氧化应激与衰老研究进展-原慧萍

··《》2015135※10073081061120527813704458147240881400790Z1211070025120582013020082012BAI10B01※【】。DNA。ＲOSＲOS、。【】doi10.3969/j.issn.1672－4860.2015.05.004OxidativestressandagingYUANHuipingYANGZe.InstituteofgeriatricsChineseministryofhealthBeijingHospitalBeijing100730China．【Abstract】Agingisabiologicalprocesswithverycomplexmechanismwhichinvolvingthestructureandfunctionchangesofthevarioussystem.Theoxidativestresstheoryclaimsthatlowdoseofreactiveoxygenspeciescanstimulatethebodyprotectiveresponseanddelaytheagingprocessintheearlystageofsenescencewhentheaging-relatedoxidativedamagewascumulatedtoohugetobeeliminatedwithagetheseＲOSwillexacerbateaging-relatedoxidativedamageandacceleratetheagingprocess.InsteadofreducingcellularＲOSmerelymaintainingtheＲOSwithinanappropriatephysiologicallevelwillbemoreimportantindiseasepreventionandagingdelay．【Keywords】oxidativestressagingfreeradicalsreactiveoxygenspecies。。1201。。。。、、、、、。2。。。1955Dr.Har-man1956《》3“”。。①。②ＲOS4。③。1.“”。－O－2、H－、Cl－、CH3－、－OH、ＲOO－、NO－、－ONOO－。O2。H2O21O2ＲOS。、、、、。·41·《》2015135··。、、5。2.。2.1①γ-α-、、、、②、、、③、。2.2reactiveoxygenspeciesＲOS。90%。1%～4%ATP。NADPHP450ＲOS。、、。3.。。VitAVitBVitCVitEβ-、、、SOD、CAT、GSH-Px、POD、Q10DNADNAC·O2－H2O2。4.1990Sohal“”。ＲOSＲOS。DNA67。。、DNA、。。CMAP、、、。。。5.、3。HelmutSies“”8。。、、、、、9。5.1ＲOS。①。ⅠⅢⅣ10。②11。DNAmtDNAmtDNAＲOSATP。③12。5.2①。、DNA、。②。③mtDNAmtDNA。·51···《》2015135mtDNA。5.3DNA。。DNADNA。①DDＲDNAdamageresponseDNADDＲp53p2113。②κBNF-κBIκBNF-κB。IκBNF-κBDNA8p5314～16。③p38MAPKsMAPK－。VirginiaProbinBusulfanＲOSp38MAPKp38MAPKSB203580p1617JangＲOSp38p1618。/p38MAPKs。④microＲNAmiＲNAＲNA20～25ntmＲNA。miＲNA1920。DavidBaltimoreMirc19microＲNA-212/132cluster21。HSCMirc19microＲNA-212/132clusterMirc19。6.ＲOS22～24。ＲOSDNA。25。ＲOSＲOS2627。ＲOS23DNAＲOSＲOS。DNAＲOSＲOSDNADNA。7.。ＲOSＲOS。ＲOSＲOS、。1GelatoMC.Agingandimmunefunctionapossibleroleforgrowthhor-moneJ．HormＲes1996451－246－49．2SohalＲSOrrWC.TheredoxstresshypothesisofagingJ．FreeＲad-icBiolMed2012523539－555．3HarmanD.Agingatheorybasedonfreeradicalandradiationchemis-tryJ．JGerontol1956113298－300．4LeeHCWeiYH.Mitochondrialalterationscellularresponsetooxi-dativestressanddefectivedegradationofproteinsinagingJ．Biogero-ntology200124231－244．5StadtmanEＲBerlettBS.Ｒeactiveoxygen-mediatedproteinoxidationinaginganddiseaseJ．ChemＲesToxicol1997105485－494．6AshokBTAliＲ.TheagingparadoxfreeradicaltheoryofagingJ．ExpGerontol1999343293－303．7WorthamMHeLGyamfiMetal.ThetransitionfromfattylivertoNASHassociateswithSAMedepletionindb/dbmicefedamethioninecholine-deficientdietJ．DigDisSci200853102761－2774．8SiesHCadenasE.OxidativestressdamagetointactcellsandorgansJ．PhilosTransＲSocLondBBiolSci19853111152617－631．9JunqueiraVBBarrosSBChanSSetal.AgingandoxidativestressJ．MolAspectsMed2004251－25－16．10KwongLKSohalＲS.Age-relatedchangesinactivitiesofmitochon-drialelectrontransportcomplexesinvarioustissuesofthemouseJ．ArchBiochemBiophys2000373116－22．11ManczakMJungYParkBSetal.Time-courseofmitochondrialgeneexpressionsinmicebrainsimplicationsformitochondrialdys-functionoxidativedamageandcytochromecinagingJ．JNeuro-chem2005923494－504．12YokozawaTSatohAChoEJ.Ginsenoside-Ｒdattenuatesoxidativedamagerelatedtoaginginsenescence-acceleratedmiceJ．JPharmPharmacol2004561107－113．13ＲaiPOnderTTYoungJJetal.ContinuouseliminationofoxidizednucleotidesisnecessarytopreventrapidonsetofcellularsenescenceJ．ProcNatlAcadSciUSA20091061169－174．14PerkinsND.Integratingcell-signallingpathwayswithNF-kappaBandIKKfunctionJ．NatＲevMolCellBiol20078149－62．15BhattacharyyaSDudejaPKTobacmanJK.ＲOSHsp27andIKK-betamediatedextransodiumsulfateDSSactivationofIkappaBaNFkappaBandIL-8J．InflammBowelDis2009155673－683．16LeeMYWangYVanhouttePM.Senescenceofculturedporcinecoronaryarterialendothelialcellsisassociatedwithacceleratedoxida-tivestressandactivationofNFkBJ．JVascＲes2009474287－298．·61·《》2015135··17ProbinVWangYZhouD.Busulfan-inducedsenescenceisde-pendentonＲOSproductionupstreamoftheMAPKpathwayJ．FreeＲadicBiolMed200742121858－1865．18JangYYSharkisSJ.Alowlevelofreactiveoxygenspeciesselectsforprimitivehematopoieticstemcellsthatmayresideinthelow-oxy-genicnicheJ．Blood200711083056－3063．19BoehmMSlackF.AdevelopmentaltimingmicroＲNAanditstargetregulatelifespaninC.elegansJ．Science200531057561954－1957．20MeltonCJudsonＲLBlellochＲ.OpposingmicroＲNAfamiliesreg-ulateself-renewalinmouseembryonicstemcellsJ．Nature20104637281621－626．21MehtaAZhaoJLSinhaNetal.TheMicroＲNA-132andMicroＲ-NA-212ClusterＲegulatesHematopoieticStemCellMaintenanceandSurvivalwithAgebyBufferingFOXO3ExpressionJ．Immunity20154261021－1032．22GanWNieBShiFetal.Age-dependentincreasesintheoxida-tivedamageofDNAＲNAandtheirmetabolitesinnormalandse-nescence-acceleratedmiceanalyzedbyLC-MS/MSurinary8-ox-oguanosineasanovelbiomarkerofagingJ．FreeＲadicBiolMed20125291700－1707．23GredillaＲSanzALopez-TorresMetal.Caloricrestrictionde-creasesmitochondrialfreeradicalgenerationatcomplexIandlowersoxidativedamagetomitochondrialDNAintheratheartJ．FASEBJ20011591589－1591．24SanzAFernandez-AyalaDJStefanatosＲKetal.MitochondrialＲOSproductioncorrelateswithbutdoesnotdirectlyregulatelifespaninDrosophilaJ．AgingAlbanyNY201024200－223．25CopelandJMChoJLoTetal.