updated 6/9/2004 3:56:36 PM ET 2004-06-09T19:56:36

Scientists say they’ve found a “genetic signature” of aging in the human brain — changes in key genes that may be linked to deteriorating mental function as we get older.

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The study suggests that some genes start working less hard soon after age 40, at least in some people.

The results don’t prove that such changes cause mental decline. But other scientists said they offer important insight into how the brain changes with age.

In the study, the researchers from The Children’s Hospital and Harvard Medical School analyzed brain tissue from 30 deceased people ranging in age from 26 to 106, looking at some 11,000 genes.

Damaged genes
After age 40, they found, about 400 genes showed significant changes in how hard they had been working while the person was alive to instruct cells to make certain proteins. Many of those genes were damaged and could not function properly.

Slightly less than half of the 400 or so genes — including those involved in learning, memory and communication between brain cells — were found to be functioning at a lower level, perhaps because of some kind of damage, the researchers found.

The remaining genes were found to be working harder after age 40. They included genes involved in DNA repair, antioxidant defense and stress and inflammatory responses.

Overall, the findings suggest that the first set of genes had sustained damage that hampered their functioning, and the other genes were working harder to try to lessen or repair that damage, said Bruce A. Yankner, a professor of neurology and neuroscience at Harvard Medical School.

He said it’s too early to tell what’s causing the genetic changes — whether it’s environmental, a person’s lifestyle, his or her genetic makeup, or some combination.

“But this gives us a starting point because what we’ve shown is that there’s a genetic signature, so to speak, of this aging process and now we can work to determine how that impacts brain function,” said Yankner, who led the study.

Interactive: Take a tour of the brain The findings were published online Wednesday by the journal Nature.

Yankner and his colleagues sampled tissue from the frontal cortex, which is involved in higher cognitive functions such as long-term planning.

They found that even the brains of individuals in their late 30s and early 40s showed signs of some genetic changes, he said.

In the laboratory, the researchers exposed cultured brain cells to oxygen molecules called free radicals, which are known to damage cells and DNA. They found that genes that had showed lessened activity in the brains sustained damage in the laboratory.

Richard Weindruch, a professor of Medicine at the University of Wisconsin, said those findings are the most exciting element of the new research because they hint at the possible cause of the damage seen in some of the genes.

Caleb Finch, a professor of gerontology and neurobiology at the University of Southern California, said the research offers a “unique synthesis” in linking apparent damage to changes in how those genes function.

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