HypothalamicstemcellscontrolagingspeedpartlythroughexosomalmiRNAsYalinZhang1,2,MinSooKim1,2,BaosenJia1,2,JingqiYan1,2,JuanPabloZuniga-Hertz1,ChengHan1,andDongshengCai1,*1DepartmentofMolecularPharmacology,DiabetesResearchCenter,InstituteofAging,AlbertEinsteinCollegeofMedicine,Bronx,NY10461SUMMARYHypothalamiccontrolofagingwasrecentlyproposed,buttheresponsiblemechanismsstillremainunclear.Here,followingtheobservationthatagingofmicestartedwithasubstantiallossofhypothalamicstem/progenitorcellsthatco-expressSox2andBmi1,wedevelopedseveralmousemodelswithablationofthesehypothalamiccells,eachofthemconsistentlydisplayinganaccelerationinaging-likephysiologicalchangesorshorteninginlifespan.Conversely,agingretardationandlifespanextensionwereachievedinmid-agedmicewhenlocallyimplantedwithhealthyhypothalamicstem/progenitorcellsthatweregeneticallyengineeredtosurvivefromaging-relatedhypothalamicinflammatorymicroenvironment.Mechanistically,hypothalamicstem/progenitorcellsgreatlycontributedtoexosomalmiRNAsinthecerebrospinalfluidwhichdeclinedoveraging,whilecentraltreatmentwithhealthyhypothalamicstem/progenitorcells-secretedexosomesledtoslowdownofaging.Inconclusion,agingspeediscontrolledsignificantlybyhypothalamicstemcellspartiallythroughreleaseofexosomalmiRNAs.KeywordsAging;hypothalamus;neuralstemcell;miRNA;exosomeWhilethenervoussystemclearlyplaysaroleinaging1-6,andrecentresearchhasdemonstratedthatthehypothalamusisparticularlyimportant5-8,theresponsiblemechanismisstillunknown.Inneuroscienceresearch,ithasbeenappreciatedthatadultneuralstem/progenitorcells(NSC)resideinafewbrainregionstomediatelocalneurogenesisandthereforeseveralaspectsofbrainfunctioning9-13.DeclineinadultneurogenesisisknowntoUsersmayview,print,copy,anddownloadtextanddata-minethecontentinsuchdocuments,forthepurposesofacademicresearch,subjectalwaystothefullConditionsofuse:http://www.nature.com/authors/editorial_policies/license.html#termsCorrespondenceshouldbeaddressedtoD.C.(dongsheng.cai@einstein.yu.edu),Phone:718-430-2426...
