Eat Less, Think More?
Gene Study May Explain Why Low-Calorie Diet Slows Aging

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By Janis Kelly
WebMD Medical News

Reviewed by Dr. Jay Goldstein

Researchers have long known that the only proven way to slow the aging process, in man or mouse, is to cut the number of calories taken in each day. Now they know why diet restriction works, at least in mice: New research shows that certain genes that are "turned on" in the older mouse brain can be "turned off" by reducing
daily calories by about one-quarter.

Cheol-Koo Lee, author of the study published in the journal Nature Genetics, also found that some genes that should be "on" to protect brain function are turned "off" in the elderly brain, and that caloric restriction can also restore some of these genes to activity. Lee is a graduate student at the Environmental Toxicology Center at
the University of Wisconsin in Madison. He collaborated on this study with Richard Weindruch, MD, and Tomas A. Prolla, MD.

Lee tells WebMD that many of the genes that are "turned on" with advancing age contribute to inflammation of the brain. Experts think that some brain diseases associated with aging, such as Alzheimer's disease, are more likely to occur if there is a high level of inflammation in the nervous system.

About 24% of the overactive genes were associated with an accumulation of damaged proteins which are thought to cause age-related brain problems such as Parkinson's disease.

John Carney, MD, who reviewed the study for WebMD, says Lee's work depicts "a moment in the life of the brain" and will help scientists determine how genes change and interact as the brain ages. Carney is founder and chief technology officer at Centaur Pharmaceuticals Inc., a Sunnyvale, Calif., biotech company researching treatments for age-related changes in the brain.

Lee studied the activity of more than 6,000 genes in mouse brain tissue. He looked at gene activity in mice who were on a normal diet, compared to those who were given 25% fewer calories. Brains of elderly (30-month-old) mice were compared to those from adult (5-month-old) mice.

The low-calorie diet did not prevent the aging changes in gene activity, but it did reduce many of them. "For many age-related problems such as Alzheimer's disease or Parkinson's disease, aging might provide the background risk by
modifying gene [activity], then some other factor might be able to trigger the disease," Carney says.

"With this kind of information, we might get a lot smarter about what drugs to test in clinical trials for diseases such as Alzheimer's disease and Parkinson's disease, and that should lead to faster development of effective treatments."