Calorie restriction: understand why eating less can help you live longer

If you put a laboratory rat on a diet, reducing the animal’s caloric intake by 30% to 40%, it will live, on average, about 30% longer. Calorie restriction, as the intervention is technically called, cannot be so extreme that the animal becomes malnourished, but must be aggressive enough to trigger some key biological changes.

Scientists first discovered this phenomenon in the 1930s, and over the past 90 years it has been replicated in species ranging from worms to monkeys. Subsequent studies also found that many of the calorie-restricted animals were less likely to develop cancer and other chronic diseases related to aging.

But despite all the research on animals, there are still many unknowns. Experts are still debating how it works and whether it’s the number of calories consumed or the window of time in which they are consumed (also known as intermittent fasting) that matters more.

And it’s still frustratingly uncertain whether eating less can help people live longer, too. Aging experts are known for experimenting with different eating regimens, but actual studies on longevity are scarce and difficult to conduct because they take, well, a long time.

Here’s a look at what scientists have learned so far, mostly through animal studies, and what they think it could mean for humans.

Why would reducing calories increase longevity?

Scientists don’t know exactly why eating less would make an animal or person live longer, but many hypotheses have an evolutionary bent. In nature, animals experience periods of food abundance and famine, just like our human ancestors. Therefore, their biology (and conceivably ours) evolved to survive and thrive not only during seasons of abundance but also those of deprivation.

One theory is that, at a cellular level, calorie restriction makes animals more resilient to physical stressors. For example, calorie-restricted mice have greater resistance to toxins and recover more quickly from injuries, said James Nelson, professor of cellular and integrative physiology at the University of Texas Health Science Center in San Antonio.

Another explanation involves the fact that, in both humans and animals, eating fewer calories slows down metabolism. It’s possible that “the less the body has to metabolize, the longer it can live,” said Kim Huffman, an associate professor of medicine at Duke University School of Medicine who has studied calorie restriction in people. “Just slow down the wheels and your tires will last longer.”

Calorie restriction also forces the body to rely on fuel sources other than glucose, which aging experts find beneficial for metabolic health and, ultimately, longevity. Several researchers have pointed to a process known as autophagy, where the body consumes dysfunctional parts of cells and uses them for energy. This helps cells function better and reduces the risk of several age-related diseases.

In fact, scientists think that one of the main reasons calorie-restricted diets make mice live longer is because the animals don’t get sick as soon, if at all, said Richard Miller, a professor of pathology at the University of Michigan.

There are some notable exceptions to the results around longevity and calorie restriction. The most striking was a study that James Nelson published in 2010 on genetically diverse mice. He found that some of the mice lived longer when they ate less, but a larger percentage actually lived shorter lives.

“That was kind of really unprecedented,” Nelson said, noting that most articles on calorie restriction begin by saying, “’Food restriction is the most robust, nearly universal, means of extending lifespan in species across the animal kingdom. ‘ and blah, blah, blah.”

Other researchers disputed the significance of the results. “People cite this study as if it’s general evidence that calorie restriction only works a small part of the time, or some part of the time,” Miller said. “But you can only reach that conclusion if you ignore 50 years of strong published evidence that it almost always works.”

James Nelson’s study wasn’t the only one that didn’t find a universal longevity benefit from calorie restriction, however. For example, two studies conducted on monkeys over 20 years, published in 2009 and 2012, reported conflicting results. Animals in both experiments showed some health benefits related to calorie restriction, but only one group lived longer and had lower rates of aging-related diseases such as cardiovascular disease and diabetes.

What does intermittent fasting have to do with it?

Given these mixed results, some researchers wonder whether there might be another variable at play that is as, or even more, important than the number of calories an animal eats: the window of time in which it consumes them.

A key difference between the two monkey tests was that in the 2009 study, conducted at the University of Wisconsin, the calorie-restricted animals received just one meal per day, and the researchers removed any remaining food in the late afternoon so that the animals were forced to fast for about 16 hours. In the 2012 study, carried out by the National Institute on Aging, animals were fed twice a day and the food was left overnight. The Wisconsin monkeys lived the longest.

A more recent study in mice explicitly tested the effects of calorie restriction with and without intermittent fasting. The scientists gave the animals the same low-calorie diet, but some had access to food for just two hours, others for 12 hours, and another group for 24. Compared to a control group of mice that were allowed to eat a full-calorie diet at any given time, low-calorie mice that ate within specific time windows lived up to 35 percent longer.

Based on this collection of findings, Rafael de Cabo, who helped lead the monkey study, now believes that while calorie restriction is important for longevity, the amount of time spent eating each day is equally critical. And this may be the case not only for animals, but also for humans.

What does this mean for me?

It’s difficult to definitively answer whether intermittent fasting, calorie restriction, or a combination of the two could make people live longer.

“I don’t think we have evidence that it increases longevity in humans,” Nelson said. That doesn’t mean it can’t work, he added, just that the evidence is “very difficult to obtain because it takes a lifetime to get that data.”