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.
MeSH terms
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Acetylation / drug effects
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Aging / drug effects
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Aging / physiology*
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Caloric Restriction
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Cell Division / drug effects
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Cell Division / physiology
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Cellular Senescence / drug effects
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Cellular Senescence / physiology
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Food Deprivation / physiology*
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Histone Deacetylases / genetics
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Histone Deacetylases / metabolism*
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Longevity / drug effects
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Longevity / physiology*
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Niacinamide / metabolism*
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Niacinamide / pharmacology
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Saccharomyces cerevisiae / drug effects
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Saccharomyces cerevisiae / metabolism*
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism
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Silent Information Regulator Proteins, Saccharomyces cerevisiae / metabolism*
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Sirtuin 2
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Sirtuins / metabolism*
Substances
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Saccharomyces cerevisiae Proteins
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Silent Information Regulator Proteins, Saccharomyces cerevisiae
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Niacinamide
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HST1 protein, S cerevisiae
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HST2 protein, S cerevisiae
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Hst3 protein, S cerevisiae
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Hst4 protein, S cerevisiae
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SIR2 protein, S cerevisiae
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Sirtuin 2
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Sirtuins
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Histone Deacetylases