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Low-Cal Diet Keeps Mice Young at Heart

Less energy intake seems to prevent age-related gene changes in pump cells

MONDAY, Oct. 28, 2002 (HealthDayNews) -- Putting middle-aged mice on a low-calorie diet keeps them young at heart -- literally.

A new study shows that mature mice fed about 25 percent less energy than their usual meal plan show about 20 percent less age-related change in heart gene activity. The low-cal diet also prevented other undesirable age-related changes in cells and the immune system.

Since all the mice were killed in order to study, it wasn't clear if the dieting rodents would have lived longer than their gorging cage mates. However, Tomas Prolla, a University of Wisconsin geneticist and a co-author of the study, says his group's earlier research has shown that low-cal mice can live about 30 percent to 40 percent longer than normal.

To be sure, mice raised in a lab eat better than their wild cousins. So it's possible that, predators aside, letting rodents eat as much as they want may accelerate aging while cutting back on their energy intake returns them to a more natural rate, Prolla says.

Even so, mounting research suggests that caloric restriction slows age-related changes in mammals, from monkeys to man.

Government funded scientists have shown, for example, that animals on low-calorie diets have lower body temperatures and healthier blood insulin levels than those allowed to eat as much as they pleased. They also appear to have higher blood levels of a hormone called DHEAS, which declines with age. Eating less may also reduce the risk of precancerous colon polyps, according to a recent mouse study funded by the National Cancer Institute.

Scientists are particularly interested in a cluster of Japanese men and women in Okinawa who eat relatively little and seem to have better than average longevity and health. Yet the evidence supporting longer living through energy restriction in people is anecdotal and therefore inconclusive, says Huber Warner, who directs the biology of aging program at the National Institute on Aging. "We don't know that caloric restriction works in people, period," Huber says. "We think it works in monkeys," but even that's not proof enough.

Still, Huber calls the new study "interesting," and says it was the first time he was aware of that anyone had shown gene changes linked to aging in the heart and the impact on that process of energy intake.

A report on the findings appears in tomorrow's issue of the Proceedings of the National Academy of Sciences.

Prolla and his colleagues at the University of Wisconsin in Madison and the University of Alabama in Birmingham watched the activity of nearly 10,000 genes involved in heart function with a computer "gene chip." To get a sense of how age affects these genes, they compared May mice just five months old with a December group that was 30 months old.

The two sets of rodents had markedly different gene activity surrounding how their heart cells processed energy. In the younger animals, the chief source of fuel was fatty acids, which provide lots of energy that burns slowly. However, cells in the older mice relied more on faster-burning, lower-energy carbohydrates that taxed their efficiency. Their ability to make proteins, which are crucial to healthy cell function, was also suppressed.

When the mice were 14 months old -- middle age in rodents -- the researchers cut back calorie intake for some by 26 percent. The rest were allowed to eat almost as much as they could (giving them a fully open trough leads to obesity).

At 30 months of age, these animals had a 19 percent reduction in the age-related gene changes Prolla's group saw in the full-calorie mice. "They had a number of changes in gene expression which were consistent with a healthier profile," he says. "When the animal changes its diet as a result of the lower caloric intake, the animal has to reprogram itself to live with less calories."

Advocates of low-calorie living recommend that people trim energy across the board instead of cutting out entire meals, Prolla says. That's not too hard, Warner adds, since most of us eat too much anyway.

Caloric intake isn't one size fits all. To maintain your weight at a healthy level, you probably need to eat between 2,000 and 2,500 calories a day.

What To Do

For more on caloric restriction, try the American Federation for Aging Research. For more on healthy aging, try the National Institute on Aging.

SOURCES: Tomas Prolla, Ph.D., assistant professor, genetics, University of Wisconsin Medical School, Madison; Huber Warner, Ph.D., associate director, biology of aging program, National Institute on Aging, Bethesda, Md.; Oct. 28, 2002, Proceedings of the National Academy of Sciences
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