{"id":15058,"date":"2026-08-12T03:09:36","date_gmt":"2026-08-12T10:09:36","guid":{"rendered":"https:\/\/cellpeptides.com\/?post_type=product&p=15058"},"modified":"2026-08-12T03:25:58","modified_gmt":"2026-08-12T10:25:58","slug":"buy-foxo4-dri-2mg","status":"publish","type":"product","link":"https:\/\/cellpeptides.com\/cs\/product\/buy-foxo4-dri-2mg\/","title":{"rendered":"FOXO4-DRI 2mg"},"content":{"rendered":"

FOXO4-DRI (FOXO4-D-Retro-Inverso) je peptid, kter\u00fd je p\u0159edm\u011btem v\u00fdzkumu v oblasti dlouhov\u011bkosti a st\u00e1rnut\u00ed. Byl navr\u017een tak, aby naru\u0161oval interakci mezi transkrip\u010dn\u00edm faktorem FOXO4 a proteinem p53, co\u017e vede k apopt\u00f3ze (programovan\u00e9 bun\u011b\u010dn\u00e9 smrti) senescentn\u00edch bun\u011bk (st\u00e1rnouc\u00edch bun\u011bk, kter\u00e9 se p\u0159estaly d\u011blit, ale neodum\u0159ely). V\u011bdci jej studuj\u00ed pro jeho potenci\u00e1ln\u00ed schopnost omlazovat tk\u00e1n\u011b a bojovat proti nemocem souvisej\u00edc\u00edm s v\u011bkem, av\u0161ak dosud byl testov\u00e1n hlavn\u011b na zv\u00ed\u0159ec\u00edch modelech.<\/span><\/h2>\n

Jedn\u00e1 se o syntetick\u00fd peptid tvo\u0159en\u00fd 46 aminokyselinami, slo\u017een\u00fd v\u00fdhradn\u011b z D-aminokyselin v opa\u010dn\u00e9m po\u0159ad\u00ed. Dod\u00e1v\u00e1 se jako lyofilizovan\u00fd pr\u00e1\u0161ek pro laboratorn\u00ed pou\u017eit\u00ed a v\u00fdzkumn\u00e9 \u00fa\u010dely. <\/span>pouze<\/span><\/i>. P\u0159edev\u0161\u00edm je peptid studov\u00e1n pro selektivn\u00ed odstra\u0148ov\u00e1n\u00ed senescentn\u00edch bun\u011bk, proto\u017ee dok\u00e1\u017ee p\u0159eru\u0161it vazbu s p53 v bu\u0148k\u00e1ch st\u00e1rnouc\u00edch, co\u017e umo\u017e\u0148uje jejich z\u00e1nik. M\u011bjte v\u0161ak na pam\u011bti, \u017ee FOXO4-DRI je pouze v preklinick\u00e9 f\u00e1zi a neexistuj\u00ed o n\u011bm \u017e\u00e1dn\u00e1 data u lid\u00ed. A v\u011bt\u0161ina velk\u00fdch tvrzen\u00ed o st\u00e1rnut\u00ed a zab\u00edjen\u00ed \u201czombie bun\u011bk\u201d je pon\u011bkud vedle. Kl\u00ed\u010dov\u00fdm zji\u0161t\u011bn\u00edm z jeho aplikace u my\u0161\u00ed bylo, \u017ee obnovil kondici, hustotu srsti a ren\u00e1ln\u00ed funkce jak u my\u0161\u00ed s rychle se projevuj\u00edc\u00edm st\u00e1rnut\u00edm XpdTTD\/TTD, tak u p\u0159irozen\u011b st\u00e1rnouc\u00edch my\u0161\u00ed. \u017d\u00e1dn\u00e1 studie jej nezmi\u0148uje jako n\u011bco, co \u201cvrac\u00ed st\u00e1rnut\u00ed zp\u011bt\u201d.\u201d<\/span><\/p>\n

DRI znamen\u00e1 D-retro-inverso. V podstat\u011b to znamen\u00e1 obr\u00e1cenou sekvenci neboli zrcadlov\u00fd obraz aminokyselin. V\u011bdci takto sekvence obracej\u00ed, proto\u017ee a\u010dkoli celkov\u00fd \u00fa\u010dinek z\u016fst\u00e1v\u00e1 stejn\u00fd, degradace se v\u00fdrazn\u011b zpomaluje. Jin\u00fdmi slovy, peptidy z L-aminokyselin jsou prote\u00e1zami rychle rozlo\u017eeny, zat\u00edmco tato taktika zrcadlov\u00e9ho obrazu \/ obr\u00e1cen\u00e9 sekvence zachov\u00e1v\u00e1 topografii postrann\u00edch \u0159et\u011bzc\u016f (tak\u017ee se m\u016f\u017ee st\u00e1le norm\u00e1ln\u011b nav\u00e1zat) a z\u00e1rove\u0148 odol\u00e1v\u00e1 degradaci.<\/span><\/p>\n

Interak\u010dn\u00ed oblast p53 proteinu FOXO4 byla studov\u00e1na a varianta DRI tohoto peptidu byla odvozena Baarem a kolegy v laborato\u0159i de Keizer (Cell, 2017). Peptid m\u00e1 bun\u011b\u010dn\u011b penetra\u010dn\u00ed konec, kter\u00fd mu umo\u017e\u0148uje pronikat bun\u011b\u010dn\u00fdmi membr\u00e1nami.<\/span><\/p>\n

Jak funguje FOXO4-DRI?<\/span><\/h2>\n

Hodn\u011b z toho, jak peptidy funguj\u00ed, se omezuje na receptory. A tak je tomu i zde. Poj\u010fme ale nejd\u0159\u00edve ud\u011blat krok zp\u011bt.<\/span><\/p>\n

St\u00e1rnouc\u00ed bu\u0148ky se naz\u00fdvaj\u00ed senescentn\u00ed bu\u0148ky. Tyto bu\u0148ky se p\u0159estaly d\u011blit, jsou velk\u00e9 a \u010dasto mohou uvol\u0148ovat \u0161kodliv\u00e9 z\u00e1n\u011btliv\u00e9 chemick\u00e9 l\u00e1tky a dokonce po\u0161kozovat okoln\u00ed tk\u00e1n\u011b. V t\u011bchto bu\u0148k\u00e1ch se hromad\u00ed protein zvan\u00fd FOXO4. Kdy\u017e nav\u00edc bu\u0148ky proch\u00e1zej\u00ed senescenc\u00ed vyvolanou z\u00e1\u0159en\u00edm (nap\u0159\u00edklad b\u011bhem chemoterapie), hromad\u00ed se v nich velk\u00e9 mno\u017estv\u00ed proteinu FOXO4. \u00dakolem FOXO4 je zabr\u00e1nit apopt\u00f3ze v t\u011bchto senescentn\u00edch bu\u0148k\u00e1ch. Pokud byste dok\u00e1zali potla\u010dit expresi FOXO4, p\u0159irozen\u011b byste zaznamenali \u00fahyn v\u011bt\u0161\u00edho mno\u017estv\u00ed t\u011bchto senescentn\u00edch bun\u011bk.<\/span><\/p>\n

To, co FOXO4 ve st\u00e1rnouc\u00ed bu\u0148ce d\u011bl\u00e1, je, \u017ee zadr\u017euje p53 \u2013 protein, kter\u00fd m\u00e1 mnoho \u00fakol\u016f, p\u0159i\u010dem\u017e jedn\u00edm z nich je vys\u00edl\u00e1n\u00ed sign\u00e1l\u016f pro z\u00e1nik bu\u0148ky, aby mohla zem\u0159\u00edt. Dokud mno\u017estv\u00ed FOXO4 dr\u017e\u00ed ve\u0161ker\u00fd tento p53 v senescentn\u00edch bu\u0148k\u00e1ch, tyto bu\u0148ky nezem\u0159ou.<\/span><\/p>\n

Syntetick\u00fd peptid FOXO4-DRI, o kter\u00e9m zde diskutujeme, sout\u011b\u017e\u00ed o vazebn\u00e9 m\u00edsto. Sna\u017e\u00ed se nav\u00e1zat na p53 d\u0159\u00edve, ne\u017e to dok\u00e1\u017ee vlastn\u00ed protein FOXO4 bu\u0148ky. A je v tom docela \u00fasp\u011b\u0161n\u00fd. Bylo zji\u0161t\u011bno, \u017ee peptid m\u00e1 vy\u0161\u0161\u00ed afinitu k p53. Nyn\u00ed, kdy\u017e jsme nahradili p\u0159irozenou vazbu FOXO4\/p53 vazbou FOXO4-DRI\/p53, jsme v podstat\u011b zabr\u00e1nili tomu, aby byl p53 nav\u00e1z\u00e1n na j\u00e1dro. M\u016f\u017ee odej\u00edt a vys\u00edlat sign\u00e1ly vedouc\u00ed k z\u00e1niku, proto\u017ee peptid FOXO4-DRI tomu nebr\u00e1n\u00ed.<\/span><\/p>\n

Jednoduch\u00fdm nav\u00e1z\u00e1n\u00edm na p53 d\u0159\u00edve, ne\u017e to stihne p\u0159irozen\u00fd protein FOXO4, tak peptid umo\u017e\u0148uje st\u00e1rnouc\u00edm bu\u0148k\u00e1m zem\u0159\u00edt. Jeliko\u017e ppproti tomu nen\u00ed nav\u00e1z\u00e1n na p\u0159irozen\u00fd FOXO4 (kter\u00fd ho dr\u017e\u00ed v j\u00e1dru), p\u0159esouv\u00e1 se do mitochondri\u00ed a spou\u0161t\u00ed apopt\u00f3zu. To n\u00e1sledn\u011b zcela eliminuje senescentn\u00ed bu\u0148ku.<\/span><\/p>\n

Tento peptid je ze sv\u00e9 podstaty selektivn\u00ed, proto\u017ee samotn\u00fd FOXO4 m\u00e1 v\u011bt\u0161in\u011b zdrav\u00fdch dosp\u011bl\u00fdch bun\u011bk n\u00edzkou hladinu. Zv\u00fd\u0161en\u00fd je pouze v senescentn\u00edch bu\u0148k\u00e1ch.<\/span><\/p>\n

Interakce FOXO4-p53<\/span><\/h3>\n

Pro\u010d se po\u0161kozen\u00e9 bu\u0148ky odm\u00edtaj\u00ed vzd\u00e1t \u017eivota? Hromad\u00edc\u00ed se po\u0161kozen\u00ed DNA bu\u0148ku za norm\u00e1ln\u00edch okolnost\u00ed sm\u011b\u0159uje bu\u010f k apopt\u00f3ze, nebo k senescenci. Senescentn\u00ed bu\u0148ky zvolily druhou mo\u017enost a tuto volbu mus\u00ed neust\u00e1le obhajovat, tak\u017ee \u017eij\u00ed d\u00e1l. Jinak \u0159e\u010deno, jde o rezistenci v\u016f\u010di apopt\u00f3ze. Tato rezistence vznik\u00e1 na z\u00e1klad\u011b mnoha faktor\u016f. Jsou p\u0159ipraveny k z\u00e1niku, ale st\u00e1le se dr\u017e\u00ed. Jedn\u00edm z mechanism\u016f, kter\u00e9 toto setrv\u00e1n\u00ed zaji\u0161\u0165uj\u00ed, je sekvestrace p53 proteinem FOXO4.<\/span><\/p>\n

P\u0159irozen\u011b se nach\u00e1z\u00ed FOXO4 ve zv\u00fd\u0161en\u00e9m mno\u017estv\u00ed v senescentn\u00edch bu\u0148k\u00e1ch a je kl\u00ed\u010dovou slo\u017ekou pro udr\u017een\u00ed \u017eivotaschopnosti bun\u011bk. Zadr\u017euje p53 v j\u00e1d\u0159e, kter\u00fd by jinak vyslal sign\u00e1l k apopt\u00f3ze.<\/span><\/p>\n

FOXO4-DRI a senescentn\u00ed bu\u0148ky: K \u010demu se pou\u017e\u00edv\u00e1?<\/span><\/h2>\n

Senescence je stav, kdy se bu\u0148ka nach\u00e1z\u00ed v trval\u00e9m zastaven\u00ed cyklu. Bu\u0148ka je p\u0159ipravena zem\u0159\u00edt, ale st\u00e1le se dr\u017e\u00ed \u2013 z\u016fst\u00e1v\u00e1 metabolicky aktivn\u00ed a tak\u00e9 vylu\u010duje l\u00e1tky. Tyto bu\u0148ky vytv\u00e1\u0159ej\u00ed senescenc\u00ed asociovan\u00fd sekre\u010dn\u00ed fenotyp, p\u0159etrv\u00e1vaj\u00edc\u00ed proz\u00e1n\u011btliv\u00fd fenotyp, kter\u00fd m\u016f\u017ee p\u0159isp\u00edvat k zrychlen\u00e9mu st\u00e1rnut\u00ed a chemotoxicit\u011b.<\/span><\/p>\n

Pr\u00e1ce od roku 2011 uk\u00e1zaly, \u017ee odstran\u011bn\u00ed senescentn\u00edch bun\u011bk m\u016f\u017ee zabr\u00e1nit dysfunkci tk\u00e1n\u00ed nebo ji odd\u00e1lit a \u017ee senescentn\u00ed bu\u0148ky zauj\u00edmaj\u00ed pozici zdrav\u00fdch bun\u011bk a naru\u0161uj\u00ed lok\u00e1ln\u00ed funkci, pokud nejsou odstran\u011bny. Pro\u010d k tomu tedy doch\u00e1z\u00ed? Senescence toti\u017e nen\u00ed jednotn\u011b \u0161patn\u00e1. Bun\u011b\u010dn\u00e1 senescence m\u00e1 du\u00e1ln\u00ed povahu \u2013 je vlastn\u011b prosp\u011b\u0161n\u00e1 b\u011bhem embryon\u00e1ln\u00edho v\u00fdvoje, p\u0159i hojen\u00ed tk\u00e1n\u00ed a potla\u010dov\u00e1n\u00ed n\u00e1dor\u016f. Je v\u0161ak \u0161kodliv\u00e1 p\u0159i chronick\u00e9m stresu, p\u0159etrv\u00e1vaj\u00edc\u00edm poran\u011bn\u00ed tk\u00e1n\u00ed a zhor\u0161en\u00e9m odstra\u0148ov\u00e1n\u00ed.<\/span><\/p>\n

V\u00fdzkum bun\u011b\u010dn\u00e9ho st\u00e1rnut\u00ed<\/span><\/h3>\n

FOXO4-DRI je studov\u00e1n p\u0159edev\u0161\u00edm jako experiment\u00e1ln\u00ed senolytick\u00fd peptid, kter\u00fd se li\u0161\u00ed od malomolekul\u00e1rn\u00edch senolytik. P\u016fvodn\u00ed in-vitro model vyu\u017e\u00edval lidsk\u00e9 fibroblasty IMR90 senescentn\u00ed v d\u016fsledku ionizuj\u00edc\u00edho z\u00e1\u0159en\u00ed. Kl\u00ed\u010dov\u00fd v\u00fdsledek? Vynikaj\u00edc\u00ed selektivita. Mnoho dal\u0161\u00edch skupin tento peptid rovn\u011b\u017e pou\u017eilo jako sondu u r\u016fzn\u00fdch typ\u016f bun\u011bk, od fibroblast\u016f IMR90 a Leydigov\u00fdch bun\u011bk TM3 a\u017e po chondrocyty, endoteli\u00e1ln\u00ed bu\u0148ky a plicn\u00ed fibroblasty.<\/span><\/p>\n

V\u00fdzkum funkc\u00ed souvisej\u00edc\u00edch s v\u011bkem<\/span><\/h3>\n

Studie na zv\u00ed\u0159atech uk\u00e1zaly, \u017ee zlep\u0161uje fyzickou aktivitu, stav srsti, ledvinov\u00e9 markery a funkci tk\u00e1n\u00ed. V p\u016fvodn\u00edm v\u00fdzkumu existuj\u00ed dva kl\u00ed\u010dov\u00e9 modely: rychle st\u00e1rnouc\u00ed kmen s deficitem opravy DNA a p\u0159irozen\u011b st\u00e1rnouc\u00ed my\u0161i. V\u00fdsledky byly konzistentn\u00ed u obou. Aktivita na b\u011bhac\u00edm kole a sk\u00f3re srsti byly hodnoceny u 26t\u00fddenn\u00edch divok\u00fdch typ\u016f a my\u0161\u00ed XpdTTD\/TTD, p\u0159i\u010dem\u017e ub\u011bhnut\u00e1 vzd\u00e1lenost byla m\u011b\u0159ena v km za den. Studie rovn\u011b\u017e zaznamenala sn\u00ed\u017een\u00fd v\u00fdskyt spont\u00e1nn\u011b vznikaj\u00edc\u00ed ren\u00e1ln\u00ed glomeruloskler\u00f3zy a zlep\u0161enou filtra\u010dn\u00ed kapacitu ledvin u rychle st\u00e1rnouc\u00edch my\u0161\u00ed.<\/span><\/p>\n

V\u00fdzkum reproduk\u010dn\u00edho st\u00e1rnut\u00ed<\/span><\/h3>\n

Prob\u011bhly dv\u011b samostatn\u00e9 \u010d\u00ednsk\u00e9 studie od stejn\u00e9 skupiny. V prvn\u00ed (Zhang et al. 2020) zlep\u0161en\u00e9 markery uk\u00e1zaly zv\u00fd\u0161en\u00fd testosteron v s\u00e9ru, zv\u00fd\u0161enou 3\u03b2-HSD a CYP11A1, sn\u00ed\u017eenou interstici\u00e1ln\u00ed SA-\u03b2-gal aktivitu, ni\u017e\u0161\u00ed p53, p21 a p16 a sn\u00ed\u017een\u00e9 IL-1\u03b2, IL-6 a TGF-\u03b2. Druh\u00e1 studie (Li et al. 2024) m\u011bla jin\u00e9 uspo\u0159\u00e1d\u00e1n\u00ed a del\u0161\u00ed expozici. Hl\u00e1\u0161en\u00fdm v\u00fdsledkem byla zv\u00fd\u0161en\u00e1 kvalita spermi\u00ed a zlep\u0161en\u00e1 spermatogeneze u l\u00e9\u010den\u00fdch star\u00fdch my\u0161\u00ed, p\u0159i\u010dem\u017e navrhovan\u00fdm mechanismem bylo sn\u00ed\u017een\u00e9 vylu\u010dov\u00e1n\u00ed SASP z Leydigov\u00fdch bun\u011bk.\u00a0<\/span><\/p>\n

Fibr\u00f3za a v\u00fdzkum tk\u00e1n\u00ed<\/span><\/h3>\n

V\u011bdci tak\u00e9 zkoumali FOXO4-DRI v experiment\u00e1ln\u00edch modelech plicn\u00ed fibr\u00f3zy, chrupavek a st\u00e1rnut\u00ed c\u00e9v.<\/span><\/p>\n