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Accelerated epigenetic ageing in congenital heart disease: the AccelerAGE study
Tijs K Tournoy1, Bo Daelman2, Laurent Demulier1
1Department of Cardiology, Ghent University Hospital, Corneel Heymanslaan 10, Ghent, Belgium.
European Heart Journal
|June 11, 2026
Summary
Adults with moderate and complex congenital heart disease show accelerated epigenetic ageing compared to healthy individuals. Simple congenital heart disease does not show this accelerated ageing, suggesting disease complexity impacts biological aging.
Area of Science:
- Cardiology
- Genetics
- Gerontology
Background:
- Adults with congenital heart disease (CHD) experience earlier onset of age-related comorbidities, indicating accelerated biological aging.
- Epigenetic clocks, based on DNA methylation, offer a method to estimate biological age.
- The relationship between CHD complexity and epigenetic age acceleration is not well understood.
Purpose of the Study:
- To investigate if adults with CHD exhibit accelerated epigenetic aging.
- To determine if the degree of epigenetic age acceleration correlates with CHD complexity.
- To assess the pace of aging in CHD patients using epigenetic markers.
Main Methods:
- Included 120 adults with CHD (ages 29-50) and 120 age/sex-matched healthy controls.
- Categorized CHD patients into simple, moderate, and complex groups (n=40 each).
- Utilized Horvath, Hannum, Zhang, GrimAge2, and PhenoAge epigenetic clocks, plus DunedinPACE for aging pace assessment.
Main Results:
- Moderate and complex CHD groups showed significant age acceleration with PhenoAge and GrimAge2 clocks compared to controls.
- Patients with moderate and complex CHD exhibited a higher pace of aging (DunedinPACE).
- No significant epigenetic age differences were found between simple CHD patients and healthy controls.
Conclusions:
- Accelerated epigenetic aging is evident in adults with moderate and complex CHD, but not simple CHD.
- These findings support biological evidence of premature aging in CHD, highlighting systemic vulnerability.
- Incorporating biological aging metrics in CHD follow-up may aid early detection of complications and improve long-term healthspan.
