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Published Online November 6, 2003
Science DOI: 10.1126/science.1088697

Reports

Submitted on July 2, 2003
Accepted on October 23, 2003

Yeast Life-Span Extension by Calorie Restriction Is Independent of NAD Fluctuation

Rozalyn M. Anderson 1, Magda Latorre-Esteves 1, Ana Rute Neves 2, Siva Lavu 3, Oliver Medvedik 1, Christopher Taylor 4, Konrad T. Howitz 4, Helena Santos 2, David A. Sinclair 1*

1 Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston MA 02115, USA.
2 Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa, Rua da Quinta Grande 6, Apartado 127, 2780-156 OEIRAS, Portugal.
3 Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston MA 02115, USA; Biomol Research Laboratories, Inc., 5120 Butler Pike, Plymouth Meeting, PA 19462, USA.
4 Biomol Research Laboratories, Inc., 5120 Butler Pike, Plymouth Meeting, PA 19462, USA.

* To whom correspondence should be addressed. E-mail: David_Sinclair{at}hms.harvard.edu.

Calorie restriction (CR) slows aging in numerous species. In the yeast S. cerevisiae, this effect requires Sir2, a conserved NAD+-dependent deacetylase. We report that CR reduces nuclear NAD+levels in vivo. Moreover, the activity of Sir2 and its human homologue SIRT1 are not affected by physiological alterations in the NAD+:NADH ratio. These data implicate alternate mechanisms of Sir2 regulation by CR.


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