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Figure 4. Inflammation in aging and AF. Aging causes adipocyte hypertrophy and malfunction in immune cells. The production of damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs) causes activation of the NLRP3 inflammasome. The release of double-stranded DNA (dsDNA) into the cytosolic activates the cGAS-STING signaling pathway, although there is currently no direct evidence implicating this pathway in aging-related AF. Activation of cGAS leads to the development of the senescence-associated secretory phenotype (SASP) and recruitment of immune cells to eliminate damaged and senescent cells. These processes lead to increased expression of proinflammatory cytokines such as IL-1β, IL-6, and TNF-α. The elevated cytokine levels result in chronic inflammation within the heart, which can promote ectopic activity and the formation of substrates that trigger AF. Targeting inflammation by reducing senescence with senolytics and senomorphics and addressing the inflammatory role of epicardial adipose tissue (EAT) with ANGPTL2-targeting therapies may offer potential therapies for managing age-related AF. The figure was generated with BioRender.com.