Research Paper Volume 4, Issue 1 pp 13—27
Deficiency of the lipid synthesis enzyme, DGAT1, extends longevity in mice
- 1 Gladstone Institute of Cardiovascular Disease, San Francisco, California, USA
- 2 Gladstone Institute of Virology and Immunology, San Francisco, California, USA
- 3 Cardiovascular Research Institute, San Francisco, California, USA
- 4 Department of Medicine, University of California, San Francisco, California, USA
- 5 Departments of Biochemistry and Biophysics, University of California, San Francisco, California, USA
Received: January 22, 2012 Accepted: January 28, 2012 Published: January 29, 2012
https://doi.org/10.18632/aging.100424How to Cite
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.