Clinical Epigenetics最新文献

{"title":"DNA methylation in primary myelofibrosis is partly associated with driver mutations and distinct from other myeloid malignancies.","authors":"Esra Dursun Torlak, Vithurithra Tharmapalan, Kim Kricheldorf, Joelle Schifflers, Madeline Caduc, Martin Zenke, Steffen Koschmieder, Wolfgang Wagner","doi":"10.1186/s13148-025-01877-1","DOIUrl":"https://doi.org/10.1186/s13148-025-01877-1","url":null,"abstract":"<p><strong>Background: </strong>Primary myelofibrosis (PMF) is a clonal blood disorder characterized by mutually exclusive driver mutations in JAK2, CALR, or MPL genes. So far, it is largely unclear if the driver mutations have a specific impact on DNA methylation (DNAm) profiles and how epigenetic alterations in PMF are related to other myeloid malignancies.</p><p><strong>Results: </strong>When we compared DNAm profiles from PMF patients we found very similar epigenetic modifications in JAK2 and CALR mutated cases, whereas MPL mutations displayed less pronounced and distinct patterns. Furthermore, induced pluripotent stem cell (iPSC) models with JAK2 mutations indicated only a moderate association with PMF-related epigenetic changes, suggesting that these alterations may not be directly driven by the mutations themselves. Additionally, PMF-associated epigenetic changes showed minimal correlation with allele burden and seemed to be largely influenced by shifts in the cellular composition. PMF DNAm profiles compared with those from other myeloid malignancies-such as acute myeloid leukemia, juvenile myelomonocytic leukemia, and myelodysplastic syndrome-showed numerous overlapping changes, making it difficult to distinguish PMF based on individual CpGs. However, a PMF score created by combining five CpGs was able to discern PMF from other diseases.</p><p><strong>Conclusion: </strong>These findings demonstrate that PMF driver mutations do not directly evoke epigenetic changes. While PMF shares epigenetic alterations with other myeloid malignancies, DNA methylation patterns can distinguish between PMF and related diseases.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"72"},"PeriodicalIF":4.8,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989705","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":"Maternal uniparental disomy of chromosome 7: how chromosome 7-encoded imprinted genes contribute to the Silver-Russell phenotype.","authors":"Matthias Begemann, Anna Lengyel, Eva Pinti, Árpád Ferenc Kovács, György Fekete, Svea Stratmann, Jeremias Krause, Miriam Elbracht, Florian Kraft, Thomas Eggermann","doi":"10.1186/s13148-025-01867-3","DOIUrl":"https://doi.org/10.1186/s13148-025-01867-3","url":null,"abstract":"<p><strong>Background: </strong>Silver-Russell syndrome (SRS) is a rare congenital growth disorder which is associated with molecular alterations affecting imprinted regions on chromosome 11p15 and maternal uniparental disomy of chromosome 7 (upd(7)mat). In 11p15, imprinted regions contributing to the SRS phenotype could be identified, whereas on chromosome 7 at least two regions in 7q32 and 7p13 are in discussion as SRS candidate regions. We report on DNA and RNA data from upd(7)mat patients and a monozygotic twin pair with a postnatal SRS phenotype carrying a small intragenic deletion within GRB10 to delineate the contribution of upd(7)mat and imprinted genes on this chromosome to the SRS phenotype.</p><p><strong>Results: </strong>Genome sequencing in the monozygotic twins revealed a 18 kb deletion within the paternal allele of the GRB10 gene. Expression of GRB10 in blood of the twins as well as in cells from upd(7)mat and upd(7q)mat patients was not altered, whereas RNAseq indicates noticeable changes of the expression of other genes encoded by chromosomes 7 and other genomic regions.</p><p><strong>Conclusions: </strong>Our data indicate that intrauterine growth restriction as the prenatal phenotype of upd(7)mat is caused by defective paternal alleles of the 7q32 region, as well as by overexpression of the maternal GRB10 allele whereas a defective GRB10 paternal allele does not cause this feature. The altered expression of MEST in 7q32 by upd(7)mat is associated with the complete SRS phenotype, whereas maternalization or deletion of the paternal GRB10 copy and duplication of the chromosomal region 7p12 are associated with a postnatal SRS-like phenotype.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"70"},"PeriodicalIF":4.8,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977311","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":"DNA methylation in melanoma immunotherapy: mechanisms and therapeutic opportunities.","authors":"Maya G Deshmukh, Veronica T Brooks, Simon F Roy, Simon Milette, Marcus Bosenberg, Goran Micevic","doi":"10.1186/s13148-025-01865-5","DOIUrl":"https://doi.org/10.1186/s13148-025-01865-5","url":null,"abstract":"<p><p>Abnormal DNA methylation is a hallmark of cancer and a nearly universal feature of melanoma. DNA methylation plays well-appreciated melanoma cell-intrinsic roles, including silencing tumor-suppressor genes, regulating genomic stability, deregulating expression of oncogenes to potentiate proliferative signaling and tumor migration. With the recent success of immunological therapies for melanoma, important roles for DNA methylation are also emerging at the interface between melanoma and immune cells with the potential to regulate the anti-tumor immune response. These newly recognized roles for DNA methylation in controlling melanoma cell immunogenicity, expression of MHC and immune checkpoint molecules as well as T cell phenotypes in the tumor microenvironment raise the possibility of using DNA methylation to develop improved therapies and methylation-based biomarkers. In addition to reviewing the \"immune dimension\" of DNA methylation, we summarize recent developments with potential clinical applications in melanoma, such as targeted DNA methylation editing, single-cell methylation approaches, and measurement of circulating methylated DNA. An improved understanding of the immune roles of DNA methylation presents an exciting opportunity for continued improvement of care and outcomes for patients with melanoma.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"71"},"PeriodicalIF":4.8,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143956223","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":"Thirteen cases support the clinical significance of imprinting center 1 (IC1) microdeletions in Beckwith-Wiedemann syndrome.","authors":"Qiliang Ding, Zinandre Stander, Brandon J Elizalde, Erica S Stelmach, Jaime C Duncan, Noemi Vidal-Folch, Linda Hasadsri, Kandelaria M Rumilla, Wei Shen","doi":"10.1186/s13148-025-01873-5","DOIUrl":"https://doi.org/10.1186/s13148-025-01873-5","url":null,"abstract":"<p><p>Most Beckwith-Wiedemann syndrome (BWS) cases are sporadic; nonetheless, imprinting center 1 (IC1) microdeletions have been suggested as a rare cause of familial BWS, with ~ 20 reported cases. We report 13 cases from nine families with IC1 microdeletions. Recurrent 1.4-kb, 1.8-kb, and 2.2-kb deletions were observed. IC1 hypermethylation was identified in all families, and we established a statistically significant relationship between IC1 microdeletions and hypermethylation (OR: 108.17, p = 2.76e-13). This study confirms IC1 microdeletions as a cause of familial BWS, expands the understanding of their molecular mechanisms, and supports a Likely Pathogenic clinical classification for IC1 microdeletions.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"67"},"PeriodicalIF":4.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12039090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975335","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":"Reverse genotyping: unveiling Alu element insertion as a new cause of Kabuki syndrome using DNA methylation signature.","authors":"Quentin Sabbagh, Nathalie Ruiz-Pallares, Cassandra Rastin, Jacques Puechberty, Thomas Guignard, Claire Jeandel, Fanny Merklen, Pascal Pujol, Jennifer Kerkhof, Bekim Sadikovic, Mouna Barat-Houari, David Geneviève","doi":"10.1186/s13148-025-01879-z","DOIUrl":"https://doi.org/10.1186/s13148-025-01879-z","url":null,"abstract":"<p><p>Kabuki syndrome type 1 (KS1) is a monogenic disorder arising from pathogenic variants within KMT2D and characterized by syndromic neurodevelopmental delay. We report the retrospective identification of a causative AluY insertion within KMT2D in a genetically unsolved individual with typical KS1 features, after identification of a DNA methylation signature. This is the first documentation of Alu insertion as a molecular mechanism responsible for KS1. This study emphasizes the need for reanalyzing inconclusive sequencing data in individuals with gene-specific phenotypes and reinforces episignature as a reliable diagnostic tool when NGS approaches fail to provide conclusive results in individuals with rare diseases.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"69"},"PeriodicalIF":4.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990042","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":"Associations between five indicators of epigenetic age acceleration and all-cause and cause-specific mortality among US adults aged 50 years and older.","authors":"Yun Zou, Jing Huang, Xiaoli Tang, Jixiong Xu","doi":"10.1186/s13148-025-01872-6","DOIUrl":"https://doi.org/10.1186/s13148-025-01872-6","url":null,"abstract":"<p><strong>Background: </strong>Although DNA methylation age estimators (DNAmAges) are reliable tools for predicting aging, their effectiveness in predicting mortality risk has not been fully validated. This study compared the predictive utility of five different DNAmAges (HorvathAge, HannumAge, PhenoAgeAge, GrimAge and GrimAge2) for all-cause and cause-specific mortality among adults aged ≥ 50 years.</p><p><strong>Methods: </strong>We screened 1966 participants adults aged ≥ 50 from the National Health and Nutrition Examination Survey (1999-2002) and linked them to the National Death Index to obtain cause and status of death. We used weighted Cox proportional hazards models to examine the associations between epigenetic age acceleration (EAA) measured by different DNAmAges and all-cause and cause-specific mortality in the general population, adjusting for various covariates including age, smoking status and chronic diseases. We used restricted cubic splines to explore nonlinear associations. Finally, stratified analyses were performed to assess the relationship between DNA age estimators and stratification variables.</p><p><strong>Results: </strong>The multivariable adjustment model showed that EAA measured by HorvathAge (AAHorvathAge), HannumAge (AAHannumAge), PhenoAge (AAPhenoAge), GrimAge (AAGrimAge) and GrimAge2 (AAGrimAge) were significantly associated with the risk of death, among which AAGrimAge and AAGrimAge2 had stronger statistical correlation and the correlation pattern was positively correlated. Specifically, each 5-year increase in AAGrimAge was associated with a 44% increased risk of all-cause death, a 33% increased risk of cardiovascular death and a 54% increased risk of non-cardiovascular death. And each 5-year increase in AAGrimAge2 was associated with a 40% increased risk of all-cause death, a 33% increased risk of cardiovascular death and a 47% increased risk of non-cardiovascular death. In contrast, AAHorvathAge, AAHannumAge and AAPhenoAge showed a J-shaped correlation with the risk of all-cause mortality and non-cardiovascular mortality, with the inflection points of all-cause mortality and non-cardiovascular mortality occurring at AAHorvathAge of 2.29 and 2.8, AAHannumAge of 3.07 and 2.97, and AAPhenoAge of - 7.65 and 7.04, respectively. No interaction was found between DNAmAges and stratification variables.</p><p><strong>Conclusions: </strong>AAGrimAge and AAGrimAge2 outperformed AAHorvathAge, AAHannumAge and AAPhenoAge in predicting mortality risk, and the association pattern was positive.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"66"},"PeriodicalIF":4.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983727","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":"Regulation of nc886 (vtRNA2-1) RNAs is associated with cardiometabolic risk factors and diseases.","authors":"Sonja Rajić, Thomas Delerue, Justiina Ronkainen, Ruiyuan Zhang, Joanna Ciantar, Daria Kostiniuk, Pashupati P Mishra, Leo-Pekka Lyytikäinen, Nina Mononen, Laura Kananen, Annette Peters, Juliane Winkelmann, Marcus E Kleber, Stefan Lorkowski, Mika Kähönen, Terho Lehtimäki, Olli Raitakari, Melanie Waldenberger, Christian Gieger, Winfried März, Emily W Harville, Sylvain Sebert, Saara Marttila, Emma Raitoharju","doi":"10.1186/s13148-025-01871-7","DOIUrl":"https://doi.org/10.1186/s13148-025-01871-7","url":null,"abstract":"<p><p>Non-coding 886 (nc886, vtRNA2-1) is a polymorphically imprinted gene. The methylation status of this locus has been shown to be associated with periconceptional conditions, and both the methylation status and the levels of nc886 RNAs have been shown to associate with later-life health traits. We have previously shown that nc886 RNA levels are associated not only with the methylation status of the locus, but also with a genetic polymorphism upstream from the locus. In this study, we describe the genetic and epigenetic regulators that predict lifelong nc886 RNA levels, as well as their association with cardiometabolic disease (CMD) risk factors and events. We utilised six population cohorts and one CMD cohort comprising 9058 individuals in total. The association of nc886 RNA levels, as predicted by epigenetic and genetic regulators, with CMD phenotypes was analysed using regression models, with a meta-analysis of the results. The meta-analysis showed that individuals with upregulated nc886 RNA levels have higher diastolic blood pressure (β = 0.07, p = 0.008), lower HDL levels (β =  - 0.07, p = 0.006) and an increased incidence of type 2 diabetes (OR = 1.260, p = 0.013). Moreover, CMD patients with upregulated nc886 RNA levels have an increased incidence of stroke (OR = 1.581, p = 0.006) and death (OR = 1.290, p = 0.046). In conclusion, we show that individuals who are predicted to present elevated nc886 RNA levels have poorer cardiovascular health and are at an elevated risk of complications in secondary prevention. This unique mechanism yields metabolic variation in human populations, constituting a CMD risk factor that cannot be modified through lifestyle choices.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"68"},"PeriodicalIF":4.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978992","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":"Integrative DNA methylome and transcriptome analysis identify potential genes on the influence of dilated cardiomyopathy-associated heart failure.","authors":"Zhenglong Guo, Yunfei Liu, Zhiming Zhou, Jianchao Chen, Lin Guo, Keke Liang, Yibin Hao, Bingtao Hao, Bin Yang, Shixiu Liao","doi":"10.1186/s13148-025-01876-2","DOIUrl":"https://doi.org/10.1186/s13148-025-01876-2","url":null,"abstract":"<p><strong>Objective: </strong>Dilated cardiomyopathy (DCM)-associated heart failure (HF) presents a significant clinical challenge, underlying epigenetic mechanisms remaining poorly understood. This study aims to investigate the interplay between DNA methylation and gene expression in the hearts of patients with DCM-associated HF (DCM-HF).</p><p><strong>Methods: </strong>Atrial tissues were collected from five healthy donors and five heart transplant recipients suffering from heart failure due to DCM. We conducted RNA-sequencing (RNA-seq) to analyze mRNA expression profiles and performed whole-genome bisulfite sequencing (WGBS) to evaluate DNA methylation levels. Correlation analyses between RNA-seq and WGBS data were executed by integrating differentially expressed genes (DEGs) with genes associated with differentially methylated regions (DMRs) located in the promoter regions.</p><p><strong>Results: </strong>The RNA-seq analysis identified a total of 681 DEGs, comprising 406 significantly downregulated genes and 275 upregulated genes in DCM-HF tissues, which were enriched in pathways related to cardiomyopathy. WGBS revealed 16,158 hypomethylated and 6,857 hypermethylated differentially methylated regions (DMRs), with 3,185 of these located in promoter regions. The integration of promoter-hypomethylated and hypermethylated DMRs-related genes (DMGs) with DEGs resulted in the identification of 46 hub genes associated with cardiac development and function. Protein-protein interaction and disease association analyses highlighted five key genes-NPPA, NPPB, ACTN2, NEBL, and MYO18B-that exhibited promoter hypomethylation and increased expression, potentially linked to the activity of transcription factors such as HIF1A and KLF4.</p><p><strong>Conclusions: </strong>These findings suggest that the epigenetic dysregulation of cardiac stress-response and structural genes contributes to the pathogenesis of DCM-HF. Furthermore, the detection of promoter methylation levels in these loci may offer new opportunities for developing diagnostic tools and therapeutic strategies for DCM-HF management.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"64"},"PeriodicalIF":4.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961547","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":"DNA methylation associated with the serum alanine aminotransferase concentration: evidence from Chinese monozygotic twins.","authors":"Jingxian Li, Jia Luo, Tong Wang, Xiaocao Tian, Chunsheng Xu, Weijing Wang, Dongfeng Zhang","doi":"10.1186/s13148-025-01869-1","DOIUrl":"https://doi.org/10.1186/s13148-025-01869-1","url":null,"abstract":"<p><strong>Background: </strong>To identify nongenetic factors influences on DNA methylation (DNAm) variations associated with blood Alanine Aminotransferase (ALT) concentration, this study conducted an epigenome-wide association study (EWAS) on Chinese monozygotic twins.</p><p><strong>Methods: </strong>A total of 61 pairs of Chinese monozygotic twins involved in this study. Whole blood samples were analyzed for DNAm profiling using the Reduced Representation Bisulfite Sequencing (RRBS) technique. We examined the relationship between DNAm levels at each CpG site and serum ALT using a linear mixed-effects model. Enrichment analysis and causal inference analysis was conducted, and differentially methylated regions (DMRs) were further identified. Candidate CpGs were validated in a community sample. Genome-wide significance were calculated by Bonferroni correction (p < 2.14 × 10^-7).</p><p><strong>Results: </strong>We identified 85 CpGs reaching genome-wide significance (p < 2.14 × 10^-7), located in 16 genes including FLT4, ADARB2, MRPS31P2, and RELB. Causal inference suggested that DNAm at 61 out of 85 significant CpGs within 14 genes influenced ALT level. 52 DMRs and 1765 pathways such as low voltage-gated calcium channel activity and focal adhesion were identified having influences on ALT levels. Further validation using community population found four CpGs mapped to FLT4 and three to RELB showing hypomethylation and hypermethylation in cases with abnormal ALT (ALT > 40 U/L), respectively.</p><p><strong>Conclusion: </strong>This study identified several differentially methylated CpG sites associated with serum ALT in the Chinese population, particularly within FLT4 and RELB. These findings provide new insights into the epigenetic modifications underlying liver function.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"65"},"PeriodicalIF":4.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12039056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962229","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":"Low blood levels of selenium, selenoprotein P and GPx3 are associated with accelerated biological aging: results from the Berlin Aging Study II (BASE-II).","authors":"Valentin Max Vetter, Kamil Demircan, Jan Homann, Thilo Samson Chillon, Michael Mülleder, Orr Shomroni, Elisabeth Steinhagen-Thiessen, Markus Ralser, Christina M Lill, Lars Bertram, Lutz Schomburg, Ilja Demuth","doi":"10.1186/s13148-025-01863-7","DOIUrl":"10.1186/s13148-025-01863-7","url":null,"abstract":"<p><strong>Background: </strong>Biological age reflects inter-individual differences in biological function and capacity beyond chronological age. DNA methylation age (DNAmA) and its deviation from chronological age, DNAmA acceleration (DNAmAA), which was calculated as residuals of leukocyte cell count adjusted linear regression of DNAmA on chronological age, were used to estimate biological age in this study. Low levels of serum selenium, selenoprotein P (SELENOP), and the selenocysteine-containing glutathione peroxidase 3 (GPx3) are associated with adverse health outcomes and selenium supplementation is discussed as an anti-aging intervention.</p><p><strong>Methods: </strong>In this study, we cross-sectionally analyzed 1568 older participants from the observational Berlin Aging Study II (mean age ± SD: 68.8 ± 3.7 years, 51% women). Serum selenium was measured by total reflection X-ray fluorescence (TXRF) spectroscopy and SELENOP was determined by sandwich ELISA. GPx3 was assessed as part of a proteomics dataset using liquid chromatography-mass spectrometry (LC-MS). The relationship between selenium biomarkers and epigenetic clock measures was analyzed using linear regression analyses. P values and 95% confidence intervals (not adjusted for multiple testing) are stated for each analysis.</p><p><strong>Results: </strong>Participants with deficient serum selenium levels (< 90 μg/L) had a higher rate of biological aging (DunedinPACE, β = - 0.02, SE = 0.01, 95% CI - 0.033 to - 0.004, p = 0.010, n = 865). This association remained statistically significant after adjustment for age, sex, BMI, smoking, and first four genetic principal components (β = - 0.02, SE = 0.01, 95% CI - 0.034 to - 0.004, p = 0.012, n = 757). Compared to the highest quartile, participants in the lowest quartile of SELENOP levels showed an accelerated biological aging rate (DunedinPACE, β = - 0.03, SE = 0.01, 95% CI - 0.051 to - 0.008, p = 0.007, n = 740, fully adjusted model). Similarly, after adjustment for confounders, accelerated biological age was found in participants within the lowest GPx3 quartile compared to participants in the fourth quartile (DunedinPACE, β = - 0.04, SE = 0.01, 95% CI - 0.06 to - 0.02, p = 0.001, n = 674 and GrimAge, β = - 0.98, SE = 0.32, 95% CI - 1.6 to - 0.4, p = 0.002, n = 608). Only the association with GPx3 remained statistically significant after multiple testing correction.</p><p><strong>Conclusion: </strong>Our study suggests that low levels of selenium biomarkers are associated with accelerated biological aging measured through epigenetic clocks. This effect was not substantially changed after adjustment for known confounders.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"17 1","pages":"62"},"PeriodicalIF":4.8,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12023433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978796","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}