Deficiency of the lipid synthesis enzyme, DGAT1, extends longevity in mice.

Authors: Streeper RS; Grueter CA; Salomonis N; Cases S; Levin MC; Koliwad SK; Zhou P; Hirschey MD; Verdin E; Farese RV Jr

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.

Keywords: Adipose Tissue/physiology; Aging/metabolism; Animals; Body Composition; Bone Density/genetics/physiology; Caloric Restriction; Diacylglycerol O-Acyltransferase/deficiency/genetics/*metabolism; Energy Metabolism/genetics/physiology; Female; Fertility; Gene Expression Profiling; Gene Expression Regulation; Genotype; Litter Size; Longevity/*genetics/*physiology; Mice; Mice, Knockout; Thinness/enzymology/metabolism
Journal: Aging
Volume: 4
Issue: 1
Pages: 13-27
Date: Feb. 1, 2012
PMID: 22291164
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Streeper RS, Grueter CA, Salomonis N, Cases S, Levin MC, Koliwad SK, Zhou P, Hirschey MD, Verdin E, Farese RV Jr (2012) Deficiency of the lipid synthesis enzyme, DGAT1, extends longevity in mice. Aging 4: 13-27.

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