• Open Access

Sirtuin-independent effects of nicotinamide on lifespan extension from calorie restriction in yeast

Authors



Brian K. Kennedy, Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. Tel.: 206 543 4849; fax: 206 543 3644; e-mail: bkenn@u.washington.edu
Matt Kaeberlein, Department of Pathology, University of Washington, Seattle, WA 98195, USA. Tel.: 206 543 4849; fax: 206 543 3644; e-mail: kaeber@u.washington.edu

Summary

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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