The senescent heart and atrial fibrillation

Abstract

Atrial fibrillation (AF) is increasing in prevalence and burden worldwide as the population grays. Aging, a multifaceted universal biological process, is a primary driver of AF development and persistence. However, the mechanistic connection between aging and atrial myopathy, the main substrate for the development and sustenance of AF, remains poorly elucidated. Cellular senescence is a foundational aging component characterized by cell cycle arrest, an antiapoptotic phenotype, and a unique secretome linking it to many chronic and aging-related diseases, including atherosclerosis, arrhythmia, and myocardial diseases. In this review, we discuss the literature on the molecular basis of cardiac senescence and the associated secretory phenotype. Then, we discuss its relationship to atrial myopathy and remodeling through the activation of the renin-angiotensin-aldosterone system, mitochondrial alterations, and epigenetic changes. We then offer insights into preclinical studies on senolytic and senomorphic agents specifically in cardiology and finally discuss the challenges and future directions.

Keywords: Aging; Atrial fibrillation; Atrial fibrosis; Atrial myopathy; Senescence.