The results showed that (1) the left atrial tissues of older AF patients, aging mouse, and senescence human atrial fibroblasts had more severe atrial fibrosis and higher protein expression levels of p300, p53/acetylated p53 (ac‐p53)/p21, Smad3/p‐Smads, and fibrosis‐related factors. This evidence concerns the gene TP53 and atrial fibrillation.