Clinical Epigenetics最新文献

{"title":"Prognostic value of PRAME gene promoter methylation and expression in hepatocellular carcinoma.","authors":"Jintao Zheng, Guoqiang Cao, Jialing Zhao, Longjie Yu, Xiujin Ye, Junru Chen, Haiyang Xie, Jianhui Li, Changku Jia","doi":"10.1186/s13148-026-02152-7","DOIUrl":"https://doi.org/10.1186/s13148-026-02152-7","url":null,"abstract":"<p><strong>Background: </strong>PRAME is a member of the cancer-testis antigen family and exhibits abnormally high expression in various solid tumors. Epigenetic regulation plays a critical role in the development and progression of hepatocellular carcinoma (HCC). Alterations in promoter methylation of specific genes have been widely recognized as valuable biomarkers for predicting cancer risk and assessing prognosis.</p><p><strong>Objective: </strong>This study systematically investigated the biological function and clinical relevance of PRAME promoter methylation in HCC.</p><p><strong>Methods: </strong>Using data from The Cancer Genome Atlas (TCGA) cohort, we identified methylation-associated prognostic genes and examined the association between PRAME promoter methylation, its mRNA expression levels, overall survival (OS), and clinicopathologic characteristics. We then validated these findings in an independent HCC cohort from Shulan (Hangzhou) Hospital using MethylTarget multiplex gene methylation detection technology. To investigate the potential role of PRAME in vascular invasion and metastasis, we conducted Gene Ontology (GO) enrichment analysis and Gene Set Enrichment Analysis (GSEA) at both histological and cellular levels.</p><p><strong>Results: </strong>Analyses across three HCC cohorts consistently showed that the PRAME promoter is generally hypomethylated in tumor tissues, and this hypomethylation was significantly correlated with elevated PRAME mRNA expression. In both the TCGA and Shulan (Hangzhou) Hospital cohorts, PRAME promoter hypomethylation was associated with more advanced clinicopathologic features and shorter OS. Moreover, PRAME promoter methylation status was strongly linked to vascular invasion and distant metastasis in HCC. Further functional analyses revealed significant upregulation of Wnt signaling and cell adhesion-related pathways in tissues with high PRAME expression, a finding corroborated by single-cell RNA sequencing data.</p><p><strong>Conclusion: </strong>Hypomethylation of the PRAME promoter is closely associated with poor overall survival, adverse clinicopathologic features, vascular invasion, and metastasis in HCC patients. It plays a pivotal role in regulating gene expression and promoting tumor invasiveness. These findings suggest that PRAME promoter methylation may serve as a promising epigenetic biomarker for prognostic evaluation in HCC.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856043","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":"Body mass index, physical activity, and epigenetic aging: a cross-population study.","authors":"Bojun Zhou, Dongzhe Wu, Shuting Chen, Shiyan Zhang, Xiaochuan Ge, Jiaming Li, Lianghao Zhu, Shijie Zhou, Ninghao Chang, Biao Zhou, Lei Zhang, Hua Meng","doi":"10.1186/s13148-026-02149-2","DOIUrl":"https://doi.org/10.1186/s13148-026-02149-2","url":null,"abstract":"<p><strong>Background: </strong>Observational studies have suggested that body mass index (BMI) is associated with accelerated epigenetic aging; however, the age at which this association begins and the duration of its effects have not been fully established. This study evaluated the effects of BMI and physical activity on epigenetic aging from early life to adulthood.</p><p><strong>Methods: </strong>We integrated multi-source data from populations of different racial backgrounds, including genome-wide association study (GWAS) data, the National Health and Nutrition Examination Survey (NHANES), clinical visceral adipose tissue, and blood samples from obese and physically active populations. Specifically, Mendelian randomization (MR) analysis was used to infer the causal relationship between early-life BMI and epigenetic age acceleration and to identify potential mediators. NHANES data were then analyzed to validate this association at the population level. Finally, biomarkers in blood and adipose tissue were examined to assess whether physical activity is associated with reduced aging-related signatures.</p><p><strong>Results: </strong>The Mendelian randomization analyses indicated that high early-life BMI was causally associated with accelerated epigenetic aging across multiple epigenetic clocks, with β ranging from 0.231 to 0.506; similar associations were also observed for childhood obesity, with β ranging from 0.139 to 0.231. Physical activity was identified as an important mediator that attenuated epigenetic aging acceleration, with mediation effects accounting for 10.70% to 16.22%. Analysis of the NHANES dataset further confirmed that epigenetic age acceleration increases progressively with increasing BMI: [25 ≤ BMI < 30: β = 0.83, 95% CI (0.66, 1.00); 30 ≤ BMI < 35: β = 1.73, 95% CI (1.54, 1.93); 35 ≤ BMI < 40: β = 2.93, 95% CI (2.67, 3.20); BMI ≥ 40: β = 4.64, 95% CI (4.30, 4.99)]. Subgroup analysis showed that, at the same BMI level, female exhibited more severe PhenoAA acceleration than male. Validation using multi-tissue samples showed that obesity accelerates DNA damage and significantly upregulates genes involved in cell cycle regulation. Physical activity significantly inhibited the upregulation of aging-related genes and reduced oxidative stress.</p><p><strong>Conclusion: </strong>BMI is strongly associated with accelerated epigenetic aging. This association is evident in children with obesity, becomes stronger with higher BMI, and is also observed in adults, whereas physical activity may partially attenuate this process. Trial registration Name of the registry: China-Japan Friendship Hospital National Integrated Chinese and Western Medicine Medical Center. Unique identifying number or registration ID: NCT06452303. Hyperlink to your specific registration (must be publicly accessible and will be checked): https://www.centerwatch.com/clinical-trials/listings/NCT06452303/the-patient-cohort-for-bariatric-surgery.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147856057","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":"Inhibition of PRMT5 reduces angiogenesis in a corneal neovascularization model by blocking NLRP3-mediated pyroptosis.","authors":"Jiewen Mao, Siyu Ding, Qian Deng, Zixian Yang, Xiaoshuo Shi, Yingli Wang, Wanju Yang, Yanning Yang, Shanshan Wan","doi":"10.1186/s13148-026-02134-9","DOIUrl":"https://doi.org/10.1186/s13148-026-02134-9","url":null,"abstract":"<p><p>Protein arginine methyltransferase 5 (PRMT5) is a histone methyltransferase crucial for cell proliferation, differentiation, and inflammation. However, the biological functions of PRMT5 and its underlying molecular mechanisms in corneal neovascularization (CNV) remain unclear. This study utilized corneal alkali burn and vascular endothelial growth factor (VEGF)-induced HUVEC models to examine the role of PRMT5 in CNV. We found that PRMT5 expression was significantly upregulated following corneal alkali burn. Experiments both in vitro and in vivo showed that PRMT5 knockdown or inhibition lowered pyroptosis-related protein expression and reduced cell death. PRMT5 interacts with the NACHT domain of NOD-like receptor family pyrin domain-containing 3 (NLRP3) via its Rossmann fold, catalyzing arginine methylation at the R490 and R504 residues through its methyltransferase activity. This process modulates inflammation and pyroptosis, thereby influencing the formation of CNV. In conclusion, our findings provide evidence that inhibiting PRMT5 can alleviate angiogenesis in CNV models by blocking NLRP3-mediated pyroptosis.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834545","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":"Age-varying DNA methylation patterns associated with blood pressure in mid-to-late adulthood.","authors":"Gang Xu, Xiaowei Zhuang, Amei Amei, Zuoheng Wang, Edwin C Oh","doi":"10.1186/s13148-026-02092-2","DOIUrl":"10.1186/s13148-026-02092-2","url":null,"abstract":"<p><strong>Background: </strong>Epigenome-wide association studies (EWAS) have identified associations between DNA methylation and blood pressure, yet most rely on single-time-point data and cannot capture how methylation and blood pressure relationships change with age.</p><p><strong>Methods: </strong>We conducted a longitudinal EWAS of 1945 blood samples from 976 participants in the multi-ethnic study of atherosclerosis using a spline-based varying-coefficient model to detect age-dependent associations between DNA methylation in blood and blood pressure traits. Findings were evaluated for replication in 1187 samples from the Framingham heart study. Models were adjusted for sex, ancestry, and leukocyte composition to account for cellular heterogeneity.</p><p><strong>Results: </strong>Six CpG sites showed significant age-dependent associations with systolic or pulse pressure after correction for multiple testing. These included loci within STIP1 and CSRP1 that replicated in the Framingham cohort. Several CpG sites demonstrated a reversal of effect direction with advancing age, where higher methylation was associated with higher systolic pressure in younger adults but lower pressure in mid-to-late adulthood. Pathway enrichment analyses identified focal adhesion, actin cytoskeleton remodeling, and Wnt/β-catenin signaling, which are processes relevant to vascular aging. Drug target mapping identified 23 FDA-approved agents interacting with genes at these loci.</p><p><strong>Conclusions: </strong>Blood-derived DNA methylation shows dynamic age-related associations with blood pressure, most pronounced in mid-to-late adulthood, that likely reflect systemic or vascular aging processes rather than direct cellular mediation. Longitudinal analytical frameworks can reveal temporal patterns in epigenetic variation that are not detectable in single time point studies and may inform the discovery of biomarkers for age related cardiovascular risk.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"18 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13147566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834538","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":"A scoping review of DNA methylation biomarkers for non-invasive detection of colorectal cancer at the CpG site level.","authors":"Kamilla Kolding Bendixen, Winnie Roerbaek Poulsen, Luna Katrine Gundel-Reimer, Rasmus Koefoed Petersen, Mette Soerensen","doi":"10.1186/s13148-026-02140-x","DOIUrl":"https://doi.org/10.1186/s13148-026-02140-x","url":null,"abstract":"<p><p>Colorectal cancer screening programs are well-established worldwide, but most applied methods are invasive, have insufficient accuracy, or have a low uptake rate. Several studies have reported DNA methylation biomarkers as promising alternatives to the established diagnostic tools. However, the current reviews on the topic lack information on the exact location of the CpG sites in the analyzed biomarker. As adjacent CpG sites may exert distinct clinical effects, precise identification of the specific CpG sites analyzed is essential for establishing clinical relevance and achieving consensus across studies. This scoping review aimed to uncover the accessibility of CpG site information in the scientific literature, map the CpG sites of the markers, and summarize the accuracy data from studies reporting on the same group of CpG sites. We systematically searched MEDLINE®, EMBASE, and Scopus, and the last search was conducted on the 13th of March 2025. A total of 6180 identified records were screened in Covidence, resulting in the inclusion of 149 articles. Four (2.7%) papers held precise CpG information. Locations of the CpG sites were obtained for additionally 109 (73.2%) papers by running a BLAST search using oligonucleotide sequences from the papers. For the remaining 36 (24.1%) papers without any information to locate the CpG sites, 26 used commercial kits. The three most frequently studied genes were SEPTIN9, SDC2, and SFRP2. We mapped the CpG sites of these to identify recurring sites across the studies. Sixteen of 22 papers analyzing SEPTIN9 had three CpG sites in common, seven of 19 papers analyzing SDC2 had consensus on a single CpG site, while seven of 13 studies reporting on SFRP2 had analyzed eight identical CpG sites. Lastly, we grouped all studies based on whether they targeted the same group of CpG sites within each gene. For genes examined in at least two papers, we summarized the reported accuracy measurements by presenting the average, minimum, and maximum values for each CpG group. This scoping review identifies a profound lack in the reporting of the CpG sites analyzed for non-invasive detection of CRC, which poses a challenge for the comparison of findings across studies.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834469","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":"Maternal BMI associations with cord blood DNA methylation and mid-childhood adiposity.","authors":"Grace Brolly, Miranda Gurra, Denise M Scholtens, William L Lowe, Marie-France Hivert, Jami L Josefson","doi":"10.1186/s13148-026-02119-8","DOIUrl":"https://doi.org/10.1186/s13148-026-02119-8","url":null,"abstract":"<p><strong>Background: </strong>Childhood obesity is common and associated with adverse health outcomes. Fetal programming via epigenetics is a potential mechanism underlying its pathogenesis. We conducted an epigenome-wide association study (EWAS) on cord blood DNA to identify DNA methylation sites that may mediate the association of maternal body mass index (BMI) with offspring adiposity using data from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and its follow-up study (HAPO FUS). HAPO was a prospective, multicenter, international observational study that recruited pregnant women between 2000 and 2006 for glucose tolerance testing; cord blood was collected at delivery and newborn anthropometrics were obtained. The HAPO FUS was conducted from 2013 to 2016, where the 10-14 year-old offspring underwent measures of body composition, anthropometrics, and a fasting glucose tolerance test. Eligibility for HAPO FUS included gestational age at delivery ≥ 37 weeks without major neonatal malformations. There were 3,243 samples with cord blood DNA methylation (cbDNAm) data; mean child age at follow-up was 11.5 years. The present study used cord blood DNA to conduct methylation profiling using the Infinium MethylationEPIC 850 K BeadChip. Linear regression models were used to test the association between maternal BMI and cbDNAm levels adjusting for population substructure, cell count, maternal and child co-variates; multiple testing was accounted for using Bonferroni correction. Mediation analysis tested if cbDNAm CpG sites that were associated (Bonferroni P < 0.05) with maternal BMI explained the known association between maternal BMI and child BMI.</p><p><strong>Results: </strong>This analysis included 3,116 mother-child pairs, 48% White, 21% Asian, 19% Black, 12% Hispanic and < 1% other race/ethnicity self-identified by the mother; 36% of mothers and 28.3% of children had an overweight or obese BMI. Maternal BMI was associated with DNAm at 7 CpG sites following adjustment including: cg00579423, cg07138793, cg12188424, cg19345626, cg20020844, cg02988288 and cg26974062. The 2 CpG sites on the TXNIP gene have been identified in previous EWAS of glucose metabolism and diabetes. Cord blood DNA methylation at cg20020844 (SP6) demonstrated mediation of 1.2% of the association between maternal BMI and child BMI z-score.</p><p><strong>Conclusions: </strong>Exposure to maternal obesity in utero and subsequent differential methylation present at birth may contribute to the prenatal programing of childhood obesity.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811752","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":"DNA methylation and gene expression signatures for common childhood infections.","authors":"Esther Herrera-Luis, Dolors Pelegrí Sisó, Marta Vidal, Katerina Margetaki, Angelos Athanasios Korakakis Pissanidis, Ruth Aguilar, Martine Vrijheid, Carlota Dobaño, Manolis Kogevinas, Marianna Karachaliou, Mariona Bustamante","doi":"10.1186/s13148-026-02130-z","DOIUrl":"https://doi.org/10.1186/s13148-026-02130-z","url":null,"abstract":"<p><strong>Background: </strong>Early life exposure to common pathogens and a high pathogen burden during childhood can have long-term effects on immune development and overall health. These infections can trigger molecular changes, including alterations in gene expression and DNA methylation (DNAm), which regulate immune and metabolic pathways. Our aim was to identify biological processes underlying differential patterns of DNAm and gene expression in whole blood by infection status in European children.</p><p><strong>Results: </strong>In the Rhea (Greece) and INMA (Spain) cohorts, serum/plasma samples collected at mean ages of 4 and 8 years were analyzed by multiplex serology to measure IgG against 14 antigens from 9 pathogens, and blood collected at a mean age of 8 years was used for DNAm and gene expression profiling. Epigenome- and transcriptome-wide analyses were conducted to assess association with childhood infections. A total of 290 unique CpGs were significantly associated with pathogen outcomes: 265 with seropositivity, 111 with first exposure timing, and one with viral burden. Cytomegalovirus (CMV) exposure accounted for the largest number of both epigenetic (n = 325) and transcriptomic (n = 8) associations. A total of 89 CMV-related CpGs had been described before in adults, and among novel ones, 54 showed consistent effects in adults. CMV-related CpGs were enriched for SUZ12 targets linked to morphogenesis, oxidative stress, and cognition. A previously developed CMV episcore in adults predicted serologically assessed CMV infection at 4 and 8 years of age, with area under the curve values ranging from 0.74 to 0.78 (95% CI 0.68-0.83).</p><p><strong>Conclusions: </strong>We identified novel DNAm and gene expression signatures of common childhood infections, particularly CMV, implicating immune and morphogenesis pathways. A subset of CMV-related DNAm signals showed consistent associations with those reported previously in adults, suggesting similar molecular effects across ages.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811410","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":"Association between the oxidative balance score and biological aging measured by epigenetic clock: insight from the NHANES 1999-2002.","authors":"Mingming Lv, Zhihui Jiang, Changjiang Deng, Zhiyan Du, Bingxin Bai, Zhilong Wang, Adilai Adilijiang, Ying-Ying Zheng, Xiang Xie","doi":"10.1186/s13148-026-02141-w","DOIUrl":"https://doi.org/10.1186/s13148-026-02141-w","url":null,"abstract":"<p><strong>Background: </strong>Oxidative stress is a key factor leading to oxidative damage in cells and tissues, and is a major driving force behind aging and various age-related diseases. Epigenetic clock and oxidative balance score (OBS) serve as reliable indicators for assessing an individual's aging process and oxidative stress levels, respectively. However, no study has comprehensively assessed the association between epigenetic clock and OBS.</p><p><strong>Methods: </strong>This study analysed 1,797 subjects from the 1999-2002 National Health and Nutrition Examination Survey (NHANES). Multivariate regression models were used to assess the relationship between OBS and epigenetic age as well as epigenetic age acceleration (EAA). Restricted cubic spline (RCS) analyses were used to visualize the dose-response relationship between OBS and EAA. Subgroup analysis and interaction tests were used to investigate whether this association was stable across populations.</p><p><strong>Results: </strong>Multiple linear regression analyses showed that higher OBS levels were significantly associated with lower epigenetic age. Further analyses showed that both the dietary OBS and the lifestyle OBS were significantly negatively correlated with epigenetic age. RCS analysis revealed a significant negative linear dose-response relationship between OBS and EAA. The association between OBS and EAA was homogeneous across subgroups.</p><p><strong>Conclusions: </strong>This study suggests higher OBS levels are associated with reduced epigenetic age and decelerated biological aging, and antioxidant-rich diets and lifestyles may delay biological aging.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811376","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":"Effects of exercise on peripheral blood DNA methylation and related epigenetic markers: a systematic review of human trials.","authors":"Yahui Yang, Fengshu Zhu, Aiguo Chen","doi":"10.1186/s13148-026-02123-y","DOIUrl":"https://doi.org/10.1186/s13148-026-02123-y","url":null,"abstract":"<p><strong>Background: </strong>Regular exercise promotes health through multiple mechanisms, with DNA methylation serving as a key epigenetic modification involved in the molecular regulation induced by exercise. Peripheral blood, as an accessible tissue, is commonly used to study exercise-induced DNA methylation changes.</p><p><strong>Objective: </strong>This systematic review aims to synthesize evidence from human exercise intervention studies on the effects of exercise on peripheral blood DNA methylation and related epigenetic markers, and to evaluate their potential as biomarkers of exercise efficacy.</p><p><strong>Methods: </strong>The study protocol was registered in PROSPERO (CRD420251069398). A systematic search was conducted in Pubmed, Web of Science, Cochrane Library, Embase and Scopus databases from database inception through 29 May 2025 for all English-language studies. Eligible studies were included. Risk of bias of randomized controlled trials were assessed using the Cochrane collaboration's tool (version 5.1.0) and quasi-experimental studies were assessed using the JBI Critical Appraisal Checklists for Quasi-Experimental Studies. The results were summarized using narrative synthesis.</p><p><strong>Results: </strong>Twenty-nine studies were included, covering both acute and long-term exercise interventions. Acute exercise induced minor and mostly statistically nonsignificant changes in peripheral blood DNA methylation, whereas long-term exercise elicited significant methylation remodeling in genes related to metabolism, inflammation, and immune function. Exercise dose (frequency, intensity, and duration) and population characteristics influenced the magnitude and scope of methylation responses.</p><p><strong>Conclusions: </strong>Peripheral blood DNA methylation provides robust evidence for exercise-mediated systemic epigenetic regulation and shows promise as a biomarker for exercise adaptation and intervention effects. Future research should optimize intervention designs and methodological standards to deepen understanding of exercise epigenetic mechanisms.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811476","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":"Epigenetic g predicts cognitive function in a diverse, nationally representative sample of older adults.","authors":"Jessica D Faul, Stacey Collins, Trey Smith, Eric T Klopack, Colter Mitchell, Eileen M Crimmins, Mateo P Farina","doi":"10.1186/s13148-026-02142-9","DOIUrl":"10.1186/s13148-026-02142-9","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease and related dementias (ADRD) are major public health concerns. DNA methylation (DNAm)-based biomarkers such as GrimAge and PhenoAge predict aging and health risk, but were not designed to optimize prediction of cognitive function or decline. Epigenetic g-a DNAm-derived index of general cognitive ability-is a promising marker of cognitive function that has not been assessed in a racially and socioeconomically diverse population.</p><p><strong>Methods: </strong>We used data from the 2016 Venous Blood Study of the Health and Retirement Study (HRS), a nationally representative cohort of U.S. adults aged ≥ 51 years (N = 3575 with high-quality DNAm). Epigenetic g scores were computed using CpG weights from a BayesR+ model of general cognitive ability developed in Generation Scotland. Cognitive function was measured with a modified version of the Telephone Interview for Cognitive Status (TICS) at each interview wave. Linear regression estimated associations with cognitive scores; mixed-effect growth curve models estimated the association with cognitive change. Models were adjusted sequentially for demographics, education, parental education, APOE ε4 status, and blood-based neurodegeneration markers (NfL, GFAP, Aβ42/40, pTau181).</p><p><strong>Results: </strong>Higher epigenetic g was associated with better baseline cognition (β = 2.55, 95% CI 1.80-3.30)) and cognition at the time DNAm was measured (β = 2.30, 95% CI 1.47-3.13) after demographic adjustment. Associations were attenuated but remained significant with education and parental education (β = 1.23-1.89). In growth curve models, Epigenetic g was associated with higher cognitive performance but did not have a statistically significant association with decline over a 6-year period. Results were robust to adjustment for APOE ε4 and neurodegeneration biomarkers.</p><p><strong>Conclusions: </strong>Epigenetic g is a scalable, blood-based marker of cognitive function, and potentially or cognitive reserve, that adds predictive value beyond demographics, socioeconomic indicators, APOE, and neuropathology. Its validation in a diverse, nationally representative U.S. cohort underscores its potential for early risk profiling and for research on social determinants of cognitive aging in cross-national samples.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147811765","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}