If you put a laboratory mouse on a diet and reduce the animal’s calorie intake by 30 to 40 percent, the animal will live, on average, about 30 percent longer. The calorie restriction, as the intervention is technically called, should not be so extreme that the animal becomes malnourished, but it should be aggressive enough to induce some important biological changes.
Scientists first discovered this phenomenon in the 1930s, and over the past ninety years it has been repeated 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 associated with aging.
But despite all the research on animals, there are still many unknowns. Experts still debate how it works, and whether the number of calories consumed or the time period in which they are eaten (also called intermittent fasting) is more important.
And it is still frustratingly uncertain whether eating less can also help people live longer. Experts on aging are known for experimenting with different diets on their own, but actual studies on longevity are scarce and difficult to conduct because they are, well, long.
Here’s a look at what scientists have learned so far, mainly through groundbreaking animal studies, and what they think it could mean for humans.
Why would cutting calories increase lifespan?
Scientists don’t know exactly why eating less would make an animal or person live longer, but many hypotheses have an evolutionary slant. In the wild, animals experience periods of feast and famine, just like our human ancestors. Therefore, their (and possibly our) biology evolved to survive and thrive not only during seasons of plenty, but also during seasons of hardship.
One theory is that calorie restriction makes animals more resilient to physical stressors at the cellular level. For example, calorie-restricted mice have greater resistance to toxins and recover more quickly from injury, says James Nelson, professor of cellular and integrative physiology at the University of Texas Health Science Center at San Antonio.
Another explanation relates to the fact that, in both humans and animals, eating fewer calories slows down metabolism. It’s possible that “the less your body has to metabolize, the longer it can live,” says Dr. Kim Huffman, an associate professor of medicine at Duke University School of Medicine, who has researched calorie restriction in humans. “You know, just slow down the wheels and the tires will last longer.”
Calorie restriction also forces the body to rely on fuel sources other than glucose, which aging experts believe is beneficial for metabolic health and ultimately longevity. Several researchers pointed to a process known as autophagy, in which the body eats defective parts of cells and uses them for energy. This helps the cells function better and reduces the risk of various age-related diseases.
In fact, scientists think one of the main reasons why calorie-restricted diets help mice live longer is that the animals don’t get sick as early or at all, said Dr. Richard Miller, professor of pathology at the University of Michigan. .
There are a few notable exceptions to the findings surrounding longevity and calorie restriction. Most notable was a study that Dr. Nelson in 2010 published about mice that were genetically diverse. He found that some mice lived longer when they ate less, but a larger percentage actually had a shorter lifespan.
“That was actually unheard of,” said Dr. Nelson, noting that most articles on calorie restriction start by saying, “’Food restriction is the most robust, nearly universal way to extend the lifespan of species in the animal kingdom.’ and blah, blah, blah.”
Other researchers have questioned the significance of Dr. Nelson disputes. “People cite this study as if it is general evidence that calorie restriction only works a small portion, or some of the time,” said Dr. Miller. “But you can only come to that conclusion if you ignore fifty years of strong published evidence that says it almost always works.”
The study of Dr. However, Nelson was not alone in not finding a universal longevity benefit with calorie restriction. For example, two studies conducted in monkeys for more than two decades, published in 2009 and 2012, reported conflicting findings. Animals in both experiments showed some health benefits associated with calorie restriction, but only one group lived longer and had fewer age-related diseases, such as cardiovascular disease and diabetes.
What does intermittent fasting have to do with it?
In light of these mixed results, some researchers are wondering whether there might be another variable at play that is just as important, if not more so, than the number of calories an animal eats: the time frame in which the animal 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 fed only one meal per day and the researchers took away any leftover food in the late afternoon so that the animals were forced to fast for about 16 hours. In the 2012 study, conducted 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 who lived longer.
A more recent study in mice explicitly tested the effects of calorie restriction with and without intermittent fasting. Scientists fed the animals the same low-calorie diet, but some had access to the food for only two hours, others for 12 hours and another group for 24 hours. Compared to a control group of mice 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 within specific time intervals had a 35 percent lifespan extension.
Based on this collection of findings, Rafael de Cabo, a senior researcher at the NIA who helped lead the monkey study there, now thinks that while calorie restriction is important for longevity, the amount of time you spend eating each day (and not eating) just as critical. And that may not only apply to animals, but also to people.
What does this mean for me?
It’s difficult to definitively answer whether intermittent fasting, calorie restriction, or a combination of the two can help people live longer.
“I don’t think we have any evidence that it extends human lifespan,” said Dr. Nelson. That doesn’t mean it can’t work, he added, just that the evidence is “very difficult to get because it takes a lifetime to get that data.”
One clinical trial – called the Calerie Study – attempted to answer this question by examining how cutting calories by 25 percent for two years affected a series of measurements related to aging. More than 100 healthy adults were counseled on meal planning and received regular counseling sessions to help them achieve their diet goals. But because it’s so difficult to cut calories, participants were ultimately only able to reduce their intake by about 11 percent.
Compared with control participants, the dieters improved several aspects of their cardio-metabolic health, including blood pressure and insulin sensitivity, and had lower levels of some inflammatory markers.
The study also included three measurements of ‘biological age’, comparing blood tests at the beginning and end of the two years. Two of the tests found no improvement in either group, but the third, which claims to measure how quickly people age, did show a difference in the dieters. Calorie restriction “hasn’t made people younger, but it has increased the rate at which they age,” says Dr. Huffman, who collaborated on the study.
According to Dr. Miller’s main takeaway from this study is that the 25 to 40 percent calorie restriction that has been shown to be beneficial in animals is simply not realistic in humans. “Everything that could be done to help them” was done for participants, he said, and they still fell short of the 25 percent goal.
Dr. de Cabo had a different opinion: “With only 11 percent calorie restriction achieved by participants, they still showed benefits,” he said.
Other research has focused on the short-term effects of intermittent fasting in people with different body mass indexes. Some studies testing different 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 in those who ate within an eight-hour window but did not reduce their calories, compared with a control group.
And to put a final twist on it, there is a remarkable body of evidence that appears to directly contradict the idea that calorie restriction or fasting, which typically leads to weight loss, extends human lifespan. Research consistently shows that overweight people have a lower risk of death than normal or underweight people. One hypothesis is that people with the lowest 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, said Dr. Huffman.
Despite nearly a century of research, there is still a long way to go before experts can say with certainty whether the longevity benefits of animals will translate to humans. Some research gives reason to believe that calorie restriction and intermittent fasting will help you live longer, and there are likely shorter-term benefits, especially when it comes to heart health and metabolism. But it’s also possible that eating less doesn’t do much more than make you hungry.