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1、Free-RadicalTheoryofAgingIncreasingtheFunctionalLifeSpanDENHAMHARMANUniversityofNebraskaCollegeofMedicineOmaha,Nebraska68198-4635INTRODUCTIONAgingistheaccumulationofdiverseadversechanges1+2-agingchanges-thatincreasetheriskofdeath.Theseareresponsibleforboththecommonlyrecognize
2、dsequentialalterationsthataccompanyadvancingagebeyondtheearlyperiodoflifeandtheprogressiveincreasesinthechanceofdiseaseanddeathassociatedwiththem.Agingchangescanbeattributedtodevelopment,geneticdefects,theenviron-ment,disease,andaninbornprocess,theagingprocess.Thechanceofdeat
3、h-readilyavailablefromvitalstatisticsdata-servesasameasureofthenumberofaccumulatedagingchanges,i.e.,ofphysiologicage,andtherateofchangeofthisparameterwithtimeastherateofaging.Conventionalmeansofdecreasingthechanceofdeathinapopulationarebecomingincreasinglyfutile.Thisisillustr
4、atedinFIGURE1bythecurvesofthelogarithmofthechanceofdeathversusageforSwedishfemalesforvariousperiodsfrom1751to1988;astraightlinerepresentsexponentialincreaseswithage.Thechanceofdeath1-5dropsprecipitouslyforashortperiodafterbirth,largelyduetodeathsrelatedtodevelopmentandbirth,t
5、oreachaminimumaroundpuberty.Itthenincreaseswithageasdeleteriouseffectsofothercontributors,e.g.,environmentanddisease,tothechanceofdeathincrease.Theseadverseeffectseventuallygiverisetothesequentialchangesassociatedwithagingandtheexponentialincreasesinthechanceofdeath;thelatter
6、ensuresthatfewindividualsreach100yearsandthatnonelivebeyondabout115years6AslivingconditionsimprovedinSweden,includingbetterhousing,nutrition,medicalcare,publichealthfacilitiesandaccidentprevention,thechanceofdeathdecreased-moresointheyoungthanintheold-whilethestraightterminal
7、portionofthecurveofthechanceofdeathversusagemovedessentiallyparalleltoitselfandstartedatprogressivelylowerages,reachinganageofabout28today.Todaythechancesfordeathforbothsexes,inSwedenandtheotherdevelopedcountries,arenearlimitingOnly2-3%ofacohortdiebeforeage28,whileaveragelife
8、expectanciesatbirth-determinedbythechancesfordeath-approachplateauva
