en Clinical Physiology/Pharmacology Clinical Physiology/Pharmacology Review Review <span style="font-size:12px;"><span style="font-family:Arial;">Many individuals experience age-related hearing loss (ARHL), yet it frequently goes unnoticed. Its prevalence increases two-fold with every ten years of age. Epigenetics is linked to heritable modifications in gene activity that are not caused by alterations in DNA sequence. In this review, our goal is to assess the variety of DNA methylation in individuals with ARHL. Methods: We conducted a systematic review of studies that report changes in DNA methylation among patients with presbycusis. The study used the PECO framework to establish the eligibility criteria for patients with ARHL. A search was performed on Embase, PubMed, Scopus, Google Scholar, and ScienceDirect. Furthermore, a bioinformatics analysis was performed. Results: A total of seven studies were reviewed. Eighteen genes including P2RX2, KCNQ5, SOCS3, ERBB3, TCF25, POLE, ESPN, TNFRSF25, FGFR1, CDH23, SLC26A4, MEF2D, LCK, ACP6, ALG10, DUSPK4, C21orf58 and GBX2 were differentially methylated. To contextualize these in ARHL pathways, we integrated them with 136 ARHLassociated genes for PPI network analysis, identifying nine hub genes. Then we performed the overlap analysis using R to identify intersections between 18 methylated genes and the hub genes. After conducting enrichment analysis for hub genes, differentially methylated genes, and intersected genes, it was revealed that ERBB3, P2RX2, and FGFR1 were involved in the calcium signaling pathway. Besides, the overlap of methylated genes with ARHL hubs identifies SLC26A4, ERBB3, and CDH23 as key candidates. Conclusion: This review demonstrated that DNA methylation could cause the development of ARHL. Changes in gene methylation can disrupt the calcium signaling pathway, potentially leading to presbycusis.</span></span> DNA Methylation,Age-Related Hearing Loss,Systematic Review,Bioinformatics Analysis 22 37 http://ppj.phypha.ir/browse.php?a_code=A-10-1299-5&slc_lang=en&sid=1 Shahrokh Khoshsirat dr_khoshsirat@yahoo.com 3200319475328460039095 3200319475328460039095 No Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran narges bazgir drnargesbazgir1996@gmail.com 3200319475328460039096 3200319475328460039096 No Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran haideh mosleh haidehmosleh@yahoo.com 3200319475328460039097 3200319475328460039097 No Department of Otolaryngology, Head and Neck Surgery, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran Simin Raissi raissisimin@gmail.com 3200319475328460039098 3200319475328460039098 No Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran elanaz amanzadeh jajin elnazamanzadehjajin@gmail.com 3200319475328460039099 3200319475328460039099 No Functional Neurosurgery Research Center, Research Institute of Functional Neurosurgery, Shohada Tajrish Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Somayeh Niknazar niknazar.somayeh@gmail.com 3200319475328460039100 0000000299852144 Yes Functional Neurosurgery Research Center, Research Institute of Functional Neurosurgery, Shohada Tajrish Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences, Tehran, Iran.