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To make sure the study is as applicable to humans as possible, the Wisconsin scientists provide the monkeys with human-like health care: diabetic monkeys are given insulin; the animals get dental care; and female monkeys suffering endometriosis–a painful condition of the uterine lining common to humans–may undergo surgery. The only other study of caloric restriction in nonhuman primates, at the National Institute on Aging, is larger (120 monkeys) and two years longer-running than the Wisconsin study. However, it may not be as applicable to humans because those monkeys are not given extensive medical care, and were put on their restricted diets at a much younger age, some immediately after weaning, which stunts growth, according to Colman.

The Wisconsin researchers use all human medical equipment on the monkeys, Colman says, including an MRI scanner for upcoming brain-imaging studies. Each monkey will have two scans over a five-year period to monitor changes. Because caloric restriction’s effects on the body seem to be general, there’s no reason it shouldn’t be good for the brain if it’s good for other organs, says Sterling Johnson, assistant professor of medicine at the University of Wisconsin. Normal aging is accompanied by a slight decrease in brain volume, he says.

When the monkeys die, samples of their brain tissue will be saved for future studies of caloric restriction’s effects on gene expression in that organ, Johnson says. As mice age, genes associated with inflammation and the death of brain cells, for example, become more active, while many of those associated with metabolism become less active. Studies of aging in calorie-restricted mice in Weindruch’s lab have demonstrated that the diet prevents about 70 percent of such age-related changes.

In 2001, when the rhesus monkeys were middle-aged, Weindruch published a study showing that, although differences in gene expression existed between those primates on caloric restriction and the control group, the diet did not seem to prevent age-related changes in gene expression. Weindruch expects to get different results when his group does another round of tests, however, now that the monkeys are truly old–and now that technology exists to test specifically for rhesus monkey genes. In the previous round of testing, Weindruch and colleagues had to use chips with human genes on them, since rhesus monkey chips became available only recently.

Whatever the mechanisms turn out to be, “there’s something that happens with that extra reduction of food intake that really affects the aging process,” says Joseph Kemnitz, director of the Wisconsin primate research center. Ultimately, the researchers hope to take what they learn about this process to help people maintain a high quality of life throughout old age.

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