If you put a laboratory mouse on a diet and reduce the animal’s calorie intake by 30 to 40 percent, she will live an average of 30 percent longer. The ‘calorie restriction’, as the intervention is technically called, must not go so far as to cause the animal to become malnourished, but must be sufficiently drastic to bring about a number of important biological changes.
Scientists discovered this phenomenon in the 1930s. Over the past 90 years, the experiment has been repeated in species ranging from worms to monkeys. The studies showed that many of the animals that undergo such calorie restriction are 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 still debate how the mechanism works and whether the number of calories consumed or the time interval in which they are eaten is the most important.
And it is still very uncertain whether eating less can also help you live longer. Aging experts like to experiment with different diet regimens, but real studies on longevity are scarce and difficult to conduct because they take a lot of time.
An overview of what science has taught us so far, in most cases thanks to animal studies, and what those findings could mean for people.
Why can a limited calorie intake extend lifespan?
Scientists do not know exactly why eating less makes an animal or human live longer, but many hypotheses have an evolutionary background. In the wild, animals, just like our human ancestors, experience periods of abundance and hunger. Therefore, they (and probably we) have evolved to survive and thrive even in periods of hardship.
One theory is that, at the cellular level, calorie restriction makes animals more resilient to physical stress. For example, mice that undergo calorie restriction have greater resistance to toxins and recover more quickly from injuries, according to James Nelson, professor of cellular and integrative physiology at the University of Texas Health Science Center at San Antonio.
Another explanation is that eating fewer calories slows down metabolism in both humans and animals. It’s possible that “the less you have to metabolize your body, the longer it can live,” says Kim Huffman, an associate professor of medicine at Duke University School of Medicine who has studied calorie restriction in humans. “If you spin the wheels slower, the tires will last longer.”
Calorie restriction also forces the body to rely on fuel sources other than glucose, which aging experts say is good for metabolic health and ultimately leads to a longer life. Several scientists point to a process called “autophagy,” in which the body consumes malfunctioning parts of its own cells and extracts energy from them. This helps cells function better and reduces the risk of various age-related diseases.
Scientists even think that one of the main reasons why mice live longer when calorie restricted is that the animals do not get sick as quickly. This is stated by Richard Miller, professor of pathology at the University of Michigan.
There are a few notable exceptions to the above trends. The most striking came to light in a study on genetically diverse mice that Nelson published in 2010. In that study, some mice lived longer when they ate less, but a larger percentage actually had a shorter lifespan when calorie restricted.
“That was really unheard of,” Nelson says. He notes that most articles on calorie restriction start with, “’Food restriction is the most reliable, near-universal way to extend lifespan in species across the animal kingdom’ and blah, blah, blah.”
Other researchers dispute Nelson’s findings. “People cite that study as if it’s general evidence that calorie restriction only works in some cases,” Miller said. “But you can only come to that conclusion if you ignore 50 years of strong research showing that it almost always works.”
However, Nelson’s study wasn’t the only one that failed to find a universal longevity benefit. For example, two studies conducted in monkeys over more than 20 years, published in 2009 and 2012, reported conflicting findings. Both experiments showed that calorie restriction has some health benefits, but only one group lived longer and had lower rates of age-related diseases such as cardiovascular disease and diabetes.
What has intermittent fasting or intermediate fasting?
Given these mixed results, some researchers wonder whether there might be another variable at play that is as important as or even more important than the number of calories an animal eats. An important candidate is the time frame in which the calories are consumed.
A key difference between the two monkey studies was that in the 2009 study, conducted at the University of Wisconsin, the animals that consumed a limited amount of calories were fed only one meal per day, and the researchers left the leftover food at the end. taken away in the afternoon, so that the animals were forced to fast for about 16 hours. In the 2012 study, conducted by the US National Institute on Aging, the animals were fed twice a day and the food was left overnight. The Wisconsin monkeys 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 2 hours, others for 12 hours and a third group for 24 hours a day. Compared to a control group of mice that could enjoy a complete diet at any time of the day, the mice that were fed a restricted diet and had access to it 24 hours a day lived 10 percent longer, while the mice that were fed a restricted calorie amount and who within specific time windows lived up to 35 percent longer.
Based on these findings, Rafael de Cabo, a researcher at the NIA who co-led the institution’s monkey study, now thinks that while calorie restriction is important for longevity, the time spent each day eating – and not eating – is just as important. And that may not only apply to animals, but also to people.
What does this mean for us, humans?
It is difficult to give a definitive answer to the question of whether intermittent fastingcalorie restriction or a combination of the two can ensure that you live longer.
“I don’t think we have evidence that it extends lifespan in humans,” Nelson said. That doesn’t mean it couldn’t be done, he says, it just means that the evidence for it is “very difficult to obtain because you need lifelong studies to get that data.”
One clinical trial—called the Calerie Study—tried to answer this question by examining how cutting calories by 25 percent for two years affected a range of indicators of aging. More than a hundred healthy adults received meal planning advice and attended regular counseling sessions to achieve their diet goals. But because it is so difficult to reduce calorie intake, participants were ultimately only able to limit their intake by about 11 percent.
Compared to the control group in the study, the dieters improved several aspects of their cardiometabolic health, including their blood pressure and insulin sensitivity. They also had lower levels of a number of inflammatory markers.
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 showed no improvement in either group, but the third test, which measured how quickly people age, did show a difference. Calorie restriction turned out to “not make people younger, but it does make people age more slowly,” said Huffman, who collaborated on the study.
For Miller, the most important conclusion from this study is that a 25 to 40 percent calorie restriction, which has been shown to be beneficial in animals, is simply not realistic in humans. “Everything that could be done to help participants consume fewer calories was done effectively,” he says, “and they still couldn’t achieve the target 25 percent reduction.” De Cabo looks at it differently: “Even with a calorie restriction of only 11 percent, the benefits are visible.”
Other research has focused on the short-term effects of intermittent fasting in people with different BMIs. Some studies testing different fasting schedules found participants improved metabolic health and reduced inflammation. But a study of 116 people with a BMI that classified them as overweight or obese found no health benefits among those who ate within an eight-hour period but did not reduce their calories compared to the control group.
And there’s one final twist. In fact, there is a remarkable amount of evidence that seems to contradict the idea that calorie restriction or fasting, which usually leads to weight loss, extends people’s lifespans. 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 BMIs may be thin because they are older or have a chronic illness. Another hypothesis is that people with a higher BMI have more muscle, which has a higher specific weight than fat. But it is also conceivable that a larger body mass, especially later in life, actually has a protective effect, says Huffman.
Despite nearly a century of research, there is still a long way to go before scientists can say with certainty whether the results we see in animals also apply to humans. Some research gives reason to believe that calorie restriction and… intermittent fasting help you live longer, and there are likely shorter-term benefits, especially when it comes to heart and metabolic health. But it’s also possible that eating less just makes you hungry.
© The New York Times
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