X-Message-Number: 31385
Date: Sat, 14 Feb 2009 10:05:36 -0800 (PST)
From: 
Subject: Antioxidants Are Unlikely To Prevent Aging, Study Suggests

[Results from tests in nematodes, rodents and even humans all point to
the Free Radical Theory of Aging being false. IMHO, the popularity of
this false theory looks to be the single biggest roadblock preventing the
true causes of aging being uncovered. Proving the Free Radical Theory of
Aging is correct, despite all the negative results has absorbed for far
too long, far too much of the limited budget for aging research.]

Antioxidants Are Unlikely To Prevent Aging, Study Suggests

ScienceDaily (Dec. 2, 2008) Diets and beauty products which claim to have 
anti-oxidant properties are unlikely to prevent aging, according to research 
funded by the Wellcome Trust. Researchers at the Institute of Healthy aging at 
UCL (University College London) say this is because a key fifty year old theory 
about the causes of aging is wrong.


"Superoxide" free radicals" oxygen molecules that have an imbalance of electrons
to protons" are generated in the body through natural processes such as 
metabolism. These free radicals can cause oxidation in the body, analogous to 
rust when iron is exposed to oxygen. Biological systems, such as the human body,
are usually able to restrict or repair this damage.

In 1956, Denham Harman proposed the theory that aging is caused by an 
accumulation of molecular damage caused by "oxidative stress", the action of 
reactive forms of oxygen, such as superoxide, on cells. This theory has 
dominated the field of aging research for over fifty years. But now, a study 
published online today in the journal Genes & Development suggests that this 
theory is probably incorrect and that superoxide is not a major cause of aging.

"The fact is that we don't understand much about the fundamental mechanisms of 
aging," says Dr David Gems from UCL. "The free radical theory of aging has 
filled a knowledge vacuum for over fifty years now, but it just doesn't stand up
to the evidence."

Dr Gems and colleagues at the Institute of Healthy aging studied the action of 
key genes involved in removing superoxide from the bodies of the nematode worm 
C. elegans, a commonly-used model for research into aging. By manipulating these
genes, they were able to control the worm's ability to "mop up" surplus 
superoxide and limit potential damage caused by oxidation.

Contrary to the result predicted by the free radical theory of aging, the 
researchers found that the lifespan of the worm was relatively unaffected by its
ability to tackle the surplus superoxide. The findings, combined with similar 
recent findings from the University of Texas using mice, imply that this theory 
is incorrect.

"One of the hallmarks of aging is the accumulation of molecular damage, but what
causes this damage?" says Dr Gems. "It's clear that if superoxide is involved, 
it only plays a small part in the story. Oxidative damage is clearly not a 
universal, major driver of the aging process. Other factors, such as chemical 
reactions involving sugars in our body, clearly play a role."

Dr Gems believes the study suggests that anti-aging products which claim to have
anti-oxidant properties are unlikely to have any effect.

"A healthy, balanced diet is very important for reducing the risk of developing 
many diseases associated with old age, such as cancer, diabetes and 
osteoporosis," he says. "But there is no clear evidence that dietary 
antioxidants can slow or prevent aging. There is even less evidence to support 
the claims of most anti-aging products."

The research was welcomed by Dr Alan Schafer, Head of Molecular and 
Physiological Sciences at the Wellcome Trust.

"With increasing lifespan comes greater exposure and vulnerability to the aging 
process," comments Dr Schafer. "Research such as this points to how much we have
to learn about aging, and the importance of understanding the mechanisms behind
this process. This new study will encourage researchers to explore new avenues 
in aging research."

Journal reference:
Genes Dev. December 1, 2008 22:3236-3241; doi:10.1101/gad.504808

Against the oxidative damage theory of aging: superoxide dismutases protect 
against oxidative stress but have little or no effect on life span in 
Caenorhabditis elegans
Ryan Doonan1,3,
Joshua J. McElwee1,3,
Filip Matthijssens2,3,
Glenda A. Walker1,
Koen Houthoofd2,
Patricia Back2,
Andrea Matscheski1,
Jacques R. Vanfleteren2, and
David Gems1,4
+Author Affiliations

1 Institute of Healthy Ageing and Research Department of Genetics, Evolution and
Environment, University College London, London WC1E 6BT, United Kingdom;
2 Department of Biology, Ghent University, B-9000 Ghent, Belgium
a u3 These authors contributed equally to this work.
Abstract

The superoxide radical (O2a ') has long been considered a major cause of aging. 
O2a ' in cytosolic, extracellular, and mitochondrial pools is detoxified by 
dedicated superoxide dismutase (SOD) isoforms. We tested the impact of each SOD 
isoform in Caenorhabditis elegans by manipulating its five sod genes and saw no 
major effects on life span. sod genes are not required for daf-2 insulin/IGF-1 
receptor mutant longevity. However, loss of the extracellular Cu/ZnSOD sod-4 
enhances daf-2 longevity and constitutive diapause, suggesting a signaling role 
for sod-4. Overall, these findings imply that O2a ' is not a major determinant 
of aging in C. elegans.

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