2021
Aging 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 Statements
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 ResearchMeSH KeywordsAge DistributionAgedAged, 80 and overCohort StudiesGeriatricsHumansIncidenceLongitudinal StudiesMiddle AgedMortalityPrevalenceConceptsMyocardial 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 individuals
2017
Contemporaneous 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 acceleration
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 ResearchMeSH KeywordsAgedAged, 80 and overAlzheimer DiseaseAmyloidogenic ProteinsBiomarkersEpigenesis, GeneticFemaleHumansMalePlaque, AmyloidPrefrontal CortexConceptsCognitive 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 loadA 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 scoreResistanceLoneliness, eudaimonia, and the human conserved transcriptional response to adversity
Cole SW, Levine ME, Arevalo JM, Ma J, Weir DR, Crimmins EM. Loneliness, eudaimonia, and the human conserved transcriptional response to adversity. Psychoneuroendocrinology 2015, 62: 11-17. PMID: 26246388, PMCID: PMC4637182, DOI: 10.1016/j.psyneuen.2015.07.001.Peer-Reviewed Original ResearchConceptsRisk factorsBehavioral health risk factorsCommunity-dwelling older adultsPeripheral blood samplesPro-inflammatory genesHealth risk factorsSocial isolationMixed effect linear model analysesChronic social adversityCTRA gene expressionStrength of associationGene expressionPsychological resilience factorsResilience factorsAdversity factorsBlood samplesIncreased expressionMeasures of lonelinessOlder adultsSocial adversityAnxiety symptomsUS HealthLinear model analysisRetirement StudyHealth risksChildhood and later life stressors and increased inflammatory gene expression at older ages
Levine ME, Cole SW, Weir DR, Crimmins EM. Childhood and later life stressors and increased inflammatory gene expression at older ages. Social Science & Medicine 2015, 130: 16-22. PMID: 25658624, PMCID: PMC4394113, DOI: 10.1016/j.socscimed.2015.01.030.Peer-Reviewed Original ResearchConceptsChildhood traumaLow SESPro-inflammatory gene expressionProinflammatory gene expression levelsEarly lifeLater lifeLife health outcomesInflammatory gene expressionLater-life health outcomesHigh riskInflammatory genesAdulthood adversityChildhood healthHealth outcomesAdverse experiencesAdult traumaOlder ageTraumaLate-life stressorsGene expressionElevated levelsFuture healthComposite scoreLife stressorsChildhood
2014
Evidence of accelerated aging among African Americans and its implications for mortality
Levine ME, Crimmins EM. Evidence of accelerated aging among African Americans and its implications for mortality. Social Science & Medicine 2014, 118: 27-32. PMID: 25086423, PMCID: PMC4197001, DOI: 10.1016/j.socscimed.2014.07.022.Peer-Reviewed Original ResearchConceptsBiological ageNutrition Examination SurveyThird National HealthHigher biological ageMajor age-related diseasesChronological ageCancer mortalityExamination SurveyAge-related diseasesNational HealthEarly deathAge 60Age 30MortalityAge accountRacial disparitiesAgePremature declineWhite participantsAfrican AmericansCurrent studyMortality selectionHealthWhitesAging processA Polygenic Risk Score Associated with Measures of Depressive Symptoms Among Older Adults
Levine ME, Crimmins EM, Prescott CA, Phillips D, Arpawong TE, Lee J. A Polygenic Risk Score Associated with Measures of Depressive Symptoms Among Older Adults. Biodemography And Social Biology 2014, 60: 199-211. PMID: 25343367, PMCID: PMC4298361, DOI: 10.1080/19485565.2014.952705.Peer-Reviewed Original ResearchConceptsHigher CESD scoresPolygenic risk scoresCESD scoresDepressive symptomsEpidemiological Studies Depression Scale scoreWeighted polygenic risk scoreLogistic regression modelsReplication sampleMultinomial logistic regression modelsRisk scoreScale scoreDiscovery setIndividual susceptibilitySymptomsOlder adultsAnalytic sampleGenetic riskSingle nucleotide polymorphismsScoresRetirement StudyRegression modelsDepressionPercent increaseAssociationHigh levelsNot All Smokers Die Young: A Model for Hidden Heterogeneity within the Human Population
Levine M, Crimmins E. Not All Smokers Die Young: A Model for Hidden Heterogeneity within the Human Population. PLOS ONE 2014, 9: e87403. PMID: 24520332, PMCID: PMC3919713, DOI: 10.1371/journal.pone.0087403.Peer-Reviewed Original ResearchConceptsLung function levelsProportional hazards modelMost age groupsCurrent smokersSimilar inflammationNHANES IIIMortality riskSmokersAge 50Age 80Hazards modelExtreme old ageAge groupsMeans of biomarkersOlder ageResilient phenotypeHigh exposureFunction levelUnderstanding of heterogeneityDamaging factorsLongevity extensionAging processBiological advantagesSmokingInflammation
2012
Be Well
Kogan AC, Gonzalez J, Hart B, Halloran S, Thomason B, Levine M, Enguidanos S. Be Well. Journal Of Applied Gerontology 2012, 32: 889-901. PMID: 25474803, PMCID: PMC5923899, DOI: 10.1177/0733464812440043.Peer-Reviewed Original ResearchConceptsCommunity-based senior centersMore emergency department visitsOlder adultsCommunity-dwelling older adultsEmergency department visitsLow-impact exerciseMultiple chronic conditionsNutritional education interventionDepartment visitsHospital admissionNutritional counselingChronic conditionsWeekly exerciseWeight managementCohort designPhysical activityHigh riskEducation interventionWeight lossGood nutritionFitness programPerson interviewsSenior centersDepressionFitness tests