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Figure 4. Epigenetic dysregulation in cardiac aging. Aberrant regulation across DNA methylation, histone modification, and non-coding RNA layers is depicted within cardiomyocyte nuclei during aging. Global DNA hypomethylation is associated with epigenetic clock alterations and environmental exposures, accompanied by promoter-specific changes involving p16INK4a, GPX1, and ITGBL1 that link senescence, oxidative stress, and fibrosis. Histone modification imbalance is characterized by increased histone deacetylase activity, reduced acetylation, chromatin compaction, enrichment of H3K27me3, and enhanced p300/CBP-associated metabolic reprogramming. Dysregulated non-coding RNAs, including miR-34a, miR-21, and miR-1468-3p, together with age-related changes in lncRNAs and circular RNAs, modulate apoptotic, fibrotic, and inflammatory pathways through exosome-mediated RNA communication. These coordinated epigenetic alterations converge on transcriptional programs related to oxidative stress, inflammation, angiogenesis, and metabolism, contributing to myocardial structural and functional decline. Created by PowerPoint and figdraw.com. (Copyright Code: TYIUR916b4). TGF-β: Transforming growth factor beta; HDAC: histone deacetylase; CBP: CREB-binding protein.