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Sirtuin activators mimic caloric restriction and delay ageing in metazoans

Nature volume 430, pages 686689 (05 August 2004) | Download Citation

Subjects

  • A Corrigendum to this article was published on 02 September 2004

Abstract

Caloric restriction extends lifespan in numerous species. In the budding yeast Saccharomyces cerevisiae this effect requires Sir2 (ref. 1), a member of the sirtuin family of NAD+-dependent deacetylases2,3. Sirtuin activating compounds (STACs) can promote the survival of human cells and extend the replicative lifespan of yeast4. Here we show that resveratrol and other STACs activate sirtuins from Caenorhabditis elegans and Drosophila melanogaster, and extend the lifespan of these animals without reducing fecundity. Lifespan extension is dependent on functional Sir2, and is not observed when nutrients are restricted. Together these data indicate that STACs slow metazoan ageing by mechanisms that may be related to caloric restriction.

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Acknowledgements

We thank S. Parkhurst for the dSir2-pRSETc plasmid, and J. Whetstine, H. Yang and Y. Shi for advice and reagents. C. elegans strain VC199 (sir-2.1(ok434)) was generated by the C. elegans Reverse Genetics Core Facility at the University of British Columbia. This work was supported by the National Institute on Aging, the Harvard-Armenise Foundation, the Donaghue Foundation, and a generous gift from Harmon Rasnow. S.L.H. is an Ellison Medical Research Foundation Senior Investigator, and D.S. and M.T. are Ellison Medical Research Foundation Fellows. J.W. is supported by an NSF Graduate Research Fellowship.

Author information

Author notes

    • Jason G. Wood
    •  & Blanka Rogina

    These authors contributed equally to this work

Affiliations

  1. Department of Pathology, Harvard Medical School, 77 Ave. Louis Pasteur, Boston, Massachusetts 02115, USA

    • Jason G. Wood
    • , Siva Lavu
    •  & David Sinclair
  2. Department of Genetics and Developmental Biology, University of Connecticut Health Center, 263 Farmington Ave., Farmington, Connecticut 06030, USA

    • Blanka Rogina
    •  & Stephen L. Helfand
  3. BIOMOL Research Laboratories, Inc., 5120 Butler Pike, Plymouth Meeting, Pennsylvania 19462, USA

    • Konrad Howitz
  4. Department of Ecology and Evolutionary Biology, Box G-W, Brown University, Providence, Rhode Island 02912, USA

    • Marc Tatar

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Competing interests

D.S. and K.H. have filed a provisional patent based on this and other studies. D.S. expects that he will own more than $10,000 equity in a company after September 2004; however, this will not exceed 5% equity.

Corresponding authors

Correspondence to Marc Tatar or David Sinclair.

Supplementary information

PDF files

  1. 1.

    Supplementary Figure S1

    Mortality plots for C. elegans (on dead and live E. coli) and D. melanogaster (males and females) on resveratrol treatment.

  2. 2.

    Supplementary Table ST1

    Summary of results from lifespan trials of C. elegans treated with resveratrol on both live and dead E. coli. Wild-type and sir-2.1 mutants are shown.

  3. 3.

    Supplementary Table ST2

    Summary of results from lifespan trials of D. melanogaster males and females treated with resveratrol and fisetin. Various strain backgrounds, dSir2 alleles, and dietary conditions are shown.

Word documents

  1. 1.

    Supplementary methods

    Methods for sirtuin purification and sirtuin deacetylation assays.

About this article

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DOI

https://doi.org/10.1038/nature02789

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