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) akwadobeghị 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.
1.Nchịkọta
N'ihe gbasara sayensị ndụ, ịka nká na autophagy bụ ebe nyocha dị mkpa nke dọtara mmasị dị ukwuu. Telomeres, dị ka ihe owuwu pụrụ iche na njedebe nke chromosomes, na-arụ ọrụ dị mkpa na usoro abụọ ahụ. Ka nyocha na-aga n'ihu, mmekọrịta dị mgbagwoju anya n'etiti telomeres, ịka nká, na autophagy na-apụtawanye ìhè.
Ọgụgụ 1 Telomere attrition, ogologo telomere, na telomerase.
2.Nyochaa Ọdịdị na Ọrụ Telomere
2.1 Ọdịdị Telomere
Telomeres bụ usoro nucleotide ugboro ugboro echekwara nke ukwuu dị na nsọtụ chromosomes linear na ntule eukaryotic. Ha nwere usoro ugboro ugboro dị mfe bara ụba na guanine (G), yana usoro nkwugharị telomere mmadụ bụ TTAGGG. Ihe owuwu a na-echebe nsọtụ chromosomes ka ọ ghara imebi site na nucleases, na-egbochi njikọ chromosome, ma na-eme ka chromosomal kwụsie ike. Nhazi nke telomeres bụ isi bụ DNA telomeric na protein ndị jikọtara ya na ya. Ndị na-edozi protein ndị a na DNA telomeric na-emekọ ihe iji mepụta usoro dị elu dị elu, na-eme ka nkwụsi ike telomere na-aga n'ihu.
2.2 Ọrụ nke Telomeres
Otu n'ime isi ọrụ nke telomeres bụ ileba anya na nsogbu ngbanwe nke njedebe.'' N'ihi njirimara DNA ngbanwe, DNA polymerases enweghị ike ịmegharị njedebe nke chromosomes linear nke ọma, na-eduga na telomere nwayọọ nwayọọ na-ebelata na nkewa sel ọ bụla. Ọnụnọ nke telomeres buffers njedebe a na-ebelata, na-ahụ na iguzosi ike n'ezi ihe na nkwụsi ike nke chromosomes. Telomeres na-arụkwa ọrụ dị mkpa na nhazi usoro okirikiri cell. Mgbe telomeres na-ebelata ruo n'ókè ụfọdụ, ha na-akpalite ebe nlele okirikiri cell, na-eme ka mkpụrụ ndụ banye senescence ma ọ bụ apoptosis, si otú ahụ na-amachi ikike ha maka mmụba na-akparaghị ókè. Usoro a dị oke mkpa n'igbochi nhazi etuto ma nwee njikọ chiri anya na usoro ịka nká nke ihe ndị dị ndụ.
3. Mmekọrịta dị n'etiti Telomeres na ịka nká
3.1 Telomere Shortening dị ka akara nke ịka nká
Ka afọ na-abawanye, ogologo nke telomeres na ọtụtụ mkpụrụ ndụ somatic nkịtị na-eji nwayọọ nwayọọ na-ebelata, ihe a na-ahụ n'anụ ahụ na akụkụ dị iche iche. N'ime mkpụrụ ndụ mononuclear dị n'akụkụ ọbara mmadụ, ogologo telomere na-ebelata nke ukwuu na afọ. Nnyocha na-egosi na mkpirisi telomere nwere njikọ chiri anya na mgbanwe mgbanwe anụ ahụ dị iche iche metụtara ịka nká, dị ka mbelata ikike ịba ụba cell, ike imeghachi anụ ahụ adịghị ike, na ịba ụba nke ọrịa dị iche iche na-adịghị ala ala. N'ọkwa cellular, mgbe telomeres dị mkpụmkpụ ruo ogologo oge dị oke egwu, mkpụrụ ndụ na-efunahụ ike ha na-amụba ma na-abanye n'ọnọdụ mmetụta uche, nke a na-eme mgbanwe mgbanwe mkpụrụ ndụ cell, mbelata ọrụ metabolic, na mmụba nke senescence-metụtara β-galactosidase (SA-β-Gal).
3.2 Usoro nke telomere dị mkpụmkpụ na-ebute ịka nká
Usoro nke telomere na-ebelata ịka nká na-agụnye ụzọ nzaghachi mmebi DNA. Mgbe telomeres na-ebelata ruo n'ókè ụfọdụ, usoro ha na-aghọ nke na-adịghị akwụsi ike, na ọrụ nchebe na njedebe telomere na-efunahụ, na-eduga na njedebe nke chromosome dị ka ebe DNA mebiri site na mkpụrụ ndụ. Nke a na-eme ka usoro mgbama nzaghachi mmebi DNA rụọ ọrụ, dị ka ụzọ ATM/ATR-p53-p21. Mgbe arụ ọrụ, ATM (ataxia-telangiectasia mutated) ma ọ bụ ATR (ataxia-telangiectasia na Rad3 metụtara) protein phosphorylate downstream p53 protein, na-abawanye nkwụsi ike ha na ịkwalite ntinye ha n'ime oghere cell. Dị ka ihe dị mkpa ederede ederede, na-achịkwa okwu nke usoro nke mkpụrụ ndụ ihe nketa metụtara njide okirikiri cell na senescence, gụnyere p21. p21 na-egbochi ọrụ nke cyclin-based kinases (CDKs), si otú ahụ na-egbochi mkpụrụ ndụ ka ọ ghara ịga n'ihu na usoro G1 ruo oge S, na-eduga na njide okirikiri cell na n'ikpeazụ ịkpalite senescence cellular. Mkpirisi Telomere nwekwara ike ịkwalite ịdị ndụ site na imetụta ọrụ mitochondrial. Nbibi Telomere na-eduga n'ịbawanye nrụgide oxidative mitochondrial yana ibelata ikike nke mitochondrial, si otú ahụ na-emetụta mitochondrial ume metabolism na intracellular redox itule, na-eme ka usoro ịka nká dịkwuo elu.
3.3 Telomeres na Ọrịa metụtara afọ
Ọtụtụ ọrịa ndị metụtara afọ, dị ka ọrịa obi, ọrịa neurodegenerative, na ọrịa kansa, na mbelata telomere nwere njikọ chiri anya. N'ọrịa obi, mkpirisi telomere nwere njikọ chiri anya na arụ ọrụ sel endothelial na mmepe nke atherosclerosis. Ogologo ọbara leukocyte telomere dị n'akụkụ ọbara n'ime ọrịa obi na-arịa ọrịa obi dị mkpụmkpụ karịa na njikwa ahụike, yana ogologo telomere na-ejikọta ya na oke ọrịa. N'ọrịa neurodegenerative dị ka ọrịa Alzheimer na ọrịa Parkinson, ogologo telomere na neurons na ụbụrụ na-ebelata nke ukwuu. Mkpirisi Telomere nwere ike iduga nchikota DNA mebiri emebi na apoptosis na-abawanye na neurons, si otú a na-eme ka ọganihu nke usoro neurodegenerative dịkwuo elu. Na ọrịa kansa, ọ bụ ezie na mkpụrụ ndụ kansa na-enwekarị usoro iji nọgide na-enwe ogologo telomere (dị ka telomerase activation), mbelata telomere n'oge mmalite nke tumorigenesis nwere ike ịkpalite ọgba aghara mkpụrụ ndụ ihe nketa, na-abawanye ohere nke mmụgharị mkpụrụ ndụ ihe nketa na inye ntọala maka mmepe tumor.
4. Mmekọrịta dị n'etiti Telomeres na Autophagy
4.1 Iwu nke Autophagy nke Telomeres
Autophagy bụ ihe dị mkpa na-emebi onwe onye na imegharị ihe nke intracellular nke na-ewepụ akụkụ ahụ ndị mebiri emebi, protein ndị na-emegharị emegharị, na pathogens na cell, na-ejigide nkwụsi ike nke gburugburu intracellular. Nnyocha e mere n'oge na-adịbeghị anya egosila na e nwere mmekọrịta dị mgbagwoju anya n'etiti telomeres na autophagy. Mkpirisi Telomere nwere ike ịkpata autophagy. Mgbe telomeres na-ebelata ruo n'ókè ụfọdụ n'ihi nkewa sel ma ọ bụ ihe ndị ọzọ, ha na-eme ka ụzọ mgbaàmà nrụgide intracellular rụọ ọrụ, si otú ahụ na-ebute autophagy. N'ụdị cell ụfọdụ enweghị telomerase, ka telomeres na-eji nke nta nke nta na-ebelata, ọkwa ngosipụta nke protein ndị metụtara autophagy na-abawanye nke ukwuu, ọnụọgụ autophagosomes na-arị elu nke ukwuu. Autophagy nwekwara ike imetụta nkwụsi ike telomere. Site na ikpochapụ ihe mmebi DNA na idowe nkwụsi ike gburugburu ebe obibi cellular, autophagy na-echebe telomeres na-apụtaghị ìhè na mmebi ma na-ebelata usoro mbelata telomere.
Ọnụọgụ 2 Ọnụ ọgụgụ nke ihe owuwu telomeric na-adịghị mma na PBMC na-abawanye na afọ ndị na-enye onyinye.
4.2 Usoro molecular nke usoro telomere nke autophagy
Usoro molekụla nke telomeres ji achịkwa autophagy gụnyere ọtụtụ ụzọ mgbaàmà. N'ime ndị a, ụzọ akara mTOR (mechanistic target of rapamycin) na-arụ ọrụ dị ka isi mmiri na-ejikọta telomeres na autophagy. mTOR bụ serine/threonine protein kinase nke na-achọpụta ọnọdụ nri intracellular, ọkwa ike, na ihe nrịbama uto, si otú a na-achịkwa usoro cellular dị ka uto, mmụba, na autophagy. Nnyocha egosila na mpaghara catalytic nke telomerase, TERT (telomerase reverse transcriptase), nwere ike imekọ ihe na mTOR ma gbochie ọrụ kinase nke mTOR complex 1 (mTORC1). N'okpuru ọnọdụ nkịtị, mTORC1 nọ na ọnọdụ arụ ọrụ, na-egbochi omume nke autophagy. Agbanyeghị, mgbe telomeres na-ebelata ma ọ bụ okwu TERT adịghị mma, a na-abawanye mmetụta mgbochi nke TERT na mTORC1, na-eduga n'ibelata ọrụ mTORC1, si otú a na-ebuli ihe mgbochi na autophagy na ịkwalite mmalite ya.
Na mgbakwunye, ụzọ akara p53 na-arụkwa ọrụ dị mkpa na nhazi telomere nke autophagy. Mkpirisi Telomere na-eme ka ụzọ akara p53 rụọ ọrụ, na p53 nwere ike ịhazi autophagy site n'ịgbanwe okwu nke mkpụrụ ndụ ihe nketa metụtara autophagy ma ọ bụ na-emetụta ụzọ akara mTOR ozugbo. Kpọmkwem, p53 nwere ike imeziwanye okwu nke mkpụrụ ndụ ihe nketa metụtara autophagy dị ka LC3 na Beclin1, na-akwalite nhazi nke autophagosomes ma si otú a na-ebute autophagy.
4.3 Mmetụta nke autophagy na nkwụsi ike telomere
Mmetụta nke autophagy na nkwụsi ike telomere bụ nke a na-enweta nke ọma site na idobe homeostasis na gburugburu intracellular. Autophagy nwere ike ikpochapụ ụdị oxygen na-emeghachi omume (ROS) n'ime sel, na-ebelata nrụgide oxidative mebiri na telomere DNA. ROS bụ ụmụ irighiri ihe na-arụ ọrụ nke ukwuu na-emepụta n'oge metabolism cell, na oke ROS nwere ike ime ka DNA oxidative mebiri emebi, gụnyere mmebi nke telomere DNA. Autophagy nwekwara ike imebi mitochondria mebiri emebi n'ime sel, na-egbochi mmepụta ROS gabigara ókè nke arụrụ arụ mitochondrial kpatara. Na mgbakwunye, autophagy nwere ike ikpochapụ ụdị ezighi ezi ma ọ bụ chịkọtara ụdị protein nrụzi DNA na protein ndị ọzọ metụtara nrụzi telomere, na-ahụ na ọrụ nkịtị ha na-arụ wee si otú a na-edobe nkwụsi ike telomere. Nnyocha e mere egosiwo na mkpụrụ ndụ ndị nwere nkwarụ autophagy na-egosipụta mmụba telomere DNA mebiri yana mbelata telomere dị mkpụmkpụ, ebe ịkpata autophagy nwere ike imeziwanye ihe ndị a.
Ngwa nke Telomere Theory na nyocha mgbochi ịka nká
5.1 Atụmatụ ịgbalite Telomerase
Ebe ọ bụ na mkpirisi telomere nwere njikọ chiri anya na ịka nká, ịnọgide na-enwe ogologo telomere site n'ịgbalite telomerase aghọwo ihe dị mkpa na nchọpụta mgbochi ịka nká. Telomerase bụ ihe mgbagwoju anya ribonucleoprotein nke nwere RNA na protein nwere ike iji RNA nke ya dị ka template iji mepụta DNA telomere ma tinye ya na nsọtụ chromosomes, si otú ahụ na-agbatị ogologo telomere. Ụfọdụ ọmụmụ ejirila ogige obere molecule rụọ ọrụ telomerase. TA-65 bụ obere ngwongwo molecule ewepụtara na Astragalus, nke a kọrọ na ọ nwere mmetụta na-arụ ọrụ telomerase. N'ime nnwale anụmanụ, mgbe nchịkwa nke TA-65 gasịrị, ogologo telomere nke ụmụ oke na-agbatị ruo n'ókè ụfọdụ, na ụfọdụ phenotypes metụtara afọ dịka ịcha akpụkpọ ahụ na ntutu isi na-emekwa ka mma.
5.2 Strategy Regulation Autophagy
N'iburu ọrụ dị mkpa nke autophagy n'ịkwado homeostasis cellular na ichekwa telomeres, ịchịkwa autophagy aghọwokwa atụmatụ nwere ike ime maka mgbochi ịka nká. N'otu aka, enwere ike ịkpalite autophagy site na ọgwụ ma ọ bụ ihe oriri na-edozi ahụ. Rapamycin bụ ihe mgbochi mTOR kpochapụrụ nke na-ebute autophagy site na igbochi ọrụ mTORC1. N'ime nnwale anụmanụ, ọgwụgwọ rapamycin gbatịpụrụ ogologo ndụ òké yana kwalite ọrụ physiological metụtara afọ. A kọwokwa ụfọdụ ngwaahịa sitere n'okike, dị ka resveratrol na curcumin na-ebute autophagy. Ngwaahịa ndị a sitere n'okike nwere ike ịhazi autophagy site n'ịgbalite ụzọ mgbama dị ka SIRT1 (onye na-ahụ maka ozi nzuzo 1). Maka mkpụrụ ndụ ma ọ bụ ndị mmadụ nwere ọrụ autophagy na-adịghị mma, ọrụ autophagy nwere ike iweghachite site na ọgwụgwọ mkpụrụ ndụ ihe nketa. Enwere ike iwebata mkpụrụ ndụ ihe nketa metụtara autophagy n'ime mkpụrụ ndụ site na mkpụrụ ndụ ihe nketa iji kwalite ikike autophagy cell.
5.3 Atụmatụ ntinye aka jikọtara ọnụ
Nyere mgbagwoju anya mmekọrịta dị n'etiti telomeres, ịka nká, na autophagy, ntinye aka na-elekwasị anya ma telomeres na autophagy nwere ike ịnọchite anya atụmatụ mgbochi ịka nká dị irè karị. Enwere ike iji Telomerase activators na autophagy inducers n'otu oge: telomerase activators na-agbatị ogologo telomere, ebe autophagy inducers na-ekpochapụ akụkụ cellular mebiri emebi, na-ejigide homeostasis cellular na synergistically na-egosipụta mmetụta mgbochi ịka nká. N'ime nnwale anụmanụ, ijikọ ọnụ nke telomerase activators na autophagy inducers gosipụtara mmetụta mgbochi ịka nká karịa onye ọ bụla naanị ya, dị ka mmụba ka mma nke ọrụ physiological metụtara afọ yana ogologo ndụ anụmanụ.
Mmechi
Telomeres na-arụ ọrụ dị mkpa na usoro ịka nká na autophagy. Mkpirisi Telomere, dị ka isi akara nke ịka nká, na-ebute ịka nká cellular na ọrịa dị iche iche metụtara ịka nká site na usoro dị ka ime ka ụzọ nzaghachi DNA mebie ma na-emetụta ọrụ mitochondrial. Enwere mmekọrịta dị mgbagwoju anya n'etiti telomeres na autophagy. Telomeres nwere ike ịhazi autophagy site na ụzọ mgbaàmà dị ka mTOR na p53, ebe autophagy na-echebe nkwụsi ike telomere site na idowe homeostasis intracellular gburugburu ebe obibi. Nnyocha mgbochi ịka nká dabere na telomere tiori, dị ka telomerase activation strategy, autophagy regulation strategy, and jikọtara ọnụ usoro ntinye aka, na-enye atụmanya sara mbara maka igbu oge ịka nká na ịgwọ ọrịa ndị metụtara afọ.
Isi mmalite
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