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 ProjectEvidence of accelerated epigenetic aging of breast tissues in patients with breast cancer is driven by CpGs associated with polycomb-related genes
Rozenblit M, Hofstatter E, Liu Z, O’Meara T, Storniolo AM, Dalela D, Singh V, Pusztai L, Levine M. Evidence of accelerated epigenetic aging of breast tissues in patients with breast cancer is driven by CpGs associated with polycomb-related genes. Clinical Epigenetics 2022, 14: 30. PMID: 35209953, PMCID: PMC8876160, DOI: 10.1186/s13148-022-01249-z.Peer-Reviewed Original ResearchConceptsNormal breast tissueBreast cancerEpigenetic age accelerationBreast tissuePeripheral bloodAge accelerationStrong risk factorBreast cancer riskTissue/blood samplesGood surrogate markerBreast cancer diagnosisHealthy controlsRisk factorsSurrogate markerCancer riskBlood samplesTumor tissueCancerCancer diagnosisNew scoreTissueUnaffected individualsBloodEpigenetic aging signaturesEpigenetic aging
2021
Epigenetic age acceleration, fatigue, and inflammation in patients undergoing radiation therapy for head and neck cancer: A longitudinal study
Xiao C, Beitler JJ, Peng G, Levine ME, Conneely KN, Zhao H, Felger JC, Wommack EC, Chico CE, Jeon S, Higgins KA, Shin DM, Saba NF, Burtness BA, Bruner DW, Miller AH. Epigenetic age acceleration, fatigue, and inflammation in patients undergoing radiation therapy for head and neck cancer: A longitudinal study. Cancer 2021, 127: 3361-3371. PMID: 34027995, DOI: 10.1002/cncr.33641.Peer-Reviewed Original ResearchConceptsC-reactive proteinIL-6 levelsEpigenetic age accelerationNeck cancerInterleukin-6Inflammatory markersHigher epigenetic age accelerationLower C-reactive proteinAge accelerationHigher C-reactive proteinMultidimensional Fatigue Inventory-20Poor functional outcomeBlood DNA methylationMonths postradiotherapyAdvanced diseaseConcurrent chemoradiationMost patientsDistant metastasisFunctional outcomeSevere fatigueTreatment completionRadiation therapyPatientsGreater fatigueInflammationAssociation of Epigenetic Age Acceleration With Risk Factors, Survival, and Quality of Life in Patients With Head and Neck Cancer
Xiao C, Miller AH, Peng G, Levine ME, Conneely KN, Zhao H, Eldridge RC, Wommack EC, Jeon S, Higgins KA, Shin DM, Saba NF, Smith AK, Burtness B, Park HS, Irwin ML, Ferrucci LM, Ulrich B, Qian DC, Beitler JJ, Bruner DW. Association of Epigenetic Age Acceleration With Risk Factors, Survival, and Quality of Life in Patients With Head and Neck Cancer. International Journal Of Radiation Oncology • Biology • Physics 2021, 111: 157-167. PMID: 33882281, PMCID: PMC8802868, DOI: 10.1016/j.ijrobp.2021.04.002.Peer-Reviewed Original ResearchConceptsProgression-free survivalBody mass indexQuality of lifeHigher epigenetic age accelerationTreatment-related symptomsOverall survivalEpigenetic age accelerationRadiation therapyRisk factorsClinical characteristicsNeck cancerAge accelerationWorse overall survivalHuman papilloma virusFaster biological agingAdverse eventsDistant metastasisLifestyle factorsMass indexCancer outcomesBlood biomarkersPapilloma virusFunctional assessmentHigher HRPatients
2017
Epigenetic clock analysis of diet, exercise, education, and lifestyle factors
Quach A, Levine ME, Tanaka T, Lu AT, Chen BH, Ferrucci L, Ritz B, Bandinelli S, Neuhouser ML, Beasley JM, Snetselaar L, Wallace RB, Tsao PS, Absher D, Assimes TL, Stewart JD, Li Y, Hou L, Baccarelli AA, Whitsel EA, Horvath S. Epigenetic clock analysis of diet, exercise, education, and lifestyle factors. Aging 2017, 9: 419-437. PMID: 28198702, PMCID: PMC5361673, DOI: 10.18632/aging.101168.Peer-Reviewed Original ResearchConceptsIntrinsic epigenetic age accelerationExtrinsic epigenetic age accelerationModerate alcohol consumptionMetabolic syndromeLifestyle factorsAlcohol consumptionEpigenetic age accelerationHealth initiativesItalian cohort studyPostmenopausal female participantsFirst-line medicationWomen's Health InitiativeBlood carotenoid levelsType 2 diabetesAge accelerationAge-related functional declineHealth-related outcomesEpigenetic clock analysisFemale participantsIndicator of fruitCause mortalityCohort studyPoultry intakeChronic conditionsFish intake
2016
DNA methylation-based measures of biological age: meta-analysis predicting time to death
Chen BH, Marioni RE, Colicino E, Peters MJ, Ward-Caviness CK, Tsai PC, Roetker NS, Just AC, Demerath EW, Guan W, Bressler J, Fornage M, Studenski S, Vandiver AR, Moore AZ, Tanaka T, Kiel DP, Liang L, Vokonas P, Schwartz J, Lunetta KL, Murabito JM, Bandinelli S, Hernandez DG, Melzer D, Nalls M, Pilling LC, Price TR, Singleton AB, Gieger C, Holle R, Kretschmer A, Kronenberg F, Kunze S, Linseisen J, Meisinger C, Rathmann W, Waldenberger M, Visscher PM, Shah S, Wray NR, McRae AF, Franco OH, Hofman A, Uitterlinden AG, Absher D, Assimes T, Levine ME, Lu AT, Tsao PS, Hou L, Manson JE, Carty CL, LaCroix AZ, Reiner AP, Spector TD, Feinberg AP, Levy D, Baccarelli A, van Meurs J, Bell JT, Peters A, Deary IJ, Pankow JS, Ferrucci L, Horvath S. DNA methylation-based measures of biological age: meta-analysis predicting time to death. Aging 2016, 8: 1844-1859. PMID: 27690265, PMCID: PMC5076441, DOI: 10.18632/aging.101020.Peer-Reviewed Original ResearchConceptsCause mortalityBlood cell compositionRisk factorsTraditional risk factorsBlood cell countAdditional risk factorsChronological ageEpigenetic ageCell compositionBiological ageEpigenetic age accelerationStudy ACell countEthnic groupsSignificant associationHuman cohortsRobust biomarkersMortalityTotal sample sizeMethylation-based measuresDNA methylation-based measuresEpigenetic age estimatesAgeAge accelerationDifferent cohortsEpigenetic Aging and Immune Senescence in Women With Insomnia Symptoms: Findings From the Women’s Health Initiative Study
Carroll JE, Irwin MR, Levine M, Seeman TE, Absher D, Assimes T, Horvath S. Epigenetic Aging and Immune Senescence in Women With Insomnia Symptoms: Findings From the Women’s Health Initiative Study. Biological Psychiatry 2016, 81: 136-144. PMID: 27702440, PMCID: PMC5536960, DOI: 10.1016/j.biopsych.2016.07.008.Peer-Reviewed Original ResearchConceptsNaive T cellsWomen's Health Initiative studyDifferentiated T cellsT cellsInsomnia symptomsAge-related morbidityShort sleepSleep durationInitiative studyLarge population-based studyEpigenetic agePopulation-based studyLong sleep durationSymptoms of insomniaImmune senescenceImmune cellsLong sleepAdvanced epigenetic ageCell countSymptomsInfluence riskSleepCross-sectional dataAgeAge accelerationMenopause accelerates biological aging
Levine ME, Lu AT, Chen BH, Hernandez DG, Singleton AB, Ferrucci L, Bandinelli S, Salfati E, Manson JE, Quach A, Kusters CD, Kuh D, Wong A, Teschendorff AE, Widschwendter M, Ritz BR, Absher D, Assimes TL, Horvath S. Menopause accelerates biological aging. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: 9327-9332. PMID: 27457926, PMCID: PMC4995944, DOI: 10.1073/pnas.1604558113.Peer-Reviewed Original ResearchConceptsEpigenetic age accelerationBilateral oophorectomyBuccal epitheliumAge accelerationHealth initiativesMedical Research Council National SurveyMenopausal hormone therapyWomen's Health InitiativeEpigenetic clock analysisHigher epigenetic ageMendelian randomization approachMendelian randomization analysisEpigenetic ageHormone therapyEarly menopauseParkinson's diseaseMenopauseReproductive agingSignificant associationLarger studyBloodRandomization analysisDiseaseAgeEpithelium
2015
Epigenetic age of the pre-frontal cortex is associated with neuritic plaques, amyloid load, and Alzheimer’s disease related cognitive functioning
Levine ME, Lu AT, Bennett DA, Horvath S. Epigenetic age of the pre-frontal cortex is associated with neuritic plaques, amyloid load, and Alzheimer’s disease related cognitive functioning. Aging 2015, 7: 1198-1211. PMID: 26684672, PMCID: PMC4712342, DOI: 10.18632/aging.100864.Peer-Reviewed Original ResearchConceptsCognitive functioningBrain ageCognitive declineGlobal cognitive functioningAccurate epigenetic biomarkerPre-frontal cortexEpisodic memoryAge related neurodegenerationReligious Orders StudyRush MemoryMemoryAging ProjectAlzheimer's diseaseNeuropathological measurementsNeuropathological markersFunctioningRelated neurodegenerationDorsolateral prefrontal cortex samplesOrders StudyEpigenetic age accelerationComplex trait analysisDLPFCSignificant genetic correlationsAge accelerationAmyloid load