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The earliest evidence of DNA methylation\u2014a key epigenetic mechanism\u2014existed before Watson and Crick described the DNA double helix. Main forms of epigenetic regulation include DNA methylation, histone modifications, and mechanisms mediated by non-coding RNA. DNA methylation, which mainly happens at cytosine residues within cytosine-phosphate-guanine dinucleotides, is usually linked to transcriptional repression. Histone modifications, such as acetylation, methylation, and phosphorylation, affect chromatin structure and thereby alter transcriptional access. Simultaneously, non-coding RNAs like microRNAs and long non-coding RNAs regulate gene expression through transcriptional and post-transcriptional pathways. Abnormal epigenetic regulation has been strongly connected to the development of various human diseases, including cancers, diabetes mellitus, cardiovascular diseases, and neurodegenerative disorders. Recent evidence now points to epigenetic dysregulation as a key factor in the systemic and localized responses to severe burn injuries. These modifications control inflammatory signaling, immune cell polarization, and wound-healing processes. For example, DNA methylation and histone alterations in macrophages influence the balance between pro- and anti-inflammatory pathways, angiogenesis, and tissue regeneration. Additionally, severe burns are recognized as significant accelerators of epigenetic aging, with a direct link between injury severity and biological age advancement. However, the full extent of epigenetic roles in post-burn physiological changes remains poorly understood. The present review aims to explore these mechanisms and provide an insight into the complex network of factors shaping the pathophysiological response to these modifications post-burn injury.<\/jats:p>","DOI":"10.1042\/cs20250585","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T05:06:16Z","timestamp":1779771976000},"page":"1077-1098","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Therapeutic implications of epigenetic alterations in burns: a new frontier in burn medicine"],"prefix":"10.1042","volume":"140","author":[{"given":"Sara","family":"Timpano","sequence":"first","affiliation":[{"name":"1Department of Surgery, McMaster University, Hamilton, Ontario, Canada"},{"name":"2Centre for Burn Research, Hamilton Health Sciences, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud","family":"Farahat","sequence":"additional","affiliation":[{"name":"1Department of Surgery, McMaster University, Hamilton, Ontario, Canada"},{"name":"2Centre for Burn Research, Hamilton Health Sciences, Hamilton, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0870-1664","authenticated-orcid":false,"given":"Marc\u00a0G.","family":"Jeschke","sequence":"additional","affiliation":[{"name":"1Department of Surgery, McMaster University, Hamilton, Ontario, Canada"},{"name":"2Centre for Burn Research, Hamilton Health Sciences, Hamilton, Ontario, Canada"},{"name":"3Hamilton General Hospital, Hamilton Health Sciences, Hamilton, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"2026052601060963900_B1","doi-asserted-by":"publisher","first-page":"2077","DOI":"10.3390\/healthcare13162077","article-title":"Global, regional, and national burden of burn injury by total body surface area (TBSA) involvement from 1990 to 2021, with projections of prevalence to 2050","volume":"13","author":"Lee","year":"2025","journal-title":"Healthcare (Basel)"},{"key":"2026052601060963900_B2","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s41038-019-0163-2","article-title":"Understanding acute burn injury as a chronic disease","volume":"7","author":"Barrett","year":"2019","journal-title":"Burns Trauma"},{"key":"2026052601060963900_B3","doi-asserted-by":"publisher","first-page":"e0324481","DOI":"10.1371\/journal.pone.0324481","article-title":"Global, regional and national burden of injuries caused by fire, heat, and hot substances from 1990 to 2021","volume":"20","author":"Huang","year":"2025","journal-title":"PloS One"},{"key":"2026052601060963900_B4","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1097\/SLA.0000000000002097","article-title":"Pathophysiological response to burn injury in adults","volume":"267","author":"Stanojcic","year":"2018","journal-title":"Ann. 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