The results of a 20-year-long study on caloric restriction in rhesus monkeys provides the strongest evidence yet that a low-calorie diet produces life-extending metabolic changes in primates — even, perhaps, in people.
Fed a diet that provided adequate nutrition on 30 percent fewer calories than is considered normal, the monkeys have largely escaped the ravages of heart disease, cancer and other age-related diseases.
“We’ve published before on some of the positive effects, but this is the big picture that says it works,” said Ricki Colman, a gerontologist at the Wisconsin National Primate Research Center. “This gives us what we need to look at what caloric restriction is doing to the aging process.”
Caloric restriction came to scientific attention in the mid-1930s, when Cornell researchers showed that it extended the lives of mice by about 40 percent. The feat was subsequently duplicated in many other animals, from roundworms to dogs, but until now had not been conclusively demonstrated in primates.
Despite the uncertainty, it’s estimated that several thousand people already practice caloric restriction, with several hundred doing so within carefully monitored studies. But such dietary limitation may prove undesirable or impossible for most people. Instead, scientists want to find drugs that mimic the effects of caloric restriction, and over the last decade have described some of its underlying biology.
Caloric restriction appears to trigger energy-saving metabolic changes, activating metabolic pathways involved in regulating cell growth and repair. These pathways are targeted by several drugs currently under development, including resveratrol, which has protected animals from age-related diseases and is now being tested as a diabetes treatment. Another intriguing drug is rapamycin, an immune system suppressor that — though unproven and likely unsafe for human use as a longevity enhancer — has dramatically extended the lives of elderly mice.
Research on these experimental drugs is validated by today’s findings, which suggest that effects observed in animals may be similar in people.
“Up until now, all the clear-cut evidence that caloric restriction slows aging has come from lower organisms,” said John Holloszy, a Washington University gerontologist who studies caloric restriction in people and was not involved in the current monkey study. “This is the first study to show that caloric restriction slows aging in a primate species. And of course, we’re primates, too. It’s a lot more relevant to humans than the mouse.”
The new research was published Thursday in Science and traces its origins to 1989, when the study began with 30 adult monkeys. Another 46 monkeys were added in 1994.
Half the monkeys were fed a low-calorie diet, and the other half a standard diet. All were closely monitored, with researchers regularly measuring their body composition, blood chemistry and endocrine function, as well as heart and brain function. When monkeys died, they were necropsied and the causes of death established.
All the surviving monkeys are now at least 27 years old, the rhesus equivalent of old age. Those fed a calorically restricted diet have dramatically lower levels of cancer, diabetes, heart disease, brain atrophy and lean-muscle loss. Just five of the 38 restricted monkeys have died from age-related causes, compared to 14 of 38 in the control group.
“Now we know that it works in a species closely related to humans. We can probe at the mechanisms, and hopefully understand them well enough to modulate them in some other way,” said Colman.
Whether drugs that mimic caloric restriction will benefit humans remains to be seen, and side effects are yet to be determined. But researchers can at least contemplate the possibility of slowing aging.
“It used to be said that it’s not going to be possible to affect aging, because there are so many different factors involved,” said Holloszy. “That’s no longer true. There are studies showing that affecting just one pathway produces long increases in longevity.”