GDF11 Increases with Age and Inhibits Skeletal

GDF11IncreaseswithAgeandInhibitsSkeletalMuscleRegenerationskeletalmuscleregeneration→Age-relatedfrailty↑myostatinandGDF11↓︱Age↑?增加作者观点：reagents→notGDF11specificAge↑→GDF11↑Age↑→GDF11mRNA↑(inratmuscle)GDF11andmyostatin→SMAD2/3phosphorylation↑myoblastdifferentiation↓regulateidenticaldownstreamsignalingPriorReagentsUsedtoDetectGDF11AreNotGDF11Specificbindingtest:indicatingcross-reactivityandalackofpreferentialbindingtoGDF11thecombinationofmyostatinandGDF11declinedwithage?itappearsthatthetotallevelsofmyostatin/GDF11actuallyincreasewithage,contradictingthepriorreports.ECLimmunoassayThisimmunoassaydidnotdetectmyostatin.AGDF11-SpecificMethodDemonstratesaTrendofGDF11IncreasingwithAgeinRatandHumanSeraRNA水平上检测GDF11的表达量MyostatinandGDF11treatmentbothresultedinincreasesinSMAD2andSMAD3phosphorylation。功能差异MyoblastDifferentiationGDF11andMyostatinBothInhibitMyoblastDifferentiationGDF11是否促进了肌肉的再生（CTX注射实验）GDF11treatmentinduced(A)aleftwardshiftinfibercross-sectionalareafrequencydistribution,butnochangein(B)totalmeanfiberarea;however,(C)meanfiberareaoffiberswithcross-sectionalareas%600mm2wassignificantlyreducedwithGDF11treatment高浓度regeneratingmuscleshadagreaterfrequencyofsmaller-sizefibers.Totalmeanfiberarea)andmeanareaoffibers%600mm2wassignificantlydecreasedwithGDF11treatment。anti-lamininantibody(green)andHoechst(blue)H&E-stainedGDF11InhibitsMuscleRegeneration。theimpactofGDF11ongrowthandlineageprogressionofSCsfromadultandagedmuscletreatmentwithGDF11decreasedthegrowthofadultandagedSCculturesinadose-dependentmannerDAPIGDF11doesnotimpactcellfateofSCs，GDF11limitstheexpansionofadultandagedSCsandtheirprogeny总结1.AGDF11-SpecificMethodDemonstratesaTrendofGDF11IncreasingwithAgeinRatandHumanSera。2.GDF11ExpressionIncreaseswithAgeinRatSkeletalMuscle。3.GDF11andMyostatinSimilarlyInduceSMAD,p38,andERKPhosphorylation。4.GDF11andMyostatinBothInhibitMyoblastDifferentiation。5.GDF11InhibitsMuscleRegeneration。