Genetic switch makes old mice forgetful

Reversing chemical change restores memory-making ability

Researchers may have found a clue to age-related memory loss among the coiled strands of DNA in the brain cells of elderly mice. If the process they unraveled also occurs in humans, the discovery could lead to new ways of helping older people remember.

In the new study, researchers found that older mice have less of a kind of genetic packing material that helps strands of DNA involved in the memory formation process spring into action.

Like older humans, elderly mice often don’t remember where they were when something happened. In the study, published May 7 in Science, researchers put mice into a box with particular lighting, smells and other cues the animals should remember, and then delivered a foot shock. Young mice, encountering the same box 24 hours later, remembered the foreboding place and froze in fear. But middle-aged 16-month-old mice had trouble recalling the danger and scurried about unafraid.

To figure out what caused this memory decline, a team led by André Fischer of the European Neuroscience Institute in Göttingen, Germany looked for minute chemical changes that might literally hide some of the genes needed for memory formation. Earlier studies had found that as memories are encoded in the brain, a suite of over 1,000 genes turn on and act as helpers in the memory-making process. To activate helper genes, chemical tags called acetyl groups must first loosen tightly wrapped DNA. This signals that the helper genes are open for business.

In the new study, Fischer and his colleagues found that these chemical decorations were responsible for the old mice’s inability to remember. Old mice had many fewer acetyl groups at the time that they should have been storing the memory of the shock. As a result, the suite of genes that should have been loosened up and ready for action remained turned off.

 In additional experiments, the researchers injected a drug into the brains of older mice to counter the drop in acetyl tag attachment, or acetylation. As a result, the battery of memory genes kicked on, and the mice were able to remember the shock as well as the younger mice did, freezing just as often.

If memory formation works the same way in people, scientists might be able to counter memory loss by boosting acetylation. One challenge: acetylation has many roles in the body, so a drug would have to boost this process specifically in the brain.

“Everyone’s looking for some way to alleviate these age-related deficits,” says molecular neuroscientist Farah Lubin at the University of Alabama at Birmingham. “There’s a lot more work to be done,” she says.

Laura Sanders is the neuroscience writer. She holds a Ph.D. in molecular biology from the University of Southern California.

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