Project description:Leanness is associated with increased lifespan and is linked to favorable metabolic conditions promoting life extension. We show here that deficiency of the lipid synthesis enzyme acyl CoA:diacylglycerol acyltransferase 1 (DGAT1), which reduces body fat in mice, promotes longevity. Female DGAT1-deficient mice were protected from age-related increases in body fat, non-adipose tissue triglycerides, and markers of inflammation in white adipose tissue. These metabolic changes were accompanied by an increased mean and maximal lifespan of ~25% and ~10%, respectively. The gene expression profile of DGAT1-deficient mice was not highly correlated with calorie restriction of sex and age matched wild-type littermates. Our findings indicate that loss of DGAT1-mediated lipid synthesis results in leanness, protects against age-related metabolic consequences, and thus extends longevity. Liver gene expression profiles between short-term calorie restricted wild-type (WTCR) and Dgat1 deficient (KO) middle-aged (15-16 mo) female mice were compared to determine if calorie restriction and Dgat1 deficiency rely on common regulatory pathways for the promotion of longevity. Both CR and KO were compared to middle-aged wild-type female littermates fed a standard chow diet ad libitum (WTAL).
Project description:Leanness is associated with increased lifespan and is linked to favorable metabolic conditions promoting life extension. We show here that deficiency of the lipid synthesis enzyme acyl CoA:diacylglycerol acyltransferase 1 (DGAT1), which reduces body fat in mice, promotes longevity. Female DGAT1-deficient mice were protected from age-related increases in body fat, non-adipose tissue triglycerides, and markers of inflammation in white adipose tissue. These metabolic changes were accompanied by an increased mean and maximal lifespan of ~25% and ~10%, respectively. The gene expression profile of DGAT1-deficient mice was not highly correlated with calorie restriction of sex and age matched wild-type littermates. Our findings indicate that loss of DGAT1-mediated lipid synthesis results in leanness, protects against age-related metabolic consequences, and thus extends longevity.
Project description:The effect of a short-term calorie restricted diet was evaluated in six strains of mice The dietary intervention was initiated at 8 weeks of age and continued until 22 weeks of age Tissues were collected from mice at 22 weeks of age; there were 96 microarrays used in total: for each of the 6 strains of mice, there were 8 control-fed mice and 8 calorie restricted mice (one individual mouse per microarray)
Project description:The effect of a short-term calorie restricted diet was evaluated in six strains of mice The dietary intervention was initiated at 8 weeks of age and continued until 22 weeks of age
Project description:The effect of a short-term calorie restricted diet was evaluated in heart in seven strains of mice The dietary intervention was initiated at 8 weeks of age and continued until 22 weeks of age
Project description:The effect of a short-term calorie restricted diet was evaluated in cerebral cortex in seven strains of mice The dietary intervention was initiated at 8 weeks of age and continued until 22 weeks of age
Project description:The effect of a short-term calorie restricted diet was evaluated in gastrocnemius muscle (GASTROC) in seven strains of mice The dietary intervention was initiated at 8 weeks of age and continued until 22 weeks of age
Project description:The effect of a short-term calorie restricted diet was evaluated in epididymal white adipose tissue (WAT) in seven strains of mice The dietary intervention was initiated at 8 weeks of age and continued until 22 weeks of age
