2022
Aging the brain: multi-region methylation principal component based clock in the context of Alzheimer’s disease
Thrush KL, Bennett DA, Gaiteri C, Horvath S, Dyck CHV, Higgins-Chen AT, Levine ME. Aging the brain: multi-region methylation principal component based clock in the context of Alzheimer’s disease. Aging 2022, 14: 5641-5668. PMID: 35907208, PMCID: PMC9365556, DOI: 10.18632/aging.204196.Peer-Reviewed Original ResearchConceptsDisease risk increasesBrain agingAD brain tissueΕ4 carrier statusClinical AD dementiaMultiple brain regionsEpigenetic alterationsReligious Orders StudyAD dementiaTest-retest reliabilityCortical samplesAD riskEpigenetic age accelerationSubcortical regionsPathologic ADAlzheimer's diseaseBrain regionsBrain tissueEpigenetic clocksCarrier statusStrong associationRush MemoryAge accelerationRisk increaseAging ProjectLongitudinal Study of DNA Methylation and Epigenetic Clocks Prior to and Following Test-Confirmed COVID-19 and mRNA Vaccination
Pang APS, Higgins-Chen AT, Comite F, Raica I, Arboleda C, Went H, Mendez T, Schotsaert M, Dwaraka V, Smith R, Levine ME, Ndhlovu LC, Corley MJ. Longitudinal Study of DNA Methylation and Epigenetic Clocks Prior to and Following Test-Confirmed COVID-19 and mRNA Vaccination. Frontiers In Genetics 2022, 13: 819749. PMID: 35719387, PMCID: PMC9203887, DOI: 10.3389/fgene.2022.819749.Peer-Reviewed Original ResearchSevere COVID-19T cellsCOVID-19 diagnosisMRNA vaccinationCOVID-19B cellsCOVID-19 vaccine responsesNon-hospitalized COVID-19MRNA COVID-19 vaccineSARS-CoV-2 infectionHost epigenetic landscapeMedian time frameExhausted T cellsNaïve T cellsCOVID-19 vaccinationCOVID-19 exposureCOVID-19 vaccineEpigenetic clock analysisModerna mRNAVaccine responsesImmune cellsEpigenetic clocksHealthy individualsVaccinationLongitudinal assessmentTick tock, tick tock: Mouse culture and tissue aging captured by an epigenetic clock
Minteer C, Morselli M, Meer M, Cao J, Higgins‐Chen A, Lang SM, Pellegrini M, Yan Q, Levine ME. Tick tock, tick tock: Mouse culture and tissue aging captured by an epigenetic clock. Aging Cell 2022, 21: e13553. PMID: 35104377, PMCID: PMC8844113, DOI: 10.1111/acel.13553.Peer-Reviewed Original ResearchConceptsMouse embryonic fibroblastsDNA methylationEpigenetic agingImportant chromatin regulatorsPolycomb group (PcG) factorsAnti-aging interventionsChromatin regulatorsEmbryonic fibroblastsCellular senescenceTissue agingCellular agingEpigenetic clocksMultiple tissuesMouse tissuesCaloric restrictionMechanistic insightsAging changesKidney fibroblastsReduced representationTime pointsPhysiological agingMouse culturesSuch alterationsTick-TockTissue
2021
The Socioeconomic Gradient in Epigenetic Ageing Clocks: Evidence from the Multi-Ethnic Study of Atherosclerosis and the Health and Retirement Study
Schmitz LL, Zhao W, Ratliff SM, Goodwin J, Miao J, Lu Q, Guo X, Taylor KD, Ding J, Liu Y, Levine M, Smith JA. The Socioeconomic Gradient in Epigenetic Ageing Clocks: Evidence from the Multi-Ethnic Study of Atherosclerosis and the Health and Retirement Study. Epigenetics 2021, 17: 589-611. PMID: 34227900, PMCID: PMC9235889, DOI: 10.1080/15592294.2021.1939479.Peer-Reviewed Original ResearchConceptsMulti-Ethnic StudySocioeconomic statusSocioeconomic gradientFaster biological agingEpigenetic agingBiological agingRetirement StudyAlcohol consumptionHealth behaviorsSignificant associationDisease riskSES gradientOlder adultsGenetic riskPolygenic riskEpigenetic clocksAtherosclerosisSES measuresAssociationInconsistent resultsRobust associationRiskMultiple tissues
2020
A rat epigenetic clock recapitulates phenotypic aging and co-localizes with heterochromatin
Levine M, McDevitt RA, Meer M, Perdue K, Di Francesco A, Meade T, Farrell C, Thrush K, Wang M, Dunn C, Pellegrini M, de Cabo R, Ferrucci L. A rat epigenetic clock recapitulates phenotypic aging and co-localizes with heterochromatin. ELife 2020, 9: e59201. PMID: 33179594, PMCID: PMC7661040, DOI: 10.7554/elife.59201.Peer-Reviewed Original ResearchConceptsTranscriptional factor bindingNovel epigenetic clockEpigenetic signalsIntergenic regionEpigenetic age measuresDNA methylationFactor bindingSequencing dataEpigenetic clocksBiochemical advantagesNetwork analysisH3K9me3H3K27me3HeterochromatinCaloric restrictionRobust biomarkersSubstantial overlapMethylationPhenotypicCpGDNAmAgeBindingMiceClockUnderlying features of epigenetic aging clocks in vivo and in vitro
Liu Z, Leung D, Thrush K, Zhao W, Ratliff S, Tanaka T, Schmitz LL, Smith JA, Ferrucci L, Levine ME. Underlying features of epigenetic aging clocks in vivo and in vitro. Aging Cell 2020, 19: e13229. PMID: 32930491, PMCID: PMC7576259, DOI: 10.1111/acel.13229.Peer-Reviewed Original ResearchConceptsEpigenetic clocksTranscriptional associationsTissues/cellsHuman tissues/cellsEpigenetic aging clockMultiple tissues/cellsDifferent biological processesMulti-omics analysisDNA methylation dataMulti-omics dataBiological processesMethylation dataAging clockMitochondrial dysfunctionEpigenetic agingBiological agingClockHallmarkCellsSenescenceAutophagyStriking lackPathwayCpGMetabolismSchizophrenia and Epigenetic Aging Biomarkers: Increased Mortality, Reduced Cancer Risk, and Unique Clozapine Effects
Higgins-Chen AT, Boks MP, Vinkers CH, Kahn RS, Levine ME. Schizophrenia and Epigenetic Aging Biomarkers: Increased Mortality, Reduced Cancer Risk, and Unique Clozapine Effects. Biological Psychiatry 2020, 88: 224-235. PMID: 32199607, PMCID: PMC7368835, DOI: 10.1016/j.biopsych.2020.01.025.Peer-Reviewed Original ResearchConceptsAge-associated proteinsEpigenetic clocksDNA methylation data setsMethylation data setsEpigenetic ageing biomarkersReduced cancer riskCD8 T cellsBody mass indexLong-term outcomesHorvath's epigenetic clockLower cancer ratesDNA methylationDNA methylation predictorsBiological age differencesMitotic clockMitotic divisionAge clocksCause mortalityNatural killerMass indexEarly mortalityMedication dataSZ casesClozapine's effectIncreased Mortality
2017
Eleven Telomere, Epigenetic Clock, and Biomarker-Composite Quantifications of Biological Aging: Do They Measure the Same Thing?
Belsky DW, Moffitt TE, Cohen AA, Corcoran DL, Levine ME, Prinz JA, Schaefer J, Sugden K, Williams B, Poulton R, Caspi A. Eleven Telomere, Epigenetic Clock, and Biomarker-Composite Quantifications of Biological Aging: Do They Measure the Same Thing? American Journal Of Epidemiology 2017, 187: 1220-1230. PMID: 29149257, PMCID: PMC6248475, DOI: 10.1093/aje/kwx346.Peer-Reviewed Original Research
2016
Genetic variants near MLST8 and DHX57 affect the epigenetic age of the cerebellum
Lu AT, Hannon E, Levine ME, Hao K, Crimmins EM, Lunnon K, Kozlenkov A, Mill J, Dracheva S, Horvath S. Genetic variants near MLST8 and DHX57 affect the epigenetic age of the cerebellum. Nature Communications 2016, 7: 10561. PMID: 26830004, PMCID: PMC4740877, DOI: 10.1038/ncomms10561.Peer-Reviewed Original ResearchConceptsWide association studyCis-acting effectsDNA methylation levelsAge-related diseasesGWAS analysisSignificant SNPsGene setsMLST8Association studiesEpigenetic clocksMethylation levelsEpigenetic biomarkersGenetic variantsExpression levelsSNPsUnderstanding agingEpigenetic ageTissue ageCerebellar samplesSignificant overlapGWASLociAlzheimer's diseaseClockVariants