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 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 tight-rope (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.
Navarro
Ana
A
Department of Biochemistry and Molecular Biology, School of Medicine, University of Cádiz, Spain. ana.navarro@uca.es
Gómez
Carmen
C
Sánchez-Pino
María-Jesús
MJ
González
Hipólito
H
Bández
Manuel J
MJ
Boveris
Alejandro D
AD
Boveris
Alberto
A
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000032:analysis / Q000378:metabolism*; D001522:Behavior, Animal / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism; D005106:Exploratory Behavior; D005260:Female; D008099:Liver / Q000378:metabolism; D008136:Longevity; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008928:Mitochondria / Q000201:enzymology*; D009043:Motor Activity; D009245:NADH Dehydrogenase / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010101:Oxygen Consumption; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis / Q000378:metabolism; D024502:alpha-Tocopherol / Q000032:analysis / Q000378:metabolism*
D000975:Antioxidants; D017392:Thiobarbituric Acid Reactive Substances; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D009245:NADH Dehydrogenase; D003576:Electron Transport Complex IV; D024502:alpha-Tocopherol