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
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 tissues
2020
Underlying 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 GrimAgeSymptoms
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 Research
2015
Quantification of biological aging in young adults
Belsky DW, Caspi A, Houts R, Cohen HJ, Corcoran DL, Danese A, Harrington H, Israel S, Levine ME, Schaefer JD, Sugden K, Williams B, Yashin AI, Poulton R, Moffitt TE. Quantification of biological aging in young adults. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: e4104-e4110. PMID: 26150497, PMCID: PMC4522793, DOI: 10.1073/pnas.1506264112.Peer-Reviewed Original ResearchConceptsYoung adultsYoung humansSame chronological ageSelf-reported bad healthCognitive declineOlder adultsBiological agingYoung individualsChronological ageMultiple organ systemsBrain agingLongitudinal measuresAge-related diseasesChronic diseasesAdultsFourth decadeBirth cohortOrgan systemsWorse healthIndividualsRejuvenation therapyTime pointsHuman agingMultiple biomarkersTherapy