An Engineering Approach to Extending Lifespan in C. elegans 英文参考文献.docVIP

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An Engineering Approach to Extending Lifespan in C. elegans 英文参考文献.doc

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An Engineering Approach to Extending Lifespan in C. elegans 英文参考文献

AnEngineeringApproachtoExtendingLifespaninC. elegans DrorSagi,StuartK.Kim* DepartmentsofGeneticsandDevelopmentalBiology,StanfordUniversityMedicalCenter,Stanford,California,UnitedStatesofAmerica Abstract WehavetakenanengineeringapproachtoextendingthelifespanofCaenorhabditiselegans.Agingstandsoutasacomplex trait,becauseeventsthatoccurinoldanimalsarenotunderstrongnaturalselection.Asaresult,lifespancanbelengthened rationally using bioengineering to modulate gene expression or to add exogenous components. Here, we engineered longer lifespan by expressing genes from zebrafish encoding molecular functions not normally present in worms. Additionally,weextendedlifespanbyincreasingtheactivityoffourendogenouswormagingpathways.Next,weuseda modularapproachtoextendlifespanbycombiningcomponents.Finally,weusedcell-andworm-basedassaystoanalyze changesincellphysiologyandasarapidmeanstoevaluatewhethermulti-componenttransgeniclineswerelikelytohave extended longevity. Using engineering to add novel functions and to tune endogenous functions provides a new frameworkforlifespanextensionthatgoesbeyondtheconstraintsofthewormgenome. Citation:SagiD,KimSK(2012)AnEngineeringApproachtoExtendingLifespaninC.elegans.PLoSGenet8(6):e1002780.doi:10.1371/journal.pgen.1002780 Editor:GaryRuvkun, MassachusettsGeneralHospitalandHarvardMedicalSchool,UnitedStatesofAmerica ReceivedFebruary14,2012;AcceptedMay8,2012;PublishedJune21,2012 Copyright:?2012Sagi,Kim.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricted use,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisworkwasfundedbyR01AG025941toSKKandtheLarryL.HillblomfellowshiptoDS.Thefundershadnoroleinstudydesign,datacollectionand analysis,decisiontopublish,orpreparationofthemanuscript. CompetingInterests:Theauthorshavedeclaredthatnocompetinginterestsexist. *E-mail:stuartkm@ Introduction WechosetouseC.elegansbecauseithasashortlifespanoftwo weeksandas