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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
https://doi.org/10.18632/aging.100424

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.