An extremely low-calorie diet slows the aging of the immune system in an elderly population of rhesus monkeys, according to research at the National Institute on Aging. A similar immune boost has already been observed in rodents on the calorie-restriction diet, and the monkey results–the first in primates–are an important step in determining whether such a diet could also strengthen the immune system in humans.

The rhesus monkeys on a calorie-restriction diet in the study have significantly more young T cells–an important component of the immune system–and these T cells can proliferate vigorously, says Janko Nikolich-Zugich, senior scientist at the Oregon Health and Science University’s Vaccine and Gene Therapy Institute, who led the research. In addition, these monkeys have lower levels of the inflammatory immune compounds that can cause cardiovascular and neurodegenerative disease in humans.

“The increased production and function of so-called naive T cells in calorie-restricted monkeys is encouraging,” says Rita Effros, professor of pathology and laboratory medicine at the University of California-Los Angeles’s Jonsson Comprehensive Cancer Center. Naive, or freshly made, T cells are a crucial component of the immune system because they can learn to recognize and attack pathogens the body has never before encountered.

The results are the latest findings on the health benefits of a diet with 30 percent fewer calories than normal but with complete nutrition. In mice and other small animals, calorie restriction increases life span by 30 percent and has many health benefits, including reduced cancer rates. The jury is still out on the diet’s effects on life span and age-related diseases in rhesus monkeys, which live longer and are more closely related to humans than any other animals in which the diet has been studied. But so far, the news is good. Research at the University of Wisconsin’s National Primate Research Center–the only other large, long-term study of the diet in nonhuman primates–shows that the diet prevents diabetes in these animals (see “Do Dieting Monkeys Live Longer, Healthier Lives?”).

The finding that calorie restriction also benefits the immune system could provide invaluable clues to ways to help those with a compromised ability to fight infections. Indeed, increased susceptibility to infectious diseases is one of the top causes of illness and death among the elderly. As people age, their weakened immune systems can’t always generate enough immune cells and antibodies to protect them. AIDS patients suffer the same weaknesses. Both groups could benefit from new therapies if the molecular mechanisms by which the diet impacts the immune system are uncovered.

As we age, we produce fewer and fewer T cells, says Nikolich-Zugich, and we become more and more vulnerable. In elderly people, as in the elderly monkeys on normal diets in the study, T cells not only exist in lower numbers, but are also less responsive to key signals that alert them to the presence of pathogens in the body, and are slower to proliferate and attack.

While she calls the results encouraging, UCLA’s Effros says that to really know whether these monkeys’ immune systems function better, the researchers need to expose them to infection or to a vaccine. “Infecting them with something like the flu virus would give us a much closer approximation of what goes on in elderly humans,” she says. Such studies are very difficult to carry out, says David Woodland, a researcher at the Trudeau Institute, an immunological research center. But he says Nikolich-Zugich has “laid the foundation for future calorie-restriction studies, which can be designed with the intent of doing [immune] challenge studies.”

It’s unlikely that the primate researchers will expose the valuable aged monkeys in their 20-year studies to infection, Nikolich-Zugich admits. But his group will put the monkeys to the test in January with a weak variant of the smallpox vaccine. He expects to see differences in the calorie-restricted monkeys’ ability to produce antibodies.

Richard Weindruch, a professor of medicine who heads the University of Wisconsin’s long-term study of calorie restriction in rhesus monkeys, and who has studied the aging of the immune system since his graduate work in the 1970s, says it’s not clear by what mechanism the calorie-restriction diet impacts the immune system. “It’s possible that the calorie-restricted animals are not investing their limited energy in making immune cells,” Weindruch says. If these animals are creating fewer T cells during their lifetime, and an animal can only make so many during its lifetime, this could explain why those on the diet are still able to make new cells at an advanced age.

Weindruch says the study of calorie restriction in monkeys is now at the same place as studies in mice were 25 years ago, when many findings were being published in major journals. The next decade will show whether the diet has all the same benefits in primates as it does in smaller animals like mice, what the mechanism might be, and what role the immune system plays.