Metabolic Rate Regulates L1 Longevity in C. elegans 英文参考文献.docVIP

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Metabolic Rate Regulates L1 Longevity in C. elegans 英文参考文献.doc

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Metabolic Rate Regulates L1 Longevity in C. elegans 英文参考文献

MetabolicRateRegulatesL1LongevityinC.elegans InhwanLee1,AmberHendrix1,JeonghoKim2,JenniferYoshimoto3,Young-JaiYou1* 1Departments of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, Virginia, United States of America, 2Department of Biological Science,InhaUniversity,Incheon,Korea,3DepartmentofInternalMedicine,UniversityofMichigan,AnnArbor,Michigan,UnitedStatesofAmerica Abstract Animalshavetocopewithstarvation.Themolecularmechanismsbywhichanimalssurvivelong-termstarvation,however, arenotclearlyunderstood.Whentheyhatchwithoutfood,C.elegansarrestsdevelopmentatthefirstlarvalstage(L1)and survives more than two weeks. Here we show that the survival span of arrested L1s, which we call L1 longevity, is a starvation response regulated by metabolic rate during starvation. A high rate of metabolism shortens the L1 survival span,whereasalowrateofmetabolismlengthensit.Thelongerwormsarestarved,theslowertheygrowoncetheyarefed, suggestingthatL1arresthasmetaboliccosts.Furthermore,mutantsofgenesthatregulatemetabolismshowalteredL1 longevity. Among them, we found that AMP-dependent protein kinase (AMPK), as a key energy sensor, regulates L1 longevitybyregulatingthismetabolicarrest.OurresultssuggestthatL1longevityisdeterminedbymetabolicrateandthat AMPKasamasterregulatorofmetabolismcontrolsthisarrestsothattheanimalssurvivelong-termstarvation. Citation: Lee I, Hendrix A, Kim J, Yoshimoto J, You Y-J (2012) Metabolic Rate Regulates L1 Longevity in C. elegans. PLoS ONE 7(9): e44720. doi:10.1371/ journal.pone.0044720 Editor:PatrickCallaerts,VIBKatholiekeUniversiteitLeuven,Belgium ReceivedFebruary27,2012;AcceptedAugust9,2012;PublishedSeptember6,2012 Copyright:?2012Leeetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricted use,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ILandYYreceivedsupportfromtheAmericanHeartAssociationgrant(09SDG2150070).Noadditio