DAMAGED CHEMICALS IN BRAIN LINKED TO AGING.

Byline: Sue Goetinck Dallas Morning News

For some it's the mind; for others it's the body.

Everyone ages a little differently. But scientists don't know why one person becomes forgetful while the next is forever as sharp as a tack.

Now, researchers from Fort Worth and Dallas think they might have a clue. By studying elderly mice, scientists have linked damaged chemicals in the animals' brains with some typical signs of aging - such as trouble with balance or a loss of memory. What's even more exciting, the researchers say, is that the specific part of the brain that's affected correlates with the particular aging symptom.

The new results, taken together with previous studies, suggest that the chemical damage contributes to aging symptoms. Drugs that prevent the damage might be useful to alleviate aging symptoms or problems caused by neurological disorders, said Michael Forster, a neuroscientist at the University of North Texas Health Science Center at Fort Worth.

``It's such a glaring target for the development of new treatments,'' he said.

The targets in question are chemicals known as oxygen-based free radicals. A natural byproduct of metabolism, the free radicals can react with important body molecules such as proteins and DNA, the chemical that makes up hereditary material. The chemical reaction can damage the molecules and prevent them from working right.

Researchers know that as animals and people age, the amount of protein damaged in this way rises. Some scientists suspect the free-radical damage contributes to the aging process.

In the new study, led by Forster and Rajindar Sohal of Southern Methodist University, the scientists looked at the amount of one type of chemical damage from free radicals in the brains of mice.

The mice were 22 months old, equivalent to about 75 years old in people. First, the researchers put the mice through a series of tests to measure how well the animals' brains were working.

In one test, the scientists put mice - which are good swimmers - in a tub of water made cloudy with paint powder. As the mice swim around, they discover that hidden in the murky water is a platform.

``They are motivated to find this hidden platform,'' Forster said.

After several attempts, the mice have learned how to find the platform more quickly.

``It's analogous to remembering where you left your keys,'' he said. Perhaps not surprisingly, it took some of the older mice longer to remember where the platform was.

The mice also took a balance test - they had to walk from one end of a narrow beam to the other. To make it across, the mice's brains have to integrate visual cues as well as the sensations from their paws on the beam. Again, some of the older mice had trouble.

Different mice had trouble with different tests, Dr. Forster said, just as some people might lose their balance as they get older, but others don't.

After the tests were completed, the researchers analyzed tissue from different parts of the mice's brains and checked to see how much protein in different parts of the brain had been modified by free radicals to form chemical groups known as carbonyls.

``The amount of carbonyl you find in a pile of protein is a good estimate of the amount of protein that is dysfunctional,'' Forster said.

Mice that had the most trouble finding the platform had the highest level of carbonyls in the cerebral cortex, a part of the brain known to be useful in learning and remembering. The mice that had trouble on the beam had the most chemical damage in the cerebellum, the region of the brain that controls movement and balance.

The researchers reported the results in a recent issue of the Proceedings of the National Academy of Sciences.

One explanation, Forster said, is that the damaged proteins don't work well, and that translates into lapses in brain function. But, he acknowledged, the scientists still don't know whether the link is anything more than a correlation.

``We haven't distinguished cause and effect,'' he said. ``One doesn't know if you're looking at the cause of the wreck, or just the wreck.''

In other words, the protein damage may not be the reason the brain's function declines with age. The damage simply may be a side effect of aging.

But other studies suggest that getting rid of free radicals can slow down some symptoms of aging, said Earl Stadtman, a biochemist at the National Heart, Lung and Blood Institute in Bethesda, Md. In gerbils, for example, drugs that convert free radicals to harmless chemicals can reverse age-related changes.

And, Forster said, studies with monkeys also suggest that free radicals contribute to aging. When monkeys are placed on a restricted diet, they produce fewer of the damaging chemicals.

``The less food you eat, the less free radicals are formed,'' he said.

The monkeys also live longer.

Forster cautioned that people should not try to restrict their diets in an attempt to live longer.

``It's obviously not been tested in humans,'' he said.

Assuming that free radicals do contribute to age-related changes, researchers still don't know why individual animals age differently.

In the new study, all the mice were genetically identical, so genes couldn't explain the differences in aging. Stadtman said he suspects the type of protein changes that occur may be the luck of the draw.

``The whole process of free radical damage is a random process,'' he said. ``Over time, you get an accumulation of errors that may be different from one individual to another.''

If free radicals really do contribute to the degeneration that comes with age, it's possible that drugs to prevent free-radical damage may help people who have had a stroke or have diseases like Parkinson's or Alzheimer's, Forster said.