By Cocer Peptides 
Watanni 1 da suka gabata
DUKKANIN LABARI DA BAYANIN KYAUTATAWA DA AKE BAYAR A WANNAN SHAFIN KAWAI DOMIN WATSA BAYANI NE DA MANUFOFIN ILIMI.
Kayayyakin da aka bayar akan wannan gidan yanar gizon an yi niyya ne kawai don binciken in vitro. Binciken in vitro (Latin: *a cikin gilashi*, ma'ana a cikin gilashin gilashi) ana gudanar da shi a wajen jikin mutum. Waɗannan samfuran ba magunguna ba ne, Hukumar Abinci da Magunguna ta Amurka (FDA) ba ta amince da su ba, kuma dole ne a yi amfani da su don hanawa, magani, ko warkar da duk wani yanayi na likita, cuta, ko cuta. Doka ta haramta shigar da waɗannan samfuran cikin jikin mutum ko dabba ta kowace hanya.
1.Dubawa
A fagen ilimin kimiyyar rayuwa, tsufa da gyaran jiki sune muhimman wuraren bincike da suka ja hankali sosai. Telomeres, a matsayin sifofi na musamman a ƙarshen chromosomes, suna taka muhimmiyar rawa a cikin matakai biyu. Yayin da bincike ke ci gaba, hadaddun dangantaka tsakanin telomeres, tsufa, da autophagy yana ƙara fitowa fili.
Hoto 1 Telomer attrition, tsayin telomere, da telomerase.
2.Bayanin Tsarin Telomere da Aiki
2.1 Tsarin Telomere
Telomeres jerin jerin nucleotide ne da aka kiyaye su sosai a ƙarshen chromosomes masu layi a cikin kwayoyin eukaryotic. Sun ƙunshi jeri mai sauƙi mai sauƙi mai wadata a cikin guanine (G), tare da jerin maimaita telomere na ɗan adam shine TTAGGG. Wannan tsarin yana kare ƙarshen chromosomes daga lalacewa ta hanyar ƙwayoyin cuta, yana hana haɗin chromosome, kuma yana kiyaye kwanciyar hankali na chromosomal. Tsarin telomeres da farko ya ƙunshi DNA telomeric da sunadaran da ke ɗaure su. Waɗannan sunadaran suna yin hulɗa tare da DNA na telomeric don samar da takamaiman sifofi masu girma, suna ƙara haɓaka kwanciyar hankali na telomere.
2.2 Ayyukan Telomeres
Ɗaya daga cikin manyan ayyuka na telomeres shine magance matsalar 'ƙarshen kwafi.' Saboda halayen kwafi na DNA, DNA polymerases na al'ada ba zai iya cika ƙarshen chromosomes na layi ba, yana haifar da raguwa a hankali telomere tare da kowane rarraba tantanin halitta. Kasancewar telomeres buffers wannan ƙarshen yana raguwa, yana tabbatar da mutunci da kwanciyar hankali na chromosomes. Telomeres kuma suna taka muhimmiyar rawa wajen daidaita tsarin sake zagayowar tantanin halitta. Lokacin da telomeres ya gajarta zuwa wani matsayi, suna haifar da wuraren bincike na tantanin halitta, suna haifar da sel su shiga cikin jin daɗi ko apoptosis, don haka suna iyakance ikon su na yaduwa mara iyaka. Wannan tsari yana da mahimmanci wajen hana samuwar ƙari kuma yana da alaƙa da tsarin tsufa na kwayoyin halitta.
3. Dangantaka Tsakanin Telomeres da Tsufa
3.1 Telomere Shortening a matsayin Alamar Tsufa
Yayin da shekaru ke ƙaruwa, tsayin telomeres a yawancin ƙwayoyin somatic na yau da kullun yana raguwa a hankali, al'amarin da aka gani a cikin kyallen takarda da gabobin daban-daban. A cikin sel mononuclear na jikin mutum, tsayin telomere yana raguwa sosai tare da shekaru. Bincike ya nuna cewa raguwar telomere yana da alaƙa da sauye-sauyen physiological daban-daban da suka shafi tsufa, kamar rage yawan ƙarfin haɓakar ƙwayoyin cuta, raunin nama na farfadowa, da kuma ƙara haɗarin cututtuka daban-daban. A matakin salon salula, lokacin da telomeres ya gajarta zuwa tsayi mai mahimmanci, sel sun rasa ƙarfin haɓakawa kuma sun shiga yanayin jin dadi, wanda ke da alaƙa da canza yanayin halitta, rage yawan aiki na rayuwa, da kuma ƙara yawan maganganun β-galactosidase (SA-β-Gal).
3.2 Hanyoyi wanda rage telomere ke haifar da tsufa
Hanyoyin da rage telomere ke haifar da tsufa da farko sun haɗa da hanyoyin mayar da martani ga lalacewar DNA. Lokacin da telomeres ya gajarta zuwa wani matsayi, tsarin su ya zama marar ƙarfi, kuma aikin kariya a ƙarshen telomere ya ɓace, yana haifar da gane ƙarshen chromosome a matsayin wuraren lalata DNA ta sel. Wannan yana kunna jerin hanyoyin siginar amsa lalacewar DNA, kamar hanyar ATM/ATR-p53-p21. Bayan kunnawa, ATM (ataxia-telangiectasia mutated) ko ATR (ataxia-telangiectasia da Rad3 masu alaƙa) sunadaran sunadaran phosphorylate na ƙasa p53 sunadaran, suna haɓaka kwanciyar hankali da haɓaka shigar su cikin tsakiya ta tantanin halitta. A matsayin mahimmancin rubutun rubutu, yana daidaita bayanin jerin kwayoyin halittar da ke da alaƙa da kama da sake zagayowar tantanin halitta, gami da p21. p21 yana hana ayyukan kinases masu dogara da cyclin (CDKs), don haka yana hana sel daga ci gaba daga lokaci na G1 zuwa lokacin S, wanda ke haifar da kamawa da sake zagayowar tantanin halitta kuma a ƙarshe yana haifar da senescence na salula. Gajartawar Telomere kuma na iya haɓaka jin daɗi ta hanyar shafar aikin mitochondrial. Lalacewar Telomere yana haifar da ƙara yawan damuwa na mitochondrial oxidative da kuma rage yuwuwar mitochondrial membrane, ta haka yana shafar makamashin mitochondrial metabolism da ma'auni na redox na intracellular, yana haɓaka tsarin tsufa.
3.3 Telomeres da Cututtuka masu alaƙa da Shekaru
Yawancin cututtukan da suka shafi shekaru, irin su cututtukan zuciya, cututtukan neurodegenerative, da ciwon daji, suna da alaƙa da gajeriyar telomere. A cikin cututtukan zuciya da jijiyoyin jini, raguwar telomere yana da alaƙa da haɓakar ƙwayoyin endothelial da haɓakar atherosclerosis. Tsawon leukocytes na jini na telomere a cikin marasa lafiya na cututtukan zuciya ya fi guntu sosai fiye da yadda ake sarrafa lafiya, kuma tsayin telomere yana da alaƙa da mummunar cuta. A cikin cututtukan neurodegenerative irin su cutar Alzheimer da cutar Parkinson, tsayin telomere a cikin jijiyoyi a cikin kwakwalwa shima yana raguwa sosai. Tsuntsaye na Telomere na iya haifar da tarawar lalacewar DNA da ƙara yawan apoptosis a cikin ƙananan ƙwayoyin cuta, don haka yana hanzarta ci gaba da tafiyar matakai na neurodegenerative. A cikin ciwon daji, kodayake ƙwayoyin kansa suna da hanyoyin da za su kula da tsawon telomere (kamar kunna telomerase), raguwar telomere a farkon matakan tumorigenesis na iya haifar da rashin zaman lafiya na kwayoyin halitta, yana kara yiwuwar maye gurbin kwayoyin halitta da kuma samar da tushe don bunkasa ciwon daji.
4. Dangantaka Tsakanin Telomeres da Autophagy
4.1 Dokokin autophagy ta Telomeres
Autophagy wani muhimmin tsarin lalata kansa na cikin salula da sake yin amfani da shi wanda ke kawar da lalacewar gabobin jiki, da batattu sunadaran, da ƙwayoyin cuta daga cikin tantanin halitta, yana kiyaye kwanciyar hankali na muhallin ciki. Binciken da aka yi kwanan nan ya nuna cewa akwai dangantaka mai rikitarwa tsakanin telomeres da autophagy. Gajerun Telomere na iya haifar da autophagy. Lokacin da telomeres ya gajarta zuwa wani matsayi saboda rarraba tantanin halitta ko wasu dalilai, suna kunna hanyoyin siginar damuwa na ciki, ta haka yana haifar da autophagy. A cikin wasu nau'ikan tantanin halitta marasa ƙarancin telomerase, yayin da telomeres ke ci gaba da raguwa, matakan maganganun sunadaran da ke da alaƙa da autophagy suna ƙaruwa sosai, kuma adadin autophagosomes shima yana ƙaruwa sosai. Autophagy kuma na iya yin tasiri akan kwanciyar hankali na telomere. Ta hanyar share abubuwan lalacewa na DNA da kuma kiyaye zaman lafiyar muhalli ta salula, autophagy a kaikaice yana kare telomeres daga lalacewa kuma yana jinkirta tsarin rage telomere.
Hoto 2 Yawancin tsarin telomeric aberrant a cikin PBMCs yana ƙaruwa tare da shekarun masu bayarwa.
4.2 Hanyoyin kwayoyin halitta na tsarin telomere na autophagy
Hanyoyin kwayoyin da telomeres ke tsara autophagy sun ƙunshi hanyoyin sigina da yawa. Daga cikin waɗannan, hanyar siginar mTOR (maƙasudin makanikai na rapamycin) hanyar sigina tana aiki azaman babbar gada mai haɗa telomeres da autophagy. mTOR shine furotin serine/threonine kinase wanda ke jin matsayin sinadirai na cikin salula, matakan makamashi, da sigina mai girma, ta haka ne ke daidaita hanyoyin salula irin su girma, yaduwa, da autophagy. Bincike ya nuna cewa sashin catalytic na telomerase, TERT (telomerase reverse transcriptase), na iya yin hulɗa tare da mTOR kuma ya hana aikin kinase na mTOR complex 1 (mTORC1). A ƙarƙashin yanayin al'ada, mTORC1 yana cikin yanayin kunnawa, yana hana faruwar autophagy. Koyaya, lokacin da telomeres ya gajarta ko magana ta TERT ba ta da kyau, tasirin hanawa na TERT akan mTORC1 yana haɓaka, yana haifar da raguwar ayyukan mTORC1, ta haka yana ɗaga hanawa akan autophagy da haɓaka farawa.
Bugu da ƙari, hanyar siginar p53 kuma tana taka muhimmiyar rawa a cikin tsarin telomere na autophagy. Ƙaddamarwa na Telomere yana kunna hanyar siginar p53, kuma p53 na iya tsara autophagy ta hanyar daidaita yanayin maganganun kwayoyin da ke da alaka da autophagy ko a kaikaice yana rinjayar hanyar siginar mTOR. Musamman, p53 na iya daidaita maganganun kwayoyin halitta masu alaka da autophagy irin su LC3 da Beclin1, suna inganta samuwar autophagosomes kuma ta haka ne ya haifar da autophagy.
4.3 Sakamakon autophagy akan kwanciyar hankali na telomere
Tasirin autophagy a kan kwanciyar hankali na telomere yana samuwa ne ta hanyar kiyaye homeostasis a cikin yanayin intracellular. Autophagy na iya share tarin nau'in oxygen mai amsawa (ROS) a cikin sel, yana rage lalacewar danniya na oxidative ga DNA telomere. ROS kwayoyin halitta ne masu amsawa sosai da aka samar a lokacin metabolism na salula, kuma yawan ROS zai iya haifar da lalacewar DNA oxidative, ciki har da lalacewa ga DNA telomere. Hakanan autophagy na iya lalata mitochondria mai lalacewa a cikin sel, yana hana haɓakar ROS da yawa wanda lalacewa ta mitochondrial ya haifar. Bugu da ƙari, autophagy na iya share ɓarna ko tara nau'ikan sunadaran gyara lalata DNA da sauran sunadaran da ke da alaƙa da kulawar telomere, tabbatar da aikin su na yau da kullun kuma ta haka ne ke kiyaye kwanciyar hankali na telomere. Nazarin ya nuna cewa ƙwayoyin da ke da lahani na autophagy suna nuna ƙarar lalacewar DNA na telomere da ƙaddamar da raguwar telomere, yayin da haifar da autophagy na iya inganta waɗannan abubuwan mamaki.
Aikace-aikace na ka'idar Telomere a cikin Binciken Anti-tsufa
5.1 Dabarun Kunna Telomerase
Tun da raguwar telomere yana da alaƙa da tsufa, kiyaye tsayin telomere ta hanyar kunna telomerase ya zama jagora mai mahimmanci a binciken rigakafin tsufa. Telomerase wani hadadden ribonucleoprotein ne wanda ya hada da RNA da sunadaran da zasu iya amfani da nasa RNA a matsayin samfuri don hada DNA telomere da kuma kara shi zuwa karshen chromosomes, ta haka ne ke kara tsayin telomere. Wasu nazarin sun yi amfani da ƙananan mahadi don kunna telomerase. TA-65 wani ƙananan ƙwayoyin ƙwayoyin cuta ne da aka samo daga Astragalus, wanda aka ruwaito yana da tasirin telomerase. A cikin gwaje-gwajen dabbobi, bayan gudanar da TA-65, an tsawaita tsawon telomere na beraye zuwa wani matsayi, kuma an inganta wasu nau'o'in dabi'un da suka shafi shekaru kamar fatar fata da gashin gashi.
5.2 Dabarun Ka'idodin Ka'idojin Jiki
Ganin muhimmiyar rawar da autophagy ke da shi wajen kiyaye homeostasis na salula da kuma kare telomeres, daidaita autophagy kuma ya zama dabarun da za a iya magance tsufa. A gefe ɗaya, ana iya haifar da autophagy ta hanyar magunguna ko matakan abinci mai gina jiki. Rapamycin babban mai hana mTOR ne wanda ke haifar da autophagy ta hanyar hana ayyukan mTORC1. A cikin gwaje-gwajen dabba, jiyya na rapamycin ya tsawaita tsawon rayuwar linzamin kwamfuta da inganta ayyukan ilimin lissafi masu alaƙa da shekaru. Wasu samfuran halitta, irin su resveratrol da curcumin, an kuma bayar da rahoton haifar da autophagy. Waɗannan samfuran na halitta na iya daidaita autophagy ta hanyar kunna hanyoyin sigina kamar SIRT1 (mai sarrafa bayanan shiru 1). Ga sel ko mutanen da ke da aikin autophagy mai rauni, ana iya dawo da aikin autophagy ta hanyar maganin kwayoyin halitta. Za a iya shigar da kwayoyin halittar da ke da alaƙa da autophagy cikin sel ta hanyar ƙwayoyin halitta don haɓaka ƙarfin autophagy na salula.
5.3 Haɗin Dabarun Sashi
Idan aka ba da haɗaɗɗiyar hulɗar tsakanin telomeres, tsufa, da autophagy, haɗin kai da aka yi niyya ga duka telomeres da autophagy na iya wakiltar dabarun rigakafin tsufa mafi inganci. Ana iya amfani da masu kunnawa na Telomerase da masu haifar da autophagy a lokaci guda: masu kunnawa telomerase suna tsawaita tsayin telomere, yayin da inducers na autophagy ke share ɓangarori na salon salula da suka lalace, kula da homeostasis na salon salula da daidaita tasirin tsufa. A cikin gwaje-gwajen dabba, haɗuwa da amfani da masu kunnawa telomerase da masu haifar da autophagy sun nuna mafi mahimmancin tasirin tsufa fiye da ko dai wakili kaɗai, kamar ingantaccen haɓaka ayyukan ilimin lissafi da ke da alaƙa da shekaru da tsawon rayuwar dabba.
Kammalawa
Telomeres suna taka muhimmiyar rawa a cikin tafiyar matakai na tsufa da autophagy. Telomere yana ragewa, a matsayin maɓalli mai mahimmanci na tsufa, yana haifar da tsufa na salula da cututtuka daban-daban masu alaka da tsufa ta hanyar hanyoyi kamar kunna hanyoyin amsawar lalacewar DNA da kuma tasiri aikin mitochondrial. Akwai hadadden dangantaka tsakanin telomeres da autophagy. Telomeres na iya daidaita autophagy ta hanyar sigina irin su mTOR da p53, yayin da autophagy yana kare kwanciyar hankali na telomere ta hanyar kula da homeostasis na muhalli na ciki. Binciken anti-tsufa bisa ka'idar telomere, kamar dabarun kunnawa telomerase, dabarun sarrafa autophagy, da dabarun shiga tsakani, yana ba da kyakkyawan fata don jinkirta tsufa da magance cututtukan da suka shafi shekaru.
Sources
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