Accepted on July 7, 2005
Vitamin E at high doses improves survival, neurological performance and brain mitochondrial function in aging male mice
Ana Navarro1*, Carmen Gomez1, Maria-Jesus Sanchez-Pino1, Hipolito Gonzalez1, Manuel J Bandez1, Alejandro D Boveris2, and Alberto Boveris21 Department of Biochemistry and Molecular Biology, School of Medicine, University of Cadiz, 11003-Cadiz, Spain
2 Laboratory of Free Radical Biology, School of Pharmacy and Biochemistry, University of Buenos Aires, C1113AAD-Buenos Aires, Argentina
* To whom correspondence should be addressed. E-mail: ana.navarro@uca.es .
Male mice receiving vitamin E (5.0 g 
-tocopherol acetate/kg of food) from 28 wk of age showed a 40 % increased median lifespan, from 61 ± 4 wk to 85 ± 4 wk, and 17 % increased maximal lifespan, whereas female mice equally supplemented exhibited only 14 % increased median lifespan. The -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 considered time points. The activities of mtNOS and Mn-SOD decreased 28-67 % upon aging and these effects were partially (41-68 %) prevented by vitamin E treatment. Liver mitochondrial activities showed similar effects of aging and of vitamin E supplementation, although less marked. Brain mitochondrial enzymatic activities correlated negatively with the mitochondrial content of protein and lipid oxidation products (r2 = 0.58-0.99, p < 0.01), and the rates of respiration and of complex I and IV activities correlated positively (r2 = 0.74-0.80, p < 0.01) with success in the behavioral tests and with maximal lifespan.