Na Cocer Peptides 
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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.
1.Incamake
Mubyerekeranye nubumenyi bwubuzima, gusaza na autophagy nibice byingenzi byubushakashatsi byakunze kwitabwaho. Telomeres, nkibintu bidasanzwe kumpera ya chromosomes, bigira uruhare runini mubikorwa byombi. Mugihe ubushakashatsi bugenda butera imbere, umubano utoroshye hagati ya telomereri, gusaza, na autophagy uragenda ugaragara.
Igishushanyo 1 Kwiyongera kwa Telomere, uburebure bwa telomere, na telomerase.
2.Incamake yimiterere ya Telomere n'imikorere
2.1 Imiterere ya Telomere
Telomeres ibitswe cyane nucleotide ikurikirana iherereye kumpera ya chromosomes yumurongo mubinyabuzima bya eukaryotic. Zigizwe nuburyo bworoshye bwo gusubiramo bukungahaye kuri guanine (G), hamwe na telomere yumuntu isubiramo ikurikirana ni TTAGGG. Iyi miterere irinda impera za chromosomes kwangirika na nuclease, ikarinda guhuza chromosome, kandi ikagumana ituze rya chromosomal. Imiterere ya telomereri ahanini igizwe na ADN ya telomeric na proteyine zihuza nayo. Izi poroteyine zikorana na ADN ya telomerike kugirango ikore urwego rwihariye rwo hejuru, irusheho kuzamura itumanaho rya telomere.
2.2 Imikorere ya Telomeres
Imwe mumikorere yibanze ya telomereri ni ugukemura 'ikibazo cyo kwigana iherezo. ' Bitewe nibiranga kwigana ADN, polymerase isanzwe ya ADN ntishobora kwigana byimazeyo impera za chromosomes, bigatuma telomere igabanuka buhoro buhoro hamwe na buri gice kigabanijwe. Kubaho kwa telomeres buffers kurangiza kugabanuka, kwemeza ubunyangamugayo no guhagarara kwa chromosomes. Telomeres nayo igira uruhare runini mugutunganya ingirabuzimafatizo. Iyo telomereri igabanutse ku rugero runaka, itera kugenzura ingirabuzimafatizo, bigatuma selile zinjira muri senescence cyangwa apoptose, bityo bikagabanya ubushobozi bwabo bwo gukwirakwizwa kutagira umupaka. Ubu buryo ni ingirakamaro mu gukumira ibibyimba kandi bifitanye isano rya bugufi no gusaza kw'ibinyabuzima.
3. Isano Hagati ya Telomeres no Gusaza
3.1 Kugabanuka kwa Telomere nk'ikimenyetso cyo gusaza
Uko imyaka igenda yiyongera, uburebure bwa telomereri mu ngirabuzimafatizo zisanzwe za somatike buragenda bugabanuka buhoro buhoro, ibintu bigaragara mu ngingo no mu ngingo zitandukanye. Mu maraso ya peripheri yumuntu mononuclear selile, uburebure bwa telomere buragabanuka cyane uko imyaka igenda ishira. Ubushakashatsi bwerekana ko kugabanuka kwa telomere bifitanye isano rya bugufi n’imihindagurikire itandukanye ya physiologique ijyanye no gusaza, nko kugabanya ubushobozi bwo gukwirakwiza ingirabuzimafatizo, intege nke zo kuvugurura ingirabuzimafatizo, ndetse no kongera ibyago by’indwara zidakira. Ku rwego rwa selire, iyo telomereri igabanutse kugera ku burebure bukomeye, selile zitakaza ubushobozi bwazo kandi zikinjira muri reta ya senescent, irangwa na morphologie selile ihindagurika, igabanya ibikorwa bya metabolike, kandi ikongera imvugo ya senescence ifitanye isano β-galactosidase (SA-β-Gal).
3.2 Uburyo bwo kugabanya telomere itera gusaza
Uburyo bwo kugabanya telomere butera gusaza cyane cyane inzira zangiza ADN. Iyo telomereri igabanutse kurwego runaka, imiterere yabyo iba idahindagurika, kandi ibikorwa byo kurinda impera ya telomere biratakara, biganisha ku kumenyekanisha amaherezo ya chromosome nkibibanza byangiza ADN na selile. Ibi bikora urukurikirane rwibisubizo bya ADN byerekana inzira, nka ATM / ATR-p53-p21 inzira. Nyuma yo gukora, ATM (ataxia-telangiectasia yahinduwe) cyangwa ATR (ataxia-telangiectasia na Rad3 ifitanye isano) na poroteyine fosifora munsi ya p53 za poroteyine, bikongera umutekano muke no guteza imbere kwinjira muri nucleus selile. Nkimpamvu yingenzi yo kwandukura, igenga imvugo yuruhererekane rwa genes zijyanye no gufata ingirabuzimafatizo hamwe na senescence, harimo p21. p21 ibuza ibikorwa bya kinase iterwa na cyclin (CDKs), bityo ikabuza ingirabuzimafatizo gutera imbere kuva mu cyiciro cya G1 kugera mu cyiciro cya S, biganisha ku gufatwa kwakagari kandi amaherezo bigatera senescence ya selile. Kugabanuka kwa telomere birashobora kandi guteza imbere senescence muguhindura imikorere ya mito-iyambere. Kwangirika kwa telomere biganisha ku kongera imbaraga za okiside ya mitochondial no kugabanya ubushobozi bwa mitochondial membrane, bityo bikagira ingaruka ku mbaraga za mitochondial metabolism no kuringaniza imitsi ya redox, byihutisha gusaza.
3.3 Telomeres n'indwara zijyanye n'imyaka
Indwara nyinshi zijyanye n'imyaka, nk'indwara z'umutima-damura, indwara zifata ubwonko, na kanseri, zifitanye isano rya bugufi no kugabanya telomere. Mu ndwara zifata umutima, kugabanuka kwa telomere bifitanye isano rya bugufi no kudakora neza kwa endoteliyale no gukura kwa aterosklerose. Amaraso ya periferique leukocyte telomere uburebure bw'abarwayi b'indwara z'umutima ni ngufi cyane ugereranije no kugenzura neza, kandi uburebure bwa telomere bufitanye isano nabi n'uburemere bw'indwara. Mu ndwara zifata ubwonko nk'indwara ya Alzheimer n'indwara ya Parkinson, uburebure bwa telomere muri neuron mu bwonko nabwo buragabanuka cyane. Kugabanuka kwa telomere birashobora gutuma habaho kwangirika kwa ADN no kwiyongera kwa apoptose muri neuron, bityo bikihutisha iterambere ryimikorere ya neurodegenerative. Muri kanseri, nubwo kanseri isanzwe ifite uburyo bwo gukomeza uburebure bwa telomere (nko gukora telomerase), kugabanuka kwa telomere mugihe cyambere cya tumorigenez bishobora gutera ihungabana rya genomic, bikongerera amahirwe yo guhinduka kwa gene kandi bigatanga umusingi witerambere ryibibyimba.
4. Isano iri hagati ya Telomeres na Autophagy
4.1 Amabwiriza ya Autophagy na Telomeres
Autophagy ni uburyo bwingenzi bwo kwangirika no kwangiza ibintu bikuraho ingirangingo zangiritse, poroteyine zitabitswe neza, hamwe na virusi zitera ingirabuzimafatizo, bikomeza umutekano w’ibidukikije. Ubushakashatsi buherutse gukorwa bwerekanye ko hari isano ikomeye yo kugenzura hagati ya telomereri na autophagy. Kugabanya Telomere birashobora gutera autophagy. Iyo telomereri igabanije kurwego runaka bitewe no kugabana selile cyangwa izindi mpamvu, zikora imyitozo ngororamubiri yerekana inzira, bityo bigatera autophagy. Muri selile zimwe na zimwe zabuze selile, nkuko telomereri igenda igabanuka buhoro buhoro, imvugo yerekana poroteyine zijyanye na autofagy ziyongera cyane, kandi umubare wa autophagosomes nawo uragenda wiyongera. Autophagy irashobora kandi gusubiranamo itumanaho rya telomere. Mugukuraho ibintu byangiza ADN no kubungabunga ibidukikije byangiza ibidukikije, autophagy irinda mu buryo butaziguye telomereri kwangirika kandi igabanya umuvuduko wa telomere.
Igishushanyo 2 Ubwinshi bwimiterere ya telomeric aberrant muri PBMCs yiyongera hamwe nimyaka yabaterankunga.
4.2 Uburyo bwimikorere ya telomere igenga autophagy
Uburyo bwa molekuline uburyo telomereri igenga autophagy ikubiyemo inzira nyinshi zerekana ibimenyetso. Muri ibyo, inzira ya mTOR (ubukanishi bwa rapamycin) yerekana inzira ikora nkikiraro cyingenzi gihuza telomereri na autophagy. mTOR ni serine / threonine protein kinase yumva intungamubiri zintangangore, urwego rwingufu, nibimenyetso byikura, bityo bikagenga imikorere ya selile nko gukura, gukwirakwira, na autophagy. Ubushakashatsi bwerekanye ko catalitike subunit ya telomerase, TERT (telomerase reverse transcriptase), ishobora gukorana na mTOR ikabuza ibikorwa bya kinase yikigo cya mTOR 1 (mTORC1). Mubihe bisanzwe, mTORC1 iri mumikorere ikora, ikabuza kubaho kwa autophagy. Ariko, iyo telomeres igabanije cyangwa imvugo ya TERT idasanzwe, ingaruka zo guhagarika TERT kuri mTORC1 ziriyongera, bigatuma ibikorwa bya mTORC1 bigabanuka, bityo bikuraho ibibujijwe kuri autophagy no guteza imbere itangizwa ryayo.
Byongeye kandi, inzira ya p53 yerekana inzira nayo igira uruhare runini mugutondekanya telomere ya autophagy. Kugabanuka kwa telomere gukora inzira ya p53 yerekana inzira, kandi p53 irashobora kugenga autofagy muguhindura byimazeyo imvugo ya gen ifitanye isano na autofagy cyangwa bigira ingaruka kuburyo butaziguye inzira ya signal ya mTOR. By'umwihariko, p53 irashobora kugenzura imvugo ya gen zifitanye isano na autofagy nka LC3 na Beclin1, bigatera imiterere ya autophagosomes bityo bigatera autofagy.
4.3 Ingaruka ya autophagy kuri telomere ituje
Ingaruka ya autophagy kuri telomere ituje igerwaho cyane cyane kubungabunga homeostasis mubidukikije. Autophagy irashobora gukuraho ubwoko bwa ogisijeni ikora (ROS) mu ngirabuzimafatizo, bikagabanya kwangirika kwa okiside kuri ADN ya telomere. ROS ni molekile ikora cyane mugihe cya metabolisme selile, kandi ROS ikabije irashobora kwangiza ADN ya okiside, harimo no kwangiza ADN ya telomere. Autophagy irashobora kandi gutesha agaciro mitochondriya yangiritse muri selile, ikarinda umusaruro wa ROS ukabije uterwa no gukora nabi mitochondrial. Byongeye kandi, autophagy irashobora gukuraho uburyo butemewe cyangwa buteranijwe bwa ADN yangiza ibyubaka proteine hamwe nizindi poroteyine zijyanye no gufata neza telomere, bigatuma imikorere yabo isanzwe bityo bikomeza ituze rya telomere. Ubushakashatsi bwerekanye ko selile zifite inenge za autofagy zigaragaza kwangirika kwa ADN ya telomere no kwihuta kwa telomere, mugihe gutera autofagy bishobora kunoza ibyo bintu.
Gushyira mu bikorwa Igitekerezo cya Telomere mu bushakashatsi bwo kurwanya gusaza
5.1 Ingamba zo Gukora Telomerase
Kuva kugabanuka kwa telomere bifitanye isano rya bugufi no gusaza, gukomeza uburebure bwa telomere ukoresheje telomerase byabaye icyerekezo cyingenzi mubushakashatsi bwo kurwanya gusaza. Telomerase ni uruganda rwa ribonucleoprotein rugizwe na RNA na proteyine zishobora gukoresha RNA yacyo nk'icyitegererezo cyo guhuza ADN ya telomere no kuyongera ku mpera za chromosomes, bityo ikagura uburebure bwa telomere. Ubushakashatsi bumwe bwakoresheje ibice bito bya molekile kugirango bikore telomerase. TA-65 ni agace gato ka molekile yakuwe muri Astragalus, bivugwa ko ifite ingaruka za telomerase. Mu bushakashatsi bw’inyamaswa, nyuma yubuyobozi bwa TA-65, uburebure bwa telomere yimbeba bwongerewe ku rugero runaka, kandi na fenotipike zimwe na zimwe zijyanye nimyaka nko kunaniza uruhu no kunaniza umusatsi nabyo byatejwe imbere.
5.2 Ingamba zo kugenzura Autophagy
Urebye uruhare rukomeye rwa autophagy mukubungabunga homeostasis selile no kurinda telomereri, kugenzura autophagy nabyo byahindutse ingamba zo kurwanya gusaza. Ku ruhande rumwe, autophagy irashobora guterwa no gufata ibiyobyabwenge cyangwa gufata imirire. Rapamycin ninzitizi ya mTOR isanzwe itera autophagy muguhagarika ibikorwa bya mTORC1. Mu bushakashatsi bw’inyamaswa, kuvura rapamycin byongereye igihe cyimbeba no kunoza imikorere yumubiri bijyanye nimyaka. Ibicuruzwa bimwe na bimwe, nka resveratrol na curcumin, nabyo byavuzwe ko bitera autophagy. Ibicuruzwa karemano birashobora kugenga autofagy mugukoresha inzira zerekana ibimenyetso nka SIRT1 (kugenzura amakuru acecetse 1). Kuri selile cyangwa abantu bafite imikorere mibi ya autophagy, imikorere ya autophagy irashobora kugarurwa hakoreshejwe imiti ya gene. Autophagy ijyanye na gen irashobora kwinjizwa muri selile ikoresheje gene vectors kugirango yongere ubushobozi bwa selile.
5.3 Ingamba zihuriweho hamwe
Urebye imikoranire igoye hagati ya telomereri, gusaza, na autophagy, guhuza ibikorwa byibanda kuri telomereri na autofagy bishobora kwerekana ingamba nziza zo kurwanya gusaza. Abakora kuri teleomerase hamwe na autofagy inducers zirashobora gukoreshwa icyarimwe: abakora telomerase bongera uburebure bwa telomere, mugihe indodogisi ya autofagy isiba ibice bigize selile byangiritse, bikomeza homeostasis ya selile kandi bigakorana ingaruka zo kurwanya gusaza. Mu bushakashatsi bw’inyamaswa, hamwe hamwe nogukoresha telomerase hamwe na autofagy inducers byagaragaje ingaruka zikomeye zo kurwanya gusaza kuruta abakozi bonyine, nko kunoza imikorere yimikorere ya physiologique ijyanye nimyaka ndetse no kuramba kwinyamaswa.
Umwanzuro
Telomeres igira uruhare runini mugikorwa cyo gusaza na autophagy. Kugabanuka kwa telomere, nk'ikimenyetso cy'ingenzi cyo gusaza, bitera gusaza kwa selile n'indwara zitandukanye ziterwa no gusaza hakoreshejwe uburyo nko gukora inzira zangiza ADN no kugira ingaruka ku mikorere ya mito-iyambere. Hariho umubano utoroshye hagati ya telomereri na autophagy. Telomeres irashobora kugenga autophagy ikoresheje inzira zerekana nka mTOR na p53, mugihe autophagy irinda itumanaho rya telomere mukubungabunga homeostasis idasanzwe. Ubushakashatsi bwo kurwanya gusaza bushingiye ku nyigisho za telomere, nk'ingamba zo gukora za telomerase, ingamba zo kugenzura autofagy, hamwe n'ingamba zo gutabara, zitanga amahirwe menshi yo gutinda gusaza no kuvura indwara ziterwa n'imyaka.
Inkomoko
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