Curbing calories

Forget about super-sizing, a restricted-calories diet may add up health, youthfulness and longevity to your life.

Calorie restriction prolongs lifespan and diminishes the risk for age-associated disorders. Available evidence indicates that calorie restriction may have contributed to an extension of average and maximum lifespan. Maintaining a high-quality diet along with calorie restriction is a necessary condition for manifesting its beneficial effects.

Calorie restriction involves the reduction of food intake without causing malnutrition and maintaining a healthy diet and healthy weight.

Recent animal studies have found the health benefits of calorie restriction which included longer life spans, enhanced metabolism, and delayed onset of age-associated diseases. But extreme caloric restriction—a 30% reduction in calories—is associated with impaired immune function, which can lead to more severe diseases.

Researchers have been studying calorie restriction in both animal and human models to understand how it brings about metabolic benefits and changes. Knowing this could lead to therapies that confer the benefits without the drawbacks.

A team of scientists led by Dr.Vishwa Deep Dixit at Yale University School of Medicine investigated the metabolic and immune effects of calorie restriction. NIH’s National Institute on Aging (NIA) and National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) partially supported the research. Results appeared in Science on February 11, 2022.

The team used samples from a clinical trial called CALERIE in which participants, aged 25-45, were asked to lessen their calorie intake by 25% over two years. The participants whose samples were used decreased their calorie intake by an average of about 14%.

Dixit’s team noted that MRI scans showed that the volume of the thymus increased among participants who reduced their calories for the two-year CALERIE research but was not crucially different in the control group. The enlargement in thymus size in the group restricting calories was accompanied by a rise in indicators of new T cell production.

Prolonging the health of the thymus is a particularly notable benefit of calorie restriction. There has been little proof before that this organ could be rejuvenated in humans.

The team established that calorie restriction led to changes in gene metabolism and activity in body fat and associated immune cells. Numbers of these genes hadn’t been previously identified in animal studies. The team decided to focus on one gene in particular for further research: the gene for Pla2g7. Pla2g7 regulates inflammation, and caloric restriction inhibited its activity.

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

Together, these findings suggest that caloric restriction boosts health, at least in part, by reducing Pla2g7 activity. Therapies that target Pla2g7 may give benefits similar to calorie restriction without the drawbacks.

“These findings demonstrate that PLA2G7 is one of the drivers of the effects of calorie restriction,” Dixit explains. “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 enhance immune function, decrease inflammation, and potentially even enhance healthy lifespan.”

Anti-aging benefits of calorie-restricted meal timing

The study also revealed that calorie-restricted diets could boost the animals’ regulation of glucose levels and insulin sensitivity – dominant healthy aging markers – with the greatest improvements reported in mice that only ate during their active phase.

In all mice, aging increased inflammatory activity and reduced gene activity in metabolism and circadian rhythms. While caloric restriction decelerated age-related changes, mice that only ate during their active phase showed the most notable improvements.

Should we restrict our calories?

Instead of chronic calorie restriction, Longo is a proponent of mini-fasts. These are short depletions in calories to just 900 a day for five days a month, which he says have the advantages of fasting without the potentially negative long-term effects.

Indeed, he wrote the book on it: The Longevity Diet Longo stresses the importance of eating more fruits and vegetables and less meat.

It may not consequently lengthen your life, he says, but it can definitely help you maintain a healthy weight and condense the kinds of chronic illnesses that can shorten it.