Resveratrol Delays Age-Related Deterioration and Mimics Transcriptional Aspects of Dietary Restriction without Extending Life Span

Kevin J. Pearson, Joseph A. Baur, Kaitlyn N. Lewis, Leonid Peshkin, Nathan L. Price, Nazar Labinskyy, William R. Swindell, Davida Kamara, Robin K. Minor, Evelyn Perez, Hamish A. Jamieson, Yongqing Zhang, Stephen R. Dunn, Kumar Sharma, Nancy Pleshko, Laura A. Woollett, Anna Csiszar, Yuji Ikeno, David Le Couteur, Peter J. ElliottKevin G. Becker, Placido Navas, Donald K. Ingram, Norman S. Wolf, Zoltan Ungvari, David A. Sinclair, Rafael de Cabo

Research output: Contribution to journalArticlepeer-review

1022 Scopus citations

Abstract

A small molecule that safely mimics the ability of dietary restriction (DR) to delay age-related diseases in laboratory animals is greatly sought after. We and others have shown that resveratrol mimics effects of DR in lower organisms. In mice, we find that resveratrol induces gene expression patterns in multiple tissues that parallel those induced by DR and every-other-day feeding. Moreover, resveratrol-fed elderly mice show a marked reduction in signs of aging, including reduced albuminuria, decreased inflammation, and apoptosis in the vascular endothelium, increased aortic elasticity, greater motor coordination, reduced cataract formation, and preserved bone mineral density. However, mice fed a standard diet did not live longer when treated with resveratrol beginning at 12 months of age. Our findings indicate that resveratrol treatment has a range of beneficial effects in mice but does not increase the longevity of ad libitum-fed animals when started midlife.

Original languageEnglish
Pages (from-to)157-168
Number of pages12
JournalCell Metabolism
Volume8
Issue number2
DOIs
StatePublished - Aug 6 2008

Bibliographical note

Funding Information:
David A. Sinclair declares he is a consultant to Sirtris, a GSK sirtuin company, and a board member/shareholder of Genocea Biosciences, a vaccine company. Peter J. Elliott declares he is a full-time employee and shareholder of GSK/Sirtris. We would like to thank Dawn Phillips for animal care, Hank Rasnow for purchasing the mice, William Wood for microarray assistance, Katie Burke for help with the plasma lipid and lipoprotein cholesterol concentrations, Patrick Loerch for helpful suggestions and advice, and Mark Beasley and David Allison for assistance with Cox Regression Modeling. We would like to thank Steve Sollott, Alexei Sharov, and Dan Longo for critical reading of the manuscript. This work utilized the facilities of the HSS Musculoskeletal Repair and Regeneration Core Center (NIH AR46121) and was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health. D.A.S. is an Ellison Medical Foundation Senior Scholar. This work was supported by grants from the American Heart Association (0425834T to J.A.B. and 0435140N to A.C.) and from the NIH (RO1GM068072, AG19972, and AG19719 to D.A.S.), (HL077256 to Z.U.), (HD034089 to L.W), (2RO1 EY011733 to N.S.W.), Spanish grant (BFU2005-03017 to P.N.), and by the generous support of Mr. Paul F. Glenn and The Paul F. Glenn Laboratories for the Biological Mechanisms of Aging.

Keywords

  • HUMDISEASE
  • SYSBIO

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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