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?

In 1935 scientists at Cornell University made an extraordinary discovery. By placing rats on a very low calorie diet, Clive M. McCay and his colleagues extended the outer limit of the animals' life span by 33 percent, from three years to four. They subsequently found that rats on low-calorie diets stayed youthful longer and suffered fewer late-life diseases than did their normally fed counterparts.Since the 1930s, calorie restriction has been the only intervention shown convincingly to slow aging in rodents (which are mammals, like us) and in creatures ranging from single-celled protozoans to roundworms, fruit flies and fish.

Naturally, the great power of the method raises the question of whether it can extend survival and good health in people. That issue is very much open, but the fact that the approach works in an array of organisms suggests the answer could well be yes. Some intriguing clues from monkeys and humans support the idea, too.

Of course, even if calorie austerity turns out to be a fountain of youth for humans, it might never catch on. After all, our track record for adhering to severe diets is poor. But scientists may one day develop drugs that will safely control our appetite over the long term or will mimic the beneficial influences of calorie control on the bodys tissues. This last approach could enable people to consume fairly regular diets while still reaping the healthful effects of limiting their food intake. Many laboratories, including mine at the University of Wisconsin-Madison, are working to understand the cellular and molecular basis of how calorie restriction retards aging in animals. Our efforts may yield useful alternatives to strict dieting, although at the moment most of us are focused primarily on understanding the aging process (or processes) itself.

Less Is More for Rodents
RESEARCH into calorie restriction has uncovered an astonishing range of benefits in animals--provided that the nutrient needs of the dieters are guarded carefully. In most studies the test animals, usually mice or rats, consume 30 to 50 percent fewer calories than are ingested by control subjects, and they weigh 30 to 50 percent less as well. At the same time, they receive enough protein, fat, vitamins and minerals to maintain efficient operation of their tissues. In other words, the animals follow an exaggerated form of a prudent diet, in which they consume minimal calories without becoming malnourished.

If the nutrient needs of the animals are protected, calorie restriction will consistently increase not only the average life span of a population but also the maximum life span--that is, the lifetime of the longest-surviving members of the group. This last outcome means that calorie restriction tinkers with some basic aging process. Anything that forestalls premature death, such as is caused by a preventable or treatable disease or by an accident, will increase the average life span of a population. But one must truly slow the rate of aging in order for the hardiest individuals to surpass the existing maximum.

Beyond altering survival, low-calorie diets in rodents have postponed most major diseases that are common late in life [see box on page 57], including cancers of the breast, prostate, immune system and gastrointestinal tract. Moreover, of the 300 or so measures of aging that have been studied, some 90 percent stay "younger" longer in calorie-restricted rodents than in well-fed ones. For example, certain immune responses decrease in normal mice at one year of age (middle age) but do not decline in slimmer but genetically identical mice until age two. Similarly, as rodents grow older they generally clear glucose, a simple sugar, from their blood less efficiently than they did in youth (a change that can progress to diabetes); they also synthesize needed proteins more slowly, undergo increased cross-linking (and thus stiffening) of long-lived proteins in tissues, lose muscle mass and learn less rapidly. In calorie-restricted animals, all these changes are delayed.

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