Aging
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Research Paper|Volume 4, Issue 1|pp 13—27

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

Ryan S. Streeper1,3,*, Carrie A. Grueter1,*, Nathan Salomonis1, Sylvaine Cases1, Malin C. Levin1, Suneil K. Koliwad1,3,4, Ping Zhou1, Matthew D. Hirschey2, Eric Verdin2,4, Robert V. Farese Jr.1,3,4,5
  • 1Gladstone Institute of Cardiovascular Disease, San Francisco, California, USA
  • 2Gladstone Institute of Virology and Immunology, San Francisco, California, USA
  • 3Cardiovascular Research Institute, San Francisco, California, USA
  • 4Department of Medicine, University of California, San Francisco, California, USA
  • 5Departments of Biochemistry and Biophysics, University of California, San Francisco, California, USA

* Equal contribution

Received: January 22, 2012Accepted: January 28, 2012Published: January 29, 2012

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-aged Dgat1−/− 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.