Accelerated epigenetic ageing worsens survival and mediates environmental stressors in fibrotic interstitial lung disease.
Summary
Across two fILD cohorts, epigenetic age acceleration exceeded chronological age by a median of 11.7 years, associated with worse survival. Ambient PM2.5 exposure related to poorer outcomes, with epigenetic age acceleration statistically mediating adverse exposure effects.
Key Findings
- Median epigenetic age in fILD exceeded chronological age by 11.7 years.
- Higher PM2.5 exposure associated with worse survival in combined cohort analyses.
- Epigenetic age acceleration statistically mediated the adverse impact of PM2.5 on outcomes.
Clinical Implications
Epigenetic age measures could refine prognostication and identify patients most susceptible to environmental harms, supporting exposure mitigation and personalized follow-up strategies.
Why It Matters
Links a modifiable environmental exposure to biologic ageing and prognosis in fILD, integrating environmental health and epigenetics and suggesting biomarker-guided risk stratification.
Limitations
- Observational design with potential residual confounding
- Exposure estimates based on ambient PM2.5 rather than personal monitoring
Future Directions
Prospective validation of epigenetic clocks as prognostic tools; interventional studies testing whether exposure reduction modifies epigenetic ageing and outcomes.
Study Information
- Study Type
- Cohort
- Research Domain
- Prognosis
- Evidence Level
- III - Retrospective/prospective observational cohorts with multivariable and mediation analyses
- Study Design
- OTHER