Calorie Restriction and Aging [Preview]

Eating less--while maintaining adequate nutrition--is a recipe for longer life in many animals. Might it help humans as well?

Until research into primates has progressed further, few scientists would be prepared to recommend that large numbers of people embark on a severe calorie-restriction regimen. Nevertheless, the accumulated findings do offer some concrete lessons for those who wonder how such programs might be implemented in humans.

One implication is that sharp curtailment of food intake would probably be detrimental to children, considering that it retards growth in young rodents. Also, because children cannot tolerate starvation as well as adults can, they would presumably be more susceptible to any as yet unrecognized negative effects of a low-calorie diet (even though calorie restriction is not equivalent to starvation). An onset at about 20 years of age in humans should avoid such drawbacks and would probably provide the greatest extension of life.

The speed with which calories are reduced needs to be considered, too. Early researchers were unable to prolong survival of rats when diet control was instituted in adulthood. I suspect the failure arose because the animals were put on the regimen too suddenly or were given too few calories, or both. Working with year-old mice, my colleagues and I have found that a gradual tapering of calories to about 65 percent of normal did increase survival.

How might one determine the appropriate calorie intake for a human being? Extrapolating from rodents is difficult, but some findings imply that many people would do best by consuming an amount that enabled them to weigh 10 to 25 percent less than their personal set point. The set point is essentially the weight the body is "programmed" to maintain, if one does not eat in response to external cues, such as television commercials. The problem with this guideline is that determining an individuals set point is tricky. Instead of trying to identify their set point, dieters (with assistance from their health advisers) might engage in some trial and error to find the calorie level that reduces the blood glucose or cholesterol level, or some other measures of health, by a predetermined amount.

The research in animals further implies that a reasonable calorie-restriction regimen for humans might involve a daily intake of roughly one gram (0.04 ounce) of protein and no more than about half a gram of fat for each kilogram (2.2 pounds) of current body weight. The diet would also include enough complex carbohydrate (the long chains of sugars abundant in fruits and vegetables) to reach the desired level of calories. To attain the standard recommended daily allowances for all essential nutrients, an individual would have to select foods with extreme care and probably take vitamins or other supplements.

Anyone who contemplated following a calorie-restriction regimen would also have to consider potential disadvantages beyond hunger pangs and would certainly want to undertake the program with the guidance of a physician. Depending on the severity of the diet, the weight loss that inevitably results might impede fertility in females. Also, a prolonged anovulatory state, if accompanied by a diminution of estrogen production, might increase the risk of osteoporosis (bone loss) and loss of muscle mass later in life. It is also possible that calorie restriction would compromise a persons ability to withstand stress, such as injury, infection or exposure to extreme temperatures. Oddly enough, stress resistance has been little studied in rodents on low-calorie diets, and so they have little to teach about this issue.

It may take another 10 or 20 years before scientists have a firm idea of whether calorie restriction can be as beneficial for humans as it clearly is for rats, mice and a variety of other creatures. Meanwhile investigators studying this intervention are sure to learn much about the nature of aging and to gain ideas about how to slow it--whether through calorie restriction, through drugs that reproduce the effects of dieting or by methods awaiting discovery.

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