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Biomedicine

Caloric Restriction Slows Aging in Monkeys

The diet delays or prevents diabetes, cancer, heart disease, and brain atrophy.

A 20-year study involving rhesus monkeys has provided the first strong evidence that caloric restriction slows the aging process in primates.

Senior citizen: Canto, 27, is on a calorie-restricted diet as part of a study examining the effects of diet on aging.

A diet that’s nutritionally adequate but provides 30 percent fewer calories than normal has been shown to extend life span and delay the onset of age-related diseases in other animals, including flies, worms, and rodents. But because studies on primates take much longer, the benefits had not yet been demonstrated to extend to them. Now researchers at the National Primate Research Center at the University of Wisconsin-Madison report that in rhesus monkeys, caloric restriction begun in adulthood reduces risk of the most common age-related conditions–diabetes, cancer, heart disease, and brain atrophy–by a third.

“With these results, we have become convinced that aging retardation is happening,” says Richard Weindruch, a professor of medicine at the University of Wisconsin-Madison, who began the study in 1989. The research involved 76 monkeys, half of them on the extreme diet. By now, the 33 surviving monkeys have reached old age. Thirty-seven percent of the monkeys on a normal diet have died of age-related diseases, compared with just 13 percent of the monkeys on the restricted diet. It’s still unknown whether caloric restriction extends the animals’ life span, but the results published today in the journal Science detail the benefits of the diet in preventing the most common such diseases.

The strongest evidence from the study concerns metabolic disorders. While five of the monkeys on a normal diet became diabetic and 11 were prediabetic (having blood glucose levels higher than normal), monkeys on the restricted diet were completely free of the disease. The incidence of both cardiovascular disease and tumors was reduced by 50 percent in the diet group. And magnetic resonance imaging showed that caloric restriction preserved gray-matter volume in the brain as the monkeys aged. In general, the dieting group appeared to be biologically younger: age-related diseases, if they developed, occurred later in life.

The work is significant because rhesus monkeys are more closely related to humans than other animals used so far in studies of caloric restriction. “Monkeys are so closely related to us; it’s a much easier jump that this is likely to work in humans,” says Ricki Colman, a lead researcher on the study. The Wisconsin researchers also took pains to make the study as applicable to humans as possible. “We treat each animal as an individual patient,” Colman says. The animals receive physical exams every six months, along with full dental care and medical interventions as needed. “We treat the diabetes with insulin, and when we identify tumors we remove them,” she explains.

Calorie consumption: The rhesus monkey on the left, Canto, eats a calorie-restricted diet and is 27 years old. The monkey on the right, Owen, consumes a normal diet and is 29.

Of course, as Colman points out, “it’s not a realistic goal for humans to practice caloric restriction.” The ultimate goal of the study, she says, is to better understand the underlying mechanisms of aging in order to learn how people can live healthier, longer lives: “It’s something we use to understand the aging process better.”

There is some evidence that caloric restriction has metabolic and cardiovascular benefits in humans, but data from monkeys are important because these studies are difficult to perform in people, especially over the long term. “Human data are still sketchy–it’s difficult to get controlled experiments in humans,” says Leonard Guarente, a professor of biology at MIT. Even in monkeys, he says, “these are very difficult and long-, long-term studies to do.”

Two big questions remain, the researchers say. First, does caloric restriction extend life span in the primates? “Meaningful maximum-life-span data are probably 15 years away,” says Weindruch. The monkeys in the Wisconsin study fall into two age groups; the average age of the oldest group is 29, which is very old considering that these animals, on average, live to about 25 in captivity. However, the longest a rhesus monkey has been known to live is 40 years. “If the last of the monkeys on caloric restriction die at the same time as the last control monkeys, it means there is only a delay of the onset of disease, but not an extension of life span,” says Luigi Fontana, a research professor at the Washington University School of Medicine in St. Louis who is leading a study of the diet in people.

The other unresolved question is how caloric restriction actually works in the monkeys. Now that they have strong evidence of the diet’s benefits, Weindruch says, his group will establish another group of animals to study the underlying mechanisms.

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