Yeast life-span extension by calorie restriction is independent of NAD fluctuation

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.