Eating less linked to healthier brain in old age

Eating less may be good for the health of your brain, and may help keep debilitating ailments such as Alzheimer’s and Parkinson’s diseases at bay.

That is the message derived from a pathbreaking study that employed a powerful new gene-scanning technique to analyze activity in thousands of genes to create a molecular portrait of the aging brain in mice.

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The new study focuses on genetic activity related to two critical regions of the brain: the cerebral cortex, the part of the brain involved in the higher functions of thought, and the cerebellum, the brain structure that helps coordinate motor and muscle function.

Conducted by scientists at the university and to be reported in July in the British scientific journal Nature Genetics, the study provides new insight into the cognitive and motor skill deficits that occur with age. The results may also help to explain the basis of common neurological disorders such as Parkinson’s and Alzheimer’s diseases.

Cheol-Koo Lee, Richard Weindruch and Tomas A. Prolla, all of UW–Madison, profiled the action of 6,347 genes. The scientists charted changes in genetic activity in two groups of aging mice, one group on a standard diet and another group whose diet had been trimmed to 76 percent of the standard diet. The study builds on similar work of aging skeletal muscle by the same group of Wisconsin scientists and reported last year in the journal Science.

The new Wisconsin study shows that a reduced-calorie diet selectively lowers the age-associated increase in the activity of genes that encode inflammatory and free-radical-generated stress responses, says Weindruch, a UW–Madison professor of medicine. Free radicals are highly reactive molecules that circulate in the body and can damage cells over time. Previous studies suggest that both inflammation and free-radical damage may play a role in the onset of Alzheimer’s and Parkinson’s disease.

The study’s findings, Weindruch notes, add to mounting evidence that a reduced-calorie diet, the only known method of slowing aging in several species of animals, not only extends life, but confers health benefits that contribute significantly to a better quality of life in old age.

The study also suggests that basic aging mechanisms in the brain, including inflammation and free radical damage, are shared among different species of animals, including mice, monkeys and humans.

Scientific opinion on the value of the mouse as a model for human neurological disorders is divided, says Prolla, a UW–Madison professor of genetics. But the Wisconsin study shows that many genes related to inflammation become more active with normal aging, a phenomenon suppressed in mice placed on a low-calorie diet.

“Although it is known that caloric restriction retards certain aspects of aging in the brain, the mechanism is not known,” says Weindruch, an authority on caloric restriction and aging. “However, these new findings advance our understanding of caloric restriction’s effects on aging in the brain.”

Prolla says this new understanding of the relationship between genes and brain health in mice could take on importance as a testing ground for new drugs: “It means we can use mice to screen for drugs that might prevent these processes in humans,” Prolla says.

“Gene expression changes observed with aging in the two brain regions can be used to measure the aging process on a tissue-specific and molecular basis,” Weindruch says. “This should facilitate the development of interventions – drugs, dietary modifications – to retard aging in the brain.”

Prolla says the study also indicates that diet alterations may lower the risk of developing some of the most common and debilitating age-associated neurological disorders.

The Wisconsin study depended on a powerful new technology known as the “gene chip,” a small DNA-laden plate that, when read with a laser, reveals activity levels for thousands of individual genes at once. The technique can show which genes are in play in a given circumstance. The more than 6,000 genes surveyed for the new Wisconsin study represent 5 percent to 20 percent of the mouse genome.

The Wisconsin group is extending its gene chip studies to monkeys and humans. UW–Madison, at its Wisconsin Regional Primate Research Center, is the site of a decade-old study of rhesus macaques on a reduced-calorie diet.