Caloric Restriction Appears To Prevent Primary Aging In The Heart

Ultrasound examinations showed that the hearts of people on caloric 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 in younger people. "This is the first study to demonstrate that long-term calorie restriction with optimal nutrition has cardiac-specific effects that ameliorate age-associated declines in heart function," says principal investigator Luigi Fontana, M.D., Ph.D., assistant professor of medicine at Washington University in St. Louis and an investigator at the Istituto Superiore di Sanita, Rome, Italy.

Research on mice and rats has shown that stringent and consistent caloric restriction increases the animals' maximum lifespan by about 30 percent and protects them against atherosclerosis and cancer, but human study has been difficult because the caloric restriction lifestyle requires a strict diet regimen, both to keep the total number of calories low and to insure that people consume the proper balance of nutrients.

The researchers studied 25 calorie-restricted individuals who had voluntarily been consuming a very low-calorie diet for an average of six years (consuming about 1,400 to 2,000 calories per day). They ranged in age from 41 to 65. The study compared their heart function to 25 age- and gender-matched individuals who ate a typical Western diet (about 2,000 to 3,000 calories per day).

In Western countries, heart attacks and strokes are responsible for about 40 percent of all deaths. Cancer causes about another 30 percent. According to Fontana, deaths in both groups can be attributed to what scientists call secondary aging. That's the term used to characterize health problems that result from conditions such as high cholesterol, diabetes, high blood pressure and other preventable conditions that contribute to premature death. A healthy diet and regular exercise can reduce risks from secondary aging. But this study suggests calorie restriction with optimal nutrition can do even more.

Normal aging causes a decline in cardiac performance. Before it pumps blood to the rest of the body, the heart's left ventricle fills with blood in a two-phase process. The first phase, which fills the ventricle in healthy hearts to about 80 percent capacity, is a passive, suction-mediated mechanism called early ventricular filling. The second phase is more active because the heart's atrium contracts to completely fill the ventricle with blood. As we get older, less blood gathers during the passive, diastolic phase, so the atrium has to work harder to increase the amount of blood it forces into the ventricle.

"This decline in diastolic function is a marker of primary aging," Fontana says. "Diastolic function declines in most people as they get older, but in this study we found that diastolic function in calorie-restricted people resembled diastolic function in individuals about 15 years younger." It may even be possible that eating a very low-calorie, nutrient dense diet reverses declines in diastolic function. People in the study averaged only six years on the diet, but their hearts looked 15 years younger. So Fontana says it's possible that the diet has a rejuvenating effect.

He notes that most study subjects had parents, grandparents or siblings who suffered heart attacks or strokes, making it unlikely that their genetic makeup is a contributor to the unusual healthiness of their hearts. In the case of one subject, both parents and younger brother currently take medication for high blood pressure and high cholesterol. Some subjects actually took medicine for high blood pressure themselves before they started on caloric restriction.

Fontana and colleagues previously have found that people on the very low-calorie diet have low blood levels of cholesterol and triglycerides, blood pressure scores equivalent to those of much younger individuals, a lower risk of developing diabetes and reduced body fat. These markers indicate less secondary aging.

In this study, Fontana's team found that markers of inflammation indicative of primary aging were much lower in the caloric restriction group. Their serum levels of a pro-inflammatory molecule called tumor necrosis factor-alpha (TNFa) were significantly lower. They also had less C-reactive protein (CRP).

In addition, they had lower amounts of a substance called transforming growth factor-beta (TGFb), a molecule that both helps reverse inflammation and activates cells called fibroblasts to produce collagen. If, for example, you cut yourself, your body will work to repair the damage by activating fibroblasts to produce collagen and make scar tissue to heal the wound.

Fontana says the low levels of TNFa, CRP and TGFb, combined with evidence of "younger" hearts in people on caloric restriction, has led his research team to hypothesize that inflammation may play a key role in the aging process.

"Our hypothesis is that low-grade, chronic inflammation is mediating primary aging," he says. "It's not the only factor, of course -- aging is a complex process. But we found less inflammation in these people -- less TNFa, C-reactive protein and TGFb -- as well as a more flexible ventricle in their hearts."

Overweight and obese people also tend to have higher levels of inflammation than lean people. In this study, those on caloric restriction had about 7 percent total body fat. The control group had about 25 percent body fat.

"It's very clear from these studies that caloric restriction has a powerful, protective effect against diseases associated with aging," says co-investigator John O. Holloszy, M.D., professor of medicine. "We don't know how long each individual will end up living, but they certainly have a longer life expectancy than average because they're most likely not going to die from a heart attack, stroke or diabetes. And if, in fact, their hearts are aging more slowly, it's conceivable they'll live for a very long time."

Members of the Caloric Restriction Optimal Nutrition Society try to consume between 10 and 25 percent fewer calories than average Americans while still maintaining proper nutrition. Fontana says that's a very important point. People on this type of diet don't simply consume less food. "Caloric restriction does not mean eating half a hamburger and half a pack of French fries and drinking half of a sugary beverage," he says. "These people have very good nutrition. They eliminate calories by eating nutrient-dense foods."

He says caloric restriction tends to resemble a traditional Mediterranean diet, which includes a wide variety of vegetables, olive oil, beans, whole grains, fish and fruit. The diet avoids refined and processed foods, soft drinks, desserts, white bread and other sources of so-called "empty" calories.

But Fontana and Holloszy don't believe that caloric restriction is for everyone. Instead, they recommend a moderate reduction in calories, combined with moderate, regular exercise.

"If you change the quality of your diet by increasing the servings of nutrient-dense food and reducing -- actually, it would be better to slowly eliminate -- all of the servings of 'empty' calorie foods, you improve your chances of living a healthier and longer life," Fontana says.

Meyer TE, Kovacs SJ, Ehsani AA, Klein S, Holloszy JO, Fontana L. Long-term caloric restriction ameliorates the decline in diastolic function in humans. Journal of the American College of Cardiology, vol. 47:2, pp. 398-402, Jan. 17, 2006.

This research was supported by was supported by the National Heart, Lung and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health; the Whitaker Foundation; the American Heart Association; and the Alan A and Edith L. Wolff Charitable Trust.

Washington University School of Medicine's full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.