Aging : Calories

by National Institute on Aging

(Page 13 of 15)

Why calorically restricted animals live far beyond their normal lifespans remains unclear. Because cutting down on calories slows metabolism, and free radicals are byproducts of metabolism, caloric restriction may reduce oxidative damage to cells. Calorie restricted animals also have less glucose circulating in their blood than their freely feeding counterparts. This may lessen the potential for protein crosslinking, a biochemical process implicated in cellular aging. And because caloric restriction lowers body temperature slightly, cells may sustain less genetic damage than at normal body temperature. In addition, scientists speculate that caloric restriction preserves the capacity of cells to proliferate, and that it keeps the immune system functioning at youthful levels. Caloric restriction also may work through other mechanisms. It may, for instance, influence hormonal balance, cell senescence, or gene expression. Or, it might work through a combination of all of these mechanisms, plus other factors.

Many gerontologists are particularly intrigued by findings suggesting that animals on calorie restricted diets have reduced rates of disease. In one of the largest studies to date, Roderick Bronson, D.V.M., at Tufts University found that caloric restriction not only extended lifespan in mice, but also prevented or slowed down development of every disease and all types of tumors. Other rodent studies have found that caloric restriction may increase resistance of neurons in the brain to dysfunction and death. These results, described as "stunning" by gerontologists, have raised hope that further study of caloric restriction will help uncover the mechanisms responsible for disease in old age.

However, whether caloric restriction might have the same effect in primates remains a major question. In studies underway at NIA, rhesus and squirrel monkeys are growing up on a calorically restricted diet. Similar studies are also ongoing at the University of Wisconsin and the University of Maryland. Preliminary results from these studies show some promising early signs of improved health - including greater resistance to diabetes and heart disease - in these primates as they age.

Yet even if caloric restriction is successful in primates, it is unlikely that most people could maintain a diet of 30 percent fewer calories without drastic and, in all probability, unpalatable changes in their eating habits. For this reason, most gerontologists doubt that caloric restriction will ever become a widespread means of extending the human lifespan. But investigators are exploring the question of whether drugs might mimic its effects, negating the need for sweeping alterations in diet. In rodent and other animal studies, gerontologists are testing a number of synthetic substances that produce some of the same effects as caloric restriction, such as reducing body temperature and lowering the amount of insulin in the blood. So far, the preliminary results have been promising. However, none of these substances has yet proved to extend lifespan, and some have potentially toxic side effects that may make human use impractical. Still, the search goes on. Meanwhile, it is becoming increasingly clear that lifestyle - particularly diet and exercise - can have a powerful influence on how people age.

The Next Step: Caloric Restriction in Primates

At the NIH Animal Center in Poolesville, Maryland, about 75 rhesus and squirrel monkeys are on diets; they eat 30 percent less than they would normally but get all the necessary nutrients. Another 75 monkeys, the control group, are eating as much as they want. The differences between the two groups, as they age, are beginning to provide insights into how caloric restriction influences lifespan.

The monkeys that arrived at the Poolesville laboratory in 1987 have responded to caloric restriction as expected; their maturation, measured by factors such as skeletal development and onset of puberty, has been delayed by about a year or year and a half. This is comparable to the delays in maturation seen in calorically restricted rodents.

As the monkeys continue to grow into middle age and beyond, Donald Ingram, Ph.D., and his colleagues at the NIA's Gerontology Research Center in Baltimore, where the project is coordinated, are monitoring dozens of signs of aging, ranging from immune response to activity level to antioxidant levels to fingernail growth. The measurements are being compared with those of the monkeys in the control group and should provide leads to some of the mechanisms at work in caloric restriction.

The monkeys on the restricted diet are smaller and weigh about 20 percent less than monkeys in the control group. However, the calorically restricted monkeys are no less physically active than animals allowed to eat at will.

So far, some positive trends have been detected, including the possibility of reduced incidence of heart disease and cancer in the calorically restricted monkeys. But it is important to keep in mind that these data are preliminary, and investigators caution that it may be many more years before it can be determined if caloric restriction does indeed improve the health and extend the lifespan of aging primates.

About the Author

www.nia.nih.gov
NIA, one of the 27 Institutes and Centers of NIH, leads a broad scientific effort to understand the nature of aging and to extend the healthy, active years of life. In 1974, Congress granted authority to form NIA to provide leadership in aging research, training, health information dissemination, and other programs relevant to aging and older people.