Why calorie restriction may be the key to a healthier life 

A new study finds that humans benefit from moderate calorie restriction, backing up decades of animal studies — and there might even be a way to enjoy those benefits without cutting down on what we eat.

The challenge: In 1935, Cornell University researcher Clive McCay discovered that rats placed on low-calorie diets lived up to 33% longer than those fed the average diet. Since then, calorie restriction has been shown to extend the lives of many other species, from flies to monkeys.

While some people have adopted a calorie-restricted diet in the hope of living longer, healthier lives, studying the effects of nutrition and dietary changes on humans the way we do animals is difficult. 

Lab mice live for a year or two, on average, so it’s easy to see big changes in lifespan in controlled experiments. Humans live for most of a century and their diets generally can’t be controlled, only observed, and correlation does not prove causation.

Rats placed on low-calorie diets lived up to 33% longer than those fed the average diet.

The trial: To clear up some of the mystery, a Yale-led team conducted the first controlled study of calorie restriction in humans: the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) clinical trial.

During the trial, the researchers determined how many calories their 200 participants typically ate. They then randomly had some of the participants cut back their calories by 14% and monitored the health of all of the participants for two years.

The results: The team reported a number of differences between the treatment and control groups that suggest humans can enjoy health benefits from calorie restriction.

One involved the thymus, the organ that produces T cells. Those cells are an essential part of the immune system, and as we age, the thymus tends to produce fewer of them.  

“As we get older, we begin to feel the absence of new T cells because the ones we have left aren’t great at fighting new pathogens,” senior author Vishwa Deep Dixit said. “That’s one of the reasons why elderly people are at greater risk for illness.”

Based on MRIs, the researchers could see that the thymuses of people in the calorie restriction group were more functional at the end of the study than at the beginning, while those of people in the control group showed no such changes.

“The fact that this organ can be rejuvenated is, in my view, stunning because there is very little evidence of that happening in humans,” Dixit said. “That this is even possible is very exciting.”

Back to animals: Body fat (called “adipose tissue” by scientists) contains a significant number of immune cells, so the researchers took a close look at it as well. They discovered changes in the gene expression of cells in fat tissue in people in the calorie restriction group.

One gene, PLA2G7, was severely inhibited in the calorie restricted group. That caused the researchers to wonder if it played a significant role in producing the benefits of calorie restriction, so they inhibited the gene in mice to see what would happen.

“From a public health standpoint, I think it gives hope.”

Vishwa Deep Dixit

“We found that reducing PLA2G7 in mice yielded benefits that were similar to what we saw with calorie restriction in humans,” lead author Olga Spadaro said.

This suggests that manipulating the PLA2G7 gene in humans might allow us to enjoy some of the benefits of calorie restriction without having to actually eat a lot fewer calories.

The big picture: This study alone can’t tell us whether calorie restriction can actually increase the lifespan of people — to find that out we’d need to compare people on a calorie-restricted diet to people who eat a “normal” amount of calories for, well, their entire lives.

Still, thanks to this study we finally have some scientifically sound evidence that calorie restriction can be beneficial to human health, even over just a couple years.

“CALERIE is a very well-controlled study that shows a simple reduction in calories, and no specific diet, has a remarkable effect in terms of biology and shifting the immuno-metabolic state in a direction that’s protective of human health,” Dixit said. “So from a public health standpoint, I think it gives hope.”

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