title: SirT1 regulates energy metabolism and response to caloric restriction in mice.
abstract: The yeast sir2 gene and its orthologues in Drosophila and C. elegans have well-established roles in lifespan determination and response to caloric restriction. We have studied mice carrying two null alleles for SirT1, the mammalian orthologue of sir2, and found that these animals inefficiently utilize ingested food. These mice are hypermetabolic, contain inefficient liver mitochondria, and have elevated rates of lipid oxidation. When challenged with a 40% reduction in caloric intake, normal mice maintained their metabolic rate and increased their physical activity while the metabolic rate of SirT1-null mice dropped and their activity did not increase. Moreover, CR did not extend lifespan of SirT1-null mice. Thus, SirT1 is an important regulator of energy metabolism and, like its orthologues from simpler eukaryotes, the SirT1 protein appears to be required for a normal response to caloric restriction.
authors.affiliation: Center for Cancer Therapeutics, Ottawa Health Research Institute, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Gino
authors.initials: G
authors.lastname: Boily
authors.forename: Erin L
authors.initials: EL
authors.lastname: Seifert
authors.forename: Lisa
authors.initials: L
authors.lastname: Bevilacqua
authors.forename: Xiao Hong
authors.initials: XH
authors.lastname: He
authors.forename: Guillaume
authors.initials: G
authors.lastname: Sabourin
authors.forename: Carmen
authors.initials: C
authors.lastname: Estey
authors.forename: Cynthia
authors.initials: C
authors.lastname: Moffat
authors.forename: Sean
authors.initials: S
authors.lastname: Crawford
authors.forename: Sarah
authors.initials: S
authors.lastname: Saliba
authors.forename: Karen
authors.initials: K
authors.lastname: Jardine
authors.forename: Jian
authors.initials: J
authors.lastname: Xuan
authors.forename: Meredith
authors.initials: M
authors.lastname: Evans
authors.forename: Mary-Ellen
authors.initials: ME
authors.lastname: Harper
authors.forename: Michael W
authors.initials: MW
authors.lastname: McBurney
mesh_terms: D000818:Animals; D002151:Calorimetry; D002149:Energy Intake; D004734:Energy Metabolism / Q000502:physiology*; D006728:Hormones / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D008930:Mitochondria, Liver / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D056564:Sirtuin 1; D037761:Sirtuins / Q000502:physiology*
chemical_list: D006728:Hormones; D017382:Reactive Oxygen Species; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D037761:Sirtuins