Vitamin E at high doses improves survival, neurological performance, and brain mitochondrial function in aging male mice

Male mice receiving vitamin E (5.0 g α-tocopherol acetate/kg of food) from 28 wk of age showed a 40% increased median life span, from 61 ± 4 wk to 85 ± 4 wk, and 17% increased maximal life span, whereas female mice equally supplemented exhibited only 14% increased median life span. The α-tocopherol content of brain and liver was 2.5-times and 7-times increased in male mice, respectively. Vitamin E-supplemented male mice showed a better performance in the tightrope (neuromuscular function) and the T-maze (exploratory activity) tests with improvements of 9–24% at 52 wk and of 28–45% at 78 wk. The rates of electron transfer in brain mitochondria, determined as state 3 oxygen uptake and as NADH-cytochrome c reductase and cytochrome oxidase activities, were 16–25% and 35–38% diminished at 52–78 wk. These losses of mitochondrial function were ameliorated by vitamin E supplementation by 37–56% and by 60–66% at the two time points considered. The activities of mitochondrial nitric oxide synthase and Mn-SOD decrea...