Researchers Startled by Findings on Rodents : Lower Intake of Calories Linked to Longer, Healthier Life
Although cutting back on food intake has long been thought to improve health, scientists conducting the first wide-scale study on calorie restriction are startled by how clearly it reduces disease and prolongs life.
Less than a third of the way into a nine-year study expected to involve 100,000 rats and mice, government researchers are reporting dramatic preliminary findings about the health benefits of reducing calories.
“We believe the preliminary data will have significant impact on human health. Results are much more short-term than we expected,” said Ronald Hart, director of the Food and Drug Administration’s National Center for Toxicological Research in Jefferson, Ark.
The study, a joint effort of the FDA and National Institute on Aging, is exploring indications that calorie restriction without vitamin or mineral deficiency can extend life expectancy, retard some disease and possibly even slow the aging process.
Doctors believe eating patterns play a major role in health patterns, with dietary factors being blamed for about 35% of all heart disease, 22% of all cancers and about 2% of diabetes mellitus.
“For over 50 years it has been known that reducing calories reduces age-associated diseases and extends the life of a species,” Hart said. “But we know almost nothing about the mechanisms by which this takes place.”
In the $9-million study, which involves eight strains of mice and rats at 24 laboratories nationwide, half of the rodents are given unlimited access to food. The other half of the animals are restricted to about 60% of the calories consumed by their counterparts who can eat all they want.
Hart said the calorie-restricted group is given vitamin and mineral supplements. “They are not nutritionally deprived. . . . This experiment would not work if they were starved,” he explained. “This is not in support of anorexia or bulimia, which is malnutrition.”
Preliminary findings show the calorie-restricted rodents have a “significantly higher survival rate” than those allowed to eat all they want, Hart said.
About 80% of calorie-restricted mice were alive after 28 months, compared to just 50% of the controls, the researcher said. The average life expectancy of a laboratory mouse or rat is about 36 to 39 months.
None of the calorie-restricted rodents had cancer after 30 months, while 25% of the controls had malignant tumors. And in a strain of mice genetically prone to skin disease, less than 1% of the calorie-restricted animals had skin problems, but 95% of the controls suffered from skin disorders.
“These (calorie-restricted) animals are living longer, healthier, more active lives,” Hart said.
The researchers not only looked at the prevalence of death and disease but at their underlying factors, such as body temperature, production of fatty acids, elimination of harmful cells and repair of normal cells.
Calorie-restricted rodents had a lower mean body temperature than the controls, averaging 93 to 95 degrees contrasted to 98 to 100 degrees.
“When you reduce body temperature, you reduce the incidence of DNA damage,” Hart said. Deoxyribonucleic acid is the body’s carrier of genetic information.
Another major source of naturally occurring DNA damage within the body is the synthesis of fatty acids, which creates fatty acid epoxides that bind to DNA molecules. Hart said that means when enzymes try to get essential information from the affected DNA molecules, they run into genetic garble somewhat like “a scratch on a record.”
Researchers found that by reducing calorie intake in rodents, they also cut the amount of fatty acid synthesis in the animals about 40%.
As for foreign substances that may attack the body, Hart said calorie-restricted rodents appear better able to disarm such agents. When exposed to aflatoxins, a cancer-causing substance caused by a type of mold, calorie-restricted rodents held onto their ability to fight off the toxins much longer than the controls, whose capacity to detoxify aflatoxins diminished with age.
Curtailing food intake also appears to enhance the body’s ability to repair itself, Hart said.
Looking at two types of DNA damage, the researchers found cells from calorie-restricted animals were 45% better than controls’ at repairing bulky damage, such as that caused by ultraviolet light and 73% better at fixing smaller damage, like that caused by X-rays.
“In 20 years of research, no one has found a way to enhance DNA repair,” Hart commented.
In the latest project, the researcher said the mice and rats were placed on their dietary regimen at an age equivalent to “young teen-agers” in humans. Most previous studies have concentrated on limiting calorie intake in rodents starting at birth.
Questions to be answered in the remaining years of the study include whether restricting calories in older mice can produce health benefits and whether altering only certain components of the diet, such as fat or carbohydrates, may have an impact similar to overall calorie reduction.
Researchers will also try to determine if 40% is the optimum level to reduce calories or if smaller or larger reductions may generate better results. It is known that even with vitamin-mineral supplements, the body enters a starvation mode and health drops off sharply when calories are cut by more than 50%.
Although studies involving dietary changes in humans are probably two to three years away, Hart offered people a few words of advice.
“Maintain a reasonable weight and maintain it by not overeating continuously. This data reinforces the importance of not--as we would say back home--’pigging out at the trough.’ ”
