Los ntawm Cocer Peptides 
1 month ago
Tag nrho cov kab lus thiab cov ntaub ntawv ntawm cov khoom lag luam muab rau ntawm lub vev xaib no tsuas yog rau cov ntaub ntawv tshaj tawm kev tshaj tawm thiab cov hom phiaj kev kawm.
Cov khoom muab rau hauv lub vev xaib no yog npaj tshwj xeeb rau kev tshawb fawb hauv vitro. Kev tshawb fawb hauv vitro (Latin: * hauv iav *, lub ntsiab lus hauv iav) yog ua los ntawm tib neeg lub cev. Cov khoom no tsis yog tshuaj, tsis tau txais kev pom zoo los ntawm US Food and Drug Administration (FDA), thiab yuav tsum tsis txhob siv los tiv thaiv, kho, lossis kho txhua yam mob, kab mob, lossis mob. Nws raug txwv nruj raws li txoj cai los qhia cov khoom no rau hauv tib neeg lossis tsiaj lub cev hauv txhua daim ntawv.
Txheej txheem cej luam
Kev laus yog tus cwj pwm los ntawm kev maj mam poob ntawm lub cev ua haujlwm thiab ua rau muaj kab mob ntau ntxiv. Kev nkag siab txog cov cim qhia thiab cov yam ntxwv ntawm kev laus yog qhov tseem ceeb rau elucidating cov txheej txheem lom neeg ntawm kev laus thiab tsim cov tswv yim kom qeeb kev laus thiab tiv thaiv kab mob.
Daim duab 1. Anti-wrinkle mechanism.
Cov cim thiab cov yam ntxwv ntawm kev laus
(1) Genomic Instability
Genomic instability yog tus tsav tsheb tseem ceeb ntawm kev laus. Kev puas tsuaj ntawm DNA tshwm sim los ntawm endogenous yam xws li reactive oxygen hom (ROS) tsim thaum lub sij hawm metabolic dab, nrog rau cov exogenous yam xws li ultraviolet hluav taws xob thiab tshuaj. Raws li cov kab mob muaj hnub nyoog, qhov ua tau zoo ntawm DNA kho cov cuab yeej txo qis, ua rau tsis muaj kev puas tsuaj DNA. Yog tias ob-strand DNA tawg tsis raug kho kom zoo, lawv yuav ua rau chromosomal structural abnormalities thiab gene rearrangements, cuam tshuam gene qhia thiab cellular function. Hauv cov hlwb laus, kev hloov pauv hauv kev qhia ntawm cov protein tseem ceeb hauv DNA kev puas tsuaj teb txoj hauv kev txo cov cell lub siab ntev rau DNA puas, yog li ua kom cov txheej txheem kev laus. Qhov no genomic instability tsis tsuas yog cuam tshuam rau ib txwm cellular muaj nuj nqi, tab sis kuj yog ze ze rau qhov pib thiab kev loj hlob ntawm ntau yam hnub nyoog cov kab mob xws li mob cancer thiab neurodegenerative kab mob.
(2) Telomere attrition
Telomeres yog cov txheej txheem DNA rov ua dua ntawm qhov kawg ntawm chromosomes uas ua raws li lub kaus mom tiv thaiv, tiv thaiv fusion thiab degradation ntawm chromosome kawg. Thaum lub sij hawm faib cell, telomeres maj mam luv vim DNA polymerase tsis tuaj yeem rov ua dua qhov kawg ntawm chromosomes. Thaum telomeres luv luv rau qee qhov, cov hlwb nkag mus rau lub xeev senescent lossis raug apoptosis. Qhov no yog vim hais tias luv luv telomeres raug lees paub los ntawm cov hlwb raws li DNA puas, yog li ua kom lub voj voog ntawm tes los tiv thaiv kev faib tawm ntawm tes. Telomerase tuaj yeem txuas ntxiv telomere ntev, tab sis nws cov haujlwm tsis tshua muaj nyob rau hauv feem ntau cov hlwb somatic. Raws li lub hnub nyoog nce, telomeres txuas ntxiv luv, dhau los ua tus cim tseem ceeb ntawm cellular senescence. Qee qhov kev tshawb fawb tau pom tias ua kom telomerase los yog siv cov tshuaj kho noob kom ntev telomere tuaj yeem ua rau qee qhov qeeb cellular senescence, muab kev nkag siab tshiab rau kev tshawb fawb los tiv thaiv kev laus.
(3) Epigenetic Hloov
Kev tswj hwm ntawm Epigenetic plays lub luag haujlwm tseem ceeb hauv spatiotemporal tshwj xeeb ntawm cov noob qhia, thiab cov txheej txheem kev laus yog nrog los ntawm kev hloov pauv ntawm epigenetic thoob plaws. Kev hloov pauv hauv DNA methylation qauv yog ib qho kev hloov pauv ntawm epigenetic. Thaum lub sij hawm kev laus, tag nrho DNA methylation qib txo, tab sis qee qhov tshwj xeeb gene txhawb cov cheeb tsam nthuav tawm hypermethylation, ua rau lub suab ntawm cov noob no. Cov noob muaj feem xyuam nrog kev tswj hwm lub voj voog ntawm tes, kho DNA, thiab lwm yam, muaj kev txo qis kev qhia vim kev txhawb nqa hypermethylation, yog li cuam tshuam rau cov haujlwm ntawm tes. Histone hloov kho xws li acetylation thiab methylation kuj tau hloov pauv, cuam tshuam cov qauv chromatin thiab cov noob nkag tau. Cov kev hloov pauv hauv epigenetic no tuaj yeem tswj hwm cov txheej txheem ntawm tes xws li kev loj hlob, kev sib txawv, thiab kev laus los ntawm kev cuam tshuam cov noob qhia, thiab cov kev hloov pauv hauv epigenetic pom tau tias muaj kev hloov pauv, muab lub hom phiaj rau kev cuam tshuam kev laus.
(4) Poob protein homeostasis
Protein homeostasis yog lub hauv paus rau kev tswj cov cellular muaj nuj nqi, nrog rau cov txheej txheem xws li protein folding, thauj, thiab degradation. Nrog lub hnub nyoog, cov txheej txheem ntawm cov protein homeostasis hauv cov hlwb maj mam ua tsis zoo. Kev qhia thiab kev ua haujlwm ntawm molecular chaperones xws li cov proteins uas muaj cua sov poob qis, tiv thaiv cov proteins tshiab los ntawm folding kom raug, ua rau cov khoom sib txuam ntawm cov proteins tsis zoo hauv cov hlwb. Cov haujlwm ntawm cov proteasome thiab autophagy-lysosomal systems kuj deteriorate, txo lawv lub peev xwm los tshem tawm misfolded thiab puas cov proteins. Kev sib sau ntawm cov proteins uas txawv txav no ua rau sib sau ua ke uas cuam tshuam cov txheej txheem physiological nyob rau hauv cov hlwb, ua kom intracellular kev nyuaj siab qhia txoj hauv kev, thiab ua rau kev laus ntawm cellular. Hauv cov kab mob neurodegenerative, misfolded proteins xws li β-amyloid thiab tau cov proteins sib sau ua ke hauv cov khoom loj, ua rau cov neuronal tsis ua haujlwm thiab tuag, uas cuam tshuam nrog kev poob ntawm cov protein homeostasis thaum lub sijhawm laus.
(5) Dysregulation ntawm nutrient signaling
Txoj hauv kev pom cov zaub mov muaj lub luag haujlwm tseem ceeb hauv kev loj hlob ntawm tes, metabolism, thiab kev laus. Siv cov mTOR (mammalian lub hom phiaj ntawm rapamycin) txoj hauv kev ua piv txwv; Nws tuaj yeem nkag siab txog kev noj zaub mov hauv cov hlwb thiab tswj cov txheej txheem xws li protein synthesis, cell loj hlob, thiab autophagy. Thaum cov as-ham muaj ntau, mTOR tau qhib, txhawb kev loj hlob ntawm tes thiab kev loj hlob; Txawm li cas los xij, kev ua kom ntau dhau ntawm mTOR txoj hauv kev yog txuam nrog kev laus, vim tias nws inhibits autophagy, ua rau cov organelles puas thiab cov proteins, thaum tseem txhawb cov inflammatory teb. Kev txwv tsis pub muaj calorie tsawg tuaj yeem cuam tshuam mTOR kev ua si, qhib autophagy, thiab tshem tawm cov khib nyiab ntawm tes, yog li ua rau kev laus qeeb. Cov tshuaj insulin/insulin-zoo li kev loj hlob zoo-1 (IGF-1) qhia txoj hauv kev kuj tseem muaj feem cuam tshuam nrog kev tswj hwm kev noj haus thiab kev laus; dysregulation ntawm txoj kev no cuam tshuam cov cellular metabolism thiab lifespan. Los ntawm kev tswj cov khoom noj khoom haus-sensing txoj hauv kev, cellular metabolic xeev tuaj yeem txhim kho, yog li qeeb cov txheej txheem kev laus.
(6) Mitochondrial ua haujlwm tsis zoo
Mitochondria, raws li lub cellular powerhouses, ua lub luag haujlwm tseem ceeb hauv kev laus. Nrog rau cov hnub nyoog dhau los, cov qauv thiab kev ua haujlwm ntawm mitochondria tau hloov pauv tseem ceeb. Mitochondrial DNA (mtDNA), tsis muaj kev tiv thaiv histone thiab nyob ze ntawm ROS cov chaw tsim khoom, nws nquag ua rau oxidative puas tsuaj, ua rau muaj kev sib txuam ntawm mtDNA kev hloov pauv. Cov kev hloov pauv no cuam tshuam kev ua haujlwm ntawm mitochondrial respiratory chain complexes, txo ATP kev ua tau zoo, thiab nce ROS ntau lawm. ROS ntau dhau ua rau kev puas tsuaj rau mitochondria thiab lwm yam biomolecules hauv hlwb, tsim kom muaj lub voj voog tsis zoo. Kev tsis sib xws hauv mitochondrial dynamics (xws li fusion thiab fission) kuj cuam tshuam rau mitochondrial kev ua haujlwm thiab kev faib tawm. Hauv cov hlwb senescent, ntau dhau mitochondrial fission ua rau luv luv, fragmented mitochondria nrog kev ua haujlwm tsis zoo. Mitochondrial dysfunction-induced zog metabolism abnormalities thiab nce oxidative kev nyuaj siab yog cov yam ntxwv tseem ceeb ntawm cellular thiab organism aging, ze ze rau qhov pib thiab kev loj hlob ntawm ntau yam muaj hnub nyoog kab mob xws li kab mob plawv thiab neurodegenerative kab mob.
(7) Cellular senescence
Cellular senescence yog hais txog qhov poob ntawm kev loj hlob muaj peev xwm thiab nkag mus rau hauv ib qho kev ruaj khov, tsis tuaj yeem rov qab los ntawm kev loj hlob raug ntes. Senescent hlwb pom cov yam ntxwv phenotypic tshwj xeeb, suav nrog kev ntim ntawm tes, flattened morphology, thiab nce β-galactosidase kev ua haujlwm. Cov txheej txheem ua haujlwm ntawm cellular senescence muaj ntau haiv neeg, suav nrog telomere shortening, DNA puas, thiab oxidative kev nyuaj siab. Senescent hlwb secrete series ntawm cytokines, chemokines, thiab proteases, tsim ib tug senescence-associated secretory phenotype (SASP). SASP tsis tsuas yog ua rau cov kab mob paracrine ntawm cov hlwb nyob ib puag ncig, ua rau cov lus teb inflammatory thiab hloov kho cov kab mob extracellular matrix, tab sis kuj tseem tuaj yeem txhawb cov ntaub so ntswg fibrosis thiab tsim cov qog microenvironment. Thaum cellular senescence tuaj yeem txo cov qog cell proliferation rau qee qhov, qhov ntev ntawm cov cell senescent nyob rau hauv lub cev tuaj yeem cuam tshuam tsis zoo rau cov ntaub so ntswg thiab lub cev ua haujlwm, ua kom cov txheej txheem kev laus.
(8) Stem Cell Exhaustion
Stem cells muaj lub peev xwm los hloov nws tus kheej thiab sib txawv rau ntau hom cell, ua lub luag haujlwm tseem ceeb hauv kev txhim kho, tu, thiab kho cov ntaub so ntswg thiab lub cev. Raws li lub hnub nyoog nce, qia cell muaj nuj nqi maj mam poob, nrog txo tus kheej rov muaj peev xwm thiab tsis muaj peev xwm sib txawv. Thaum lub sij hawm kev laus, qhov sib npaug ntawm hematopoietic qia cell sib txawv rau hauv cov qe ntshav sib txawv raug cuam tshuam, ua rau lub cev tsis muaj zog. Kev loj hlob thiab kev sib txawv muaj peev xwm ntawm mesenchymal qia hlwb kuj tsis muaj zog, cuam tshuam rau kev kho thiab rov tsim dua tshiab ntawm pob txha, pob txha mos, thiab cov ntaub so ntswg adipose. Qhov ua rau qia cell qaug zog suav nrog kev hloov pauv hauv microenvironment, dysregulation ntawm intracellular signaling pathways, thiab tsub zuj zuj ntawm DNA puas. Kev poob ntawm qia cell muaj nuj nqi txo qhov kho lub peev xwm ntawm cov ntaub so ntswg thiab lub cev, ua rau lawv tsis tuaj yeem teb tau zoo rau kev raug mob thiab kab mob, yog li ua rau lub cev laus.
(9) Kev hloov pauv hauv kev sib txuas lus Intracellular
Kev sib txuas lus intercellular yog qhov tseem ceeb rau kev tswj hwm homeostasis ntawm cov ntaub so ntswg thiab lub cev. Thaum lub sij hawm kev laus, kev sib txuas lus intracellular muaj kev hloov pauv loj. Raws li lub hnub nyoog nce, qhov sib txawv ntawm kev sib txuas lus ntawm cov hlwb txo qis, cuam tshuam cov khoom sib pauv thiab cov teeb liab kis ntawm cov hlwb. Tsis tas li ntawd, kev ua haujlwm ntawm endocrine system kuj hloov pauv, ua rau hormonal tsis txaus. Kev hloov pauv hauv kev zais cia thiab kev ua haujlwm ntawm cov tshuaj hormones xws li insulin thiab kev loj hlob hormone cuam tshuam rau lub cev metabolism thiab kev ua haujlwm ntawm tes. Kev ua kom cov kab mob inflammatory kab mob yog lwm qhov tseem ceeb ntawm kev hloov kev sib txuas lus intracellular. Senescent hlwb secrete SASP yam uas ua rau cov kab mob inflammatory teb, cuam tshuam kev sib txuas lus ntawm tes thiab cov ntaub so ntswg microenvironment. Cov kev hloov pauv no hauv kev sib txuas lus intracellular ua rau kev ua haujlwm tsis zoo ntawm cov ntaub so ntswg thiab cov kabmob, yog li txhawb kev loj hlob ntawm kev laus.
Kev sib txuas ntawm Kev Laus Markers thiab yam ntxwv
Cov cim ntau yam thiab cov yam ntxwv ntawm kev laus tsis yog cais tawm tab sis muaj kev sib cuam tshuam thiab kev sib koom ua ke, sib sau ua ke tsav cov txheej txheem kev laus. Genomic instability ua rau DNA kev puas tsuaj, uas nyob rau hauv lem ua rau cellular aging thiab qia cell qaug zog. Telomere attrition kuj activates DNA kev puas tsuaj teb, exacerbating genomic instability. Kev hloov pauv ntawm Epigenetic tuaj yeem cuam tshuam cov noob qhia, yog li tswj cov txheej txheem xws li protein homeostasis, kev tswj hwm zaub mov, thiab kev ua haujlwm mitochondrial. Mitochondrial dysfunction-induced ROS tuaj yeem ua rau DNA puas tsuaj ntxiv, ua rau genomic instability, thaum tseem cuam tshuam rau intracellular signaling pathways thiab hloov intercellular kev sib txuas lus. Cellular senescence thiab qia cell exhaustion impairs kho cov ntaub so ntswg thiab regenerative muaj peev xwm, thaum hloov nyob rau hauv cov ntaub so ntswg microenvironment, nyob rau hauv lem, muaj feem xyuam rau cellular senescence thiab qia cell muaj nuj nqi.
Kev siv cov cim kev laus thiab cov yam ntxwv hauv kev noj qab haus huv thiab kab mob
(1) Raws li Biomarkers
Cov cim kev laus thiab cov yam ntxwv tuaj yeem ua tus biomarkers los ntsuas tus neeg qhov kev laus thiab kev noj qab haus huv. Piv txwv li, los ntawm kev ntsuas telomere ntev, DNA methylation qauv, thiab mitochondrial muaj nuj nqi ntsuas, nws muaj peev xwm kwv yees ib tug neeg lub hnub nyoog lom thiab kev pheej hmoo ntawm kev tsim cov kab mob uas muaj hnub nyoog rau qee yam. Cov biomarkers no pab tshawb pom ntxov ntawm cov teeb meem kev noj qab haus huv, muab lub hauv paus rau kev tswj hwm tus kheej thiab kev cuam tshuam. Hauv kev tiv thaiv cov kab mob plawv, kev tshawb nrhiav qhov mob ntsig txog kev laus biomarkers hauv cov ntshav pab txheeb xyuas cov tib neeg uas muaj kev pheej hmoo siab thiab ua rau muaj kev cuam tshuam ntxov, xws li kev hloov pauv kev ua neej lossis kev kho tshuaj.
(2) Cov Hom Phiaj Tshuaj Txhim Kho
Cov cim ntau yam thiab cov yam ntxwv ntawm kev laus muab ntau lub hom phiaj rau kev txhim kho tshuaj. Rau genomic instability, cov tshuaj uas txhawb kev kho DNA tuaj yeem tsim tau; rau telomere attrition, tshuaj uas qhib telomerase lossis tiv thaiv telomeres tuaj yeem tshawb pom; rau kev poob ntawm cov protein homeostasis, cov tshuaj uas txhim kho molecular chaperone muaj nuj nqi los yog txhawb cov protein degradation tuaj yeem tsim tau, thiab lwm yam. Nyob rau hauv xyoo tas los no, kev tshawb fawb ntawm rapamycin thiab nws cov analogues tsom rau mTOR txoj hauv kev tau ua rau muaj kev vam meej hauv kev qeeb aging thiab ncua lub neej, muab cov qauv zoo rau kev txhim kho tshuaj tiv thaiv kev laus. Rau kev laus ntawm cov cellular, tsim cov tshuaj uas tuaj yeem tshem tawm cov hlwb los yog inhibit SASP tuaj yeem txhim kho cov tsos mob ntawm cov kab mob uas muaj feem rau kev laus thiab qeeb cov txheej txheem kev laus.
(3) Cov Tswv Yim Pabcuam Kev Noj Qab Haus Huv
Raws li kev nkag siab ntawm cov cim kev laus thiab cov yam ntxwv, cov tswv yim kev cuam tshuam kev noj qab haus huv tuaj yeem tsim tau. Nyob rau hauv cov nqe lus ntawm kev noj zaub mov, txwv tsis pub calorie thiab Mediterranean noj zaub mov muaj peev xwm tswj tau txoj hauv kev paub txog cov zaub mov, txhim kho cov txheej txheem metabolic, thiab ncua kev laus. Kev tawm dag zog tuaj yeem txhim kho mitochondrial muaj nuj nqi, txhawb cov qia cell proliferation thiab sib txawv, thiab txhim kho kev sib txuas lus ntawm tes, txhua yam muaj txiaj ntsig zoo ntawm kev ncua kev laus. Kev siv cov tshuaj antioxidants tuaj yeem txo cov kev ntxhov siab oxidative, tiv thaiv cov hlwb los ntawm ROS kev puas tsuaj, thiab tswj cov cellular muaj nuj nqi. Cov tswv yim kev pabcuam kev noj qab haus huv zoo no pab txo qis cov txheej txheem kev laus thiab txhim kho lub neej zoo rau cov neeg laus.
Xaus
Cov cim thiab cov yam ntxwv ntawm kev laus muaj ntau yam kev hloov pauv ntawm cov molecular mus rau cov cellular thiab cov ntaub so ntswg / cov khoom nruab nrog cev, uas muaj kev sib cuam tshuam thiab kev sib koom ua ke, sib sau ua ke tsim cov txheej txheem lom neeg ntawm kev laus. Kev nkag siab txog cov cim thiab cov yam ntxwv no muab lub hauv paus theoretical rau kev tiv thaiv, kev kuaj mob, thiab kev kho mob ntawm cov kab mob laus.
Qhov chaw
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