2024
Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk
Brandhorst S, Levine M, Wei M, Shelehchi M, Morgan T, Nayak K, Dorff T, Hong K, Crimmins E, Cohen P, Longo V. Fasting-mimicking diet causes hepatic and blood markers changes indicating reduced biological age and disease risk. Nature Communications 2024, 15: 1309. PMID: 38378685, PMCID: PMC10879164, DOI: 10.1038/s41467-024-45260-9.Peer-Reviewed Original ResearchConceptsMultiple cardiometabolic risk factorsAssociated with reduced insulin resistanceCardiometabolic risk factorsFasting-mimicking dietImmune system agingRandomized clinical trialsAnalysis of blood samplesAutoimmune cellsBiological ageClinical trialsReduce inflammationMarker changesRisk factorsHepatic fatInsulin resistanceAdult study participantsBlood samplesNormal cellsWeight lossReducing biological ageBiomarker of biological agingDamaged cellsStudy participantsDisease riskAge
2023
OxPhos defects cause hypermetabolism and reduce lifespan in cells and in patients with mitochondrial diseases
Sturm G, Karan K, Monzel A, Santhanam B, Taivassalo T, Bris C, Ware S, Cross M, Towheed A, Higgins-Chen A, McManus M, Cardenas A, Lin J, Epel E, Rahman S, Vissing J, Grassi B, Levine M, Horvath S, Haller R, Lenaers G, Wallace D, St-Onge M, Tavazoie S, Procaccio V, Kaufman B, Seifert E, Hirano M, Picard M. OxPhos defects cause hypermetabolism and reduce lifespan in cells and in patients with mitochondrial diseases. Communications Biology 2023, 6: 22. PMID: 36635485, PMCID: PMC9837150, DOI: 10.1038/s42003-022-04303-x.Peer-Reviewed Original ResearchConceptsIntegrated stress responseOXPHOS defectsMitochondrial diseaseCellular energy expenditureMitochondrial DNA instabilityPatient-derived fibroblastsMitochondrial oxidative phosphorylationCell divisionExtracellular secretionOxidative phosphorylationStress responseDNA instabilityMechanistic basisEnergetic costEpigenetic agingGeneral mechanismOXPHOSBiological agingExcess energy expenditurePotential mechanismsEnergy expenditureCellsMulti-system disorderMetabokinesRNAseq
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 ProjectLife course traumas and cardiovascular disease—the mediating role of accelerated aging
Cao X, Zhang J, Ma C, Li X, Kuo C, Levine ME, Hu G, Allore H, Chen X, Wu X, Liu Z. Life course traumas and cardiovascular disease—the mediating role of accelerated aging. Annals Of The New York Academy Of Sciences 2022, 1515: 208-218. PMID: 35725988, PMCID: PMC10145586, DOI: 10.1111/nyas.14843.Peer-Reviewed Original ResearchEvidence 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 agingEpigenetic aging of the demographically non-aging naked mole-rat
Kerepesi C, Meer MV, Ablaeva J, Amoroso VG, Lee SG, Zhang B, Gerashchenko MV, Trapp A, Yim SH, Lu AT, Levine ME, Seluanov A, Horvath S, Park TJ, Gorbunova V, Gladyshev VN. Epigenetic aging of the demographically non-aging naked mole-rat. Nature Communications 2022, 13: 355. PMID: 35039495, PMCID: PMC8763950, DOI: 10.1038/s41467-022-27959-9.Peer-Reviewed Original Research
2021
Extending human healthspan and longevity: a symposium report
DeVito LM, Barzilai N, Cuervo AM, Niedernhofer LJ, Milman S, Levine M, Promislow D, Ferrucci L, Kuchel GA, Mannick J, Justice J, Gonzales MM, Kirkland JL, Cohen P, Campisi J. Extending human healthspan and longevity: a symposium report. Annals Of The New York Academy Of Sciences 2021, 1507: 70-83. PMID: 34498278, PMCID: PMC10231756, DOI: 10.1111/nyas.14681.Peer-Reviewed Original ResearchConceptsAge-related diseasesEarly-stage clinical trialsField of geroscienceReduction of morbidityBiological agingEnd of lifeClinical trialsNovel agentsClinical developmentGeroscience hypothesisFDA approvalDrug evaluationMultiple disordersTherapyDiseaseSymposium reportConcept studyHuman healthspanHealthspanAging processSignificant barriersMorbidityDysfunctionAgingTrialsThe 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 tissuesGenetic associations for two biological age measures point to distinct aging phenotypes
Kuo C, Pilling LC, Liu Z, Atkins JL, Levine ME. Genetic associations for two biological age measures point to distinct aging phenotypes. Aging Cell 2021, 20: e13376. PMID: 34038024, PMCID: PMC8208797, DOI: 10.1111/acel.13376.Peer-Reviewed Original ResearchConceptsGenome-wide association scansAssociation scanEuropean descent participantsHomeostasis pathwaysPathway enrichmentAging phenotypesGenesGenetic associationCell functionStrong signalBiological age measuresPathwayUK BiobankGenetic predispositionClinical biochemistry markersImmune systemEnrichmentSNPsPhenotypeAPOE geneLipidsPredispositionDomainMarkersEpigenetic 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 fatigueInflammationA systematic review of biological, social and environmental factors associated with epigenetic clock acceleration
Oblak L, van der Zaag J, Higgins-Chen AT, Levine ME, Boks MP. A systematic review of biological, social and environmental factors associated with epigenetic clock acceleration. Ageing Research Reviews 2021, 69: 101348. PMID: 33930583, DOI: 10.1016/j.arr.2021.101348.Peer-Reviewed Original ResearchAssociation 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
Reprogramming to recover youthful epigenetic information and restore vision
Lu Y, Brommer B, Tian X, Krishnan A, Meer M, Wang C, Vera DL, Zeng Q, Yu D, Bonkowski MS, Yang JH, Zhou S, Hoffmann EM, Karg MM, Schultz MB, Kane AE, Davidsohn N, Korobkina E, Chwalek K, Rajman LA, Church GM, Hochedlinger K, Gladyshev VN, Horvath S, Levine ME, Gregory-Ksander MS, Ksander BR, He Z, Sinclair DA. Reprogramming to recover youthful epigenetic information and restore vision. Nature 2020, 588: 124-129. PMID: 33268865, PMCID: PMC7752134, DOI: 10.1038/s41586-020-2975-4.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsAxonsCell Line, TumorCell SurvivalCellular ReprogrammingDependovirusDioxygenasesDisease Models, AnimalDNA MethylationDNA-Binding ProteinsEpigenesis, GeneticEyeFemaleGenetic VectorsGlaucomaHumansKruppel-Like Factor 4Kruppel-Like Transcription FactorsMiceMice, Inbred C57BLNerve RegenerationOctamer Transcription Factor-3Optic Nerve InjuriesProto-Oncogene ProteinsRetinal Ganglion CellsSOXB1 Transcription FactorsTranscriptomeVision, OcularConceptsDNA methylation patternsMethylation patternsTissue functionCentral nervous systemGene expression patternsCause of agingEpigenetic noiseEpigenetic informationDNA methylationEctopic expressionExpression patternsKLF4 geneMouse retinal ganglion cellsMammalian tissuesRetinal ganglion cellsAged miceGanglion cellsVision lossTissue dysfunctionMouse modelCNS tissueAxon regenerationNervous systemDegenerative processOlder individualsUnderlying 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 lackPathwayCpGMetabolismVasomotor 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 GrimAgeSymptomsSchizophrenia 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 MortalityAssessment of Epigenetic Clocks as Biomarkers of Aging in Basic and Population Research
Levine ME. Assessment of Epigenetic Clocks as Biomarkers of Aging in Basic and Population Research. The Journals Of Gerontology Series A 2020, 75: 463-465. PMID: 31995162, PMCID: PMC7328198, DOI: 10.1093/gerona/glaa021.Peer-Reviewed Original Research