Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
HST2 Mediates SIR2-Independent Life-Span Extension by Calorie Restriction
Dudley W. Lamming,1*Magda Latorre-Esteves,1*Oliver Medvedik,1*Stacy N. Wong,2*Felicia A. Tsang,2Chen Wang,2Su-Ju Lin,2David A. Sinclair1
Calorie restriction (CR) extends the life span of numerous species,from yeast to rodents. Yeast Sir2 is a nicotinamide adeninedinucleotide (NAD+-dependent histone deacetylase that has beenproposed to mediate the effects of CR. However, this hypothesishas been challenged by the observation that CR can extend yeastlife span in the absence of Sir2. Here, we show that Sir2-independentlife-span extension is mediated by Hst2, a Sir2 homolog thatpromotes the stability of repetitive ribosomal DNA, the samemechanism by which Sir2 extends life span. These findings demonstratethat the maintenance of DNA stability is critical for yeastlife-span extension by CR and suggest that, in higher organisms,multiple members of the Sir2 family may regulate life span inresponse to diet.
1 Paul F. Glenn Laboratories for the Biological Mechanisms of Aging, Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. 2 Center for Genetics and Development, and Section of Microbiology, University of California Davis, 351 Briggs Hall, Davis, CA 95616, USA.
Published online 28 July 2005
Include this information when citing this paper.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: slin{at}ucdavis.edu (S.-J.L.), david_sinclair{at}hms.harvard.edu (D.A.S.)
The editors suggest the following Related Resources on Science sites:
In Science Magazine
TECHNICAL COMMENTS
Matt Kaeberlein, Kristan K. Steffen, Di Hu, Nick Dang, Emily O. Kerr, Mitsuhiro Tsuchiya, Stanley Fields, and Brian K. Kennedy (2 June 2006) Science312 (5778), 1312b.
[DOI: 10.1126/science.1124608] |Abstract »|Full Text »|PDF »
TECHNICAL COMMENTS
Dudley W. Lamming, Magda Latorre-Esteves, Oliver Medvedik, Stacy N. Wong, Felicia A. Tsang, Chen Wang, Su-Ju Lin, and David A. Sinclair (2 June 2006) Science312 (5778), 1312c.
[DOI: 10.1126/science.1124767] |Abstract »|Full Text »|PDF »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The malate-aspartate NADH shuttle components are novel metabolic longevity regulators required for calorie restriction-mediated life span extension in yeast.
E. Easlon, F. Tsang, C. Skinner, C. Wang, and S.-J. Lin (2008)
Genes & Dev.
22, 931-944
|Abstract »|Full Text »|PDF »
SIRT1 Acts as a Nutrient-sensitive Growth Suppressor and Its Loss Is Associated with Increased AMPK and Telomerase Activity.
S. R. Narala, R. C. Allsopp, T. B. Wells, G. Zhang, P. Prasad, M. J. Coussens, D. J. Rossi, I. L. Weissman, and H. Vaziri (2008)
Mol. Biol. Cell
19, 1210-1219
|Abstract »|Full Text »|PDF »
Sirtuin Functions in Health and Disease.
H. Yamamoto, K. Schoonjans, and J. Auwerx (2007)
Mol. Endocrinol.
21, 1745-1755
|Abstract »|Full Text »|PDF »
The Dihydrolipoamide Acetyltransferase Is a Novel Metabolic Longevity Factor and Is Required for Calorie Restriction-mediated Life Span Extension.
E. Easlon, F. Tsang, I. Dilova, C. Wang, S.-P. Lu, C. Skinner, and S.-J. Lin (2007)
J. Biol. Chem.
282, 6161-6171
|Abstract »|Full Text »|PDF »
The role of protein arginine methylation in the formation of silent chromatin.
M. C. Yu, D. W. Lamming, J. A. Eskin, D. A. Sinclair, and P. A. Silver (2006)
Genes & Dev.
20, 3249-3254
|Abstract »|Full Text »|PDF »
Mammalian sirtuins--emerging roles in physiology, aging, and calorie restriction..
Comment on "HST2 Mediates SIR2-Independent Life-Span Extension by Calorie Restriction".
M. Kaeberlein, K. K. Steffen, D. Hu, N. Dang, E. O. Kerr, M. Tsuchiya, S. Fields, and B. K. Kennedy (2006)
Science
312, 1312b
|Abstract »|Full Text »|PDF »
Response to Comment on "HST2 Mediates SIR2-Independent Life-Span Extension by Calorie Restriction".
D. W. Lamming, M. Latorre-Esteves, O. Medvedik, S. N. Wong, F. A. Tsang, C. Wang, S.-J. Lin, and D. A. Sinclair (2006)
Science
312, 1312c
|Abstract »|Full Text »|PDF »
SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis.
A. Vaquero, M. B. Scher, D. H. Lee, A. Sutton, H.-L. Cheng, F. W. Alt, L. Serrano, R. Sternglanz, and D. Reinberg (2006)
Genes & Dev.
20, 1256-1261
|Abstract »|Full Text »|PDF »
Use of Substrate Analogs and Mutagenesis to Study Substrate Binding and Catalysis in the Sir2 Family of NAD-dependent Protein Deacetylases.
Regulation of Yeast Replicative Life Span by TOR and Sch9 in Response to Nutrients.
M. Kaeberlein, R. W. Powers III, K. K. Steffen, E. A. Westman, D. Hu, N. Dang, E. O. Kerr, K. T. Kirkland, S. Fields, and B. K. Kennedy (2005)
Science
310, 1193-1196
|Abstract »|Full Text »|PDF »
To whom correspondence should be addressed. E-mail: 
