13 cell aging and apoptosis

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1、Chapter13Cellsenescence(Cellsenescence(细胞衰老细胞衰老))andapoptosis(andapoptosis(细胞凋亡细胞凋亡))I.Cellsenescenceorcellaging1.EarlyresearchesaboutcellularagingTheworkofEbelingandCarrelhadsuggestedthatcellsthemselvesdidnotageand,tothecontrary,agingwasaphenomenono

2、fcellularinteraction.什么是衰老？什么是衰老？衰老是生物学最热门的研究领域之一。衰老的最新定义为：一个细胞或一个个体生理机能和代谢逐渐恶化的过程。这一过程在正常细胞应对多种内源和外源压力时被激活。端粒“脱帽”,DNA损伤,细胞衰老氧化应激,致癌基因活化，其它2.HayflickLimitation(1)Normalcellscannotdivideindefinitely—proliferativelifespanInbiology,senescenceisthes

3、tateorprocessofaging.Cellularsenescenceisaphenomenonwhereisolatedcellsdemonstratealimitedabilitytodivideinaculturedish,whileorganismalsenescenceistheagingoforganisms.Youngcellsafter20populationdoublings(PDs)Oldercellsenteringasenescentphaseafter50pop

4、ulationdoublingsTheHayflickLimitation(2)Proliferativelifespanisrelatedtothedonor’sageFibroblastHumanMiddleOldembryoagedDoubling40-60202-4times(3)Proliferativelifespaniscorrelatedtothespecieslifespan物种寿命(年)培养细胞传代数海龟17590-125小鼠3.514-28(4)Cellsenescence

5、isdeterminedbyitselfYounggirlOldmanCo-culturedCellCytoplastDividingornotFusionSenescencehappensatthelevelsofmolecule,cell,organortissueandorganismThefactorsresultinginsenescenceinclude:—IntrinsicfactorsGeneticfactorsEpigeneticfactors—Extrinsicfactors

6、Environmentalfactors3.CellsenescenceinvivoInvivo:Cellsenescenceisaffectedbybothitselfandenvironment.Evenstemcellswillbesenescent.4.CharacteristicsofagedcellSenescentphenotype:alarge,flatmorphology,ahighfrequencyofnuclearabnormalities.ß-galactosidase:

7、Activityincrease(pH6.0)SenescentcellsundergothreephenotypicchangesSenescentcellsundergothreephenotypicchanges.▪Cellirreversiblyarrestgrowth▪Cellacquireresistancetoapoptoticdeath▪CellacquirealtereddifferentiatedfunctionsII.MolecularmechanismsaboutII.M

8、olecularmechanismsaboutcellsenescencecellsenescenceReplicativesenescenceandtelomereshortening复制性衰老和端粒缩短MitochondriaageingReactiveoxygenspecies(ROS)活性氧基团TheevolutionarytheoriesofsenescenceSenescenceprocessesandapoptosisEpigeneticregulationofsene