Anti-aging Effects Ntawm Vitamin C Rau Tib Neeg Pluripotent Stem Cell-derived Cardiomyocytes Ⅱ

Kev sib tham

Kev tshawb fawb biomedical nrhiav kev piav qhia txog qhov tshwm simntawm tib neeg metabolism thiab nws cov mechanisms. Qhov nokev tshawb fawb xav tau tib neeg cov hlwb los ntawm lub cev's ntau yamcov kab mob hauv nruab nrog cev; Txawm li cas los xij, rau kev kho mob thiab kev coj ncaj ncees,cov ntaub so ntswg nyob ntawm tib neeg lub cev nws tus kheej tsis tuaj yeem ua tautau txais los ua ib qho kev tshawb fawb biomedicalqauv. hESCs muab tau los ntawm lub cell loj ntawm ibembryo (Thomson et al.1998) thiab hiPSCs muab los ntawmtus neeg mob's fibroblasts (Takahashi li al.2007) tuaj yeem ua haujlwmraws li cov kev xaiv tsim nyog rau tib neeg kev tshawb fawb vim lawvkeeb kwm thiab kev loj hlob muaj peev xwm (Pera et al.2000; Reubinoff et al.2000). Tib neeg stem cell derivativesxws li cov kab mob plawv yog ib qho tshwj xeeb thiab rov tsim duacellular qauv siv nyob rau hauv tib neeg txoj kev loj hlob biology,Kev tshawb fawb biomedical, thiab kev tshawb fawb tshuaj.

Nyem qhov no Kom Paub Cistanche Anti-Aging Vs Vitamin

Kev laus yog qhov tshwm sim dav dav uas cuam tshuam rau somaticcov cell thiab ua rau txo qis cellular thiab lub cev ua haujlwm,sawv cev los ntawmshortening ntawm telomeres, lub tsuj rojntawm mutations, thiab covkev loj hlob ntawm mitochondrialkev ua haujlwm tsis zoo(Goldstein1990; Finkel thiab Holbrook2000). Kev laus tshwm sim yog ib ntus uas nws kim heev;yog li ntawd, kev tshawb fawb txog kev laus ntawm tib neeg lub cev hlwbnyuaj rau kev coj.Kev laus ntawm cardiomyocytesyogtshwm sim los ntawm hnub nyoog, reactive oxidative hom tsim, thiabmitochondrial puas(Terman et al.2004; Termanthiab Brunk2005). Cov teebmeem no rov tsim dua hauvvitro kab lis kev cai ntawm cardiomyocytes.

Ntawm no, peb pom qhov aging phenomenon nyob rau hauvhPSC-derived CMs. Tib neeg PSC-derived CMs yog spontaneously hnub nyoog nyob rau hauv vitro kab lis kev cai tej yam kev mob. Hnub 24cov hlwb pom muaj hnub nyoog tshwj xeeb pigmented tshwmance tshaj cov hlwb nyob rau hnub 12 thiab 18. Cov morphologicalkev hloov correlated nrog txo qhia ntawmcell cycle-related genes, slower beating rate, and lowyog mitochondrial membrane muaj peev xwm. Qhov kev qhiantawm cyclin noob tau txo qis nyob rau lub sijhawm.Qhov no downregulation ntawm cyclin noob nyob rau hauv peb txoj kev tshawb no yogzoo ib yam li paub txog kev hloov pauv hauv kev laus ntawm lubqib molecular (Sheydina et al.2011). Peb nrhiavntawm qeeb qeeb hauv cov hlwb laus tau zoo ib yam nrog pebtsab ntawv tshaj tawm dhau los (Kim et al.2011). Peb ntsuas mitochondrialfunctionality siv JC-1 zas xim rau hnub 24 thiabpom tias tsuas yog 30 feem pua ​​​​ntawm cov hlwb sib txawv khaws ciamitochondrial muaj nuj nqi. Tsis tas li ntawd, kev nthuav qhia ntawmtelomere-encoding noob tau downregulated.

Ib qho nthuav nrhiav yog qhov uas tsis tshua muaj qhov tshwj xeebkev laus thiab vitamin C's rov qab los tau pomhauv hiPSC-derived CM. Tib neeg iPSCs yog neeg laussomatic hlwb uas tau reprogrammed rau ib pluripotentxeev (Yu et al.2007) los ntawm kev xa khoom ntawmexogenous pluripotency yam (Takahashi et al.2007). Vim yog qhov xwm txheej ntawm lawv qhov kev hloov pauv, iPSCsraug suav hais tias muaj qhov sib txawv ntawm lub xeev epigeneticlos ntawm ESCs (Chin et al.2009) thiab ua qauv qhiatxo qhov sib txawv efficiency rau hauv ib kabmuaj hnub nyoog (Mauritz et al.2008). Lub exogenous reprogramming yam uas tau xaiv rau tso rau hauv somatic hlwb yuavaccount rau qhov kev tshawb pom no. Reprogrammed hiPSCs muajqhia tsis tiav reprogramming lossis ntxov senescencethaum nyob rau hauv vitro sib txawv thaum piv rau hESCs(Hanna et al.2010). Yog li, hESC-derived CMs zoo liua kom haum rau kev kawm txog kev laus lossis cuam tshuamkev tshawb fawb.

Vitamin C muaj ntau lub luag haujlwm hauv kev tiv thaiv kev laus thiab muajqhiacardiovascular-tiv thaiv cov teebmeem(Zhou et al.2006; Luiking et al.2010). Peb siv ntau yam concentrationsntawm vitamin C los ua kom pom cov kev tiv thaiv kev lauscov teebmeem ntawm hESC-derived CMs. Vitamin C khocuam ​​tshuam qhov ntaus zaus ntawm hESC-derived CMsthiab txo qis qhov nyiam hESC-derived CMs muajntawm kev ntaus qeeb qeeb nrog hnub nyoog. Tsis tas li ntawd, kev kho mobnrog vitamin C cuam tshuam qhov kev qhia ntawm kev laus-txognoob thiab mitochondrial muaj nuj nqi hauv hESC-derivedCMs. Ua ntej, kev hloov pauv hauv hTERT, hTR, thiabTRF2 tau soj ntsuam. Human TR (hTR) thiab hTERTencode human telomerase-related RNA thiab protein,raws. Lawv lub luag haujlwm hauv kev laus yog paub zoo(Hiyama et al.1995) raws li ob lub noob muaj feem xyuam nrogtelomeres thiab telomerase (Huffman et al.2000; Blackburn2001). Hauv peb txoj kev tshawb fawb, kev kho mob nrog cov vitaminC nyob rau hauv sib txawv staged CMs nce qhov kev qhia ntawmhTERT. Tib neeg TR kev nthuav qhia kuj nce ntxiv nyob rau theem kawghESC-derived CMs. Cov txiaj ntsig no qhia tau tiashais tias vitamin C muaj kev cuam tshuam ncaj qha rau kev ua telomerasehauv hESC-derived CMs. Tsis tas li ntawd, vitamin C tuaj yeem ua tautxhim kho kev hloov pauv ntawm telomerase ntsig txog cov noob,thiab qhov kev tiv thaiv kev laus no tuaj yeem yog theem-nyob rau hauvhnub nyoog hESC-derived CMs. Kev nthuav qhia ntawm TRF2 dramaticallynce nyob rau theem kawg ntawm hESC-derivedCMs kho nrog vitamin C, thiab cov txiaj ntsig no qhiatias TRF2 plays lub luag haujlwm hauv kev tswj hwm caj ces ntawmhnub nyoog hESC-derived CMs. TRF2 kev ua haujlwm txuas nrogaging nyob rau hauv somatic hlwb, uas ntxiv qhia covanti-agingcov teebmeem tsim los ntawm vitamin C.

Peb kuj tau pom cov txiaj ntsig ntawm vitamin C ntawm mitochondrialmembrane muaj peev xwm. Cov nyhuv anti-aging ntawmvitamin C cuam tshuam nrog kev rov qab los ntawm kev ntaus nqi hauvhESC-derived CMs. Ua ke, cov txiaj ntsig no qhiauas paub zoo cardioprotective luag hauj lwm ntawm vitamin Ckuj tseem siv tau rau hESC-derived CMs hauv vitro. Ntawm covkuaj mob, kho vitamin C ntawm 100μM rau48 h tau zoo tshaj plaws thiab qhov concentration yog ze rauqhov pom zoo noj zaub mov ntawm vitamin C. Cov noCov txiaj ntsig tau txhawb nqa qhov kev lees paub ntawm hESC-derivedCMs raws li qhov siv tau ntawm tes uas tuaj yeem ua haujlwm tshwj xeebqauv ntawm tib neeg lub plawv cell aging.

Hauv kev xaus, peb tau pom tias hESC-derivedCMs yog tsim rau siv los ua lwm yam qauv raukev laus nyob rau hauv tib neeg lub plawv hlwb. Cov qauv no tuaj yeem ua tautxuas mus rau lwm qhov chaw ntawm kev tshawb fawb biomedical raws li ib qholwm txoj rau cov tib neeg lub plawv hlwb, thiab ntau yamCov neeg sib tw tiv thaiv kev laus tuaj yeem kawm nroghESC-derived CMs yav tom ntej.

Kev lees paubTxoj haujlwm no tau txais kev txhawb nqa los ntawm cov nyiaj pabKorean Health Technology R & D Project, Ministry of Health thiabWelfare, Republic of Kauslim (A111539) thiab los ntawm Basic ScienceKev Tshawb Fawb Kev Tshawb Fawb los ntawm National Research Foundation ntawmKaus Lim Kauslim (NRF) tau nyiaj los ntawm Ministry of Education, Science thiabTechnology (2012-0004131). Cov neeg sau ntawv txaus siab rau lub siab dawb paugkev pab los ntawm Myung Soo Cho, Sun Mi Baek, Jun BeomKu, thiab Yong Jin Kim.

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