Caloric restriction extends life in monkeys, study finds

Another study suggests an immune-suppressing drug helps elderly mice live longer

People who believed calorie restriction wouldn’t extend life in primates might now have to declare themselves a monkey’s uncle.

LESS IS MORE Canto, 27, (left) and Owen, 29, (right) are among the oldest surviving Rhesus monkeys in an ongoing study of calorie restriction in primates. Monkeys in Canto’s group eat a nutritious diet with 30 percent fewer calories than the diet fed to Owen’s group. Researchers have found that monkeys on a calorie-restricted diet have healthier hearts and brains and fewer age-related diseases than those on the full-calorie diet. © Univ. of Wisconsin-Madison Communications/Jeff Miller

PUMPIN’ IT Owen, a 29-year-old Rhesus monkey at the Wisconsin Primate Research Center in Madison, checks out his reflection while hefting a toy dumbbell. Owen is the oldest surviving monkey in a decades-long study of diet and aging in primates. He is part of a control group fed a healthy diet with unrestricted calories. Monkeys in an experimental group are fed a diet with 30 percent fewer calories. © Univ. of Wisconsin-Madison Communications /Jeff Miller

A 20-year study found that Rhesus monkeys fed a nutritious, low-calorie diet have fewer age-related diseases than counterparts on a normal diet, researchers report July 10 in Science. Also, MRIs reveal less shrinking with age in areas important for decision-making and controlling movement in the brains of calorie-restricted animals, report Ricki Colman and Richard Weindruch, both of the Wisconsin National Primate Research Center at the University of Wisconsin–Madison, and colleagues.

These results show that calorie restriction helps preserve primates’ bodies and brains, says Luigi Fontana, of Washington University in St. Louis and the Italian National Health Service in Rome. Calorie restriction has already been shown to extend the lifespan of mice and dogs, as well as yeast, fruit flies and worms.

The findings may have ramifications for fighting aging and disease in humans, Fontana says. “I’m confident that everything that happens in [non-human] primates will happen in humans.” Since both groups of monkeys are on a very healthy diet, people who go from a high-fat Western diet to a healthy, restricted diet may experience even greater health benefits than seen in this study.
The study began in 1989 with 30 adult male monkeys. In 1994, 30 female and 16 more male monkeys were added to boost statistical power. The monkeys were 7 to 14 years old when they entered the study. Since Rhesus monkeys live, on average, 27 years in captivity, it has taken this long to determine whether cutting calories by 30 percent would fend off aging and death.

Over the course of the study, monkeys on the full-calorie diet were three times more likely to die from an aging-related disease than monkeys that ate 30 percent fewer calories, the researchers found.

Since the study began, 21 of 38 control monkeys and 14 of 38 calorie-restricted monkeys have died. Of the control monkeys, 14 died of age-related causes, such as cancer, heart disease or diabetes. In the calorie-restricted group, only five died from aging-associated diseases, and none have developed symptoms of diabetes. The remaining deaths — seven control and nine calorie-restricted monkeys — were from complications of anesthesia, gastric bloat, endometriosis or injury.

“We were frankly blown away by these findings,” Weindruch says.

Maximal lifespan for Rhesus monkeys is about 40 years old, so researchers won’t know for another decade or two if — or for how long — calorie restriction can prolong life in primates.

Another study, published online July 8 in Nature, may provide hope for people who want to live longer but don’t want to tightly control calories. Researchers in the National Institute on Aging’s Interventions Testing Program prolonged the lifespan of elderly mice by feeding the mice high doses of rapamycin, a drug commonly used to suppress the immune system of organ transplant recipients. The drug is the first molecular mimic of caloric restriction proven to extend lifespan in mammals. A highly touted compound called resveratrol is still in testing, but in other studies has failed to prolong lifespan of mice on a normal diet.

Rapamycin targets an energy-sensing protein called TOR, perhaps tricking cells into thinking their calorie intake has been cut.

Team members at the Jackson Laboratory in Bar Harbor, Maine, the University of Michigan in Ann Arbor and the University of Texas Health Science Center at San Antonio each fed rapamycin to mice starting when the animals were 600 days old, about 60 years old in human terms.

Female mice fed rapamycin lived about 14 percent longer than female mice that didn’t get the drug. Male mice on rapamycin lived, on average, 9 percent longer than male mice in the control group. The increase might seem minimal, says David Harrison, a physiological geneticist at the Jackson Lab and a lead author of the new mouse study, but the researchers were surprised to see any effect at all in the older animals. Calorie restriction has generally not been effective for prolonging lifespan in mice when started after 18 months of age. Eliminating all deaths from cancer and cardiovascular disease would increase human lifespan less than 9 percent, he says.

But living longer doesn’t mean much if the intervention doesn’t also improve health, says Matt Kaeberlein, a molecular biologist at the University of Washington in Seattle.

“Most people don’t want to live an extra 10 years of frailty in old age, what we want is another 10 years of youth and vitality,” he says.

The researchers did not directly examine the health effects of rapamycin in the study, but the results suggest that rapamycin does extend the health-span as well as the lifespan of mice, Kaeberlein says. The researchers tested only one dose of the drug. Other doses may have even more beneficial effects on lifespan. Before such a drug could be used in humans, scientists need to separate the immune-suppressing properties of the drug from its life-extending potential, he says.

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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