Calorie restriction in laboratory animals enhances their lifespan, prior research shows, but does the same hold true for humans? Researchers at Yale University concluded the first controlled study of the dietary regimen in healthy humans to determine if it is indeed as beneficial for people. Results confirm that calorie restriction in humans leads to “remarkable” long-term health benefits. They also identified a protein connected to calorie restriction that may ensure a longer, healthier life.
The clinical trial, entitled the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE), first established the baseline calorie intake of more than 200 participants. Then, some of the subjects were instructed to reduce their total calorie consumption by 14 percent. The other subjects continued their baseline calorie intake. The researchers analyzed the health effects of calorie restriction over two years.
Led by Vishea Deep Dixit, a professor of pathology at Yale, study authors also wanted to find out how calorie restriction confers better health. They wanted to determine how the practice may be linked to the immune system and inflammation. “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,” Dixit says in a statement. “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?”
Diving into the impact of calorie restriction
The team analyzed the thymus gland, which is above the heart and produces T cells, white blood cells important to immune function. The thymus ages faster than the rest of the body, interfering with the gland’s immune function. They found that calorie restriction rejuvenated the thymus gland, increasing T-cell production, to levels greater than at the start of the study.
On closer examination of the thymus they determined that it was not the T cells that had the beneficial effect. It was in adipose (fat) tissue in the gland. They studied the genes which have a role in fat production. Calorie restriction changed how the genes were expressed in the adipose tissue. “We found remarkable changes in the gene expression of adipose tissue after one year that were sustained through year two,” says Dixit. “This revealed some genes that were implicated in extending life in animals but also unique calorie restriction-mimicking targets that may improve metabolic and anti-inflammatory response in humans.”
‘Simple reduction in calories has remarkable effect’
Researchers also honed in on the action of one gene with a site described as PLA2G7, which is a protein produced by immune cells called macrophages. It was inhibited by calorie restriction.
“These findings demonstrate that PLA2G7 is one of the drivers of the effects of calorie restriction,” explains Dixit. “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 life span.”
Dixit continues, “There’s so much debate about what type of diet is better – how carbohydrates, fat, increased protein, intermittent fasting, etc. – and I think time will tell which of these are important. The CALERIE study shows a simple reduction in calories, and no specific diet, has a remarkable effect in terms of biology and shifting the immune-metabolic state in a direction that’s protective of human health. So, from a public health standpoint, I think it gives hope.”
The study is published in the journal Science.