Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial.
Level 2 - randomized trial
Post hoc analysis of a randomized controlled trial (CALERIE)
PubMed 37118425 · doi:10.1038/s43587-022-00357-y
What was done
Researchers conducted a post hoc analysis of blood samples from the CALERIE randomized controlled trial, in which 220 healthy, non-obese adults were randomized to either 25% caloric restriction (CR) or an ad libitum control diet for 2 years. They evaluated changes in biological aging using multiple DNA methylation (DNAm) algorithms, including DunedinPACE, PhenoAge, and GrimAge.
What was found
The caloric restriction intervention slowed the pace of aging as measured by the DunedinPACE algorithm. However, it did not produce statistically significant changes in biological age estimates assessed by PhenoAge or GrimAge. Treatment effect sizes were described as small, and specific numerical effect sizes, confidence intervals, or p-values were not reported in the abstract.
Why it matters
This provides randomized human trial evidence that the pace of biological aging can be modified by behavioral intervention, supporting the geroscience hypothesis that slowing molecular aging processes is feasible in humans.
Limits
The study is a post hoc analysis evaluated on surrogate epigenetic biomarkers rather than primary clinical endpoints like chronic disease onset or mortality. Effect sizes were small, changes were inconsistent across different epigenetic clocks, and results from healthy, non-obese adults over 2 years may not generalize to other populations or translate to long-term healthspan extension.
Cited by
- supports The CALERIE trial showed that calorie restriction in humans improved health biomarkers with lasting effects, including on the epigenome.