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Mouse Research Bolsters Controversial Theory of Aging

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Aging is a process we humans tend to fight every step of the way. The results of a mouse study underscore the potential of antioxidants as a weapon in that battle: animals genetically modified to produce more antioxidant enzymes lived longer than control animals did. They also exhibited fewer age-related health problems overall.

The free radical theory of aging posits that substances with unpaired electrons attack the body's molecules and cause the functional decline of organs over time. Thus, antioxidants, which neutralize free radicals, should slow this deterioration. But animal models of aging designed to test the hypothesis have so far shown contradictory results.

In the new work, Peter S. Rabinovitch of the University of Washington and his colleagues engineered mice to produce higher-than-normal amounts of the enzyme catalase. Within cells, catalase removes hydrogen peroxide, a waste product of metabolism that could otherwise lead to damaging oxygen free radicals. In a paper published online this week by Science, the team reports that animals with higher levels of catalase in their mitochondria--the cell's energy-producing organelles--lived 20 percent longer on average than control animals did. What is more, mice in this so-called MCAT group had healthier heart tissue than normal mice and showed fewer mutations in their mitochondrial DNA. "This study is very supportive of the free-radical theory of aging," Rabinovitch says. "It shows the significance of free radicals, and of reactive oxygen species in particular, in the aging process."

Animals that overexpressed catalase in other parts of the cell, such as the nucleus, also exhibited longer life spans than their normal counterparts did, but the gains were modest. As such, the scientists note, the results reinforce the importance of mitochondria as a supplier of free radicals. The researchers have no plans to modify humans to increase protein expression, but they point out that future drug development could focus on protecting the body from free radicals.

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