Individual and additive effects of vitamin D, omega-3 and exercise on DNA methylation clocks of biological aging in older adults from the DO-HEALTH trial.
Level 2 - randomized trial
Post hoc analysis of an individual randomized controlled trial
PubMed 39900648 · doi:10.1038/s43587-024-00793-y
What was done
Post hoc analysis of 777 older adult participants from the 3-year DO-HEALTH randomized controlled trial. The study evaluated the individual and combined effects of vitamin D (2,000 IU per day), omega-3 (1 g per day), and a home exercise program on biological aging measured over 3 years using four DNA methylation (DNAm) clocks: PhenoAge, GrimAge, GrimAge2, and DunedinPACE.
What was found
Omega-3 alone slowed the DNAm clocks PhenoAge, GrimAge2, and DunedinPACE. All three treatments showed additive benefits on PhenoAge. From baseline to year 3, standardized effect sizes ranged from 0.16 to 0.32 units, corresponding to a slowing of biological aging by 2.9 to 3.8 months.
Why it matters
It provides randomized trial evidence that omega-3 supplementation, particularly when combined with vitamin D and exercise, modestly decelerates several epigenetic clocks in older adults over 3 years.
Limits
This was a post hoc analysis rather than a prespecified primary trial outcome. The observed slowing in biological age was small (2.9-3.8 months over 3 years), and the abstract does not report whether these changes translate into improved clinical endpoints or reduced disease risk.