Could we live longer by eating less?

The latest in a conflicting series of studies suggests calorie restriction does slow ageing in primates, and potentially in people. James Mitchell Crow reports.

Rhesus monkeys in lab
Rhesus monkeys 27-year-old Canto, on a restricted diet (left), and 29-year-old Owen, a control subject on an unrestricted diet (right), at the Wisconsin National Primate Research Center at the University of Wisconsin-Madison. Canto and Owen were among the subjects in a pioneering long-term study of the links between diet and ageing. – Jeff Miller, University Communications, UW-Madison

Calorie restriction, or “semi-starvation” as some refer to it, has been proven to extend lifespan in many species from yeast to mice, but the picture for primates like us is not so clear.

Research published in Nature Communications this month by a team at the University of Wisconsin, shows that rhesus monkeys, our close cousins, also live longer on a calorie-restricted diet. But those findings disagree with research by the National Institute on Aging (NIA) in Maryland.

Rozalyn Anderson, a member of the Wisconsin team, says the research is not intended as a recommendation of calorie restriction. “I find the idea monumentally unattractive!” she says. “We study it because it is so effective at delaying ageing and the onset of age-related disease. It’s a way to tease out what it is that creates increased disease vulnerability as a function of age.”

Both groups started long-term trials on rhesus monkeys in the late 1980s to answer the question of whether calorie restriction would extend the lifespan of primates. In mice many experiments had come to the same finding: feed them a diet with 30% fewer calories and see a life-span extension of 40%. The monkey trials were set up a similar way: take the calorie content of a standard monkey diet, cut it by 30% (while continuing to supply all essential nutrients) and monitor whether those monkeys lived longer, healthier lives than those on the standard diet.

In 2009, with the monkeys approaching old age, the preliminary results of the two trials started trickling in. For the Wisconsin monkeys, calorie restriction seemed to be working. Compared to well-fed control animals, the lean monkeys were living longer and suffering less from the diseases of aging: diabetes, heart disease and brain diseases.

Three years later, the NIA results emerged with a dramatically different conclusion: their monkeys were not living any longer than the controls, although they were healthier.

If you take an overweight person who goes to McDonalds every day and cut back their calories by 30% you are going to have an obvious benefit.

The Wisconsin group has now reported their latest results, confirming their calorie-restricted monkeys are living longer than the controls. They also offer a possible explanation why the two groups’ findings don’t agree – differences in what was considered a normal caloric intake for a rhesus monkey, in other words the treatment of the control group.

The Wisconsin study began with monkeys in early adulthood. Initially, all the monkeys were allowed to eat as much as they liked. A few months into the trial, the monkeys were placed into one of two groups: the controls, who continued to be fed as much as they wished, and the calorie-restricted monkeys which were given an individualised diet of 30% less than they were previously eating. “It was set up to look like a human study,” Anderson says.

The NIA study differed in two ways. First, the control group of monkeys were not allowed to eat as much as they wished. They were given a diet considered to represent a normal calorie count, while the calorie-restricted monkeys were fed 30% less than that. Second, whereas the Wisconsin monkeys were given highly processed food high in sucrose, making it easy to standardise, the NIA diet was based on whole grains, fish oils, and was very low in sugar.

These different settings for the normal control diet may provide an explanation of why the two groups showed different results.

Rhesus monkey eating corn
A rhesus macaque monkey eats a cob of corn. Two apparently conflicting studies used different settings for a normal control diet. – TAO Images Limited/Getty Images

The Wisconsin group may in effect have studied the effects of “overeating”. Their control animals weighed up to 10% more than average for their age and gender. Compared to them, the calorie-restricted animals not only suffered fewer diseases, they lived longer. “If you take an overweight person who goes to McDonalds every day and cut back their calories by 30% then you are going to have an obvious benefit,” argues Julie Mattison, head of the NIA study.

On the other hand, the NIA study fed their control monkeys what they considered a “standard” caloric intake and saw no difference in longevity in monkeys that were fed 30% less. But in Anderson’s view, the NIA control monkeys were not fed enough. The NIA, in other words, was calorie restricting both groups of animals. Their older female control monkeys, for example, weighed nearly 20% less than the national average. Indeed Anderson points out that several of the NIA animals have lived past the age of 40, far exceeding the 27-year average lifespan for captive rhesus monkeys.

“That’s the maximum lifespan ever detected for the species, so the idea that their intervention is doing nothing is really at odds with the data,” says Anderson.

What we learn from these two studies then becomes a question of who has the right notion of a standard diet. And neither group quite got it right, says Leonie Heilbronn, who researches calorie restriction and healthy ageing at the University of Adelaide. The NIA controls are a very healthy set of monkeys, “leaner than a control monkey maybe should be, but on the flipside the Wisconsin controls were a little bit bigger than they had to be”, she says. On balance, Heilbronn agrees with the Wisconsin researcher’s argument. “I think these studies suggest calorie restriction definitely will increase lifespan,” she says.

Both studies agree that cutting calories is beneficial to health – in both cases the calorie-restricted monkeys had fewer age-related diseases. As to the fundamental question of whether calorie restriction extends lifespan in primates, Anderson and Mattison and their colleagues are currently working together to compare the two studies’ raw data. They plan to co-publish a joint analysis with an overall conclusion later in the year.

The current data conflict will ultimately provide deeper insights into the aging process, Anderson predicts. “The fact the two studies were set up differently, asking the same question in different ways – I think we will gain maximally from that.”

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