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Fish oil with calorie restriction improves survival and reduces liver PON1 expression in aging mice

Dietary modifications, like calorie‐restriction (CR) and n‐3 fatty acids (FA) supplementation, are widely utilized in animals and humans to improve health and lifespan. In this study, we investigated the effect of n‐3 fatty acids (fish oil: FO) vs n‐6 fatty acids (corn oil: CO), with and without CR on survival, serum metabolites, anti‐oxidative capacity, adipocyte pathology and left ventricular function. Four month old C57Bl/6J female mice were maintained on ad libitum (AL) or CR (40% less than AL) AIN‐93 diet supplemented with 6% corn oil (rich in n‐6 FA:CO/AL and CO/CR) or 1% CO plus 5% concentrated fish oil [(30/20:eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA)] (rich in n‐3 FA FO/AL and FO/CR) and also standard lab chow (LC) group for 16 months. At 20 months of age, we measured survival, serum metabolites, left ventricular function, liver anti‐oxidant enzymes (SOD, CAT) and paraoxonase 1 (PON1) expression. Results showed that FO/CR food intake prolongs lifespan, reduces triglycerides and decreases adipocyte cell size compared to FO/AL, CO/AL, CO/CR and standard diet in mice. We also noted left ventricular hypertrophy in CO/CR mice, but not in FO/CR mice. Furthermore, the longevity gene, PON1 expression was significantly lowered in liver of FO/CR mice, as compared to that of CO/AL, CO/CR, FO/AL and LC fed mice. These data suggest that n‐3 FA, along with CR is effective in prolonging lifespan and needs to be tested in humans.