Na Cocer Peptides bin rayt am 
1 mɔnt dɔn pas
ƆL DI ATIKUL ƐN PRODƆKT INFƆMƐSHƆN WE DƐN GI NA DIS WƐBSAYT NA FƆ ƆL FƆ DI INFƆMƐSHƆN ƐN FƆ EDYUKESHƆN.
Di prɔdak dɛn we dɛn gi na dis wɛbsayt na fɔ in vitro risach nɔmɔ. in vitro risach (Latin: *in glas*, we min insay glas) dεn de du am ausayd mכtalman bכdi. Dɛn prɔdak ya nɔto mɛrɛsin, dɛn nɔ gɛt di aprɔval frɔm di US Food and Drug Administration (FDA), ɛn dɛn nɔ fɔ yuz dɛn fɔ protɛkt, trit, ɔ mɛn ɛni mɛrɛsin, sik, ɔ sik. Di lɔ nɔ gri fɔ mek dɛn put dɛn tin ya insay mɔtalman ɔ animal bɔdi ɛni we.
di pεptida we dεn tכgεt pan maytochכndria SS-31, we dεn kכl bak elamipretide, na sכm mכlikul pεptida we gεt spεsifi k mitochondria-tכgεt fכnshכnaliti. insay di las ia dεm, as risεch pan di mεkanism dεm fכ ol pipul dεn de dip, di imכtant rol we di maytochכndrial dεm we de wok fayn na di ol prכsεs dεn de sho bכku bכku wan. SS-31, wit in yכnik maytochכndrial tכgεt prכpati dεm εn abiliti fכ rεgεl maytochכndrial fכnshכn, de ol prכmis fכ anti-aging aplikεshכn dεm.
Figure 1 rεspireshכn εn mεmbran pכtεnshal rεspכns to ADP stimulashכn insay isolεt mכsul maytochכndria dεm nid supliment saytokrכm c εn hεksokinase klem. ADP/ATP transpכt path εn binding fכ ELAM to ATP Synthase εn ANT.
I. Ovaviu fɔ di Rilayshɔn Bitwin Maytochondria ɛn Aging
di maytochכndria dεm, as di sεl in pawa, na dεn de rispansabl fכ sכntez di mכtalman in ATP insay di sεl εn dεn de involv bak insay difrεn mεtabolik rεguleshכn εn signal transdyushכn prכsεs dεm. as di ej de go כp, di maytochכndrial fכnshכn de dכn sכmtεm, we na wan pan di kכl mak dεm fכ ol. di maytochכndrial disfכnkshכn de sho in mכltipכl we dεm, inklud di akyumyuleshכn fכ mכtεshכn dεm na di maytochכndrial DNA (mtDNA), di rεdכks aktiviti fכ di maytochכndrial rεspiretכri chen kכmpleks dεm, we de mek i nכ prodyuz εnεji; inkrεs prodakshכn fכ riaktiv כksijεn spεs (ROS) bay maytochכndria, we de trigεr כksidεtiv strεs dεmεj, we de fכs disrupt intasεlulyar bayomכlikul dεm lεk protin, lipid, εn nyukliyk asid, aksεleret sεl dεm we de ol εn day. di abnכmal mitochondrial fכnshכn de disrupt intasεlulyar kalsiכm homכstasis bak, we de intafεr wit nכmal sεlyul fysiolojikal fכnshכn dεm. dis chenj dεm de intarakt wit dεn wan dεm, we de fכm wan bad bad saykl we kכlektif wan de drεb di ol prכsεs.
II. Mekanism fɔ Akshɔn fɔ SS-31
Improving Mitochondrial Enaji Mεtabolism
εnhans ADP Sεnsitiviti: We yu de ol, di maytochכndrial sεnsitiviti to ADP de dכn, we de impεr di ATP sεntesis efyushכn. stכdi dεm sho se SS-31 kin biεn dayrekt wan to di maytochכndrial ADP transpכrta ANT, we de inkrεs di ANT in כptek fכ ADP, we de εnhans di maytochכndrial sεnsitiviti to ADP. insay ol mכsul maytochכndria, SS-31 tritmεnt inkrεs ADP כptek via ANT, dat de εnhans maytochכndrial rεspireshכn כnda ADP stimulashכn, inkrεs ATP prodakshכn, εn impruv εnεji mεtabolism insay ol mכsul maytochכndria.
rεgulεshכn fכ di maytochכndrial rεspiretכri chen kכmpleks dεm: di maytochכndrial rεspiretכri chen kכmpleks dεm na di kכmכpכnεnt dεm fכ di maytochכndrial εnεji prodakshכn. we yu de ol, di aktiviti fכ di rεspiretכri chen kכmpleks dεm kin dכn bכku tεm. SS-31 kin mεnten כ εnhans di aktvכti fכ di rεspiretכri chen kכmpleks dεm bay we i de stεbyul dεn strכkchכral integriti כ rεgεl di εksprεshכn fכ di rilayt protin dεm. stכdi dεm we dεn bin dכn du bifo dis tεm dεn bin si se insay εj-rεlatεd maytochכndrial disfכnkshכn mכdel dεm, di aktvכti fכ di rεspiretכri chen kכmpleks dεm de rεstכr afta SS-31 tritmεnt, we sho se in pכsitiv rεgεdyushכn ifekt pan di maytochכndrial rεspiretכri chen.
Figure 2 SS-31 tritmεnt de rivεs di kadyak εj fεnotayp dεm
Ridyus ɔksidativ strɛs damej
fכ ridyus di ROS prodakshכn: di maytochכndria na wan pan di praymar sכs dεm fכ ROS insay di sεl dεm, εn di ROS prodakshכn de inkrεs na di maytochכndria we i de ol. SS-31 kin ridyus ROS prodakshכn tru mכltipכl path dεm. i de impruv di maytochכndrial εnεji mεtabolism, we de mek di maytochכndrial εlektrכn transpכt chen mכr efyushכn εn i de ridyus εlektrכn lik, we de lכs ROS prodakshכn. SS-31 kin akt dayrekt pan di maytochכndrial mεmbran, altεr in fכs prכpati dεm, ridyus כksidεtiv dεmεj sayt dεm na di mεmbran, εn inhεbit ROS prodakshכn. insay kadyak sεl dεm frכm ol mays, tritmεnt wit SS-31 sכmtεm rεdכks di maytochכndrial ROS lεvεl, we sho se i efεktiv fכ ridyus ROS prodakshכn.
rεgulεshכn fכ di antioksidant εnzym sistεm: di sεl dεm gεt wan antioksidant εnzym sistεm, we inklud supεrכksayd dismutεz (SOD), katalaz (CAT), εn glutathione pεrכksidεz (GSH-Px), we de rispansabl fכ skavεnj ROS. rεsכch sho se SS-31 kin εnhans sεlyul antioksidant difεns kεpabiliti bay we i de upregulate di εksprεshכn כ aktvכti fכ dεn antioksidant εnzym dεm ya. insay sכm sεlyul mכdel dεm, tritmεnt wit SS-31 rεsult in sכm inkrεs pan di aktvכti fכ SOD εn GSH-Px, we εp fכ kliar εksyכs ROS insay sεl dεm insay di tεm εn εliviet כksidεtiv strεs-indyus dεmεj.
fכ mεnten di maytochכndrial mεmbran stεbiliti
di biεn to di maytochכndrial mεmbran fכsfolipid dεm: SS-31 gεt wan yכnik strכkchכ we de alaw am fכ fכs fכ biεn di rijyכn dεm na di maytochכndrial mεmbran we rich wit fכsfatidylserin. fכsfatidylserin na fכsfolipid we spεsifi k to di maytochכndrial mεmbran εn i implεnt fכ mεnten di strכkchכral εn fכnshכnal integriti fכ di maytochכndrial mεmbran. we yu de ol, fכsfatidylserin kin izi fכ כksidεtiv dεmεj, we kin mek i nכmal tin dεm na di maytochכndrial mεmbran strכkchכ εn fכnshכn. afta i biεn to fכsfatidilserin, SS-31 kin protεkt fכsfatidilserin frכm כksidεshכn we i de stεbyul di maytochכndrial mεmbran strכkchכ, we de mek di maytochכndrial mεmbran pכtεnshal dεn dכn εn di opin fכ di maytochכndrial pεrmiabiliti transishכn por (mPTP). in vitro εkspεriεns dεn sho se SS-31 de inhεbit ifektivli inhεbit כksidεtiv strεs-indyus dεkrεshכn in maytochכndrial mεmbran pכtεnshal εn mPTP opin, we de mεnten maytochכndrial mεmbran stεbiliti.
rεgulεshכn fכ di mεmbran-asכsiet protin dεm: di maytochכndrial mεmbran gεt difrεn protin dεm we de involv insay di maytochכndrial mεtirial transpכt, enεji mεtabolism, εn signal transdyushכn prכsεs dεm. SS-31 kin indaykt infכlכw di maytochכndrial mεmbran stεbiliti bay we i de rεgεl di aktvכti כ εksprεshכn fכ dεn mεmbran-asכsiet protin dεm ya. i kin rεgεl di fכnshכn fכ vכltεj-dipεndεnt aniכn chεnal dεm (VDAC), we na imכtant chanεl protin dεm na di כta maytochכndrial mεmbran εn de ple wan kכl rol fכ mεnten mεtirial εkshεnj εn signal transmishכn bitwin maytochכndria εn di saytoplasm. SS-31 in rεguleshכn fכ VDAC de εp fכ mεnten nכmal maytochכndrial mεmbran fכnshכn εn stεbiliti.
III. Spesifi k ifekt dm f SS-31 in anti-aging
Efεkt dεm pan di kכdivaskyul sistεm
Fɔ mek di at wok fayn: di at na ɔgan we gɛt bɔku ɛnaji, ɛn di maytochondrial wok impɔtant fɔ mek di at wok fayn. pan di mays dεm we dεn ol, di at kin sho bכku tεm tin dεm we de kכmכt frכm di ej lεk diastolik disfכnkshכn. Sayɛnsman dɛn dɔn si se afta 8 wiks we dɛn tek SS-31 tritmɛnt, di dayastolik wok we di ol mays dɛn at gɛt bin rili impɔtant. dis impruvmεnt bin kכmpan wit di nכmalizeshכn fכ di maytochכndrial protכn lik insay mayokardial sεl dεm, ridyus di maytochכndrial ROS lεvεl dεm, di dכn di kadyak protin כksidεshכn lεvεl dεm, εn wan shift in di tiol rεdכks stet fכ di protin dεm tכwכd wan mכr rεdכks stet. SS-31 inkrεs bak di fכsfכrayleshכn lεvεl fכ cMyBP-C Ser282 insay mayokardial sεl dεm, we kכlכsכl wit impruv kadyak dayastolik fכnshכn.
Figure 3 Lanin impεryans in ol maws we indyuz bay slip dεprivεshכn bin prεvεnt wit SS31.
di vaskul protεkshכn: We di εndoteyl sεl dεm de ol, di εndoteyl sεl dεm nכ de wok fayn, di vaskul εlastisiti de dכn, εn di sik dεm we de kכmכt na di at kin apin. insay wan haypatεnshכn-induse maykroblidin mכdel na di bren fכ ol mays, tritmεnt wit SS-31 de sho sכm vaskulεr prכtektiv ifekt dεm. i de ridyus di maytochondrial fri radikal prodakshכn we haypatεnshכn de indyuz, i de mek di כksidεtiv strεs dεm we di vaskulכr wכl de dכn, we de mek i delay di biginin fכ maykroblid bכku bכku wan εn i de ridyus in insidεns. fכ dat, SS-31 de ple imכtant rol fכ mεnten di nכmal strכkchכ εn fכnshכn fכ di bכdi vεsul dεm εn fכ mek di vaskulεr sik dεm we de kכmכt frכm di ej.
Ifekt pan di nervous system
Fɔ stɔp di kɔgnitiv disfɔkshɔn: As di ej de go ɔp, di nεv sistɛm de wok de dכn sכmtεm, εn di kכgnitiv disfכnkshכn lεk fכ mεmכri εn di rεdכks fכ lan de kam bכku bכku wan. di maytochכndrial disfכnkshכn de ple imכtant rol fכ di biginin εn di prכgreshכn fכ nyurodijεnεraytiv sik dεm εn di kכgnitiv disfכnkshכn. insay wan mכdel fכ kכgnitiv disfכnkshכn we isoflurane indyuz insay ol mays, SS-31 kin rivεs maytochכndrial disfכnkshכn, rεsכk isoflurane-indyus kכgnitiv dεfisit dεm. SS-31 de promuot di rεguleshכn fכ BDNF signal, i de rivεs di dכwnrεgulεshכn fכ di sinaptik plastisiti-rεlatεd protin dεm lεk sinaptophysin, PSD-95, εn p-CREB, εn i de uprεgul NR2A, NR2B, CaMKIIα, εn CaMKIIβ, we de εnhans sinaptik plastisiti εn protεkt kכgnitiv fכnshכn.
Fɔ stɔp di bad tin dɛn we kin apin we pɔsin nɔ slip fayn: We pɔsin nɔ kin slip fayn na wan tin we kin mek pɔsin strɛs, ɛn di bad tin dɛn we i kin du pan di nervɔs sistɛm kin mɔna am we i de ol, we kin mek i nɔ ebul fɔ ɔndastand fayn ɛn i kin mek i gɛt nyurodijɛnɛraytiv sik dɛn. Insay 20 mɔnt ol mays, dɛn bin gi SS-31 (3 mg/kg) bay sabkyutan injɛkshɔn ɛvride fɔ 4 kɔnsɛkutiv dez, wit 4 awa we dɛn nɔ bin de slip pan di las tu dez. di rizulεt sho se di mays dεm we nכ de slip we dεn trit wit SS-31 nכ sho nכ signifyant impεryans pan lanin abiliti, wit rεstכr bren maytochכndrial ATP lεvεl dεm εn sinaptik plastisiti-rεgulεt protin dεm, εn bak rεdכks lεvεl dεm fכ riaktiv כksijεn spεs (ROS) εn inflammatory cytokines in di hippocampus. dis sho se SS-31 kin gεt pכtεnshal tεrapi bεnεfit dεm fכ mitigate di advεs nyurolכjik ifekt dεm we sכt tεm slip dεprivεshכn de gi insay ol mays dεm.
ifekt dεm pan di rεnal sistεm: Insay di kidni dεm fכ di mays dεm we dεn ol, di glomerulosclerosis de sho se di maytochכndrial dεm we dεn dכn pwεl na di glomerular εpitεlial sεl dεm. Afta 8 wiks SS-31 tritmεnt in 26 mכnt ol εj mays, SS-31 impruv εj-rεlatεd maytochכndrial mכfכlכji εn εliviet glomerulosclerosis. sכm spεshal, i rεdכks di εksprεshכn fכ di ol mak dεm (p16, ej-asכsiet β-Gal), inkrεs di dεnsiti fכ di apikal εpitεlial sεl dεm, εn dεkrεs di εksprεshכn fכ mak dεm fכ parietal εpitεlial sεl aktibכshכn (kכlagen IV, pERK1/2, εn α-smooth mכsul aktin). pan ɔl we SS-31 nɔ bin afɛkt di podosayt dɛnsiti, i bin ridyus di mak dɛn fɔ di podosayt damej (desmin), i bin impruv di saytoskɛlɛtal intɛgriti (synaptophysin), ɛn i bin de wit ay glomerular ɛndoteyl sɛl dɛnsiti (CD31). dis sho se sכt tεm SS-31 tritmεnt de gεt prכtektiv ifekt bak pan glomerular mitochondria εn i de impruv glomerular strכkchכ.
Ifekt dεm na di sεl lεvεl
Dilay sεlyul εj: Insay sεl εkspεriεns, dεn yuz H2O2 fכ indyuz wan strεs-indyus εj mכdel in HEK293T sεl dεm, we dεn fכlכw wit intavεnshכn wit SS-31. di risalts sho se di SA-β-gal positifu rεt bin sכmtεm rεdכks insay di SS-31 grup, we sho se di sεlyul εj lεvεl dεm dכn dכn. apat frכm dat, di intasεlulyar ROS fכrosεns intanεs dεn dכn, di maytochכndrial mεmbran pכtεnshal inkrεs, εn di ATP lεvεl dεm rεs insay di SS-31 grup. Protein immunoblotting analysis rivεl se di εksprεshכn lεvεl dεm fכ P53, P21, εn Acetyl-p53 protin dεm bin hכy insay di mכdel grup kכmpεr to di kכntrol grup, we di SS-31 grup sho dεkrεshכn kכmpεr to di mכdel grup. Konvεsivli, di εksprεshכn lεvεl fכ Sirt1 protin bin lכw in di mכdel grup kכmpεr to di kכntrol grup, we di SS-31 grup sho inkrεs kכmpεr to di mכdel grup. so, dεn kin kכnklud se SS-31 kin delay HEK293T sεl dεm we de ol bay we i de impruv di maytochכndrial fכnshכn εn rεgεl di εksprεshכn fכ di protin dεm we rilet to ol insay sεl dεm.
Protekshכn εgεst כksidεtiv strεs-indyus sεlyul dεmεj: Insay di H2O2-indyus כksidεtiv strεs dεmεj mכdel fכ ARPE-19 sεl dεm, tritmεnt wit SS-31 sכmtεm inkrεs sεl sכvayv rεt, rεdכks intasεlulyar ROS lεvεl, dεkrεs di prכpכshכn fכ sεl dεm wit rεdכks maytochכndrial mεmbran pכtεnshal, mak lכw PI positiviti rεt (riflekt di εkstenshכn di sεl dεd), εn sכmtεm attenuated di upregulation fכ RIP3 protin εksprεshכn. dis rizulεt dεm sho se SS-31 gεt sכm prכtektiv ifekt εgεst H2O2-indyus כksidεtiv strεs dεmεj in ARPE-19 sεl dεm, we kin εp fכ kכntrכl di dεmεj we rilet to di ej.
Dɔn
di maytochכndrial-tכgεt pεptida SS-31 de kכntribyut to anti-aging. frכm in mכltifasεt rεgεdyushכn mεkanism dεm pan maytochכndrial fכnshכn to in signifyant anti-aging ifekt dεm na difrεn sistεmik εn sεlyul lεvεl dεm, i de sho pכtεnshal as imכtant anti-aging stratεji.
Sos dɛn we dɛn pul
[1] Patai R, Patel K, Csik B, ɛn ɔda pipul dɛn. Ej, maytochondrial disfכnkshכn, εn sεribra maykroεmoraj: wan prεklinik evalueshכn fכ SS-31 (elamipretide) εn divεlכpmεnt fכ wan hεy-throughput mashin lanin-driv imej paip layn fכ sεribromaykrovaskul protεkshכn tεrapi skrεnin[J]. Gɛrosayns, 2025.DOI: 10.1007/s11357-025-01634-5.
[2] Fɛro G, Kamat V, Kannan S, ɛn ɔda pipul dɛn. di maytochכndrial tכgεt pεptida εlamipretide (SS-31) de impruv ADP sεnsitiviti in εj maytochכndria bay we i de inkrεs כptek tru di adenin nyukliotayd translכkεtכr (ANT)[J]. Gεrosayns, 2023,45 (6): 3529-3548.DOI: 10.1007/s11357-023-00861-y.
[3] Chiao YA, Zhang H, Sweetwyne M, ɛn ɔda pipul dɛn. let-layf ristכreshכn fכ di maytochכndrial fכnshכn de rivεs di kadyak disfכnkshכn in ol mays[J]. Elife, 2020,9.DOI: 10.7554/eLayf.55513. Di wan dɛn we de stɔdi bɔt di Baybul.
[1] Wu J, Dou Y, Ladiges W C. Advεs Nyurכlכjik Efεkt dεm we Sכt-Tεm Slip Dεprivεshכn de Gεt pan Aging Mays dεm de Prεvεnt bay SS31 Pεptid[J]. Klɔk & Slip, 2020, 2 (3): 325-333.DOI: 10.3390 / kloks slip2030024.
[4] Sweetwyne M. T., Pippin J. W., Eng D. G., ɛn ɔda pipul dɛn. di maytochכndrial-tכgεt pεptida, SS-31, de impruv glomerular akitekchכ in mays dεm we advans ej[J]. Kidni Int ɛ rnash ɔ nal, 2017,91(5):1126-1145.DOI:10.1016/j.kint.2016.10.036.
[5] Wu J, Zhang M, Li H, ɛn ɔda pipul dɛn. BDNF path de involv in di protεktiv ifekt dεm we SS-31 de gi pan isoflurane-induse kכgnitiv dεfisit in ol mays[J]. Bihayvyural Bren Risach, 2016,305:115-121.DOI:10.1016/j.bbr.2016.02.036.
Prodak we de fɔ yuz fɔ risach nɔmɔ:
