Calorie restriction slows age-related epigenetic changes

Explorers may have stopped seeking the mythical fountain of youth, but biologists have found one practice that can increase longevity across multiple species: calorie restriction. Eating a nutritionally complete, reduced-calorie diet is linked to increased life span in mice and monkeys. However, the mechanism by which calorie restriction promotes longevity has eluded scientists.

New research suggests that the mechanism may involve changing patterns of DNA methylation. Over time, our cells add and remove methyl groups to and from cytosine nucleotide bases, an epigenetic process called methylation drift. The link between age-related methylation drift and age-related diseases, such as cancer and diabetes, prompted a team of geneticists to investigate the role methylation plays in aging and calorie restriction across species.

Led by Jean-Pierre Issa at Temple University, the team used powerful deep-sequencing analyses to measure methylation drift in the DNA of mice, rhesus macaques, and humans. They also assessed the degree to which calorie restriction affected methylation drift in mice and monkeys.

The rate of methylation drift was lower in longer-lived species—monkeys and humans—than in shorter-lived mice. Additionally, monkeys and mice that ate calorie-restricted diets for a significant portion of their lives had less age-related methylation drift than animals of the same age with unlimited access to food (Nat. Commun. 2017, DOI: 10.1038/s41467-017-00607-3).

Lead author Shinji Maegawa, of the University of Texas MD Anderson Cancer Center, says understanding how calorie restriction delays age-related methylation drift could help identify potential drug targets to treat age-related diseases.