Researchers extend mouse lifespan by protecting against fre...( made them produce more human catalase ...)

made them produce more human catalase, the enzyme that breaks down hydrogen peroxide. They targeted delivery of the catalase to different areas of the cell: the cytoplasm, where catalase normally goes to decompose hydrogen peroxide; the nucleus, the DNA-containing "control center" for the cell; and the mitochondrion, the cell's power plant that converts organic matter into energy.

They compared the different groups of mice to a control group and found that increased production of catalase could affect the mouse lifespan. The mice with higher catalase levels in the mitochondria, dubbed the MCAT group, had about a 20 percent increase in average and maximum lifespan, or about four and a half months. The mice with increased catalase levels in the nucleus and cytoplasm saw only modest increases in lifespan. These results fit with the theory that mitochondria can be an important source of free radicals created as a byproduct of energy production. Removing hydrogen peroxide "at the source" seems to be the most effective strategy for enhancing lifespan, Rabinovitch said.

The scientists also found that the mitochondrion-targeted catalase mice had healthier heart muscle tissue, indicating that the catalase helped protect from age-related heart problems seen in wild-type mice. The MCAT mitochondria also had fewer mutations, and the MCAT nuclear DNA had fewer oxidized components.

"This study is very supportive of the free-radical theory of aging," said Rabinovitch. "It shows the significance of free radicals, and of reactive oxygen species in particular, in the aging process."

This study and others that are able to extend animal lifespan beyond the normal limits are very powerful in that they most clearly demonstrate the important steps and pathways in the aging process, Rabinovitch said. By identifying these steps and pathways, scientists could pave the way for future development of drugs or other treatments that protect the body from free ra
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Contact: Justin Reedy
jreedy@u.washington.edu
206-685-0382
University of Washington
5-May-2005

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