuben J.

AU - Navas, Placido

AU - Puigserver, Pere

AU - Ingram, Donald K.

AU - De Cabo, Rafael

AU - Sinclair, David A.

N1 - Funding Information: Acknowledgements We thank H. Rasnow for his donation towards purchasing the mice; V. Massari for help with electron microscopy; W. Matson for HPLC assays of resveratrol; M. Chachich and M. Tatar for help with statistical analysis; W. Wood for microarray assistance; D. Phillips for animal care; J. Egan’s group for insulin measurements; the Sinclair laboratory, N. Wolf, P. Elliott, C. Westphal, R. Weindruch, P. Lambert, J. Milne and M. Milburn for advice on experimental design; and S. Luikenhuis and M. Dipp for critical reading of the manuscript. D.A.S. was supported by The Ellison Medical Research Foundation, J.A.B. by The American Heart Foundation, H.J. and D.LeC. by an Australian NHMRC project grant and an NHMRC post-graduate scholarship, and C.L. and P.P. by the American Diabetes Association and NIH. This research was supported (in part) by the Intramural Research Program of the NIH, NIA, a Spanish MCyT grant to P.N., NIH grants to D.A.S., and by the support of P. F. Glenn and The Paul F. Glenn Laboratories for the Biological Mechanisms of Aging.

PY - 2006/11/16

Y1 - 2006/11/16

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33751072349&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33751072349&partnerID=8YFLogxK

U2 - 10.1038/nature05354

DO - 10.1038/nature05354

M3 - Article

C2 - 17086191

AN - SCOPUS:33751072349

SN - 0028-0836

VL - 444

SP - 337

EP - 342

JO - Nature

JF - Nature

IS - 7117

ER -

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

Abstract

Bibliographical note

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this