Researchers have long known that 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. Now scientists have found a gene in mice that allows them to live longer without active calorie restriction.
Calorie restriction results in leanness, which is linked to metabolic conditions that favor longevity. Scientists at the Gladstone Institute of Cardiovascular Disease have now shown that deficiency of the triglyceride synthesis enzyme acyl CoA:diacylglycerol acyltransferase 1 (DGAT1), which promotes leanness, also extends longevity without limiting food intake.
In the study, 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.
According to the researchers:
Our findings show that deletion of the TG synthesis enzyme, DGAT1, promotes leanness and extends lifespan in female mice and therefore suggests a link between murine lipid metabolism and longevity. These results are consistent with a study linking lipid metabolism and longevity in Caenorhabditis elegans, where activation of lipid hydrolysis resulted in decreased fat mass and extended lifespan [*]. We presume that the effects of DGAT1 deficiency are the result of reduced TG and related lipid metabolites in tissues. However, notably, DGAT1 has several biochemical activities [^], and we therefore cannot exclude the possibility that changes in other DGAT1-associated pathways contribute to these effects.
...Our findings suggest that inhibition of DGAT1, or other strategies to promote leanness, may have the potential to retard age-related metabolic disease and prolong lifespan in humans.
AGING Journal
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