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

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

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

Calorie restriction (CR) slows aging in numerous species. In the yeast Saccharomyces 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.