Authors: Tsuchiya M; Dang N; Kerr EO; Hu D; Steffen KK; Oakes JA; Kennedy BK; Kaeberlein M
Abstract: Two models have been proposed for how calorie restriction (CR) enhances replicative longevity in yeast: (i) suppression of rDNA recombination through activation of the sirtuin protein deacetylase Sir2 or (ii) decreased activity of the nutrient-responsive kinases Sch9 and TOR. We report here that CR increases lifespan independently of all Sir2-family proteins in yeast. Furthermore, we demonstrate that nicotinamide, an inhibitor of Sir2-mediated deacetylation, interferes with lifespan extension from CR, but does so independent of Sir2, Hst1, Hst2, and Hst4. We also find that 5 mm nicotinamide, a concentration sufficient to inhibit other sirtuins, does not phenocopy deletion of HST3. Thus, we propose that lifespan extension by CR is independent of sirtuins and that nicotinamide has sirtuin-independent effects on lifespan extension by CR.Keywords: Acetylation/drug effects; Aging/drug effects/*physiology; Caloric Restriction; Cell Aging/drug effects/physiology; Cell Division/drug effects/physiology; Food Deprivation/*physiology; Histone Deacetylases/genetics/*metabolism; Longevity/drug effects/*physiology; Niacinamide/*metabolism/pharmacology; Saccharomyces cerevisiae/drug effects/*metabolism; Saccharomyces cerevisiae Proteins/genetics/metabolism; Silent Information Regulator Proteins, Saccharomyces cerevisiae/*metabolism; Sirtuin 2; Sirtuins/*metabolism
Journal: Aging cell
Date: Nov. 30, 2006
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Tsuchiya M, Dang N, Kerr EO, Hu D, Steffen KK, Oakes JA, Kennedy BK, Kaeberlein M (2006) Sirtuin-independent effects of nicotinamide on lifespan extension from calorie restriction in yeast. Aging cell 5: 505-14.