Bya Cocer Peptides 
omwezi gumu emabega
EBINTU BYONNNA N’AMAWULIRE GW’EBINTU EBIweereddwa KU MUTINDO GUNO BIKOZESEBWA KU KUSASANYA AMAWULIRE N’EBIKOLWA BY’OKUSOMESA.
Ebintu ebiweereddwa ku mukutu guno bigendereddwamu kunoonyereza mu kisenge (in vitro research) byokka. Okunoonyereza mu vitro (Olulattini: *mu ndabirwamu*, ekitegeeza mu bikozesebwa mu ndabirwamu) kukolebwa ebweru w’omubiri gw’omuntu. Ebintu bino si bya ddagala, tebikkiriziddwa kitongole kya Amerika ekivunaanyizibwa ku by’emmere n’eddagala (FDA), era tebirina kukozesebwa kuziyiza, kujjanjaba oba kuwonya mbeera yonna ya bujjanjabi, bulwadde oba bulwadde. Kikugirwa nnyo mu mateeka okuyingiza ebintu bino mu mubiri gw’omuntu oba ebisolo mu ngeri yonna.
Okulambika okutwaliza awamu
Okukaddiwa kumanyiddwa olw’emirimu gy’omubiri okukendeera mpolampola n’okweyongera okukwatibwa endwadde. Okutegeera obubonero n‟engeri z‟okukaddiwa kikulu nnyo mu kunnyonnyola enkola z‟ebiramu ez‟okukaddiwa n‟okukola obukodyo okukendeeza ku kukaddiwa n‟okuziyiza endwadde ezikwatagana nabyo.
Ekifaananyi 1. Enkola y’okulwanyisa okunyiganyiga.
Obubonero n’Engeri z’Okukaddiwa
(1) Obutabeera mu ntebenkevu mu nsengekera y’obutonde (Genomic Instability).
Obutabeera mu ntebenkevu mu nsengekera y’obutonde (genomic instability) kye kikulu ekiviirako okukaddiwa. Okukuŋŋaanyizibwa kw’okwonooneka kwa DNA kusibuka ku bintu eby’omunda nga ebika bya okisigyeni ebikola (ROS) ebikolebwa mu nkola z’enkyukakyuka mu mubiri, awamu n’ensonga ez’ebweru nga emisinde gya ultraviolet n’eddagala. Ebiramu bwe bikaddiwa, obulungi bw’enkola z’okuddaabiriza DNA bukendeera, ekivaako okwonooneka kwa DNA okutagonjoolwa. Singa okukutuka kwa DNA okw’emiguwa ebiri tekuddaabirizibwa bulungi, kuyinza okuvaamu obutabeera bulungi mu nsengeka y’ensengekera y’obutonde (chromosomal structure) n’okuddamu okusengeka obuzaale, ekikosa okulaga kw’obuzaale n’enkola y’obutoffaali. Mu butoffaali obukaddiye, enkyukakyuka mu kwolesebwa kwa puloteyina enkulu mu kkubo ly’okuddamu okwonooneka kwa DNA zikendeeza ku kugumiikiriza kw’obutoffaali okwonooneka kwa DNA, bwe kityo ne kyanguya enkola y’okukaddiwa. Obutabeera mu ntebenkevu buno mu nsengekera y’obutonde (genomic instability) tebukoma ku kukosa nkola ya butoffaali eya bulijjo wabula bukwatagana nnyo n’okutandika n’okukulaakulana kw’endwadde ez’enjawulo ezeekuusa ku myaka nga kookolo n’endwadde z’obusimu.
(2) Okusasika kwa telomere
Telomeres ze nsengekera za DNA eziddiŋŋana ku nkomerero za chromosomes ezikola nga enkoofiira ezikuuma, okuziyiza okuyungibwa n’okuvunda kw’enkomerero za chromosomes. Mu kiseera ky’okugabanya obutoffaali, telomeres zikendeera mpolampola kubanga DNA polymerase tesobola kukoppa mu bujjuvu enkomerero za chromosomes. Telomeres bwe zikendeera okutuuka ku kigero ekimu, obutoffaali buyingira mu mbeera y’okukaddiwa oba ne buyita mu apoptosis. Kino kiri bwe kityo kubanga telomeres ennyimpi zimanyibwa obutoffaali ng’okwonooneka kwa DNA, bwe kityo ne zikola ebifo ebikebera enzirukanya y’obutoffaali okuziyiza okwongera okugabanya obutoffaali. Telomerase esobola okwongera ku buwanvu bwa telomere, naye emirimu gyayo giba mitono mu butoffaali obusinga obungi obw’omubiri. Emyaka bwe gyeyongera, telomeres zeeyongera okukendeera, ne zifuuka akabonero akakulu ak’okukaddiwa kw’obutoffaali. Okunoonyereza okumu kuzudde nti okukola telomerase oba okukozesa obujjanjabi bw’obuzaale okwongera ku buwanvu bwa telomere kiyinza okutuuka ku ddaala eritali limu okulwawo okukaddiwa kw’obutoffaali, ne kiwa amagezi amapya mu kunoonyereza ku kulwanyisa okukaddiwa.
(3) Enkyukakyuka mu Epigenetic
Okulungamya epigenetic kukola kinene mu spatiotemporal specificity of gene expression, era enkola y’okukaddiwa ewerekerwako enkyukakyuka za epigenetic ezisaasaanidde. Enkyukakyuka mu nkola za DNA methylation y’emu ku nkyukakyuka ezitera okubaawo mu epigenetic. Mu kiseera ky’okukaddiwa, okutwalira awamu emiwendo gya DNA methylation gikendeera, naye ebitundu ebimu ebitongole ebitumbula obuzaale biraga hypermethylation, ekivaako okusirisa obuzaale buno. Ensengekera z’obuzaale ezikwatagana n’okulungamya enzirukanya y’obutoffaali, okuddaabiriza DNA n’ebirala, zifuna okukendeera kw’okwolesebwa olw’okukendeera kw’obutafaali obuyitibwa promoter hypermethylation, bwe kityo ne kikosa emirimu gy’obutoffaali egya bulijjo. Enkyukakyuka za histone nga acetylation ne methylation nazo zifuna enkyukakyuka, ne zikwata ku nsengekera ya chromatin n’okutuuka ku gene. Enkyukakyuka zino ez’obuzaale zisobola okulung’amya enkola z’obutoffaali nga okukula, okwawukana, n’okukaddiwa nga zikosa okwolesebwa kw’obuzaale, era enkyukakyuka z’obuzaale ziraga eddaala ly’okuddamu, ne ziwa ebigendererwa ebiyinza okuyingira mu kukaddiwa.
(4) Okufiirwa obutoffaali obuyitibwa protein homeostasis
Protein homeostasis gwe musingi gw’okukuuma enkola y’obutoffaali eya bulijjo, nga mulimu enkola nga okuzimba puloteyina, okutambuza, n’okuvunda. Ng’emyaka gigenda giyitawo, enkola za puloteyina homeostasis mu butoffaali zigenda zitakwatagana mpolampola. Okwolesebwa n’enkola ya molekyu chaperones nga heat shock proteins zikendeera, ne kiremesa proteins empya ezikoleddwa okuzinga obulungi, ekivaako okukuŋŋaanyizibwa kwa proteins ezikubiddwa obubi munda mu butoffaali. Emirimu gy’enkola za proteasome ne autophagy-lysosomal nagyo gyonooneka, ekikendeeza ku busobozi bwazo okugogola obutoffaali obubikkuddwa obubi n’obwonoonebwa. Okukuŋŋaanyizibwa kwa puloteyina zino ezitali za bulijjo kukola ebikuŋŋaanyizibwa ebitaataaganya enkola z’omubiri eza bulijjo mu butoffaali, ne bikola amakubo g’obubonero bw’okunyigirizibwa mu butoffaali, era ne bivaako obutoffaali okukaddiwa. Mu ndwadde z’obusimu, puloteyina ezibikkiddwa obubi nga β-amyloid ne tau proteins zikuŋŋaanyizibwa mu bungi, ne zireeta obusimu obutakola bulungi n’okufa, ekikwatagana ennyo n’okufiirwa protein homeostasis mu nkola y’okukaddiwa.
(5) Obutakola bulungi ku bubonero bw’ebiriisa
Amakubo agakwata ebiriisa gakola kinene mu kukula kw’obutoffaali, okukyusakyusa ebiriisa, n’okukaddiwa. Twala ekkubo lya mTOR (mammalian target of rapamycin) ng’ekyokulabirako; esobola okuwulira embeera y’emmere mu butoffaali n’okulungamya enkola nga okukola puloteyina, okukula kw’obutoffaali, n’okulya (autophagy). Ebiriisa bwe biba bingi, mTOR ekola, n’etumbula okukula n’okukula kw’obutoffaali; wabula, okukola okuyitiridde kw’ekkubo lya mTOR kukwatagana n’okukaddiwa, kubanga kuziyiza autophagy, ekivaako okukuŋŋaanyizibwa kw’ebitundu by’omubiri ebyonooneddwa ne puloteyina, ate nga nakyo kitumbula okuddamu kw’okuzimba. Okuziyiza kalori okw’ekigero kuyinza okuziyiza emirimu gya mTOR, okukola autophagy, n’okulongoosa kasasiro w’obutoffaali, bwe kityo ne kikendeeza ku kukaddiwa. Ekkubo ly’obubonero erikwata ku insulini/insulin-like growth factor-1 (IGF-1) nalyo likwatagana nnyo n’okulungamya ebiriisa n’okukaddiwa; okutaataaganyizibwa kw’ekkubo lino kikosa enkyukakyuka y’obutoffaali n’obulamu. Nga tulung’amya amakubo agategeera ebiriisa, embeera z’okukyusakyusa ebiriisa mu butoffaali zisobola okulongoosebwa, bwe kityo ne kikendeeza ku nkola y’okukaddiwa.
(6) Obutakola bulungi mu mitochondria
Mitochondria, nga amaanyi g’obutoffaali, zikola kinene mu nkola y’okukaddiwa. Ng’emyaka gigenda gikula, ensengekera n’enkola ya mitochondria bifuna enkyukakyuka ez’amaanyi. DNA ya mitochondrial (mtDNA), etalina bukuumi bwa histone era esangibwa okumpi n’ebifo ebikola ROS, etera okwonooneka mu ngeri ya oxidative, ekivaako okukuŋŋaanyizibwa kw’enkyukakyuka za mtDNA. Enkyukakyuka zino zikosa enkola y’ebizibu by’olujegere lw’okussa mu mitochondrial, zikendeeza ku bulungibwansi bw’okukola ATP, era zongera ku kukola ROS. ROS esukkiridde eyongera okwonoona mitochondria ne biomolecules endala munda mu butoffaali, ne kivaamu enzirukanya embi. Obutakwatagana mu nkyukakyuka za mitochondria (nga mw’otwalidde n’okuyungibwa n’okukutuka) nazo zikwata ku nkola ya mitochondria n’okusaasaana. Mu butoffaali obukaddiye, okukutuka kwa mitochondria okuyitiridde kuvaamu mitochondria ennyimpi, ezikutusekutuse nga zirina obuzibu mu kukola. Obutakola bulungi bwa mitochondrial-induced energy metabolism abnormalities n’okweyongera mu oxidative stress bye bintu ebikulu eby’okukaddiwa kw’obutoffaali n’ebiramu, ebikwatagana nnyo n’okutandika n’okukulaakulana kw’endwadde ez’enjawulo ezeekuusa ku myaka ng’endwadde z’emisuwa n’endwadde z’obusimu.
(7) Okukaddiwa kw’obutoffaali
Okukaddiwa kw’obutoffaali kitegeeza okufiirwa obusobozi bw’okukula n’okuyingira mu mbeera enywevu ennyo, etakyukakyuka ey’okukwata okukula. Obutoffaali obukaddiye bulaga engeri ez’enjawulo ez’enkula, omuli okweyongera kw’obunene bw’obutoffaali, enkula y’obutoffaali okufuukuuse, n’okukola kwa β-galactosidase okulinnya. Enkola eziviirako okukaddiwa kw’obutoffaali za njawulo, omuli okufunza telomere, okwonooneka kwa DNA, n’okunyigirizibwa okw’okwokya. Obutoffaali obukaddiye bufulumya omuddirirwa gwa cytokines, chemokines, ne proteases, ne bukola ekirungo ekiyitibwa senescence-associated secretory phenotype (SASP). SASP tekoma ku kukola bikolwa bya paracrine ku butoffaali obubeetoolodde, okuleeta okuddamu kw’okuzimba n’okuddamu okukola matrix ey’ebweru w’obutoffaali, naye era eyinza okutumbula tissue fibrosis n’okutondebwawo kw’obutonde obutono obw’ekizimba. Wadde ng’okukaddiwa kw’obutoffaali kuyinza okuziyiza okukula kw’obutoffaali bw’ekizimba okutuuka ku ddaala eritali limu, okukuŋŋaanyizibwa kw’obutoffaali obukaddiye mu mubiri okumala ebbanga eddene kuyinza okukosa obubi enkola y’ebitundu n’ebitundu by’omubiri, okwanguya enkola y’okukaddiwa.
(8) Okukoowa kw’obutoffaali obusibuka mu nsiko
Obutoffaali obusibuka bulina obusobozi okwezza obuggya n’okwawukana mu bika by’obutoffaali eby’enjawulo, nga bukola kinene nnyo mu nkula, okulabirira, n’okuddaabiriza ebitundu by’omubiri n’ebitundu by’omubiri. Emyaka bwe gyeyongera, enkola y’obutoffaali obusibuka mu mubiri ekendeera mpolampola, ng’obusobozi bw’okwezza obuggya bukendedde ate n’obusobozi bw’okwawula obutono. Mu kiseera ky’okukaddiwa, bbalansi y’enjawulo y’obutoffaali obusibuka omusaayi mu nnyiriri z’obutoffaali bw’omusaayi ez’enjawulo etaataaganyizibwa, ekivaako enkola y’abaserikale b’omubiri okukosa. Obusobozi bw’okukula n’okwawukana kw’obutoffaali obusibuka mu mesenchymal nabwo bunafuwa, ne bukosa okuddaabiriza n’okuddamu okukola amagumba, amagumba, n’ebitundu by’amasavu. Ebivaako okukoowa kw’obutoffaali obusibuka mulimu enkyukakyuka mu butonde obutonotono, okutaataaganyizibwa kw’amakubo g’obubonero mu butoffaali, n’okukuŋŋaanyizibwa kw’okwonooneka kwa DNA. Okufiirwa enkola y’obutoffaali obusibuka mu mubiri kikendeeza ku busobozi bw’okuddaabiriza ebitundu n’ebitundu by’omubiri, ne bitasobola kukola bulungi ku buvune n’endwadde, bwe kityo ne kivaako omubiri okukaddiwa.
(9) Enkyukakyuka mu mpuliziganya y’omu butoffaali
Empuliziganya wakati w’obutoffaali kikulu nnyo mu kukuuma homeostasis y’ebitundu n’ebitundu by’omubiri. Mu kiseera ky’okukaddiwa, empuliziganya mu butoffaali efuna enkyukakyuka ez’amaanyi. Nga emyaka gyeyongera, empuliziganya y’okuyunga ebituli wakati w’obutoffaali ekendeera, ekikosa okuwanyisiganya ebintu n’okutambuza obubonero wakati w’obutoffaali. Okugatta ku ekyo, enkola y’ensengekera y’omubiri (endocrine system) nayo ekyuka, ekivaako obusimu obutakwatagana. Enkyukakyuka mu kufulumya n’okukola kw’obusimu nga insulini n’obusimu obukula zikwata ku nkyukakyuka y’omubiri n’enkola y’obutoffaali. Okukola kw’amakubo g’obubonero obuzimba kye kintu ekirala ekikulu eky’empuliziganya ey’omu butoffaali ekyusiddwa. Obutoffaali obukaddiye bufulumya ensonga za SASP ezireeta okuddamu kw’okuzimba okutambula obutasalako, okutaataaganya empuliziganya eya bulijjo wakati w’obutoffaali n’obutonde obutono obw’ebitundu. Enkyukakyuka zino mu mpuliziganya mu butoffaali zireeta okukwatagana okutakola wakati w’ebitundu by’omubiri n’ebitundu by’omubiri, bwe kityo ne kitumbula okukula kw’okukaddiwa.
Enkolagana y’obubonero n’engeri z’okukaddiwa
Obubonero obw’enjawulo n’engeri z’okukaddiwa tebyawuddwamu wabula bikwatagana era bikwatagana, nga byonna awamu bivuga enkola y’okukaddiwa. Obutabeera mu ntebenkevu mu nsengekera y’obutonde (genomic instability) buvaako DNA okwonooneka, ekivaako obutoffaali okukaddiwa n’okukoowa kw’obutoffaali obusibuka mu mubiri. Telomere attrition era ekola ku DNA okwonooneka response, ekyongera okuleeta genomic instability. Enkyukakyuka mu nsengekera y’obutonde (epigenetic changes) zisobola okukwata ku kwolesebwa kw’obuzaale, bwe kityo ne zilungamya enkola nga protein homeostasis, okulungamya ebiriisa, n’enkola ya mitochondria. ROS ereetebwa obutakola bulungi bwa mitochondrial esobola okwongera okwonoona DNA, ekivaako obutabeera mu ntebenkevu mu genomic, ate nga era ekosa amakubo g’obubonero mu butoffaali n’okukyusa empuliziganya wakati w’obutoffaali. Okukaddiwa kw’obutoffaali n’okukoowa kw’obutoffaali obusibuka bikosa okuddaabiriza kw’ebitundu n’obusobozi bw’okuzza obuggya, ate enkyukakyuka mu butonde obutonotono bw’ebitundu, mu ngeri endala, zikwata ku kukaddiwa kw’obutoffaali n’enkola y’obutoffaali obusibuka.
Okukozesa obubonero n’engeri z’okukaddiwa mu bulamu n’endwadde
(1) Nga Ebiraga Ebiramu
Obubonero n‟engeri z‟okukaddiwa bisobola okukola ng‟ebiraga obulamu okwekenneenya eddaala ly‟omuntu ssekinnoomu ery‟okukaddiwa n‟embeera y‟obulamu. Okugeza, nga tupima obuwanvu bwa telomere, enkola ya DNA methylation, n’ebiraga emirimu gya mitochondrial, kisoboka okulagula emyaka gy’omuntu ssekinnoomu egy’obuzaale n’obulabe bw’okufuna endwadde ezeekuusa ku myaka okutuuka ku ddaala eritali limu. Ebiraga obulamu bino biyamba mu kuzuula amangu ensonga z‟ebyobulamu eziyinza okubaawo, ne biwa omusingi gw‟okuddukanya ebyobulamu mu ngeri ey‟obuntu n‟okuyingira mu nsonga. Mu kuziyiza endwadde z’emisuwa, okuzuula obubonero bw’okukaddiwa obukwatagana n’okuzimba mu musaayi kiyamba okuzuula abantu abali mu bulabe obw’amaanyi era kisobozesa okuyingira mu nsonga nga bukyali, gamba ng’okukyusa mu bulamu oba obujjanjabi bw’eddagala.
(2) Ebigendererwa by’okukola eddagala
Obubonero obw’enjawulo n’engeri z’okukaddiwa biwa ebigendererwa bingi eby’okukola eddagala. Ku butabeera mu ntebenkevu mu nsengekera y’obutonde (genomic instability), eddagala eritumbula okuddaabiriza DNA liyinza okukolebwa; ku telomere attrition, eddagala erikola telomerase oba okukuuma telomeres liyinza okunoonyezebwa; for loss of protein homeostasis, drugs that enhance molecular chaperone function or promote protein degradation can be developed, etc. Mu myaka egiyise, okunoonyereza ku rapamycin ne analogues zaayo ezigenderera ekkubo lya mTOR kukoze enkulaakulana ey’amaanyi mu kukendeeza ku kukaddiwa n’okwongera ku bulamu, nga kiwa ekyokulabirako ekirungi eky’okukola eddagala eriziyiza okukaddiwa. Ku kukaddiwa kw’obutoffaali, okukola eddagala eriyinza okugogola obutoffaali obukaddiye oba okuziyiza SASP kiyinza okulongoosa obubonero bw’endwadde ezeekuusa ku kukaddiwa n’okukendeeza ku nkola y’okukaddiwa.
(3) Enkola z’okuyingira mu nsonga z’ebyobulamu
Okusinziira ku kutegeera obubonero n‟engeri z‟okukaddiwa, enkola ezikwatagana ez‟okuyingira mu nsonga z‟ebyobulamu zisobola okukolebwa. Mu nsonga y’okuyingira mu mmere, okukugira kalori n’emmere y’omu Mediterranean bisobola okulung’amya amakubo g’okutegeera ebiriisa, okulongoosa embeera y’enkyukakyuka y’emmere, n’okulwawo okukaddiwa. Okuyingira mu nsonga z’okukola dduyiro kuyinza okutumbula enkola ya mitochondria, okutumbula okukula n’okwawukana kw’obutoffaali obusibuka, n’okulongoosa empuliziganya wakati w’obutoffaali, byonna nga birina akakwate akalungi ku kulwawo okukaddiwa. Okukozesa ebirungo ebiziyiza obuwuka obuleeta obulwadde buno kiyinza okukendeeza ku situleesi y’okwokya, okukuuma obutoffaali okuva mu kwonooneka kwa ROS, n’okukuuma enkola y’obutoffaali eya bulijjo. Enkola zino ez‟okuyingira mu nsonga z‟ebyobulamu ezijjuvu ziyamba okukendeeza ku nkola y‟okukaddiwa n‟okutumbula omutindo gw‟obulamu bw‟abakadde.
Mu bufunzi
Obubonero n’engeri z’okukaddiwa bizingiramu enkyukakyuka nnyingi okuva ku molekyu okutuuka ku mitendera gy’obutoffaali n’ebitundu by’omubiri/ebitundu, ebikwatagana era ebikwatagana, nga byonna awamu bikola enkola z’ebiramu enzibu ez’okukaddiwa. Okutegeera obubonero buno n‟engeri zino kiwa omusingi gw‟enzikiriziganya ogw‟okuziyiza, okuzuula, n‟okujjanjaba endwadde ezeekuusa ku kukaddiwa.
Ensonda
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