DOES CALORIC RESTRICTION SLOW THE PROCESS OF BIOLOGICAL AGING? EVIDENCE FROM THE CALERIE TRIAL

Calorie restriction (CR) slows aging and increases healthy lifespan in model organisms. We tested if CR slowed biological aging in humans using DNA methylation analysis of blood samples from N=197 participants in the Comprehensive Assessment of Long-term Effects ofReducing Intake of Energy (CALERIE™) randomized controlled trial. We quantified CR effects on biological aging by comparing change scores for six epigenetic-clock and Pace-of-Aging measures between n=128 CR-group and n=69 ad-libitum-control-group participants at 12- and24-month follow-ups. CR effects were strongest for DunedinPACE Pace of Aging (12-month Cohen’s d=0.3; 24-month Cohen’s d=0.2, p<0.01 for both), followed by DunedinPoAm and the GrimAge epigenetic clock, although effects for these measures were not statistically differentfrom zero (p>0.08). CR effects for other epigenetic clocks were in the opposite direction (all p>0.15). CALERIE intervention slowed Pace of Aging but showed minimal effect on epigenetic clocks hypothesized to reflect longer term accumulation of aging burden.