Long-term intake of fish oil increases oxidative stress and decreases lifespan in senescence-accelerated mice

Objective: The effects of fish oil including ω-3 polyunsaturated fatty acids on aging and lifespan are not well understood. In this study, the influence of long-term ingestion of fish oil on lifespan was examined in senescence-accelerated (SAMP8) mice. Methods: We investigated the effects of dietary fish oil on lifespan and on lipid composition and oxidative stress in plasma and liver in SAMP8 mice. Male mice were fed a fish oil diet (5% fish oil and 5% safflower oil) or a safflower oil diet (10% safflower oil) from 12 wk of age. Results: The SAMP8 mice fed fish oil did not have a longer maximum lifespan and had a shorter average lifespan than mice fed safflower oil. To examine the mechanism underlying these results, the effects on oxidative stress of long-term ingestion of fish oil were also examined. SAMP8 mice fed fish oil for 28 wk showed strong oxidative stress that caused hyperoxidation of membrane phospholipids and a diminished antioxidant defense system due to a decrease in tocopherol compared with mice fed safflower oil. Conclusion: These findings suggest that intake of fish oil increases oxidative stress, decreases cellular function, and causes organ dysfunction in SAMP8 mice, thereby promoting aging and shortening the lifespan of the mice.