| | |  | | | | Record from Web of Science® | | | | | | |
| Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan |
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| Author(s): Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA |
| Source: NATURE Volume: 425 Issue: 6954 Pages: 191-196 Published: SEP 11 2003 |
| Times Cited: 603 References: 30 |
| Abstract: In diverse organisms, calorie restriction slows the pace of ageing and increases maximum lifespan. In the budding yeast Saccharomyces cerevisiae, calorie restriction extends lifespan by increasing the activity of Sir2 (ref. 1), a member of the conserved sirtuin family of NAD(+)-dependent protein deacetylases(2-6). Included in this family are SIR-2.1, a Caenorhabditis elegans enzyme that regulates lifespan(7), and SIRT1, a human deacetylase that promotes cell survival by negatively regulating the p53 tumour suppressor(8-10). Here we report the discovery of three classes of small molecules that activate sirtuins. We show that the potent activator resveratrol, a polyphenol found in red wine, lowers the Michaelis constant of SIRT1 for both the acetylated substrate and NAD(+), and increases cell survival by stimulating SIRT1-dependent deacetylation of p53. In yeast, resveratrol mimics calorie restriction by stimulating Sir2, increasing DNA stability and extending lifespan by 70%. We discuss possible evolutionary origins of this phenomenon and suggest new lines of research into the therapeutic use of sirtuin activators. |
| Document Type: Article |
| Language: English |
| Reprint Address: Sinclair, DA (reprint author), Harvard Univ, Sch Med, Dept Pathol, 200 Longwood Ave, Boston, MA 02115 USA |
Addresses:
1. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
2. BIOMOL Res Labs Inc, Plymouth Meeting, PA 19462 USA |
| Publisher: NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: 719ZT |
| ISSN: 0028-0836 |
| DOI: 10.1038/nature01960 |
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