Calorie Restriction, Intermittent Fasting, Resveratrol, and Rapamycin
Scientists are discovering that what you eat, how frequently, and how much may have an effect on quality and years of life. Of particular interest has been calorie restriction, a diet that is lower by a specific percent of calories than the normal diet but includes all needed nutrients. Research in some animals has shown calorie restriction of up to 40 percent fewer calories than normal to have an impressive positive effect on disease, markers of aging, and, perhaps, life span.
Even though calorie restriction appears to work in a variety of species, its effects on longevity are far from universal. It has been found to extend the life of protozoa (very small, one-celled organisms), yeast, fruit flies, some strains of mice, and rats, as well as other species. However, several animal models, including wild mice, show no lifespan extension by calorie restriction. In some strains of mice, calorie restriction even appears to shorten lifespan. Studies in nonhuman primates have also had conflicting results.
Calorie restriction studies with humans and other primates, such as monkeys, are ongoing. Some studies in nonhuman primates have shown that calorie restriction reduces the incidence of certain diseases such as cancer. Other studies in primates have not yet reached final conclusions.
Findings of the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) pilot study in humans showed that overweight adults who cut their calorie consumption by 20 to 30 percent lowered their fasting insulin levels and core body temperature. Both of these changes correlate with increased longevity in animal models. The lower calorie intake also reduced their risk for major causes of mortality such as heart disease and diabetes. CALERIE is currently evaluating a 2-year, 25 percent reduction in caloric intake for feasibility, safety, and effects on factors influencing longevity and health.
Scientists do not yet know if long-term calorie restriction is safe, beneficial, or practical for humans. However, the study of calorie restriction offers new insights into the aging process and biological mechanisms that could influence healthy aging. This research may also provide clues about how to prevent or delay diseases that become more prevalent with age and inform the development of treatments for such diseases.
Some studies focus on identifying chemicals that somehow mimic calorie restriction’s benefits. Resveratrol, a compound found naturally in foods like grapes and nuts, is of interest. In one study, scientists compared two groups of overweight mice on a high-fat diet. One group was given a high dose of resveratrol together with the high-fat diet. The overweight mice receiving resveratrol were healthier and lived longer than the overweight mice that did not get resveratrol. In a follow-up study, researchers found that, when started at middle age, resveratrol slowed age-related deterioration and functional decline of mice on a standard diet, but did not increase longevity. A recent study in humans reported that resveratrol may have some similar health benefits to those in animals; however, it is still too early to make any definitive conclusions about how resveratrol affects human health and aging. More research is needed before scientists know if there is a proper and safe dose of resveratrol or if it has any clinical applicability in people.
Rapamycin is also being investigated. This compound is used to help suppress the immune system in transplant patients so that the body does not reject the new organ. Rapamycin has been found to extend median and maximum lifespan of mice, even when fed to the animals beginning at early-old age. This finding suggests that an intervention started later in life may still increase longevity. Researchers are now looking for rapamycin’s effects on health span of animal models. Since rapamycin treatment in people is associated with serious toxicities, its potential for human long-term use is uncertain. Researchers do not know if rapamycin has any effect on human aging or if any potential benefit would outweigh risks. But, this discovery in mice has led to an exciting new research direction.
Scientists are also looking at the effect of intermittent fasting or reduced meal frequency. In animals, like mice, reduced meal frequency appears to have a protective effect on the brain and may also help with heart function and regulation of sugar content in the blood. However, here, too, the influence of intermittent fasting on human health and longevity is currently unclear.
While research into these types of approaches continues, it is important to remember there is already plenty of research supporting the value of a healthy, balanced diet and physical activity to help delay or prevent age-related health problems.
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