Calorie Restriction to Extend Human Life

Calorie restriction consists in reducing the average daily caloric intake below what is typical or habitual, without malnutrition or deprivation of essential nutrients. In a fasting diet, a person does not eat at all or severely limits intake during certain times of the day, week, or month.

In a new study published in the journal Science, researchers from Yale confirmed the health benefits of moderate calorie restrictions in humans, identifying a protein that could be harnessed to extend health in humans.

The research was based on results from the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) clinical trial, the first controlled study of calorie restriction in healthy humans. For the trial researchers established a baseline calorie intake for around 200 participants. Some of those participants were asked to reduce their calorie intake by 14%, and the rest of the participants remained with their regular diet. The study lasted 2 years. 

The goal of the study was to evaluate the use of calorie restriction in humans to see if the health benefits observed in animal studies could be replicated in humans. 

The researchers wanted to evaluate what calorie restriction does to the immune and metabolic systems and if it is indeed beneficial. 

For the study researchers evaluated the thymus of the participants using MRI to determine if there were any differences between the glands in those restricting calories compared with those who were not. The thymus is a gland that produces T cells, which are essential to fight different pathogens including virus infected cells and cancer cells, and which normally decreases its size by 70% at the age of 40.

They found that the thymus glands of those with limited calorie intake had less fat and greater functional volume after 2 years of calorie restriction, which means that they were producing more T cells than the other participants. 

The team found that there were no changes in gene expression in the T cells of the restricted diet group or the control group, but the changes were mainly in the microenvironment. Gene expression changes were found in adipose tissue.

One of the genes found was PLA2G7 or group VII A platelet activating factor acetylhydrolase, which was one of the genes significantly inhibited following calorie restriction. This protein is produced by macrophages.

Using a mice model researchers evaluated what happened when the protein was reduced and found that by reducing PLA2G7 mice yielded benefits that were similar to what they saw on calorie restriction in humans. The thymus was functional for a longer time, the mice were protected against diet-induced weight gain and form age-related inflammation.

The effects of PLA2G7 occured because it targets an inflammatory mechanism called NLRP3 inflammasome, and by lowering PLA2G7 the mice were protected from inflammation.

The researchers believe that this process could be targeted in the future to improve immune function, reduce inflammation and enhance healthy lifespan


Yale University. “Calorie restriction trial reveals key factors in extending human health.” ScienceDaily. ScienceDaily, 10 February 2022.

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