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The 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