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

Date Published: January 29, 2012

Publisher: Impact Journals LLC

Author(s): Ryan S. Streeper, Carrie A. Grueter, Nathan Salomonis, Sylvaine Cases, Malin C. Levin, Suneil K. Koliwad, Ping Zhou, Matthew D. Hirschey, Eric Verdin, Robert V. Farese.



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.

Partial Text

The amount of fat mass of an organism is emerging as key determinant in longevity. Too little or too much fat is associated with early mortality in rodents and humans, whereas leanness, intermediate with respect to these two extremes is associated with relative longevity, possibly reflecting an optimal amount of fat. The most effective intervention to promote leanness and increase lifespan is calorie restriction (CR) [1]. CR, with adequate nutrient intake, extends the lifespan of yeast, invertebrates (worm and fly) and mice [2-4], and is associated with favorable changes in energy metabolism [5]. However, CR requires markedly restricting food intake, which stimulates appetite and induces hunger, making CR difficult to maintain.