Na Cocer Peptides 
ukwezi gushize
INGINGO ZOSE N'AMAKURU Y’IBICURUZWA BITANZWE KURI URU RUBUGA BISANZWE KUBONA AMAKURU N'INTEGO Z'UBUREZI.
Ibicuruzwa byatanzwe kururu rubuga bigenewe gusa mubushakashatsi bwa vitro. Mu bushakashatsi bwa vitro (Ikilatini: * mu kirahure *, bisobanura mu bikoresho by'ibirahure) bikorwa hanze y'umubiri w'umuntu. Ibicuruzwa ntabwo ari imiti, ntabwo byemejwe n’ikigo cy’Amerika gishinzwe ibiryo n’ibiyobyabwenge (FDA), kandi ntigomba gukoreshwa mu gukumira, kuvura, cyangwa gukiza indwara iyo ari yo yose y’ubuvuzi, indwara, cyangwa indwara. Birabujijwe rwose n'amategeko kwinjiza ibyo bicuruzwa mumubiri wabantu cyangwa inyamaswa muburyo ubwo aribwo bwose.
Incamake
Gusaza kurangwa no kugabanuka gahoro gahoro imikorere yumubiri no kongera kwandura indwara. Gusobanukirwa ibimenyetso nibiranga gusaza ningirakamaro mugusobanura uburyo bwibinyabuzima bwo gusaza no gushyiraho ingamba zo gutinda gusaza no kwirinda indwara zifitanye isano.
Igishushanyo 1. Uburyo bwo kurwanya inkeke.
Ibimenyetso n'ibiranga gusaza
(1) Ihungabana rusange
Ihungabana rusange ni umushoferi wingenzi wo gusaza. Ikwirakwizwa ry’ibyangiritse kuri ADN bituruka ku bintu biterwa na endogenous nk'ubwoko bwa ogisijeni ikora (ROS) ikorwa mu gihe cyo guhindagurika, hamwe n'impamvu zidasanzwe nk'imishwarara ya ultraviolet n'imiti. Uko ibinyabuzima bigenda bisaza, imikorere yuburyo bwo gusana ADN igabanuka, bigatuma ADN yangirika. Niba ibice bibiri bya ADN bimenetse bidakosowe neza, birashobora kuvamo imiterere idasanzwe ya chromosomal no guhinduranya gene, bikagira ingaruka kumagambo no mumikorere ya selile. Mu ngirabuzimafatizo zishaje, impinduka mu kwerekana poroteyine z'ingenzi mu nzira yo kwangiza ADN zigabanya kwihanganira ingirabuzimafatizo kwangirika kwa ADN, bityo byihuta mu gusaza. Uku guhungabana kwa genomic ntabwo bigira ingaruka kumikorere isanzwe ya selile gusa ahubwo bifitanye isano rya bugufi no gutangira no gutera imbere kwindwara zitandukanye ziterwa nimyaka nka kanseri n'indwara zifata ubwonko.
(2) Kwiyongera kwa Telomere
Telomeres ni ADN isubiramo ikurikiranye kumpera ya chromosomes ikora nk'imipira irinda, ikumira guhuza no kwangirika kwa chromosome. Mugihe cyo kugabana selile, telomereri igabanuka buhoro buhoro kuko polymerase ya ADN idashobora kwigana neza amaherezo ya chromosomes. Iyo telomereri igabanutse kurwego runaka, selile zinjira muri senescent cyangwa zikagira apoptose. Ni ukubera ko telomereri ngufi izwi na selile nkibyangiritse kuri ADN, bityo igakora igenzura ryizunguruka kugirango irinde amacakubiri. Telomerase irashobora kwagura uburebure bwa telomere, ariko ibikorwa byayo ni bike muri selile nyinshi. Uko imyaka igenda yiyongera, telomereri ikomeza kugabanuka, ihinduka ikimenyetso cyingenzi cya senescence. Ubushakashatsi bumwe bwerekanye ko gukora telomerase cyangwa gukoresha imiti ya gene kugirango wongere uburebure bwa telomere bishobora gutinda kurwego runaka rwa selile, bitanga ubumenyi bushya kubushakashatsi bwo kurwanya gusaza.
(3) Impinduka za Epigenetike
Epigenetike igira uruhare runini muburyo bwihariye bwo kwerekana imiterere ya gene, kandi gusaza biherekejwe nimpinduka za epigenetike. Guhindura muburyo bwa ADN methylation ni imwe mumpinduka zisanzwe. Mugihe cyo gusaza, muri rusange urwego rwa methylation ya ADN rugabanuka, ariko uturere tumwe na tumwe twamamaza gene tugaragaza hypermethylation, bigatuma gucecekesha izo genes. Imirasire ijyanye no kugenzura ingirabuzimafatizo, gusana ADN, nibindi, uburambe bugabanya imvugo bitewe na hypermethylation ya porotokoro, bityo bikagira ingaruka kumikorere isanzwe ya selile. Guhindura amateka ya Histone nka acetylation na methylation nabyo bigenda bihinduka, bigira ingaruka kumiterere ya chromatin no kuboneka kwa gene. Izi mpinduka za epigenetike zirashobora kugenga imikorere ya selile nko gukwirakwizwa, gutandukana, no gusaza bigira ingaruka kumagambo ya gene, kandi impinduka za epigenetike zigaragaza urwego rwo guhinduka, zitanga intego zishobora guterwa no gusaza.
(4) Gutakaza protein homeostasis
Poroteyine homeostasis ni umusingi wo gukomeza imikorere isanzwe ya selile, ikubiyemo inzira nko kugwiza poroteyine, gutwara, no kwangirika. Hamwe n'imyaka, uburyo bwa protein homeostasis muri selile buhoro buhoro buringaniza. Imvugo n'imikorere ya molekuline ya chaperone nka poroteyine yubushyuhe bugabanuka, bikabuza poroteyine nshya zashizwemo kuzunguruka neza, biganisha ku kwegeranya poroteyine zitabitswe neza mu ngirabuzimafatizo. Imikorere ya proteasome na autophagy-lysosomal nazo ziragenda nabi, bikagabanya ubushobozi bwabo bwo gukuraho poroteyine zitabitswe neza kandi zangiritse. Ikwirakwizwa rya poroteyine zidasanzwe ziteranya ibintu bihagarika imikorere isanzwe ya physiologique mu ngirabuzimafatizo, igakora imihangayiko yo mu nda yerekana inzira, kandi biganisha ku gusaza kwa selile. Mu ndwara zifata ubwonko, poroteyine zitabitswe nka β-amyloide na tau proteyine zegeranya ku bwinshi, bigatera imikorere mibi y’urupfu ndetse n’urupfu, ibyo bikaba bifitanye isano rya hafi no gutakaza poroteyine homeostasis mu gihe cyo gusaza.
(5) Kugabanya ibimenyetso byintungamubiri
Inzira zintungamubiri zigira uruhare runini mu mikurire yimikorere, metabolism, no gusaza. Fata inzira ya mTOR (inyamaswa z’inyamabere za rapamycin) nkurugero; irashobora kumva imirire muri selile ikanagenga inzira nka synthesis ya protein, imikurire ya selile, na autophagy. Iyo intungamubiri ari nyinshi, mTOR irakora, igatera imbere gukura no gukwirakwira; icyakora, gukora cyane inzira ya mTOR bifitanye isano no gusaza, kuko ibuza autofagy, biganisha ku kwegeranya ingirangingo na poroteyine byangiritse, mu gihe binateza imbere ibisubizo byaka umuriro. Kugabanya kalori ntarengwa birashobora guhagarika ibikorwa bya mTOR, gukora autophagy, no gukuraho imyanda ya selile, bityo bikadindiza gusaza. Inzira yo gukura ya insuline / insuline-1 (IGF-1) inzira yerekana inzira nayo ifitanye isano rya bugufi no kugaburira intungamubiri no gusaza; kudashyira mu bikorwa iyi nzira bigira ingaruka kuri metabolism selile no kubaho. Muguhindura intungamubiri-zumva inzira, selile metabolike imiterere irashobora kunozwa, bityo bikadindiza gusaza.
(6) Imikorere mibi ya mitochondrial
Mitochondria, nkimbaraga za selile, zigira uruhare runini mugusaza. Hamwe no gusaza, imiterere n'imikorere ya mitochondriya ihinduka cyane. ADN ya Mitochondrial (mtDNA), idafite uburinzi bwa histone kandi iherereye hafi y’ahantu hakorerwa ROS, ikunze kwangirika kwa okiside, bigatuma habaho ihindagurika rya mtDNA. Ihinduka ry’imiterere ryangiza imikorere y’imyanya y’ubuhumekero ya mitochondrial, kugabanya umusaruro wa ATP, no kongera umusaruro wa ROS. ROS ikabije yangiza mitochondriya hamwe na biyomekile mu ngirabuzimafatizo, bigatera uruziga rukabije. Ubusumbane mubikorwa bya mitochondrial dinamike (harimo fusion na fission) nabyo bigira ingaruka kumikorere ya mito-iyambere. Mu ngirabuzimafatizo za senescent, mitochondial irenze urugero itera mitochondriya igabanijwe kandi igabanije imikorere mibi. Imikorere mibi ya Mitochondrial iterwa ningufu za metabolisme zidasanzwe hamwe no kongera imbaraga za okiside ni ibintu byingenzi biranga gusaza kwingirangingo n’ibinyabuzima, bifitanye isano rya bugufi no gutangira no gutera imbere kwindwara zitandukanye ziterwa nimyaka nkindwara zifata umutima nindwara zifata ubwonko.
(7) Senescence ya selile
Senescence ya selile bivuga gutakaza ubushobozi bwo kwiyongera no kwinjira muburyo butajegajega, budasubirwaho bwo gufatwa gukura. Ingirabuzimafatizo za Senescent zigaragaza imiterere yihariye ya fenotipiki, harimo kwiyongera kwingirabuzimafatizo, morfologiya yoroheje, hamwe nibikorwa β-galactosidase. Uburyo bukurura senescence ya selile buratandukanye, harimo kugabanya telomere, kwangirika kwa ADN, hamwe na stress ya okiside. Ingirabuzimafatizo za Senescent zisohora urukurikirane rwa cytokine, chemokine, na protease, bigakora senescence ifitanye isano na senotype yibanga (SASP). SASP ntabwo igira gusa ingaruka za parasrine kuri selile ikikije, itera ibisubizo byokongoka no guhindura matrice idasanzwe, ariko irashobora no guteza imbere fibrosis ya tissue no gushiraho mikorobe yibidukikije. Mugihe ingirabuzimafatizo zishobora guhagarika ikwirakwizwa ryikibyimba ku rugero runaka, kwirundanya kwigihe kirekire kwingirabuzimafatizo mu mubiri bishobora kugira ingaruka mbi kumikorere no mumubiri, byihutisha gusaza.
(8) Umunaniro w'akagari
Ingirabuzimafatizo zifite ubushobozi bwo kwivugurura no gutandukanya ubwoko butandukanye, bigira uruhare runini mugutezimbere, kubungabunga, no gusana ingirangingo ningingo. Uko imyaka igenda yiyongera, imikorere yimikorere ya selile igenda igabanuka gahoro gahoro, hamwe nubushobozi bwo kwiyubaka bushya hamwe nubushobozi buke bwo gutandukana. Mugihe cyo gusaza, uburinganire bwimikorere ya hematopoietic stem selile itandukanye mumirongo itandukanye yamaraso burahungabana, bigatuma imikorere yumubiri idahungabana. Ubushobozi bwo gukwirakwiza no gutandukanya ingirabuzimafatizo ya mesenchymal nabwo bugabanuka, bigira ingaruka ku gusana no kuvugurura amagufwa, karitsiye, hamwe na adipose. Impamvu zitera umunaniro w'ingirabuzimafatizo zirimo impinduka mu bidukikije, kutagabanya inzira zerekana ibimenyetso, no kwegeranya ibyangiritse. Gutakaza imikorere yimikorere ya selile bigabanya ubushobozi bwo gusana ingirangingo ningingo, bigatuma badashobora kwitabira neza imvune nindwara, bityo bigatuma gusaza kumubiri.
(9) Impinduka mu Itumanaho ridasanzwe
Itumanaho hagati yingirakamaro ningirakamaro mugukomeza homeostasis yimitsi ningingo. Mugihe cyo gusaza, itumanaho ridasanzwe rihinduka cyane. Uko imyaka igenda yiyongera, itumanaho rihuza itumanaho rigabanuka, bigira ingaruka ku guhanahana ibintu no guhererekanya ibimenyetso hagati ya selile. Byongeye kandi, imikorere ya sisitemu ya endocrine nayo irahinduka, biganisha ku busumbane bwa hormone. Impinduka mu gusohora no gukora imisemburo nka insuline na hormone yo gukura bigira ingaruka kuri metabolisme ya sisitemu n'imikorere ya selile. Gukora inzira yerekana ibimenyetso byinzira ni ikindi kintu cyingenzi cyitumanaho ryahinduwe. Utugingo ngengabuzima twa Senescent dusohora ibintu bya SASP bitera ibisubizo bidakira byangiza, bigahagarika itumanaho risanzwe ryimitsi hamwe nibidukikije bya mikorobe. Izi mpinduka mu itumanaho ridasanzwe zitera guhuza imikorere idahwitse hagati yinyama ningingo, bityo bigatera imbere gusaza.
Guhuza kw'abasaza bageze mu za bukuru n'ibiranga
Ibimenyetso bitandukanye nibiranga gusaza ntibitandukanijwe ahubwo birahujwe kandi bigira uruhare runini, hamwe bigatera gusaza. Ihungabana rusange ritera kwangirika kwa ADN, ari naryo ritera gusaza ingirabuzimafatizo no kunanirwa kw'ingirabuzimafatizo. Kwiyongera kwa Telomere kandi bituma ADN isubiza ibyangiritse, byongera ihungabana rya genomic. Imihindagurikire ya Epigenetike irashobora guhindura imiterere ya gene, bityo igenga inzira nka protein homeostasis, kugaburira intungamubiri, n'imikorere ya mito-iyambere. Imikorere mibi ya mitochondial iterwa na ROS irashobora kwangiza ADN, biganisha ku ihungabana rya genomique, mugihe kandi bigira ingaruka kumihanda yerekana ibimenyetso no guhindura itumanaho. Senescence ya selile hamwe no kunanirwa kwingirangingo zangiza ingirabuzimafatizo zangiza no gusana imbaraga, mugihe impinduka ziterwa na mikorobe yibidukikije, nazo zigira ingaruka kumikorere ya selile no mumikorere ya selile.
Gushyira mu bikorwa Ibisaza n'ibiranga ubuzima n'indwara
(1) Nka Biomarkers
Ibimenyetso byo gusaza nibiranga birashobora kuba biomarkers kugirango basuzume urugero rwumuntu ugeze mu za bukuru ndetse nubuzima bwe. Kurugero, mugupima uburebure bwa telomere, uburyo bwa methylation ya ADN, hamwe nibipimo byerekana imikorere ya mito-iyambere, birashoboka guhanura imyaka umuntu yibinyabuzima hamwe ningaruka zo kwandura indwara ziterwa nimyaka. Izi biomarkers zifasha mugutahura hakiri kare ibibazo byubuzima, bitanga urufatiro rwo gucunga ubuzima bwihariye no gutabara. Mu gukumira indwara z'umutima-damura, gutahura ibinyabuzima biterwa no gutwika ibinyabuzima mu maraso bifasha kumenya abantu bafite ibyago byinshi kandi bigafasha ingamba zo gutabara hakiri kare, nko guhindura imibereho cyangwa kuvura ibiyobyabwenge.
(2) Intego zo Guteza Imbere Ibiyobyabwenge
Ibimenyetso bitandukanye nibiranga gusaza bitanga intego nyinshi zo guteza imbere ibiyobyabwenge. Kubudahangarwa bwa genomic, imiti iteza imbere gusana ADN irashobora gutezwa imbere; kubijyanye na telomere, ibiyobyabwenge bikora telomerase cyangwa birinda telomereri birashobora gushakishwa; kubura proteine homeostasis, ibiyobyabwenge byongera imikorere ya molekuline ya chaperone cyangwa bigatera kwangirika kwa poroteyine birashobora gutezwa imbere, nibindi. Mu myaka yashize, ubushakashatsi bwakozwe na rapamycin hamwe n’ibigereranyo byabwo bugamije inzira ya mTOR bwateye intambwe igaragara mu gutinda gusaza no kwagura igihe, bitanga urugero rwiza rwo kurwanya ibiyobyabwenge. Kubusaza bwa selile, guteza imbere imiti ishobora gukuraho selile cyangwa guhagarika SASP irashobora kunoza ibimenyetso byindwara ziterwa no gusaza kandi bigatinda gusaza.
(3) Ingamba zo Gutabara Ubuzima
Hashingiwe ku gusobanukirwa ibimenyetso bishaje n'ibiranga, hashobora gutegurwa ingamba zijyanye no kwivuza. Kubijyanye no kwitabira imirire, kugabanya kalori hamwe nimirire ya Mediterane birashobora kugenga inzira-zumva intungamubiri, kunoza imiterere ya metabolike, no gutinda gusaza. Imyitozo ngororamubiri irashobora kongera imikorere ya mitochondial, igatera ikwirakwizwa ry'ingirabuzimafatizo no gutandukanya, kandi igateza imbere itumanaho, ibyo byose bigira ingaruka nziza zo gutinda gusaza. Gukoresha antioxydants birashobora kugabanya imbaraga za okiside, kurinda selile kwangirika kwa ROS, no gukomeza imikorere isanzwe ya selile. Izi ngamba zuzuye zita kubuzima zifasha gutinda gusaza no kuzamura imibereho yabasaza.
Umwanzuro
Ibimenyetso n'ibiranga gusaza bikubiyemo ibintu byinshi byahindutse kuva kuri molekile kugera kuri selile na tissue / urwego, ibyo bikaba bifitanye isano kandi bigira uruhare runini, hamwe bigakora uburyo bukomeye bwibinyabuzima bwo gusaza. Gusobanukirwa ibi bimenyetso n'ibiranga bitanga umusingi w'amahame yo gukumira, gusuzuma, no kuvura indwara ziterwa no gusaza.
Inkomoko
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