A Systematic Review on the Contribution of Epigenetics to Noise‐Induced Hearing Loss

ABSTRACT Noise‐induced hearing loss (NIHL) is a prevalent sensorineural impairment with significant inter‐individual variability in susceptibility, suggesting epigenetic factors play crucial roles in disease pathogenesis. This systematic review aimed to synthesize evidence on epigenetic mechanisms in NIHL and evaluate their biomarker potential. Following PRISMA guidelines, we searched PubMed, Scopus, and Web of Science databases up to August 2025. A total of 33 studies were considered for the study which included the following: 15 animal studies investigating mechanistic pathways and 18 human studies examining biomarker associations. Key findings revealed that: (1) DNA methylation alterations in nuclear genes (SOD2, DNMTs) and mitochondrial DNA (CYB, ATP6, MT‐RNR1) are associated with NIHL susceptibility; (2) microRNAs, particularly the miR‐183 family, show significant dysregulation post‐noise exposure, with circulating miRNAs (miR‐185‐5p, miR‐451a, miR‐1229‐5p) demonstrating potential as noninvasive biomarkers; and (3) histone modifications (H3K9me2, acetylation changes) regulate hair cell survival and can be therapeutically targeted using HDAC inhibitors (SAHA) and G9a inhibitors (BIX01294). These findings establish epigenetic mechanisms as integral regulators of NIHL pathophysiology. Future research should prioritize longitudinal studies to validate circulating microRNA panels for clinical screening and translate epigenetic modulators into therapeutic applications.