More than bad luck: Cancer and aging are linked to replication-driven changes to the epigenome
Minteer C, Thrush K, Gonzalez J, Niimi P, Rozenblit M, Rozowsky J, Liu J, Frank M, McCabe T, Sehgal R, Higgins-Chen A, Hofstatter E, Pusztai L, Beckman K, Gerstein M, Levine M. More than bad luck: Cancer and aging are linked to replication-driven changes to the epigenome. Science Advances 2023, 9: eadf4163. PMID: 37467337, PMCID: PMC10355820, DOI: 10.1126/sciadv.adf4163.Peer-Reviewed Original ResearchConceptsStem cell divisionImmortalized human cellsTissue-specific cancer riskTumorigenic stateCell divisionDNA methylationEpigenetic changesAge-related accumulationHuman cellsMultiple tissuesSomatic mutationsClinical tissuesTissue differencesEpigenomeCellsTissueNormal tissuesMethylationMutationsReplicationNormal breast tissueSignaturesVitroAccumulationDivisionOxPhos 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