Clinical Epigenetics最新文献

{"title":"Later-generation epigenetic aging clocks outperform first-generation models in predicting survival in TCGA breast cancer.","authors":"Xianglong Tan, Matteo Pellegrini, Su Yon Jung","doi":"10.1186/s13148-026-02102-3","DOIUrl":"10.1186/s13148-026-02102-3","url":null,"abstract":"<p><strong>Background: </strong>Epigenetic aging bridges the gap between biological and chronological age by exploiting DNA methylation (DNAm) patterns. Over the past decade, successive DNAm-based clocks have been introduced, beginning with the first-generation Horvath and Hannum models and extending to second-generation PhenoAge and the GrimAge family; complementary measures include DNAm-estimated telomere length and mitotic indices such as epiTOC/pcgtAge. We previously conducted a side-by-side evaluation of these metrics in colorectal cancer using publicly available data from The Cancer Genome Atlas (TCGA) COAD and READ cohorts, but an equally systematic assessment in breast cancer has been lacking.</p><p><strong>Result: </strong>Here, using TCGA-BRCA tumor methylomes linked to clinical data (analytic n = 781), we compared seven metrics (Horvath, Hannum, PhenoAge, GrimAge1, GrimAge2, epiTOC/pcgtAge, DNAmTL) via Kaplan-Meier grouping (median and tertiles) and Cox models adjusted for menopausal status, age at diagnosis, receptor subtype, stage, race, and ethnicity, with overall survival truncated at 4000 days. Our analysis reproduced expected benchmark patterns: Triple Negative Breast Cancer (TNBC) had the worst outcomes, Luminal A the best, and higher stage and older age predicted poorer survival, supporting analytic validity. We found first-generation clocks did not separate survival, whereas PhenoAge and GrimAge2 stratified outcomes; in multivariable analyses, only GrimAge1 provided independent prognostic information. DNAmTL was inversely associated with mortality in univariate models, and epiTOC stratified tertiles but showed wide, nonsignificant Cox estimates.</p><p><strong>Conclusions: </strong>Second-generation clocks demonstrated stronger prognostic signal than first-generation models in unadjusted analyses. Among them, GrimAge1 retained independent prognostic value beyond established clinicopathologic factors in breast cancer, supporting further external validation with richer covariates to refine clinical utility.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"18 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13097738/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNMT inhibitor ameliorates hyperglycemia and renal inflammation partially via reversing hypermethylation-induced Klotho suppression in diabetic mice.","authors":"Qianling Liu, Xiaoyan Li, Wenxing Peng, Jiaqing Tan, Lanping Jiang, Xiaolei Shi, Zilv Luo, Ning Luo, Jinjin Fan, Qinghua Liu, Wei Chen","doi":"10.1186/s13148-026-02116-x","DOIUrl":"https://doi.org/10.1186/s13148-026-02116-x","url":null,"abstract":"","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated m6A methylome and transcriptome profiling of mRNAs and lncRNAs in nasal mucosal epithelial cells of allergic rhinitis patients undergoing allergen-specific immunotherapy.","authors":"Shimin Lai, Lei Yu, Lin Sun, Hongyuan Zheng, Tong Lu, Zhengqi Li, Changhui Chen, Yi Wei, Weiping Wen","doi":"10.1186/s13148-026-02128-7","DOIUrl":"https://doi.org/10.1186/s13148-026-02128-7","url":null,"abstract":"<p><strong>Background: </strong>Allergic rhinitis (AR) affects 10-25% of the global population, with nasal epithelial cell (NEC) dysfunction acting as a central driver of its pathogenesis. Allergen-specific immunotherapy (AIT) is the sole disease-modifying treatment for AR; however, its optimization is hindered by the lack of validated predictive biomarkers. N6-methyladenosine (m6A) is a pivotal epitranscriptomic regulator of immune and epithelial homeostasis. This study aims to delineate the m6A modification landscape in NECs during AIT to identify candidate genes associated with clinical efficacy and elucidate the underlying molecular mechanisms.</p><p><strong>Methods: </strong>We performed methylated RNA immunoprecipitation sequencing (MeRIP-Seq) and RNA sequencing (RNA-Seq) on NECs from house dust mite (HDM)-sensitized AR patients who completed a 3-year AIT course and severity-matched non-AIT controls. Bioinformatics analyses, including Gene Set Enrichment Analysis (GSEA), were conducted to explore biological functions and signaling pathways. Key differentially methylated and expressed mRNAs and lncRNAs were validated using qRT-PCR and MeRIP-qPCR in an independent cohort (n = 12). Clinical relevance was assessed via correlation with the Total Nasal Symptom Score (TNSS).</p><p><strong>Results: </strong>MeRIP-Seq revealed distinct m6A topographies, identifying 1,455 hypermethylated and 4,636 hypomethylated mRNAs, alongside 267 hypermethylated and 799 hypomethylated lncRNAs in the AIT group. Integrated multi-omics analysis and GSEA demonstrated that AIT significantly downregulates pro-inflammatory cascades (e.g., PI3K-Akt, MAPK, and Ras signaling) while upregulating pathways related to cell adhesion and apoptotic regulation. We identified and validated four key mRNAs (KANK2, DBI, IL18, and TNFRSF10A) exhibiting inverse correlations between m6A modification and gene expression, which also correlated with the patients' TNSS. Furthermore, 28.7% of differentially m6A-methylated lncRNAs were chromatin-associated. Notably, within this subset, the m6A methylation level of LUCAT1 was positively correlated with the patients' TNSS, suggesting its potential role in epigenetic regulation during AIT.</p><p><strong>Conclusions: </strong>This study delineates the m6A epitranscriptomic landscape in NECs following AIT, revealing its critical role in orchestrating epithelial barrier restoration and immune microenvironment homeostasis. The identified candidate mRNAs (KANK2, DBI, IL18, TNFRSF10A) and chromatin-associated lncRNAs (e.g., LUCAT1) offer novel mechanistic insights into epitranscriptomic remodeling and serve as promising molecular candidates for future therapeutic or diagnostic development in precision AR management.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Late-onset epi-cblC methylmalonic aciduria with tissue-variable MMACHC promoter methylation due to a stop retained PRDX1 variant.","authors":"Martina Škopková, Pavlína Kabelíková, Andrea Andrésová, Katarína Brennerová, Silvia Dallemule, Miroslav Sabo, Róbert Petrovič, Daniela Gašperíková","doi":"10.1186/s13148-026-02135-8","DOIUrl":"https://doi.org/10.1186/s13148-026-02135-8","url":null,"abstract":"","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721853","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ultra-mild bisulphite sequencing for DNA methylation analysis from low-input clinical specimens.","authors":"Ram Abou Zaki, Ishant Khurana, Assam El-Osta","doi":"10.1186/s13148-026-02110-3","DOIUrl":"10.1186/s13148-026-02110-3","url":null,"abstract":"<p><p>In a recent paper published in Nature Communications, Dai and colleagues offer a practical re-engineering of a workhorse: ultra-mild bisulphite sequencing (UMBS-seq), which re-tunes classical bisulphite conversion so that fragmented, low-input clinical DNA can yield methylomes that are not merely usable, but technically reliable. In this commentary, we set the advance in its proper frame-less a revolution than a highly optimized re-engineering-and trace the practical consequences of minimising chemical damage to input DNA: reduced DNA damage, higher library complexity, and more uniform recovery across GC content, with performance that, on key metrics, performs better than conventional bisulphite workflows and is competitive with enzymatic alternatives. In the benchmarking presented by Dai et al., these gains are reflected in higher library yield and complexity at inputs spanning nanograms to picograms, profiles shifted toward longer fragments, improved CpG/GC coverage uniformity, and more consistent C-to-U conversion with minimal background at the lowest inputs-features that matter most when clinical DNA is both scarce and fragmented. The point isn't optimisation for its own sake; it's what steadier methylomes make possible. In pregnancy cohorts-where cord-blood methylation patterns have been associated with later islet autoimmunity risk and later metabolic risk-UMBS-seq becomes an enabling instrument: it turns limited, fragmented clinical material into data robust enough to support methylation risk scores-turning scarcity from a limitation into a design criterion.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"18 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13085640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tracking DNA methylation-based biological age over 8 years and its association with mortality in community-dwelling older adults.","authors":"Qiming Yin, Ben Schöttker, Bernd Holleczek, Ziwen Fan, Joshua Stevenson-Hoare, Hermann Brenner","doi":"10.1186/s13148-026-02067-3","DOIUrl":"10.1186/s13148-026-02067-3","url":null,"abstract":"","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"18 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13085702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early blood DNA methylation patterns associated with glycemic progression in a prospective Indian cohort.","authors":"Gopika Satheesh, Aneesh K Asokan, Gadadharan Vijayakumar, Arumugam Rajavelu, Sudha Narayana Rao, Krishnankutty Chandrika Sivakumar, Abdul Jaleel","doi":"10.1186/s13148-026-02064-6","DOIUrl":"10.1186/s13148-026-02064-6","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of Type 2 diabetes mellitus (T2DM) is rapidly increasing in India, yet molecular markers that reflect early disease susceptibility remain limited. Epigenetic modifications such as DNA methylation may reflect early metabolic vulnerability preceding overt dysglycemia. In this study, we examined genome-wide DNA methylation patterns in a pilot subset nested within a prospective Indian cohort using Nanopore sequencing and assessed their associations with previously identified metabolite predictors from the same cohort.</p><p><strong>Results: </strong>Genome-wide DNA methylation profiling was performed on buffy-coat DNA from 12 participants who were normoglycemic at baseline and later classified into normoglycemia, prediabetes, or T2DM based on their glycemic status at 6-year follow-up. At baseline, gene-level aggregation of CpG methylation revealed directionally consistent hypermethylation of seven genes (ABCG1, ADARB2, BCL2, DLC1, EGFLAM, SYK, ZNF516) in individuals who later developed T2DM, while those progressing to prediabetes exhibited six hypermethylated (ABCG1, FLT3, LCP1, MBP, NCOA2, TCF7L2) and five hypomethylated genes (ZFHX3, PAX6, PTPRN2, ERC1, HIPK1). ABCG1 showed consistent hypermethylation across both groups. Longitudinal within-individual comparisons identified additional gene-associated methylation changes, including ANK1, IQSEC1, and RUNX1, and shared alterations in CACNA1C, KANSL1, PTPRN2, and TTC34, while six genes showed stage-dependent directional shifts in methylation (ASB3, EFR3A, PCSK5, KLHL14, PDE4C, UNC5C). Correlation analyses at baseline suggested associations between ABCG1 and EGFLAM methylation, fasting glucose, phosphatidylethanolamine [PE (20:3_18:0)] and insulin sensitivity indices.</p><p><strong>Conclusion: </strong>This pilot longitudinal study suggests that gene-associated DNA methylation changes in blood may be detectable prior to the onset of dysglycemia. These findings are exploratory and hypothesis-generating, highlighting candidate genes and epigenetic-metabolic associations for targeted validation in larger, independent cohorts using alternative analytical approaches.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"18 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13085709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNMT3A in cancer: from epigenetic writer to oncogenic driver.","authors":"Thomas Dupas, Enola Gautreau, Josianne Clavel, Noël J-M Raynal, Serge McGraw","doi":"10.1186/s13148-026-02127-8","DOIUrl":"https://doi.org/10.1186/s13148-026-02127-8","url":null,"abstract":"<p><p>Cancer is the leading cause of mortality, accounting for one in six deaths worldwide. Despite the emergence of new therapies, cancer mortality remains high. Cancer cells share many traits, such as reprogrammed metabolism and exacerbated proliferation. All these alterations are in part orchestrated by changes in gene expression, notably due to the reshaping of the epigenetic landscape, including DNA methylation marks. Over the past decades, the enzymes responsible for DNA methylation, the DNA methyltransferases (DNMTs), have emerged as important actors in tumorigenesis and therefore as therapeutic targets of choice. Of particular interest is DNMT3A, which plays a critical role in de novo DNA methylation and has been strongly implicated in the pathogenesis of acute myeloid leukemia. Considering the large number of recent studies, this review aims to provide an up-to-date view of knowledge regarding DNMT3A-dependant DNA methylation and its implications for cancer pathophysiology. This review highlights the central position of DNMT3A in cell proliferation, metabolic reprogramming and drug resistance in tumor cells, reinforcing the need for further studies on this protein, which appears to be a key therapeutic target.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147688438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disrupted epigenetic regulation in human senile lentigines revealed by characterizing gene expression and DNA methylation alterations.","authors":"Takako Shibata, Shohei Komaki, Daigo Inoue, Makoto Kunisada, Susumu Fujiwara, Ryusuke Ono, Tsuyoshi Hachiya, Chikako Nishigori","doi":"10.1186/s13148-026-02122-z","DOIUrl":"https://doi.org/10.1186/s13148-026-02122-z","url":null,"abstract":"<p><strong>Background: </strong>Senile lentigines (SL) are common hyperpigmented lesions. While previous studies have characterized morphological changes and gene expression profiles in SLs, the relationship between epigenetic regulation and these transcriptional alterations has not been thoroughly investigated. In this study, we aimed to characterize the transcriptional and epigenetic profiles of SLs by integrating RNA sequencing (RNA-seq) and whole-genome bisulfite sequencing (WGBS).</p><p><strong>Results: </strong>Our gene expression profiling revealed 139 upregulated and 56 downregulated genes, with key pathways related to \"collagen formation\" and \"mitochondrial respiratory chain complex assembly.\" DNA methylation analysis detected 1,580 hypermethylated and 2,708 hypomethylated differentially methylated promoter regions (DMRs). Consistent with the \"information theory of aging\", we found a global disruption of tight epigenetic regulation in SLs, with methylation states of promoter-proximal regions drifting from extreme (0% or 100%) toward intermediate levels. Furthermore, we specifically focused on an inflammatory gene IL-6R, which was hypomethylated at promoter-associated DMRs and upregulated at the RNA level in SLs; immunostaining confirmed increased IL-6R protein, supporting a correlation between IL-6R hypomethylation and protein expression and suggesting that SLs exhibit a chronic inflammatory condition.</p><p><strong>Conclusions: </strong>To our knowledge, this study provides the first evidence that SLs are characterized by a widespread disruption of promoter-proximal epigenetic regulation. Our findings suggest that the disruption of epigenetic information contributes to the formation of SLs and points to the possibility that these disrupted states might be repairable through epigenetic reprogramming.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147671048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lung microbiome predictors of epigenetic aging and potential associations with smoking and electronic cigarette use.","authors":"Ajmal Khan, Boseung Choi, Seungbae Kang, Daniel Y Weng, Kevin Ying, Joseph P McElroy, Sahar Kamel, Sarah A Reisinger, Mark D Wewers, Peter G Shields, Min-Ae Song","doi":"10.1186/s13148-026-02126-9","DOIUrl":"https://doi.org/10.1186/s13148-026-02126-9","url":null,"abstract":"<p><strong>Background: </strong>The lungs harbor diverse microbial communities that may influence pulmonary health, potentially through lung aging. While accelerated lung aging can increase susceptibility to pulmonary diseases, no studies have yet linked the lung microbiome to biological aging in disease-free individuals.</p><p><strong>Materials and methods: </strong>We assessed well-studied methylation-based biological aging (mAge) markers (Horvath, GrimAge, PhenoAge, and telomere-length) in the lungs of healthy smokers (SM), electronic cigarette (EC) users, and never-smokers (NS) (n = 26, 21-30 years). We used metatranscriptome profiling to detect live bacteria. Using XGBoost, we performed feature selection on 1016 bacterial species to predict faster or slower lung mAge, and the selected bacterial species were used as explanatory variables in a logistic regression model. Linear regression analyses examined the associations between identified bacterial species and urinary metabolites of exposure to smoking and EC use, including volatile organic compounds (VOCs) and polycyclic aromatic hydrocarbons (PAHs).</p><p><strong>Results: </strong>The logistic regression models identified bacterial species that classified individuals with faster or slower lung aging based on each mAge estimate (accuracy 77%-85%; AUC 0.78-0.91). Two species strongly predictive of GrimAge, Alistipes finegoldii and Arachidicoccus sp.BS20 were significantly less present in SM compared to NS. Arachidicoccus sp.BS20 was significantly associated with nicotine-intake-adjusted metabolites of several VOCs and PAHs in SM and EC users.</p><p><strong>Conclusion: </strong>For the first time, our study suggests potential associations of the microbiome with biological aging in the lungs of healthy individuals. In addition, the findings indicate that exposure to smoking and EC may be linked to shifts in particular microbial profiles associated with biological aging of the lungs. These results support the need for larger studies to better understand the direction and possible mechanisms of these relationships, and to further explore the lung microbiome as a potential target for interventions aimed at mitigating pulmonary aging and disease risk.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147662292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}