Activation of AMPK by the Putative Dietary Restriction Mimetic Metformin Is Insufficient to Extend Lifespan in Drosophila 英文参考文献.docVIP

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Activation of AMPK by the Putative Dietary Restriction Mimetic Metformin Is Insufficient to Extend Lifespan in Drosophila 英文参考文献.doc

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Activation of AMPK by the Putative Dietary Restriction Mimetic Metformin Is Insufficient to Extend Lifespan in Drosophila 英文参考文献

ActivationofAMPKbythePutativeDietaryRestriction MimeticMetforminIsInsufficienttoExtendLifespanin Drosophila CathySlack1,AndreaFoley1,LindaPartridge1,2* 1InstituteofHealthyAgeing,DepartmentofGeneticsEvolutionandEnvironment,UniversityCollegeLondon,London,UnitedKingdom,2MaxPlanckInstituteforBiology ofAgeing,ZMMKForshungsgebaude,Koln,Germany Abstract Thebiguanidedrug,metformin,commonlyusedtotreattype-2diabetes,hasbeenshowntoextendlifespanandreduce fecundityinC.elegansthroughadietaryrestriction-likemechanismviatheAMP-activatedproteinkinase(AMPK)andthe AMPK-activating kinase, LKB1. We have investigated whether the longevity-promoting effects of metformin are evolutionarily conserved using the fruit fly, Drosophila melanogaster. We show here that while feeding metformin to adultDrosophilaresultedinarobustactivationofAMPKandreducedlipidstores,itdidnotincreaselifespanineithermale orfemaleflies.Infact,wefoundthatwhenadministeredathighconcentrations,metforministoxictoflies.Furthermore,no decreases in female fecundity were observed except at the most toxic dose. Analysis of intestinal physiology after metformin treatment suggests that these deleterious effects may result from disruptions to intestinal fluid homeostasis. Thus,metforminappearstohaveevolutionarilyconservedeffectsonmetabolismbutnotonfecundityorlifespan. Citation: Slack C, Foley A, Partridge L (2012) Activation of AMPK by the Putative Dietary Restriction Mimetic Metformin Is Insufficient to Extend Lifespan in Drosophila.PLoSONE7(10):e47699.doi:10.1371/journal.pone.0047699 Editor:GreggRoman,UniversityofHouston,UnitedStatesofAmerica ReceivedJune22,2012;AcceptedSeptember14,2012;PublishedOctober16,2012 Copyright: ? 2012 Slack et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding: This work was funded by the Wellcome Trust (http://www.wel