Sirtuin-independent effects of nicotinamide on lifespan extension from calorie restriction in yeast.
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.
Tsuchiya
Mitsuhiro
M
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Dang
Nick
N
Kerr
Emily O
EO
Hu
Di
D
Steffen
Kristan K
KK
Oakes
Jonathan A
JA
Kennedy
Brian K
BK
Kaeberlein
Matt
M
D000107:Acetylation / Q000187:drug effects; D000375:Aging / Q000187:drug effects / Q000502:physiology*; D031204:Caloric Restriction; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology; D005508:Food Deprivation / Q000502:physiology*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D008136:Longevity / Q000187:drug effects / Q000502:physiology*; D009536:Niacinamide / Q000378:metabolism* / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000378:metabolism*; D056565:Sirtuin 2; D037761:Sirtuins / Q000378:metabolism*
D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D009536:Niacinamide; C103934:HST1 protein, S cerevisiae; C423033:HST2 protein, S cerevisiae; C512517:Hst3 protein, S cerevisiae; C512518:Hst4 protein, S cerevisiae; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D006655:Histone Deacetylases