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NIH Record - 75th Anniversary - National Institutes of Health

Can Restricting Calories Extend Your Life?

A woman looks in a refrigerator crisper

Researchers are studying potential health benefits of calorie restriction.

Photo: SHUTTERSTOCK/ANDREY POPOV

Calorie restriction—reducing food intake without causing malnutrition—can yield health benefits that include improved metabolism and delayed onset of age-associated diseases. But extreme caloric restriction—a 40 percent reduction in calories—is associated with impaired immune function, which can lead to more severe infections. 

A team of researchers led by Dr. Vishwa Deep Dixit at Yale University School of Medicine explored the metabolic and immune effects of calorie restriction in a study partly supported by NIA and NIAMS. Results appeared in Science.

The team used samples from a clinical trial called CALERIE in which participants, ages 25-45, were asked to reduce their calorie intake by 25 percent over 2 years. Participants whose samples were used reduced their calorie intake by an average of about 14 percent.

MRI was used to examine the thymus, an organ in the chest that produces immune system T cells. The thymus usually accumulates fat with age and produces fewer T cells. After 2 years of calorie restriction, participants had larger thymuses than at the beginning of the study. These enlarged thymuses had less fat and produced more T cells. Control participants who did not restrict calories showed no change in thymus size or function.

The team found that calorie restriction led to changes in gene activity in body fat and associated immune cells. They chose to study the gene Pla2g7, which regulates inflammation. Caloric restriction inhibited its activity.

To study the effects of this inhibition, the scientists bred mice that lacked the gene Pla2g7. Mice without Pla2g7 gained less weight from eating a high-fat diet than control mice and were less likely to develop fatty liver disease. They also burned more fat than control mice. In addition, aged mice lacking Pla2g7 had less inflammation and larger, more productive thymuses. 

“These findings demonstrate that PLA2G7 is one of the drivers of the effects of calorie restriction,” Dixit said. “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.”—adapted from NIH Research Matters

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