New Genes Tied to Endocrine, Metabolic, and Dietary Regulation of Lifespan from a Caenorhabditis elegans Genomic RNAi Screen 英文参考文献.docVIP

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New Genes Tied to Endocrine, Metabolic, and Dietary Regulation of Lifespan from a Caenorhabditis elegans Genomic RNAi Screen 英文参考文献.doc

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New Genes Tied to Endocrine, Metabolic, and Dietary Regulation of Lifespan from a Caenorhabditis elegans Genomic RNAi Screen 英文参考文献

NewGenesTiedtoEndocrine,Metabolic, andDietaryRegulationofLifespanfrom aCaenorhabditiselegansGenomicRNAiScreen Malene Hansen[,Ao-Lin Hsu[¤a,Andrew Dillin¤b,Cynthia Kenyon* DepartmentofBiochemistryandBiophysics,UniversityofCalifornia,SanFrancisco,California,UnitedStatesofAmerica Mostofourknowledgeabouttheregulationofagingcomesfrommutantsoriginallyisolatedforotherphenotypes.To askwhetherourcurrentviewofaginghasbeenaffectedbyselectionbias,andtodeepenourunderstandingofknown longevitypathways,wescreenedagenomicCaenorhabditiselegansRNAilibraryforclonesthatextendlifespan.We identified23newlongevitygenesaffectingsignaltransduction,thestressresponse,geneexpression,andmetabolism andassignedthesegenestospecificlongevitypathways.Ourmostimportantfindingsare(i)thatdietaryrestriction extendsC.elegans’lifespanbydown-regulatingexpressionofkeygenes,includingagenerequiredformethylationof manymacromolecules,(ii)thatintegrinsignalingislikelytoplayageneral,evolutionarilyconservedroleinlifespan regulation, and (iii) that specific lipophilic hormones may influence lifespan in a DAF-16/FOXO-dependent fashion. Surprisingly,ofthenewgenesthathaveconservedsequencedomains,onlyonecouldnotbeassociatedwithaknown longevitypathway.Thus,ourcurrentviewofthegeneticsofaginghasprobablynotbeendistortedsubstantiallyby selectionbias. Citation:HansenM,HsuAL,DillinA,KenyonC(2005)Newgenestiedtoendocrine,metabolic,anddietaryregulationoflifespanfromaCaenorhabditiselegansgenomicRNAi screen.PLoSGenet1(1):e17. suggestingthatitisdistinctfromtheinsulin/IGF-1signaling pathway[18,19]andthesir-2histonedeacetylase[14].Sofar, Introduction Anumberofmutationsandenvironmentalconditionscan extend the lifespan of Caenorhabditis elegans. Although the underlying mechanisms are not fully understood, these perturbations appear to affect at least three distinct regulatory systems. The ?rst is the insulin/IGF-1/FOXO system [1,56]. Inhibiting insulin/IGF-1 signaling can double the lifespan of the animal [54]. This lifespan exte