Sirtuins Hauv raum Kev Noj Qab Haus Huv Thiab Kab Mob Ⅱ

Sirtuins nyob rau hauv mammalian physiology

Cov kev tshawb fawb pib ntawm SIRTs tau tsom mus rau kev txheeb xyuas cov substrates tshwj xeeb rau lawv cov kev ua haujlwm enzymatic, qhia lawv cov kev koom tes tshwj xeeb rau ntau yam txheej txheem ntawm tes. Raws li kev nkag siab ntawm SIRTs txuas ntxiv mus, cov lus qhia tawm tshiab qhia tias SIRTs tswj cov haujlwm ua haujlwm ntawm cov hom phiaj proteins, orchestrating finely tuned physiological teb nyob rau hauv ntau lub cellular txheej txheem, nrog rau cov kev cai metabolic, oxidative kev nyuaj siab, cell ciaj sia taus, thiab kev saib xyuas ntawm genome stability. poj niam deev. Lawv txoj kev koom tes hauv ntau txoj hauv kev lom neeg tsim SIRTs ua tus tswj hwm tseem ceeb ntawm cellular homeostasis.

Nyem rau Cistanche rau mob raum

kev cai metabolic

SIRT thawj zaug tau txais kev nyiam rau nws cov txiaj ntsig zoo hauv kev hloov pauv kev txwv caloric, tsuas yog kev cuam tshuam ntawm lub cev kom ntev lub neej ntawm ntau yam kev sim ua qauv. Cov kev tshawb fawb tob tob tau piav qhia txog lub network ntawm SIRT cov txheej txheem tswj hwm cov protein uas tswj hwm lub zog homeostasis, qhia tias txhua tus SIRTs tswj cov cellular metabolism mus rau qhov sib txawv.

Lub luag haujlwm muaj peev xwm ntawm SIRT3 hauv cellular metabolism tau txais kev saib xyuas thoob plaws vim nws qhov tseem ceeb mitochondrial localization. Tshwj xeeb, SIRT3 tau pom los tswj cov deacetylation thiab kev hloov pauv ntawm ntau lub hom phiaj hauv cov saw hlau thauj hluav taws xob (ETC) txoj hauv kev los ntawm deacetylation ntawm mitochondrial ribosomal protein 10 (MRPL10). SIRT3 tswj cov metabolism hauv homeostasis los ntawm stimulating fatty acid -oxidation thiab ketone lub cev tsim. Nuclear SIRTs kuj tseem ua lub luag haujlwm hauv kev tswj hwm metabolic. SIRT1 tswj cov haujlwm ntawm cov khoom siv hloov pauv, suav nrog peroxisome proliferator-activated receptor- (PPAR), peroxisome proliferator-activated receptor-coactivator 1- (peroxisome proliferator-activated receptor gamma coactivator 1- , PGC-1 } ) thiab forkhead box type O transcription factors (FOXO), uas tswj ntau txoj hauv kev, suav nrog lipid metabolism, glucose homeostasis, thiab Gluconeogenesis. SIRT6 inhibits cov kev ua haujlwm ntawm hypoxia-inducible factor 1 (HIF-1) los ntawm deacetylation ntawm H3K9 hauv HIF{21}} txhawb nqa, yog li inhibiting kev qhia ntawm glycolysis noob thiab yog li ua haujlwm tseem ceeb ntawm cov piam thaj. homeostasis. regulating yam. Cov txheej txheem no ua rau SIRT6 tswj cov piam thaj kom zoo rau hauv lub voj voog TCA raws li kev noj zaub mov zoo. Kev tshem tawm ntawm SIRT6 hauv cov hlwb myeloid predisposes nas rau cov piam thaj intolerance thiab insulin tsis kam.

Mitochondrial dynamics thiab biogenesis

Mitochondria yog cov organelles ubiquitous, tab sis lawv cov morphology thiab tus lej sib txawv ntawm cov ntaub so ntswg thiab hloov pauv sai nrog cov khoom noj khoom haus. Mitochondria muaj nyob rau hauv dynamic networks uas nws morphology yog txiav txim los ntawm cov txheej xwm tawm tsam ntawm fission thiab fusion (Fig. 3b), nruj nreem tswj los tswj lub zog tso zis.

Fission ua rau mitochondria sib faib, ua rau me me mitochondria, yog li ua rau tag nrho cov huab hwm coj ntawm lub organelle thiab ua rau kom muaj zog txaus. Txawm li cas los xij, me me mitochondria tau ua rau muaj kev cuam tshuam rau daim nyias nyias depolarization thiab oxidative puas tsuaj. Cov txheej txheem molecular ntawm kev faib suav nrog kev nrhiav neeg ua haujlwm ntawm cytoplasmic dynamin-related protein 1 (Drp1) mus rau sab nrauv mitochondrial membrane. Drp1 khi rau mitochondrial fission factor (Mff), thiab qhov ua tau zoo tsim ib lub nplhaib zoo li cov qauv nyob ib ncig ntawm mitochondria, severing lub organelle.

Nyob rau hauv sib piv, fusion induces ib tug interconnected mitochondrial network uas dilutes cov tshuaj lom los ntawm reactive oxygen hom (ROS) generated thaum lub sij hawm ib txwm metabolism thiab txhawb nqa lub zog ntau lawm. Fusion tshwm sim los ntawm kev sib sau ua ke ntawm GTPases, uas yog mitochondrial fusion proteins (Mfn1 thiab Mfn2) thiab optic atrophy 1 (Opa1), nyob rau sab hauv thiab sab nrauv mitochondrial membranes. SIRT1 thiab SIRT3 txhawb nqa mitochondrial fusion los ntawm kev ncaj qha deacetylate Mfn2 thiab Opa1 feem, thaum SIRT6 txhawb nqa mitochondrial fusion los ntawm kev tiv thaiv Drp1 phosphorylation los ntawm Rho-txuas protein kinase 1 (ROCK1).

Tus naj npawb ntawm mitochondria nyob rau hauv ib lub cell kuj nyob ntawm cov txheej txheem ntawm biogenesis thiab mitophagy. Mitochondrial biogenesis yog kev yug dua tshiab ntawm mitochondria tshiab thiab feem ntau yog tswj los ntawm PGC1. SIRT1 tuaj yeem tswj hwm mitochondrial biogenesis los ntawm kev ncaj qha deacetylation PGC1, thaum SIRT6 tuaj yeem cuam tshuam tsis ncaj qha rau deacetylation ntawm PGC1. SIRT3 induces PGC1 qhia nyob rau hauv AMP-activated protein kinase (AMPK)-raws li, yog li txhawb mitochondrial biogenesis.

Mitophagy yog txheej txheem tswj kom zoo uas cais cov mitochondria puas los ntawm kev noj qab haus huv tes hauj lwm rau kev pov tseg. SIRT1 thiab SIRT3 tuaj yeem cuam tshuam ncaj qha rau serine / threonine kinase PTEN-induced putative kinase 1 (PINK1)-Parkin-dependent mitotic phagocytosis, thiab indirectly los ntawm cov txheej txheem xws li FOXO1/3 deacetylation. SIRT1 kuj txo qhov Kev Tshaj Tawm ntawm lub hom phiaj mammalian ntawm rapamycin (mTOR) thiab induces mitochondrial phagocytosis. SIRT3 indirectly txhim kho mitochondrial phagocytosis los ntawm activating AMPK thiab ua kom mitochondrial membrane muaj peev xwm. Txog niaj hnub no, lub luag haujlwm ntawm SIRT6 hauv mitophagy tsis tau tshaj tawm.

oxidative kev nyuaj siab

Enzymes thiab subcellular compartments ntsig txog kev tswj hwm metabolic feem ntau yog cov neeg tsim khoom loj tshaj plaws ntawm ROS, uas yog qhov kawg tshem tawm los ntawm endogenous antioxidant system. Kev puas tsuaj Oxidative tshwm sim thaum ROS ntau lawm tshaj qhov kev tshem tawm ntawm cov cellular antioxidant enzymes thiab ua lub luag haujlwm tseem ceeb hauv kev ua rau ntau yam kab mob hauv lub cev sib txawv.

SIRTs ua haujlwm sib koom ua ke kom nkag siab sai thiab txhim kho kev tiv thaiv kab mob hauv lub cev (Daim duab 3c). SIRT1 thiab SIRT6 tuaj yeem qhib qhov kev sib cais ntawm qhov transcription factor nuclear-erythroid 2-txog yam 2 (Nrf2) los ntawm inhibitory protein Keap1, inducing kev qhia ntawm antioxidant noob. Tsis tas li ntawd, SIRT1 thiab SIRT3 qhib ob peb FOXO tsev neeg koom nrog hauv kev tswj cov kev ntxhov siab oxidative. FOXO1 tuaj yeem tshem tawm ROS ntau dhau los ntawm kev tswj hwm cov noob caj noob ces xws li superoxide dismutase 2 (SOD2) thiab catalase. Tsis tas li ntawd, SIRT1, SIRT3, thiab SIRT6 yog deacetylated, yog li inhibiting qhov ua rau ntawm qhov transcription factor NF-κB. Cov txheej txheem no txwv qhov kev tswj hwm ntawm cov noob caj noob ces uas txhawb nqa ROS ntau lawm.

Mitochondria, qhov chaw ntawm oxidative phosphorylation, yog lub hauv paus cellular ntawm ROS thiab tshwj xeeb tshaj yog raug rau ROS-vim kev puas tsuaj. Mitochondrial SIRTs txhawb kev ua kom cov enzymes tshwj xeeb koom nrog ROS tshem tawm. Tshwj xeeb, SIRT3 deacetylase SOD2 pab txhawb kev tshem tawm ntawm superoxide thiab isocitrate dehydrogenase 2, uas txhawb kev tsim cov tshuaj tiv thaiv antioxidants thiab catalyzes cov ntsiab lus tseem ceeb hauv lub voj voog tricarboxylic acid (TCA).

DNA puas thiab apoptosis

Thaum cov kab mob antioxidant detoxification tsis tuaj yeem tswj tau ROS nyob rau theem siab, qhov ntau dhau ntawm cov cellular pro-oxidative ib puag ncig tuaj yeem ua rau muaj kev puas tsuaj DNA ntau thiab tsis tuaj yeem, suav nrog kev hloov pauv hauv paus, DNA hla kev sib txuas, thiab ib leeg- lossis ob txoj hlua tawg. thaum kawg txhawb kev tuag ntawm tes. Nuclear SIRT muaj lub luag haujlwm tiv thaiv DNA los ntawm kev puas tsuaj. Spatiotemporal tswj kev kho DNA los ntawm SIRT1 thiab SIRT6. SIRT1 deacetylation ntawm SIRT6 ntawm K33 ua ntej SIRT6 polymerization thiab kev lees paub ntawm ob-stranded DNA so, ua rau hauv cheeb tsam chromatin remodeling. Tsis tas li ntawd, SIRT1 antagonizes DNA strand tawg los ntawm Ku70 deacetylation.

SIRT kuj muaj ntau lub luag haujlwm hauv kev tiv thaiv apoptosis. Hauv cov hlwb mesangial, SIRT1 inhibits apoptosis los ntawm kev ua kom p53 thiab Smad7. SIRT1 kuj txo qis glomerular podocyte apoptosis los ntawm FOXO4- nyob ntawm inhibition ntawm Bim, qhov tseem ceeb txiav txim siab hauv kev pib txoj hauv kev apoptotic intrinsic. SIRT3 exerts anti-apoptotic los ntawm kev tswj ROS tsub zuj zuj, thaum SIRT6 tiv thaiv hlwb los ntawm apoptosis los ntawm kev tswj Notch signaling thiab actin cytoskeleton.

Autophagy

Autophagy yog cov txheej txheem nruj nruj uas tso cai rau kev pov tseg ntawm cov hloov pauv hloov pauv hloov pauv, sib sau ua ke, thiab cov kab mob puas tsuaj los ntawm lysosomal degradation, yog li tiv thaiv cov hlwb los ntawm apoptosis. SIRTs koom nrog kev tswj hwm ntawm cov txheej txheem autophagy los ntawm kev ncaj qha deacetylates cov proteins tseem ceeb ntawm cov txheej txheem autophagy nrog rau cov txheej txheem tsis ncaj.

Kev tshaib kev nqhis ua rau SIRT1, uas nyob rau hauv lem deacetylates autophagy Cheebtsam, xws li Atg5, Atg7, thiab LC3. SIRT1 kuj ua rau autophagy los ntawm deacetylation ntawm Mfn2 hauv mitochondria. Cov ntaub ntawv uas twb muaj lawm qhia tau hais tias SIRT3 thiab SIRT6 tuaj yeem tswj hwm autophagy los ntawm kev ua kom muaj ntau yam kev taw qhia hauv qab. SIRT3 nce qhov kev qhia ntawm Beclin-1 thiab LC3II hauv lub raum tubular hlwb los ntawm kev txo qis hauv Notch-1-Hes{12}} txoj hauv kev, yog li txhawb nqa autophagy thiab ERK-CREB txoj kev taw qhia. Ib yam li ntawd, SIRT6 overexpression induces autophagy los ntawm attenuating lub insulin-zoo li kev loj hlob yam (IGF)-Akt-mTOR signaling pathway; Txawm li cas los xij, nws cov txheej txheem molecular yuav tsum tau kawm ntxiv.

cellular senescence

Cellular senescence yog ib daim ntawv ruaj khov ntawm lub voj voog ntawm tes uas raug ntxias los ntawm telomere shortening thaum lub caij nyoog laus thiab los ntawm ntau yam endogenous thiab exogenous stimuli. Senescence yog ib qho kev ua haujlwm zoo, ntau txoj hauv kev uas cov hlwb tau txais kev hloov pauv ntau hauv cov noob qhia, ua tsis tau raws li kev loj hlob txhawb cov cim, thiab tsim kom muaj kev sib koom ua ke ntawm secretory phenotype (SASP). Txawm hais tias tseem muaj kev tsis sib haum xeeb, cov pov thawj ntxiv qhia tau hais tias SIRT txo cov kev laus ntawm cov cellular feem ntau los ntawm kev tswj hwm ntawm cov noob caj noob ces, kev txhawb nqa ntawm autophagy, thiab txhim kho DNA kev puas tsuaj.

SIRT1 tuaj yeem tswj hwm H3K9 thiab H4K16 acetylation, yog li inhibiting kev qhia ntawm SASP pro-inflammatory Cheebtsam IL-6 thiab IL-8. Tsis tas li ntawd, SIRT1 antagonizes cellular senescence los ntawm fine-tuning ERK signaling txoj kev thiab tswj lub deacetylation ntawm LKB1 thiab nws downstream lub hom phiaj protein AMPK. SIRT6 khi rau telomeres, thiab inhibition ntawm SIRT6 tuaj yeem ua rau telomere puas thiab senescence, uas cuam tshuam nrog telomeric H3K9 hyperacetylation thiab p53-binding protein 1 (53BP1) khi. Tsis tas li ntawd, SIRT6 txwv kev kaw lub voj voog ntawm tes los ntawm proteasomal degradation ntawm p27Kip1, ib tug tswv cuab ntawm lub cell voj voog-dependent kinase inhibitor tsev neeg, yog li ncua kev laus. SIRT3 thaum kawg stabilizes heterochromatin los ntawm kev cuam tshuam nrog lub hnab ntawv nuclear proteins thiab heterochromatin-txog cov proteins, yog li tiv thaiv kev laus, alleviating oxidative kev nyuaj siab, thiab txhawb autophagy.

Inflammation thiab tiv thaiv kab mob

Ib lub tswv yim tshiab hauv bioenergetics yog qhov txuas ntxiv ntawm cellular metabolism nrog kev nrhiav neeg ua haujlwm thiab ua kom lub cev tiv thaiv kab mob thiab mob. Txawm hais tias kev tshawb fawb txog lub luag haujlwm ntawm SIRT hauv qhov mob tseem nyob rau theem pib, cov pov thawj nce ntxiv qhia tias NAD + qib thiab SIRT cov ntawv sau tseg thiab / lossis cov qib protein tau txo qis hauv cov ntaub so ntswg tshwj xeeb thaum mob o. Lub peev xwm los inhibit NF-κB ua kom muaj SIRT1 muaj zog tiv thaiv kev ua haujlwm hauv ntau hom cell. SIRT1 kuj tswj kev mob los ntawm kev deacetylation ntawm high-mobility pawg thawv 1 (HMGB1). Nws yog ib qho tshwj xeeb uas tsis yog-histone structural protein uas feem ntau nyob hauv lub nucleus thiab tswj cov qauv thiab kev ua haujlwm ntawm chromosomes. Kev poob ntawm SIRT1 nce HMGB1 acetylation thiab tso tawm rau hauv qhov chaw ntxiv, ua rau muaj teeb meem ua rau muaj kab mob hauv lub cev. Kev ua kom SIRT1 thiab SIRT3 kuj muaj cov teebmeem tiv thaiv, xws li txo cov qog necrosis (TNF) ntau lawm los ntawm macrophages thiab monocytes thaum mob hnyav. Myeloid cell-specific deletion ntawm SIRT1 exacerbates lub cev tsis ua haujlwm thiab kev tuag hauv cov qauv kev sim ntawm cov kab mob o. SIRT3 txo qhov mob los ntawm kev tswj cov NLRP3 inflammasome, yog li inhibiting oxidative kev nyuaj siab thiab pro-inflammatory cytokines. Hauv lub raum pob zeb nas qauv, SIRT3 noob knockout ua rau txo qis hauv cov neeg nyob hauv B hlwb hauv lub raum thiab nce hauv macrophage thiab granulocyte infiltration, qhia tias SIRT3 qhia cuam tshuam rau lub cev tiv thaiv kab mob hauv cov ntaub so ntswg.

Ib txoj kev tshawb fawb xyoo 2023 tau txheeb xyuas cov txheej txheem uas cuam tshuam mitochondrial cuam tshuam nrog kev mob thaum lub raum raug mob. Cov kws tshawb fawb pom tias cytoplasmic to ntawm mitochondrial RNA (mtRNA) thiab ua kom lub cytoplasmic qauv lees paub receptor retinoic-inducible gene 1 protein (RIG1, tseem hu ua DDX58) ua rau inflammatory cell koom haum recruitment. RIG1-zoo li receptors yog cov sensors tseem ceeb ntawm kev kis tus kab mob los yog kab mob, thiab ua kom RIG1- nyob ntawm cytoplasmic RNA sensing txoj hauv kev tuaj yeem ua rau muaj kev mob tshwm sim. Lub peev xwm ntawm mtRNA los txhawb kev ua kom muaj kev cuam tshuam ntawm txoj kev ua rau muaj kev mob tshwm sim tuaj yeem yog qhov tshwm sim ntawm endosymbiotic keeb kwm ntawm mitochondria, uas tau hloov zuj zus los ntawm cov kab mob thiab sib faib cov qauv tsim qauv nrog prokaryotes. Ntxiv NAD + precursors tuaj yeem rov qab NAD + qib, txhim kho mitochondrial muaj nuj nqi, thiab tiv thaiv lub raum puas. Qhov kev tshawb pom no qhia tias SIRTs, tshwj xeeb tshaj yog SIRT3, tuaj yeem ua lub luag haujlwm tiv thaiv los ntawm kev tswj hwm mitochondrial kev ncaj ncees thiab tiv thaiv mitochondrial RNA to.

Cistanche kho mob raum li cas?

Cistancheyog ib hom tshuaj suav tshuaj ntsuab siv rau ntau pua xyoo los kho ntau yam mob, suav nrograumkab mob. Nws yog muab los ntawm qhuav stems ntawmCistanchedeserticola, ib tsob nroj nyob rau hauv cov suab puam ntawm Tuam Tshoj thiab Mongolia. Lub ntsiab active Cheebtsam ntawm cistanche yogphenylethanoidglycosides, echinacoside cov tshuaj, thiabacteoside, uas tau pom tias muaj txiaj ntsig zoo rau lub raum kev noj qab haus huv.

Kab mob raum, tseem hu ua kab mob raum, hais txog ib yam mob uas lub raum ua haujlwm tsis zoo. Qhov no tuaj yeem ua rau muaj cov khoom pov tseg thiab cov co toxins hauv lub cev, ua rau muaj ntau yam tsos mob thiab teeb meem. Cistanche tuaj yeem pab kho mob raum ase los ntawm ntau lub tswv yim.

Ua ntej, cistanche tau pom tias muaj cov nyhuv diuretic, txhais tau tias nws tuaj yeem ua rau cov zis ntau ntxiv thiab pab tshem tawm cov khoom pov tseg ntawm lub cev. Qhov no tuaj yeem pab txo lub nra ntawm lub raum thiab tiv thaiv kev tsim cov co toxins. Los ntawm kev txhawb nqa diuresis, cistanche kuj tseem tuaj yeem pab txo qis ntshav siab, ib qho teeb meem ntawm cov kab mob raum.

Ntxiv mus, cistanche tau pom tias muaj cov teebmeem antioxidant. Kev ntxhov siab oxidative, tshwm sim los ntawm qhov tsis sib xws ntawm kev tsim cov dawb radicals thiab lub cev tiv thaiv antioxidant, ua lub luag haujlwm tseem ceeb hauv kev mob raum. ies pab neutralize dawb radicals thiab txo Oxidative kev nyuaj siab, yog li tiv thaiv lub raum los ntawm kev puas tsuaj. Cov phenylethanoid glycosides pom hauv cistanche tau tshwj xeeb hauv kev tshem tawm cov dawb radicals thiab inhibiting lipid peroxidation.

Tsis tas li ntawd, cistanche tau pom tias muaj cov nyhuv anti-inflammatory. Kev mob yog lwm yam tseem ceeb hauv kev loj hlob thiab kev loj hlob ntawm cov kab mob raum. Cistanche's anti-inflammatory zog pab txo cov zus tau tej cov pro-inflammatory cytokines thiab inhibit qhov ua kom o yuav tsum tau txoj kev, yog li alleviating o nyob rau hauv lub raum.

Tsis tas li ntawd, cistanche tau pom tias muaj cov teebmeem immunomodulatory. Hauv kab mob raum, lub cev tiv thaiv kab mob tuaj yeem ua rau tsis zoo, ua rau muaj kev mob ntau dhau thiab cov ntaub so ntswg puas. Cistanche pab tswj lub cev tiv thaiv kab mob los ntawm kev hloov kho kev tsim khoom thiab kev ua haujlwm ntawm lub cev tiv thaiv kab mob, xws li T hlwb thiab macrophages. Txoj cai tiv thaiv kab mob no pab txo qhov mob thiab tiv thaiv kev puas tsuaj ntxiv rau lub raum.

Ntxiv mus, cistanche tau pom los txhim kho lub raum kev ua haujlwm los ntawm kev txhawb nqa kev tsim kho ntawm lub raum hlab nrog cov hlwb. Lub raum tubular epithelial hlwb ua lub luag haujlwm tseem ceeb hauv kev pom thiab rov nqus cov khoom pov tseg thiab electrolytes. Hauv kab mob raum, cov hlwb no tuaj yeem raug puas tsuaj, ua rau lub raum ua haujlwm puas. Cistanche lub peev xwm los txhawb kev tsim kho ntawm cov hlwb no pab kho lub raum kom zoo thiab txhim kho lub raum tag nrho.

Ntxiv nrog rau cov kev cuam tshuam ncaj qha rau lub raum, cistanche tau pom tias muaj txiaj ntsig zoo rau lwm yam kabmob thiab lub cev hauv lub cev. Txoj hauv kev zoo rau kev noj qab haus huv no tseem ceeb tshwj xeeb hauv cov kab mob raum, vim tias tus mob feem ntau cuam tshuam rau ntau lub cev thiab lub cev. che tau pom tias muaj kev tiv thaiv rau lub siab, lub plawv, thiab cov hlab ntsha, uas feem ntau cuam tshuam los ntawm kab mob raum. Los ntawm kev txhawb nqa kev noj qab haus huv ntawm cov kabmob no, cistanche pab txhim kho lub raum tag nrho thiab tiv thaiv kev mob ntxiv.

Hauv kev xaus, cistanche yog cov tshuaj suav tshuaj ntsuab siv rau ntau pua xyoo los kho mob raum. Nws cov active Cheebtsam muaj diuretic, antioxidant, anti-inflammatory, immunomodulatory, thiab regenerative teebmeem, uas pab txhim kho lub raum ua haujlwm thiab tiv thaiv ob lub raum los ntawm kev puas tsuaj ntxiv. , cistanche muaj txiaj ntsig zoo rau lwm yam kabmob thiab lub cev, ua rau nws txoj hauv kev zoo rau kev kho mob raum.