REVIEW article
Front. Cell Dev. Biol.
Sec. Signaling
Atrial myocyte senescence as a driver of atrial fibrillation: mechanisms and therapeutic implications
Provisionally accepted
- 1The First Hospital of Jilin University, Changchun, China
- 2Jilin Medical University, Jilin, China
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Atrial fibrillation (AF) is the most common arrhythmia encountered in the clinical setting, and its occurrence is influenced by various factors, particularly aging. Senescence of atrial myocytes plays an important role in the development of AF, although the precise mechanisms underlying this association remain unclear. This review explores the pivotal role of atrial myocyte senescence in AF pathogenesis, moving beyond chronological age. It synthesizes evidence that aging creates a pro-arrhythmic substrate via three interconnected mechanisms: 1) inflammatory activation (mitochondrial ROS, NLRP3, SASP), 2) dysregulated calcium handling (RyR2, SERCA2), and 3) cell cycle disruption (p16, p21, p53). These pathways, compounded by epigenetic changes and SIRT1/mTOR signaling dysregulation, drive the electrical and structural remodeling that triggers and sustains AF. The review highlights promising therapeutic targets like SIRT1 activators and NLRP3 inhibitors, proposing an integrated "Senescence-AF Axis" model, while identifying key research gaps in cell-type specificity and clinical translation. This comprehensive review outlines current progress in research in this area and future research directions and provides valuable references for forthcoming studies.
Keywords: Atrial Fibrillation, Atrial myocytes, Cell cycle-related genes, Cellular ion balance, Inflammasomes, senescence
Received: 09 Sep 2025; Accepted: 10 Dec 2025.
Copyright: © 2025 Wei, Li and Quan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Nanhu Quan
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