Nuclear Sirtuins Thiab Kev Laus Ntawm Kev Tiv Thaiv Kab Mob

Thov hu rauoscar.xiao@wecistanche.comyog xav paub ntxiv

Abstract:Lub cev tiv thaiv kab mob ua rau muaj kev hloov pauv loj nrog lub hnub nyoog uas ua rau muaj kev hloov pauv ntawm lub cev tiv thaiv kab mob, mob tsis tu ncua, thiab txo qis peev xwm los txhim kho lub cev tiv thaiv kab mob tiv thaiv kab mob thiab cov qog nqaij hlav cancer. Kev laus-kev hloov pauv hauv lub cev tiv thaiv kab mob txuas nrog rau lwm cov kab mob uas muaj hnub nyoog, qhia tias kev tiv thaiv kab mob tiv thaiv kab mob tuaj yeem muab txoj hauv kev ua tau los txhim kho kev noj qab haus huv tag nrho ntawm cov neeg laus. Sir2 tsev neeg ntawm cov proteins, tseem hu ua sirtuins, tau cuam tshuam dav hauv genome homeostasis, cellular metabolism, thiab kev laus. Sirtuins yog cov lus teb tseem ceeb rau cov xov tooj ntawm tes thiab ib puag ncig kev ntxhov siab thiab, nyob rau hauv rooj plaub ntawm nuclear sirtuins, lawv ua li ntawd los ntawm kev coj cov lus teb rau chromatin uas suav nrog cov kev cai ntawm noob caj noob ces, retrotransposon repression, txhim kho DNA puas tsuaj, thiab kev ncaj ncees chromosome segregation. Nyob rau hauv lub cev tiv thaiv kab mob, sirtuins qhia cellular sib txawv ntawm hematopoietic precursors thiab txhawb leukocyte polarization thiab ua kom. Nyob rau hauv hematopoietic qia hlwb, sirtuins tiv thaiv quiescence thiab stemness los tiv thaiv cellular qaug zog. Kev tswj hwm ntawm cytokine ntau lawm, uas, nyob rau hauv ntau zaus, yuav tsum tau NF-KB kev cai, yog qhov zoo tshaj plaws-tus cwj pwm mechanism uas sirtuins tswj innate lub cev tsis muaj zog. Hauv kev tiv thaiv kev tiv thaiv kab mob, sirtuins txhawb T cell subset sib txawv los ntawm kev tswj hwm tus tswj hwm, yog li ua kom muaj kev pom zoo sib npaug ntawm tus pab (Th) T cell-dependent teb. Sirtuins yog ib qho tseem ceeb heev rau kev tiv thaiv kab mob, tab sis txoj kev uas lawv tswj kev tiv thaiv kab mob tsis tau nkag siab zoo. Qhov kev tshuaj xyuas no muab kev sib koom ua ke ntawm cov kev hloov pauv cuam tshuam nrog kev tiv thaiv kab mob kev laus thiab nws txoj kev sib raug zoo nrog lub luag haujlwm ntawm nuclear sirtuins hauv lub cev tiv thaiv kab mob thiab tag nrho cov kab mob kev laus. Muab cov khoom tiv thaiv kev laus ntawm sirtuins, kev nkag siab tias lawv pab txhawb kev tiv thaiv kab mob li cas yog qhov tseem ceeb thiab tuaj yeem pab peb tsim cov tswv yim tshiab los txhim kho kev tiv thaiv kab mob hauv lub cev laus.

Ntsiab lus:sirtuins; epigenetics; kev laus; tiv thaiv kab mob; tiv thaiv kab mob; mob

1. Taw qhia

Cellular thiab lub cev ua haujlwm inevitably ua rau muaj kev cuam tshuam nrog lub hnub nyoog.bioflavonoidsNrog rau lub hnub nyoog nruab nrab ntawm cov zej zog, tau muaj kev loj hlob ntawm kev tshawb fawb kev siv zog ua lag luam nyob rau hauv molecular thiab cellular hauv paus ntawm kev laus. Lub hom phiaj kawg yog kom ncua lub neej lossis kev noj qab haus huv los ntawm kev kho mob lossis kev coj cwj pwm uas ncua sij hawm qhov tshwm sim ntawm degenerative syndromes lossis palliate lawv qhov tshwm sim. Nyob rau hauv 2013, Lopez-Otin et al. txhais tau cuaj lub cim ntawm kev laus ntawm mammalian los ntawm kev pom ntawm tes. Cov no suav nrog kev hloov pauv hauv epigenome, genomic instability, mitochondrial thiab qia cell tsis ua haujlwm, thiab poob ntawm proteostasis[1]. Kev poob ntawm cellular zog uas tshwm sim los ntawm kev loj hlob ntawm cov kab mob pathological no nws thiaj li ua rau lub cev tsis muaj zog thiab xav tias yuav kho tau zoo.

Thov nias ntawm no kom paub ntxiv

Nyob rau hauv cov ntsiab lus no, lub cev tiv thaiv kab mob tam sim no tau lees paub tias yog ib qho tseem ceeb ntawm cov txheej txheem kev laus. Piv txwv li, kev tshem tawm tshwj xeeb ntawm DNA kho qhov Excision Repair Cross-Complementation Group 1 (ERCC1) hauv hematopoietic qia hlwb tsis tsuas yog ua rau DNA puas ntau dua hauv cov kab mob hauv lub cev tab sis kuj tseem ntxov ntxov ntxov thiab kev laus ntawm cov kab mob. Tsis tas li ntawd, kev hloov pauv ntawm cov laus splenocytes rau hauv cov nas me yog txaus los ua kom cov laus phenotypes, thaum transplantation ntawm cov tub ntxhais hluas splenocytes mus rau cov nas laus txo cov cim senescence nyob rau hauv ntau cov ntaub so ntswg uas tsis muaj zog [2].

Cistanche tuaj yeem tiv thaiv kev laus

Txawm hais tias muaj pov thawj txaus ntshai tsis ntev los no, cov txheej txheem los ntawm kev laus cuam tshuam rau lub cev tsis muaj zog tau ntev los ntawm kev txaus siab. Kev ua haujlwm tiv thaiv kab mob kom zoo feem ntau nyob ntawm qhov kev sib koom ua ke ntawm nws cov khoom sib txawv, thiab kev laus ntawm lub cev tiv thaiv kab mob tau pom nyob thoob plaws txhua hom kev tiv thaiv kab mob. Yog li ntawd, cumulative perturbations nyob rau hauv lub physiology ntawm lub cev tiv thaiv kab mob nws thiaj li txo nws lub peev xwm los teb rau ob exogenous thiab endogenous insults [3]. Cov txiaj ntsig ntawm kev tiv thaiv kab mob tiv thaiv kab mob cuam tshuam nrog kev tshem tawm ntawm cov hlwb puas thiab puas tsuaj; concomitant nce ntawm senescence markers nyob rau hauv lub cev tsis muaj zog; kev pheej hmoo siab ntawm kev tsim mob qog noj ntshav, ntshav qab zib mellitus, neurodegenerative disorders, autoimmunity, thiab lwm yam mob hnyav; thiab cov lus teb tsis zoo rau kev kis kab mob thiab tshuaj tiv thaiv[4-6]. Ib qho kev tshwm sim loj ntawm kev tiv thaiv kab mob hauv lub cev yog kev ua yeeb yaj kiab, ib qho mob qis qis uas maj mam ua rau, ntawm lwm tus, hematopoietic qia cell (HSC) thiab T cell qaug zog, yog li ua rau lub cev tsis muaj zog.muab cistancheTsis tas li ntawd, qhov mob yog xav kom pab txhawb qhov pib ntawm cov kab mob muaj hnub nyoog [7] Piv txwv li, exacerbated reactivity ntawm microglia (ib hom macrophage hauv lub hlwb) tau txuas rau neurotoxicity thiab neurodegenerative kab mob [8]. Ua ke, cov kev tsis zoo no hauv kev tiv thaiv kab mob ua rau muaj kev cuam tshuam rau lub cev lub cev, qhia txog lub luag haujlwm tseem ceeb ntawm kev tiv thaiv kab mob hauv kev laus tag nrho.

Sirtuins yog ib qho kev hloov pauv hloov pauv tsev neeg ntawm cov proteins uas harbor NADt-dependent deacetylase thiab ADP-ribosyltransferase enzymatic kev ua ub no[9]. Hauv cov tsiaj nyeg, muaj xya sirtuins [10], uas tuaj yeem nyob hauv thaj tsam ntawm lub hauv paus, ib yam li cov ntaub ntawv rau SIRT1, SIRT6, thiab SIRT7, lossis hauv mitochondria, ib yam li SIRT3, SIRT4, thiab SIRT5.SIRT2. Feem ntau pom nyob rau hauv cytoplasm tab sis khi rau chromosomes thaum lub sij hawm mitosis. Sirtuins txhawb nqa cellular adaptation rau kev ntxhov siab los ntawm kev tswj cov epigenetics nyob rau hauv lub nucleus, cellular metabolism hauv mitochondria, thiab crosstalk ntawm lawv. Nuclear sirtuins tswj chromatin muaj nuj nqi los ntawm txoj kev tswj hwm kev sib txuas ntawm histone thiab nonhistone substrates. Nyob rau hauv no hais txog, sirtuin-dependent kev cai ntawm epigenetic cov ntaub ntawv yog ze ze nrog lysine (K) acetylation (ac) ntawm histones H3 thiab H4, xws li H4K16ac, H3K9ac, H3K56ac, H3, H3K18ac, thiab H3K36ac (Daim duab 1). -dependent histone deacetylation yog nruj me ntsis txuas rau kev tswj hwm ntawm histone methylation (kuv) ntawm tib yam lossis nyob ze lysine residues. Piv txwv li, SIRT1 orchestrates heterochromatin tsim los ntawm H3K9ac deacetylation thiab suppressor ntawm variegation 3-9 homolog 1 (SUV39H1) activation [11] yog li nce H3K9me3, ib qho cim archetypal heterochromatic. Thaum lub sij hawm hloov G2 / M, SIRT2 txhawb nqa chromosome condensation los ntawm deacetylating H4K16ac thiab concomitantly activating PR / SET domain-muaj protein 7 (PR-SET7)methyltransferase rau induce monomethylation ntawm H4K20 (H4K20mel) [12], nrog rau lwm yam kev ua haujlwm ntawm epigenetic. SIRT6 ua lub luag haujlwm tseem ceeb hauv gene silencing[13], DNA puas kho [14] thiab chromosome cais [15] los ntawm H3K9ac, H3K56ac, thiab H3K18ac kev tswj hwm, feem, thiab SIRT7 ua haujlwm hauv noob [16] thiab retrotransposon silencing [17] thiab DNA kev puas tsuaj kho [18] los ntawm H3K18ac thiab H3K36ac deacetylation. Nws yog ib qho tseem ceeb uas yuav tsum nco ntsoov tias, nyob rau hauv kev ntxhov siab ntawm tes, SIRT7 auto-ribosylation ua rau nws cov neeg ua haujlwm rau chromatin los ntawm kev sib cuam tshuam ntawm macro-H2Al, ua rau cov noob hloov pauv hloov pauv [16]. Sirtuins yog ubiquitously nthuav qhia cov proteins nrog lub luag haujlwm tseem ceeb hauv ntau cov ntaub so ntswg [19]. Nyob rau hauv lub cev, nuclear sirtuins ua lub luag haujlwm tseem ceeb hauv kev txiav txim siab qhov pib ntawm kev laus thiab kev noj qab haus huv. SIRT1, SIRT6, thiab SIRT7 yog txuam nrog tib neeg thiab nas ntev [20-22], thiab nas overexpressing SIRT6 thoob plaws hauv lub cev lossis SIRT1 tshwj xeeb hauv lub hlwb ob qho tib si ncua lub neej [23,24]. Raws li, nas tsis txaus rau Sirt1, Sirt6 thiab Sirt7 cov noob tsim cov kab mob progeroid.-zoo li cov tsos mob [18,25,26], thiab Sirt2-cov nas tsis muaj peev xwm muaj kev pheej hmoo mob qog noj ntshav [12,27]. Sirtuins tau hais tawm hauv lub cev tiv thaiv kab mob thiab ua si ntau lub luag haujlwm hauv cytokine ntau lawm, o, thiab kev loj hlob ntawm innate thiab adaptive teb. Ntawm no, peb tshuaj xyuas lub luag haujlwm ntawm nuclear sirtuins hauv lub cev tiv thaiv kab mob thiab sib tham txog lawv cov kev sib txuas nrog kev laus ntawm lub cev tiv thaiv kab mob.

2. HCS

HSCs yog lub luag haujlwm rau lub sijhawm ntev ntawm cov qe ntshav thiab tuaj yeem faib ua HSCs ntev thiab luv. Long-term HSCs (LT-HSCs) yog ib tug quiescent pej xeem uas txhawb nqa lub neej-ntev tiam ntawm cov ntshav celltypes. Lawv thawj zaug sib txawv rau hauv lub sijhawm luv luv HSCs (ST-HSCs), uas muaj peev xwm rov tsim cov myeloid thiab lymphoid compartments rau ob peb lub lis piam (Daim duab 2). Thaum lub sij hawm laus, HSCs tau txais cov hnub nyoog muaj feem cuam tshuam txog kev puas tsuaj. Cell-intrinsic thiab cell-extrinsic alterations nce qib thawj-hnub nyoog HSCs los ua ib qho phenotype uas zoo li cov tub ntxhais hluas HSCs [28]. Nyob rau hauv lub xeev khov kho, cov tub ntxhais hluas HSC yog quiescent tshwj tsis yog tias muaj teeb meem hauv lub cev, tshwj xeeb yog kis kab mob, tshwm sim, nyob rau hauv rooj plaub uas lawv hloov pauv lawv cov metabolism los txhawb nqa qhov loj de novo ntau lawm ntawm cov tshuaj tiv thaiv kab mob. Yog li, qhov ntau zaus ntawm cov teeb meem no nrog lub hnub nyoog, nrog rau kev mob ntev thiab cov kab mob hauv lub cev, maj mam cuam tshuam HSC so. Kev ua HSC txawv txav nws thiaj li ua rau HSC qaug zog, txo qhov muaj peev xwm rov tsim dua tshiab thiab myeloid bias [29]. Tsis tas li ntawd, clonal hematopoiesis pab hierarchically dampen lub zog ntawm lub cev tsis muaj zog thaum nws muaj hnub nyoog. Nyob rau hauv cov laus HSCs, kho DNA tsis zoo, cumulative DNA puas, thiab replication kev nyuaj siab nce ua rau genomic instability uas yuav clonally inherited los ntawm lawv cellular progeny [30]. Yog li, HSC kev laus cuam tshuam rau qhov ntau thiab zoo ntawm progenitor thiab paub tab ntawm lub cev tiv thaiv kab mob.

Daim duab 2. Txheej txheem cej luam ntawm lub cev tiv thaiv kab mob ontogeny thiab nws txoj kev sib raug zoo nrog nuclear sirtuin kev ua. Hematopoiesis pib nyob rau hauv cov pob txha pob txha los ntawm kev sib txawv ntawm cov kab mob hematopoietic qia hlwb (HSC) rau hauv cov kab mob sib txawv ntawm cov kab mob hauv lub cev (sab sauv). Innate lub cev tiv thaiv kab mob tshwm sim los ntawm ib hom kab mob myeloid progenitor (MCP) thiab koom nrog ntau hom kev tiv thaiv kab mob xws li monocytes (Mo), macrophages (Mϕ), eosinophils (Eos), basophils (Baso), thiab neutrophils (Neu) (sab laug). Cov lymphoid progenitors (CLP) ua rau cov B hlwb nyob rau hauv cov pob txha pob txha thiab T hlwb hauv thymus (koj) (txoj cai qis). Natural killer (NK) hlwb, txawm tias muaj cov qog ntshav qog ntshav, ua lub luag haujlwm tseem ceeb hauv kev tiv thaiv kab mob hauv lub cev tiv thaiv cov qog thiab cov kab mob kis kab mob. Dendritic cells (DC) muaj cov lymphoid thiab myeloid keeb kwm (tsis muaj nyob rau hauv daim duab no) thiab zaum ntawm interphase ntawm innate thiab adaptive tiv thaiv. Sirtuins icons qhia txog sirtuin xov tooj ntawm tes-cov luag haujlwm tshwj xeeb. ST-HSC: luv luv HSC; LT-HSC: gong-term; MPP: Multipotent progenitor. Daim duab tsim nrog BioRender.com.

Concomitantly, metabolic deregulation, epigenetic alterations, thiab poob ntawm mitochon-drial homeostasis yog cov cim tseem ceeb ntawm HSC laus [28,29]. Cov kev tsis xws luag no muaj kev sib cuam tshuam heev, thiab sirtuins tau thov kom nyob ntawm lawv txoj kev sib tshuam [29]. Tseeb tiag, SIRT1, SIRT2, thiab SIRT7 yog downregulated thaum laus hauv HSCs (Figures 2 thiab 3), thiab SIRT7 qhia tau txo nyob rau hauv senescent iPSCs [31-33]. Ntxiv mus, SIRT1 thiab SIRT2 lub hom phiaj histone cim H4K16ac raug txo qis hauv cov hnub nyoog HSCs [34].Ntau qhov kev tshawb fawb tau tshaj tawm SIRT1 yog qhov tseem ceeb rau HSC kev ncaj ncees thiab kev tswj hwm lawv tus kheej lub peev xwm rov ua dua tshiab thiab cov kab ke tshwj xeeb. Sirt1/HSCs recapitulate ob peb yam ntxwv ntawm hnub nyoog HSCs [39]. Zoo ib yam li qhov tau pom thaum lub sijhawm laus, Sirtl / HSCs khiav tawm quiescence thiab nthuav dav DNA puas thiab ROS tsub zuj zuj. Qhov tseem ceeb, kev ua haujlwm ntawm qhov kev hloov pauv ntawm Forkhead Box (FOXO3), uas txhawb nqa quiescence thiab nws tus kheej rov muaj peev xwm hauv HSCs, tau tswj hwm zoo los ntawm SIRT1 deacetylation hauv HSCs thiab lwm hom cell.cistanchSIRT1 tshem tawm hauv cov nas laus ua rau HSCs myeloid-biased thiab induces anemia thiab lymphopenia. Ib yam li ntawd, ntau cov noob uas feem ntau tau tswj hwm hauv cov hnub nyoog HSCs qhia tau hais tias muaj zog ntxiv thaum Sirt1 tshem tawm. Thaum lub sij hawm laus, tus naj npawb ntawm HSCs paradoxically nce raws li qhov tshwm sim ntawm qhov poob ntawm quiescence, uas xaus li txo HSC regenerative muaj peev xwm. Yog li, thaum tsis muaj SIRT1, qhov zaus ntawm LSK (Linage-Sca-1 ntxiv rau Cov Khoom Siv Ntxiv , cov neeg muaj ntau hom cellular uas muaj HSCs) cov hlwb thiab LT-HSCs nce, txawm hais tias qhov zaus ntawm ST-HSCs tsis cuam tshuam [39 ].Qhov sib txawv, qhov kev siv tshuaj tua kab mob hnyav ntawm SIRT1 nrog Sirtinol (Table 1) hauv murine fetal LSK hlwb txo qhov zaus ntawm LSK hlwb, qhia tias kev poob ntawm lub cev lossis ntev ntawm SIRTI ac-tivity tuaj yeem muaj qhov cuam tshuam sib txawv ntawm HSC biology. Hauv ex vivo-cultured LSK hlwb, lub lauj kaub-sirtuin inhibitor nicotinamide (NAM) txhawb nqa HSC qhov sib txawv, thaum sirtuin agonist resveratrol txhawb nqa stemness los ntawm kev tawm tsam HSC sib txawv. Ib yam li ntawd, hauv vitro-cultured LSK hlwb los ntawm Sirtl / nas qhia qis dua tus kheej lub peev xwm raws li qhov tshwm sim ntawm cov txheej txheem cuam tshuam nrog FOXO kev tawm tsam, p53 ua kom, thiab ROS tsub zuj zuj [35].Txawm hais tias SIRT1 downregulation tau raug tshaj tawm hauv cov hnub nyoog HSCs, muaj qee qhov kev pom tsis sib haum xeeb hauv qhov no, yog li nws yog qhov kev sib cav. Rimmele thiab cov neeg ua haujlwm tau tshaj tawm hauv cov nas hais tias SIRT1 qhia tau siab dua hauv LSK hlwb dua li ntawm tag nrho cov pob txha pob txha (BM) hlwb, thaum muaj hnub nyoog murine HSCs tau txo qis SIRT1 qib [39]. Hauv kev sib piv, Chambers et al. tsis pom muaj hnub nyoog cuam tshuam txog kev hloov pauv ntawm SIRT1 hauv murine HSCs [32]. Txoj kev tshawb no ua los ntawm Xu et al. tsis tau qhia qhov sib txawv ntawm SIRTl hauv LSK hlwb los ntawm cov nas muaj hnub nyoog, ib yam nkaus. Txawm li cas los xij, lawv tau tshaj tawm cov txheej txheem nthuav dav uas cov qib SIRT1 protein ntau tau txo qis vim kev xaiv autophagic degradation ntawm SIRT1 protein [49].

Sirtuins kuj tau cuam tshuam rau kev khaws cia ntawm mitochondrial kev ncaj ncees hauv HSCs thaum laus. Tseeb tiag, SIRT2 tau txuas nrog kev saib xyuas ntawm HSC homeostasis hauv cov nas muaj hnub nyoog los ntawm kev tawm tsam ntawm NLR tsev neeg pyrin domain uas muaj 3 (NLRP3) inflammasome, multimeric protein complex koom nrog hauv kev hnov ​​​​mob puas tsuaj- thiab cov kab mob cuam tshuam nrog cov qauv hauv HSCs, mitochondrial kev nyuaj siab tuaj yeem ua rau kev ua kom NLRP3, thiab kev ua kom tsis zoo ntawm NLRP3 inflammasome paub tias yuav ua rau cov cell tuag thiab kev ua haujlwm poob hauv HSCs thaum laus.cistanche AustraliaThaum cov tub ntxhais hluas Sirt2 / nas muaj ib txwm HSC zaus nrog lub peev xwm rov tsim dua tshiab, qhov ntawm HSCs qis dua qub Sirt27 nas. Qhov tseem ceeb, SIRT2 tau hais tawm ntawm qhov txo qis hauv cov hnub nyoog HSCs, uas cuam tshuam nrog ntau dua NLRP3 inflammasome activation, yog li sawv cev rau lub tswv yim zoo ntawm HSC poob rau hnub nyoog Sirt2- / nas [36].

SIRT6 tsis tau cuam tshuam ncaj qha rau HSCs hauv cov ntsiab lus ntawm kev laus, tab sis nws paub tias tsim nyog rau HSC quiescence thiab kev noj qab haus huv. SIRT6 tsis muaj peev xwm ua rau muaj qhov progeroid HSC phenotype vim yog kev tswj hwm ntawm epigenetic dysregulation ntawm Wnt signaling. HSC homeostasis feem ntau cuam tshuam los ntawm Wnt ligands thiab teeb liab, uas pab tswj HSC kev ncaj ncees [50,51]. SIRT6 cuam tshuam nrog Wnt signaling transcription factor LEF1 (lymphoid enhancer binding factor 1), uas recruits SIRT6 rau Wnt lub hom phiaj noob. Ntawm cov neeg txhawb nqa ntawm cov noob no, SIRT6 deacetylates nws lub hom phiaj H3K56ac thiab yog li ntsiag to lawv cov lus.cov txiaj ntsig cistancheThaum tsis muaj SIRT6, Wnt lub hom phiaj cov noob tau dhau los ua dhau los, ua rau muaj qhov tsis zoo ntawm HSC kev loj hlob uas thaum kawg ua rau HSC qaug zog thiab txo qis tus kheej rov muaj peev xwm. Qhov Sirt6 deficient phenotype tuaj yeem thim rov qab los ntawm inhibition ntawm Wnt signaling [37].

SIRT7 tau nthuav tawm heev thoob plaws hauv lub cev hematopoietic [52]. SIRT7 knock-out nas nthuav tawm tag nrho lub cev progeroid phenotype [18], thiab Sirt7 / HSCs qhia ntau yam ntawm cov hnub nyoog HSCs: poob ntawm quiescence, myeloid bias, thiab nce propensity nkag mus rau lub cell voj voog thaum txhawb nrog cytokines ex vivo [31 ].Nyob rau hauv HSCs, SIRT represses qhov kev qhia ntawm ntau lub noob coding rau mitochondrial ribosomal proteins thiab tran-scription yam los ntawm kev sib cuam tshuam ncaj qha nrog lawv cov promoters nyob rau hauv ib tug nuclear respiratory factor 1 (NRF1)-nyob. Cov hnub nyoog ntawm lub cev tiv thaiv kab mob ua rau muaj kev cuam tshuam ntawm mitochondrial dysregulation, uas cuam tshuam nrog kev ua haujlwm tsis zoo ntawm mitochondrial thiab nce mitochondrial loj [38] Mitochondrial dysfunction ua rau tsub zuj zuj ntawm misfolded proteins thiab invokes lub mitochondrial unfolded protein cov lus teb (mtUPR) cov tshuaj tiv thaiv kev sib txuas lus (mtUPR). . Sirt7/HSCs tso saib mitochondrial loj thiab txhim kho basal qhia ntawm mtUPR noob, thaum SIRT7-knocked. down (KD) hlwb qhia tsis muaj peev xwm tshem tawm cov proteins uas tsis zoo. Qhov no qhia tau hais tias Sirt7-h HSCs raug tsim los ntawm kev ntxhov siab mitochondrial, uas ua rau lawv txais yuav lub cev muaj hnub nyoog phenotype. Nyob rau hauv cov laus HSCs, ribosomal DNA (rDNA) transcription tau txuas mus rau replication thiab nce DNA puas. SIRT7 yog tus tswj hwm loj ntawm rDNA transcription [52], ua los ntawm kev tswj hwm ntawm cov khoom sib txawv ntawm cov tshuab basal transcriptional, tab sis seb qhov haujlwm no puas tuaj yeem ua lub luag haujlwm hauv proteostasis thiab metabolism hauv cov hnub nyoog HSCs tsis paub.

3.Innate Immunity

Innate tiv thaiv muaj ntau hom cell, nrog rau cov neeg tua neeg (NK) hlwb, ntau yam macrophage pejxeem, monocytes, dendritic hlwb, neutrophils, eosinophils, thiab basophils (Daim duab 2). Innate lub cev tiv thaiv kab mob tshwm sim los ntawm hematopoietic qia hlwb hauv cov pob txha pob txha thiab, qee zaum, los ntawm kev rov ua nws tus kheej ncaj qha [53]. Hauv cov neeg laus, cov kab mob hauv lub cev tsis muaj zog nyob hauv feem ntau ntawm peb cov ntaub so ntswg, qhov chaw uas lawv ua lub luag haujlwm tseem ceeb hauv kev teb rau kev hem sab nraud thiab hauv cov ntaub so ntswg homeostasis. Kev nplua nuj, kev faib tawm thiab kev ua haujlwm ntawm lub cev tiv thaiv kab mob hauv lub cev tau hloov pauv nrog kev laus, lub sij hawm ntev thiab kev sib koom ua ke qis qis ntawm proinflammatory cytokines yog ib qho tseem ceeb hauv kev ua rau kev laus. Tseeb tiag, lub xeev no ntawm kev mob o, lossis mob, yog ib qho tseem ceeb ntawm kev tiv thaiv kab mob uas ua rau muaj kev cuam tshuam ntawm kev tiv thaiv kab mob thiab cov ntaub so ntswg tsis zoo [54]. Sirtuins tswj kev ua haujlwm ntawm lub cev tiv thaiv kab mob hauv ntau theem nrog qhov cuam tshuam tseem ceeb rau kev tiv thaiv kab mob thiab kab mob kev laus (Daim duab 2). Rau feem ntau, sirtuin downregulation nyob rau hauv tib neeg lub cev tiv thaiv kab mob yog txuam nrog proinflammatory dab, thiab lawv overexpression yog xav los tiv thaiv cov ntaub so ntswg. Ib yam li ntawd, tag nrho lub cev los yog myeloid-specific sirtuin deficiency hauv cov nas ua rau muaj kev txhim kho ntawm cov kab mob sib txawv, suav nrog autoimmunity, rog rog, thiab neurodegeneration [55-58].

Kab lus no yog muab rho tawm los ntawm Genes 2021, 12, 1856. https://doi.org/10.3390/genes12121856 https://www.mdpi.com/journal/genes