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. 2006 Dec;5(6):505-14.
doi: 10.1111/j.1474-9726.2006.00240.x.

Sirtuin-independent Effects of Nicotinamide on Lifespan Extension From Calorie Restriction in Yeast

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Sirtuin-independent Effects of Nicotinamide on Lifespan Extension From Calorie Restriction in Yeast

Mitsuhiro Tsuchiya et al. Aging Cell. .
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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.

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