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 tissuesAssociation 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 HRPatientsBiological Aging Predicts Vulnerability to COVID-19 Severity in UK Biobank Participants
Kuo CL, Pilling LC, Atkins JL, Masoli JAH, Delgado J, Tignanelli C, Kuchel GA, Melzer D, Beckman KB, Levine ME. Biological Aging Predicts Vulnerability to COVID-19 Severity in UK Biobank Participants. The Journals Of Gerontology Series A 2021, 76: e133-e141. PMID: 33684206, PMCID: PMC7989601, DOI: 10.1093/gerona/glab060.Peer-Reviewed Original ResearchConceptsCOVID-19 severity outcomeCOVID-19 severityDiseases/conditionsAge-related comorbid conditionsCOVID-19-related mortalityPrevalent chronic diseasesCOVID-19 infectionBiggest risk factorCOVID-19Severity outcomesUK Biobank participantsLogistic regression modelsComorbid conditionsTest positivityRisk factorsChronic diseasesInpatient settingFurther adjustmentSymptom severityEarly pandemicBiobank participantsDisease prevalenceAgeSeverityCOVID-19 pandemicAging biomarkers and the brain
Higgins-Chen AT, Thrush KL, Levine ME. Aging biomarkers and the brain. Seminars In Cell And Developmental Biology 2021, 116: 180-193. PMID: 33509689, PMCID: PMC8292153, DOI: 10.1016/j.semcdb.2021.01.003.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsAssociations of Age, Sex, Race/Ethnicity, and Education With 13 Epigenetic Clocks in a Nationally Representative U.S. Sample: The Health and Retirement Study
Crimmins EM, Thyagarajan B, Levine ME, Weir DR, Faul J. Associations of Age, Sex, Race/Ethnicity, and Education With 13 Epigenetic Clocks in a Nationally Representative U.S. Sample: The Health and Retirement Study. The Journals Of Gerontology Series A 2021, 76: 1117-1123. PMID: 33453106, PMCID: PMC8140049, DOI: 10.1093/gerona/glab016.Peer-Reviewed Original Research
2020
Vasomotor Symptoms and Accelerated Epigenetic Aging in the Women’s Health Initiative (WHI)
Thurston RC, Carroll JE, Levine M, Chang Y, Crandall C, Manson JE, Pal L, Hou L, Shadyab AH, Horvath S. Vasomotor Symptoms and Accelerated Epigenetic Aging in the Women’s Health Initiative (WHI). The Journal Of Clinical Endocrinology & Metabolism 2020, 105: dgaa081. PMID: 32080740, PMCID: PMC7069347, DOI: 10.1210/clinem/dgaa081.Peer-Reviewed Original ResearchConceptsVasomotor symptomsWomen's Health InitiativePostmenopausal womenHealth initiativesMenopausal vasomotor symptomsSevere hot flashesBody mass indexAdverse health indicatorsPoor health outcomesYears of ageBiological agingRace/ethnicityAccelerated Epigenetic AgingHormone therapyHot flashesMass indexMenopausal symptomsSleep disturbancesEpigenetic agingEarly deathDNAm PhenoAgeHealth outcomesTiming groupsDNAm GrimAgeSymptoms
2019
Changing Disease Prevalence, Incidence, and Mortality Among Older Cohorts: The Health and Retirement Study
Crimmins EM, Zhang YS, Kim JK, Levine ME. Changing Disease Prevalence, Incidence, and Mortality Among Older Cohorts: The Health and Retirement Study. The Journals Of Gerontology Series A 2019, 74: s21-s26. PMID: 31724057, PMCID: PMC6853787, DOI: 10.1093/gerona/glz075.Peer-Reviewed Original ResearchConceptsMyocardial infarctionHeart diseaseOlder cohortDisease prevalencePopulation healthPrevalence of cancerPrevalence of peopleYounger cohortsRetirement StudyStart of observationCardiovascular conditionsAge 70CohortOlder personsInfarctionPrevalenceIncidenceDeath rateStrokeDiseaseImportant signCancerMortalityHealthDiabetesAssociations of genetics, behaviors, and life course circumstances with a novel aging and healthspan measure: Evidence from the Health and Retirement Study
Liu Z, Chen X, Gill TM, Ma C, Crimmins EM, Levine ME. Associations of genetics, behaviors, and life course circumstances with a novel aging and healthspan measure: Evidence from the Health and Retirement Study. PLOS Medicine 2019, 16: e1002827. PMID: 31211779, PMCID: PMC6581243, DOI: 10.1371/journal.pmed.1002827.Peer-Reviewed Original ResearchConceptsCoronary artery diseaseArtery diseasePhenotypic agingUS older adultsSelf-reported circumstancesRetirement StudyLife course circumstancesAssociation of geneticMorbidity riskMultivariable associationsPotential policy targetsRetrospective natureAdulthood circumstancesPhenotypic AgeAdulthood adversityGenetic predispositionHealth behaviorsSocioenvironmental circumstancesUS populationOlder adultsPotential interventionsDisadvantaged subpopulationsGenetic riskGenetic scoreUS HealthThe role of epigenetic aging in education and racial/ethnic mortality disparities among older U.S. Women
Liu Z, Chen BH, Assimes TL, Ferrucci L, Horvath S, Levine ME. The role of epigenetic aging in education and racial/ethnic mortality disparities among older U.S. Women. Psychoneuroendocrinology 2019, 104: 18-24. PMID: 30784901, PMCID: PMC6555423, DOI: 10.1016/j.psyneuen.2019.01.028.Peer-Reviewed Original Research
2018
A new aging measure captures morbidity and mortality risk across diverse subpopulations from NHANES IV: A cohort study
Liu Z, Kuo PL, Horvath S, Crimmins E, Ferrucci L, Levine M. A new aging measure captures morbidity and mortality risk across diverse subpopulations from NHANES IV: A cohort study. PLOS Medicine 2018, 15: e1002718. PMID: 30596641, PMCID: PMC6312200, DOI: 10.1371/journal.pmed.1002718.Peer-Reviewed Original ResearchConceptsPhenotypic AgeNHANES IVCause mortalityMortality riskHealth behaviorsRepresentative US adult populationDisease-free personsOld-old adultsChronological ageRisk of deathAge 85 yearsCause-specific mortalityCause of deathProportional hazards modelUS adult populationHealth behavior characteristicsDisease countsPotential biological mechanismsEfficacy of interventionsRace/ethnicityNormal BMICohort studyDiverse subpopulationsHazards modelRisk individualsPredictors and implications of accelerated cognitive aging
Levine ME, Harrati A, Crimmins EM. Predictors and implications of accelerated cognitive aging. Biodemography And Social Biology 2018, 64: 83-101. PMID: 31007841, PMCID: PMC6469682, DOI: 10.1080/19485565.2018.1552513.Peer-Reviewed Original ResearchConceptsCognitive ageCognitive agingCognitive declineNon-demented older adultsPathological cognitive declineAge-related declineIndividual differencesCognitive slopesOlder adultsLongitudinal studyComposite measureRetirement StudyAPOE ε4Performance testsDementia transitionSubsequent dementiaDementiaMeasuresRate of declineParticipantsAgingDeclineDifferent conclusionsRace/ethnicityAbsolute levelsIs 60 the New 50? Examining Changes in Biological Age Over the Past Two Decades
Levine ME, Crimmins EM. Is 60 the New 50? Examining Changes in Biological Age Over the Past Two Decades. Demography 2018, 55: 387-402. PMID: 29511995, PMCID: PMC5897168, DOI: 10.1007/s13524-017-0644-5.Peer-Reviewed Original ResearchConceptsBiological ageModifiable health behaviorsModifiable risk factorsLife expectancySex-specific changesNHANES IVMedication useNHANES IIIRisk factorsDegree of improvementHealth behaviorsOlder groupOlder adultsPace of agingAgeSex groupsGreater declineGreater improvementChronological ageContribution of changesHealthExpectancy
2017
Biological Age, Not Chronological Age, Is Associated with Late-Life Depression
Brown PJ, Wall MM, Chen C, Levine ME, Yaffe K, Roose SP, Rutherford BR. Biological Age, Not Chronological Age, Is Associated with Late-Life Depression. The Journals Of Gerontology Series A 2017, 73: 1370-1376. PMID: 28958059, PMCID: PMC6132120, DOI: 10.1093/gerona/glx162.Peer-Reviewed Original ResearchConceptsLate-life depressionCES-D scoresDepressive symptomsBaseline CES-D scoreBiological ageChronological ageCovariate-adjusted regression modelsOlder biological ageEpidemiologic Studies Depression ScaleSignificant depressive symptomsBody Composition StudyMean chronological ageAge-associated changesNumerous physiological systemsAge-related processesKidney functioningLife depressionDepression ScaleDepression groupBrain disordersHealth AgingLongitudinal associationsSymptomsAgeRegression modelsContemporaneous Social Environment and the Architecture of Late-Life Gene Expression Profiles
Levine ME, Crimmins EM, Weir DR, Cole SW. Contemporaneous Social Environment and the Architecture of Late-Life Gene Expression Profiles. American Journal Of Epidemiology 2017, 186: 503-509. PMID: 28911009, PMCID: PMC5860329, DOI: 10.1093/aje/kwx147.Peer-Reviewed Original ResearchConceptsTranscriptional responseGene expression programsGene regulation pathwaysBioinformatics-based approachGene expression profilesTranscription factor activationGene expression levelsExpression programsLow socioeconomic statusRegulation pathwaysExpression profilesStress response systemNeuroendocrine signalingFactor activationAntiviral responseExpression levelsSocioeconomic statusPhysiological changesDistinct patternsChronic activationLong-term healthActivationGenesSignalingBiologyGenetic architecture of epigenetic and neuronal ageing rates in human brain regions
Lu AT, Hannon E, Levine ME, Crimmins EM, Lunnon K, Mill J, Geschwind DH, Horvath S. Genetic architecture of epigenetic and neuronal ageing rates in human brain regions. Nature Communications 2017, 8: 15353. PMID: 28516910, PMCID: PMC5454371, DOI: 10.1038/ncomms15353.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAged, 80 and overAgingBrainBrain MappingCalcium-Binding ProteinsChildChild, PreschoolCognitive DysfunctionDNA MethylationEpigenesis, GeneticFemaleGenome, HumanGenome-Wide Association StudyHumansInfantMaleMiddle AgedNerve Tissue ProteinsNeurodegenerative DiseasesNeuronsQuantitative Trait LociConceptsGenome-wide association studiesCis-expression quantitative trait lociGenome-wide significant lociProportion of neuronsQuantitative trait lociEpigenetic aging ratesDNA methylation-based biomarkersEpigenetic agingMethylation-based biomarkersGenetic architectureTrait lociSignificant lociAssociation studiesBrain regionsAge-related macular degenerationType 2 diabetesAging rateGenesLociHuman brain regionsUlcerative colitisWaist circumferenceMacular degenerationParkinson's diseaseBrain samplesEpigenetic 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
An epigenetic clock analysis of race/ethnicity, sex, and coronary heart disease
Horvath S, Gurven M, Levine ME, Trumble BC, Kaplan H, Allayee H, Ritz BR, Chen B, Lu AT, Rickabaugh TM, Jamieson BD, Sun D, Li S, Chen W, Quintana-Murci L, Fagny M, Kobor MS, Tsao PS, Reiner AP, Edlefsen KL, Absher D, Assimes TL. An epigenetic clock analysis of race/ethnicity, sex, and coronary heart disease. Genome Biology 2016, 17: 171. PMID: 27511193, PMCID: PMC4980791, DOI: 10.1186/s13059-016-1030-0.Peer-Reviewed Original ResearchConceptsMortality rateRace/ethnicityRisk factorsTraditional cardio-metabolic risk factorsCardio-metabolic risk factorsCHD risk factorsCoronary heart diseaseCardio-metabolic diseasesEpigenetic clock analysisIntrinsic epigenetic age accelerationAfrican AmericansEpigenetic aging ratesLonger life expectancyCHD outcomesOlder African AmericansHeart diseaseHigh burdenEpigenetic age accelerationLower mortalityDifferent mortality ratesBrain samplesEthnic groupsBrain tissueBloodSocioeconomic differencesEpigenetic 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 accelerationEducation and Psychosocial Functioning Among Older Adults: 4-Year Change in Sense of Control and Hopelessness
Mitchell UA, Ailshire JA, Brown LL, Levine ME, Crimmins EM. Education and Psychosocial Functioning Among Older Adults: 4-Year Change in Sense of Control and Hopelessness. The Journals Of Gerontology Series B 2016, 73: 849-859. PMID: 27013537, PMCID: PMC6283311, DOI: 10.1093/geronb/gbw031.Peer-Reviewed Original Research
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