SirT1 regulates energy metabolism and response to caloric restriction in mice.
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.
Boily
Gino
G
Center for Cancer Therapeutics, Ottawa Health Research Institute, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Seifert
Erin L
EL
Bevilacqua
Lisa
L
He
Xiao Hong
XH
Sabourin
Guillaume
G
Estey
Carmen
C
Moffat
Cynthia
C
Crawford
Sean
S
Saliba
Sarah
S
Jardine
Karen
K
Xuan
Jian
J
Evans
Meredith
M
Harper
Mary-Ellen
ME
McBurney
Michael W
MW
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*
D006728:Hormones; D017382:Reactive Oxygen Species; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D037761:Sirtuins