Calorie restriction: How does it increase life span?

• Laboratory studies have found that some animals on calorie-restricted diets live longer.
• Researchers are keen to find out whether there is a similar effect in people.
• Now, a small-scale study suggests that moderate calorie restriction may benefit human health.
• The researchers identified a key protein that might increase the “health span,” the number of disease-free years a person lives.

Laboratory studies of animals, including rats, fruit flies, worms, and mice, show that those fed a calorie-restricted diet may live up to twice as long as those with an unrestricted diet.

Now, a team led by researchers from Yale University has investigated the effects of calorie restriction in people. Their findings, which appear in Science, may eventually lead to new ways to extend healthy life.

In animal studies, calorie reductions of 40% are common. However, as the authors of the new study explain, this effects growth, reproduction, and immunity. In the human study, calories were reduced by only 14%.

Unlike many weight loss diets, a calorie-restricted diet involves small reductions of habitual calorie intake over a long period. People usually lose some weight, but this is not the main aim of calorie restriction.

The researchers set out to investigate whether calorie restriction had similar health benefits in people as they did in other animals. They also wanted to identify any mechanisms behind these benefits.

Healthy adults

Over 2 years, the team assessed just over 200 people, aged 21–50 years. All were participants in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) clinical trial.

All the participants had a body mass index of 22.0 to 27.9, putting them in the healthy, non-obese category.

The CALERIE trial had already shown a reduction in cardiometabolic risk factors, involving cholesterol levels and blood pressure, in this group.

Kristin Kirkpatrick, a registered dietitian nutritionist at the Cleveland Clinic, told Medical News Today:

“The data presented in the study was very interesting. There have been multiple research studies on calorie restriction and lower carbohydrate profiles that are important to consider. The addition of this research is beneficial to advancing and supporting other findings.”

Effects on the thymus

The researchers looked at the effect of calorie restriction on the thymus. This gland, situated in the chest, just above the heart, is part of the immune system. The thymus produces T cells — white blood cells that are essential for fighting infections.

Hormones released by the thymus inhibit the aging process. As people age, their thymus becomes fatty and smaller, and it produces fewer T cells. Older people are more susceptible to infections because of this reduced immunity.

The scientists performed MRI scans of the participants’ thymus glands. They found that those with calorie-restricted diets had greater functional thymus volume than those with unchanged diets.

The thymus glands of the restricted diet group were also less fatty and produced more T cells than those of the unrestricted diet group.

Although the thymus was being rejuvenated, there were no changes to the immune cells that the gland was producing.

Body fat changes

The researchers then looked at body fat, or adipose tissue, which is key to the functioning of the immune system. Some immune cells in this tissue can cause inflammatory responses when wrongly activated.

They found changes in the gene expression of adipose tissue, with some genes inhibited in those with restricted diets. The scientists investigated these changes further, to see whether they were driving the beneficial effects of calorie restriction.

Key gene

The gene that seemed to be linked to these effects was the gene for PLA2G7 — a protein produced by immune cells called macrophages.

To test their theory that PLA2G7 was causing the effects of calorie restriction, they deleted the gene that codes for this protein in mice.

These mice showed less diet-induced weight gain, less age-related inflammation, and, crucially, the same improvement in thymus function.

According to Prof. Vishwa Deep Dixit, the director of the Yale Center for Research on Aging and senior author of the study:

“These findings demonstrate that PLA2G7 is one of the drivers of the effects of calorie restriction. 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.”

Alternative to restricting calories

Restricting calories can be harmful to some people, and manipulating PLA2G7 might provide the benefits without the need for restriction, Prof. Dixit suggested.

Kirkpatrick described the risks of calorie restriction. “If calorie restriction is not explained thoroughly to those interested in utilizing it, the technique may introduce risk to overall health. Calorie restriction does not mean you eat just 15% less of your favorite junk food.”

“When utilizing calorie restriction,” she continued, “it is important to convey to participants that because they are consuming less, the food calories are coming from for the day need to be from nutrient-dense sources.”

“Studies with larger sample sizes would be a great next step for additional research,” she added.

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