How Calorie Restriction Works

In an article published on September 14, 2017 in Nature Communications, Temple University researchers reveal an explanation for the life extending effect of calorie restriction. Jean-Pierre J. Isaa, MD, and colleagues discovered that restricting the amount of calories consumed slows the aging-related rate of change of the epigenome, which consists of proteins and other compounds that can attach to DNA and control its action. The team is also the first to demonstrate that the rate of epigenomic change is associated with lifespan.

“Our study shows that epigenetic drift, which is characterized by gains and losses in DNA methylation in the genome over time, occurs more rapidly in mice than in monkeys and more rapidly in monkeys than in humans,” explained Dr Issa, of the Fels Institute for Cancer Research at Temple’s Lewis Katz School of Medicine. “Our next question was whether epigenetic drift could be altered to increase lifespan.”

After studying age-related DNA methylation, Dr Issa and colleagues compared the age-related epigenetic drift of 22 to 30-year-old rhesus monkeys that received calorie restricted diets beginning at 7 to 14 years of age to a group of monkeys that were fed non-restricted diets. They found that the calorie restricted animals’ blood methylation age was 7 years less than their chronologic age. Similar effects were observed in older mice that were fed restricted diets.

“The impacts of calorie restriction on lifespan have been known for decades, but thanks to modern quantitative techniques, we are able to show for the first time a striking slowing down of epigenetic drift as lifespan increases,” Dr Issa stated. “Our lab was the first to propose the idea of modifying epigenetic drift as a way of modifying disease risk. But why epigenetic drift occurs faster in some people and slower in others is still unclear.”