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

Am J Physiol Regul Integr Comp Physiol. 2005 Nov;289(5):R1392-9. doi: 10.1152/ajpregu.00834.2004. Epub 2005 Jul 14.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / metabolism*
  • Animals
  • Antioxidants / analysis
  • Antioxidants / metabolism*
  • Behavior, Animal / physiology*
  • Brain / metabolism*
  • Electron Transport Complex IV / metabolism
  • Exploratory Behavior
  • Female
  • Liver / metabolism
  • Longevity
  • Male
  • Mice
  • Mice, Inbred Strains
  • Mitochondria / enzymology*
  • Motor Activity
  • NADH Dehydrogenase / metabolism
  • Nitric Oxide Synthase / metabolism
  • Oxygen Consumption
  • Superoxide Dismutase / metabolism
  • Thiobarbituric Acid Reactive Substances / analysis
  • Thiobarbituric Acid Reactive Substances / metabolism
  • alpha-Tocopherol / analysis
  • alpha-Tocopherol / metabolism*


  • Antioxidants
  • Thiobarbituric Acid Reactive Substances
  • Nitric Oxide Synthase
  • Superoxide Dismutase
  • NADH Dehydrogenase
  • Electron Transport Complex IV
  • alpha-Tocopherol