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Single and multi-omic characterization of a porcine model of ethanol-induced hepatic fibrosis. 猪乙醇性肝纤维化模型的单组学和多组学特征。
IF 2.9 3区 生物学
Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-03-04 DOI: 10.1080/15592294.2025.2471127
Mark Hieromnimon, Daniel P Regan, R Peter Lokken, Lawrence B Schook, Ron C Gaba, Kyle M Schachtschneider
{"title":"Single and multi-omic characterization of a porcine model of ethanol-induced hepatic fibrosis.","authors":"Mark Hieromnimon, Daniel P Regan, R Peter Lokken, Lawrence B Schook, Ron C Gaba, Kyle M Schachtschneider","doi":"10.1080/15592294.2025.2471127","DOIUrl":"10.1080/15592294.2025.2471127","url":null,"abstract":"<p><p>Cirrhosis is a form of end-stage liver disease characterized by extensive hepatic fibrosis and loss of liver parenchyma. It is most commonly the result of long-term alcohol abuse in the United States. Large animal models of cirrhosis, as well as of one of its common long-term sequelae, HCC, are needed to study novel and emerging therapeutic interventions. In the present study, liver fibrosis was induced in the Oncopig cancer model, a large animal HCC model, via intrahepatic, intra-arterial ethanol infusion. Liver sections from five fibrosis induced and five age-matched controls were harvested for RNA-seq (mRNA and lncRNA), small RNA-seq (miRNA), and reduced representation bisulfite sequencing (RRBS; DNA methylation). Single- and multi-omic analysis was performed to investigate the transcriptomic and epigenomic mechanisms associated with fibrosis deposition in this model. A total of 3,439 genes, 70 miRNAs, 452 lncRNAs, and 7,715 methylation regions were found to be differentially regulated through individual single-omic analysis. Pathway analysis indicated differentially expressed genes were associated with collagen synthesis and turnover, hepatic metabolic functions such as ethanol and lipid metabolism, and proliferative and anti-proliferative pathways including PI3K and BAX/BCL signaling pathways. Multi-omic latent variable analysis demonstrated significant concordance with the single-omic analysis. lncRNA's associated with <i>UHRF1BP1L</i> and <i>S1PR1</i> genes were found to reliably discriminate the two arms of the study. These genes were previously implicated in human cancer development and vasculogenesis, respectively. These findings support the validity and translatability of this model as a useful preclinical tool in the study of alcoholic liver disease and its treatment.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2471127"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11901410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143556204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Alpha-linolenic acid-mediated epigenetic reprogramming of cervical cancer cell lines. α -亚麻酸介导的宫颈癌细胞系表观遗传重编程。
IF 2.9 3区 生物学
Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-02-02 DOI: 10.1080/15592294.2025.2451551
Amrita Ulhe, Prerna Raina, Amol Chaudhary, Ruchika Kaul-Ghanekar
{"title":"Alpha-linolenic acid-mediated epigenetic reprogramming of cervical cancer cell lines.","authors":"Amrita Ulhe, Prerna Raina, Amol Chaudhary, Ruchika Kaul-Ghanekar","doi":"10.1080/15592294.2025.2451551","DOIUrl":"10.1080/15592294.2025.2451551","url":null,"abstract":"<p><p>Cervical cancer, the fourth most common cancer globally and the second most prevalent cancer among women in India, is primarily caused by Human Papilloma Virus (HPV). The association of diet with cancer etiology and prevention has been well established and nutrition has been shown to regulate cancer through modulation of epigenetic markers. Dietary fatty acids, especially omega-3, reduce the risk of cancer by preventing or reversing the progression through a variety of cellular targets, including epigenetic regulation. In this work, we have evaluated the potential of ALA (α linolenic acid), an ω-3 fatty acid, to regulate cervical cancer through epigenetic mechanisms. The effect of ALA was evaluated on the regulation of histone deacetylases1, DNA methyltransferases 1, and 3b, and global DNA methylation by ELISA. RT-PCR was utilized to assess the expression of tumor regulatory genes (hTERT, DAPK, RARβ, and CDH1) and their promoter methylation in HeLa (HPV18-positive), SiHa (HPV16-positive) and C33a (HPV-negative) cervical cancer cell lines. ALA increased DNA demethylase, HMTs, and HATs while decreasing global DNA methylation, DNMT, HDMs, and HDACs mRNA expression/activity in all cervical cancer cell lines. ALA downregulated hTERT oncogene while upregulating the mRNA expression of TSGs (Tumor Suppressor Genes) CDH1, RARβ, and DAPK in all the cell lines. ALA reduced methylation in the 5' CpG island of CDH1, RARβ, and DAPK1 promoters and reduced global DNA methylation in cervical cancer cell lines. These results suggest that ALA regulates the growth of cervical cancer cells by targeting epigenetic markers, shedding light on its potential therapeutic role in cervical cancer management.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2451551"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11792827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Blood transcriptomic associations of epigenetic age in adolescents. 青少年表观遗传年龄的血液转录组学关联。
IF 2.9 3区 生物学
Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-05-16 DOI: 10.1080/15592294.2025.2503824
Dennis Khodasevich, Anne K Bozack, Saher Daredia, Julianna Deardorff, Kim G Harley, Brenda Eskenazi, Weihong Guo, Nina Holland, Andres Cardenas
{"title":"Blood transcriptomic associations of epigenetic age in adolescents.","authors":"Dennis Khodasevich, Anne K Bozack, Saher Daredia, Julianna Deardorff, Kim G Harley, Brenda Eskenazi, Weihong Guo, Nina Holland, Andres Cardenas","doi":"10.1080/15592294.2025.2503824","DOIUrl":"10.1080/15592294.2025.2503824","url":null,"abstract":"<p><p>Epigenetic aging in early life remains poorly characterized, and patterns of gene expression can provide biologically meaningful insights. Blood DNA methylation was measured using the Illumina EPICv1.0 array and RNA sequencing was performed in blood in 174 adolescent participants (age range: 14-15 years) from the CHAMACOS cohort. Thirteen widely used epigenetic clocks were calculated, and their associations with transcriptome-wide RNA expression were tested using the <i>limma-voom</i> pipeline. We found evidence for substantial shared associations with RNA expression between different epigenetic clocks, including differential expression of <i>MYO6</i> and <i>ZBTB38</i> across five clocks. The epiTOC2, principal component (PC) PhenoAge, Hannum, PedBE and PC Hannum clocks were associated with differential expression of the highest number of RNAs, exhibiting associations with 22, 8, 5, 3, and 2 transcripts respectively. Generally, biological clocks were associated with differential expression of more genes than chronological clocks, and PC clocks were associated with differential expression of more genes relative to their CpG-trained counterparts. A total of 17 associations in our study were replicated in an independent adult sample (age range: 40-54 years). Our findings support the biological relevance of epigenetic clocks in adolescents and provide direction for selection of epigenetic ageing biomarkers in adolescent research.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2503824"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The role of histone methyltransferases in therapeutic resistance of NSCLC. 组蛋白甲基转移酶在非小细胞肺癌耐药中的作用。
IF 3.2 3区 生物学
Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-07-23 DOI: 10.1080/15592294.2025.2536786
Fuze Zhu, Xudong Yang, Yanlong Yang, Xinghe Tong, Jie Jia, Xingkun Gu, Yunping Zhao, Xiaobo Chen
{"title":"The role of histone methyltransferases in therapeutic resistance of NSCLC.","authors":"Fuze Zhu, Xudong Yang, Yanlong Yang, Xinghe Tong, Jie Jia, Xingkun Gu, Yunping Zhao, Xiaobo Chen","doi":"10.1080/15592294.2025.2536786","DOIUrl":"10.1080/15592294.2025.2536786","url":null,"abstract":"<p><p>Conventional treatments, including chemotherapy, immunotherapy, targeted therapy and radiotherapy, are effective clinical strategies for non-small cell lung cancer (NSCLC) patients, which can significantly improve life quality and prolong survival time. However, the application of drugs in NSCLC patients inevitably leads to therapeutic resistance. In recent years, many studies have shown that histone methyltransferases (HMTs), including both protein arginine methyltransferases (PRMTs) and lysine methyltransferases (KMTs), play pivotal roles in tumor initiation, progression, and treatment resistance. This review synthesizes current insights into histone methylation dynamics driving therapeutic resistance, with a focus on key HMTs and their mechanisms. Additionally, we discuss the molecular mechanisms underlying histone methylation-mediated therapeutic resistance and potential therapeutic strategies targeting histone methylation for overcoming therapeutic resistance in NSCLC.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2536786"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144697850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Differential methylation patterns in cord blood associated with prenatal exposure to neighborhood crime: an epigenome-wide association study and regional analysis. 脐带血甲基化差异模式与产前暴露于社区犯罪相关:一项全表观基因组关联研究和区域分析。
IF 2.9 3区 生物学
Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-06-10 DOI: 10.1080/15592294.2025.2511553
Chantel L Martin, Jiawen Chen, Alena S D'Alessio, Cavin K Ward-Caviness, Ai Ye, Evans K Lodge, Lea Ghastine, Radhika Dhingra, Dereje D Jima, Susan K Murphy, Cathrine Hoyo
{"title":"Differential methylation patterns in cord blood associated with prenatal exposure to neighborhood crime: an epigenome-wide association study and regional analysis.","authors":"Chantel L Martin, Jiawen Chen, Alena S D'Alessio, Cavin K Ward-Caviness, Ai Ye, Evans K Lodge, Lea Ghastine, Radhika Dhingra, Dereje D Jima, Susan K Murphy, Cathrine Hoyo","doi":"10.1080/15592294.2025.2511553","DOIUrl":"10.1080/15592294.2025.2511553","url":null,"abstract":"<p><p>Exposure to prenatal social stressors during pregnancy is associated with adverse birth outcomes and has been linked to epigenetic changes in DNA methylation (DNAm); however, less understood is the effect of neighborhood-level stressors like crime during pregnancy on offspring DNAm. Using data from the Newborn Epigenetic Study, we conducted epigenome-wide and regional analyses of the association between exposure to neighborhood crime and DNAm in offspring cord blood using Illumina's HumanMethylation450k BeadChip among 185 mother-offspring pairs. Prenatal exposure to neighborhood crime at the census block group level was mapped to participants' residential addresses during the gestational window from the date of last menstrual period to delivery. Models for the epigenome-wide and regional analyses were adjusted for maternal age, race/ethnicity, education, smoking, cell-type composition, and offspring sex. Genetic influence and gene expression enrichment were assessed using methylation quantitative trait loci (mQTLs) and expression quantitative trait methylation (eQTMs) analyses. Functional enrichment was determined using Gene Ontology and KEGG databases. We did not find evidence of epigenome-wide associations between prenatal neighborhood crime exposure and DNAm; however, we identified nine differentially methylated regions (DMRs) comprising 51 CpG sites associated with neighborhood crime. CpG sites within significant differentially methylated regions were associated with mQTLs at birth and eQTMs upon further examination. KEGG analysis identified a significant Th1 and Th2 cell differentiation pathway. Our results suggest potential links between prenatal neighborhood crime exposure and offspring DNAm; however, additional research is needed in larger cohorts across wider geographic areas to confirm our results.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2511553"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12153387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144265735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
PIK3R1 and G0S2 are human placenta-specific imprinted genes associated with germline-inherited maternal DNA methylation. PIK3R1和G0S2是与种系遗传的母体DNA甲基化相关的人类胎盘特异性印迹基因。
IF 2.9 3区 生物学
Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-06-26 DOI: 10.1080/15592294.2025.2523191
Dagne Daskeviciute, Becky Sainty, Louise Chappell-Maor, Caitlin Bone, Sarah Russell, Isabel Iglesias-Platas, Philippe Arnaud, Ana Monteagudo-Sánchez, Maxim V C Greenberg, Keran Chen, Africa Manerao-Azua, Guiomar Perez de Nanclares, Jon Lartey, David Monk
{"title":"<i>PIK3R1</i> and <i>G0S2</i> are human placenta-specific imprinted genes associated with germline-inherited maternal DNA methylation.","authors":"Dagne Daskeviciute, Becky Sainty, Louise Chappell-Maor, Caitlin Bone, Sarah Russell, Isabel Iglesias-Platas, Philippe Arnaud, Ana Monteagudo-Sánchez, Maxim V C Greenberg, Keran Chen, Africa Manerao-Azua, Guiomar Perez de Nanclares, Jon Lartey, David Monk","doi":"10.1080/15592294.2025.2523191","DOIUrl":"10.1080/15592294.2025.2523191","url":null,"abstract":"<p><p>Genomic imprinting is the parent-of-origin specific monoallelic expression of genes that result from complex epigenetic interactions. It is often achieved by monoallelic 5-methylcytosine, resulting in the formation of differentially methylated regions (DMRs). These show a bias towards oocyte-derived methylation and survive reprogramming in the pre-implantation embryo. Imprinting is widespread in the human placenta. We have recently performed whole-genome screens for novel imprinted placenta-specific germline DMRs (gDMRs) by comparing methylomes of gametes, blastocysts and various somatic tissues, including placenta. We observe that, unlike conventional imprinting, for which methylation at gDMRs is observed in all tissues, placenta-specific imprinting is associated with transient gDMRs, present only in the pre-implantation embryo and extra-embryonic lineages. To expand the list of <i>bona fide</i> imprinted genes subject to placenta-specific imprinting, we reinvestigated our list of candidate loci and characterized two novel imprinted genes, <i>PIK3R1</i> and <i>G0S2</i>, both of which display polymorphic imprinting. Interrogation of placenta single-cell RNA-seq datasets, as well as cell-type methylation profiles, revealed complex cell-type specificity. We further interrogated their methylation and expression in placental samples from complicated pregnancies, but failed to identify differences between intrauterine growth restricted or pre-eclamptic samples and controls, suggesting they are not involved in these conditions.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2523191"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144495310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Astrocyte-derived exosomes regulate sperm miR-34c levels to mediate the transgenerational effects of paternal chronic social instability stress. 星形胶质细胞衍生的外泌体调节精子miR-34c水平,介导父亲慢性社会不稳定压力的跨代效应。
IF 2.9 3区 生物学
Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-01-27 DOI: 10.1080/15592294.2025.2457176
Alexandre Champroux, Mitra Sadat-Shirazi, Xuan Chen, Jonathan Hacker, Yongjie Yang, Larry A Feig
{"title":"Astrocyte-derived exosomes regulate sperm miR-34c levels to mediate the transgenerational effects of paternal chronic social instability stress.","authors":"Alexandre Champroux, Mitra Sadat-Shirazi, Xuan Chen, Jonathan Hacker, Yongjie Yang, Larry A Feig","doi":"10.1080/15592294.2025.2457176","DOIUrl":"10.1080/15592294.2025.2457176","url":null,"abstract":"<p><p>The effects of chronically stressing male mice can be transmitted across generations by stress-specific changes in their sperm miRNA content, which induce stress-specific phenotypes in their offspring. However, how each stress paradigm alters the levels of distinct sets of sperm miRNAs is not known. We showed previously that exposure of male mice to chronic social instability (CSI) stress results in elevated anxiety and reduced sociability specifically in their female offspring across multiple generations because it reduces miR-34c levels in sperm of stressed males and their unstressed male offspring. Here, we describe evidence that astrocyte-derived exosomes (A-Exos) carrying miR-34c mediate how CSI stress has this transgenerational effect on sperm. We found that CSI stress decreases miR-34c carried by A-Exos in the prefrontal cortex and amygdala, as well as in the blood of males. Importantly, miR-34c A-Exos levels are also reduced in these tissues in their F1 male offspring, who despite not being exposed to stress, exhibit reduced sperm miR-34c levels and transmit the same stress-associated traits to their male and female offspring. Furthermore, restoring A-Exos miR-34c content in the blood of CSI-stressed males by intravenous injection of miR-34c-containing A-Exos restores miR-34c levels in their sperm. These findings reveal an unexpected role for A-Exos in maintaining sperm miR-34c levels by a process that when suppressed by CSI stress mediates this example of transgenerational epigenetic inheritance.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2457176"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11776480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
CpG island demethylation and recruitment of SP1 to the promoter region regulates human thymic stromal lymphopoietin expression. CpG岛去甲基化和SP1在启动子区域的募集调节人胸腺基质淋巴生成素的表达。
IF 2.9 3区 生物学
Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-07-14 DOI: 10.1080/15592294.2025.2529358
Krishna Priya Ganti, Milan Surjit
{"title":"CpG island demethylation and recruitment of SP1 to the promoter region regulates human thymic stromal lymphopoietin expression.","authors":"Krishna Priya Ganti, Milan Surjit","doi":"10.1080/15592294.2025.2529358","DOIUrl":"10.1080/15592294.2025.2529358","url":null,"abstract":"<p><p>Thymic Stromal Lymphopoietin (TSLP), an immunomodulatory cytokine, plays a pivotal role in the development and progression of atopic and allergic diseases. Atopy follows familial inheritance, and genome-wide studies have shown association of atopy with TSLP polymorphisms. Here, we analysed the conserved transcriptional regulatory elements in the human TSLP promoter, which revealed the presence of three CpG islands. Demethylation of the CpG island using 5-azacytidine or siRNA-mediated knockdown of DNA methyl transferases significantly upregulated TSLP expression. Sequence analysis revealed the presence of two overlapping SP1 transcription factor DNA-binding sites (DBSs), between -1494 and -1510 nucleotides on the human TSLP promoter. Further experiments showed that demethylation of the CpG island enables the binding of SP1 to its cognate DBS present on the TSLP promoter, resulting in its transcriptional activation. Moreover, retinoic acid-induced transcription of human TSLP was associated with CpG island demethylation and SP1 binding to the TSLP promoter. These findings unravel a distinct mechanism of transcriptional regulation of the human TSLP gene and suggest possible epigenetic regulation of TSLP expression in modulating atopic and allergic disease severity in different individuals.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2529358"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12269656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
GrimAge and GrimAge2 Age Acceleration effectively predict mortality risk: a retrospective cohort study. 年龄加速有效预测死亡风险:一项回顾性队列研究。
IF 2.9 3区 生物学
Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-07-14 DOI: 10.1080/15592294.2025.2530618
Tieshi Zhu, Yong He, Yixi Wang, Le Zhao
{"title":"GrimAge and GrimAge2 Age Acceleration effectively predict mortality risk: a retrospective cohort study.","authors":"Tieshi Zhu, Yong He, Yixi Wang, Le Zhao","doi":"10.1080/15592294.2025.2530618","DOIUrl":"10.1080/15592294.2025.2530618","url":null,"abstract":"<p><p>Epigenetic clocks have been widely applied to assess biological ageing, with Age Acceleration (AA) serving as a key metric linked to adverse health outcomes, including mortality. However, the comparative predictive value of AAs derived from different epigenetic clocks for mortality risk has not been systematically evaluated. In this retrospective cohort study based on 1,942 NHANES participants (median age 65 years; 944 women), we examined the associations between AAs from multiple epigenetic clocks and the risks of all-cause, cancer-specific, and cardiac mortality. Restricted cubic spline models were used to assess the shape of these associations, and Cox proportional hazards regression was employed to quantify risk estimates. Model performance was compared using the Akaike Information Criterion (AIC) and concordance index (C-index). Our findings revealed that only GrimAge AA and GrimAge2 AA demonstrated approximately linear and positive associations with all three mortality outcomes. Both were significantly associated with increased risks of death, and these associations were consistent across most subgroups. GrimAge and GrimAge2 AAs showed very similar performance in predicting all-cause, cancer and cardiac mortality, with only small differences in AIC values and C-index scores. These findings suggest that both GrimAge and GrimAge2 are effective epigenetic biomarkers for mortality risk prediction and may be valuable tools in future ageing-related research.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2530618"},"PeriodicalIF":2.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12269703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mapping DNA methylation to cardiac pathologies induced by beta-adrenergic stimulation in a large panel of mice. 将DNA甲基化映射到大组小鼠中β -肾上腺素能刺激引起的心脏病变。
IF 3.2 3区 生物学
Epigenetics Pub Date : 2025-12-01 Epub Date: 2025-07-07 DOI: 10.1080/15592294.2025.2524411
Caitlin Lahue, Eleanor Wong, Aryan Dalal, Wilson Tan Lek Wen, Shuxun Ren, Roger Foo, Yibin Wang, Christoph D Rau
{"title":"Mapping DNA methylation to cardiac pathologies induced by beta-adrenergic stimulation in a large panel of mice.","authors":"Caitlin Lahue, Eleanor Wong, Aryan Dalal, Wilson Tan Lek Wen, Shuxun Ren, Roger Foo, Yibin Wang, Christoph D Rau","doi":"10.1080/15592294.2025.2524411","DOIUrl":"10.1080/15592294.2025.2524411","url":null,"abstract":"<p><p>Heart failure (HF) is a major global health challenge, contributing to over 18 million deaths annually. While the roles of genetic and environmental factors are widely studied, the role of DNA methylation in HF pathogenesis is not fully understood. This study leverages the Hybrid Mouse Diversity Panel (HMDP) to investigate the relationship between DNA methylation, gene expression, and HF phenotypes under isoproterenol-induced cardiac stress. Using reduced representational bisulfite sequencing, we analyzed DNA methylation profiles in the left ventricles of 90 HMDP strains. Epigenome-wide association studies identified 56 CpG loci linked to HF phenotypes, with 18 loci predicting HF progression. Key genes, including Prkag2, Anks1a, and Mospd3, were implicated through integration with gene expression and phenotypic data. In vitro validation confirmed the roles of Anks1aand Mospd3 in attenuating isoproterenol-induced hypertrophy. Additionally, treatment with the DNA methyltransferase inhibitor RG108 mitigated cardiac hypertrophy, preserved ejection fraction, and restored methylation-sensitive gene expression, underscoring the therapeutic potential of targeting DNA methylation in HF. This study highlights the interplay between DNA methylation, gene expression, and HF progression, offering new insights into its molecular underpinnings. The findings emphasize the role of epigenetic regulation in HF and suggest DNA methylation as a promising target for therapeutic intervention.</p>","PeriodicalId":11767,"journal":{"name":"Epigenetics","volume":"20 1","pages":"2524411"},"PeriodicalIF":3.2,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12239773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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