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Am J Physiol Regul Integr Comp Physiol 289: R1392-R1399, 2005. First published July 14, 2005; doi:10.1152/ajpregu.00834.2004
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ENVIRONMENTAL, EXERCISE AND RESPIRATORY PHYSIOLOGY

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

Ana Navarro,1 Carmen Gómez,1 María-Jesús Sánchez-Pino,1 Hipólito González,1 Manuel J. Bández,1 Alejandro D. Boveris,2 and Alberto Boveris2

1Department of Biochemistry and Molecular Biology, School of Medicine, University of Cádiz, Spain; and 2Laboratory of Free Radical Biology, School of Pharmacy and Biochemistry, University of Buenos Aires, Buenos Aires, Argentina

Submitted 13 December 2004 ; accepted in final form 7 July 2005

Male mice receiving vitamin E (5.0 g {alpha}-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 {alpha}-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 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 life span.

mitochondrial nitric oxide synthase; mitochondrial respiration; complex I; complex IV; oxidative damage


Address for reprint requests and other correspondence: A. Navarro, Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Plaza Fragela 9, 11003 Cádiz, Spain (e-mail: ana.navarro{at}uca.es)




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