Seattle Times 5/05
In a study that bolsters the free-radical theory of aging, University of Washington scientists have genetically engineered mice to live 20 percent longer than normal.
The Methuselah mice produce large amounts of an antioxidant enzyme that protects their cells from damage and also staves off the cataracts and heart damage that usually come with age.
But don`t go rushing for the Vitamin E and other antioxidant supplements, cautions lead researcher Peter Rabinovitch, a UW pathologist.
While the experiment shows a specific antioxidant can slow the aging process in mice, it also demonstrates how difficult it will be to translate that into a pill for people.
To get a significant increase in life span, the researchers not only had to insert a souped-up gene into the mice, they had to target the gene to cell structures called mitochondria. That suggests where and how antioxidants are delivered to tissues and cells may be key to any life-extending benefits, Rabinovitch said.** See footnote
This may help explain why scientists have not been able to find clear improvements in the health or life span of people who take antioxidants - despite the mega-million-dollar industry`s claims.
"There is more and more evidence that antioxidant supplements are not beneficial, and there have been a few examples where they might have been harmful," Rabinovitch said.
A study this year hinted that high doses of Vitamin E may raise the risk of heart disease. Earlier research has found beta carotene, another popular antioxidant, puts smokers at higher risk of lung cancer.
Yet it`s clear health improves when people eat antioxidant-rich fruits and vegetables, Rabinovitch said.
"We don`t know yet how to deliver the health benefits of fruit and vegetable antioxidants in a pill form."
The free-radical theory of aging blames highly reactive byproducts of metabolism, like hydrogen peroxide, for cell damage that builds up over a lifetime. The mitochondria, where cells "burn" glucose for energy, churn out high levels of these oxidizing free-radicals.
Working with colleagues from the University of California and the University of Texas, the UW researchers focused on catalase, an enzyme in mice and people that neutralizes hydrogen peroxide.
Mice with higher levels of catalase in their mitochondria lived 5.5 months longer than the controls, whose average life span is about two years. Mice with high catalase in other cell structures, including the nucleus, showed only modest life extension.
The oldest of nearly 1,000 experimental mice lived to the ripe age of three years and four months - watched closely by scientists who couldn`t start their analysis until all the mice had died.
"Waiting those last few months for the experiment to be done was like waiting until the day finally arrives to open a present," Rabinovitch said.
In addition to living longer, the genetically engineered mice had less heart damage and fewer cataracts than normally aging mice.
"It`s a pretty strong case that several different aspects of aging, including terminal disease, have been delayed or decelerated," said pathologist Richard Miller, of the University of Michigan Geriatrics Center. Miller, who was not involved in the UW study, analyzed its significance for Science Express, the online version of Science magazine that published the study yesterday.
Miller and several other scientists have extended mouse, worm and fruit-fly life spans by genetically tampering with growth hormones. The resulting dwarf mice can live 50 percent longer, though most are infertile.
Small dogs, which produce low levels of growth hormone, live longer than big breeds. And mice and rats fed near-starvation diets also have life spans up to 50 percent longer than animals that eat normally.
The UW study is the first to extend mouse life spans by reducing free-radical damage, Miller said.
The big question researchers are trying to answer now is how all these bits of evidence fit together to explain the underlying causes of aging - and whether the process can be slowed.
The only way to increase maximum life span to a major extent is by fiddling around with the aging process itself," Miller said.
It`s possible antioxidants may be tied in with growth hormones, diet and cell structures called telomeres, which break down with age, blocking cell division. Or there could be several separate mechanisms responsible for different aspects of aging.
That`s the 64,000 dollar question," Rabinovitch said. "Now that we know antioxidants can extend life spans, we want to know whether they work through similar or different mechanisms than caloric restriction or dwarfism."
He and his co-workers are raising a new generation of genetically engineered mice, hoping to boost life spans further by targeting antioxidants to more types of tissue throughout the animals` bodies.
"We propose this is just the tip of the iceberg."
** According to Dr. Hidemitsu Hayashi, M.D., the Director of the Water Institute of Japan,
"We take vitamins, mineral supplements and trace minerals with the hope of improving our health. However, if the body acid/alkaline balance is not maintained well, the body cannot absorb these things well and we wind up throwing them out.
The solution to combat adult diseases caused by aging is to drink alkaline water. It is too simple for modern medicine to understand ... Ionized Water quickly permeates the body and blocks the oxidation of biological molecules by donating its abundant electrons to active oxygen, enabling biological molecules to replace themselves naturally without damage caused by oxidation that can cause diseases."
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