title: The Caenorhabditis elegans nicotinamidase PNC-1 enhances survival.
abstract: In yeast, increasing the copy number of the nicotinamide adenine dinucleotide (NAD)-dependent deacetylase Sir2 extends lifespan, which can be inhibited by nicotinamide (Nam), the end-product of Sir2-mediated NAD-breakdown. Furthermore, the yeast pyrazinamidase/nicotinamidase PNC-1 can extend yeast lifespan by converting Nam. In Caenorhabditis elegans (C. elegans), increased dosage of the gene encoding SIR-2.1 also increases lifespan. Here, we report that knockdown of the C. elegans homologue of yeast PNC-1 as well as growing worms on Nam-containing medium significantly decreases adult lifespan. Accordingly, increased gene dosage of pnc-1 increases adult survival under conditions of oxidative stress. These data show for the first time the involvement of PNC-1/Nam in the survival of a multicellular organism and may also contribute to our understanding of lifespan regulation in mammals.
authors.affiliation: Department of Physiological Chemistry, Centre for Biomedical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands. A.A.vanderHorst-2@umcutrecht.nl
authors.forename: Armando
authors.initials: A
authors.lastname: van der Horst
authors.forename: Jolanda M
authors.initials: JM
authors.lastname: Schavemaker
authors.forename: Wendy
authors.initials: W
authors.lastname: Pellis-van Berkel
authors.forename: Boudewijn M T
authors.initials: BM
authors.lastname: Burgering
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000254:growth & development*; D008136:Longevity / Q000502:physiology*; D009536:Niacinamide / Q000378:metabolism; D009535:Nicotinamidase / Q000502:physiology*; D018384:Oxidative Stress / Q000502:physiology
chemical_list: D009536:Niacinamide; D009535:Nicotinamidase