By Cocer Peptides 
1 ọnwa gara aga
Edemede na ozi ngwaahịa niile enyere na webụsaịtị a bụ naanị maka mgbasa ozi na ebumnuche mmụta.
Ngwaahịa ndị enyere na webụsaịtị a bụ naanị maka nyocha in vitro. A na-eme nyocha in vitro (Latin: * na iko *, nke pụtara na ihe eji enyo) na mpụga ahụ mmadụ. Ngwaahịa ndị a abụghị ọgwụ, ndị US Food and Drug Administration (FDA) akwadoghị ya, ha agaghịkwa eji ya gbochie, gwọọ, ma ọ bụ gwọọ ọnọdụ ahụike ọ bụla, ọrịa, ma ọ bụ ọrịa. Iwu amachibidoro nke ọma iwebata ngwaahịa ndị a n'ime ahụ mmadụ ma ọ bụ anụmanụ n'ụdị ọ bụla.
Nchịkọta
A na-akọwa ịka nká site na iji nwayọọ nwayọọ na-ebelata ọrụ physiological na ịba ụba nke ọrịa. Ịghọta ihe ịrịba ama na njirimara nke ịka nká dị oké mkpa maka ịkọwapụta usoro ndu nke ịka nká na ịmepụta atụmatụ iji belata ịka nká na igbochi ọrịa ndị metụtara ya.
Ọgụgụ 1. Usoro mgbochi mgbochi.
Ihe ịrịba ama na njirimara nke ịka nká
(1) Akwụsịghị nwoke na nwanyị
Akwụsịghị ike nke mkpụrụ ndụ ihe nketa bụ isi ihe na-akpata ịka nká. Mkpokọta mmebi DNA sitere na ihe ndị dị ndụ dị ka ụdị oxygen na-emeghachi omume (ROS) nke a na-emepụta n'oge usoro metabolic, yana ihe ndị dịpụrụ adịpụ dị ka ultraviolet radiation na chemicals. Ka ihe dị ndụ na-akawanye nká, arụmọrụ nke usoro nrụzi DNA na-ebelata, na-eduga na mmebi DNA na-edozibeghị. Ọ bụrụ na emezighị mgbawa DNA nke eriri abụọ nke ọma, ha nwere ike ibute nrụrụ nrụzi chromosomal na nhazigharị mkpụrụ ndụ ihe nketa, na-emetụta mkpụrụ ndụ ihe nketa na ọrụ ekwentị. N'ime mkpụrụ ndụ ịka nká, mgbanwe na ngosipụta nke protein ndị bụ isi na ụzọ nzaghachi mmebi DNA na-ebelata nnabata cell na mmebi DNA, si otú ahụ na-eme ka usoro ịka nká dịkwuo elu. Nkwụsị nke genomic a abụghị naanị na-emetụta ọrụ cellular nkịtị kamakwa ọ na-ejikọta ya na mmalite na ọganihu nke ọrịa dị iche iche metụtara afọ dịka ọrịa cancer na ọrịa neurodegenerative.
(2) Telomere attrition
Telomeres bụ usoro DNA ugboro ugboro na njedebe nke chromosomes nke na-arụ ọrụ dị ka mkpuchi nchebe, na-egbochi njikọ na mmebi nke njedebe chromosome. N'oge nkewa cell, telomeres ji nwayọọ nwayọọ na-ebelata n'ihi na DNA polymerase enweghị ike ịmegharị njedebe nke chromosomes kpamkpam. Mgbe telomeres na-ebelata ruo n'ókè ụfọdụ, mkpụrụ ndụ na-abanye n'ọnọdụ seescent ma ọ bụ nweta apoptosis. Nke a bụ n'ihi na mkpụrụ ndụ na-amata telomeres dị mkpụmkpụ dị ka mmebi DNA, si otú a na-eme ka ebe nlele okirikiri cell na-eme ka ọ ghara ịdị n'ihu nkewa sel. Telomerase nwere ike ịgbatị ogologo telomere, mana ọrụ ya dị ala na ọtụtụ sel somatic. Ka afọ na-abawanye, telomeres na-aga n'ihu na-ebelata, na-aghọ ihe dị mkpa akara nke senescence cell. Ụfọdụ nnyocha achọpụtala na ịgbalite telomerase ma ọ bụ iji usoro ọgwụgwọ mkpụrụ ndụ gbatịa ogologo telomere nwere ike igbu oge senescence cellular ruo n'ókè ụfọdụ, na-enye nghọta ọhụrụ maka nchọpụta mgbochi ịka nká.
(3) Mgbanwe Epigenetic
Ụkpụrụ epigenetic na-arụ ọrụ dị mkpa na spatiotemporal kpọmkwem nke okwu mkpụrụ ndụ ihe nketa, na usoro ịka nká na-esonyere mgbanwe epigenetic zuru oke. Mgbanwe na usoro methylation DNA bụ otu n'ime mgbanwe epigenetic a na-ahụkarị. N'oge ịka nká, mkpokọta DNA methylation na-ebelata, mana ụfọdụ mpaghara ndị na-akwalite mkpụrụ ndụ ihe nketa na-egosipụta hypermethylation, na-eduga na nkwụsị nke mkpụrụ ndụ ihe nketa ndị a. Mkpụrụ ndụ ihe nketa metụtara usoro okirikiri cell, nrụzi DNA, wdg, na-enweta mbelata okwu n'ihi hypermethylation na-akwalite, si otú ahụ na-emetụta ọrụ cellular nkịtị. Mgbanwe nke akụkọ ihe mere eme dị ka acetylation na methylation na-enwekwa mgbanwe, na-emetụta nhazi chromatin na nnweta mkpụrụ ndụ ihe nketa. Mgbanwe epigenetic ndị a nwere ike ịhazi usoro cellular dị ka mmụba, ọdịiche, na ịka nká site na imetụta mkpụrụ ndụ ihe nketa, na mgbanwe epigenetic na-egosipụta ogo nke mgbanwe, na-enye ihe ndị nwere ike ime maka ịka nká.
(4) Mfu nke protein homeostasis
Protein homeostasis bụ ntọala maka ịnọgide na-arụ ọrụ cellular nkịtị, gụnyere usoro dị ka mpịakọta protein, mbugharị, na mmebi. Ka oge na-aga, usoro protein homeostasis dị n'ime sel na-eji nwayọọ nwayọọ na-adaba adaba. Okwu na ọrụ nke chaperones molekụla dị ka protein ndị na-ekpo ọkụ na-ada ada, na-egbochi protein ndị emepụtara ọhụrụ ka ha mpịachi nke ọma, na-eduga n'ịchịkọta protein ndị gbajiri agbagọ n'ime sel. Ọrụ nke sistemu proteasome na autophagy-lysosomal na-akawanye njọ, na-ebelata ikike ha iji kpochapụ protein ndị ezighi ezi na mebiri emebi. Mkpokọta nke protein ndị a na-adịghị mma na-etolite mkpokọta na-akpaghasị usoro physiological nkịtị n'ime sel, na-eme ka ụzọ mgbaàmà nrụgide intracellular na-eduga, na-eduga n'ịka nká. N'ọrịa neurodegenerative, ndị na-edozi ahụ na-ezighị ezi dị ka β-amyloid na protein tau na-agbakọta n'ọtụtụ buru ibu, na-akpata nkwụsị nke neuronal na ọnwụ, nke nwere njikọ chiri anya na nkwụsị nke protein homeostasis n'oge usoro ịka nká.
(5) Ngbanwe nke nrịbama nri
Ụzọ nhụta nri na-arụ ọrụ dị mkpa na uto cell, metabolism, na ịka nká. Were ụzọ mTOR (mammalian target of rapamycin) dịka ọmụmaatụ; ọ nwere ike ịhụ ọnọdụ nri n'ime mkpụrụ ndụ ma na-ahazi usoro dịka njikọ protein, uto cell, na autophagy. Mgbe nri dị ukwuu, a na-arụ ọrụ mTOR, na-akwalite uto cell na mmụba; Otú ọ dị, imebiga ihe ókè nke ụzọ mTOR na-ejikọta ya na ịka nká, n'ihi na ọ na-egbochi autophagy, na-eduga na nchịkọta nke organelles na protein ndị mebiri emebi, ma na-akwalite nzaghachi mkpali. Mmachi kalori na-agafeghị oke nwere ike igbochi ọrụ mTOR, mee ka autophagy rụọ ọrụ, ma kpochapụ ihe mkpofu cellular, si otú ahụ na-ebelata ịka nká. Ụzọ mgbaàmà nke insulin/insulin-dị ka ihe na-eto eto-1 (IGF-1) nwekwara njikọ chiri anya na nhazi nhazi na ịka nká; dysregulation nke ụzọ a na-emetụta metabolism cellular na ndụ. Site n'ịhazi ụzọ nhụta nri, enwere ike imeziwanye steeti metabolic cellular, si otú a na-ebelata usoro ịka nká.
(6) Mitochondrial adịghị arụ ọrụ
Mitochondria, dị ka ụlọ ọrụ ekwentị, na-ekere òkè dị mkpa na usoro ịka nká. Site na ịka nká, nhazi na ọrụ nke mitochondria na-enwe mgbanwe dị ukwuu. Mitochondrial DNA (mtDNA), enweghị nchebe histone ma dị nso na saịtị mmepụta ROS, na-enwekarị mmebi nke oxidative, na-eduga n'ịgbakọta mtDNA mmụgharị. Mgbanwe ndị a na-emebi ọrụ nke mitochondrial respiratory chain complexs, belata nrụpụta mmepụta ATP, ma na-abawanye mmepụta ROS. Oke ROS na-emebi mitochondria na biomolecules ndị ọzọ n'ime sel, na-eke usoro ọjọọ. Mgbanwe dị na mitochondrial dynamics (gụnyere ngwakọta na fission) na-emetụtakwa ọrụ mitochondrial na nkesa. N'ime mkpụrụ ndụ sesenescent, oke mitochondrial fission na-ebute mkpirisi mitochondria nke kewara ekewa nwere arụrụ arụ. Mitochondrial dysfunction-induced ume metabolism abnormalities na ịba ụba oxidative nrụgide bụ isi njirimara nke cellular na organismal ịka nká, jikọtara chiri anya na mmalite na ọganihu nke ọrịa dị iche iche metụtara afọ dịka ọrịa obi na ọrịa neurodegenerative.
(7) Senescence cell
Senescence cellular na-ezo aka na mfu nke ikike ịmụba na ịbanye n'ọnọdụ siri ike, nke enweghị ike ịgbanwe agbanwe nke njide. Mkpụrụ ndụ Senescent na-egosipụta njirimara phenotypic pụrụ iche, gụnyere ụbara ụda cell, mpụta agbasaghị, na ọrụ β-galactosidase dị elu. Usoro na-akpali akpali nke senescence cell dị iche iche, gụnyere mbelata telomere, mmebi DNA, na nrụgide oxidative. Mkpụrụ ndụ Senescent na-ezobe usoro cytokines, chemokines, na proteases, na-eme ka senescence-metụtara secretory phenotype (SASP). Ọ bụghị nanị na SASP na-arụ ọrụ paracrine na sel ndị gbara ya gburugburu, na-ebute nzaghachi mkpali na nhazigharị matrix extracellular, ma ọ pụkwara ịkwalite fibrosis anụ ahụ na nhazi nke microenvironment tumor. Ọ bụ ezie na senescence cellular nwere ike igbochi mmụba cell tumor ruo n'ókè ụfọdụ, nchịkọta ogologo oge nke mkpụrụ ndụ senescent n'ime ahụ nwere ike imetụta anụ ahụ na ọrụ akụkụ ahụ na-adịghị mma, na-eme ka usoro ịka nká dịkwuo elu.
(8) Ike ọgwụgwụ cell stem
Mkpụrụ ndụ stem nwere ikike imeghari onwe ya na ịwapụta n'ụdị sel dị iche iche, na-arụ ọrụ dị oke mkpa na mmepe, mmezi, na nrụzi anụ ahụ na akụkụ ahụ. Ka afọ na-abawanye, ọrụ sel stem na-eji nwayọọ nwayọọ na-agbada, na-enwe ike iweghachite onwe ya na oke ike dị iche iche. N'oge usoro ịka nká, nguzozi nke ọdịiche nke mkpụrụ ndụ hematopoietic n'ime usoro mkpụrụ ndụ ọbara dị iche iche na-akụghasị, na-eduga n'ịrụ ọrụ usoro ahụ ji alụso ọrịa ọgụ. Mmụba na ike dị iche iche nke mkpụrụ ndụ sel mesenchymal na-ebelatakwa, na-emetụta nrụzi na mmeghari nke ọkpụkpụ, cartilage, na anụ ahụ adipose. Ihe na-akpata ike ọgwụgwụ nke cell sel gụnyere mgbanwe na microenvironment, dysregulation nke ụzọ mgbaàmà intracellular, na nchịkọta DNA mebiri emebi. Ọnwụ nke cell cell na-ebelata ikike nrụzi nke anụ ahụ na akụkụ ahụ, na-eme ka ha ghara ịzaghachi nke ọma maka mmerụ ahụ na ọrịa, si otú ahụ na-eduga n'ịka nká.
(9) Mgbanwe na nzikọrịta ozi intracellular
Nkwurịta okwu intercellular dị oké mkpa maka ịnọgide na-enwe homeostasis nke anụ ahụ na akụkụ ahụ. N'oge usoro ịka nká, nkwurịta okwu intracellular na-enwe mgbanwe dị ukwuu. Ka afọ na-abawanye, nkwurịta okwu ọdịiche dị n'etiti mkpụrụ ndụ na-ebelata, na-emetụta mgbanwe ihe onwunwe na nnyefe mgbaàmà n'etiti sel. Tụkwasị na nke ahụ, ọrụ nke usoro endocrine na-agbanwekwa, na-eduga n'ịba ụba nke hormonal. Mgbanwe na nzuzo na arụ ọrụ nke homonụ dị ka insulin na hormone uto na-emetụta metabolism sistemu na ọrụ cellular. Ịgbalite ụzọ mgbama mkpali bụ akụkụ ọzọ dị mkpa nke mgbanwe nzikọrịta ozi intracellular. Mkpụrụ ndụ Senescent na-ezobe ihe SASP na-ebute nzaghachi mkpali na-adịghị ala ala, na-akpaghasị nzikọrịta ozi intercellular nkịtị na microenvironment anụ ahụ. Mgbanwe ndị a na nkwurịta okwu intracellular na-eduga n'ịchịkọta adịghị arụ ọrụ n'etiti anụ ahụ na akụkụ ahụ, si otú a na-akwalite ọganihu nke ịka nká.
Njikọ njikọ nke Aging Markers na Characteristics
Ihe nrịbama dị iche iche na njirimara ịka nká abụghị ndị dịpụrụ adịpụ kama ha na-ejikọta ọnụ ma na-emetụta ibe ha, na-ejikọta ọnụ na usoro ịka nká. Enweghi ike nke genomic na-eduga na mmebi DNA, nke na-ebute ịka nká na ike ọgwụgwụ cell. Telomere attrition na-emekwa ka mmeghachi omume mmebi DNA na-eme ka ọ dịkwuo njọ, na-eme ka enweghi ike genomi ka njọ. Mgbanwe nke epigenetic nwere ike imetụta okwu mkpụrụ ndụ ihe nketa, si otú a na-ahazi usoro dị ka protein homeostasis, nhazi ihe oriri, na ọrụ mitochondrial. Mitochondrial dysfunction-induced ROS nwere ike mebie DNA ọzọ, na-eduga n'ọgba aghara genomic, ebe ọ na-emetụtakwa ụzọ mgbaàmà intracellular ma na-agbanwe nkwurịta okwu intercellular. Senescence cell na ike ọgwụgwụ cell na-emebi nrụzi anụ ahụ na ikike nrụpụta, ebe mgbanwe na microenvironment anụ ahụ, n'aka nke ya, na-emetụta senescence cell na ọrụ sel stem.
Ngwa nke akara ịka nká na njirimara na ahụike na ọrịa
(1) Dị ka Biomarkers
Ihe nrịbama ịka nká na njirimara nwere ike ịrụ ọrụ dị ka ndị na-ahụ maka ndụ iji chọpụta ogo ịka nká na ọnọdụ ahụike mmadụ. Dịka ọmụmaatụ, site n'ịtụ ogologo telomere, usoro DNA methylation, na ihe ngosi ọrụ mitochondrial, ọ ga-ekwe omume ịkọ afọ ndụ ndụ mmadụ na ihe ize ndụ nke ịmalite ọrịa ndị metụtara afọ ruo n'ókè ụfọdụ. Ndị biomarkers ndị a na-enyere aka na nchọpụta mmalite nke nsogbu ahụike nwere ike ime, na-enye ihe ndabere maka njikwa ahụike ahaziri iche na ntinye aka. Na mgbochi nke ọrịa obi, ịchọpụta ndị na-ahụ maka ịka nká na-emetụta mbufụt n'ime ọbara na-enyere aka ịchọpụta ndị nwere nnukwu ihe ize ndụ ma mee ka usoro ntinye aka n'oge, dị ka mgbanwe ndụ ma ọ bụ ọgwụgwọ ọgwụ.
(2) Ebumnuche mmepe ọgwụ
Ihe nrịbama dị iche iche na njirimara ịka nká na-enye ọtụtụ ebumnuche maka mmepe ọgwụ. Maka enweghị ike genomic, ọgwụ ndị na-akwalite nrụzi DNA nwere ike ịmepụta; maka telomere attrition, ọgwụ ndị na-arụ ọrụ telomerase ma ọ bụ na-echebe telomeres nwere ike nyochaa; maka ọnwụ nke protein homeostasis, ọgwụ ndị na-eme ka ọrụ chaperone molecular ma ọ bụ na-akwalite mmebi protein nwere ike ịmepụta, wdg N'ime afọ ndị na-adịbeghị anya, nchọpụta banyere rapamycin na analogues na-ezubere ụzọ mTOR emeela ọganihu dị ukwuu n'ịkwụsị ịka nká na ịgbatị ndụ ndụ, na-enye ihe nlereanya na-aga nke ọma maka mmepe ọgwụ mgbochi ịka nká. Maka ịka nká cellular, ọgwụ ndị na-emepụta ọgwụ ndị nwere ike ikpochapụ mkpụrụ ndụ senescent ma ọ bụ gbochie SASP nwere ike imeziwanye mgbaàmà nke ọrịa ndị metụtara ịka nká ma belata usoro ịka nká.
(3) Atụmatụ itinye aka na ahụike
Dabere na nghọta nke akara nrịbama na njirimara ịka nká, enwere ike ịmepụta atụmatụ enyemaka ahụike kwekọrọ. N'ihe gbasara itinye aka na nri, mmachi calorie na nri Mediterranean nwere ike ịhazi ụzọ nhụta nri, meziwanye ọnọdụ metabolic, na igbu oge ịka nká. Ntinye aka na mmega ahụ nwere ike ịkwalite ọrụ mitochondrial, na-akwalite mmụba nke cell cell na ọdịiche, ma melite nkwurịta okwu intercellular, nke niile nwere mmetụta dị mma na igbu oge ịka nká. Ojiji nke antioxidants nwere ike ibelata nrụgide oxidative, chebe mkpụrụ ndụ site na mmebi ROS, ma nọgide na-arụ ọrụ cellular nkịtị. Usoro ọgwụgwọ ahụike ndị a zuru oke na-enyere aka mee ka usoro ịka nká kwụsịlata ma melite ogo ndụ maka ndị agadi.
Mmechi
Ihe nrịbama na njirimara nke ịka nká na-agụnye mgbanwe dịgasị iche iche site na molekụla gaa na ọkwa cellular na anụ ahụ / akụkụ ahụ, nke jikọtara ọnụ ma na-emetụta ibe ya, na-ejikọta ọnụ na-emepụta usoro mgbagwoju anya nke ndụ ịka nká. Ịghọta akara ndị a na njirimara ndị a na-enye ntọala usoro maka mgbochi, nchọpụta, na ọgwụgwọ ọrịa ndị metụtara ịka nká.
Isi mmalite
[1] Pintea A, Manea A, Pintea C, et al. Peptides: Ndị Candidates na-apụta maka Mgbochi na Ọgwụgwọ nke Senescence Skin: Nyochaa [J]. Biomolecules, 2025,15 (1}, AKỤKWU-ỌMBA = {88).DOI:10.3390/biom15010088.
[2] Yıldız C, Ozilgen M. Gịnị kpatara ọrụ ụbụrụ nwere ike isi na-akawanye njọ site na ịka nká: A thermodynamic evaluation[J]. Akwụkwọ akụkọ International nke Exergy, 2021.
[3] Joseph AW, Jeevitha Shree DV, Saluja KPS, et al. Nyocha anya iji ghọta mmetụta ịka nká na ngwa ekwentị mkpanaaka[C]//, Singapore, 2021. Springer Singapore, 2021-01-01.DOI: 10.1007/978-981-16-0041-8_27.
[4] Joseph AW, Dv J, Saluja KS, et al. Nyocha anya iji ghọta mmetụta ịka nká na ngwa ekwentị mkpanaaka[J]. Arxiv, 2021, abs/2101.00792. https://api.semanticcholar.org/CorpusID:230435965
[5] Wiesman AI, Rezich MT, O'Neill J, et al. Ihe nrịbama Epigenetic nke ịka nká na-ebu amụma nhụsianya akwara na-enye nlebara anya nhọrọ[J]. Cerebral Cortex, 2020,30 (3): 1234-1243.DOI:10.1093/cercor/bhz162.
[6] Marron M M. Ike na-adịghị ike na ije ije dị ka ihe nrịbama nke ịka nká na mbinye aka metabolomic ha, 2019[C]. https://api.semanticcholar.org/CorpusID:202009741
[7] Wang Y, Huang T, Sha X, et al. Ụdị nhazi onwe onye na-ekpughe njirimara nhazi nke ịka nká [J]. Theoretical Biology & Medical Modelling, 2018,17.
[8] Juhász D, Németh D. [Mgbanwe nke ọrụ ọgụgụ isi na ịka nká [J]. Ideggyogyaszati Szemle-Clinical Neuroscience, 2018,71(3-04):105-112.DOI:10.18071/isz.71.0105.
