Gene Changes by Mid-Life Affect Memory Later

Study finds 150 genes that govern what happens as people age

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By
HealthDay Reporter

WEDNESDAY, May 7, 2003 (HealthDayNews) -- A broad-based analysis that maps the changes in genes related to aging has found that the genetic changes affecting memory occur in a very widespread and "choreographed" manner, and that the changes start by mid-life.

In an animal study that matches gene activity with behavioral and cognitive performance over time, scientists at the University of Kentucky College of Medicine identified almost 150 aging-and-cognition-related genes (ARCG's) and found that, even before middle age, changes in the activities of these genes were associated with memory decline down the road.

"These changes were not a response to mutation or just a random breakdown of the system, but a very choreographed event, a clear-cut cluster of related genes and genetic programs that are being turned on and off," says Kentucky professor Philip Landfield, the senior author of the study. That this happens "was surprising, as was the fact that this is happening before mid-life."

Landfield says that even though his findings suggest that cognitive decline is orchestrated into your genes, the identification of how and when this decline occurs could be useful in preventing disease.

"Brain aging is the major risk factor for diseases like Alzheimer's, so if you can retard aging, you can reduce the vulnerability to these diseases," he says. "By understanding gene activity, we can intervene to some degree and enhance their function."

The study, whose results appear in the May issue of the Journal of Neuroscience, was supported primarily by the National Institute on Aging (NIA).

For the study, Landfield and his colleagues trained 30 young, middle-age, and aged rats in two memory tasks. After the training, they killed the rats and studied tissue from the hippocampal region of the brain, the seat of memory in the brain, to identify and study the animals' gene activity relating to memory.

To do this, they used gene microarray technology, an innovative method that is able to analyze ribonucleic acid (RNA), an indicator of gene activity, and produce gene activity profiles that show how the brain works.

The scientists then compared the resulting data with the results of the memory tests to look for links between gene activity and cognitive performance.

What they found was that while cognitive performance did not decline until old age, genetic changes started in what would be before the age of 40 in humans. This suggests, Landfield says, that at that age the body is setting the stage for cellular and biological changes that could affect how the brain works as people get older.

Many of the genes they studied have already been associated with aging-dependent activities, like inflammation of cells. But the scientists also found other activities generated by the gene changes that could be new biomarkers for aging, like changes in the activities of neurons and an increase in cellular calcium levels stress, the study reports.

Mark Danielson, an associate professor of biochemistry and molecular biology at Georgetown University Medical School, says the data for this study is "reasonably impressive."

"Lots of people are doing this kind of technology for looking at genes, but not many use so many arrays because they are expensive," he says, "As a basis for further study, this is fine, but it's not comprehensive of all the genes that relate to aging."

More information

The American Academy of Family Physicians has an online brochure with information about memory and aging. More information on memory loss comes from the American Geriatrics Society.

SOURCES: Philip W. Landfield, Ph.D., professor and chairman, department of medical and biomedical pharmacology, University of Kentucky College of Medicine, Lexington; Mark Danielson, Ph.D., associate professor, department of biochemistry and molecular biology, Georgetown University Medical School, Washington, D.C.; May 2003 Journal of Neuroscience

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