Premature aging in children and adults with a Fontan circulation

Abstract

AbstractThe Fontan circulation predisposes to multiple morbidities typically associated with older age but occurring in their third and fourth decades, consistent with premature aging. In this pilot study, we evaluated whether the Fontan circulation is associated with premature epigenetic aging. We found that in whole blood, Δage, the difference between chronological age and estimated epigenetic DNAge™, was significantly higher in those living with a Fontan circulation than in a reference cohort (z=5.59, p<0.0001), with a mean Δage in adults post-Fontan of +4.9 years (95% CI 3.3-6.5, p<0.0001). Our results suggest that the Fontan circulation is associated with accelerated epigenetic aging, mirroring the premature aging clinical phenotype. In a life-limiting condition with few treatment options, targeting epigenetic aging may represent a novel opportunity for intervention.