2025
Systems Age: a single blood methylation test to quantify aging heterogeneity across 11 physiological systems
Sehgal R, Markov Y, Qin C, Meer M, Hadley C, Shadyab A, Casanova R, Manson J, Bhatti P, Moore A, Crimmins E, Hagg S, Assimes T, Whitsel E, Higgins-Chen A, Levine M. Systems Age: a single blood methylation test to quantify aging heterogeneity across 11 physiological systems. Nature Aging 2025, 5: 1880-1896. PMID: 40954326, DOI: 10.1038/s43587-025-00958-3.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAgingBiomarkersDNA MethylationEpigenesis, GeneticFemaleHumansMachine LearningMaleMiddle AgedStudy protocol for the Health Outcomes in Pregnancy and Early Childhood (HOPE) Study: A mother-infant study in American Samoa
Heinsberg L, Loia M, Tasele S, Faasalele-Savusa K, Carlson J, Anesi S, Desobry K, Yuchongco E, Guevara B, Sesaga A, Iloilo A, Tofaeono V, Bryan K, Tauasosi-Posiulai T, Kershaw E, Conley Y, Weeks D, Hawley N, Muasau-Howard B. Study protocol for the Health Outcomes in Pregnancy and Early Childhood (HOPE) Study: A mother-infant study in American Samoa. PLOS ONE 2025, 20: e0326644. PMID: 40952996, PMCID: PMC12435730, DOI: 10.1371/journal.pone.0326644.Peer-Reviewed Original ResearchConceptsGestational diabetes mellitusBody mass indexHealth outcomesBurden of gestational diabetes mellitusLower risk of type 2 diabetesAmerican Samoa Department of HealthAssociated with higher body mass indexLow riskGestational diabetes statusRisk of type 2 diabetesHigher Body Mass IndexCord blood DNA methylationLongitudinal cohort studyDepartment of HealthInfant body sizePacific IslandersPeer-reviewed publicationsType 2 diabetesBlood DNA methylationInstitutional review boardAmerican SamoaPregnant womenInfant growthFollow-upMass indexHigh MGMT expression identifies aggressive colorectal cancer with distinct genomic features and immune evasion properties
Zhang J, Rajendran B, Desai S, Gibson J, DiPalermo J, LoRusso P, Kong Y, Zhao H, Cecchini M, Schalper K. High MGMT expression identifies aggressive colorectal cancer with distinct genomic features and immune evasion properties. Journal For ImmunoTherapy Of Cancer 2025, 13: e011653. PMID: 40935566, DOI: 10.1136/jitc-2025-011653.Peer-Reviewed Original ResearchConceptsTumor-infiltrating lymphocytesCD8+ tumor-infiltrating lymphocytesPromoter methylation statusMGMT expressionMGMT overexpressionClinical significanceAllogeneic peripheral blood mononuclear cellsCD8+ T cellsMGMT promoter methylation statusKilling of malignant cellsMGMT-expressing cellsMultiplexed quantitative immunofluorescencePeripheral blood mononuclear cellsAggressive clinical courseMGMT protein expressionAggressive colorectal cancerMethylation statusExpression of MGMTLevels of MGMT proteinMGMT protein levelsImmune evasion propertiesBlood mononuclear cellsMutational featuresAdaptive immune evasionSomatic mutation burdenEpigenetic regulation of cancer stemness
Galassi C, Manic G, Esteller M, Galluzzi L, Vitale I. Epigenetic regulation of cancer stemness. Signal Transduction And Targeted Therapy 2025, 10: 243. PMID: 40744921, PMCID: PMC12314033, DOI: 10.1038/s41392-025-02340-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDNA MethylationEpigenesis, GeneticGene Expression Regulation, NeoplasticHumansNeoplasmsNeoplastic Stem CellsConceptsEpigenetic controlEpigenetic control of transcriptionReversible modificationsControl of transcriptionImpact of epigenetic alterationsModification of DNAEpigenetic marksDeubiquitinating enzymesUbiquitin ligasePreservation of homeostasisTranscription factorsEpigenetic defectsPostembryonic developmentEpigenetic alterationsEpigenetic modifiersRegulation of cancer stemnessGene expressionAdult tissuesHuman disordersActivation statusCancer stem cellsCancer stemnessAntagonistic activitySmall populationMalignant cellsDirect genetic transformation bypasses tumor-associated DNA methylation alterations
Hetzel S, Hodis E, Torlai Triglia E, Kovacsovics A, Steinmann K, Gnirke A, Cui M, McQuaid D, Weigert R, Pohl G, Muzumdar M, Leyvraz S, Keilholz U, Yaspo M, Regev A, Kretzmer H, Smith Z, Meissner A. Direct genetic transformation bypasses tumor-associated DNA methylation alterations. Genome Biology 2025, 26: 212. PMID: 40676699, PMCID: PMC12273271, DOI: 10.1186/s13059-025-03650-2.Peer-Reviewed Original ResearchConceptsDe novo methylationEpigenetic aspectsDNA methylation landscapeDNA methylation alterationsDNA methylation levelsMethylation landscapeMutant cellsPromoter sequencesExtensive proliferation in vitroMethylation alterationsCellular transformationMethylation levelsHuman cellsGenetic transformationGlobal changeHealthy human cellsClinical samplesAnimal systemsConclusionsOur resultsMolecular referenceProliferation in vitroCellsMouse modelTumor modelDNAMechanism of EHMT2-mediated genomic imprinting associated with Prader-Willi syndrome
Wang S, Cheng Y, Lim J, Jang M, Forrest E, Kim Y, Donahue M, Jo S, Qiao S, Lee D, Hong J, Xiong Y, Jin J, Wang S, Jiang Y. Mechanism of EHMT2-mediated genomic imprinting associated with Prader-Willi syndrome. Nature Communications 2025, 16: 6125. PMID: 40610428, PMCID: PMC12229668, DOI: 10.1038/s41467-025-61156-8.Peer-Reviewed Original ResearchConceptsPWS-ICMaternal chromosomeImprinted domainExpression of paternally expressed genesPrader-Willi syndromeBipartite imprinting centerPaternally expressed genesHeterochromatin complexExpression of SNRPNImprinting centerPatient-derived cellsEHMT2 genesImprinted genesMaternal imprintingChromosomeMaternal deletionGenesPrader-WilliNoncoding RNAsEHMT2Imprint maintenanceEditing resultsPostnatal brainDerived cellsExpressionIncorporating local ancestry information to predict genetically associated DNA methylation in admixed populations
Cheng Y, Zhou G, Li H, Zhang X, Justice A, Martinez C, Aouizerat B, Xu K, Zhao H. Incorporating local ancestry information to predict genetically associated DNA methylation in admixed populations. Briefings In Bioinformatics 2025, 26: bbaf325. PMID: 40622482, PMCID: PMC12232425, DOI: 10.1093/bib/bbaf325.Peer-Reviewed Original ResearchConceptsMethylome-wide association studiesAdmixed populationsComplex traitsLocal ancestryAssociation studiesDNA methylationAssociated with complex traitsLocal ancestry informationPopulations of European ancestryCpG methylation levelsNon-European populationsMeasurement of methylationAncestry informationCpG sitesMethylation levelsEuropean ancestryEpigenetic underpinningsCpGAncestryTraitsMethylationAmerican populationAfrican American populationDNAPopulationA scoping review of functional genomics in perinatal depression
Bruzzone S, Garre V, Høgh S, Frokjaer V, O'Donnell K, Eid R. A scoping review of functional genomics in perinatal depression. Frontiers In Neuroendocrinology 2025, 78: 101202. PMID: 40581107, DOI: 10.1016/j.yfrne.2025.101202.Peer-Reviewed Original ResearchMeSH KeywordsDepressionDepression, PostpartumDNA MethylationFemaleGenomicsHumansPregnancyPregnancy ComplicationsConceptsPerinatal depressionMental health problemsPublic mental health problemPsychosocial adaptationComprehensive assessmentPostpartum periodClinically useful biomarkersInclusion criteriaHealth problemsAssociated with PDGenome functionPregnant womenCandidate-gene approachSystematic overviewEstrogen signalingMolecular profiling methodsImmune functionReview studiesSample sizeDepressionWomenSignature of PDDNA methylationGene expressionFunctional genomicsCharacterizing the Social Epigenome in Mexican Patients with Early-Onset Psychosis
Ruiz-Ramos D, Martínez-Magaña J, Juárez-Rojop I, Nolasco-Rosales G, Sosa-Hernández F, Cruz-Castillo J, Cavazos J, Callejas A, Zavaleta-Ramírez P, Zorrilla-Dosal J, Lanzagorta N, Nicolini H, Montalvo-Ortiz J, Glahn D, Genis-Mendoza A. Characterizing the Social Epigenome in Mexican Patients with Early-Onset Psychosis. Genes 2025, 16: 591. PMID: 40428414, PMCID: PMC12111507, DOI: 10.3390/genes16050591.Peer-Reviewed Original ResearchConceptsEarly-onset psychosisRisk scoreEpigenetic ageEpigenome-wide association studiesAssociation studiesYears of educationShort life expectancyMexican patientsPsychiatric admissionsAssociation of DNA methylationSocial epigenomicsYears of schoolingAccelerated Epigenetic AgingLife expectancyAssociated with panic disorderEnvironmental exposuresEarly-onsetGlobal functioningClinical characteristicsClinical manifestationsDNA methylationAgeEpigenetic mechanismsPsychosisManifestation of psychosisAir Pollution Control Mitigates Frailty Progression: Evidence from Two Cohorts of Older Adults and DNA Methylation Insights
Jiang M, Wang Y, Tian S, Liu S, Luo Y, Song H, Qin J, Lv Y, Baccarelli A, Zhang Z, Shi X, Gao X. Air Pollution Control Mitigates Frailty Progression: Evidence from Two Cohorts of Older Adults and DNA Methylation Insights. Environmental Science And Technology 2025, 59: 9907-9917. PMID: 40353491, DOI: 10.1021/acs.est.4c13675.Peer-Reviewed Original ResearchMeSH KeywordsAgedAir PollutionChinaCohort StudiesDNA MethylationFemaleFrailtyHumansMaleParticulate MatterConceptsChinese Longitudinal Healthy Longevity StudyAssociated with PM<sub>2.5</sub> exposure inOlder adultsAir quality improvementHealth and Aging StudyClean Air ActEnvironmental policy interventionsQuasi-experimental studyRisk of worsening frailtyAir ActRange reductionKnowledge gapsLikelihood of improvementFrailty progressionNationwide cohortFollow-up visitFrailty burdenQuality improvementProspective cohortSurvey wavesAging StudyFrailtyMultistate modelling analysisFollow-up dataHealth benefitsAccelerated Aging in Cancer and Cancer Treatment: Current Status of Biomarkers
Abraham S, Parekh J, Lee S, Afrin H, Rozenblit M, Blenman K, Perry R, Ferrucci L, Liu J, Irwin M, Lustberg M. Accelerated Aging in Cancer and Cancer Treatment: Current Status of Biomarkers. Cancer Medicine 2025, 14: e70929. PMID: 40322791, PMCID: PMC12051034, DOI: 10.1002/cam4.70929.Peer-Reviewed Original ResearchMeSH KeywordsAgingBiomarkersBiomarkers, TumorCellular SenescenceDNA MethylationEpigenesis, GeneticHumansNeoplasmsConceptsBiological age of patientsLeukocyte telomere lengthInterleukin-6Treatment-related toxicityAge of patientsTherapy-induced toxicityExpression of p16INK4aPredictors of toxicityStatus of biomarkersMarkers of cellular senescenceRadiation therapyBiological ageCancer patientsCancer therapyFunctional reserveAging biomarkersPhysiological reserveCancer treatmentCancerConfirmatory studiesTherapyClinical practiceFunctional capacityPatientsFunctional statusTranscriptomic and epigenomic signatures of liver metabolism and insulin sensitivity in aging mice
González J, Scharfman O, Zhu W, Kasamoto J, Gould V, Perry R, Higgins-Chen A. Transcriptomic and epigenomic signatures of liver metabolism and insulin sensitivity in aging mice. Mechanisms Of Ageing And Development 2025, 225: 112068. PMID: 40324540, PMCID: PMC12151592, DOI: 10.1016/j.mad.2025.112068.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsDNA MethylationEpigenesis, GeneticEpigenomicsInsulin ResistanceLiverMaleMiceTranscriptomeConceptsDNA methylation modulesHepatic insulin resistanceRNA modulesProtein-protein interaction network analysisMetabolic pathwaysMethylation modulatorsPyruvate carboxylase fluxInteraction network analysisCitrate synthase fluxDNA methylation analysisCanonical metabolic pathwaysLipid metabolic pathwaysDecreased fatty acid oxidationComprehensive phenotypic characterizationMZF-1Fatty acid oxidationEpigenomic signaturesInsulin-stimulated conditionsModule genesNetwork analysisPhenotypic characterizationMitochondrial metabolic defectsInsulin resistanceLiver insulin resistanceMethylation analysisDNA methylation in melanoma immunotherapy: mechanisms and therapeutic opportunities
Deshmukh M, Brooks V, Roy S, Milette S, Bosenberg M, Micevic G. DNA methylation in melanoma immunotherapy: mechanisms and therapeutic opportunities. Clinical Epigenetics 2025, 17: 71. PMID: 40307913, PMCID: PMC12044936, DOI: 10.1186/s13148-025-01865-5.Peer-Reviewed Original ResearchMeSH KeywordsBiomarkers, TumorDNA MethylationEpigenesis, GeneticHumansImmunotherapyMelanomaTumor MicroenvironmentConceptsAnti-tumor immune responseImmune checkpoint moleculesT-cell phenotypeDeregulated expression of oncogenesExpression of MHCDNA methylationCell-intrinsic roleSilencing tumor suppressor genesTumor suppressor geneExpression of oncogenesCheckpoint moleculesImmunological therapiesMelanoma immunotherapyCell immunogenicityAbnormal DNA methylationTumor microenvironmentImmune cellsImproved therapiesMelanomaImmune responseMethylation-based biomarkersTherapeutic opportunitiesDeregulated expressionProliferative signalsTumor migrationAberrant DNA methylation of genes regulating CD4+ T cell HIV‐1 reservoir in women with HIV
Xu K, Zhang X, Asam K, Quach B, Page G, Konkle‐Parker D, Martinez C, Lahiri C, Topper E, Cohen M, Kassaye S, DeHovitz J, Kuniholm M, Archin N, Valizadeh A, Tien P, Marconi V, Hancock D, Johnson E, Aouizerat B. Aberrant DNA methylation of genes regulating CD4+ T cell HIV‐1 reservoir in women with HIV. Clinical And Translational Medicine 2025, 15: e70267. PMID: 40070009, PMCID: PMC11896887, DOI: 10.1002/ctm2.70267.Peer-Reviewed Original ResearchMeSH KeywordsAdultCD4-Positive T-LymphocytesDNA MethylationFemaleHIV InfectionsHIV-1HumansMiddle AgedVirus ReplicationConceptsCD4+ T cellsHIV-1 reservoirHIV-1 latencyT cellsHIV-1Aberrant DNA methylationMechanisms of HIV-1 latencyViral replicationVirally suppressed womenDNA methylationHIV-1 integration sitesHIV-1 replicationMolecular targetsDifferentially methylated CpG sitesImmune defenceDNA methylation sequencingHost epigenetic landscapeDNA methylation sitesHIV-1 DNA integrationDifferentially methylated sitesHost genome integrityInterferon signaling genesCure HIVHost-virus interactionsCD4Epigenomic pathways from racism to preterm birth: secondary analysis of the Nulliparous Pregnancy Outcomes Study: monitoring Mothers-to-be (nuMoM2b) cohort study in the USA to examine how DNA methylation mediates the relationship between multilevel racism and preterm birth in black women: a study protocol
Barcelona V, Ray M, Zhao Y, Samari G, Wu H, Reho P, McNeil R, Reddy U. Epigenomic pathways from racism to preterm birth: secondary analysis of the Nulliparous Pregnancy Outcomes Study: monitoring Mothers-to-be (nuMoM2b) cohort study in the USA to examine how DNA methylation mediates the relationship between multilevel racism and preterm birth in black women: a study protocol. BMJ Open 2025, 15: e091801. PMID: 40037666, PMCID: PMC11881185, DOI: 10.1136/bmjopen-2024-091801.Peer-Reviewed Original ResearchConceptsNulliparous Pregnancy Outcomes StudyMonitoring Mothers-to-BeMothers-to-beBlack womenPregnancy Outcomes StudyParticipants' electronic health recordsPreterm birthSecondary analysisCohort studyGeocoded participant addressesSecondary analysis of dataStudy protocolElectronic health recordsStructural racism measuresUniversity Institutional Review BoardEffects of individual-Black pregnant womenOutcome studiesRacial residential segregationProspective cohort studyPregnancy-related morbidityParticipant's addressHealth recordsAdverse pregnancy outcomesWhite womenEpigenetic signatures of intergenerational exposure to violence in three generations of Syrian refugees
Mulligan C, Quinn E, Hamadmad D, Dutton C, Nevell L, Binder A, Panter-Brick C, Dajani R. Epigenetic signatures of intergenerational exposure to violence in three generations of Syrian refugees. Scientific Reports 2025, 15: 5945. PMID: 40016245, PMCID: PMC11868390, DOI: 10.1038/s41598-025-89818-z.Peer-Reviewed Original ResearchConceptsSyrian refugeesExposure to violenceWar-related violenceExposed to violenceExposure to warAdult health outcomesViolenceIntergenerational exposureSurvey dataRefugeesHealth outcomesEpigenome-wide association studiesTrauma effectsInfluence infantsImpact future generationsEpigenetic age accelerationFuture generationsMothersAssociated with germlineMaternal traumaFamilyAssociation studiesPregnant mothersWarDNA methylationEpigenetic age acceleration in idiopathic pulmonary fibrosis revealed by DNA methylation clocks
Kurbanov D, Ahangari F, Adams T, De Man R, Tang J, Carlon M, Abu Hussein N, Cortesi E, Zapata M, De Sadelaar L, Wuyts W, Vanaudenaerde B, Kaminski N, McDonough J. Epigenetic age acceleration in idiopathic pulmonary fibrosis revealed by DNA methylation clocks. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2025, 328: l456-l462. PMID: 39970931, PMCID: PMC12169420, DOI: 10.1152/ajplung.00171.2024.Peer-Reviewed Original ResearchMeSH KeywordsAgedAgingDNA MethylationEpigenesis, GeneticFemaleHumansIdiopathic Pulmonary FibrosisLungMaleMiddle AgedConceptsIdiopathic pulmonary fibrosisIdiopathic pulmonary fibrosis tissuePulmonary fibrosisLung tissueEpigenetic clocksPotential of DNA methylationDNA methylation levelsDebilitating lung diseaseIllumina MethylationEPIC arrayHuman lung tissueEpigenetic ageDNA methylation clocksBiological ageAffected lung tissueIPF casesClinical prognosisMethylation patternsDNA methylationLung diseaseHealthy controlsAcceleration of biological agingMethylation levelsMethylationEPIC arrayAge accelerationClinical assessmentBidirectional relationship between epigenetic age and stroke, dementia, and late-life depression
Rivier C, Szejko N, Renedo D, Clocchiatti-Tuozzo S, Huo S, de Havenon A, Zhao H, Gill T, Sheth K, Falcone G. Bidirectional relationship between epigenetic age and stroke, dementia, and late-life depression. Nature Communications 2025, 16: 1261. PMID: 39893209, PMCID: PMC11787333, DOI: 10.1038/s41467-024-54721-0.Peer-Reviewed Original ResearchThis study shows a bidirectional link between accelerated epigenetic aging and brain health events like stroke, dementia, and depression, supporting new prevention strategies for aging-related conditions.Evaluation of a biomarker for amyotrophic lateral sclerosis derived from a hypomethylated DNA signature of human motor neurons
Harvey C, Nowak A, Zhang S, Moll T, Weimer A, Barcons A, Souza C, Ferraiuolo L, Kenna K, Zaitlen N, Caggiano C, Shaw P, Snyder M, Mill J, Hannon E, Cooper-Knock J. Evaluation of a biomarker for amyotrophic lateral sclerosis derived from a hypomethylated DNA signature of human motor neurons. BMC Medical Genomics 2025, 18: 10. PMID: 39810183, PMCID: PMC11734586, DOI: 10.1186/s12920-025-02084-w.Peer-Reviewed Original ResearchMeSH KeywordsAmyotrophic Lateral SclerosisBiomarkersCell-Free Nucleic AcidsDNA MethylationHumansInduced Pluripotent Stem CellsMotor NeuronsImpact of age-related changes in buccal epithelial cells on pediatric epigenetic biomarker research
Merrill S, Konwar C, Fatima F, Dever K, MacIsaac J, Letourneau N, Giesbrecht G, Dewey D, England-Mason G, Lewis C, Wang D, Teh A, Meaney M, Gonzalez A, Noll J, De Weerth C, Bush N, O’Donnell K, Stewart S, Kobor M. Impact of age-related changes in buccal epithelial cells on pediatric epigenetic biomarker research. Nature Communications 2025, 16: 609. PMID: 39800776, PMCID: PMC11725590, DOI: 10.1038/s41467-025-55909-8.Peer-Reviewed Original ResearchConceptsBuccal epithelial cellsAge-related changesObsessive-compulsive disorderEpithelial cellsDiurnal cortisol slopeCheek swabsImpact of age-related changesCortisol slopeAssociated with ageOral cellsDevelopmental rangeAge accelerationDNA methylation studiesHeterogeneous sampleNeutrophil proportionBiomarker researchMethylation studiesAgeSwabsWeak associationEpigenetic age
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