Endogenous Stem Cells in Homeostasis Thiab Aging Part 1
Jul 10, 2023
AbstractNyob rau hauv yuav luag tag nrho cov tib neeg cov ntaub so ntswg thiab lub cev, cov laus qia hlwb los yog cov ntaub so ntswg qia hlwb muaj nyob rau hauv ib tug tshwj xeeb qhov chaw, lub thiaj li hu ua qia cell niche los yog nws sib npaug, tsis tu ncua replenishing functional txawv hlwb. Cov kab mob endogenous tuaj yeem nthuav dav rau kev kho mob ntawm tes siv ex vivo cell kab lis kev cai lossis rov qab los kho cov ntaub so ntswg hauv qhov chaw los ntawm kev lag luam ntawm tes thiab tsev. Nyob rau hauv txoj kev laus, inefficiency nyob rau hauv lub endogenous stem cell-mediated kho mechanism tuaj yeem tshwm sim los ntawm ntau yam kev puas tsuaj uas sib sau ua ke hauv cov txheej txheem ntawm qia cell nws tus kheej rov ua dua tshiab, ua haujlwm, muaj peev xwm sib txawv, thiab kev lag luam los ntawm cov xov tooj ntawm tes-autonomous intrinsic pathways (xws li epigenetic alterations) los yog systemic extrinsic pathways. Qhov kev tshuaj xyuas no tshuaj xyuas cov homeostasis ntawm cov qia hlwb endogenous, tshwj xeeb tshaj yog cov pob txha pob txha qia hlwb, thiab lawv cov dysregulation hauv kab mob thiab kev laus thiab sib tham txog cov tswv yim cuam tshuam. Ob peb lub cev pro-aging thiab rejuvenating yam, lees paub nyob rau hauv heterochronic parabiosis los yog ntxov ntxov laus progeroid tsiaj qauv, raug tshuaj xyuas raws li qhov ua tau los tiv thaiv kev laus lub hom phiaj los ntawm kev xav ntawm ib puag ncig noj qab haus huv rau cov kab mob endogenous. Ntau yam kev hloov kho epigenetic thiab chromosome architectures raug tshuaj xyuas raws li txoj hauv kev ntawm tes rau kev laus thiab kev laus. Ib qho maj mam nce hauv lub nra hnyav thaum laus kuj raug tshuaj xyuas. Thaum kawg, cov ntaub so ntswg kho thiab tiv thaiv kev laus los ntawm Tshuaj-P, peptide stimulating qia cell lag luam los ntawm cov pob txha pob txha thiab hloov cov lus teb inflammatory, tau tham txog yav tom ntej los tiv thaiv kev laus lub hom phiaj.
Glycoside ntawm cistanche tuaj yeem ua rau muaj kev ua haujlwm ntawm SOD hauv plawv thiab daim siab cov ntaub so ntswg, thiab txo cov ntsiab lus ntawm lipofuscin thiab MDA hauv txhua cov ntaub so ntswg, tshem tawm ntau yam reactive oxygen radicals (OH-, H₂O₂, thiab lwm yam) thiab tiv thaiv DNA puas. los ntawm OH-radicals. Cistanche phenylethanoid glycosides muaj peev xwm tshem tawm cov dawb radicals, muaj peev xwm txo tau ntau dua li cov vitamin C, txhim kho cov haujlwm ntawm SOD hauv cov phev ncua, txo cov ntsiab lus ntawm MDA, thiab muaj qee yam kev tiv thaiv ntawm cov phev ua haujlwm. Cistanche polysaccharides tuaj yeem txhim kho kev ua haujlwm ntawm SOD thiab GSH-Px hauv erythrocytes thiab ntsws cov ntaub so ntswg ntawm cov nas senescent sim los ntawm D-galactose, nrog rau txo cov ntsiab lus ntawm MDA thiab collagen hauv lub ntsws thiab ntshav, thiab nce cov ntsiab lus ntawm elastin, muaj Cov nyhuv scavenging zoo ntawm DPPH, ncua lub sijhawm ntawm hypoxia hauv cov nas senescent, txhim kho cov haujlwm ntawm SOD hauv cov ntshav, thiab ncua lub physiological degeneration ntawm lub ntsws hauv kev sim cov nas nrog cellular morphological degeneration, kev sim tau pom tias Cistanche muaj peev xwm antioxidant zoo. thiab muaj peev xwm los ua ib qho tshuaj tiv thaiv thiab kho cov kab mob ntawm daim tawv nqaij laus. Nyob rau tib lub sijhawm, echinacoside hauv Cistanche muaj lub peev xwm tseem ceeb los tshem tawm DPPH dawb radicals thiab tuaj yeem tshem tawm cov pa oxygen reactive, tiv thaiv dawb radical-induced collagen degradation, thiab kuj muaj kev kho zoo ntawm thymine dawb radical anion puas.
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Ntsiab lusHematopoietic stem cell · Pob txha pob txha stem cell · Endothelial precursor cell · Kev laus Rejuvenation
1 Kev Taw Qhia
Kev laus yog ib qho tshwm sim tshwm sim los ntawm kev nce zuj zus hauv lub cev lub cev homeostatic thiab rov ua haujlwm, suav nrog hnub nyoog cuam tshuam txog kev ua haujlwm ntawm qia cell [1]. Cov kev tshawb fawb tsis ntev los no ntawm cov tsiaj me thiab cov laus thiab tib neeg tau qhia txog kev hloov pauv hnub nyoog ntawm cov qia cell, qhov loj ntawm cov qia cell, thiab qhov sib txawv ntawm qhov sib txawv [2–4]. Nyob rau hauv cov laus, cell-autonomous epigenetic alterations nyob rau hauv qia hlwb sau, uas yuav ua rau senescence ntawm qia / progenitor hlwb thiab txo ob lub qia cell pas dej ua ke thiab qia cell muaj nuj nqi. Heterochronic parabiosis thwmsim ntawm cov menyuam yaus thiab cov laus tau pom tias muaj kev hloov pauv ntawm lub hnub nyoog ntsig txog hauv lub cev thiab hauv cheeb tsam ib puag ncig, suav nrog cov txheej txheem rov ua dua tshiab thiab cov kev laus laus [5-7], uas tuaj yeem tswj hwm kev ua haujlwm thiab kev ua neej ntawm cov kab mob endogenous thiab qia. cell niches. Qhov tseem ceeb tshaj, cov kev sim tau qhia txog cov hnub nyoog ntsig txog qhov nce ntawm cov kab mob cytokines thiab mob ntev [8-10], uas tuaj yeem cuam tshuam rau qia cell muaj nuj nqi, qia cell niche, qia cell lag luam, thiab kev sib txawv sib txawv. Cov ntawv tshaj tawm txog kev laus thiab cov kab mob degenerative xws li Parkinson's disease, Alzheimer's disease, ntshav qab zib, kab mob vascular ntev, thiab osteoarthritis tau taw qhia txog kev sib txuas ntawm cov qia cell thiab kab mob etiology thiab nruab nrab ntawm cov qia cell thiab lub neej expectancy.
Xyoo 2013, Carlos Lopez-Otin et al. [2] txheeb xyuas thiab categorized cuaj cellular thiab molecular cov cim uas ua rau cov txheej txheem kev laus: genomic instability, telomere attrition, epigenetic alterations, poob ntawm proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, thiab stems. Feem ntau ntawm cov hnub nyoog txog kev puas tsuaj thiab kev puas tsuaj nce zuj zus mus rau lub sijhawm, uas tau kawm ntau yam hauv kev mob qog noj ntshav, kab mob metabolic, thiab kab mob degenerative. Tshwj xeeb, lub tswv yim ntawm qia cell qaug zog, los ntawm txoj hauv kev ntawm tes-autonomous intrinsic pathways lossis extrinsic pathways, tuaj yeem piav qhia txog kev sib koom ua ke ntawm ntau hom kev laus cuam tshuam nrog kev puas tsuaj thiab qhov poob ntawm cov peev xwm rov ua dua tshiab [11, 12]. Progeroid nas thiab cov kev sim parabiosis tsis ntev los no siv cov nas me me thiab laus tau pom tias muaj cov kab mob xws li hepatocyte growth factor activator (HGFA) uas muaj ntau hauv cov nas me tuaj yeem thim rov qab qhov poob ntawm neural thiab cov leeg pob txha muaj nuj nqi pom hauv cov nas laus lossis progeroid nas [13 — 15]. Cov kev ua haujlwm hauv lub cev qhia tias cov txheej txheem extrinsic, ua raws li kev cuam tshuam tshuaj, tuaj yeem txhawb cov qia cell rejuvenation thiab thim rov qab phenotype kev laus.
Qhov kev tshuaj xyuas no tham txog cov kab mob endogenous hauv vivo, tshwj xeeb tshaj yog cov pob txha pob txha stem hlwb xws li hematopoietic stem cells (HSCs), pob txha pob txha stromal (los yog mesenchymal) qia hlwb (BMSCs), thiab endothelial precursor cells (EPCs), raws li lawv cov ontogeny, ib txwm muaj. kev ua haujlwm, thiab muaj hnub nyoog txog kev ua haujlwm hloov pauv. Qhov thib ob, kev hloov pauv hnub nyoog txog kev hloov pauv hauv lub cev, cov neeg sib tw rau kev tiv thaiv kev laus lossis kev laus, raug txiav txim siab rau lawv txoj kev txuas mus rau qia cell homeostasis thiab kev laus thiab rau lawv lub peev xwm raws li lub hom phiaj tshuaj rau retard lossis tswj cov txheej txheem kev laus. Thib peb, kev hloov pauv hnub nyoog cuam tshuam hauv cov pob txha pob txha qia cell niche raug tshuaj xyuas. Thib plaub, kev hloov pauv hloov pauv hloov mus rau qia hlwb thaum lub sijhawm laus, hu ua cell autonomous stem cell aging, raug tshuaj xyuas thiab sib tham txog kev hloov kho histone, DNA methylation, thiab tsis-coding RNA. Thib tsib, cov teebmeem ntawm kev txhim kho inflammatory teb thaum lub sij hawm laus yog tham txog, tshwj xeeb tshaj yog nyob rau hauv lub hnub nyoog ntawm cov kab mob degenerative thiab kho cov nqaij mos. Cov lus xaus thiab kev xav rau kev tshawb fawb yav tom ntej suav nrog kev txiav txim siab seb lub hnub nyoog cuam tshuam txog kev puas tsuaj hauv cov qia hlwb endogenous thiab lawv ib puag ncig tuaj yeem tswj tau thiab cov hom phiaj tshuaj tshiab rau tib neeg kev noj qab haus huv.
2 Endogenous qia hlwb hauv cov pob txha pob txha thiab kev laus
Homeostasis, kho cov ntaub so ntswg, thiab rov tsim dua tshiab yog txuas ntxiv tswj thiab txhawb nqa los ntawm cov kab mob endogenous qia hlwb hauv lub cev. Cov pob txha pob txha yog cov qia cell reservoir rau HSCs, BMSCs, EPCs, thiab lwm yam qia hlwb tseem tsis tau txheeb xyuas. Cov qia hlwb hauv cov pob txha pob txha yog qhov tseem ceeb hauv kev tsim cov ntaub so ntswg, thiab kev ua haujlwm tsis zoo los yog poob ntawm cov qia hlwb yog qhov ua rau tsis ua haujlwm ntawm cov ntaub so ntswg homeostasis thiab kho (Fig. 1) [4].
HSCs tsis tu ncua muab cov qe ntshav, suav nrog cov tshuaj tiv thaiv kab mob, cov qe ntshav liab, thiab cov qe ntshav dawb, thoob plaws lub neej. Hematopoietic dysfunction tshwm sim nyob rau hauv lub hnub nyoog, uas ua rau txo qis lub cev tiv thaiv kab mob thiab ua rau muaj zog myeloid teb, thiab anemia. Ib qho kev hloov pauv tseem ceeb ntawm kev laus, uas yog hu ua mob, ib qho smoldering pro-inflammatory phenotype [9, 16], kuj tuaj yeem tshwm sim los ntawm HSC tsis ua haujlwm lossis poob ntawm kev sib txawv ntawm kev sib txawv. BMSCs yog stromal hlwb nyob rau hauv cov pob txha pob txha uas yuav pab txhawb hematopoiesis li qia cell niche hlwb thiab osteogenesis rau pob txha tsim. Hauv cov laus, BMSCs kuj poob qis, thiab lawv qhov sib txawv muaj peev xwm skews mus rau adipogenesis, ua rau cov pob txha daj thiab pob txha. EPCs, precursors rau endothelial hlwb, kuj poob thaum lub sij hawm kev laus, ua rau kev puas tsuaj ntawm vascular kho thiab impaired vascular niche muaj nuj nqi rau HSCs.
2.1 HSC txhais/ontogeny/aging
HSCs yog tib lub hlwb uas tuaj yeem tsim tag nrho cov qe ntshav. Lawv tsim * 1 9 1010 cov qe ntshav liab thiab * 1 9 108 cov qe ntshav dawb txhua teev hauv lub neej [11]. Cov txheej txheem txuas ntxiv ntawm kev tsim cov qe ntshav dawb, hu ua hematopoiesis, suav nrog kev loj hlob, kev rov ua dua tshiab ntawm tus kheej, thiab kev sib txawv ntawm HSCs thiab egress ntawm mature progenitor cells rau hauv cov ntshav ncig [12]. Hematopoiesis tshwm sim hauv ontogenetic ntws. Cov theem pib thiab cov theem tseeb tsim HSCs tseeb. Qhov tshwm sim ntawm HSCs thaum ub pib nyob rau hauv lub yolk sac ntawm 30 hnub tom qab kev xeeb tub nyob rau hauv tib neeg thiab E7.5 nyob rau hauv nas thiab ces tsiv mus rau allantois thiab placenta. Thaum 4 lub lis piam tom qab kev xeeb tub (wpc) hauv tib neeg thiab E10.5 hauv nas, HSCs nyob hauv aorta-gonad mesonephros, thaj tsam ntawm embryonic mesoderm uas ua rau muaj qhov tseeb HSCs. HSCs tom qab tau cog rau hauv cov placenta, thymus, thiab siab ntawm 5 wpc hauv tib neeg thiab E11 hauv cov nas, rau hauv cov poov xab ntawm 8 wpc hauv tib neeg thiab E14 hauv cov nas, thiab rau hauv cov pob txha ntawm 12 wpc hauv tib neeg thiab E18 hauv cov nas. Tom qab yug me nyuam, HSCs tsuas muaj nyob hauv cov pob txha pob txha thiab thymus, thiab cov pob txha pob txha txhawb nqa feem ntau ntawm hematopoiesis [17]. HSCs muab nce rau ob qho tib si myeloid progenitor cells (CMPs) thiab cov lymphoid progenitors (CLPs) los tsim tag nrho cov ntshav. CMPs sib txawv rau hauv monocytes, macrophages, dendritic hlwb, neutrophils, basophils, eosinophils, erythrocytes, megakaryocytes, thiab platelets. CLPs sib txawv rau hauv T hlwb, B hlwb, thiab NK hlwb (Fig. 2).
Ib qho HSC hierarchy tuaj yeem txhais tau raws li cov pob txha pob txha-repopulation muaj peev xwm, muaj peev xwm sib txawv, thiab ntau qhov chaw cim npe. Xyoo 1994, Spangrude et al. [18, 19] faib cov pej xeem ntawm HSCs ua peb hom ntau ntau: ntev (LT)-HSCs, luv-term (ST)- HSCs, thiab multipotent progenitors (MPPs). Lawv txheeb xyuas cov hlwb uas siv cov cim sib txawv ntawm cov cim sib txawv, xws li CD34, CD38, CD90, CD133, CD105, CD45, thiab cov qia cell factor c-kit. Hauv xyoo 2005, txhawm rau txheeb xyuas qhov sib txawv ntawm cov neeg nyob hauv HSCs los ntawm MPPs tsis yog tus kheej, Morrison li al. [20, 21] tau tshaj tawm tias cov signaling lymphocyte activation molecule (SLAM) tsev neeg ntawm cov receptors suav nrog CD150 (slamf1), CD48 (slamf2), CD229 (slamf3), thiab CD224 (slamf4) tau sib txawv ntawm kev ua haujlwm sib txawv ntawm cov qia hlwb thiab cov hlwb progenitor. hauv nas. Tsis tas li ntawd, tsis muaj zog staining nrog cov xim tseem ceeb xws li Hoechst 33342 (sab pejxeem) lossis rhodamine 123 tuaj yeem siv los cais HSCs nrog cov xov tooj me me. Lub peev xwm ntawm hematopoietic progenitors rau proliferate thiab sib txawv rau hauv cov cheeb tsam yog tshuaj xyuas nrog lub colony forming unit (CFU) assay siv methylcellulose-based semi-solid media nyob rau hauv teb rau cytokine stimulation rau lymphocytes (CFU-L), pre-B hlwb (CFU- Pre-B), granulocytes, erythrocytes, macrophages, thiab megakaryocytes (CFU-GEMM). Txhawm rau txheeb xyuas qhov xwm txheej ntawm lub voj voog ntawm tes, Ki-67 daim ntawv lo, BrdU kev txheeb xyuas kev koom ua ke, thiab cov fluorescence ubiquitination-based cell cycle indicator (Fucci) system yog siv. Siv cov fusion ntawm cov proteins fluorescent rau lub voj voog ntawm tes-cov proteins tshwj xeeb geminin, cdt1, thiab p27, Fucci system tuaj yeem pom cov hlwb los ntawm staining cell nuclei hauv G1, S / G2 / M, thiab G0 theem ntawm lub voj voog ntawm tes hauv cyan, ntsuab, thiab liab, feem [22].
Ntau yam ntawm cov hnub nyoog ntsig txog cellular thiab molecular hloov pauv hauv HSCs thiab hematopoiesis tau raug tshaj tawm. Hauv HSC kev ua haujlwm, kev laus ua rau muaj kev loj hlob ntawm HSCs, thaum kev laus txo qis qia cell thiab kev ua haujlwm ntawm tes hauv cov leeg pob txha, cov kab mob germline, thiab neural qia hlwb [1, 23]. Yuav ua li cas cov kev hloov pauv tau tswj thiab tswj tsis tau meej. Txawm li cas los xij, nws tau tshaj tawm tias cov hnub nyoog HSCs tau pom tias txo qis kev rov ua dua tshiab ntawm tus kheej, poob ntawm cov cell polarity, tawm mus rau hauv cov hlab ntsha, tsis muaj peev xwm ua kom muaj peev xwm, thiab myeloid- thiab platelet-biased sib txawv [12, 24].
Cov hnub nyoog cuam tshuam txog kev hloov pauv hauv cov txheej txheem hauv lub cev, txoj hauv kev taw qhia hauv lub cev, thiab kev tswj lub voj voog ntawm tes kuj zoo li cuam tshuam rau hauv HSC tus kheej rov ua dua tshiab thiab muaj ntau yam sib txawv. TGF-b1 txhim kho myeloid sib txawv es tsis yog lymphoid sib txawv [25], thiab chromatin regulator Satb1, uas yog induced thaum lub sij hawm lymphoid sib txawv, txo cov hnub nyoog HSCs [26]. Hnub nyoog HSCs qhib txoj kev uas tsis yog-canonical Wnt signaling txoj kev es tsis txhob ntawm canonical Wnt txoj kev, uas ua rau kom Wnt5a qhia thiab activates cell division tswj protein 42 (Cdc42) polarity. Txoj cai ntawm Cdc42 polarity thiab kev faib tawm yog ib qho tseem ceeb rau kev muaj peev xwm rov tsim dua tshiab thiab cov pob txha pob txha homing [27]. Tsis tas li ntawd, nyob rau hauv cov hnub nyoog, cov chaw kuaj xyuas ntawm tes xws li p16INK4a, BCL-2, BATF, thiab p53 tau qhib. Kev tshem tawm p16INK4a nce lub peev xwm ntawm cov qia hlwb los ntawm cov pob txha pob txha thiab lub hlwb, thiab qib qis ntawm p53 txhawb nqa cov qia cell, thaum qib siab ua rau cov cell tuag thiab senescence [28].
Reactive oxygen hom (ROS) thiab nitric oxide (NO) tuaj yeem yog cov tswj hwm tseem ceeb hauv HSC kev laus. Kev sib sau ntawm ROS nyob rau hauv cov laus hlwb induces FOXO depletion, NF-jB activation, p38-mTOR activation, telomere shortening, DNA puas, thiab mitochondrial dysfunction [12]. Insulin thiab IGF qhib lub PI3K-Akt signaling pathway thiab phosphorylate FOXO, ua raws li inhibition ntawm kev qhia ntawm anti-oxidant N-acetyl-L-cysteine [28]. Tom qab oxidative kev nyuaj siab, HSCs nce NO theem, uas ua rau poob ntawm nws tus kheej-renewal, txawv txav proliferation, thiab malignancy [12, 29].
2.2 BMSCs hauv cov pob txha hluas thiab laus
BMSCs, feem ntau hu ua mesenchymal qia hlwb (BMSCs), tsis qhia HSC thiab EPC cim CD34, tab sis lawv nthuav tawm cov khoom siv clonogenic thiab sib txawv rau ntau hom cell, xws li osteoblasts, chondrocytes, adipocytes, thiab myocytes, thaum hauv vitro cell culture [30–32]. BMSCs nthuav qhia CD73, CD90, CD105, CD29, CD44, CD71, CD106, CD120a, CD124, CD56, thiab CD271 ntawm lawv qhov chaw, tab sis lawv tsis muaj CD11b, CD14, CD117, CD19, CD34, CD45, CD79a, thiab HLA- cov cim [33]. Thaum nyob hauv vivo BMSCs nthuav qhia CD146, SCA1, PDGFRa, CXCL12, thiab nestin, ex vivo aged BMSCs nthuav qhia CD106 thiab CD295 [34]. Txhim kho kev qhia ntawm CD295, ib qho leptin receptor, cim cov hlwb apoptotic thiab cov hlwb uas tsis yog nws tus kheej.
BMSCs muaj peev xwm rov ua dua nws tus kheej, npaj mus rau qhov chaw raug mob, thiab koom nrog hauv kev tiv thaiv kab mob, kho qhov txhab, thiab kho yuav luag tag nrho cov ntaub so ntswg [34–37]. Lub peev xwm tseem ceeb ntawm lub cev ntawm BMSCs yog lub cev tiv thaiv kab mob los ntawm kev tso tawm cytokines, uas zoo li tsis muaj kev ywj pheej ntawm kev ua haujlwm qia cell. Nyob rau hauv kev laus, lub peev xwm loj hlob, muaj peev xwm sib txawv, thiab genomic stability ntawm BMSCs poob. Txawm hais tias kev tshawb fawb txog kev laus HSC tau ua tiav, kev tshawb fawb rau BMSCs hauv cov txheej txheem kev laus tseem tsis txaus. Nyob rau hauv cov laus cov pob txha, aberrations nyob rau hauv lub BMSC microenvironment, xws li mob o, ua rau muaj roj deposits uas coincide nrog ib tug txo nyob rau hauv mesenchymal progenitors, pob txha poob, thiab fibrosis [38]. Qhov kev poob qis ntawm lub hnub nyoog no hauv BMSC muaj nuj nqi ua rau nws lub cev tiv thaiv kab mob tsis muaj peev xwm. BMSCs los ntawm cov pob txha pob txha ntawm cov nas muaj hnub nyoog tau pom tias muaj peev xwm ua kom muaj zog tsawg. Ntxiv mus, BMSCs los ntawm cov laus pob txha pob txha pom tau hais tias txo qis kev mob, tej zaum los ntawm kev txo qis ntawm phosphorylation ntawm JNK signaling [39]. Yog li ntawd, tswj kom muaj lub pas dej BMSC txaus thiab muaj peev xwm BMSC kev lag luam los ntawm cov pob txha pob txha yog qhov tseem ceeb rau kev noj qab haus huv ntawm cov pob txha ib puag ncig rau kev kho mob thiab tseem yuav pab txhawb cov ntaub so ntswg rov qab los ntawm ntau hom peripheral cov ntaub so ntswg puas. Nyob rau hauv cov laus, tsis muaj peev xwm rov tsim dua tshiab, txhim kho autoimmune teb, thiab txhim kho cov lus teb inflammatory tuaj yeem cuam tshuam nrog lub hnub nyoog ntsig txog BMSC lwj thiab tsis ua haujlwm [38].
2.3 EPCs hauv pob txha pob txha thiab kev laus
EPCs nyob rau hauv cov pob txha pob txha thiab circulating EPCs nyob rau hauv peripheral cov ntshav tuaj yeem sib txawv rau hauv cov hlwb endothelial thiab tsim cov kab mob endothelial ntawm vasculature. Ob leeg EPCs thiab HSCs hauv cov pob txha pob txha yog muab los ntawm hemangioblast [40]. EPCs hauv pob txha pob txha nthuav qhia CD34, CD133, thiab VEGFR2 (KDR/Flk1). Tom qab tsiv los ntawm cov pob txha pob txha mus rau cov ntshav, circulating EPCs poob lawv progenitor muaj peev xwm thiab pib endothelial sib txawv, qhia von Willebrand factor, CD31, CD144, VEcadherin, thiab eNOS [41, 42].
EPCs tuaj yeem tsim los ntawm cov pob txha pob txha thiab ua lub luag haujlwm tseem ceeb hauv kev kho cov ntaub so ntswg nrog cov txheej txheem los tsim thiab tswj cov endothelium los ntawm kev tswj cov coagulation, arterial tone, permeability, hlab ntsha loj hlob, thiab o. Raws li kev laus zuj zus, tus naj npawb ntawm EPCs thiab lawv txoj haujlwm tau txo qis nrog kev nce oxidative kev nyuaj siab, o, senescent phenotype oxidized low-density lipoprotein (ox-LDL), thiab telomere shortening, uas nws thiaj li ua rau muaj kev pheej hmoo rau cov kab mob vascular xws li atherosclerosis thiab kab mob plawv. [43]. EPCs los ntawm cov neeg laus yog cov rhiab heev rau oxidative kev nyuaj siab, tej zaum vim txo qis thiab kev ua ntawm cov antioxidant enzyme glutathione peroxidase-1 (GPX1), uas tom qab ntawd txo qis cell ciaj sia [44]. Ox-LDL, uas muaj feem cuam tshuam rau cov kab mob plawv, suav nrog hnub nyoog thiab txo qis kev muaj sia nyob thiab kev ua haujlwm ntawm EPCs los ntawm inhibiting eNOS kev qhia thiab kev ua haujlwm [45]. Cov hnub nyoog EPCs raug txheeb xyuas los ntawm lawv lub peev xwm ciaj sia taus ntawm tes thiab kev soj ntsuam colony-forming unit, txawm tias cov txheej txheem ntawm EPC kev laus tsis tau kawm txaus. Yog li, EPC kev ua haujlwm tsis zoo nrog kev laus kuj tuaj yeem cuam tshuam nrog kev kho qeeb ntawm ischemic vascular puas thiab muaj kev pheej hmoo siab ntawm cov kab mob plawv.
3 Systemic rejuvenation yam thiab pro-aging yam
Kev hloov pauv hauv lub cev ua rau muaj qhov sib txawv ntawm cov neeg hluas thiab cov laus thiab ntawm cov neeg noj qab haus huv thiab muaj mob. Cov yam tseem ceeb hauv cov qia hlwb tuaj yeem cuam tshuam ncaj qha rau lawv lub zog thiab coj lawv txoj hmoo.
Heterochronic parabiosis thwmsim tau elucidated lub xub ntiag ntawm systemic rejuvenating thiab pro-aging yam thiab lawv hloov nrog lub hnub nyoog (Fig. 3). Xyoo 1864, tus kws kho mob Fab Kis Fab Kis Paul Bert tau ua qhov kev sim heterochronic parabiosis ntawm albino nas los kawm txog cov teebmeem ntawm kev laus. Parabiosis (los ntawm cov lus Greek, para 'ntxiv' thiab bios 'lub neej') siv cov txheej txheem phais kom lub cev txuas cov hlab ntsha thiab tsim kom muaj kev sib koom ua ke rau ob yam kab mob uas muaj hnub nyoog sib txawv [5]. Nyob rau xyoo 1950, cov kws tshawb fawb pom tias cov nas qub tau ntsib cov teebmeem zoo dua qub, thiab cov nas me me tau luv dua li qhov nruab nrab ntawm kev sib txuas ntawm ob tus tsiaj. Hauv xyoo 1970s, kev sim parabiosis raug txwv los ntawm cov cai tshawb fawb tsiaj. Txawm li cas los xij, lawv tau rov ua haujlwm dua hauv 2000s rau kev tshawb fawb txog kev laus. Cov kev tshawb fawb parabiosis tsis ntev los no tau pom tias cov txiaj ntsig zoo ntawm cov ntshav tuaj yeem tig rov qab lub qia cell moos: cov haujlwm ntawm cov qia hlwb qub tau rov ua dua tshiab, thiab cov qia cell ua haujlwm tsis muaj zog thaum lawv raug rau cov tub ntxhais hluas lossis laus cov ntshav, feem. Cov txheej txheem rov ua kom rov zoo dua qub thiab ua rau muaj kev laus yog cov ntsiab lus nyob rau hauv Table 1. Kev loj hlob sib txawv (GDF) 11, oxytocin, bursicon, thiab HGFA yog txhua tus neeg sib tw systemic rejuvenating yam thiab C-C motif chemokine (CCL) 11 thiab b2- microglobulin (B2M) yog qhov ua rau kev laus.
3.1 TSI 11
Cov nyhuv rejuvenating ntawm GDF11 tau pom thawj zaug hauv kev sim parabiosis. Pob txha morphogenetic protein 11, lwm lub npe rau GDF11, tau tshaj tawm tias yog ib qho kev ncig uas cuam tshuam lub hnub nyoog ntsig txog plawv hypertrophy hauv nas [6]. GDF11, tus tswv cuab ntawm TGF-b superfamily, txo qis thaum lub sijhawm laus. Restoring hluas GDF11
Txawm li cas los xij, hauv 2016-2017, kev tshuaj xyuas tsis sib haum xeeb tau luam tawm qhia tias GDF11 ua rau cov leeg pob txha thiab mob plawv [48-51] thiab tias GDF11 tsis poob rau nas lossis tib neeg thaum laus [48]. Kev laus yog ib qho tshwm sim nyob rau hauv lub neej, complex tshwm sim uas accumulates nyob rau hauv lub sij hawm. Yog li ntawd, kev tshawb fawb ntau qhov ua rau-thiab-tshuaj yuav tsum tau ua kom txiav txim siab lub luag haujlwm ntawm GDF11 uas yog qhov ua kom rov zoo dua qub.
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