Mice that lives 20 percent longer

The canny world of advertising has caught on to the free radical theory of aging, marketing a whole array of antioxidants for preventing anything from wrinkles to dry hair to reducing the risk of heart disease — promising to help slow the hands of time.

Nevertheless, numerous studies of people taking antioxidant pills have failed to show a benefit, and the supplements may even be harmful. A study earlier this year hinted that high doses of the antioxidant vitamin E may raise the risk of heart disease, while earlier research has found that beta carotene, another popular antioxidant, puts smokers at higher risk of lung cancer. But that doesn’t mean the free radical theory of aging is wrong, “We think that it is fundamental to the understanding and the implications of aging,” says University of Washington pathologist, Peter Rabinovitch.

Working with genetically engineered mice — to produce a natural antioxidant enzyme called catalase — Rabinovitch’s group found that, on average, the mice live longer. But don’t go running to the medicine cabinet for your bottle of Vitamin C or other antioxidant supplement, only naturally-occurring antioxidants seem to offer a dip in the fountain of youth, and so far, only in mice.

Mitochondria – the powerhouses of the cell.

Rabinovitch’s group genetically engineered mice to produce a natural antioxidant enzyme called catalase. The mice lived 20 percent longer than normal mice – on average they lived five and a half months longer than the control animals, whose average life span was about two years. “It means that an individual who lives to age 70, now, with the benefits that we achieved in the mice if these could be carried forth to humans, they might live instead to 84 years old,” Rabinovitch says. “What we have achieved is the best documentation yet that increasing the level of antioxidants in a general fashion can enhance the health and the lifespan of mice.”

“Free radicals are highly energetic molecules. They have what we call unpaired electrons, but what this really means is that they are very chemically active. They will react with molecules including DNA and protein that is in cells and when they do so, they oxidize and damage those molecules and give rise to mutations and abnormalities, which cause them to be dysfunctional,” Rabinovitch explains. “So protecting the cells against free radicals is fundamental to the hypothesis that these free radicals are damaging and limiting to lifespan.” Antioxidants mop-up free radicals in the body, helping to reduce their damaging effects.

The free radical theory of aging, first proposed by Dr. Denham Harman, is one of several mechanisms within our bodies that have been blamed for aging, disease development and death.

Working in collaboration with researchers at the University of California and the University of Texas, Rabinovitch’s team gave mice a gene for making higher-than-normal amounts of catalase, an antioxidant enzyme in mice and people that neutralizes the free radical hydrogen peroxide that is naturally produced in the body, breaking it down into harmless elements.

“We had differing hypotheses about where putting catalase might do the best in terms of the advantage to life and health of the mice,” Rabinovitch explains. So they targeted the gene in three different places in the mouse cells — the cytoplasm, the nucleus — where they thought it might protect the all-important DNA of the cell — and the powerhouses of the cells, the mitochondria — where cells “burn” glucose for energy and churn out high levels of these oxidizing free-radicals. The mice that lived longest had the gene in their mitochondria.

“What we learned was that increasing the levels of catalase specifically in mitochondria was the way in which we could most effectively increase the ‘healthspan,’ as we call it, the increased time of healthy life for the mice,” Rabinovitch says. Mice with high catalase levels in the other cell structures showed only modest life extension.

The antioxidant effect was not only obvious in how long the mice lived, “When we looked at the hearts of these mice that there was less evidence of heart disease in the mice that had increased amounts of catalase in the mitochondria,” explains Rabinovitch.

There were also fewer cataracts than in normally aging mice. He points out that many human diseases are actually very much associated with aging. “That is to say the risk for diseases such as heart disease, cancer, stroke, diabetes, all of these very important diseases increase dramatically as the individual increases in age,” Rabinovitch says. “If we can delay or retard the underlying process of aging, then the frequency of these diseases with age will also be reduced. Not just one of them but we believe that many or all of these could be delayed in their onset.” Rabinovitch adds that his study helps explain why taking anti-oxidant supplements like Vitamin C and E has not been found to benefit people, but he hopes his finding could lead to an anti-aging pill.

But, in the meantime, eating fruits and vegetables rich in antioxidants is known to improve peoples’ health.

Source: ScienCentral.com – published in the May 5, 2005 advance online issue of Science.

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