Putting monkeys on a diet delays the health problems of old age, new science says. But whether it makes them live longer is still open for debate. These findings in our close evolutionary relatives could help us better understand our own aging process — and how to slow it down. What’s more, these latest conclusions begin to resolve a scientific debate that has been unfolding (amicably, the scientists say) over the past three decades.
“Well, Great Scott! We have to resolve this!”
The two research teams that jointly published today’s study in the journal Nature Communications have been publishing contradictory results for nearly the last decade. Calorie restriction is one of the surest ways to stave off aging-related diseases and boost longevity in creatures with short lifespans, like mice, yeast, and worms. But it’s harder to figure out whether the same is true in longer-lived mammals like us.
That’s partly because humans are notoriously difficult to study. Still, one clinical study of over 200 people with healthy weights found cutting a person’s calories by about 11 percent for two years reduced their inflammation and risk factors for heart and metabolic disease by the end of the study. But they also had much lower bone density, which worried the researchers. And the clinical study couldn’t answer any questions about longevity, because investigating how calorie restriction affects the human lifespan would be a very long, very expensive project.
That’s why, in the late 1980s, one team of researchers at the University of Wisconsin and another from the National Institutes on Aging turned to rhesus macaques. Their lifespans are about a third the length of ours, but they develop and age very similarly. They get gray hair, their skin sags, and they get sick with the same diseases that aging humans do, like cancer, diabetes, and dementia.
The studies agree that restricting calories can improve health and delay age-related diseases
In 2009, the team at the University of Wisconsin published their first findings 20 years into the multi-decade study: they’d found that restricting the monkeys’ calories by 30 percent reduced their rates of diabetes, cancer, heart disease, and death. The problem was, three years later the National Institutes on Aging (NIA) scientists published the opposite results; in their study, caloric restriction didn’t affect survival, although it did improve the monkeys’ health. The Wisconsin team published a rebuttal soon after, arguing that the NIA’s control monkeys weren’t eating enough to be good comparisons for the calorie restricted monkeys.
“They had looked at some published data and took snippets, and by that data one would suggest that the NIA control monkeys were eating less than the Wisconsin control monkeys,” says Julie Mattison, the lead author on the NIA’s 2012 study and on today’s joint publication. But, Mattison added, when she looked at 25 years of data, it was clear that the NIA’s control monkeys were eating as much as they wanted.
“It was like, ‘Well, Great Scott! We have to resolve this!’” says Rozalyn Anderson, the senior investigator on the latest studies coming out of Wisconsin and a co-author on today’s paper. So, 30 years and nearly 100 monkeys-on-a-diet after they started, the two different research groups directly compared their data.
“It puts emphasis now on the idea of aging itself being a druggable target.”
Combined, the studies agree that restricting calories can improve health and delay age-related diseases. The point of contention remains whether caloric restriction can improve survival. The calorie restricted Wisconsin monkeys survived about 28 years, which is longer than the average of 26 years, and longer than the controls. But caloric restriction didn’t seem to have much of a specific effect on the NIA monkeys’ lifespans: both the dieting and the control monkeys at NIA survived an extraordinarily long time — more than 40 years, in some cases.
So, what accounted for the differences? Probably diet, at least, in part. The monkeys in both studies were mostly fed pellets made up of about 60 percent carbohydrates. But the NIA monkeys’ pellets were made from natural food sources and the carbohydrates only included about 7 percent table sugar. At Wisconsin the pellets were much more processed and artificial, and the carbs were nearly 45 percent sugar. Consequently, the Wisconsin control monkeys were chubbier and less fit than the NIA’s control monkeys — which were closer in body mass to the Wisconsin calorie-restricted monkeys.
“These studies probably answer very different questions. If you feed monkeys a more westernized diet and put them on calorie restriction, you’ll see survival effects, and health benefits,” NIA’s Mattison says. “If you feed the animals a healthier diet that’s lower in sugar, you still see health benefits. But there’s no evidence that we’re going to see survival effects.”
“I’ve seen the data, and I know how cool this all looks. But I’m not doing it.”
That’s why the differences are to be expected, says Steve Austad, who studies the biology of aging at the University of Alabama. “They diverged a little bit, and they came up with some different results,” he says. “They did everybody a real service by putting their results right next to each other.“ He adds that if he could turn back time, he would have been interested to see if feeding the NIA monkeys the Wisconsin chow made the NIA monkeys chunkier. But, moving forward, Austad thinks that studying humans will teach us the most about human aging.
In the meantime, there’s still a lot more work to do to figure out how calorie restriction improved health for these monkeys, and how diet factored in. Both teams collected decades of blood samples, tissue samples, and body measurements that have yet to be analyzed.
“Life might seem longer, but it wouldn’t necessarily be longer.”
Despite the new consensus that caloric restriction is beneficial in primates, none of these researchers are inclined to go on a similar diet themselves. “I’ve seen the data, and I know how cool this all looks. But I’m not doing it,” Anderson says. “Life is too short, and I love to eat.” Instead, she sees caloric restriction as a tool to uncover the biology of aging.
“This shows that we can actually modulate aging in primate species, and it puts emphasis now on the idea of aging itself being a druggable target,“ Anderson says. “If we can figure out how [caloric restriction] works, that would provide a whole new perspective on all these age-associated diseases.”
Austad agrees that he’s not convinced it’s time to start recommending caloric restriction to healthy people. “I’m not at all certain that people who are a healthy body weight should restrict to some emaciation level,” he says. “Life might seem longer, but it wouldn’t necessarily be longer.”