Yale Study Shows Calorie Restriction May Delay Aging

A new study by scientists at Yale University offers one of the most robust investigations into the health effects of long-term calorie-restricted diets in humans ever conducted.

Photo Insert: The first discovery came when the researchers examined MRI data focused on the thymus gland.

The results have homed in on a protein that seems to play a key role in age-related immune dysfunction and the researchers hypothesize it could be therapeutically targeted to extend lifespan in humans, Rich Haridy reported for New Atlas on Feb. 11, 2022.

The researchers leveraged data from a landmark clinical trial conducted a few years ago called CALERIE (Comprehensive Assessment of Long term Effects of Reducing Intake of Energy).

The trial recruited more than 200 healthy non-obese subjects and tasked half with reducing their caloric intake by 25 percent.

The trial ran for two years, allowing for unique insights into the long-term effects of caloric restriction across a number of physiological biomarkers. In the end, the interventional cohort achieved a consistent calorie reduction of 14 percent from their baseline intake at the beginning of the study, which was published in the journal Science.

Senior author on the new study, Vishwa Deep Dixit, says this investigation into CALERIE data focused on how long-term calorie restriction in humans influenced immune response and inflammation.

“Because we know that chronic low-grade inflammation in humans is a major trigger of many chronic diseases and, therefore, has a negative effect on life span,” said Dixit. “Here we’re asking: What is calorie restriction doing to the immune and metabolic systems and if it is indeed beneficial, how can we harness the endogenous pathways that mimic its effects in humans?”

The first discovery came when the researchers examined MRI data focused on the thymus gland. The thymus produces immune T-cells and is known to age much more rapidly than other organs in the body. Age-related thymus dysfunction is one of the reasons immune responses in the elderly are weak.

The researchers found two years of calorie restriction seemed to increase the functional volume of the thymus gland compared to data gathered at the beginning of the trial. A reduction in fat around the gland was also detected, compared to little change in the control group with no dietary restriction.

A gene that codes for a protein known as PLA2G7 was strongly inhibited in the cohort eating a calorie-restricted diet for two years. High circulating volumes of PLA2G7 have long been associated with metabolic and immune diseases, including diabetes, cardiovascular disease, and some cancers.

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