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Figure 3. Mitochondrial dysregulation in aging and AF. Dysregulation of PGC-1α and PGC-1β during aging affects mitochondrial biogenesis, which results in enhanced cell death, impaired energy production, and increased RONS levels, promoting an age-dependent atrial arrhythmic phenotype. PGC-1α may serve as a potential biomarker for AF prediction, while reduced PGC-1β is associated with an increased risk of age-related arrhythmias. Mitochondrial complexes, particularly I and III, contribute to superoxide (O₂^•-) production, which interacts with nitric oxide (NO) to form RONS. Accumulated DNA damage during aging activates PARP, which depletes NAD+, further dampening ATP generation and exacerbating oxidative stress. NAD: Nicotinamide adenine dinucleotide; PGC: peroxisome proliferator-activated receptor gamma coactivator; PARP: poly (ADP-ribose) polymerase; RONS: reactive oxygen and nitrogen species. The figure was generated with BioRender.com.