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?

Not surprisingly, investigators have wondered whether calorie (energy) restriction per se is responsible for the advantages reaped from low-calorie diets or whether limiting fat or some other component of the diet accounts for the success. It turns out the first possibility is correct. Restriction of fat, protein or carbohydrate without calorie reduction does not increase the maximum life span of rodents. Supplementation alone with multivitamins or high doses of antioxidants does not work, and neither does variation in the type of dietary fat, carbohydrate or protein.

The studies also suggest, hearteningly, that calorie restriction can be useful even if it is not started until middle age. Indeed, the most exciting discovery of my career has been that calorie restriction initiated in mice at early middle age can extend the maximum life span by 10 to 20 percent and can oppose the development of cancer. Further, although limiting the calorie intake to about half of that consumed by free-feeding animals increases the maximum life span the most, less severe restriction, whether begun early in life or later, also provides some benefit.

Naturally, scientists would be more confident that diet restriction could routinely postpone aging in men and women if the results in rodents could be confirmed in studies of monkeys (which more closely resemble people) or in members of our own species. To be most informative, such investigations would have to follow subjects for many years--an expensive and logistically difficult undertaking. Nevertheless, two major trials of monkeys are in progress.

Lean, but Striking, Primate Data
IT IS TOO EARLY to tell whether low-calorie diets will prolong life or youthfulness in the monkeys over time. The projects have, however, been able to measure the effects of calorie restriction on so-called biomarkers of aging: attributes that generally change with age and may help predict the future span of health or life. For example, as primates grow older, their blood pressure and their blood levels of both insulin and glucose rise; at the same time, insulin sensitivity (the ability of cells to take up glucose in response to signals from insulin) declines. Postponement of these changes would imply that the experimental diet was probably slowing at least some aspects of aging.

One of the monkey studies, led by George S. Roth of the National Institute on Aging, began in 1987. It is examining rhesus monkeys, which typically live to about 27 years and sometimes reach 40 years, and squirrel monkeys, which rarely survive beyond 20 years. Some animals began diet restriction in youth (at one to two years), others after reaching puberty. The second project, involving only rhesus monkeys, was initiated in 1989 by William B. Ershler, Joseph W. Kemnitz and Ellen B. Roecker of the University of WisconsinMadison; I joined the team a year later. Our monkeys began calorie restriction as young adults, at eight to 14 years old. Both studies enforce a level of calorie restriction that is about 30 percent below the intake of normally fed control subjects.

So far the preliminary results are encouraging. The dieting animals in both projects seem healthy and happy, albeit eager for their meals, and their bodies seem to be responding to the regimen much as those of rodents do. Blood pressure and glucose levels are lower than in control animals, and insulin sensitivity is greater. The levels of insulin in the blood are lower as well.

No one has yet performed carefully controlled studies of long-term calorie restriction in average-weight humans over time. And data from populations forced by poverty to live on relatively few calories are uninformative, because such groups generally cannot attain adequate amounts of essential nutrients. Still, some human studies offer indirect evidence that calorie restriction could be of value. Consider the people of Okinawa, many of whom consume diets that are low in calories but provide needed nutrients. The incidence of centenarians there is high--up to 40 times greater than that of any other Japanese island. In addition, epidemiological surveys in the U.S. and elsewhere indicate that certain cancers, notably those of the breast, colon and stomach, occur less frequently in people reporting low calorie intakes.

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