Clinical Epigenetics最新文献

{"title":"Metastasis-associated DNA methylation of the lncRNAs LINC01354 and LINC01510 in clear cell renal cell carcinoma.","authors":"Pouriya Faraj Tabrizi, Inga Mareike Schimansky, Inga Peters, Mohammed Rafea Kanaan, Jörg Hennenlotter, Andre Franke, Hossein Tezval, Markus Antonius Kuczyk, Jürgen Serth","doi":"10.1186/s13148-026-02252-4","DOIUrl":"10.1186/s13148-026-02252-4","url":null,"abstract":"<p><strong>Background: </strong>Long non-coding RNAs (lncRNAs) regulate multiple cellular processes and are involved in the development and progression of human cancers, including renal cell carcinoma (RCC).</p><p><strong>Methods: </strong>Genome-wide DNA methylation profiling using Illumina EPIC arrays was performed to identify differentially methylated regions (DMR) associated with metastatic RCC. Candidate loci within LINC01354 and LINC01510 were validated by pyrosequencing in 145 primary RCC tissues, 124 paired tumor-adjacent normal tissues (adNs), and 194 metastatic tissue samples obtained from 101 patients with metastatic RCC. In addition, data from The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma Collection (TCGA-KIRC) were analyzed in silico to assess the clinical relevance of DNA methylation (DNAm) and its association with gene expression.</p><p><strong>Results: </strong>Hypermethylation across all analyzed CpG sites at both loci was associated with high-stage (≥ T3; p = 0.001) and high-grade (≥ G3; p = 0.003) RCC and was markedly increased in metastatic tissues compared with localized primary tumors (p < 0.001). In addition, primary tumors from patients with distant metastases (M+) showed significantly higher methylation at PS_307-CG1 within LINC01510 than tumors from patients without distant metastases (M0; p = 0.031). Analyses of TCGA-KIRC data confirmed associations of increased methylation with adverse clinicopathological features and reduced gene expression, supporting a potential role for epigenetic silencing.</p><p><strong>Conclusion: </strong>Our data provide further insight into the epigenetic alterations associated with RCC progression by demonstrating tumor- and metastasis-associated hypermethylation at the LINC01354 and LINC01510 loci. The association of hypermethylation with advanced disease and metastatic tissues, together with the observed inverse relationship between methylation and expression, suggests that epigenetic inactivation of these lncRNAs may contribute to RCC progression. DNAm at these loci may therefore represent a potential biomarker of aggressive disease.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"18 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149179052","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":"Nanopore long-read sequencing facilitates accurate diagnosis of KMT2B-related dystonia.","authors":"Ugo Sorrentino, Nazanin Mirza-Schreiber, Martin Pavlov, Fatemeh Peymani, Petra Havrankova, Elisabetta Indelicato, Tereza Serranová, Lukas Kunc, Sandy Lösecke, Erik Tilch, Sebastian Eck, Holger Prokisch, Juliane Winkelmann, Sylvia Boesch, Robert Jech, Elisabeth Graf, Konrad Oexle, Michael Zech","doi":"10.1186/s13148-026-02243-5","DOIUrl":"10.1186/s13148-026-02243-5","url":null,"abstract":"<p><p>Diagnosis of KMT2B-related dystonia remains challenging due to the high prevalence of variants of uncertain significance and technological constraint of short-read pipelines. To overcome these limitations, we integrated nanopore-based long-read sequencing with a validated KMT2B-episignature classifier to perform simultaneous genetic and epigenetic profiling for three cases with prior uncertain KMT2B-related findings. Our workflow detected characteristic deviations in the KMT2B-episignature score in two cases with previously unresolved or missed KMT2B variants, while refuting an ambiguous indel call. Combining genomic-variant detection with DNA-methylation analysis eliminated the need for sequential testing and enhanced accurate diagnosis of KMT2B-related dystonia, offering a basis for streamlined epigenetics-guided diagnostics.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"18 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13587463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987885","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":"Epigenetic clocks can differentiate between exogenous and endogenous skin ageing.","authors":"Christopher J Shore, Roy B Simons, Laura Ramos Del Caño, Ziyi Xiong, Luba Milena Pardo, Christina M W Eecen, Tamar Nijsten, Kerrin S Small, Athina Vidaki, Manfred Kayser, Jordana T Bell, Y Jeremy Shen, David A Gunn","doi":"10.1186/s13148-026-02230-w","DOIUrl":"10.1186/s13148-026-02230-w","url":null,"abstract":"<p><strong>Context: </strong>Whereas factors originating internally to the body, such as blood nutrients and hormones, influence endogenous skin ageing, exogenous skin ageing results from the penetration of harmful factors through the skin's outer stratum corneum layer.</p><p><strong>Aim: </strong>To test whether an exogenous skin ageing epigenetic clock is more strongly associated with aspects of sun-exposure than two endogenous epigenetic clocks.</p><p><strong>Methods: </strong>Exogenous and endogenous skin clocks were trained in more than 400 skin samples. These two clocks and the Horvath 'Skin and Blood' epigenetic clock were tested for association with chronological age and, whilst controlling for chronological age (age acceleration), sun-exposure parameters and skin gene expression.</p><p><strong>Results: </strong>Exogenous Skin clock ages were significantly (p<0.001) older in both epidermal (n=24) and cultured fibroblast (n=8) sun-exposed arm samples than in donor matched sun-protected samples. Exogenous Skin clock age acceleration was significantly correlated (Rho = 0.18, p = 0.004) with sun-seeking behaviour and mRNA levels (202 genes had q < 0.05) in whole skin abdomen samples (n=364); the latter was consistent with sun-exposed versus sun-protected older arm mRNA differences (n=12 donors). In 44 facial skin swabs, exogenous age acceleration was also significantly correlated with facial photodamage grading (rho = 0.33, p = 0.028). Although the Endogenous and Skin and Blood clocks were more strongly correlated with chronological age, their age acceleration estimates were not significantly associated with sun-exposure parameters or mRNA levels in skin.</p><p><strong>Conclusion: </strong>Skin epigenetic clocks can differentiate exogenous from endogenous skin ageing facilitating further study of the mechanisms underlying these two skin ageing phenomena.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"18 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012118","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":"Beyond redox: vitamin C in signaling, epigenetic regulation and protein modification-relevance to cancer therapy.","authors":"Amisha S Hebbar, Sandra Nixon, Hanumappa Ananda, Manasa Nune, Vinay Kumar Rao","doi":"10.1186/s13148-026-02211-z","DOIUrl":"https://doi.org/10.1186/s13148-026-02211-z","url":null,"abstract":"<p><p>Vitamin C, a classical antioxidant, is increasingly recognized as a key regulator of cellular signaling networks, epigenetic, and post-translational regulation. As a cofactor of Fe²⁺/2-oxoglutarate-dependent dioxygenases, vitamin C promotes epigenomic changes by enhancing TET-dependent DNA demethylation and the activity of Jumonji-C domain-containing histone demethylase, thereby influencing key cellular processes including pluripotency, reprogramming, and differentiation. Recent studies have also uncovered a direct role for vitamin C in proteome regulation by modifying lysine residues, to generate vitcyl-lysine (a process termed as Vitcylation), opening new avenues for its therapeutic applications. These lesser-understood functions of vitamin C underpin its context-dependent roles in cancer and other disease states. Future mechanistic studies identifying targets of vitamin C-dependent protein modification and their consequences on epigenome regulation will be critical for advancing its therapeutic applications.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"18 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13625384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149105021","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":"Stress, diet, and aging: a comprehensive analysis of allostatic load in biological aging.","authors":"Jun Liu, Song Zhou, Jihong Zhang, Shuyu Ke, Junming Huang","doi":"10.1186/s13148-026-02210-0","DOIUrl":"https://doi.org/10.1186/s13148-026-02210-0","url":null,"abstract":"<p><strong>Background: </strong>As the global population continues to age, biological aging has emerged as a significant public health challenge. It is imperative to identify modifiable factors and underlying mechanisms that can promote healthy aging. Allostatic load (AL), a comprehensive indicator of chronic stress, is linked to numerous adverse outcomes in behavioral health. However, there is a paucity of comprehensive analyses and mechanistic investigations regarding the relationship between AL and biological aging across the entire population. This study seeks to elucidate the relationship between AL and biological aging, with a particular focus on examining the mediating role of the Dietary Inflammatory Index (DII).</p><p><strong>Method: </strong>This study analyzed data from NHANES (2001-2010 and 2015-2018) with 25,775 U.S. adults, excluding those with missing data. It measured AL using 8 biomarkers and assessed biological aging with four indicators: Phenotypic Age, Biological Age, GOLD BioAge, and Light BioAge. The DII was calculated from 24-h dietary recall of 45 food items. Sociodemographic and clinical factors were covariates. Weighted linear and logistic regressions examined the complex relationship between AL, DII, and biological aging, with subgroup and mediation analyses exploring mediating role of DII in the AL-aging link.</p><p><strong>Result: </strong>A total of 21.56% of participants were in the high AL group, showing significantly higher DII scores and elevated biological aging indicators compared to the low AL group (P < 0.001). After adjusting for confounders, high AL was linked to faster biological aging, with a 2.08-year increase in Phenotypic Age and a 9.06-year increase in Biological Age. Odds ratios for elevated GOLD BioAge and Light BioAge were 1.60 and 2.16, respectively (P < 0.001). The AL-aging link was stronger in young/middle-aged adults, females, and non-obese individuals. DII was positively linked to all aging indicators, and exploratory mediation analysis suggested that DII may statistically account for a small proportion of the AL-aging association, with mediation proportions ranging from 0.33% to 5.45% (P < 0.001).</p><p><strong>Conclusion: </strong>In a nationally representative sample of U.S. adults, elevated AL is significantly associated with accelerated biological aging assessed by multiple complementary indicators, and exploratory mediation analysis suggested that DII may partly account for part of this association. These findings underscore the importance of mitigating chronic physiological stress and reducing the inflammatory potential of the diet as strategies to promote healthy aging. Clinical assessment of AL and DII may provide valuable insights for identifying individuals at risk of accelerated biological aging and guiding targeted intervention measures to improve long-term health outcomes.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"18 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223196","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":"Neuroepigenetic programming by the maternal environment: part A-epigenome-wide DNA methylation profile in the offspring's olfactory bulb following preconceptional weight loss in mice.","authors":"Karine Badonnel, Aurélie Chaulot-Talmon, Valentin Costes, Anne Frambourg, Gabriel Costa-Monteiro-Moreira, Mélanie Jouin, Lorraine Bourgeois-Brunel, Anne Gabory, Hélène Kiefer, Hélène Jammes, Christine Baly","doi":"10.1186/s13148-026-02167-0","DOIUrl":"https://doi.org/10.1186/s13148-026-02167-0","url":null,"abstract":"<p><strong>Background: </strong>Experimental models and epidemiological data suggest that the maternal nutritional environment during gestation plays important roles in brain development with consequences on cognitive health. Epigenetic marks, such as methylation and histone modifications, are likely to be involved in this programming, but little addressed the impact of maternal metabolism at the preconceptional period. In mice, we recently demonstrated lasting effects of a maternal preconceptional weight loss on metabolic outcomes and behaviors related to food intake in the male offspring, exhibiting a reduction in olfactory sensitivity, along with a lack of fasting-induced olfactory-based motivation. To evaluate if this effect was driven by epigenetic modifications in the olfactory bulb, we profiled brain DNA methylation, a fundamental process in mediating the relation between early life environment and long-term behaviors in mice according to the maternal status.</p><p><strong>Results: </strong>Using oxidative reduced representation bisulfite sequencing to specifically target 5mC in mice exposed to preconceptional weight loss versus controls, we identified 11,055 differentially methylated cytosines and 150 differential methylated regions (DMRs) located in 111 genes in the olfactory bulb, a main region involved in odor processing and integration. Among the cytosines differentially methylated, half were hypermethylated. Methylation remodeling according to the maternal group preferentially affected noncoding intragenic regions, distal regulatory elements, and open sea CpGs, while promoter CpG islands remain relatively resistant to modification in DNA methylome. The functional annotation of DMRs pointed out genes related to histones kinases, energy signaling, synaptic function, and cellular differentiation, suggesting that targeted methylation changes may simultaneously influence epigenetic regulation, metabolism, and neurobiology.</p><p><strong>Conclusion: </strong>Thanks to a single-base analysis of differential methylated CpGs, we present novel evidence that the maternal dietary environment prior to conception exerts maternally-driven epigenetic effects, markedly altering 5-methylcytosine patterns in the adult offspring brain. This long-lasting remodeling of the offspring's olfactory bulb methylome may underlie the described alterations in olfactory-driven behaviors of offspring born to WL mother.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"18 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223161","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":"FUBP1 lactylation suppresses trophoblast function in fetal growth restriction.","authors":"Xinyue Liang, Shenshen Yao, Jian Ma, Dan Wang","doi":"10.1186/s13148-026-02208-8","DOIUrl":"https://doi.org/10.1186/s13148-026-02208-8","url":null,"abstract":"<p><strong>Background: </strong>Fetal growth restriction (FGR) is a common complication of pregnancy; however, its exact molecular mechanisms remain unclear. Excessive lactate accumulation in the placenta is often observed during FGR. High concentrations of lactate can regulate the proliferation of pathological cells through lactylation of key proteins. Therefore, we aimed to screen key lactylation modification-related genes (LMRGs) and provide new directions for the diagnosis and treatment of FGR.</p><p><strong>Methods: </strong>The Differentially expressed LMRGs (DE-LMRGs) in FGR were evaluated using the Gene Expression Omnibus database. Functional enrichment analysis was performed, and a protein-protein interaction (PPI) network was created to explore the characteristics of placental gene networks associated with FGR. In addition, secondary cluster analysis was performed using a machine learning algorithm to screen critical genes. We evaluated the degree of immune cell infiltration of key genes using single-sample gene set enrichment analysis. The expression and function of key genes in FGR were verified experimentally. Furthermore, FUBP1 lactylation was assessed using mass spectrometry and immunoprecipitation. We overexpressed wild-type and mutant FUBP1 in HTR-8/SVneo cells to investigate how its lactylation regulates trophoblast function. Finally, patient-derived organoids (PDO) were cultured to confirm the underlying mechanism of FUBP1.</p><p><strong>Results: </strong>In total, 35 DE-LMRGs were identified, and their PPI network was constructed. Two distinct FGR clusters were obtained using unsupervised consensus clustering. Moreover, the DE-LMRGs between the two patterns were mainly enriched in immune cell regulation-related molecular functions. We identified 5 overlapping key genes (BCLAF1, FUBP1, S100A6, CSRP1, CSRP2) by integrating the LASSO, random forest (RF), and SVM-RFE algorithms and screening for genes with a large fold change (using log2-FC). FUBP1 and BCLAF1 expression was lower in FGR placental tissues than in normal controls. Functional assays showed that both genes typically promote HTR-8/SVneo cell proliferation and invasion. However, lactylation of FUBP1 exerted the opposite effect by inhibiting proliferation and invasion and promoting apoptosis, indicating that FUBP1 lactylation regulates trophoblast function. Furthermore, PDO derived from the trophoblast tissues of patients with FGR revealed that FUBP1 lactylation suppressed PDO formation.</p><p><strong>Conclusions: </strong>FUBP1 lactylation is identified as a novel mechanism suppressing trophoblast function in FGR. This finding expands the field of FGR research by highlighting the role of lactylation-modified proteins and provides crucial insights into the pathological mechanisms of FGR.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"18 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223183","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":"New perspective on epigenetic modification and immunotherapy in endometrial cancer.","authors":"Haoqian Zhang, Dandan Shen, Nanshan Lin, Li Yang, Chenchen Ren","doi":"10.1186/s13148-026-02174-1","DOIUrl":"10.1186/s13148-026-02174-1","url":null,"abstract":"<p><p>Endometrial carcinoma (EC) is a heterogeneous gynecological malignancy. Epigenetic dysregulation promotes the initiation, progression, immune evasion, and therapeutic resistance of EC. Aberrant DNA methylation, histone methylation, histone acetylation, and chromatin remodeling affect key EC-associated pathways and help shape distinct molecular subtypes, including POLE-mutated and mismatch repair-deficient tumours. In this review, we summarize the major epigenetic alterations implicated in EC, with emphasis on DNA methylation regulators, histone-modifying enzymes, and emerging epigenetic targets such as DNMTs, HDACs, LSD1, EZH2, PRMTs, and BET proteins. We further highlight the rapidly evolving immunotherapy landscape in EC, including clinically established or practice-changing regimens such as pembrolizumab-, dostarlimab-, durvalumab-, and lenvatinib-based strategies, particularly in advanced or recurrent disease. In parallel, we discuss investigational epigenetic therapies, including DNMT inhibitors, HDAC inhibitors, LSD1 inhibitors, EZH2-targeted agents, PRMT inhibitors, and BRD4-directed approaches, which are being explored to restore tumour suppressor pathways, enhance tumour immunogenicity, and improve sensitivity to immune checkpoint blockade. By integrating EC-specific epigenetic mechanisms with current immunotherapy advances and ongoing combination strategies, this review provides a clinically oriented perspective on biomarker-guided precision treatment for EC.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"18 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220083","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":"Direct analysis of transcription factor protected cfDNA in plasma by ChIP-seq: measurement of altered CTCF binding in cancer is a novel biomarker for liquid biopsy.","authors":"Dorian Pamart, Brieuc Cuvelier, Adrien Govaerts, Muriel Chapelier, Marielle Herzog, Andrew Retter, Thomas Bygott, Jean-Valery Turatsinze, Benjamin P Berman, Jacob Micallef","doi":"10.1186/s13148-026-02205-x","DOIUrl":"10.1186/s13148-026-02205-x","url":null,"abstract":"<p><strong>Background: </strong>The aggregate presence of cell free CTCF-DNA (cfCTCF-DNA) nucleoproteins in plasma has been reported. But the occupancy of individual CTCF binding sites in plasma cfCTCF-DNA has not been studied.</p><p><strong>Results: </strong>For the first time, we have isolated endogenous plasma cfCTCF-DNA by chromatin immunoprecipitation (ChIP) and sequenced the associated cfDNA (ChIP-Seq) in samples from cancer patients and healthy subjects. The mean observed enrichment of plasma cfCTCF-DNA by ChIP was 180-fold with a mean CTCF recovery of 48%. Background cfDNA, primarily in the form of nucleosomes, was almost completely physically removed (> 99.7%) by ChIP and the remainder was removed bioinformatically. cfCTCF-DNA sequences were partitioned into low or high affinity binding cfCTCF-DNA nucleoproteins in silico, on the basis of binding motif concordance with the consensus CTCF binding motif. We observed that cfCTCF-DNA was quantitatively and qualitatively different in samples from healthy subjects or cancer patients. High affinity cfCTCF-DNA nucleoproteins were present only in the plasma of cancer patients and not in samples from healthy subjects. Testing of small developmental and validation sample cohorts for ChIP-seq peaks for a 14 member panel of high affinity CTCF loci sequences, showed excellent specificity and sensitivity for cancer detection.</p><p><strong>Conclusions: </strong>Plasma sequence data sets comprising > 99% pure CTCF protected ctDNA can be prepared using a 2-step process involving the physical removal of most background cfDNA in vitro, followed by removal of all remaining background cfDNA in silico. CTCF plasma ChIP-seq represents a novel liquid biopsy method for a novel class of liquid biopsy biomarkers.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548075","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":"Inflammation mediates the Pace of aging based on DNA methylation on mortality from NHANES 1999-2002: a national prospective cohort study.","authors":"Jihua Feng, Yuting Liang, Jie Zhou, Yongbing Yu, Xiaowen Zheng, Jingjia Mo, Zhiqing Huang, Jianfeng Zhang","doi":"10.1186/s13148-026-02206-w","DOIUrl":"10.1186/s13148-026-02206-w","url":null,"abstract":"<p><strong>Background: </strong>Global population aging underscores the urgent need for biomarkers quantifying biological aging trajectories. While DNA methylation-derived pace of aging (DunedinPoAm) measures individual differences, its generalizability across diverse populations and mechanistic links to systemic inflammation remain underexplored. This study aimed to systematically examine the longitudinal associations between the DunedinPoAm and all‑cause mortality in a multiethnic cohort, and to quantify the extent to which systemic inflammatory biomarkers mediate these associations using causal mediation analysis.</p><p><strong>Methods: </strong>For this cohort study, information on a nationally representative cohort of 21,004 U.S. adults was extracted from the National Health and Nutrition Examination Survey (NHANES) conducted from 1999 to 2002, along with the NHANES Linked Mortality File, which ascertained mortality through December 31, 2019. The exposures were Pace of aging (DunedinPoAm) and inflammation. The survival outcome measured was all-cause mortality. We employed Cox proportional hazards models, Kaplan-Meier survival curves, restricted cubic splines, and Bayesian mediation frameworks to evaluate mortality risk, explore non-linear dose-response relationships, and investigate inflammatory mediation.</p><p><strong>Results: </strong>Data were analyzed from 2,532 participants, with a mean follow-up duration of 18.5 ± 1.29 years. Higher DunedinPoAm quartiles exhibited graded mortality risks (Q4 vs. Q1: HR = 2.50, 95% CI 1.84-3.38), which persisted after multivariable adjustment. Restricted cubic splines revealed a non-linear association (P for overall < 0.001; P for nonlinearity < 0.001), indicating the presence of threshold effects. Systemic inflammation mediated 2.33-23.5% of the mortality risk associated with DunedinPoAm, driven by CD4 + T cells, B cells, CRP and comprehensive inflammatory indices. A significant interaction with diabetes (P for interaction = 0.026) underscored metabolic dysregulation as a vulnerability factor.</p><p><strong>Conclusion: </strong>DunedinPoAm predicts all-cause mortality in a non-linearly manner across multiethnic populations, partially mediated by pathways associated with inflammaging. The observed diabetes-specific interactions and threshold effects indicate the potential for precision approaches targeting high-risk subgroups. These findings support the integration of DunedinPoAm into gerotherapeutic trials and public health strategies aimed at addressing disparities in aging.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148469357","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}