Na Cocer Peptides 
1 mahina aku nei
ʻO nā ʻatikala a me nā ʻike huahana i hāʻawi ʻia ma kēia pūnaewele pūnaewele wale nō no ka hoʻolaha ʻana i ka ʻike a me nā kumu hoʻonaʻauao.
ʻO nā huahana i hāʻawi ʻia ma kēia pūnaewele i manaʻo wale ʻia no ka noiʻi in vitro. Hana ʻia ka noiʻi in vitro (Latin: *i ke aniani*, ʻo ia hoʻi i ka ipu aniani) ma waho o ke kino kanaka. ʻAʻole kēia mau huahana he lāʻau lapaʻau, ʻaʻole i ʻae ʻia e ka US Food and Drug Administration (FDA), a ʻaʻole pono e hoʻohana ʻia no ka pale ʻana, mālama, a hoʻōla paha i kekahi maʻi olakino, maʻi, a i ʻole maʻi. Ua pāpā loa ʻia e ke kānāwai ke hoʻokomo i kēia mau huahana i loko o ke kino kanaka a holoholona paha ma kekahi ʻano.
1.Nānā nui
Ma ke kahua o ka ʻepekema ola, ʻo ka ʻelemakule a me ka autophagy nā wahi noiʻi koʻikoʻi i ʻike nui ʻia. ʻO Telomeres, ma ke ʻano he mau hale kūikawā ma nā wēlau o nā chromosomes, e pāʻani i kahi koʻikoʻi ma nā kaʻina ʻelua. Ke holomua nei ka noiʻi ʻana, ʻo ka pilina paʻakikī ma waena o nā telomeres, ka ʻelemakule, a me ka autophagy e maʻalahi loa.
Kiʻi 1 Telomere attrition, telomere lōʻihi, a telomerase.
2.ʻO ka nānā ʻana o ka Telomere Structure and Function
2.1 Hoʻolālā Telomere
ʻO nā Telomeres ka mālama nui ʻana i nā kaʻina nucleotide repetitive aia ma nā wēlau o nā chromosomes linear i nā mea ola eukaryotic. Loaʻa iā lākou nā kaʻina hana hou maʻalahi i waiwai i ka guanine (G), me ke kaʻina hana telomere kanaka ʻo TTAGGG. Mālama kēia ʻano i nā welau o nā chromosomes mai ka hōʻino ʻia e nā nucleases, pale i ka hui ʻana o nā chromosome, a mālama i ka paʻa chromosomal. ʻO ke ʻano o nā telomeres ka mea nui o ka telomeric DNA a me nā protein e hoʻopaʻa iā ia. Hoʻopili kēia mau protein me ka telomeric DNA e hoʻokumu i nā hale kiʻekiʻe kiʻekiʻe, e hoʻonui hou ana i ka paʻa telomere.
2.2 Nā hana o nā Telomeres
ʻO kekahi o nā hana nui o nā telomeres ʻo ia ka hoʻoponopono ʻana i ka 'pilikia hoʻopiʻi hope.' Ma muli o nā ʻano o ka hana hou ʻana o DNA, ʻaʻole hiki i nā polymerases DNA maʻamau ke hoʻopili piha i nā wēlau o nā chromosomes laina, e alakaʻi ana i ka pōkole telomere me kēlā me kēia māhele cell. ʻO ka loaʻa ʻana o nā telomeres e pale i kēia hopena pōkole, e hōʻoiaʻiʻo ana i ka kūpaʻa a me ka paʻa o nā chromosomes. He kuleana koʻikoʻi nō hoʻi ʻo Telomeres i ka hoʻoponopono ʻana i ka pōʻai cell. Ke hoʻopōkole ʻia nā telomeres i kekahi ʻano, hoʻomaka lākou i nā wahi hōʻoia o ka pōʻai cell, e hoʻokomo i nā cell i ka senescence a i ʻole apoptosis, a laila e kaupalena ʻia ko lākou hiki ke hoʻonui ʻole. He mea koʻikoʻi kēia ʻano hana i ka pale ʻana i ka hoʻokumu ʻana o ka tumora a pili pono i ke kaʻina hana ʻelemakule o nā mea ola.
3. Ka pilina ma waena o Telomeres a me ka ʻelemakule
3.1 ʻO ka pōkole Telomere ma ke ʻano he hōʻailona o ka ʻelemakule
I ka piʻi ʻana o ka makahiki, e pōkole ka lōʻihi o nā telomeres i ka hapa nui o nā cell somatic maʻamau, kahi mea i ʻike ʻia i loko o nā ʻiʻo a me nā ʻāpana like ʻole. I loko o ke kanaka peripheral koko mononuclear cell, telomere lōʻihi emi loa me ka makahiki. Hōʻike ka noiʻi e pili pono ana ka pōkole telomere me nā loli physiological like ʻole e pili ana i ka ʻelemakule, e like me ka hoʻemi ʻana i ka hiki ke hoʻonui ʻia o ka cell, nāwaliwali i ka hiki ke hoʻoponopono hou i ka ʻiʻo, a me ka piʻi ʻana o nā maʻi maʻi mau. Ma ka pae kelepona, i ka wā e pōkole ai nā telomeres i kahi lōʻihi koʻikoʻi, e nalowale nā pūnaewele i ko lākou mana proliferative a komo i kahi kūlana senescent, i ʻike ʻia e ka morphology cell i hoʻololi ʻia, hoʻemi ʻia ka hana metabolic, a me ka hoʻonui ʻana o ka senescence-pili β-galactosidase (SA-β-Gal).
3.2 Nā ʻano hana e hoʻopōkole ai ke telomere i ka ʻelemakule
ʻO nā hana e hoʻopōkole ai i ka telomere e hoʻomaka ai i ka ʻelemakule e pili ana i nā ala pane pōʻino DNA. Ke hoʻopōkole ʻia nā telomeres i kekahi ʻano, lilo ko lākou ʻano paʻa ʻole, a nalowale ka hana pale ma nā wēlau telomere, e alakaʻi ana i ka ʻike ʻana i nā hopena chromosome ma ke ʻano he wahi hōʻino DNA e nā cell. Hoʻoulu kēia i ke ʻano o nā ala hōʻailona hōʻailona hōʻino DNA, e like me ke ala ATM/ATR-p53-p21. Ma ka hoʻoulu ʻana, ATM (ataxia-telangiectasia mutated) a i ʻole ATR (ataxia-telangiectasia a me Rad3-related) proteins phosphorylate downstream p53 proteins, e hoʻonui ana i ko lākou kūpaʻa a hoʻolaha i ko lākou komo ʻana i ka nucleus cell. Ma ke ʻano he kumu transcription koʻikoʻi, hoʻoponopono i ka hōʻike ʻana o nā ʻano genes e pili ana i ka hopu ʻana o ka pōʻai cell a me ka senescence, me ka p21. P21 kaohi i ka hana o ka cyclin-dependent kinases (CDKs), no laila ke pale aku nei i nā pūnaewele mai ka pae G1 a hiki i ka pae S, e alakaʻi ana i ka hopu ʻana i ka pōʻaiapili cell a hoʻomaka i ka senescence cellular. Hiki i ka pōkole Telomere ke hoʻoikaika i ka senescence ma o ka hoʻopili ʻana i ka hana mitochondrial. ʻO ka pōʻino Telomere e alakaʻi i ka hoʻonui ʻana i ke koʻikoʻi o ka mitochondrial oxidative a me ka hoʻemi ʻana i ka hiki o ka membrane mitochondrial, a laila e hoʻopilikia ai i ka metabolism mitochondrial energy a me ke kaulike redox intracellular, e wikiwiki ana i ke kaʻina hana kahiko.
3.3 Telomere a me na ma'i pili makahiki
ʻO nā maʻi e pili ana i ka makahiki, e like me nā maʻi cardiovascular, nā maʻi neurodegenerative, a me ka maʻi kanesa, pili pili me ka pōkole telomere. I nā maʻi maʻi cardiovascular, pili pono ka pōkole telomere me ka hana ʻole o ka endothelial cell a me ka hoʻomohala ʻana o ka atherosclerosis. ʻOi aku ka pōkole o ka lōʻihi o ke koko leukocyte telomere i nā maʻi maʻi puʻuwai coronary ma mua o nā hoʻomalu olakino, a ua pili ʻole ka lōʻihi o telomere me ka nui o ka maʻi. I nā maʻi neurodegenerative e like me ka maʻi Alzheimer a me ka maʻi o Parkinson, ua hoʻopōkole nui ʻia ka lōʻihi telomere i nā neurons i ka lolo. ʻO ka pōkole Telomere hiki ke alakaʻi i ka hōʻiliʻili ʻana o ka pōʻino DNA a hoʻonui i ka apoptosis i nā neurons, a laila e hoʻolōʻihi i ka holomua o nā kaʻina neurodegenerative. I ka ma'i 'a'ai, 'oiai ua loa'a i nā ma'i 'a'ai nā mea hana no ka mālama 'ana i ka lō'ihi o ka telomere (e like me ka ho'ā 'ana o ka telomerase), hiki i ka pōkole telomere i ka wā mua o ka tumorigenesis ke ho'oulu i ka genomic instability, e ho'onui ana i ka likelika o ka gene mutations a me ka ho'olako 'ana i kumu no ka ulu 'ana o ka ma'i.
4. Ka pilina ma waena o Telomeres a me Autophagy
4.1 Hoʻoponopono o Autophagy e Telomeres
ʻO Autophagy kahi hana hoʻohaʻahaʻa ponoʻī intracellular a me ka hana hou ʻana e hoʻoneʻe i nā organelles i hōʻino ʻia, nā protein misfolded, a me nā pathogens mai ke kelepona, e mālama ana i ka paʻa o ke kaiapuni intracellular. Ua hōʻike ʻia nā haʻawina hou he pili hoʻoponopono paʻakikī ma waena o telomeres a me autophagy. Hiki i ka pōkole Telomere ke hoʻoulu i ka autophagy. Ke hoʻopōkole ʻia nā telomeres ma muli o ka mahele cell a i ʻole nā mea ʻē aʻe, hoʻāla lākou i nā ala hōʻailona koʻikoʻi intracellular, a laila e hoʻoulu ai i ka autophagy. I loko o kekahi mau hi'ohi'ona pūnaewele nele i ka telomerase, i ka wā e ho'opōkole ana nā telomeres, e pi'i nui a'e ka pae hō'ike o nā protein e pili ana i ka autophagy, a ke pi'i a'e nei ka nui o nā autophagosome. Hiki i ka Autophagy ke hoʻololi i ke kūpaʻa telomere. Ma ka hoʻomaʻemaʻe ʻana i nā mea pōʻino DNA a me ka mālama ʻana i ka paʻa o ke kaiapuni kelepona, pale pono ʻole ʻo autophagy i nā telomeres mai ka pōʻino a hoʻolohi i ke kaʻina hana pōkole telomere.
Kiʻi 2 Ke piʻi nei ka nui o nā hale telomeric aberrant i nā PBMC me ka makahiki hāʻawi.
4.2 Nā hana molekala o ka hoʻoponopono telomere o autophagy
ʻO nā hana molekala e hoʻoponopono ai nā telomeres i ka autophagy e pili ana i nā ala hōʻailona he nui. Ma waena o kēia mau mea, ʻo ka mTOR (mechanistic target of rapamycin) ke ala hōʻailona ma ke ʻano he alahaka kī e pili ana i nā telomeres a me autophagy. ʻO ka mTOR he serine/threonine protein kinase e ʻike ai i ke kūlana meaʻai intracellular, nā pae ikehu, a me nā hōʻailona kumu ulu, a laila e hoʻoponopono i nā kaʻina kelepona e like me ka ulu, hoʻonui, a me ka autophagy. Ua hōʻike ʻia ka noiʻi e hiki i ka subunit catalytic o telomerase, TERT (telomerase reverse transcriptase), ke launa pū me ka mTOR a ke kāohi i ka hana kinase o ka mTOR complex 1 (mTORC1). Ma lalo o nā kūlana maʻamau, aia ka mTORC1 i kahi kūlana i hoʻāla ʻia, e kāohi ana i ka hiki ʻana o ka autophagy. Eia nō naʻe, ke hoʻopōkole ʻia nā telomeres a i ʻole ka hōʻike TERT, ua hoʻonui ʻia ka hopena inhibitory o TERT ma mTORC1, e alakaʻi ana i ka hoʻemi ʻana i ka hana mTORC1, a laila e hoʻokiʻekiʻe i ka inhibition ma autophagy a hoʻolaha i kona hoʻomaka.
Hoʻohui ʻia, ʻo ke ala hōʻailona p53 ka mea koʻikoʻi i ka hoʻoponopono telomere o autophagy. Hoʻopau ka pōkole Telomere i ke ala hōʻailona p53, a hiki i ka p53 ke hoʻoponopono i ka autophagy ma o ka hoʻololi pololei ʻana i ka hōʻike ʻana o nā genes pili i ka autophagy a i ʻole ka hoʻohuli ʻole ʻana i ke ala hōʻailona mTOR. Ma keʻano kūikawā, hiki i ka p53 ke hoʻonui i ka'ōlelo o nā genes pili i ka autophagy e like me LC3 a me Beclin1, e hoʻoikaika ana i ka hoʻokumuʻana i nā autophagosome a ma laila e hoʻoulu ai i ka autophagy.
4.3 Ka hopena o ka autophagy ma ke kūpaʻa telomere
Loaʻa ka hopena o ka autophagy ma ke kūpaʻa telomere ma ka mālama ʻana i ka homeostasis i loko o ke kaiapuni intracellular. Hiki i ka Autophagy ke hoʻomaʻemaʻe i nā ʻano oxygen reactive (ROS) i hōʻiliʻili ʻia i loko o nā cell, e hōʻemi ana i ka pōʻino oxidative stress i ka telomere DNA. ʻO ka ROS he mau molekole reactive i hana ʻia i ka wā cellular metabolism, a ʻo ka nui o ka ROS hiki ke hoʻopōʻino i ka DNA oxidative, me ka pōʻino i ka telomere DNA. Hiki i ka Autophagy ke hoʻohaʻahaʻa i ka mitochondria i hōʻino ʻia i loko o nā pūnaewele, e pale ana i ka hana nui o ROS ma muli o ka mitochondrial dysfunction. Hoʻohui hou, hiki i ka autophagy ke hoʻomaʻemaʻe i nā ʻano kuhi hewa a i ʻole ka hui ʻana o nā protein hoʻoponopono hōʻino DNA a me nā protein ʻē aʻe e pili ana i ka mālama ʻana i ka telomere, e hōʻoiaʻiʻo ana i kā lākou hana maʻamau a no laila e mālama i ka paʻa telomere. Ua hōʻike nā haʻawina e hōʻike ana nā cell me nā kīnā autophagy i ka hoʻonui ʻana i ka pōʻino o ka telomere DNA a me ka hoʻopōkole ʻana i ka telomere, aʻo ka hoʻoulu ʻana i ka autophagy hiki ke hoʻomaikaʻi i kēia mau ʻano.
Nā noi o ka Telomere Theory i ka Anti-Aging Research
5.1 Nā Kuleana Ho'āla Telomerase
Ma muli o ka pili pili ʻana o ka pōkole telomere me ka ʻelemakule, ʻo ka mālama ʻana i ka lōʻihi o ka telomere ma ka hoʻāla ʻana i ka telomerase ua lilo ia i alakaʻi koʻikoʻi i ka noiʻi anti-aging. ʻO Telomerase kahi ribonucleoprotein complex i haku ʻia me ka RNA a me nā protein e hiki ke hoʻohana i kāna RNA ponoʻī ma ke ʻano he hoʻohālike e synthesize i ka telomere DNA a hoʻohui iā ia i nā wēlau o nā chromosomes, a laila e hoʻolōʻihi i ka lōʻihi telomere. Ua hoʻohana kekahi mau haʻawina i nā pūhui liʻiliʻi liʻiliʻi e hoʻāla i ka telomerase. ʻO TA-65 kahi pūhui mole liʻiliʻi i unuhi ʻia mai Astragalus, i hōʻike ʻia he mau hopena telomerase-activating. Ma nā hoʻokolohua holoholona, ma hope o ka hoʻohana ʻana i ka TA-65, ua hoʻonui ʻia ka lōʻihi o ka telomere o nā ʻiole i kekahi ʻano, a ua hoʻomaikaʻi ʻia kekahi mau mea pili i ka makahiki e like me ka ʻili ʻili a me ka lauoho lauoho.
5.2 Hoʻolālā Hoʻoponopono Autophagy
Hāʻawi ʻia i ka hana koʻikoʻi o ka autophagy i ka mālama ʻana i ka homeostasis cellular a me ka pale ʻana i nā telomeres, ʻo ka hoʻoponopono ʻana i ka autophagy ua lilo pū kekahi i hoʻolālā kūpono no ka anti-aging. Ma ka lima hoʻokahi, hiki ke hoʻoulu ʻia ka autophagy ma o ka lāʻau lapaʻau a i ʻole ka meaʻai. ʻO Rapamycin kahi mea pale mTOR maʻamau e hoʻoulu ai i ka autophagy ma ke kāohi ʻana i ka hana o mTORC1. Ma nā hoʻokolohua holoholona, hoʻonui ka mālama ʻana i ka rapamycin i ke ola o ka ʻiole a hoʻomaikaʻi i nā hana physiological pili makahiki. ʻO kekahi mau huahana kūlohelohe, e like me resveratrol a me curcumin, ua hōʻike pū ʻia e hoʻoulu i ka autophagy. Hiki i kēia mau huahana kūlohelohe ke hoʻoponopono i ka autophagy ma ka hoʻāla ʻana i nā ala hōʻailona e like me SIRT1 (silent information regulator 1). No nā pūnaewele a i ʻole nā kānaka me ka hana autophagy impaired, hiki ke hoʻihoʻi ʻia ka hana autophagy ma o ka lāʻau lapaʻau. Hiki ke hoʻokomo ʻia nā genes pili i ka autophagy i loko o nā pūnaewele ma o nā vectors gene e hoʻonui ai i ka mana autophagy cellular.
5.3 Hoʻolālā Hoʻohui Hoʻohui
Hāʻawi ʻia i ka pilina paʻakikī ma waena o nā telomeres, ka ʻelemakule, a me ka autophagy, ʻo ka hui pū ʻana e kuhikuhi ana i nā telomeres a me autophagy hiki ke hōʻike i kahi hoʻolālā anti-aging ʻoi aku ka maikaʻi. Hiki ke hoʻohana like ʻia nā mea hana Telomerase a me nā autophagy inducers: hoʻonui nā telomerase activators i ka lōʻihi o ka telomere, ʻoiai nā autophagy inducers e hoʻomaʻemaʻe i nā ʻāpana kelepona i hōʻino ʻia, e mālama ana i ka homeostasis cellular a me ka synergistically hoʻohana i nā hopena anti-aging. I nā hoʻokolohua holoholona, ʻo ka hoʻohana ʻana i nā telomerase activators a me nā autophagy inducers i hōʻike i nā hopena anti-aging nui ma mua o kēlā me kēia mea hoʻokahi wale nō, e like me ka hoʻomaikaʻi maikaʻi ʻana o nā hana physiological pili makahiki a me ka lōʻihi o ke ola holoholona.
Ka hopena
He kuleana koʻikoʻi nā Telomeres i nā kaʻina hana o ka ʻelemakule a me ka autophagy. ʻO ka pōkole Telomere, ma ke ʻano he kī nui o ka ʻelemakule, e hoʻoulu i ka ʻelemakule cellular a me nā maʻi like ʻole e pili ana i ka ʻelemakule ma o nā hana e like me ka hoʻāla ʻana i nā ala pane pōʻino DNA a me ka hoʻopili ʻana i ka hana mitochondrial. Aia kahi pilina interregulatory paʻakikī ma waena o telomeres a me autophagy. Hiki i nā Telomeres ke hoʻoponopono i ka autophagy ma o nā ala hōʻailona e like me mTOR a me p53, ʻoiai ʻo autophagy e pale i ka telomere stability ma ka mālama ʻana i ka homeostasis kaiapuni intracellular. ʻO ka noiʻi anti-aging e pili ana i ke kumumanaʻo telomere, e like me ke telomerase activation strategies, autophagy regulation planes, a me nā hoʻolālā hana hoʻohui, hāʻawi i nā manaʻo ākea no ka hoʻopaneʻe ʻana i ka ʻelemakule a me ka mālama ʻana i nā maʻi pili makahiki.
Nā kumu
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