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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.

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