title: Deficiency of the lipid synthesis enzyme, DGAT1, extends longevity in mice.
abstract: Calorie restriction results in leanness, which is linked to metabolic conditions that favor longevity. We show here that deficiency of the triglyceride synthesis enzyme acyl CoA:diacylglycerol acyltransferase 1 (DGAT1), which promotes leanness, also extends longevity without limiting food intake. Female DGAT1-deficient mice were protected from age-related increases in body fat, tissue triglycerides, and inflammation in white adipose tissue. This protection was accompanied by increased mean and maximal life spans of ~25% and ~10%, respectively. Middle-agedDgat1-/- mice exhibited several features associated with longevity, including decreased levels of circulating insulin growth factor 1 (IGF1) and reduced fecundity. Thus, deletion of DGAT1 in mice provides a model of leanness and extended lifespan that is independent of calorie restriction.
authors.affiliation: Gladstone Institute of Cardiovascular Disease, San Francisco, California, USA.
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Streeper
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Grueter
authors.forename: Nathan
authors.initials: N
authors.lastname: Salomonis
authors.forename: Sylvaine
authors.initials: S
authors.lastname: Cases
authors.forename: Malin C
authors.initials: MC
authors.lastname: Levin
authors.forename: Suneil K
authors.initials: SK
authors.lastname: Koliwad
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.forename: Mattew D
authors.initials: MD
authors.lastname: Hirschey
authors.forename: Eric
authors.initials: E
authors.lastname: Verdin
authors.forename: Robert V
authors.initials: RV
authors.lastname: Farese
mesh_terms: D000273:Adipose Tissue / Q000502:physiology; D000375:Aging / Q000378:metabolism; D000818:Animals; D001823:Body Composition; D015519:Bone Density / Q000235:genetics / Q000502:physiology; D031204:Caloric Restriction; D051048:Diacylglycerol O-Acyltransferase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology; D005260:Female; D005298:Fertility; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005838:Genotype; D008098:Litter Size; D008136:Longevity / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D013851:Thinness / Q000201:enzymology / Q000378:metabolism
chemical_list: C494882:Dgat1 protein, mouse; D051048:Diacylglycerol O-Acyltransferase