Two rhesus macaques partaking in the University of Wisconsin-Madison study. The picture, which was taken back in 2009, shows Canto (left) and Owen (right). Shockingly, Canto, who is on a CR diet, is 29, while Owen, who receives pellets consisting of 30% sugar, is 27. (Image: University of Wisconsin-Madison, photo by Jeff Miller)

Depriving ourselves of food to the point of near-starvation doesn’t sound very appealing, but it could prolong our lives and prevent the onset of age-related diseases. A combined analysis of two long-running studies shows that caloric restriction does indeed work in monkeys, hinting at its potential to work in humans. More research is needed before we can be sure this translates to humans, so you should probably avoid any drastic dietary measures for now.

A collaborative study from the University of Wisconsin-Madison and the National Institute on Aging shows that caloric restriction (CR) can improve health and survival in rhesus monkeys. The new study, published in Nature Communications, is helping to resolve one of the more controversial areas of aging research, while also clarifying how CR works in primates.

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Back in the 1930s, researchers noticed that rats who had been deprived of food appeared to live longer than their well-fed brethren. It was the first evidence showing that aging is a biological process that can be altered. Follow-up studies on yeast produced similar results, bolstering the notion that caloric intake is somehow tied to longevity and health. Since the 1980s, various research teams have sought to prove this claim by conducting experiments on animals, typically by cutting back on their normal caloric intake. Importantly, these animals aren’t starving, nor are they malnourished, but they are achingly close to the starvation point.

A pair of 27-year-old monkeys, the one of the left having eaten more over his lifetime than his calorically restricted peer. (Image: (Image: University of Wisconsin-Madison)

In a landmark 2009 study, a team from the University of Wisconsin-Madison showed that CR conferred significant benefits to rhesus monkeys, improving their survival and helping to stave-off age-related disease such as cancer, cardiovascular disease, and insulin resistance. Three years later, however, a team from the National Institute on Aging reported no significant improvement in survival rates among monkeys, but they did notice a tendency toward improved health.

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“These conflicting outcomes had cast a shadow of doubt on the translatability of the caloric-restriction paradigm as a means to understand aging and what creates age-related disease vulnerability,” noted NIA scientist Rozalyn Anderson, one of the report’s corresponding authors, in a statement.

For the new study, these rival research teams put their heads together to see if they could figure out why they ended up with such different results. To that end, they looked at data that had been collected over the years, including work done on nearly 200 monkeys. Their analysis shows that CR does indeed help monkeys live healthier and longer lives—and that there were significant discrepancies in the two studies, making correlations difficult.

For example, the rhesus monkeys used in the two studies were put on CR diets at different ages. It turns out that CR is beneficial for adult and older primates, but not for younger animals (this isn’t the case among rodents, who respond to CR even at a young age, both in terms of health and longevity). The researchers also discovered that food intake was inconsistent among the various test and control groups, and that even the smallest differences in food intake in primates were affecting aging and health.

Relatedly, they found that the quality of foods fed to the monkeys varied wildly between the two studies. The NIA monkeys were fed naturally-sourced foods, while the UW-Madison monkeys ate processed foods with a higher sugar content. This resulted in substantially fatter control-group monkeys at at UW-Madison.

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The researchers also found that moderate CR is quite effective, but more severe reductions of food intake were not beneficial to the monkeys’ health (in CR studies, 20 percent is considered mild, 30 percent is moderate, and 50 percent is severe). In the UW-Madison trial, the monkeys lived significantly longer than the controls; males on CR diets lived about two years longer, while females on CR diets lived about six years longer. The primates also exhibited lower rates of cancer and heart disease.

The exact mechanism by which CR can boost longevity is still a matter of debate. Possible contributing factors scientists have identified include reduced core body temperature, reduced cellular divisions, lower metabolic rates, and reduced DNA damage.

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“It is unprecedented that research teams like this would come together, pool their data, and find a way to explain why they found somewhat different results,” said S. Jay Olshansky, an aging expert at Chicago’s University of Illinois, who wasn’t involved in the study. “We can now add CR to the arsenal of potential interventions designed to extend the period of healthy life in humans...but now there is reason to believe that accompanying health extension will be an extension of lifespan as well.” Olshansky says we still haven’t proven that CR works the same way in humans, but we now have a “reason to be optimistic that CR yields both health and longevity benefits in humans,” he told Gizmodo.

No human trials are planned, but some early-adopters have already jumped on the CR bandwagon. The website CR Society International provides information and resources for people who are interested.

Kevin Perrott, a director of the SENS Foundation, is excited by the results, and says this work should serve as inspiration to labs who are working on the same problem. “Lack of transparency and sharing of information at the outset in the planning stages of experiments results in delays which ultimately cost lives and causes decades of stalled progress while the scientific community struggles to obtain funding to reproduce results,” he told Gizmodo. “If the earlier experiments had been coordinated and sharing of information had been built in at the design-phase of the experiments, we could have had this information a lot sooner.”

Biogerontologist Aubrey de Grey says this paper ameliorates the discrepancies found in the two papers, but he’s worried that the health benefits of CR are being exaggerated. “Unfortunately, [this study] solidifies the central conclusion that too many in the field have chosen to downplay, namely that the magnitude of the longevity impact—and even the health impact—that CR delivers in monkeys, measured as a proportion of lifespan, will never rise to even a fraction of what is seen in rodents,” he told Gizmodo. “That conclusion is actually very strongly predicted by basic evolutionary theory, so its confirmation by these immensely long and arduous experiments is heartening in a way, but it also casts grave doubt on the value of the many current efforts to develop ‘CR mimetics’ that can be used by humans.”

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By “CR mimetics,” de Grey is referring to a hypothetical class of dietary supplements or medicines that would replicate the effects of a calorically restricted diet. It’s not immediately obvious if these drugs are possible, or if they’ll have a measurable impact on health and longevity. Like other advocates of radical life extension, de Grey believes that more substantive interventions will be required to stave off the many effects of aging—and not just a drug that purportedly mimics the effects of near-starvation.

[Nature Communications]