Causal impact of genetically-determined fish and fish oil intake on epigenetic age acceleration and related serum markers.
Level 3 - non-randomized controlled study
Two-sample Mendelian randomization study using observational genetic cohort summary statistics
PubMed 40410862 · doi:10.1186/s40246-025-00756-3
What was done
A two-sample bidirectional Mendelian randomization study was performed using UK Biobank GWAS data for oily fish consumption (n = 460,443) and fish oil supplementation (n = 461,384). Outcomes included first-generation epigenetic clocks (Hannum age, IEAA) and second-generation clocks (GrimAge, PhenoAge) from an independent dataset of European-ancestry individuals (n = 34,449–34,667), along with serum markers of lipidemia and inflammation from the Integrative Epidemiology Unit database (n = 61,308–78,700). Primary analyses utilized inverse-variance weighted (IVW) and MR-Egger methods alongside sensitivity tests for reverse causation and heterogeneity.
What was found
Genetically predicted oily fish consumption was associated with decreased PhenoAge acceleration (p < 0.0086), and fish oil supplementation was associated with decreased GrimAge acceleration (p = 0.037). Fish oil consumption was also linked to reduced triglycerides (p = 0.004), while HDL and LDL were not significantly altered. A suggestive inverse relationship was identified between oily fish intake and hsCRP (p = 0.064). Specific effect sizes and confidence intervals were not reported in the abstract.
Why it matters
This study provides genetic instrumental variable support for a potential causal link between omega-3 fatty acid intake, biological age deceleration, and lower triglycerides, strengthening evidence beyond purely observational dietary associations.
Limits
The abstract reports p-values but omits numerical effect sizes and confidence intervals. Analyses were restricted to individuals of European ancestry, limiting generalizability. Mendelian randomization reflects lifetime exposure to genetic proxies and cannot directly evaluate specific supplemental dosages, preparation methods, or trial-based interventions.
Cited by
- supports Randomized controlled trials show that omega-3 supplementation slows biological aging as measured by epigenetic aging clocks.