THE NEW YORK TIMES: Could eating less help you live longer?

If you put a lab mouse on a diet, cutting the animal’s caloric intake 30% to 40%, it will live, on average, about 30% longer. The calorie restriction, as the intervention is technically called, can’t be so extreme that the animal is malnourished, but it should 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. The 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 remain a lot of 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 eaten (also known as intermittent fasting) that matters more.

And it’s still frustratingly uncertain whether eating less can help people live longer, as well. Aging experts are notorious for experimenting on themselves with different diet regimens, but actual longevity studies are scant and difficult to pull off because they take, well, a long time.

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

Q: Why would cutting calories increase longevity?

A: Scientists don’t exactly know why eating less would cause an animal or person to live longer, but many hypotheses have an evolutionary bent. In the wild, animals experience periods of feast and famine, as did our human ancestors. Therefore, their (and conceivably our) biology evolved to survive and thrive not only during seasons of abundance, but also seasons of deprivation.

One theory is that, on a cellular level, calorie restriction makes animals more resilient to physical stressors. For example, calorie-restricted mice have greater resistance to toxins and recover faster from injury, said James Nelson, a professor of cellular and integrative physiology at the University of Texas Health Science Center at 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 you have to get your body to metabolize, the longer it can live,” said Dr. Kim Huffman, an associate professor of medicine at Duke University School of Medicine who has studied calorie restriction in people. “You know, just slow the wheels down and the tires will last longer.”

Calorie restriction also forces the body to rely on fuel sources other than glucose, which aging experts think is beneficial for metabolic health and, ultimately, longevity. Several researchers pointed to a process known as autophagy, where the body eats up malfunctioning parts of cells and uses them for energy. This helps cells function better and lowers 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 early, if at all, said Dr. Richard Miller, a professor of pathology at the University of Michigan.

There are a few notable exceptions to the findings around longevity and calorie restriction. Most striking was a study Nelson published in 2010 on mice that were genetically diverse. He found that some of the mice lived longer when they ate less, but a larger percentage actually had a shorter life span.

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“That was kind of really unheard of,” Nelson said, noting that most papers on calorie restriction start out by saying: “‘Food restriction is the most robust, almost universal means of extending life span in species across the animal kingdom’ and blah, blah, blah.”

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Other researchers have disputed the significance of Nelson’s findings. “People cite this study as though it were general evidence that caloric restriction only works a tiny portion, or some portion of the time,” Miller said. “But you can reach that conclusion only if you ignore 50 years of strong published evidence saying that it works almost all the time.”

Nelson’s study wasn’t the only one that didn’t find a universal longevity benefit with calorie restriction, though. For example, two studies conducted in monkeys for over 20 years, published in 2009 and 2012, reported conflicting findings. Animals in both experiments showed some health benefits tied to caloric restriction, but only one group lived longer and had lower rates of age-related diseases, like cardiovascular disease and diabetes.

Q: What does intermittent fasting have to do with it?

A: In the face of these mixed results, some researchers wonder if there may be another variable at play that is just as, or even more, important than the number of calories an animal eats: the window of time in which they eat them.

A key difference between the two monkey trials was that in the 2009 study, conducted at the University of Wisconsin, the calorie-restricted animals only received one meal a day and the researchers took away any leftover food in the late afternoon, so the animals were forced to fast for about 16 hours. In the 2012 study, run by the National Institute on Aging, the animals were fed twice a day and the food was left out overnight. The Wisconsin monkeys were the ones that lived longer.

A more recent study conducted in mice explicitly tested the effects of calorie restriction with and without intermittent fasting. Scientists gave the animals the same low-calorie diet, but some had access to the food for just two hours, others for 12 hours and another group for 24. Compared to a control group of mice that could graze on a full-calorie diet at any time, the low-calorie mice with 24-hour access lived 10% longer, while the low-calorie mice that ate within specific time windows had up to a 35% increase in life span.

Based on this collection of findings, Rafael de Cabo, a senior investigator at the NIA who helped lead the monkey study there, now thinks that while calorie restriction is important for longevity, the amount of time spent eating — and not eating — every day is just as critical. And that might be the case not only for animals, but also for humans.

Q: What does this mean for me?

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

“I don’t think we have any evidence that it extends life span in humans,” Nelson said. That doesn’t mean it can’t work, he added, just that the evidence is “very hard to come by because it takes a lifetime to get that data.”

One clinical trial — named the Calerie study — attempted to answer this question by examining how cutting calories by 25% for two years affected a range of measurements related to aging. More than 100 healthy adults were advised on meal planning and given regular counseling sessions to help them reach their diet goals. But because it’s so difficult to reduce calories, participants were ultimately only able to reduce their intake by about 11%.

Compared to control participants, the dieters improved several aspects of their cardio-metabolic health, including blood pressure and insulin sensitivity, and they had lower levels of a few markers of inflammation.

The study also included three measures of “biological age,” comparing blood tests taken at the beginning and end of the two years. Two of the tests didn’t find an improvement in either group, but the third, which purports to measure how fast people age, did show a difference in the dieters. Calorie restriction “didn’t make people younger, but it made the rate at which they age slower,” said Huffman, who worked on the trial.

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To Miller, the most significant conclusion from this study is that the 25% to 40% calorie restriction shown to be beneficial in animals is just not realistic in people. “Everything that could be accomplished to try to help them” cut calories was done for the participants, he said, and they still fell short of the goal of 25%.

De Cabo had a different take: “With only 11% calorie restriction that was achieved by the participants, they still show benefits,” he said.

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Other research has focused on the short-term effects of intermittent fasting in people with a range of body mass indexes. Some studies, testing a variety of fasting schedules, showed improved metabolic health and reduced inflammation. But a trial of 116 people whose BMI classified them as overweight or obese found no benefit among those who ate within an eight-hour window but didn’t reduce their calories, compared with a control group.

And to add a final twist, there is a notable body of evidence that appears to directly contradict the idea that calorie restriction or fasting, which typically leads to weight loss, extends human life span. Research consistently finds that people who are classified as overweight have a lower risk of death than those who are normal or underweight. One hypothesis is that people with the lowest BMIs may be thin because they are older or have a chronic illness. Another is that people with higher BMIs have more muscle, which weighs more than fat. But it’s also conceivable that, especially later in life, having greater body mass is actually protective, Huffman said.

Despite nearly a century of research, there’s still a ways to go before experts can say for certain whether the longevity benefits seen in animals will translate to humans. Some studies provide reason to believe that calorie restriction and intermittent fasting will help you live longer, and there are likely shorter-term benefits, particularly when it comes to heart and metabolic health. But it’s also possible that eating less might not do much more than leave you hungry.

This article originally appeared in The New York Times.

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