Longevity & AgingAging Enzyme FTO Drives Atrial Fibrillation by Silencing a Key Potassium Channel Gene
Researchers from Dalian Medical University found that the m6A demethylase enzyme FTO accumulates in aging mouse hearts, stripping protective RNA methylation marks from the Kcne1 gene. This reduces Kcne1 mRNA and protein levels, which amplifies IKs potassium currents and shortens action potential duration in atrial cardiomyocytes—creating conditions ripe for atrial fibrillation. Cardiomyocyte-specific Fto knockout in aging mice rescued Kcne1 expression and reduced AF susceptibility. The inverse FTO-KCNE1 relationship was confirmed in human left atrial tissue from AF patients, and mechanistic studies in iPSC-derived atrial cells showed FTO-mediated demethylation disrupts Kcne1 pre-mRNA splicing, nuclear export, and translation.
