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Cells
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DNA Methylation in Human Health and Disease: From Molecular Mechanisms...
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DNA Methylation in Human Health and Disease: From Molecular Mechanisms to Clinical Applications

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: 15 December 2025 | Viewed by 3210

Special Issue Editors

Dr. Michele Longo

E-Mail Website
Guest Editor
Facoltà di Medicina e Chirurgia, Università degli Studi di Napoli Federico II, Naples, Italy
Interests: diabetes and metabolism; epigenetic mechanisms
Special Issues, Collections and Topics in MDPI journals
Dr. Jyotirmoy Das

E-Mail Website
Guest Editor
Department of Biomedical and Clinical Sciences (BKV), Linköping University, Linköping, Sweden
Interests: DNA methylation; computational biology; microRNA; epigenetics; human diseases

Special Issue Information

Dear Colleagues,

DNA methylation is a fundamental epigenetic modification that regulates gene expression, maintains genomic stability, and orchestrates crucial developmental and cellular processes. Alterations in DNA methylation patterns have been increasingly implicated in the initiation and progression of a wide range of human diseases, including cancers, neurological disorders, autoimmune conditions, and metabolic syndromes. Recent advances in high-throughput sequencing, single-cell epigenomics, and functional studies have greatly expanded our understanding of the dynamic and context-dependent nature of DNA methylation, revealing its pivotal role as an interface between genetic predisposition and environmental influences.

This Special Issue aims to highlight the latest discoveries in the field of DNA methylation as it pertains to human health and disease. We welcome submissions of original research articles and comprehensive reviews that explore molecular mechanisms, the contribution of methylation to disease pathogenesis, the development of methylation-based biomarkers, and emerging therapeutic strategies targeting the epigenome. Studies employing innovative technologies or providing new conceptual insights into the regulation and function of DNA methylation are particularly encouraged.

Dr. Michele Longo
Dr. Jyotirmoy Das
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • DNA methylation
  • epigenetics
  • diseases
  • biomarkers
  • functional analysis

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Published Papers (3 papers)

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Research

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26 pages, 8273 KB  
Article
Altered DNA Methylation Pattern Contributes to Differential Epigenetic Immune Signaling in the Upper Respiratory Airway of Unvaccinated COVID-19 Patients
by Melissa Govender, Jyotirmoy Das, Francis R. Hopkins, Cecilia Svanberg, Johan Nordgren, Marie Hagbom, Jonas Klingström, Åsa Nilsdotter-Augustinsson, Yean K. Yong, Vijayakumar Velu, Sivadoss Raju, Johanna Sjöwall, Esaki M. Shankar, Sofia Nyström and Marie Larsson
Cells 2025, 14(21), 1673; https://doi.org/10.3390/cells14211673 (registering DOI) - 27 Oct 2025
Abstract
SARS-CoV-2 infection remains a global health concern, with its impact on host immune responses not fully understood. In a case–control study, we examined how COVID-19 affects DNA methylation patterns in the upper respiratory airway of hospitalized individuals. DNA methylation arrays were performed on [...] Read more.
SARS-CoV-2 infection remains a global health concern, with its impact on host immune responses not fully understood. In a case–control study, we examined how COVID-19 affects DNA methylation patterns in the upper respiratory airway of hospitalized individuals. DNA methylation arrays were performed on nasopharyngeal samples at inclusion/hospitalization and 6 weeks post-inclusion. We found a distinct DNA methylation pattern in COVID-19 patients compared to healthy controls, identifying 510,099 differentially methylated CpGs. Within the transcription start sites (TSSs) and gene body, COVID-19 patients displayed a higher number of genes/CpGs with elevated methylation levels. Enrichment analysis of TSS-methylated genes revealed effects of SARS-CoV-2 on genes associated with type I interferons, anti-viral and inflammatory responses, and immune functions. Some CpG methylations were transient, and normalized at group level by 6 weeks post-inclusion. Several IFN-regulated genes, including OAS1, OAS3, IFIT3, and MX1, were identified. Among the top regulators were IL17A and ERK1/2, both involved in inflammatory processes. Networks nodes included IGF1 and EGF, associated with processes including tissue repair and activation of immune responses. Overall, our data suggests that COVID-19 can impact the upper airway by modifying gene methylation patterns. This could have implications for conditioning of the airways, how individuals respond to future airway infections, and therapeutic interventions. Full article
(This article belongs to the Special Issue DNA Methylation in Human Health and Disease: From Molecular Mechanisms to Clinical Applications)
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Review

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20 pages, 1133 KB  
Review
Exercise, Epigenetics, and Body Composition: Molecular Connections
by Ashley Williams, Danielle D. Wadsworth and Thangiah Geetha
Cells 2025, 14(19), 1553; https://doi.org/10.3390/cells14191553 - 6 Oct 2025
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Abstract
Exercise plays a crucial role in promoting overall health by activating molecular pathways that contribute to the prevention and management of chronic diseases, slowing epigenetic aging, improving body composition, and reducing the risk of obesity. In skeletal muscle, these benefits are largely mediated [...] Read more.
Exercise plays a crucial role in promoting overall health by activating molecular pathways that contribute to the prevention and management of chronic diseases, slowing epigenetic aging, improving body composition, and reducing the risk of obesity. In skeletal muscle, these benefits are largely mediated by exercise-induced transcriptional and epigenetic responses. Recent advances in epigenetics have intensified interest in understanding how physical activity influences long-term health and body composition at the molecular level. Epigenetic modifications, which regulate gene expression without altering the DNA sequence, are key mechanisms in this process. Emerging research has provided deeper insights into the processes such as DNA methylation, histone modification, and non-coding RNAs, and their connection to exercise. While numerous studies have demonstrated the influence of exercise on the epigenome, fewer have directly examined how these molecular changes relate to alterations in fat mass, lean body mass, and other components of body composition. This comprehensive review synthesizes the current evidence on the interplay between exercise, epigenetic regulation, and body composition, with a focus on adolescents and adults. We highlight key genes involved in metabolism, fat storage, muscle development, and epigenetic aging, and explore how their regulation may contribute to individual variability in exercise response. Understanding these molecular pathways may provide valuable insights for optimizing exercise interventions aimed at improving health outcomes across the lifespan. Full article
(This article belongs to the Special Issue DNA Methylation in Human Health and Disease: From Molecular Mechanisms to Clinical Applications)
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25 pages, 1343 KB  
Review
DNA Methylation: A Potential Mediator of the Memory Regulatory Effects of taVNS
by Pak On Patrick Yee, Ka Chun Tsui, Man Lung Fung, Boon Chin Heng, Ersoy Kocabicak, Ali Jahanshahi, Yasin Temel, Arjan Blokland, Luca Aquili, Allan Kalueff, Kah Hui Wong and Lee Wei Lim
Cells 2025, 14(17), 1327; https://doi.org/10.3390/cells14171327 - 27 Aug 2025
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Abstract
Transcutaneous auricular vagus nerve stimulation (taVNS), an emerging noninvasive neuromodulation technique, has shown promise for improving memory. A better understanding of the epigenetic mechanisms underlying the effects of taVNS would inform the molecular outcomes essential for memory and cognition. In this review, we [...] Read more.
Transcutaneous auricular vagus nerve stimulation (taVNS), an emerging noninvasive neuromodulation technique, has shown promise for improving memory. A better understanding of the epigenetic mechanisms underlying the effects of taVNS would inform the molecular outcomes essential for memory and cognition. In this review, we synthesize the current literature on the neurophysiological and biochemical basis of taVNS. Next, we explore how DNA methylation regulators (e.g., DNA methyltransferase 3a) and readers (e.g., methyl-CpG binding protein 2) differentially regulate memory, and how their activity and expression can be regulated by neuronal activity. Finally, we describe the potential involvement of DNA methylation in mediating the memory regulatory effects of taVNS and discuss possible directions for future studies. Full article
(This article belongs to the Special Issue DNA Methylation in Human Health and Disease: From Molecular Mechanisms to Clinical Applications)
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