Calorie restriction's effects on aging studied long-term

Can eating a low-calorie yet nutritionally balanced diet extend human life as it does in rodents? Preliminary research suggests it might, so researchers at the School of Medicine are launching a long-term study to find out.

More than a decade ago several researchers, including John O. Holloszy, M.D., professor of medicine, demonstrated that stringent and consistent caloric restriction increased the maximum lifespan in mice and rats by about 30 percent and protected them against atherosclerosis and cancer.

Human study has been difficult because calorie restriction requires a very strict diet regimen, both to keep the total number of calories low and to ensure that people consume the proper balance of nutrients. However, there is a group called the Calorie Restriction Society that is devoted to limiting caloric intake in hopes of improving health and extending lives. Society members, who call themselves CRONies (Calorie Restriction with Optimal Nutrition), have developed ways to eat low calorie/high nutrition diets.

Luigi Fontana, M.D., Ph.D., assistant professor of medicine and an investigator at the Istituto Superiore di Sanita in Rome, has done extensive research with CRONies, most recently reporting in the Jan. 17 issue of the Journal of the American College of Cardiology that the hearts of people on calorie restriction appeared more elastic than those of age- and gender-matched control subjects. Their hearts were able to relax between beats in a way similar to the hearts of younger people.

And, a team from the Pennington Biomedical Research Center is reporting in the April 5 issue of the Journal of the American Medical Association (JAMA) on a six-month study of men and women between 25 and 50 who lowered daily caloric intake by about 25 percent.

That study, called the Comprehensive Assessment of the Long-term Effects of Reducing Intake of Energy (CALERIE), found that those on a calorie restriction diet ended the study with lower fasting insulin levels and lower core body temperatures. They also had less oxidative damage to their DNA, thought to be a marker of aging at the biochemical and cellular level.

"This study has laid the groundwork for future research into the long-term effects of calorie restriction in humans to see whether it really can extend lifespan," Holloszy said. "It's becoming clear from studies with the CRONies — and from this brief, prospective study — that calorie restriction does change some of the markers we associate with aging."

Holloszy and Fontana, who also has a related editorial in the April 5 JAMA, are getting ready to launch a second phase of the CALERIE study, to look at the effects of calorie restriction over the course of two years. Later this year, that study will begin recruiting volunteers between the ages of 25 and 45.

"We know people on calorie restriction will lose weight," Fontana said. "But this study isn't a weight-loss study. We're hoping to learn more about whether calorie restriction can alter the aging process."

Fontana said, for example, that low-grade, chronic inflammation seems to mediate aging. Overweight and obese people tend to have higher levels of inflammation than lean people, so it makes sense that losing weight might increase average lifespan by lowering the risks of some age-related diseases, such as diabetes and atherosclerosis. But in animal studies, not only did more of the animals live longer, the maximum length of a rat's or mouse's life also increased. The CALERIE study hopes to get some clues about whether calorie restriction might do the same for humans.

"We want to learn whether calorie restriction can reverse some of these markers of aging in healthy young people," Holloszy said. "It's going to be many years before we know whether calorie restriction really lengthens life, but if we can demonstrate that it changes these markers of aging, such as DNA damage and inflammation, we'll have a pretty good idea that it's somehow influencing the aging process at the cellular level."

Those interested in volunteering for Phase II of the CALERIE study may call 747-3181 or 747-3180.

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