Can eating less help you live longer?

If you put a laboratory mouse on a diet, reducing the animal’s caloric intake by 30 to 40 percent, it will live, on average, 30 percent longer. Caloric restriction, as the intervention is technically called, cannot be so extreme that the animal is malnourished, but it should be aggressive enough to cause 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. Later 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 animal research, many unknowns remain. Experts are still debating how it works, and whether it’s the number of calories consumed or the window of time in which they’re eaten (also known as intermittent fasting) that matters more.

And it’s still frustratingly uncertain whether eating less can also help people live longer. Aging experts are known for experimenting with different dietary regimens, but actual longevity studies are few and far between because they take, well, a long time.

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

Why would cutting 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 the wild, animals experience periods of feast and famine, just like our human ancestors. Therefore, their biology (and possibly ours) evolved to survive and thrive not only during seasons of abundance, but also during seasons of deprivation.

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

Another explanation is that, in both humans and animals, eating fewer calories slows down the metabolism. The less your body has to metabolize, the longer you 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 down the wheels and the tires will last longer.

Caloric 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 parts of malfunctioning cells and uses them for energy. This helps cells work better and reduces the risk of various age-related diseases.

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

There are some notable exceptions to the findings on longevity and calorie restriction. The most surprising was a study that Dr. 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 had shorter lifespans.

This was truly unheard of, said Dr. Nelson, and noted that most articles on calorie restriction begin by saying, Food restriction is the most robust and nearly universal means of extending species life span across the animal kingdom and blah, blah, blah.

Other researchers have disputed the significance of Dr. Nelson. People cite this study as if it were general evidence that calorie restriction works only a small part, or part of the time, Dr. Miller said. But you can only come to that conclusion if you ignore 50 years of solid published evidence that says it works almost all the time.

However, the study of Dr. Nelsons was not alone in not finding a universal longevity benefit with caloric restriction. For example, two studies in monkeys over 20 years, published in 2009 and 2012, reported conflicting findings. Animals in both experiments showed some health benefits related to calorie restriction, but only one group lived longer and had lower rates of age-related diseases, such as cardiovascular disease and diabetes.

What does intermittent fasting have to do with it?

Faced with these conflicting results, some researchers wonder if there might be another variable at play that is just as, or even more, important than the number of calories an animal eats: the time window in which it eats 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 were given only one meal a day, and the researchers took away leftovers at the last minute in the afternoon, so the animals were forced to fast for about 16 hours. In the 2012 study, led by the National Institute on Aging, animals were fed twice a day and food was left out overnight. The monkeys from Wisconsin lived the longest.

A more recent study in mice explicitly tested the effects of caloric restriction with and without intermittent fasting. The scientists gave the animals the same low-calorie diet, but some had access to food for only two hours, others for 12 hours, and another group for 24 hours. Compared to a control group of mice that were allowed to graze on a full-calorie diet at any time, the low-calorie mice with 24-hour access lived 10 percent longer, while the low-calorie mice that ate in of specific time windows had an increase in lifespan of up to 35 percent.

Based on this collection of findings, Rafael de Cabo, an NIA senior researcher who helped lead the monkey study there, now thinks that while caloric restriction is important for longevity, the amount of time spent eating and not eating each day is just as critical. And this could be the case not only for animals, but also for humans.

What does this mean for me?

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

I don’t think we have any evidence that it extends the lifespan of humans, said Dr. Nelson. 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.

A clinical trial called the Calerie study tried to answer that question by examining how cutting calories by 25 percent over two years affected a number of measures related to aging. More than 100 healthy adults were counseled on meal planning and provided with regular counseling sessions to help them achieve their diet goals. But because it’s so difficult to cut calories, the participants were ultimately only able to reduce their intake by 11 percent.

Compared to control participants, the dieters improved several aspects of their cardiometabolic health, including blood pressure and insulin sensitivity, and had lower levels of some markers of inflammation.

The study also included three measures of biological age, comparing blood tests taken at the beginning and at the end of the two years. Two of the tests found no improvement in either group, but the third, which aims to measure how quickly people age, did show a difference between dieters. Calorie restriction didn’t make people younger, but it did slow the rate at which they aged, said Dr. Huffman, who worked on the trial.

For Dr. Miller, the most significant conclusion of this study is that the 25 to 40 percent caloric restriction shown to be beneficial in animals is not realistic in people. Everything that could be done to try to help them cut calories was done for the participants, he said, and they still fell short of the 25 percent goal.

Dr. de Cabo took a different view: With only 11 percent calorie restriction achieved by participants, they still show benefits, he said.

Other research has focused on the short-term effects of intermittent fasting in people with various body mass indexes. Some studies, which tested various 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 period but did not cut calories, compared with a control group.

And to add a final twist, there is a remarkable body of evidence that seems to directly contradict the idea that caloric restriction or fasting, which usually leads to weight loss, extends human life. Research consistently finds that people classified as overweight have a lower risk of death than normal or underweight people. One hypothesis is that people with a lower BMI may be thin because they are older or have a chronic illness. Another is that people with a higher BMI 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, Dr. Huffman.

Despite nearly a century of research, there’s still a ways to go before experts can say for sure whether the longevity benefits seen in animals will translate to humans. Some studies give reason to believe that calorie restriction and intermittent fasting will help you live longer, and there are likely short-term benefits, especially for heart and metabolic health. But it’s also possible that eating less won’t do much more than make you hungry.

Audio produced by Kate Winslett.