2021
Association 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 pandemic
2019
Midlife Study of the Louisville Twins: Connecting Cognitive Development to Biological and Cognitive Aging
Beam CR, Turkheimer E, Finkel D, Levine ME, Zandi E, Guterbock TM, Giangrande EJ, Ryan L, Pasquenza N, Davis DW. Midlife Study of the Louisville Twins: Connecting Cognitive Development to Biological and Cognitive Aging. Behavior Genetics 2019, 50: 73-83. PMID: 31820295, PMCID: PMC7033012, DOI: 10.1007/s10519-019-09983-6.Peer-Reviewed Original ResearchConceptsLouisville Twin StudyCognitive developmentCognitive agingCognitive functioningCognitive developmental trajectoriesLongitudinal Twin StudyTwin studiesPhysical health factorsEpisodic memoryLower biological ageFunctional ability measuresIQ measuresAbility measuresDevelopmental trajectoriesFSIQ scoresMidlife phaseMidlife studyPhysical functioningFunctional abilityChronological ageFunctioningPsychiatric outcomesSecond pilot studySecond studyIQChanging 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 individualsHumanin Prevents Age-Related Cognitive Decline in Mice and is Associated with Improved Cognitive Age in Humans
Yen K, Wan J, Mehta HH, Miller B, Christensen A, Levine ME, Salomon MP, Brandhorst S, Xiao J, Kim SJ, Navarrete G, Campo D, Harry GJ, Longo V, Pike CJ, Mack WJ, Hodis HN, Crimmins EM, Cohen P. Humanin Prevents Age-Related Cognitive Decline in Mice and is Associated with Improved Cognitive Age in Humans. Scientific Reports 2018, 8: 14212. PMID: 30242290, PMCID: PMC6154958, DOI: 10.1038/s41598-018-32616-7.Peer-Reviewed Original ResearchPredictors 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
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 ResearchMeSH KeywordsAgingBiological ClocksBiomarkersCohort StudiesFemaleHumansMaleMiddle AgedTelomere HomeostasisContemporaneous 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
Epigenetic 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 analysisDiseaseAgeEpitheliumEducation 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
DNA methylation age of blood predicts future onset of lung cancer in the women's health initiative
Levine ME, Hosgood HD, Chen B, Absher D, Assimes T, Horvath S. DNA methylation age of blood predicts future onset of lung cancer in the women's health initiative. Aging 2015, 7: 690-700. PMID: 26411804, PMCID: PMC4600626, DOI: 10.18632/aging.100809.Peer-Reviewed Original ResearchConceptsIntrinsic epigenetic age accelerationWomen's Health InitiativeLung cancer incidenceLung cancer susceptibilityLung cancerHealth initiativesCancer incidenceCox proportional hazards modelCancer susceptibilityLung cancer casesProportional hazards modelCurrent smokersAge-related declineAge-associated diseasesAge-related diseasesFuture onsetCancer casesCigarette smokeHazards modelUseful biomarkerEpigenetic age accelerationCandidate biomarkersOlder individualsDNA methylation ageGenotoxic carcinogensA Genetic Network Associated With Stress Resistance, Longevity, and Cancer in Humans
Levine ME, Crimmins EM. A Genetic Network Associated With Stress Resistance, Longevity, and Cancer in Humans. The Journals Of Gerontology Series A 2015, 71: 703-712. PMID: 26355015, PMCID: PMC4888382, DOI: 10.1093/gerona/glv141.Peer-Reviewed Original ResearchConceptsFunctional interaction networkSingle nucleotide polymorphismsStress resistanceNucleotide polymorphismsInteraction networksGenome-wide association studiesPathway analysisAssociation studiesPolygenic risk scoresNetworks AssociatedBiological networksHuman longevityUnique phenotypeHuman agingGenesPolymorphismLongevityPhenotypeInnate resilienceRisk scoreAge 52Threefold increasePathwayWeighted polygenic risk scoreResistanceEffects of Recent Stress and Variation in the Serotonin Transporter Polymorphism (5-HTTLPR) on Depressive Symptoms: A Repeated-Measures Study of Adults Age 50 and Older
Arpawong TE, Lee J, Phillips DF, Crimmins EM, Levine ME, Prescott CA. Effects of Recent Stress and Variation in the Serotonin Transporter Polymorphism (5-HTTLPR) on Depressive Symptoms: A Repeated-Measures Study of Adults Age 50 and Older. Behavior Genetics 2015, 46: 72-88. PMID: 26330209, PMCID: PMC4720538, DOI: 10.1007/s10519-015-9740-8.Peer-Reviewed Original ResearchMeSH KeywordsAgedAllelesDepressionDepressive DisorderEthnicityFemaleGene-Environment InteractionGenetic Association StudiesGenetic Predisposition to DiseaseHaplotypesHumansLife Change EventsMaleMiddle AgedPolymorphism, Single NucleotidePromoter Regions, GeneticSerotonin Plasma Membrane Transport ProteinsStress, PsychologicalConceptsDepressive symptomsU.S. population-based studyRecent stressOlder adultsStress-diathesis hypothesisPopulation-based studySerotonin transporter gene promoter regionSingle nucleotide polymorphismsDepressive symptom levelsPopulation-based sampleAdults age 50Race/ethnicityAge 50Repeated-measures designSerotonin transporter polymorphismDepressive symptomatologySymptomsOlder individualsSymptom levelsReverse causationTransporter polymorphismMeasures studyDifferential effectsShort alleleStressful events