烟酰胺单核苷酸在抗衰老和衰老相关疾病治疗中的作用研究进展

补充NMN能直接有效地提高机体NAD+水平。NMN进入细胞有两种途径(图1):(1)Ts转运至胞内，随后经烟酰胺核糖激酶(NMNN-甲酰太尿氨酸烟酸腺嘌呤乙酰化ADP核糖IRTs去乙酰化烟酰胺A)烟酰胺烟酸单核苷酸烟酰胺核糖烟酰胺补救合成途径未修饰烟酰胺NAM)乙酰化NAPRT—SLC12A8NRKsNMN细胞的体外激活。Martin等[10]对Frataxin(FXN)敲除的Friedreich共济失调系列证据也表明NMN对出血性卒中的预后具有改善作用。Wei等[14]在胶原酶诱导的脑出血(ICH)小鼠模型中，出血30min时静脉注射NMN提升了NAD恢复老年小鼠的卵细胞质量、胚胎发育和生育能力。Yang等[3大剂量腹腔注射13d后发现癌变组织增加，认为NMN会通过激活糖酵解通路加速上与免疫逃逸相关的PD-L1蛋白质表达[39],从而在癌症的免疫疗法中发挥积极辅助作用。Jiang等[40]在体内研究中发现NMN可以通过激活SIRT1抑制三阴乳[1]VerdinE.NADScience,2015,350(6265):1208-1213.DOI:10.1126/science.oleinlife,deathandeverythingin2017,455:62-74.DOI:10.1016/j.mce.2016.11.003中华老年医学杂志，2022,41(3):355-359.DOI:10.3760/cma.j.issn.02ndrialdynamicsandag0xidMedCellLongev,2021,2021:7207692.[6]YakuK,OkabeK,NakagawaT.NADmetabolism:Implicationsindemononucleotideattenuatemyocardialischemia/reperfusioninjuryviamodulationofmitochondrialfunctionandhemodynamicparametersinagedrats[J].JCardiovascPharmaco[8]Jafari-AzadA,Hoats[J].MolBiolRep,2021,48(4):3089-3096.DOI:10.1[9]WuK,LiB,LinQ,etalt,2017,2(14):e93885.DOI:10.11rtuin)7amelioratesstress-inducedcardiachypertrophybyinteracting[12]ParkJH,LongA,OwensK,etal.sbraindamagefol2016,95:102-110.DOI:10.101strokemice[J].CurrPharmBiotechnol,2023,24(2):299-3[14]WeiCC,KongYY,namidemononucleotideprotectsblood-brainbarrierintegrityandattenuatesdelayedtissueplasminogenactivator-inducedhaemorrhagictransformationafter[15]KissT,Nyúl-Tóthmononucleotide(NMN)supplementationpromotesneurovascularondrialprotection,anti-inflammatory,andaGeroscience,2020,42(2):527-546.DOI:10.1007/s11357-020-00165-5.[16]LongAN,OwensK,S[17]YaoZ,YangW,GaoZ,etalibitsJNKactivationtoreverseAlzheimerdisease[J].NeurosciLe2017,647:133-140.DOI:10.1016/j.neulet.2017.03.02[18]JohnsonS,WozniakDFateshippocampalcognitivephenotypesinoldmicewhichnimononucleotideimproves[J].NPJAgingMechDis,2018,4:10.DOI:10.1038/s41514-018-00[19]GuanY,WangSR,Huang[20]JiaY,KangX,TanL,eDNAdamageandsene[21]TakahashiR,KandNAD(+)metabolitesandnicotinamideN-methyltransferaseinchronintifiesbiomarkersforrenalaging[J].Aging,2020,12(21):21890-21903.DOI:10.18632/aging.104007.ermnicotinamidemononucleotidetreatmentinamousemodelofdiabeticnephropathy[J].JAmSocNephrol,2021,32(6):1355-1370.[24]HasegawaK,SakamakiY2022,12(1):13712.DOI:10.1038/s41598-022-18147-2.[25]YoshinoJ,MillsKF,YoonMJ,etal.Nicotinamidetide,akeyNAD(+)intermediate,treatsthepathophysiologyofdiet-a[26]MillsKF,Yoshonofnicotinamidemononucleotidemitigatesage-associatedphysiologilucosemetabolisminmice[J][28]YoshinoM,YoshinoScience,2021,372(6547):1224-1229.DOI:10.1126/science.a thDis,2019,10(5):336.DOI:10butestothelossofosteoprogenitorsandbonemasswithaging[J].NpjAgingandMechanismsofDisease,2021,7(1):8.DOI:10.1038/s415[31]LuZ,JiangL,LesaniP,etal.Nicotinosteoporoticmice[J].JGe186-194.DOI:10.1093[32]BertoldoMJ,ListijonoDR,HoWJ,etal.NAD(+)repletionrescuesfemalefertili30(6):1670-1681.e1677.DOI:10.1016/j.cerbatesfemalereproductiveagingviaimpairmentoftheNADH/NAD(+)redox[J].AgingCell,2020,19(9):e132[34]HuangP,ZhouY,TangW,etal.Long-termtreatmthroughenhancingthemitophagylevelofgranuloJNutrBiochem,2022,101:1089[35]WangL,ChenY,WeiJ,etal.Administrationofnicotinamidemononucleotideimprovesoocytequalityofobesemice[J].CellProlif,ernstheproinflammatorysenescencBiol,2019,21(3):397-407.DOI:1[37]PanF,KangSF,ZhaoYF,odel[J].MaterialsChemistryFrontiers,2021,5(2):995-1002.DOI:[38]ZongZ,LiuJ,WangN,etal.Nicotinamidemhibitshepaticstellatecellactivationtopreventliverf[39]TakedaK,OkumuraK.Nicotinamidem[J].BiomedRes,2021,42(5):173-179.DOI:1[40]JiangY,LuoZ,GongY,etal.NAD(+)supplementationltriple-negativebreastcancermetastasisviaSIRT1-P66S[J].Oncogene,2023,42(1[41]YooKH,TangJJ,Rashiddepreventscisplatin-inducedcogni2021,81(13):3727-3737.DOI:10.1158/00[42]MargierM,KuehnemannC,HuloN,etaldlossinphysicalactivityinmice[J].CelationofnicotinamidemononucleotideonclinicalinamidemetabolitelevelsinhealthyJapanesemen67(2):153-160.DOI:10.1507/endocrj.EJ19-0313.[44]KimuraS,Ichikawaceridelevelsinhealthyindividuals[J].Cureus,2022,14(9):e28812.3389/fragi.2022.851698.[46]0kabeK,