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.
ʻO ka peptide SS-31 i hoʻopaʻa ʻia ʻo Mitochondria, i ʻike ʻia ʻo elamipretide, he peptide liʻiliʻi me ka hana kikoʻī mitochondria-targeting. I nā makahiki i hala iho nei, ʻoiai ua hohonu ka noiʻi ʻana i nā hana o ka ʻelemakule, ua ʻike nui ʻia ke kuleana koʻikoʻi o ka mitochondrial dysfunction i ka wā ʻelemakule. ʻO SS-31, me kāna mau waiwai kikoʻī mitochondrial a me ka hiki ke hoʻoponopono i ka hana mitochondrial, paʻa i ka ʻōlelo hoʻohiki no nā noi anti-aging.
Kiʻi 1 ʻO ka hanu a me ka pane ʻana o ka membrane i ka hoʻoulu ʻana i ka ADP i loko o ka mitochondria ʻiʻo kaʻawale e koi i ka cytochrome c hou a me ka hoʻopili hexokinase. ʻO ke ala kaʻa ADP/ATP a me ka hoʻopaʻa ʻana o ELAM iā ATP Synthase a me ANT.
I. Nānā o ka pilina ma waena o ka Mitochondria a me kaʻelemakule
ʻO Mitochondria, ʻo ia ka hale mana o ka cell, ke kuleana no ka synthesizing i ka hapa nui o ATP i loko o ke kelepona a pili pū kekahi i nā ʻano hoʻoponopono metabolic a me nā kaʻina transduction hōʻailona. I ka piʻi ʻana o ka makahiki, emi mālie ka hana mitochondrial, ʻo ia kekahi o nā hōʻailona nui o ka ʻelemakule. Hōʻike ʻia ka hana ʻole o ka mitochondrial ma nā ʻano he nui, me ka hōʻiliʻili ʻana o nā mutations i ka mitochondrial DNA (mtDNA), hoʻemi i ka hana o nā kaulahao hanu mitochondrial, e alakaʻi ana i ka lawa ʻole o ka ikehu; hoʻonui i ka hana ʻana o nā ʻano oxygen reactive (ROS) e ka mitochondria, e hoʻoulu ai i ka pōʻino koʻikoʻi oxidative, kahi e hoʻopau hou ai i nā biomolecules intracellular e like me nā protein, lipids, a me nā waikawa nucleic, e hoʻolalelale ana i ka ʻelemakule a me ka make. Hoʻopilikia ka hana mitochondrial maʻamau i ka homeostasis calcium intracellular, hoʻopilikia i nā hana physiological cellular maʻamau. Hoʻopili kēia mau hoʻololi i kekahi i kekahi, e hana ana i kahi pōʻai ʻino e hoʻokau pū i ke kaʻina ʻelemakule.
II. Mechanism of Action of SS-31
Hoʻomaikaʻi i ka Mitochondrial Energy Metabolism
Hoʻonui i ka ADP Sensitivity: I ka wā ʻelemakule, e emi ana ka ʻike mitochondrial i ka ADP, e hōʻemi ana i ka pono synthesis ATP. Hōʻike nā haʻawina e hiki i ka SS-31 ke hoʻopaʻa pololei i ka mitochondrial ADP transporter ANT, e hoʻonui ana i ka lawe ʻana o ANT o ADP, a laila e hoʻonui ai i ka ʻike mitochondrial i ADP. I loko o ka mitochondria muscle kahiko, ua hoʻonui ka lāʻau SS-31 i ka ADP uptake ma o ANT, a laila e hoʻonui ai i ka hanu mitochondrial ma lalo o ka hoʻoulu ADP, hoʻonui i ka hana ATP, a me ka hoʻomaikaʻi ʻana i ka metabolism ikehu i ka mitochondria muscle kahiko.
Hoʻoponopono i nā paʻina kaulahao hanu mitochondrial: ʻO nā huila hanu mitochondrial nā mea nui o ka hana ikehu mitochondrial. I ka wā ʻelemakule, emi pinepine ka hana o nā kaulahao hanu. Hiki i ka SS-31 ke hoʻomau a hoʻonui i ka hana o nā kaulahao hanu ma o ka hoʻopaʻa ʻana i ko lākou kūpaʻa ʻana a i ʻole ka hoʻoponopono ʻana i ka ʻōlelo o nā protein pili. Ua ʻike ʻia nā haʻawina mua i nā hiʻohiʻona mitochondrial dysfunction e pili ana i ka wā kahiko, ua hoʻihoʻi ʻia ka hana o nā kaulahao hanu ma hope o ka mālama ʻana i ka SS-31, e hōʻike ana i kāna hopena hoʻoponopono maikaʻi i ke kaulahao hanu mitochondrial.
Hōʻike 2 SS-31 lapaʻau hoʻohuli i ka naʻau elemakule phenotypes
Hoʻemi i ka pōʻino koʻikoʻi oxidative
Hoʻemi i ka hana ROS: ʻO Mitochondria kekahi o nā kumu kumu mua o ROS i loko o nā cell, a hoʻonui ka hana ROS i ka mitochondria i ka wā ʻelemakule. Hiki i ka SS-31 ke hōʻemi i ka hana ROS ma o nā ala he nui. Hoʻomaikaʻi ia i ka metabolism ikehu mitochondrial, e hoʻonui ana i ke kaulahao transport electron mitochondrial a hōʻemi i ka leakage electron, a laila e hoʻohaʻahaʻa i ka hana ROS. Hiki i ka SS-31 ke hana pololei i ka membrane mitochondrial, e hoʻololi i kona mau waiwai kino, e hōʻemi ana i nā wahi pōʻino oxidative ma ka membrane, a ke kāohi nei i ka hana ROS. I loko o nā puʻuwai puʻuwai mai nā ʻiole kahiko, ʻo ka mālama ʻana me SS-31 i hōʻemi nui i nā pae ROS mitochondrial, e hōʻike ana i kona pono i ka hōʻemi ʻana i ka hana ROS.
Hoʻoponopono i ka ʻōnaehana enzyme antioxidant: Aia i loko o nā kelepona kahi ʻōnaehana enzyme antioxidant, me ka superoxide dismutase (SOD), catalase (CAT), a me ka glutathione peroxidase (GSH-Px), nona ke kuleana no ka scavenging ROS. Hōʻike ka noiʻi e hiki i ka SS-31 ke hoʻonui i ka hiki ke pale i ka antioxidant cell ma o ka hoʻoponopono ʻana i ka ʻōlelo a i ʻole ka hana o kēia mau enzyme antioxidant. I kekahi mau hiʻohiʻona kelepona, ʻo ka mālama ʻana me SS-31 ka hopena i ka piʻi nui ʻana o ka hana o SOD a me GSH-Px, e kōkua ana i ka hoʻomaʻemaʻe manawa o ka ROS keu i loko o nā cell a me ka hoʻēmi ʻana i ka pōʻino oxidative stress-induced.
Ka mālama ʻana i ka paʻa o ka membrane mitochondrial
Ka hoʻopaʻa ʻana i nā phospholipids membrane mitochondrial: He ʻano ʻokoʻa ko SS-31 e hiki ai iā ia ke hoʻopaʻa maikaʻi i nā ʻāpana o ka membrane mitochondrial waiwai i ka phosphatidylserine. ʻO ka Phosphatidylserine kahi phospholipid kikoʻī i ka membrane mitochondrial a he mea koʻikoʻi ia no ka mālama ʻana i ka hana a me ka hana pono o ka membrane mitochondrial. I ka wā ʻelemakule, hiki i ka phosphatidylserine ke maʻalahi i ka pōʻino oxidative, e alakaʻi ana i nā mea kūpono ʻole i ka hoʻokumu ʻana o ka membrane mitochondrial a me ka hana. Ma hope o ka hoʻopaʻa ʻana i ka phosphatidylserine, hiki i ka SS-31 ke pale i ka phosphatidylserine mai ka oxidation aʻo ka hoʻopaʻa ʻana i ke ʻano o ka membrane mitochondrial, e pale ana i ka emi ʻana o ka mitochondrial membrane a me ka wehe ʻana o ka mitochondrial permeability transition pore (mPTP). Ua hōʻike ʻia nā hoʻokolohua in vitro i ka SS-31 e pale maikaʻi i ka emi ʻana o ke koʻikoʻi oxidative i ka hiki ʻana o ka membrane mitochondrial a me ka wehe ʻana o ka mPTP, e mālama ai i ka paʻa o ka membrane mitochondrial.
Hoʻoponopono i nā protein e pili ana i ka membrane: Aia i loko o ka membrane mitochondrial nā proteins like ʻole e pili ana i ka lawe ʻana i nā mea mitochondrial, metabolism ikehu, a me nā kaʻina hana hoʻoili hōʻailona. Hiki i ka SS-31 ke hoʻololi i ke kūpaʻa o ka membrane mitochondrial ma o ka hoʻoponopono ʻana i ka hana a i ʻole ka hōʻike ʻana o kēia mau protein pili i ka membrane. Hiki iā ia ke hoʻoponopono i ka hana o nā kaila anion e pili ana i ka volta (VDAC), he mau protein channel koʻikoʻi ma ka membrane mitochondrial waho a pāʻani i kahi kuleana nui i ka mālama ʻana i ka hoʻololi waiwai a me ka hoʻouna ʻana i nā hōʻailona ma waena o ka mitochondria a me ka cytoplasm. ʻO ka hoʻoponopono SS-31 o VDAC e kōkua i ka mālama ʻana i ka hana maʻamau o ka membrane mitochondrial a me ka paʻa.
III. Nā hopena kikoʻī o SS-31 i ka anti-aging
Nā hopena ma ka ʻōnaehana cardiovascular
Hoʻomaikaʻi i ka hana naʻau: ʻO ka puʻuwai he mea koi nui i ka ikehu, a he mea koʻikoʻi ka hana mitochondrial no ka hana cardiac. I nā ʻiole kahiko, hōʻike pinepine ka naʻau i nā pilikia pili makahiki e like me ka diastolic dysfunction. Ua ʻike nā kānaka ʻepekema ma hope o 8 mau pule o ka mālama ʻana i ka SS-31, ua hoʻomaikaʻi maikaʻi ʻia ka hana diastolic o nā puʻuwai ʻiole kahiko. Ua hui pū ʻia kēia hoʻomaikaʻi ʻana me ka normalization o ka mitochondrial proton leakage i loko o nā cell myocardial, hoʻemi ʻia nā pae mitochondrial ROS, hoʻemi i nā pae o ka oxidation protein cardiac, a me ka hoʻololi ʻana i ka mokuʻāina thiol redox o nā protein i kahi kūlana hoʻemi. Ua hoʻonui pū ʻo SS-31 i ka pae phosphorylation o cMyBP-C Ser282 i loko o nā cell myocardial, kahi pili pili me ka hoʻomaikaʻi ʻana i ka hana diastolic cardiac.
Kiʻi 3 Ua pale ʻia ka hemahema o ke aʻo ʻana i nā ʻiole ʻelemakule i hoʻoulu ʻia e ka hiamoe hiamoe me SS31.
Palekana vascular: I ka wā ʻelemakule, pilikia ka hana o ka endothelial cell, emi ka elasticity vascular, a ʻoi aku ka nui o nā maʻi cardiovascular. I loko o kahi hiʻohiʻona microbleeding i hoʻokomo ʻia i ka hypertension ma ka lolo o nā ʻiole kahiko, ʻo ka mālama ʻana me SS-31 e hōʻike ana i nā hopena pale vascular koʻikoʻi. Hoʻemi ia i ka hana radical manuahi mitochondrial i hoʻoulu ʻia e ka hypertension, hoʻēmi i ka pōʻino o ke koʻikoʻi oxidative i ka pā vascular, a laila e hoʻopaneʻe nui i ka hoʻomaka ʻana o ka microbleeding a hoʻemi i kona hanana. No laila, he kuleana koʻikoʻi ka SS-31 i ka mālama ʻana i ka hana maʻamau a me ka hana o nā kīʻaha koko a me ka pale ʻana i nā maʻi vascular pili makahiki.
Nā hopena i ka ʻōnaehana nerve
Hoʻopau i ka hana ʻino: I ka piʻi ʻana o ka makahiki, e emi mālie ka hana ʻana o ka ʻōnaehana nerve, a ʻoi aku ka nui o ka hemahema o ka naʻau e like me ka hoʻomanaʻo ʻana a me ka emi ʻana o ka hiki ke aʻo. He kuleana koʻikoʻi ka mitochondrial dysfunction i ka hoʻomaka ʻana a me ka holomua o nā maʻi neurodegenerative a me ka cognitive dysfunction. I ke kumu hoʻohālike o ka cognitive dysfunction i hoʻoulu ʻia e ka isoflurane i nā ʻiole kahiko, hiki i ka SS-31 ke hoʻohuli i ka mitochondrial dysfunction, hoʻopakele i ka isoflurane-induced cognitive deficits. Hoʻoikaika ka SS-31 i ka hoʻoponopono ʻana i ka hōʻailona BDNF, hoʻohuli i ka downregulation o nā protein pili pili i ka synaptic plasticity e like me synaptophysin, PSD-95, a me p-CREB, a hoʻonui i ka NR2A, NR2B, CaMKIIα, a me CaMKIIβ, e hoʻonui ai i ka synaptic plasticity a me ka pale ʻana i ka hana cognitive.
Hoʻopau i nā hopena maikaʻi ʻole o ka hiamoe: ʻO ka hiamoe ka mea maʻamau, a ʻo kona mau hopena maikaʻi ʻole i ka ʻōnaehana nerve e lilo i mea nui i ka makahiki, e alakaʻi i ka cognitive dysfunction a me ka piʻi ʻana o nā maʻi neurodegenerative. I nā ʻiole 20 mau mahina, ua lawelawe ʻia ʻo SS-31 (3 mg/kg) ma o ka hoʻokele subcutaneous i kēlā me kēia lā no 4 mau lā, me 4 mau hola o ka hiamoe ʻana i nā lā ʻelua i hala. Hōʻike nā hualoaʻa i nāʻiole hiamoe i mālamaʻia me SS-31 i hōʻikeʻole i ka hōʻino nui i ka hiki ke aʻo, me ka hoʻihoʻiʻana o ka lolo mitochondrial ATP pae a me ka synaptic plasticity-regulating proteins, a me ka emi iho o nāʻano oxygen reactive (ROS) a me nā cytokines inflammatory i ka hippocampus. Hōʻike kēia e loaʻa paha i ka SS-31 nā pōmaikaʻi therapeutic kūpono i ka hoʻēmi ʻana i nā hopena neurological ʻino o ka hiamoe hiamoe pōkole i nā ʻiole kahiko.
Nā hopena ma ka ʻōnaehana renal: I loko o nā puʻupaʻa o nā ʻiole ʻelemakule, pili ka glomerulosclerosis me ka pōʻino mitochondrial i nā cell epithelial glomerular. Ma hope o 8 mau pule o ka mālama ʻana i ka SS-31 i nā ʻiole 26 mau mahina, ua hoʻomaikaʻi ʻo SS-31 i ka mitochondrial morphology pili i ka makahiki a hoʻēmi i ka glomerulosclerosis. Ma keʻano kiko'ī, ua ho'ēmiʻo ia i ka hōʻikeʻana o nā hōʻailona o kaʻelemakule (p16, β-Gal pili i kaʻelemakule), hoʻonui i ka nui o nā pūnaewele epithelial apical, a ua ho'ēmi i ka hōʻikeʻana o nā hōʻailona o ka hoʻouluʻana o ka cell epithelial parietal (collagen IV, pERK1 / 2, a me ka α-smooth muscle actin). ʻOiai ʻaʻole i hoʻopilikia ʻo SS-31 i ka nui o ka podocyte, ua hōʻemi ʻo ia i nā hōʻailona o ka pōʻino podocyte (desmin), hoʻomaikaʻi i ka cytoskeletal integrity (synaptophysin), a ua hui pū ʻia me ke kiʻekiʻe o ka glomerular endothelial cell density (CD31). Hōʻike kēia i ka mālama ʻana i ka wā pōkole SS-31 he hopena pale i ka glomerular mitochondria a hoʻomaikaʻi i ka hoʻolālā glomerular.
Nā hopena ma ka pae kelepona
Hoʻopaneʻe i ka ʻelemakule kelepona: Ma nā hoʻokolohua cell, ua hoʻohana ʻia ʻo H₂O₂ e hoʻoulu i kahi hiʻohiʻona ʻelemakule i hoʻoulu ʻia i ke koʻikoʻi i nā cell HEK293T, a ukali ʻia e ka hana me SS-31. Ua hōʻike ʻia nā hopena i hōʻemi nui ʻia ka helu maikaʻi SA-β-gal i ka hui SS-31, e hōʻike ana i ka emi ʻana o nā pae ʻelemakule cellular. Eia kekahi, ua emi ka ikaika o ka fluorescence intracellular ROS, ua hoʻonui ʻia ka hiki ke mitochondrial membrane, a ua piʻi nā pae ATP i ka hui SS-31. Ua hōʻike ʻia ka loiloi immunoblotting protein i ʻoi aku ka kiʻekiʻe o nā pae ʻōlelo o nā protein P53, P21, a me Acetyl-p53 i ka pūʻulu hoʻohālike i hoʻohālikelike ʻia i ka pūʻulu hoʻomalu, ʻoiai ua hōʻike ka hui SS-31 i ka emi ʻana i hoʻohālikelike ʻia i ka hui hoʻohālike. ʻO ka mea like ʻole, ʻoi aku ka haʻahaʻa o ka pae ʻōlelo o ka protein Sirt1 i ka pūʻulu hoʻohālike i hoʻohālikelike ʻia i ka pūʻulu hoʻomalu, aʻo ka hui SS-31 i hōʻike i ka piʻi ʻana i hoʻohālikelike ʻia i ka hui hoʻohālike. No laila, hiki ke hoʻoholo i ka SS-31 hiki ke hoʻopaneʻe i ka ʻelemakule HEK293T ma o ka hoʻomaikaʻi ʻana i ka hana mitochondrial a me ka hoʻoponopono ʻana i ka hōʻike ʻana o nā protein pili i ka wā kahiko i loko o nā cell.
Ka pale ʻana i ka pōʻino cellular stress oxidative: I ka H₂O₂-induced oxidative stress damage model of ARPE-19 cell, mālama ʻia me SS-31 i hoʻonui nui ʻia ke ola ola cell, hoʻemi i nā pae ROS intracellular, hoʻemi i ka nui o nā cell me ka hiki ke emi o ka membrane mitochondrial, hoʻohaʻahaʻa loa i ka PI positivity rate o celluten3, a me ka nui o ka protein positivity rate (e hōʻike ana i ka nui o ka protein i ka make ʻana o ka cell31). hōʻike. Hōʻike kēia mau hualoaʻa he hopena pale koʻikoʻi ko SS-31 i ka H₂O₂-induced oxidative stress pōʻino i loko o nā pūnaewele ARPE-19, hiki ke kōkua i ka pale ʻana i ka pōʻino pili makahiki.
Ka hopena
Hāʻawi ka mitochondrial-targeted peptide SS-31 i ka anti-aging. Mai kāna mau hana hoʻoponopono multifaceted e pili ana i ka hana mitochondrial a hiki i kona hopena anti-aging nui ma nā ʻano ʻōnaehana a me nā pae kelepona, hōʻike ia i ka hiki ke hoʻolālā koʻikoʻi anti-aging.
Nā kumu
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[2] Pharaoh G, Kamat V, Kannan S, et al. ʻO ka mitochondrially targeted peptide elamipretide (SS-31) e hoʻomaikaʻi i ka ʻike ADP i ka mitochondria kahiko ma o ka hoʻonui ʻana i ka lawe ʻana ma o ka adenine nucleotide translocator (ANT) [J]. Geroscience, 2023,45(6):3529-3548.DOI:10.1007/s11357-023-00861-y.
[3] Chiao YA, Zhang H, Sweetwyne M, et al. ʻO ka hoʻihoʻi hope ʻana o ka hana mitochondrial e hoʻohuli i ka maʻi cardiac i nā ʻiole kahiko [J]. Elife, 2020,9.DOI:10.7554/eLife.55513.
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[4] Sweetwyne MT, Pippin JW, Eng DG, et al. ʻO ka mitochondrial-targeted peptide, SS-31, hoʻomaikaʻi i ka hoʻolālā glomerular i nā ʻiole o ka makahiki kahiko [J]. Kidney International, 2017,91(5):1126-1145.DOI:10.1016/j.kint.2016.10.036.
[5] Wu J, Zhang M, Li H, et al. Hoʻokomo ʻia ke ala BDNF i nā hopena pale o SS-31 ma ka isoflurane-induced cognitive deficits i nā ʻiole kahiko [J]. Noiʻi Loʻo Loko, 2016,305:115-121.DOI:10.1016/j.bbr.2016.02.036.
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