Chapter 12 Apoptosis

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1、Chapter12CellAgingandApoptosis1.Cellaging/senescenceCellagingistheuniversal,graduallyirreversiblechangesinstructureandfunctionofacell.Normalhumanfibroblasts(left)andfibroblastsshowingasenescentmorphology(threecellsontheright).Noticethecommonelongatedmorphologyofsenescentcells.Hayflickli

2、mitationHayflicklimitationisthenumberoftimesacellwilldividebeforeitstopsduetothetelomerereachingacriticallength.Thelifespanofcellsislimited.Thepotentialofcellproliferationwouldlosegraduallyfollowingvigorouscelldivision,eventuallyleadingtothesenescenceanddeathofcells.Somecancerandvirus-i

3、nfectedcellsarenotrestricted,seeminglywithaninfinitedoublingpotential,andarethus“immortal”celllines.Lifespanofcellsinvitroculture¾Thelifetimeofcellsculturedinvitrodependsonthenumbersofserialsubcultivation,ratherthanthedaysofculture;¾Thenumberofsubculturingcellsinvitropositivelycorrelate

4、swiththelifespanofthedonorspecies;¾Thenumberofsubculturingcellsinvitroculturednegativelycorrelateswiththeageofdonor.Characteristicsofcellaging¾Slowdownofcellproliferation¾Increaseinresidualbodiesassociatedwithagepigments¾Increaseinthelikelihoodofneoplastictransformation¾Decreaseincellsi

5、zeassociatedwithincreaseinnucleus-cytoplasmratio¾Invaginationofnuclearmembraneandpyknosisofchromatin¾DisperseddistributionofrER¾Increaseinnumberanddecreaseinsizeofmitochondrion¾AlteredgeneexpressionTheoriesofcellagingTheprocessofagingiscomplex,andmayderivefromavarietyofdifferentmechanis

6、msandexistforavarietyofdifferentreasons.Theoriesthatexplainagingcangenerallybedividedbetweentheprogrammedanderrortheoriesofaging.Programmedtheoriesimplythatagingisregulatedbybiologicalclocksoperatingthroughoutthelifespan.Thisregulationwoulddependonchangesingeneexpressionthataffectthesys

7、temsresponsibleformaintenance,repairanddefenseresponses.Errortheoriesblameenvironmentalinsultstolivingorganismsthatinducecumulativedamageatvariouslevelsasthecauseofaging(e.g.,DNAdamage,oxygenradicals,cross-linking).Theoriesofcellaging¾Freeradicaltheory¾mtDNAmutationtheory¾Telom