益智仁提取物谷甾醇通过抑制铁死亡中的ETS-5基因表达延长秀丽隐杆线虫的寿命

打开文本图片集

β -sitosterol， an important component in the fruits of Alpinia oxyphylla Miq.， prolongs lifespan of Caenorhabditis elegans by suppressing the ferroptosis pathway

LIJuny’²，CHan，Iyao，AGJin，HG，HANoe²，，Gan，ru CHENGengxin5，ZHANGChao³，i Departmentofatognicoeyboatorofoicalsatioaleicineofstyofucaionoloficdicie andLifeSienceinanedicalesityiko9inaisthoolflicaledicieecondofcl Medicineicleittfteulaooc MedicalSciencesSouthernMedicalUniersity;GuangdongroincialKeyLaboratoryofingleCellTechnologyandiction Guangzhouina;hoolofHealthuangdongmceuticaliersityuangzhouia

Abstract： Objective To elucidate the anti-aging effectof β -sitosterol （BS），an important component in the fruits of Alpinia oxyphyllMiq.，inC.elegansanditsregulatoryeffectonET-5genetomodulateferoptosis.MethodsC.eleganstreatedwith 10μg/mL BSweremonitoredforsurvivaltimeandchangesinbodylength，motilityandreproductivefunction.Theectof ETS-5geneknockdownonsurvival timeofC.elegans wasobserved，andthechangesinfataccumulationandlipidedox homeostasis in thetransfected C.elegans were assessed using Oil Red Ostaining and by detecting MDA levels and the GSH/ GSSG ratio. The mRNA expresson levels of ferroptosis-related genes （FTN-1， GPX-1 and AAT-9） were detected using qPCR. TheefectsofBS treatmentandETS-5knockdownonAAT-9enzymeactivityinC.elegans wereexamined.Theefectof BSon nuclearlocalizationofFEV（thehumanhomologofETS-5）wasvalidatedinculturedhumanumbilicalvenousendothelialels （HUVECs）.ResultsBothBStreatmentandETS-5knockdownsignificantlyprolongedthelifespan，promotedlipid accumulationandreduced lipid peroxidationin C.elegans.ETS-5knockdownresulted inupregulated expresionsof the feroptosisrepressorsGPX-1，AAT-9andFTN-1andincreasedtheGSH/GSSGratioinC.elegans.ConclusionBSinibits feroptosisinC.elegansbysuppressngtheexpressonofET-5transcriptionfactorandhenetheactivityofAA-9enzymea key gene for ferroptosis，which in turn prolongs the lifespan of C. elegans.

Keywords： β -sitosterol; senescence;erroptosis;E-5

衰老是生物体在生命周期中，随时间推移逐渐发生的复杂生物学过程，表现为生理功能的衰退、稳态维持能力下降以及对内外环境压力的适应性减弱，最终导致死亡风险显著增加1。（剩余11081字）