Genetic Determinants of Human Health Span and Life Span Progress and New Opportunities 英文参考文献.docVIP

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Genetic Determinants of Human Health Span and Life Span Progress and New Opportunities 英文参考文献.doc

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Genetic Determinants of Human Health Span and Life Span Progress and New Opportunities 英文参考文献

Review GeneticDeterminantsofHumanHealthSpan andLifeSpan:ProgressandNew Opportunities George M.Martin*,Aviv Bergman, Nir Barzilai ABSTRACT Second,whilewehavelearnedagreatdealabout developmentalbiologyfromworms,?ies,andmice,thereisa paucityofdetailedinformationonthepathophysiologyof agingandoftheirvariationsamonggeneticallyheterogeneous wild-typepopulations,particularlyinwormsand?ies.In contrast,thereisavastliteratureontheseandallotheraspects ofhumanbiology,includingremarkableprogressinhuman genetics(Table1).Moreover,physicianshaveprovided detailedcharacterizationsoflate-lifedisabilitiesanddiseases inhumanpopulations(Table2).Third,additionalandunique DNAsequenceshaveevolvedinHomosapiens,includingrapidly evolvingfunctionallysigni?cantintronicsequencesthat distinguishusfromournearestrelative,thecommon chimpanzee(Pantroglodytes),whoselifespanisapproximately halfthatofhumans)[6,7](see,however,evidenceofasingle outlierwholivedtoage74,/ investigationsspecies/biblio.php?idofmodel?0505).organismsFourth,havemostutilizedgerontologicalhighlyinbred organismstypicallyexaminedinasingleenvironment.By contrast,humangeneticists,particularlymedicalgeneticists, seetheresultsofahugerangeofgene–geneandgene– environmentalinteractions.Theythereforehaveconsiderable opportunitiestocontributetoourunderstandingofwhy individualpatternsofagingexhibitsuchsubstantial W ereviewthreeapproachestothegeneticanalysis ofthebiologyandpathobiologyofhumanaging. The?rstandsofarthebest-developedisthe searchforthebiochemicalgeneticbasisofvarying susceptibilitiestomajorgeriatricdisorders.Theseincludea rangeofprogeroidsyndromes.Collectively,theytellusmuch aboutthegeneticsofhealthspan.Giventhatthemajorrisk factorforvirtuallyallgeriatricdisordersisbiologicalaging, theymayalsoserveasmarkersforthestudyofintrinsic biologicalaging.Thesecondapproachseekstoidentifyallelic contributionstoexceptionallylonglifespans.Whilelinkage toalocusonChromosome4hasnotbeencon?rmed, associationstudieshaverevealedanumberofsigni?cant po