Mutant worms defy aging theory

Worms that were genetically modified by McGill University researchers not only survived exposure to a banned poison, they lived even longer than normal, challenging scientists' understanding of the aging process.

Montreal university's research contradicts long-held 'free radicals' explanation

Worms that were genetically modified by McGill University researchers not only survived exposure to a banned poison, they lived even longer than normal worms, challenging scientists' understanding of the aging process.

Dr. Siegfried Hekimi and his student Dr. Wen Yang, who are in the Montreal university's biology department, planned to test the so-called "free radical theory of aging" by genetically modifying wild worms in a lab to accelerate production of free radicals — toxic molecules generated as a byproduct of oxygen use.

McGill University researchers studied C. elegans worms, such as these, that were genetically modified with accelerated free radical production. ((Simon Fraser/Canadian Press))

The theory posits that aging is blamed on free radicals, as they lead to chemical reactions that deteriorate cells, thus leading to the changes in our bodies that result in aging and, eventually, death.

Although the theory has long been held as conventional wisdom by some, Hekimi said he "stands the theory on its head" by showing in his experiment that increasing free radical production did not necessarily speed up aging.

The McGill scientists treated worms with the herbicide paraquat, which is so toxic to humans and animals it has been banned by the European Union, in order to boost their production of free radicals.

Hekimi discovered that the worms actually lived 60 per cent longer after exposure to the chemical than those that were left alone.

"Quite considerable if you think of people," Hekimi told CBC News.

Don't try this at home

What’s more, giving the worms antioxidants — long touted by some health professionals as helping to stave off death — instead shortened the modified worms’ longer lifespans by as much as 40 per cent.

"When we used poison, we actually prolonged the lifespan of normal animals," he said. "When we mimic what the mutants are doing, which is increase free radicals, we actually have normal animals live longer."

But don’t try this at home, he cautioned.

"We are just saying, during aging, stuff happens, including this free radical elevation, which is an attempt to combat aging. But that doesn’t tell you what aging is."

The production of mitochondrial free radicals may actually protect organisms from the damage of cells associated with aging, he said.

"It also suggests that free radical generation and aging are correlated because free radical generation is a positive reaction. It’s an attempt to turn on stress responses to fight the damage that accumulates during aging."

He suggested that taking antioxidants such as vitamin C, meanwhile, may actually be "misguided." As far as it goes for attempting to prolong life, they may not be the answer. Such vitamins could actually be a factor of resistance as they soak up free radicals like a sponge.

Antioxidants shortened long lifespans

Hekimi acknowledged there might be situations where antioxidants are beneficial to some people.

"It’s just a reasonable conclusion that at the very least it has to be examined very critically," he said.

Both vitamin C and N-acetyl-cysteine antioxidants shortened the lifespan of the mutant worms, yet had no effect on normal worms.

Hekimi called for further study to find out how the data might change our current understanding of the link between aging and oxidative stress.

"Free radicals are clearly involved, but maybe in a very different way than in the way people used to think," he said.

Dr. Denham Harman, an emeritus professor of internal medicine at the University of Nebraska Medical Center,  developed the free radical theory of aging in 1954. It's still considered the most widely accepted theory on aging.

"It’s really hard to have people accept that because it’s really entered the public’s consciousness," Hekimi said. "If you ask most people on the street what causes aging, many would say free radicals, but it’s a complex story."

In recent years, the theory has been challenged by various scientists, including a separate group studying worms at Palo Alto’s Stanford University.

Others have weighed in that aging cannot be caused only be free radicals, arguing that lifestyle choices, environment and genetics also play major roles.

In November, Dr. Maydianne Andrade, an associate professor of biology at the University of Toronto published findings on dietary restrictions of female spiders that suggested eating less contributed to living longer.

And in February, researchers at McMaster University in Hamilton experimented with a cocktail of 30 dietary supplements that seemed to delay the aging process of mice.


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