High doses of vitamin E boost rat survival rate 40%; brain function, neuromuscul

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http://www.eurekalert.org/pub_releases/2005-09/aps-hdo083105.php

 

Public release date: 2-Sep-2005

 

 

 

Contact: Mayer Resnick

mresnick

301-634-7209 (office)

301-332-4402 (cell)

American Physiological Society

 

 

 

 

High doses of vitamin E boost rat survival rate 40%; brain function,

neuromuscular gains

BETHESDA, Md. (Sept. 4, 2005) – Studying how much longer and " better "

mice will live on high doses of vitamin E involves much time and work

– two years of feeding, testing and studying. But based on earlier

results, a joint team from the University of Cadiz, Spain, and the

University of Buenos Aires, Argentina, figured the payoff would be

worth the effort.

 

Their just-published paper shows that using vitamin E supplementation

physiologically comparable to recent human experiments in Alzheimer's

Disease patients, resulted in these major findings:

 

* male mice showed a 40% increase in median lifespan (to 85 ± 4

weeks from 61 ± 4).

 

* 17% increase in maximal lifespan (to 136 weeks from 116 weeks).

 

* increases in the ability to perform tests measuring

neuromuscular performance (high-wire tightrope) and cognitive

exploratory activity (T-maze); the increases on both tests ranged

9%-24% at 52 weeks, and 28%-45% at 78 weeks of age.

 

* brain alpha-tocopherol content increased 2.5-fold in male mice

taking vitamin E.

 

* vitamin E supplementation offset various measures of

mitochondrial function loss in a range of 37%-66% at the 52- and

78-week test points.

 

* all results were significant to a greater than 99% confidence level.

 

The paper " Vitamin E at high doses improves survival, neurological

performance and brain mitochondrial function in aging male mice "

appears online in the American Journal of Physiology-Regulatory,

Integrative and Comparative Physiology, published by the American

Physiological Society. Research was by Ana Navarro, Carmen Gomez,

Maria-Jesus Sanchez-Pino, Hipolito Gonzalez and Manuel J. Bandez of

the University of Cadiz, Spain, and Alejandro D. Boveris and Alberto

Boveris of the University of Buenos Aires.

 

Results seen supporting 'free radical' theory of aging

 

Alberto Boveris, professor at the University of Buenos Aires, said the

results of these extended experiments " are in line with the free

radical theory of aging put forward by Gerschman and Harman in the

1950s. Our results show a significant negative correlation between the

mitochondrial content of the oxidation products of free-radical

mediated reactions and mitochondrial enzymatic activities.

 

" Moreover, brain mitochondrial enzymatic activities were linearly

related to mice success in the tests of neuromuscular function and of

exploratory and cognitive activity and to the maximal mice life span, "

Boveris reported. He noted that the amount of vitamin E

supplementation was metabolically and physiologically similar to the

1200-2000mg. daily dosage for two to three years used in two

Alzheimer's Disease experiments involving over 400 patients without

adverse effects.

 

The paper observes that the " study shows the beneficial effects of

high doses of vitamin E on the median and maximal lifespan of male

mice, an effect that is parallel to a beneficial effect on the decline

of neurological performance and mitochondrial function associated with

aging. " It said the " marked increase " in median lifespan and the

moderate rise of maximal lifespan " is properly described as a delay in

the onset of the almost linear decay in mice survival. "

 

The mice used in the experiment, the CD-1/UCadiz, are a senescence

accelerated strain with a median lifespan of 60-70 weeks and maximal

lifespan of 100-120 weeks. Vitamin E supplementation of the test group

began at age 28 weeks.

 

Role of vitamin E as antioxidant; support for 'specificity' concept

 

The researchers noted that the " mitochondrial content of lipid protein

oxidation products, an indication of free-radical mediated reactions

and oxidative damage, was increased in the brain and liver of aging

mice, and the effect was partially [and significantly] prevented by

vitamin E. The protein carbonyl content of brain mitochondria, taking

28-week-old mice as reference, increased 33%-69% at 52 and 76 weeks,

and this increase was markedly prevented (76% and 65%) by vitamin E

supplementation " measured at the two age points.

 

Vitamin E supplementation was " able to prevent the decrease in the

activities of brain enzymes that are mitochondrial markers of aging:

mtNOS (by 95%), Mn-SOD (by 60%), and NADH-cytochrome c reductase and

cytochrome oxidase activity " by 35%, the paper said

 

" The activities of the inner membrane bound mtNOS and of the matrix

enzyme MnSOD in brain and liver mitochondria also decreased upon

aging, in agreement with earlier reports and with the concept of

specificity rather than randomness in the inactivation of mitrondrial

enzymes, " according to the paper. " The activity of mtNOS was decreased

by 44%-66% and Mn-SOD by 28%-50% at 52-78 weeks of mice age, effects

that were markedly prevented by vitamin E supplementation, " it added.

 

Clues to mitochondrial dysfunction -- and next steps

 

Finally, the authors noted two " interesting correlations " : The first

is the inverse relationship between oxidative damage and enzymatic

activities in the brain and liver, " which are due to oxidized and

damaged proteins, and not to a direct inhibitory effect of lipid

oxidation products (ie., malonaldehyde) due to the high dilution of

the enzymes in the assays " where the reduced rates occurred. The

second correlation shows " that decreased electron transfer rates and

limited respiration and energy supply are the basis of the

mitochondrial dysfunction in aging and that mitochondrial dysfunction

is the pacemaker of the decline in neurological performances which has

a determinant role in survival. "

 

# Further studies are needed to find the threshold for vitamin E

" doses that provide beneficial effects in the neurological function in

aging mammals, " the study noted.

 

# Boveris said the team has completed studies on the role of calorie

reduction (CR), " which could yield interesting results especially in

comparison with similar, but much longer, rhesus monkey studies being

carried out by Richard Weindruch at the University of

Wisconsin-Madison on CR and oxidative stress. "

 

###

 

Source and funding

 

The paper " Vitamin E at high doses improves survival, neurological

performance and brain mitochondrial function in aging male mice "

appears in the online edition of the American Journal of Physiology-

Regulatory, Integrative and Comparative Physiology, published by the

American Physiological Society. Research was by Ana Navarro, Carmen

Gomez, Maria-Jesus Sanchez-Pino, Hipolito Gonzalez and Manuel J.

Bandez of the Department of Biochemistry and Molecular Biology, School

of Medicine, University of Cadiz, Spain; and Alejandro D. Boveris and

Alberto Boveris of the Laboratory of Free Radical Biology, School of

Pharmacy and Biochemistry, University of Buenos Aires, Argentina.

 

Research was supported by grants from Ministerio de Sanidad y Consumo

de España, and by Plan Andaluz de Investigación.

 

Editor's note: The media may obtain a copy of Navarro et al. by

contacting Mayer Resnick, American Physiological Society,

301.634.7209, cell 301.332.4402 or mresnick.

 

The American Physiological Society was founded in 1887 to foster basic

and applied bioscience. The Bethesda, Maryland-based society has more

than 10,000 members and publishes 14 peer-reviewed journals containing

almost 4,000 articles annually.

 

APS provides a wide range of research, educational and career support

and programming to further the contributions of physiology to

understanding the mechanisms of diseased and healthy states. In May

2004, APS received the Presidential Award for Excellence in Science,

Mathematics and Engineering Mentoring (PAESMEM).