Low-calorie diet slowed aging in monkeys

Rhesus monkeys Canto (left) and Owen (right) are among the oldest subjects in a 20-year study that found calorie restriction can slow aging. Canto, 27, is on a restricted diet. Owen, 29, is on a normal diet.
CREDIT: University of Wisconsin-Madison, photo by Jeff Miller

By Carolyn Y. Johnson, Globe Staff

Scientists have long known that dramatically cutting calories can extend the lives of yeast, flies, and rodents, discoveries that have sparked a fevered quest for a human fountain of youth.

In labs in Cambridge and elsewhere, researchers are searching for drugs that would mimic the effects of calorie restriction, and products based on this intriguing idea are already widely sold as anti-aging nostrums -- though there has been little evidence that they work in humans.

But today, researchers reported that rhesus monkeys on a low-calorie diet live longer and healthier lives, a finding two decades in the making that suggests, because monkeys and humans are genetic cousins, such diets might slow aging in people, too.

"For 70 years, people have been wondering whether this phenomenon that occurs in rats might also occur in humans," said David Sinclair, a pathology professor at Harvard Medical School who was not involved with the study. "What this paper says is while we don't know for sure, we've got one extra point on the side of the people who believe it will work in humans."

Because of the long lifespan of people and the rigors of the diet, studies of calorie restriction in humans are ongoing and have yet to show that people live longer.

Scientists said the monkey study is a significant advance in a story that began in 1935, when researchers first discovered that a nutritious but calorie-restricted diet served as a fountain of youth for rodents.

That finding grew into a body of research revealing the beneficial effects of calorie restriction in other species and sparked a search for drugs that would exploit the same biological pathways without requiring people to go on drastic diets. Sirtris, a Cambridge company that Sinclair co-founded and was bought last year by pharmaceutical giant GlaxoSmithKline for $720 million, is a leader in these efforts.

Sinclair's discovery that resveratrol, a natural ingredient found in red wine, could mimic the effects of calorie restriction in yeast and fruit flies, has helped fuel over-the-counter sales of the drug. It also spurred Sirtris to create drugs that mimic resveratrol but are more potent and might be used to treat diseases of aging. The company is currently testing one such drug in people with type 2 diabetes.

Other approaches are being investigated as well. A study published in the journal Nature this week found that rapamycin, an organ transplant drug, significantly extended lifespan in mice.

But much remains unanswered about these drugs' ability to slow aging. A study last year reported that resveratrol had health benefits for adult mice but did not help those fed a standard diet live longer. Researchers also cautioned people not to take rapamycin because it suppresses the immune system.

In the new study, published in the journal Science, researchers followed a group of 76 rhesus monkeys who took different paths in adulthood. When the monkeys were between 7 and 14 years old, half were put on a diet consuming 30 percent fewer calories and half continued as before.

After two decades, five monkeys on a restricted diet had died of age-related causes such as cardiovascular disease or cancer, compared with 14 monkeys on a normal diet. The monkeys on the restricted diet were healthier overall, with no diabetes, and fewer cases of cancer or cardiovascular disease. In key regions, their brain tissue also shrunk less than monkeys on a normal diet.

They monkeys on a normal diet also looked visibly older, their eyes more sunken in and their coats thinner and posture cramped when compared with their dieting counterparts, according to Ricki J. Colman, lead author of the paper and a scientist at the Wisconsin National Primate Research Center.

"This report in my mind represents a major transition in our project. For years, we've been asking the question: 'Will caloric restriction slow the aging process in monkeys?' Now we think that we have accumulated solid data to say yes, it will," said Richard Weindruch, a professor of medicine at the University of Wisconsin - Madison and senior author of the paper.

Leonard Guarente, an MIT biologist who did pioneering work on aging yeast and sits on the scientific advisory board of Sirtris, said the strongest result was in diabetes: dieting monkeys had no cases, while 16 of the normally fed monkeys were considered diabetic or prediabetic.

"On the critical questions of will calorie restriction work in humans, I would say that this study provides hope that it will combat diabetes and metabolic diseases, but the question of other diseases and actually living longer, are still open questions," Guarente said.

More certain answers may come with time. Weindruch is careful to call the study an interim report, with one of the most important questions still to be answered: how long will the 33 remaining monkeys -- 20 on the restricted diet, and 13 eating normally -- ultimately live? The average lifespan of a rhesus monkey in captivity is 27 years.

He also thinks that studying monkeys may explain more about the underlying reasons for human aging than rodent studies.

To Brian Delaney, president of the nonprofit Calorie Restriction Society, the research backs up something he and other members of his organization have long believed. Delaney has restricted his diet to a varying extent over the last 17 years. He skips lunch to keep his calorie count under 2,000, and is so busy, he says, that he doesn't feel hungry.

But Susan Roberts, director of the energy metabolism laboratory at the US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University and author of The Instinct Diet, pointed out that there are many other questions to be answered about the diet before recommending it to people.

Roberts, who is overseeing an ongoing clinical trial of a calorie-restricted diet in people, points out that while the monkey study provides valuable evidence of the diet's health effects, many things are left out -- including the psychological effects: Are the monkeys hungry? Happy? Able to react to stress?

She is studying 72 people, in one branch of a national calorie restriction study intended to tease out the health and psychological effects of such a diet.

"This is a good study, one that we have been waiting for a long time," Roberts wrote about the monkey research in an e-mail. "It adds to the evidence piling up that calorie restriction, independent of thinness, is a healthy way to stay alive and healthy longer. Less diseases in old age has to be something most everyone wants!"