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.
Nānā nui
He kaʻina koʻikoʻi koʻikoʻi ka ʻelemakule kelepona i nā mea ola a pili loa i nā hanana physiological a me nā pathological. I ka piʻi ʻana o ka makahiki, e hōʻiliʻili mālie ana ka ʻelemakule o ke kelepona, e alakaʻi ana i ka emi ʻana o ka hana o ke kino a me ke kino a hoʻoulu i nā maʻi like ʻole. ʻO nā peptide, ma ke ʻano he papa o nā molekole bioactive koʻikoʻi, ua loaʻa i ka manaʻo nui i ke kahua o ka noiʻi ʻelemakule kelepona i nā makahiki i hala. Hōʻike ka noiʻi he mea nui ka peptides i ka hoʻoponopono ʻana i ke kaʻina hana ʻelemakule. ʻO ka ʻimi ʻana i ka pilina ma waena o nā peptides a me ka ʻelemakule kelepona he mea koʻikoʻi nui ia no ka wehewehe ʻana i nā hana o ka ʻelemakule a me ka hoʻomohala ʻana i nā hana anti-aging.
Kiʻi 1. Nā mīkini o nā kaʻina hana kahiko o ka ʻili. (a) Nā radical manuahi a me ka manaʻo koʻikoʻi oxidative. Hoʻokumu ka Mitochondria i ka ROS ma o ka metabolism oxidative. Hiki i ka nui o ka ROS ke hōʻino i ka mitochondrial a me nā hale DNA, e alakaʻi ana i ka emi ʻana o nā pae collagen a me ka piʻi ʻana o nā pae MMP i ka ʻili o ka ʻili. ( b ) Ka manaʻo hoʻomāmā. ʻO nā fibroblasts Senescent a me nā keratinocytes e hūnā i ka nui o nā phenotypes huna e pili ana i ka senescence, me TNF-α, IL-1, IL-6, IFN-γ a me MMP. Hoʻoulu kēia mau cytokine proinflammatory i ka senescence cell cell ma ka hoʻolaha ʻana i ka hana ROS a me ka hoʻoulu ʻana i ke ala hōʻailona ATM / p53 / p21. ( c ) Ka manaʻo kiʻi kiʻi. Hoʻokumu ka Ultraviolet irradiation i ka hana ʻana o ROS a me ka huna ʻana o nā MMP, kahi e hoʻohaʻahaʻa ai i nā ʻāpana matrix extracellular matrix e like me ka collagen. ( d ) Nonenzymatic glycosyl chemistry theory. ʻO ka glycosylation non-enzymatic he hopena ma waena o nā kōpaʻa hoʻohaʻahaʻa manuahi a me nā pūʻulu amino manuahi o nā protein, DNA a me nā lipids e hana i nā AGE a me ROS. ʻO ka hōʻiliʻili ʻana o nā AGE, me ka ROS, hiki ke alakaʻi i nā loli i ka homeostasis cell a me ka hoʻolālā protein.
Kaʻelemakule Pūnaewele
(1) Manaʻo a me nā hiʻohiʻona o ka ʻelemakule kelepona
ʻO ka ʻelemakule kelepona e pili ana i ka hopu ʻia ʻana o ka ulu ʻana i ke ʻano o ke komo ʻana o nā cell ma hope o ka loaʻa ʻana o kekahi mau māhele a i ʻole ka ʻike ʻia ʻana i nā pilikia koʻikoʻi. Hōʻike ia i ke ʻano o nā hiʻohiʻona maʻamau, e like me ka hoʻololi ʻana i ka morphology cell, me ka hoʻonui ʻana i ka nui o ka cell cell, flattening, a me ka vacuolization o ka cytoplasm; ka hopu ʻia ʻana o ka pōʻai cell, me ka hoʻonui ʻole ʻana o nā cell; a me ka hoʻonuiʻana i ka hana o ka β-galactosidase pili i ka senescence (SA-β-gal), i kēia manawa kekahi o nā hōʻailona hoʻohana nui loa o ka senescence cellular. Hoʻololi ʻia ka phenotype huna, kahi e hūnā ai nā cell i nā cytokines, chemokines, a me nā proteases, e hana ana i ka senescence-associated secretory phenotype (SASP).
(2) Nā hopena o ka Senescence Cellular
ʻO ka pōʻino o ke kino a me ka hana o ke kino
ʻO nā kelepona nā poloka kūkulu kumu o nā ʻiʻo a me nā ʻāpana, a ke alakaʻi nei ka senescence cellular i nā kino a me ka hana o ke kino. I loko o ka ʻiʻo o ka ʻili, hoʻemi ka fibroblasts senescent i ka synthesis o ka collagen a me nā fibers elastic, e lilo ai ka ʻili i ka elasticity, ulu nā wrinkles, a ua hōʻemi i ka hiki ke hoʻoponopono. I loko o ka ʻōnaehana cardiovascular, hiki i nā senescent endothelial cell ke alakaʻi i ka paʻakikī o nā pā kīʻaha koko a hoʻemi ʻia ka elasticity, e hoʻonui ana i ka pilikia o ka maʻi cardiovascular. I loko o ka ʻōnaehana pale, ʻo ka ʻelemakule o nā cell immune e hoʻonāwaliwali i ka hana pale pale o ke kino, e ʻoi aku ka maʻalahi o ka poʻe i ka hoʻouka ʻana i ka pathogen a hōʻemi i kā lākou pane pale ʻana i nā kano.
Hui me na ma'i pili makahiki
Manaʻo ʻia ka ʻelemakule kelepona he kumu hoʻokele koʻikoʻi i nā maʻi pili makahiki. I nā maʻi neurodegenerative e like me ka maʻi o Alzheimer a me ka maʻi o Parkinson, pili pono ka ʻelemakule neuronal me nā kaʻina hana pathological e like me ka make neuronal a me ka neuroinflammation. I ka maʻi diabetes, hiki i ka ʻelemakule o nā pancreatic β cell ke alakaʻi i ka lawa ʻole o ka huna ʻana o ka insulin, e pili ana i ka hoʻoponopono maʻamau o ka glucose koko. He pilina koʻikoʻi ko ka senescence cell me ka tumorigenesis a me ka piʻi ʻana o ka tumor. Hiki i ka senescence mua ke hana ma ke ʻano he hana hoʻopau ʻana i ka tumo, e pale ana i ka hoʻonui palena ʻole o nā cell i poino. Eia nō naʻe, i loko o ka microenvironment tumo, ʻo nā mea SASP i hūnā ʻia e nā senescent cell hiki ke hoʻoikaika i ka ulu ʻana o ka cell tumor, invasion, a me ka metastasis.
Nā peptide
(1) Ka wehewehe a me ke ʻano o nā peptides
ʻO nā peptide nā pūhui kaulahao pōkole i hana ʻia e nā waikawa amino i hoʻopili ʻia ma o nā paʻa peptide. Ma muli o ka nui o nā koena amino acid i loko o lākou, hiki ke hoʻokaʻawale ʻia i nā dipeptides, tripeptides, tetrapeptides, a me polypeptides, a me nā mea ʻē aʻe. ʻO nā polypeptides ka lōʻihi, hoʻomau, a me nā kaulahao peptide lālā ʻole. ʻO ka maʻamau, hoʻokaʻawale ʻia nā kaulahao peptide ʻaʻole i ʻoi aku ma mua o 50 mau amino acids i peptides e hoʻokaʻawale iā lākou mai nā protein. ʻO nā kaulahao peptide a pau, koe naʻe nā peptides cyclic, loaʻa iā N-terminal (amino-terminal) a me kahi C-terminal (carboxy-terminal) koena.
(2) Hoʻokaʻawale i nā Peptides
Hoʻokaʻawale ʻia e ka Puna
Endogenous peptides: synthesized e ke kino iho a hana i nā hana physiological like ʻole i loko o ke kino. Nā Neuropeptides, ka mea i komo i ka hoʻouna ʻana i ka hōʻailona a me ka hoʻoponopono ʻana i loko o ka ʻōnaehana nerve, me nā endorphins a me nā enkephalins, nona nā hopena analgesic a me ka hoʻoponopono ʻana i ke ʻano; ʻO nā peptides hormone, e like me ka insulin, he mea koʻikoʻi ia no ka hoʻoponopono ʻana i ke kō koko.
ʻO nā peptides exogenous: loaʻa mai ka meaʻai a i ʻole nā kumu waho ʻē aʻe. No ka laʻana, hiki ke hydrolyzed i kekahi mau protein meaʻai e nā enzyme digestive e hana i nā peptides bioactive, e like me nā peptides waiū, he nui nā hana physiological, me ka antioxidant a me nā hopena immune-modulating. ʻO nā peptide i hoʻomākaukau ʻia ma o ka chemical synthesis a i ʻole biotechnology e hāʻule i lalo o nā peptides exogenous a hoʻohana mau ʻia i ka hoʻomohala lāʻau a me ka lāʻau lapaʻau.
Hoʻokaʻawale ma muli o ka hana
Antioxidant Peptides: Hiki ke ʻoki i nā radical manuahi i loko o ke kino a hōʻemi i ka pōʻino o ke kaumaha oxidative i nā cell. No ka laʻana, ua hōʻike ʻia nā peptides antioxidant bran raiki e hoʻoikaika i ka hana o nā enzyme antioxidant e like me catalase (CAT) a me glutathione peroxidase (GSH-Px) i loko o ka mitochondria o ka puʻuwai a me nā ʻiʻo lolo o D-galactose-induced ʻiole kahiko, e hoʻemi i ke kiʻekiʻe o ka mitochondrial DNA deletion mutations i ka lolo, a pale i nā cell.
ʻO nā peptides immunomodulating: Hoʻoponopono kēia i ka hana pale o ke kino, hoʻonui a hoʻopaʻa paha i nā pane kūlohelohe. Hiki i kekahi mau peptides i loaʻa mai nā meaola o ka moana ke hoʻāla i nā cell immune, hoʻomaikaʻi i ka hiki ke pale pale pale o ke kino, a kōkua i ke kūʻē ʻana i nā maʻi pathogen a me ka ulu ʻana o ka tumor.
ʻO nā peptides e hoʻoponopono i ka ulu ʻana o ka cell: Hoʻopili kēia i nā kaʻina cellular e like me ka proliferation, differentiation, a me apoptosis. ʻO kahi laʻana, epidermal growth factor (EGF) e hoʻoikaika i ka hoʻonui a me ka hoʻokaʻawale ʻana o nā cell epidermal, e hoʻolalelale ana i ka ho'ōla ʻana i ka ʻeha.
ʻO ke kuleana o nā peptides i ka wā kahiko
(1) Hoʻoponopono i ka hana mitochondrial
He kuleana koʻikoʻi ka Mitochondria i ka hana ʻana o ka ikehu cellular a me ka hoʻololi ʻana i nā hōʻailona, a ua pili pono kā lākou dysfunction i ka ʻelemakule cellular. ʻO nā peptides i loaʻa i ka Mitochondria (MDPs) e like me humanin a me MOTS-c e pāʻani i nā kuleana hoʻoponopono koʻikoʻi i ke kaʻina hana ʻelemakule. Ma hope o ka senescence i hoʻoulu ʻia e ka replicative exhaustion, doxorubicin, a i ʻole hydrogen peroxide ka mālama ʻana i nā fibroblasts kanaka mua, piʻi ka helu mitochondrial, piʻi aʻe nā pae hanu mitochondrial, a piʻi aʻe nā pae humanin a me MOTS-c. Hoʻonui ka hoʻokele ʻana o ka humanin a me MOTS-c i ka hanu mitochondrial i loko o ka doxorubicin-induced senescent cell a hoʻoponopono ʻāpana i nā ʻāpana SASP ma o ke ala JAK, e hōʻike ana he hana koʻikoʻi nā MDP i ka mitochondrial ikehu metabolism a me ka hana SASP i nā cell senescent.
Kiʻi 2 Ua hoʻololi ʻia ka nui o ka mitochondrial a me nā energetics i ka wā o ka senescence-induced doxorubicin. (A) Mitochondrial DNA (mtDNA) helu kope ma non-senescent (quiescent) and senescent cell. (B) Nā kiʻi makaʻāinana o Tom20 ('ōmaʻomaʻo; mitochondria) a me Hoechst 33258 (uliuli; nucleus) immunostaining i loko o ka non-senescent (quiescent) a me nā pūnaewele senescent. ʻO ka pā unahi, 20 μm. Ua ana ʻia ka ʻāpana o Tom20 staining i kēlā me kēia cell me ka hoʻohana ʻana iā ImageJ. (C) Nā pae ATP pūnaewele i loko o nā pūnaewele non-senescent (quiescent) a me ka senescent. (D) Ka nui o ka hoʻohana ʻana o ka oxygen kelepona (OCR) i loko o nā pūnaewele non-senescent a me ka senescent. ʻO ka hanu ʻana o Basal, ka mana hanu ʻokoʻa, a me ka hana ʻana o ATP e helu ʻia ma muli o ke kaʻina hoʻohui pūhui e like me nā ʻōlelo a ka mea hana. (E) ʻO ka nui o ka acidification extracellular (ECAR) ma nā pūnaewele non-senescent (quiescent) a me ka senescent.
(2) Nā hopena i nā ala hōʻailona pili i ka ʻelemakule
p53-p21 alahele
ʻO ka protein p53 kahi mea hoʻoponopono koʻikoʻi o ka senescence cellular. Ke hōʻikeʻia nā pūnaewele i nā mea koʻikoʻi e like me ka pōʻino DNA, ua hoʻoikaikaʻia ka p53, e hoʻoulu i ka'ōlelo o ka p21, ka mea e hoʻopaʻa ai ka pōʻaiapili pūnaewele ma ka pae G1, e alakaʻi ana i ka senescence cellular. Hiki i kekahi mau peptides ke hoʻololi i ke ala p53-p21, a laila e hoʻohuli i ka holomua o ka senescence cellular. Hiki i kekahi mau peptides liʻiliʻi liʻiliʻi ke launa pū me ka protein p53, kaohi ʻana i kāna hana a no laila ke hoʻopaneʻe nei i ka senescence cellular. Ua hōʻike nā haʻawina e hiki i nā peptides kikoʻī ke kāohi i ka pilina ma waena o ka p53 a me MDM2 (kahi protein e hoʻoponopono maikaʻi ʻole i ka p53), e hoʻopaʻa i ka protein p53 a mālama iā ia i kahi pae kūpono e pale aku i ka hoʻoulu nui ʻana e alakaʻi i ka senescence cellular.
Alanui Rb-E2F
ʻO ka protein Rb kekahi mea koʻikoʻi koʻikoʻi e hoʻoponopono i ka pōʻaiapuni o ke kelepona i hoʻopaʻa ʻia i ka helu transcription E2F e pale i ka hōʻike ʻana o nā genes pili i ka pōʻaiapili cell. Ke phosphorylated a hoʻopau ʻole ʻia ka protein Rb, hoʻokuʻu ʻia ʻo E2F, e hāpai ana i ke komo ʻana o ke kelepona i ka pae S no ka hana hou ʻana o DNA. I ka wā o ka cellular senescence, hoʻololi i ke ala Rb-E2F e alakaʻi ai i ka hopu ʻana i ka pōʻai cell. Hiki i kekahi mau peptides ke hoʻoponopono i ka senescence cellular ma o ka hoʻololi ʻana i ke kūlana phosphorylation o ka protein Rb a i ʻole ka hoʻoulu ʻana i ka hana E2F. Hiki i kekahi mau peptides ke kāohi i ka phosphorylation protein Rb, e mālama ana i ka paʻa o ka paʻakikī Rb-E2F a ma laila e hoʻopaneʻe ai i ka senescence cellular.
(III) Hooponopono o SASP
Aia ka SASP i nā cytokines like ʻole, chemokines, a me nā proteases, a me nā mea ʻē aʻe. ʻAʻole pili wale kāna mea huna i ka microenvironment o nā cell senescent iā lākou iho akā hoʻopili pū kekahi i nā ʻiʻo a me nā cell a puni, e hāpai ana i nā pane inflammatory a me ke ʻano o ke kino. Hiki i kekahi mau peptides ke hoʻoponopono i ka hana SASP a hoʻēmi i kona hopena ʻino. Ua ʻike pū ʻia kekahi mau peptides i loaʻa i nā mea kanu e hoʻoponopono i ka SASP ma ke kāohi ʻana i ka hoʻāla ʻana o nā ala hōʻailona kikoʻī a me ka hōʻemi ʻana i ka hōʻike o nā mea pili i ka SASP.
Nā noi o nā Peptides i ka hoʻopaneʻe ʻana i ka wā kahiko
(1) Nā noi i nā huahana mālama ʻili
Me ka hoʻonui ʻana i ka hopohopo lehulehu e pili ana i ka ʻelemakule ʻili, ua loaʻa nā peptides i ka noi ākea i ka ʻoihana mālama ʻili. No ka laʻana, ʻōlelo kekahi mau huahana mālama ʻili i loaʻa nā peptides he hopena anti-wrinkle a hoʻopaʻa i ka ʻili. Hōʻike ka noiʻi hiki i kekahi mau peptides ke hoʻoikaika i ka synthesis collagen a hoʻonui i ka elasticity o ka ʻili. Hiki i nā peptides ke hoʻoponopono i ka metabolism o ka ʻili, hoʻomaikaʻi i ka hana pale ʻili, hoʻemi i ka pōʻino i nā ʻili ʻili i hoʻokumu ʻia e nā kumu o waho e like me ka radiation UV, a hoʻolohi i ke kaʻina hana ʻelemakule.
Kiʻi 3 ʻO ka ʻelemakule ma ka ʻili ʻōpio a ʻoi aku.
(2) Nā noi i ka hoʻomohala lāʻau
Lapaʻau ʻana i nā maʻi neurodegenerative
ʻO ka hoʻomohala ʻana i ka lāʻau peptide e paʻa i ka ʻōlelo hoʻohiki nui no ka hoʻoponopono ʻana i ka ʻelemakule neuronal i nā maʻi neurodegenerative. ʻO nā peptide e hoʻoponopono i nā ala hōʻailona intracellular, hoʻoikaika i ke ola neuronal, a hoʻomaʻamaʻa hoʻoponopono i kūkulu ʻia no ka mālama ʻana i ka maʻi o Alzheimer a me ka maʻi o Parkinson. Hiki i kekahi mau peptides ke pale i ka hōʻuluʻulu ʻana o nā protein abnormal i loko o nā neurons, hoʻemi i ka neuroinflammation, a hoʻopaneʻe i ka ʻelemakule a me ka make. Hiki i kahi peptide i kapa ʻia ʻo AC-5216 ke kāohi i ka hōʻuluʻulu ʻana o nā protein β-amyloid a hoʻomaikaʻi i ka hana cognitive i nā ʻiole kumu hoʻohālike o Alzheimer.
Lapaʻau ʻana i nā maʻi puʻuwai
I ka mālama ʻana i nā maʻi cardiovascular, hiki i nā lāʻau peptide ke kuhikuhi i nā kaʻina pathological e like me ka vascular endothelial cell aging and myocardial cell aging. No ka laʻana, hiki i kekahi mau peptides vasoactive ke hoʻoponopono i ka leo vascular a me ka hana cell endothelial, hoʻomaikaʻi i ke kūlana kahiko o nā cell endothelial vascular, a hoʻemi i ka hopena o nā maʻi cardiovascular. Hiki i kekahi mau peptides ke hoʻoikaika i ka hoʻoponopono ʻana a me ka hana hou ʻana o nā cell myocardial, e hāʻawi ana i nā noi kūpono i ka mālama ʻana i nā kūlana e like me ka myocardial infarction.
Ka hopena
ʻO ka ʻelemakule o ke kelepona, ma ke ʻano he kaʻina olaola paʻakikī, hoʻololi i ke kaʻina olakino a me ka ʻelemakule o ke kino. ʻO Peptides, ma ke ʻano he papa koʻikoʻi o nā molekole bioactive, pāʻani i nā hana multifaceted i ka hoʻoponopono ʻana i ka ʻelemakule cell. Ma o ka hoʻoponoponoʻana i ka hana mitochondrial, ke komoʻana i nā ala hōʻailona pili i kaʻelemakule, a me ka hoʻololiʻana i ka SASP, hōʻike nā peptides i ka hiki ke hoʻopaneʻe i kaʻelemakule.
Nā kumu
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