Clinical Epigenetics最新文献

{"title":"Organelle-specific mechanisms and AI-guided stratification in gut-renal-vascular axis modulation.","authors":"Jin Chen, Xuebin Cao, Shihong Xiong, Songlin Li, Kelun Wang, Wenqi Zhen, Xinyue Wang, Ke Cheng, Shanshan Yang, Yuxin Wang, Jian Chen, Na Gong","doi":"10.1186/s13148-026-02209-7","DOIUrl":"10.1186/s13148-026-02209-7","url":null,"abstract":"<p><strong>Background: </strong>Gut-derived uremic toxins, notably indoxyl sulfate (IS), p-cresyl sulfate (PCS), and trimethylamine N-oxide (TMAO), contribute to multi-organ damage via the gut-renal-vascular axis, exacerbating chronic kidney disease (CKD) and cardiovascular pathologies. The global CKD prevalence exceeds 850 million, yet the evidence remains fragmented. Consequently, this fragmentation highlights a gap in developing integrated, mechanism-targeted strategies.</p><p><strong>Objective: </strong>This narrative review proposes an integrative framework linking subcellular organelle damage to metabolite-driven epigenetic reprogramming within the gut-renal-vascular axis. We synthesize current evidence not as a definitive efficacy assessment, but to construct and substantiate a novel paradigm for precision stratification and intervention, highlighting the gut-derived metabolites IS, PCS, and TMAO as archetypes of this multi-scale pathophysiology.</p><p><strong>Methods: </strong>A structured literature search of PubMed, Cochrane Library, Embase, Web of Science, and ClinicalTrials.gov (inception to May 2025) was conducted. Forty-eight studies were included for thematic synthesis. To enhance transparency, a documented study selection process was followed. Tools for risk-of-bias assessment were used descriptively to contextualize the evidence, acknowledging the interpretive nature of a narrative synthesis.</p><p><strong>Results: </strong>The synthesis included 48 studies, encompassing approximately 15,000 participants. A descriptive summary of a subset of interventional studies suggests that some interventions may be associated with reduced composite outcome risks (e.g., one trial reported a risk ratio of 0.85). These findings indicate substantial heterogeneity in study designs and populations. Mechanistic literature frequently implicates the attenuation of NLRP3 inflammasome activation and epigenetic reprogramming as potential pathways underlying intervention effects.</p><p><strong>Conclusions: </strong>This narrative review discusses evidence suggesting that precision-guided combined interventions may represent a potential strategy for mitigating multi-organ damage in CKM cohorts. However, the significant heterogeneity across studies necessitates a cautious, individualized approach when interpreting this evidence for clinical practice.</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/PMC13711820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149263602","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":"Early detection of esophageal squamous cell carcinoma via a CACNA1E-SNTG1 cfDNA methylation signature.","authors":"Chao Song, Jiyu Tang, Hailu Wu, Xiaoming Shi, Di Wu, Jiahuan Liu, Chenye Shao, Binxiang Xu, Linchao Dai, Sijia Li, Chenrong Huang, Ruihua Shi, Zhongze Gu","doi":"10.1186/s13148-026-02198-7","DOIUrl":"10.1186/s13148-026-02198-7","url":null,"abstract":"<p><strong>Background: </strong>Esophageal squamous cell carcinoma (ESCC) is characterized by high mortality primarily due to late-stage diagnosis. While circulating cell-free DNA (cfDNA) methylation offers a promising avenue for non-invasive screening, achieving high diagnostic sensitivity for early-stage disease using scalable clinical assays remains a technical challenge. This study aimed to identify robust methylation biomarkers and validate their diagnostic performance and biological relevance using a liquid biopsy approach and patient-derived models.</p><p><strong>Methods: </strong>Differentially methylated regions were identified through whole-genome enzymatic methyl sequencing (WEM-seq) of clinical ESCC tissues and matched normal adjacent tissues, integrated with public microarray repositories. Following a rigorous dual-filter strategy to eliminate normal blood background noise, two hypermethylated loci, CACNA1E and SNTG1, were prioritized. A targeted quantitative methylation-specific PCR (qMSP) assay was developed and evaluated in a plasma cohort of 355 individuals (215 ESCC patients across stages 0-IV and 140 healthy controls). Five independent ESCC patient-derived organoid (PDO) models were established to investigate the mechanistic coupling between promoter hypermethylation and transcriptional silencing through paired qMSP and RNA sequencing.</p><p><strong>Results: </strong>The CACNA1E/SNTG1 dual-marker cfDNA panel demonstrated high diagnostic accuracy. In the independent validation cohort, the combined classifier discriminated ESCC from healthy controls with an area under the curve (AUC) of 0.918, yielding an optimal sensitivity of 90.5% and a specificity of 85.7%. For early-stage (Stage 0-I) ESCC, the panel maintained a highly robust AUC of 0.950 with 90.0% sensitivity and 87.5% specificity. In the PDO models, Actin-normalized qMSP analysis revealed intense promoter hypermethylation at CACNA1E and SNTG1, which strictly correlated with profound transcript depletion, providing direct in situ evidence of methylation-mediated gene silencing.</p><p><strong>Conclusion: </strong>The CACNA1E/SNTG1 methylation panel, combined with a qMSP workflow, provides a highly sensitive and specific strategy for the non-invasive early detection of ESCC. The integration of PDO-based multi-omics validation confirms the biological relevance of these epigenetic alterations, supporting the panel's broad utility for scalable clinical screening programs.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"18 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13700323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149263599","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":"Multi-omics analysis reveals MICB promotes cerebral atherosclerosis through FTMT suppression in NK and plasma cells.","authors":"Yonggang Dai, Ye Liu, Yunjun Yan, Haoran Ji, Hongya Wang, Xuewei Zhuang","doi":"10.1186/s13148-026-02212-y","DOIUrl":"10.1186/s13148-026-02212-y","url":null,"abstract":"<p><strong>Background: </strong>Ferroptosis, an iron-dependent form of regulated cell death, is implicated in vascular injury, but how immune-related proteins modulate ferroptosis and cerebral atherosclerosis (CeA) remains unclear.</p><p><strong>Methods: </strong>We performed multi-step Mendelian randomization (MR) integrating plasma proteomics, single-cell eQTL, and FinnGen CeA GWAS data. Mediation MR quantified the role of the ferroptosis regulator FTMT. Cell-type-specific MR was conducted across 14 immune subtypes. Functional enrichment and RT-qPCR of clinical blood samples validated findings.</p><p><strong>Results: </strong>Four immune proteins (KIR2DL3, HLA-E, LTA, MICB) were identified as causal risk factors for CeA, acting primarily by downregulating FTMT (all β₁ < 0, P < 0.001). Mediation analysis revealed FTMT explained up to 53% of the immune protein effect. Single-cell MR demonstrated striking cell-type specificity for MICB: higher MICB in NK cells and IgJ⁺ B cells was strongly associated with CeA risk (e.g., β = 0.90, P = 4.3 × 10^-6), while higher MICB in dendritic cells was protective (β = - 0.57, P = 2.1 × 10^-30). In clinical samples, RT-qPCR confirmed reduced FTMT expression, and plasma ELISA showed elevated circulating LTA, soluble MICB, and soluble HLA-E in CeA patients. Network analysis highlighted NK cell cytotoxicity as a central pathway.</p><p><strong>Conclusions: </strong>In summary, our study demonstrates that four immune-related proteins, including MICB, promote cerebral atherosclerosis by downregulating the ferroptosis-protective factor FTMT. Importantly, single-cell MR reveals that MICB acts as a risk factor for CeA specifically in NK cells and plasma cells, providing new mechanistic insight into cell-type-dependent immune regulation of vascular disease.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"18 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13700353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149263628","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":"Accelerated biological aging mediates the associations of plasma lactate and the glucose-lactate index with MASLD: a prospective cohort study.","authors":"Xuejiao Pu, Binyu Bai, Jing Yu, Kai Zhang, Ting Zhou, Biao Xie, Peng Wang, Dan Shi","doi":"10.1186/s13148-026-02219-5","DOIUrl":"10.1186/s13148-026-02219-5","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely linked to metabolic dysfunction. Lactate and the glucose-lactate index may reflect systemic glucose-lactate metabolic dysregulation, but their associations with MASLD and the potential mediating role of accelerated biological aging remain unclear.</p><p><strong>Methods: </strong>This cohort study included 175,612 UK Biobank participants. Plasma metabolites were quantified by nuclear magnetic resonance spectroscopy. Cox models assessed associations with incident MASLD, and mediation analyses evaluated PhenoAge acceleration (PhenoAge Accel), KDM-BA acceleration (KDM-BA Accel), and relative leukocyte telomere length (rLTL). Complementary transcriptomic analyses were conducted using GSE126848, and the co-expression of selected gene pairs was further assessed using the ChIPBase v3.0 Co-Expression tool.</p><p><strong>Results: </strong>Higher lactate and the glucose-lactate index were associated with increased MASLD risk (tertile 3 vs. 1 hazard ratios: 1.19 [95% CI, 1.07-1.32; P = 0.001] and 1.29 [95% CI, 1.16-1.43; P < 0.001], respectively). Both biomarkers were associated with higher PhenoAge Accel and KDM-BA Accel and lower rLTL. PhenoAge Accel mediated 32.3% and 20.8% of the respective associations, whereas KDM-BA Accel mediated 8.2% and 11.8%; rLTL mediation was not significant. Seven lactate metabolism-related genes and 20 representative aging-related genes were differentially expressed between healthy and MASLD liver tissues, and the corresponding transcriptional scores were positively correlated. Selected gene pairs also showed significant co-expression in the ChIPBase v3.0 Co-Expression analysis.</p><p><strong>Conclusion: </strong>Elevated lactate and the glucose-lactate index were associated with higher MASLD risk, with these associations partly mediated by accelerated biological aging. These findings provide prospective population-based and tissue-level evidence suggesting potential interrelationships among metabolic dysregulation, accelerated aging, and MASLD risk.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"18 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13700495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149263642","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":"Simultaneous X-chromosome inactivation and tissue-/cell-type-specific DNA methylation in the transcriptional regulatory region of the X-linked recessive disease gene OTC.","authors":"Fuko Yamada, Shiori Hinata, Ryohei Shigeta, Hiroshi Nagashima, Kenji Yamatoya, Jun Ohgane","doi":"10.1186/s13148-026-02217-7","DOIUrl":"10.1186/s13148-026-02217-7","url":null,"abstract":"<p><strong>Background: </strong>Variability in disease onset and severity among heterozygous females with X-linked recessive disorders, such as ornithine transcarbamylase (OTC) deficiency, may result from differences in the expression level of the normal allele caused by skewed X-chromosome inactivation (XCI). However, previous studies on the mechanisms of XCI lack relevance to humans. By applying the concept of hypomethylated allele frequency, gene expression can be estimated through DNA methylation analysis of transcriptional regulatory regions, including tissue-/cell-type-specific differentially methylated regions (T-DMRs) and XCI-affected regions.</p><p><strong>Results: </strong>In this study, we identified a porcine OTC transcriptional regulatory region that functions both as a T-DMR and XCI-affected differentially methylated region. Furthermore, by distinguishing alleles using a single nucleotide polymorphism, we detected evidence of skewed XCI in female pigs.</p><p><strong>Conclusions: </strong>Accordingly, by demonstrating that hypomethylated allele frequency reflects the active X allele, this study provides possible molecular evidence of skewed X inactivation through DNA methylation within the OTC T-DMR.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"18 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13700207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149263581","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":"Bridging the gap: advanced chromatin biotechnologies for circadian epigenomic profiling in head and neck squamous cell carcinoma.","authors":"Sehrish Khan, Raed Said, Christopher Eskiw, François Thuot, Benoit Guay, Petros Papagerakis, Silvana Papagerakis","doi":"10.1186/s13148-026-02189-8","DOIUrl":"10.1186/s13148-026-02189-8","url":null,"abstract":"<p><p>Surgery, radiotherapy and chemotherapy remain the main therapies for treating head and neck cancers, however new modalities have emerged with an emphasis to understand the complexity of the tumor biology. One emerging layer of complexity is the circadian clock, disrupted in many cancers, contributes to pathogenesis and progression due to its crosstalk with cancer pathways. While transcriptional alterations of core clock genes have been described in Head and Neck squamous cell carcinoma (HNSCC), the higher-order epigenetic and chromatin-based mechanisms underlying circadian dysregulation remain poorly defined. In this review, we highlight the potential of several chromatin-based biotechnologies in characterizing circadian clock disruption and identifying epigenetic biomarkers in HNSCC. Powerful assays including Chromatin conformation capture, Chromatin immunoprecipitation, DNA methylation profiling, ATAC-seq and single cell technologies can dissect circadian disruption at multiple regulatory layers. These approaches enable genome-wide mapping of chromatin accessibility, histone modifications, and 3D chromatin organization. Integrating these approaches across HPV-positive (HPV+) and HPV-negative (HPV-) HNSCC provides a framework to determine whether circadian disruption reflects transcriptional deregulation alone or involved structural genome remodeling that actively drives tumor progression. Linking circadian disruption to epigenomic reprogramming in HNSCCs can serve to identify mechanisms of therapeutic resistance and identify vulnerabilities. Advancing chromatin-informed circadian biomarker discovery in HNSCC has the potential to shift precision oncology from static genomic profiling toward dynamic, architecture-based epigenetic regulation.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"18 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13700348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149263588","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":"Lactate-driven metabolic-epigenetic reprogramming in breast cancer: immune evasion and therapeutic resistance.","authors":"Lei Sun, Li Wang, Wanqin Zeng, Shiyan Zeng","doi":"10.1186/s13148-026-02216-8","DOIUrl":"10.1186/s13148-026-02216-8","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer develops within a metabolically heterogeneous tumor microenvironment characterized by regional hypoxia, glycolytic activation, lactate accumulation, extracellular acidification, and impaired antitumor immunity. Lactate is now recognized not only as a metabolic end product, but also as a transported substrate, a receptor ligand, and a potential source of lysine lactylation.</p><p><strong>Main body: </strong>In this Review, we summarize current evidence on lactate production, MCT1/MCT4-dependent trafficking, GPR81/HCAR1-mediated sensing, immune remodeling, and metabolic-epigenetic regulation in breast cancer. We organize these effects into three interconnected layers. First, extracellular acidification, nutrient competition, and redox stress produce rapid and potentially reversible suppression of CD8⁺ T cells, natural killer cells, and dendritic cells. Second, sustained lactate-rich conditions alter the relative fitness of immune and stromal populations, weakening cytotoxic effectors while supporting regulatory T cells, tumor-associated macrophages, suppressive myeloid populations, and stromal immune exclusion. Third, histone and non-histone lactylation, together with RNA-level and chromatin regulatory mechanisms, may contribute to more durable state fixation. We distinguish direct breast cancer evidence from mechanisms established in other cancers and from transcriptome-based lactylation-associated signatures. We also discuss methodological limitations, subtype-specific evidence, and therapeutic strategies targeting lactate production, transport, sensing, and downstream epigenetic regulation.</p><p><strong>Short conclusion: </strong>Lactate-driven metabolic and epigenetic regulation provides a useful framework for understanding immune evasion and therapeutic resistance in breast cancer. However, direct mechanistic evidence remains concentrated in triple-negative breast cancer and tumor-intrinsic phenotypes. Lactylation should therefore be considered a candidate mechanism of durable state fixation rather than a universal explanation for lactate-associated effects. Future studies integrating direct lactylation measurements, spatial multi-omics, functional perturbation, and patient-derived models will be required to define clinically actionable lactate-dependent states.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"18 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13685286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149237142","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":"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13681942/pdf/","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":"OA","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":"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":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13681779/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}