A 14% reduction in food-derived energy appears to be protective against disease. Vishwa Deep Dixit, an immunobiologist, investigated the mechanism and identified a method for developing an anti-aging pill.

When it comes to eating, less is more.

You may use it for everything from rigorous exercise to creative writing, and it defies common sense.

And now there’s mounting evidence suggesting, if you’re looking for a means to improve your overall health and possibly lengthen your life, calorie consumption — or rather, calorie restriction — can help.

Not only does a recent study headed by Yale researchers and published in Science Today reveal the health benefits of moderate calorie restriction, but it also identifies a critical protein that, if harnessed, may have life-extending properties.

In experimental settings, calorie restriction has long been proven to extend the lives of mice, worms, and flies. However, the question of whether this holds true for humans has only been thought about, and not investigated.

Researchers intended to find out if calorie restriction in people is as helpful as it is in lab animals in a clinical experiment called Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE), the first controlled investigation of calorie restriction in healthy humans.

The two-year study enrolled more than 200 people. Caloric intake was measured for all individuals, and some were asked to cut their intake by 14%, while the others continued to eat at their prior caloric amounts.

To better grasp what caloric restriction actually does to the body, one of the researchers told Science Today, they also “wanted to better understand what caloric restriction does to the immune and metabolic systems and, if it is indeed beneficial, how can we harness the endogenous pathways.”

Vishwa Deep Dixit, the study’s main author and director of the Yale Center for Research on Aging, said his team first looked at how calorie restriction affected the thymus, which is an organ that produces disease- and illness-fighting T cells in the blood.

When it comes to human thymus, it appears that we age in dog years—even in healthy individuals, it becomes “70 percent fatty and nonfunctional” by age 40.

“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,” says the lead author. “That’s one of the reasons why elderly people are at greater risk for illness.”

Thymus gland

It was shown that after two years on a calorie-restricted diet, individuals’ thymus glands had shrunk in size and were working at a significantly higher level. This increased the production of T lymphocytes by their thymus glands.

The thymus glands of the control group, on the other hand, had not improved after two years.

This, according to Dixit, is a remarkable advance.

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

The researchers, though, were thrown a curve ball by what they learned next.

According to Science Today, “Dixit and his colleagues expected to also find effects on the immune cells that the thymus was producing, changes that might underlie the overall benefits of calorie restriction. But when they sequenced the genes in those cells, they found there were no changes in gene expression after two years of calorie restriction.” 

What they later concluded, said Dixit, is that “it turns out that the action was really in the tissue microenvironment not the blood T cells.” 

Adipose tissue 

What was the microenvironment that changed the most?

Adipose (or body fat) tissue contains a wide variety of immune system cells, as well as a significant amount of internal inflammation.

Internal inflammation is linked to aging illnesses, thus reducing it in adipose tissue is critical.

“We found remarkable changes in the gene expression of adipose tissue … that may improve metabolic and anti-inflammatory response in humans,” adds Dixit. 

When searching for the specific gene(s) that may be involved in producing these benefits, they discovered that “change in PLA2G7 gene expression observed in participants who were limiting their calorie intake suggested the protein [produced by PLA2G7] might be linked to the effects of calorie restriction.” 

Reducing this gene’s expression in mice let researchers assess if the calorie-restriction benefits were caused by the change in this gene or simply coincidental.

Lowering PLA2G7 had a protective effect against internal inflammation in elderly mice, which was encouraging. 

“We found that reducing PLA2G7 in mice yielded benefits that were similar to what we saw with calorie restriction in humans,” adds Olga Spadaro, another author of the study. 

Dixit noted that “identifying these drivers helps us understand how the metabolic system and the immune system talk to each other, which can point us to potential targets that can improve immune function, reduce inflammation, and potentially even enhance healthy lifespan.” 

What’s more, said Dixit, is that as scientists gather more data related to PLA2G7, the eventual goal could be to “manipulate” this gene so that a person could “get the benefits of calorie restriction without having to actually restrict calories, which can be harmful for some people.”

Source: 10.1126/science.abg7292 and 10.1126/science.abn6576

Image Credit: Getty

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