Scientists question whether oxidative damage really is the guilty party in aging

Oxidative damage may not be the major culprit in aging, according to researchers in London.

Free radical damage has long been considered a major cause of molecular damage, thus playing an important role in the aging process. And the belief that protecting against free radical damage may help to slow the aging process is reflected in the quantity of anti-aging products on the market that advertise their anti-oxidant properties.

However, researchers at University College London suggest that their work on the aging of the nematode worm (C. elegans) may call into question the universal acceptance of this theory.

Dr David Gems and his team investigated the effect of knocking out genes that code for superoxide dismutase enzyme (SOD) – an enzyme that helps to protect the organism against free radical damage.

Removing SOD doesn’t affect lifespan

If SOD helps to reduce the presence of the superoxide anion, it should protect the organism from free radical damage. Removing SOD should, therefore, lead to an increased free radical load, accelerate aging and ultimately shorten the worm’s lifespan.

According to the researchers, however, this was not the case. The scientists knocked out 5 SOD genes and only one had a shortening effect on the worm’s lifespan, and even this effect was very slight, they argued.

Over expression of the same gene (SOD-1) did increase lifespan slightly, which according to the scientists implies a ‘small contributory role of the superoxide anion to aging’.

From the study, published in the journal Genes and Development, the researchers conclude: “SOD and superoxide anion have, at most, minor effects on aging in C. elegans.”

Relevance to humans?

Nevertheless, it is not clear what this means for higher organisms such as humans, particularly in light of the different effects that altering the SOD gene expression is known to have in the nematode worm, the mouse and the drospohila.

Gems argues that, amongst other things, the research highlights our lack of knowledge when it comes to the mechanisms of aging.

“The fact is that we don't understand much about the fundamental mechanisms of aging,” he said. “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.”

For Dr Gems, oxidative damage is not the universal culprit in the aging process; instead he suggests other factors must be involved.

“One of the hallmarks of aging is the accumulation of molecular damage, but what causes this damage?” he said.

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 ageing process. Other factors, such as chemical reactions involving sugars in our body, clearly play a role.”

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