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DNA Damage Piles Up in the Aging Brain

9 June 2004 (All day)
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Hidden damage. DNA defects begin to derail genes in the human brain during middle age.

Defective DNA has long been a suspect in the search for causes of impaired memory and learning. Now a comprehensive study of brain DNA provides solid evidence linking the culprit to the crime, which appears to be another woe of middle age.

A closer look at the crippled genes revealed damage caused by nasty free radicals, molecules that chew up DNA by the same process that turns metal to rust. Damage was most severe in the genes' promoter regions, the parts responsible for regulating when, and for how long, a gene is turned on. Compared to other sections of DNA, promoter regions are more vulnerable to attack from free radicals, and the cell can't repair them as well.

The results aren't all dismal though. The researchers also found that in older brains, activity was cranked up in genes that play a role in the body's immune response and combating stress and indicating that even if cells can't repair the damaged promoters, the brain tries to buffer the oxidative beating. And in human cells cultured in the lab, Yankner's team was able to repair much of the damage by artificially turning up the cell's DNA repair enzymes. While he cautions that the lab is a far cry from the brain, it raises the possibility that damage might be amenable to therapy in the future.

"The findings are really quite stunning," says neurologist Ann Graybiel of the Massachusetts Institute of Technology in Cambridge. "It gives new meaning to reaching 40."

Related sites
Yankner's site
Information about aging and the brain

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