Cov txiaj ntsig zoo ntawm Exogenous Ketogenic Supplements Ntawm Cov Txheej Txheem Kev Laus Thiab Cov Hnub Nyoog Txog Cov Kab Mob Neurodegenerative Part 2

SIRTs thiab AMPK kuj muaj lub luag haujlwm hauv kev hloov pauv ntawm kev ua neej nyob. Kev ua haujlwm ntawm AMPK-kev kho kom haum xeeb los ntawm qib qis zog muaj lub luag haujlwm hauv inhibition ntawm cov piam thaj ntau lawm, nce kev ua haujlwm ntawm beta-oxidation (rog hlawv), thiab txhawb kev ua haujlwm ntawm mitochondrial thiab mitochondrial biogenesis [79,80] (Daim duab 1).

Raws li cov tsim hluav taws xob tseem ceeb hauv lub xov tooj ntawm tes, mitochondria muaj qhov cuam tshuam uas mus deb dhau qhov ntawd. Nyob rau hauv xyoo tas los no, ntau thiab ntau cov kev tshawb fawb tau pom tias kev ua haujlwm ntawm mitochondria muaj feem cuam tshuam nrog peb lub peev xwm thiab kev nco. Qhov kev sib txuas no muaj txoj hauv kev tshiab kom nkag siab zoo dua thiab tiv thaiv kev puas siab puas ntsws thiab nco tsis tau.

Lub luag haujlwm ntawm mitochondria mus dhau qhov kev tsim tawm thiab tswj kev ua haujlwm ntawm tes. Kev tshawb fawb tshiab qhia tau hais tias mitochondria tseem ceeb heev rau kev tswj cov cell metabolism, txo cov cell puas, thiab tswj kev noj qab haus huv. Lawv kev sib txuas rau kev nco, kev txawj ntse, thiab ntau dua los ntawm lawv lub luag haujlwm tseem ceeb hauv cov txheej txheem muab hluav taws xob hauv cov hlwb. Cov hlwb hauv hlwb yog nyob rau hauv lub xeev ntawm kev siv zog siab thiab xav tau ntau lub zog los tswj cov kev ua haujlwm metabolic. Lub zog tsis txaus yuav cuam tshuam rau kev ciaj sia thiab kev ua haujlwm ntawm cov neurons, ua rau muaj teeb meem xws li kev nco tsis zoo thiab kev paub tsis meej.

Kev ua haujlwm ntawm mitochondria raug cuam tshuam los ntawm ntau yam khoom thiab kev ua neej nyob. Piv txwv li, kev tawm dag zog thiab kev poob phaus txhawb kev loj hlob thiab kev ua haujlwm zoo ntawm mitochondria. Kev noj zaub mov kom zoo thiab kev noj zaub mov ntau ntxiv tuaj yeem txhim kho kev ua haujlwm ntawm mitochondrial thiab txo cov cell puas.

Txawm hais tias mitochondrial muaj nuj nqi txuas nrog peb lub cim xeeb thiab kev txawj ntse, tsis yog txhua yam kev mob cuam tshuam rau mitochondria. Kev zam kev ntxhov siab ntau dhau, txo cov pa phem, thiab kev kawm tswj cov kev xav zoo kuj tseem cuam tshuam nrog kev noj qab haus huv mitochondrial.

Hauv cov ntsiab lus, mitochondria tau txuas nrog peb lub cim xeeb thiab kev txawj ntse. Kev tuav tus cwj pwm zoo thiab saib xyuas koj lub cev thiab kev noj qab haus huv yuav pab tswj kev noj qab haus huv ntawm mitochondrial thiab txav mus rau kev mob hlwb. Nws tuaj yeem pom tias peb yuav tsum txhim kho kev nco, thiab Cistanche deserticola tuaj yeem txhim kho kev nco, vim Cistanche deserticola muaj antioxidant, tiv thaiv kev mob, thiab tiv thaiv kev laus, uas tuaj yeem pab txo qis oxidation thiab inflammatory tshwm sim hauv lub hlwb, yog li tiv thaiv cov kab mob. kev noj qab haus huv ntawm lub paj hlwb. Tsis tas li ntawd, Cistanche deserticola kuj tseem tuaj yeem txhawb kev loj hlob thiab kho cov paj hlwb, yog li txhim kho kev sib txuas thiab kev ua haujlwm ntawm neural networks. Cov teebmeem no tuaj yeem pab txhim kho kev nco, kev kawm, thiab kev xav nrawm, thiab tseem tuaj yeem tiv thaiv kev loj hlob ntawm kev paub tsis meej thiab kab mob neurodegenerative.

Nyem paub los txhim kho lub sij hawm luv luv

AMPK exerts nws effecton zog metabolism los ntawm phosphorylation ntawm, piv txwv li, (i) ACCs (acetyl-CoA carboxylase), xws li ACC1, uas ACC1 inhibition ua rau kev txhim kho ntawm fatty acidoxidation / mitochondrial-oxidation thiab suppression ntawm lipogenesis; thiab (ii) qhov kev hloov pauv hloov pauv SREBP1 (sterol regulatory element-binding protein 1).

Cov nyhuv inhibitory ntawm AMPK ua rau txo qis fatty acid synthesis [80]. Nws tau pom tias kev ua kom AMPK tuaj yeem yog lub hom phiaj tiv thaiv kev laus, piv txwv li, los ntawm kev txhim kho mitochondrial dysfunction. AMPK activation tsis tsuas yog txo cov kev ua ntawm anabolic txoj hauv kev thiab nce kev ua haujlwm ntawm catabolic txoj hauv kev ua rau muaj kev nce ntxiv ntawm lub zog (ATP)-tsim txoj hauv kev thiab txo qis zog (ATP)-siv cov txheej txheem, tab sis kuj ua rau kev ua neej nyob hauv cov neeg mob ntshav qab zib [79] , 80] ib.

Tsis tas li ntawd, kev nce hauv AMPK ua rau txo qis kev qhia ntawm proinflammatory cytokines, yog li kev sib txuas lus sib txuas ntawm tes (Daim duab 1) los ntawm inhibition ntawm qib siab-glycation kawg cov khoom (AGEs)-evoked nce qib ntawm transcription factor NF-κB (nuclear factorkappa-light- chain-enhancer ntawm activated B hlwb) mRNA thiab protein [81].

Txawm li cas los xij, AMPKactivation tuaj yeem cuam tshuam qhov mob los ntawm cov lus teb inflammatory inducer NF-κBby lwm txoj hauv kev, piv txwv li, los ntawm kev ua rau inhibitory kev ua ntawm SIRT1, PGC-1 (peroxisome proliferator-activated receptor / PPAR coactivator 1), FOXOs thiab p53( transcription factor qog suppressor protein 53) ntawm NF-κB-signaling los yog ntawm inhibition ntawm NF-κB activator ER (endoplasmic reticulum) kev nyuaj siab thiab oxidative stress [82]. Ntxiv mus, AMPK tuaj yeem nce PGC-1 kev ua haujlwm tsis yog ncaj qha (los ntawm phosphorylation, ua ntej tom qab deacetylation ntawm PGC1- los ntawm SIRT1) [83] tab sis kuj los ntawm kev ntes ntawm PGC-1 inhibitoryeffect ntawm mTORC1 [66 ] (Daim duab 1).

Nws kuj tau pom tias kev txwv caloric tuaj yeem ua rau muaj kev cuam tshuam rau lub neej dhau los ntawm SIRTs [84], yog li SIRTs raug suav tias yog cov khoom tiv thaiv kev laus. SIRTs, xws li SIRT1 thiab SIRT3 tuaj yeem hnov ​​​​txog qis zog los ntawm kev tshawb pom ntawm NAD + qib siab.SIRTs yog Class III HDACs histone deacetylases, uas enzymes siv coenzyme NAD + tshem tawm acyl pawg ntawm cov protein, xws li acetyl-lysine residues ntawm histones thiab tsis. -histones, xws li PGC-1 , FOXOs, p53 thiab NF-κB [69,85].

Raws li kev noj zaub mov tsis txaus (caloric txwv), qib ntawm cov khoom noj deacetylase SIRT1 tau nce siab (uas, piv txwv li, nce cov piam thaj ntau ntxiv los ntawm PGC-1 ), tab sis nws qib txo qis los ntawm kev noj ntau dhau [86, 87].Nws tau ua pov thawj tias kev ua kom muaj zog (overexpression) ntawm SIRT1 tuaj yeem ua rau muaj sia nyob thiab muaj lub luag haujlwm txo qis hauv txhua lub hnub nyoog cov txheej txheem (hallmarks) (Daim duab 1) thiab ntau yam kab mob, xws li cov kab mob neurodegenerative [88–90]. Tseeb, SIRT1 qhia tau pom tias yuav txo qis nrog lub hnub nyoog, piv txwv li hauv lub hlwb [91].

Ntxiv mus, nws kuj tau pom tias qhov txo qis ntawm SIRT1 hauv microglia tuaj yeem ua rau kev paub tsis meej (Tau-mediated memorydeficits) hauv kev laus thiab neurodegeneration los ntawm upregulation ntawm IL-1 (interleukin-1) [91]. Nws kuj tau pom tias kev txwv caloric tuaj yeem txo qis Alzheimer's kab mob, piv txwv li, los ntawm kev txo qis ntawm A plaque [92] thiab txhawb kev noj qab haus huv thiab kev laus [93] zoo li ntawm SIRT1 activation [93-95], qhov kev pheej hmoo siab caloric yuav nce ntxiv. kev txhim kho ntawm Alzheimer's disease [96].

Kev txo qis ntawm SIRT1 qib kuj tau pom nyob rau hauv parietal cortex hauv cov neeg mob Alzheimer's kab mob, uas cuam tshuam nrog kev sib sau ntawm A thiab Tau [97], thaum ua kom SIRT1 cansuppress -synuclein aggregation [98]. Nws tau raug pom tias SIRT1-evoked neuroprotection tuaj yeem ua rau tsis yog tsuas yog txo qis hauv excitotoxicity thiab neurodegeneration [99,100] tab sis kuj txhim kho kev noj qab haus huv thiab kev ua neej ntev dua los ntawm kev ua kom PGC-1 (txoj cai ntawm mitochondrial biogenesis) (Daim duab 1) thiab FOXOs (txhim kho kev ntxhov siab ntawm autophagy, tiv thaiv oxidative kev nyuaj siab thiab DNA kev puas tsuaj thiab FOXO30s muaj peev xwm induce cell voj voog ntes), nrog rau inhibition ntawm p53 (txoj cai ntawm apoptosis thiab cell voj voog) thiab SREBP1 (txoj cai ntawm lipid metabolism. ) ua kom [6,88,101,102].

Cov txheej txheem no tuaj yeem ua rau txo qis hauv cov kab mob neurodegenerative, xws li Alzheimer's disease thiab amyotrophic lateral sclerosis ntawm, piv txwv li, SIRT1-generated deacetylation (andactivation) ntawm PGC-1 [94].

Nws tau raug pom tias SIRT1 tuaj yeem cuam tshuam cov cell agingvia p53 (deacetylation yog li inhibiting p53 thiab nws cov proapoptotic kev ua si) [103] thiab tuaj yeem hloov kho txoj kev loj hlob (txoj hmoo) ntawm neural progenitor cells [104]. Nws kuj tau pom tias cellular NAD + qib qis dua nrog lub hnub nyoog (vim los ntawm, piv txwv li, khaws DNA puas thaum laus) ua rau txo qis SIRT kev ua, mitochondrial tsis ua haujlwm [88,105], thiab kev loj hlob ntawm cov kab mob uas muaj hnub nyoog, xws li cov kab mob neurodegenerative [106]. Yog li ntawd, cov cuab yeej kho mob, xws li kev tswj hwm ntawm cov tshuaj sib txawv thiab cov kev kho mob metabolic, uas nce NAD + qib tuaj yeem ua rau txo qis kev cuam tshuam ntawm cov txheej txheem kev laus thiab kab mob, nrog rau kev txhawb nqa lub neej ntev [6,106] (Daim duab 1).

Nws kuj tau pom tias kev hloov pauv, tsis muaj, kev hloov pauv caj ces lossis tsis ua haujlwm ntawm insulin / IGF-1 receptor, nrog rau kev txwv caloric (inhibiting insulin / IGF-1 signaling) (Daim duab 1), txuas ntxiv lub neej, tsis tsuas yog nyob rau hauv cov tsiaj sib txawv, xws li nas, tab sis kuj inhumans [6,107,108] ntawm PI3K (phosphatidyl inositol-3-kinase)/Akt/FOXOs txoj kev txhawb kev tiv thaiv kev ntxhov siab.

Raws li cov xwm txheej no (piv txwv li, caloric txwv-evoked txo qis hauv cov tshuaj insulin) unphosphorylated FOXOs tuaj yeem raug thauj mus rau lub nucleus los txhawb kev hloov pauv ntawm ntau cov noob (xws li, lawv cov phosphorylation impedes lawv translocation rau lub nucleus) ua rau muaj kev ntxhov siab ntau ntxiv, cell voj voog ntes, puas tsuaj. kho thiab ua kom ntev (lifespan) [72,109].

2.2. Telomere Shortening thiab Genome Instability

Txo qhov ntev ntawm qhov rov ua dua ribonucleoprotein ib ntus ntawm qhov kawg ntawm qhov kawg ntawm eukaryotic chromosomes (telomere) thaum lub sij hawm cell faib tau pom thaum lub sij hawm physiological ("natural") kev laus ntawm cov tsiaj txhu [110].

Txawm li cas los xij, yog tias qhov ntev ntawm telomeres luv dhau nws tuaj yeem ua rau muaj kev puas tsuaj rau DNA molecules, cellular senescence, mitochondrial dysfunctions (tso qis mitochondrial biogenesis thiab kev ua haujlwm, nrog rau nce ROS / reactive oxygen hom ntawm p53-evoked tsuj ntawm PGC. -1 / ), thiab o thiaj li laus [110–112]. Nws kuj tau hais tias kev ua kom muaj kev ua haujlwm ntawm telomerase tsis tsuas yog txhim kho lub sijhawm muaj sia nyob thiab ua rau lub neej ntev ntawm cov tsiaj nyeg [3,113] tab sis kuj tseem yuav ua rau muaj txiaj ntsig zoo rau kev loj hlob ntawm cov qog nqaij hlav cancer (los ntawm kev txo qis thiab tsis txawj tuag) [2,114].

Yog li, luv luv telomeres- thiab qis (yog tias muaj) telomerase kev ua haujlwm-evoked senescence tuaj yeem tiv thaiv kev mob qog noj ntshav tsawg kawg hauv cov tsiaj uas muaj sia nyob ntev [2]. Nws kuj tau qhia tias telomereattrition yuav muaj lub luag haujlwm hauv kev txhim kho cov kab mob neurodegenerative hnub nyoog, xws li Alzheimer's disease [111]. AMPK thiab SIRT1 tuaj yeem txo cov hnub nyoog ntsig txog telomere luv luv los ntawm PGC-1 (Daim duab 1) qhia txog lub luag haujlwm muaj txiaj ntsig ntawm AMPK/SIRT1 ua kom muaj kab mob onneurodegenerative [115].

Tsis tsuas yog telomere shortening, tab sis kuj chromosomal aneuploidy, somatic kev hloov pauv, thiab kev hloov pauv yuav muaj lub luag haujlwm hauv DNA puas [116]. Ntxiv mus, qhov tsis xws luag ntawm DNArepair mechanisms (xws li lub hauv paus excision kho), mitochondrial DNA mutation, thiab perturbations ntawm nuclear lamina kuj yuav ua rau genome instability (sau ntawm caj ces puas), cell dysfunction, thiab kev laus ntawm senescence [63,117-119], uas processesmayev. (lossis muaj lub luag haujlwm hauv) cov kab mob muaj hnub nyoog [78].

Qhov tseeb, DNA puas tuaj yeem ua rau qhov pib ntawm cov kab mob neurodegenerative, xws li Parkinson's disease thiab amyotrophiclateral sclerosis [120]. Kev hloov pauv hauv kev ncaj ncees thiab kev ruaj ntseg ntawm DNA tuaj yeem tshwm sim los ntawm ob qho tib si exogenous (piv txwv li, los ntawm tshuaj lom neeg, lub cev, thiab cov kab mob lom) thiab endogenousinfluences (xws li, los ntawm kev nce qib ROS thiab DNA replication yuam kev) [118].

SIRT1 muaj kev cuam tshuam zoo rau DNA kho yog li genomic instability (Daim duab 1), qhia txog kev txo cov nyhuv ntawm SIRT1 ua rau cov kab mob neurodegenerative [115].

2.3. Kev hloov pauv ntawm Epigenetic

Lub epigenome muaj cov hloov pauv molecular uas cov noob tuaj yeem qhib lossis cuam tshuam rau tag nrho lub neej [121]. Nws tau pom tias muaj kev hloov pauv hauv cov noob caj noob ces, xws li kev hloov pauv hauv DNA methylation qauv (uas yog methylation inversely proportional to geneactivation), chromatin remodeling, expression of non-coding RNAs, and posttranslationalhistone modifications kuj tseem txhawb kev laus [78,122].

Piv txwv li, nws tau raug pom tias (hyper)methylation ntawm kev txhawb nqa cov kab ke ntawm cov noob (thiab feem ntau ntawm DNA) tuaj yeem ua rau muaj kev ntsiag to ntawm cov noob muaj feem xyuam nrog, piv txwv li, apoptosis [123], whereasDNA hypomethylation txhawb gene activation [124,125]. Nws kuj tau pom tias qhov hloov pauv ntawm cov qauv DNA methylation (hypermethylation lossis hypomethylation) los ntawm hnub nyoog tej zaum yuav yog ib qho tseem ceeb hauv cov txheej txheem ntawm kev laus [126] thiab siv los ua lub sijhawm laus (piv txwv li, qhov sib txuas ntawm methylcytosine / DNA methylation thiab hnub nyoog tau pom) [125,127 ].

Ob lub ntiaj teb kev txo qis ntawm DNA methylation (uas yog hypomethylation tuaj yeem ua rau muaj hnub nyoog txuam nrog genomic instability thiab poob ntawm telomere kev ncaj ncees) thiab qhov chaw tshwj xeeb hypermethylation ntawm cov txheej txheem promoter tau pom los ntawm hnub nyoog [122–124,128]. Ib txoj kev tshawb fawb yav dhau los tau pom tias muaj hnub nyoog-induced hypomethylation raug kho los ntawm kev txwv caloric [129].

Nws tau raug pom zoo tias kev txwv caloric tuaj yeem txhim kho SIRT1 kev hloov pauv ua rau muaj kev nce hauv histone deacetylation thiab methylation ntawm DNA, uas cov teebmeem yuav them rau qhov txo qis hauv SIRT1 kev ua thiab DNA methylation, nrog rau kev nce hauv histoneacetylation los ntawm lub hnub nyoog thiab nce hauv lifespan. (piv txwv li, los ntawm kev saib xyuas cov qauv DNA methylation txaus thiab genomic stability) [90,130] (Daim duab 1).

Histone acetyltransferases (HATs) tuaj yeem xa cov acetyl pawg mus rau histones ua rau muaj txiaj ntsig zoo, thiab txo qis kev cuam tshuam nrog DNA, thiab yog li txhim kho DNA transcription. Hloov pauv, HDACscan tshem tawm acetyl pawg los ntawm histones, uas cuam tshuam rau kev sib cuam tshuam ntawm histones thiab DNA uas ua rau txo qis dua.

Yog li ntawd, antagonists ntawm HDACsmay pab txhawb DNA transcription [131,132]. Raws li cov txiaj ntsig saum toj no, cov kev qhia ntawm cov noob tuaj yeem raug thaiv (tso tseg) los ntawm tsis yog tsuas yog methylation ntawm DNA (xws li, methylation ntawm cov noob caj noob ces) tab sis kuj deacetylation ntawm histones, uas txuas mus ntxiv ntawm cov noob yuav yog ib qho tseem ceeb hauv kev laus laus [123 ].

Ntxiv mus, histone methylation thiab demethylation (los ntawm histone methyl transferases thiab demethylase) thiab histone acetylation thiab deacetylation (los ntawm HATs thiab HDACs) tuaj yeem hloov kho lub neej, kev laus, thiab cov kab mob muaj hnub nyoog [124,133,134]. Piv txwv li, SIRT1-evoked deacetylation ntawm Nk2 homeobox 1 tuaj yeem ua rau lub neej ntev thiab ncua kev laus hauv cov nas [133]. Nws tau raug pom tias inhibitors ntawm HDACs (Classes I, II, thiab IV HDACs), xws li TrichostatinA, yuav ua tau zoo hauv kev kho mob ntawm cov kab mob neurodegenerative thiab kev ncua ntawm lifespan [135,136].

Ntxiv mus, HDAC inhibitors txo qhov kev tuag ntawm lub cev muaj zog neurons, txhim kho lub cev muaj zog, nce lub sijhawm ciaj sia, thiab ua rau lub neej txuas ntxiv rau cov nas ntawm amyotrophic lateral sclerosis [137], rov qab ntshai kev kawm, txo qis, thiab txhim kho kev txawj ntse hauv cov qauv nas. ntawm Alzheimer'sdisease [138,139] thiab generated neuroprotection nyob rau hauv ib tug qauv ntawm Parkinson tus kab mob [140].

Nws kuj tau hais tias miRNAs (microRNAs; ib chav kawm ntawm me me uas tsis yog-coding silencing RNAs, uas muaj lub luag haujlwm hauv kev tswj hwm ntawm mRNA txhais lus) yuav txhawb nqa lub neej ntev thiab muaj kev cuam tshuam hauv ob qho tib si neurodegeneration thiab hnub nyoog ntsig txog cov kab mob neurodegenerative [141,142]. Forexample, hippocampal upregulation ntawm miR-181 thiab cuam tshuam txog kev txo qis ntawm SIRT1 expressionand, vim li ntawd, kev txo qis ntawm synaptic plasticity tau pom nyob rau hauv tus qauv nas ntawm Alzheimer's disease [143].

Raws li cov lus teb rau kev puas tsuaj loj, tsis tu ncua DNA (xws li, los ntawm oxidative kev nyuaj siab), activated poly(ADP-ribose)-polymerase-1 (PARP-1) ntxiv ADP-ribose units rau histones ua rau kev txhawb nqa ntawm chromatin so [144], txhim kho PARylation (tsim PAR polymers raws li cov txiaj ntsig ntawm epigenetic) ntawm qhov chaw ntawm DNA puas (hloov pauv) [63] thiab ntxias cov cell cell tuag los ntawm kev hloov pauv ntawm cov noob qhia thiab mitochondrialdysfunction [145].

Ntxiv mus, ntau tshaj PARP1 ua kom pom tau pom nyob rau hauv cov laus thiab cov kab mob neurodegenerative ua rau mitochondrial tsis ua haujlwm, neuroinflammation, ion, anddysregulation of autophagy (thiab mitophagy; eg, ntawm mTOR activation) [144,146]. Piv txwv li, PARP1 txhim kho qhov mob ntawm NF-κB, txo qis NAD + qib thiab SIRT1 kev ua haujlwm, thiab muaj lub luag haujlwm hauv telomere shortening thiab, raws li qhov tshwm sim, txhim kho senescence, ua rau neurodegeneration thiab txo lifespan [144,146,147]. Raws li kev ua SIRT1 txo qis los ntawm hnub nyoog [91], nyob rau hauv cov xwm txheej no, ob qho tib si acetylation (ua kom ua kom muaj zog) ntawm PARP1, thiab PAPR1-evokedneuroinflammation tuaj yeem nce ntxiv. Txawm li cas los xij, txhawm rau tuav nws txoj haujlwm los ntawm kev khaws cia ntawm NAD + qib, SIRT1 tuaj yeem ua tsis tau (deacetylate) Parp1 [148].

Ntxiv mus, kev nthuav qhia ntau ntxiv thiab kev ua kom ntau dhau ntawm PARP1 tau pom hauv Parkinson's disease, Alzheimer's disease thiab amyotrophic lateral sclerosis [145,149,150]. Raws li nws tau tshwm sim, A thiab -synuclein tsub zuj zuj tuaj yeem tsim kom muaj PAPR1 ntawm, piv txwv li, nce qib ntawm ROS; Yog li, txhim kho PARP1 kev ua kom hnyav dua Alzheimer's kab mob thiab Parkinson cov tsos mob los ntawm kev txhawb nqa ntawm A thiab -synuclein aggregation, feem [145,149].

Yog li ntawd, PARP1 inhibition tuaj yeem txo cov kab mob neuroinflammation, dysregulation ntawm autophagy thiab mitochondrial dysfunction yog li inhibit kev loj hlob ntawm o (hnub nyoog) ntsig txog cov kab mob neurodegenerative (los yog txo lawv cov tsos mob), piv txwv li ntawm SIRT1 ua kom [146,151].

Nws kuj tau pom tias qhov nce hauv HBlevel tuaj yeem ua rau muaj kev hloov pauv ntawm cov noob caj noob ces los ntawm -hydroxybutyrylation of histones uas ua rau muaj kev tswj hwm ntawm cov noob qhia yog li hloov cov hlwb mus rau qhov hloov pauv ntawm lub zog [152].

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