Open AccessSirtuin‐independent effects of nicotinamide on lifespan extension from calorie restriction in yeast
Author(s) -
Tsuchiya Mitsuhiro,
Dang Nick,
Kerr Emily O.,
Hu Di,
Steffen Kristan K.,
Oakes Jonathan A.,
Kennedy Brian K.,
Kaeberlein Matt
Publication year - 2006
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/j.1474-9726.2006.00240.x
Subject(s) - sirtuin , calorie restriction , nicotinamide , biology , longevity , sirtuin 1 , acetylation , yeast , nad+ kinase , phenocopy , genetics , microbiology and biotechnology , biochemistry , gene , endocrinology , enzyme , phenotype , downregulation and upregulation
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 m m 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.