Requirement of NAD and SIR2 for life-span extension by calorie restrictionin Saccharomyces cerevisiae

Calorie restriction extends Life-span in a wide variety of organisms. Altho ugh it has been suggested that calorie restriction may work by reducing the levels of reactive oxygen species produced during respiration. the mechani sm by which this regimen slows aging is uncertain. Here, we mimicked calori e restriction in yeast by physiological or genetic means and showed a subst antial extension in Life-span. This extension was not observed in strains m utant for SIR2 (which encodes the silencing protein Sir2p) or NPT1 (a gene in a pathway in the synthesis of NAD, the oxidized form of nicotinamide ade nine dinucleotide), These findings suggest that the increased longevity ind uced by calorie restriction requires the activation of Sir2p by NAD.