Isihloko
I-methylene blue nokuphila isikhathi eside: amaseli, izilwane, nobufakazi kubantu
Ucwaningo olutholwe kulokhu kubuyekezwa alukabonisi ukuthi i-methylene blue yandisa isikhathi sokuphila kwabantu. Eminye imiphumela yaselabhorethri ihlobene nokuguga, kodwa imiphumela yokugcina elinganiswayo ihluke kakhulu: ukuqhubeka kwamaseli ehlukana, ukusinda kwamagundane aze aguge, nokuphothula kwabantu umsebenzi wokukhumbula kuyimiphumela ehlukene.
Ngakho umbuzo owusizo kakhulu uqondile: yini ephile isikhathi eside, ngaphansi kwaziphi izimo, futhi ukwanda kwesikhathi sokuphila kulinganiswe kanjani? Impendulo ivimbela indlela yokusebenza ethembisayo ekuphendukeni isimangalo sokuthi abantu bazophila iminyaka eyengeziwe.
Izincazelo ezine zesimangalo sokulwa nokuguga
- Ukuguga kwamaseli: isimo lapho amaseli eyeka ukuhlukana futhi eba nezinye izinguquko. Ukubambezela lesi simo emaselini akhuliswa elabhorethri kuhlukile ekususeni amaseli asevele egugile.
- Isikhathi sokuphila: isikhathi into ephilayo ehlala iphila ngaso. Ucwaningo lokusinda lulandelela izilwane noma abantu, kuhlanganise nokufa kwabo, kunokulinganisa amaseli abo kuphela.
- Isikhathi sokuphila okunempilo: isikhathi umuntu aphila ngaso impilo namakhono akhe kusalondolozekile. Ukuhlolwa kwesakhiwo samathambo noma ukusebenza komzimba kunganikeza ulwazi ngengxenye eyodwa yesikhathi sokuphila okunempilo ngaphandle kokubonisa ukusinda isikhathi eside.
- Iminyaka yezinto eziphilayo: isilinganiso esithathwe ezilinganisweni ezikhethiwe. Ushintsho kuleso silinganiso luwumphumela wokugcina olulinganiswayo ngokwalo, hhayi ukubona ukuthi othile usephile iminyaka eyengeziwe.
Iphepha locwaningo lingaba ubufakazi obuqinile besinye salezi zimangalo kodwa linikeze ubufakazi obuncane ngesinye. Ukubuka konke kobufakazi bezinzuzo kubantu kusebenzisa lo mehluko kwezinye izimangalo nge-methylene blue.
Okuboniswa ucwaningo lwamaseli
Esivivinyweni sama-fibroblast sika-Atamna nozakwabo, i-methylene blue eyengezwe oketshezini lokukhulisa amaseli yabambezela ukuguga kuma-fibroblast amaphaphu abantu ohlobo lwe-IMR90. Abacwaningi babika ukuthi inani lamaseli liphindeke kabili izikhathi ezingaphezu kwezingu-20 ezengeziwe uma kuqhathaniswa namaseli eqembu lokuqhathanisa. Amaseli akhulisiwe ayebalwa ngokuphindaphindiwe bese ephinde efakwa ukuze akhule, ngakho “isikhathi sokuphila” sasichaza ikhono lawo lokuqhubeka anda.
Ukuphindeka kabili kwenani lamaseli kusho ukuthi inani lawo seliphindwe kabili. Ukuphindeka kabili izikhathi ezingu-20 ezengeziwe akusho iminyaka engu-20 eyengeziwe, noma ukwanda ngo-20% kwesikhathi sokuphila komnikeli wamaseli. Isivivinyo saphinde salinganisa izinguquko kuma-mitochondria, sisekela umbono wesayensi yezinto eziphilayo ngaphandle kokufakazela ukuvuselelwa komzimba wonke. Indlela izivivinyo zama-fibroblast ezilinganisa ngayo ukuguga kwamaseli ichaza umehluko phakathi kokwanda kwamaseli nokususwa kwamaseli agugile.
Iphepha lesibili elivame ukucashunwa lacwaninga imodeli yesifo esithile. Ucwaningo lwe-progeria luka-Xiong nozakwabo lwafaka ama-fibroblast athathwe kubantu abane-Hutchinson-Gilford progeria syndrome ku-methylene blue esoketshezini lokukhulisa amaseli. Ukungajwayeleki kuma-nucleus nakuma-mitochondria kwathuthuka; ukukhula kwalandelelwa amasonto angu-12, kanti ezinye izilinganiso zenziwa ngezikhawu ezimfushane.
Lawa kwakungamaseli athathwe kubantu, hhayi abantu ababambiqhaza ababelashwa. Lesi sifo sihilela iphrotheni ye-progerin engajwayelekile, ngakho ukuthuthukisa lezo zici zamaseli akufakazeli ukwelashwa kwe-progeria noma umphumela ojwayelekile ekugugeni okunempilo. Incazelo yemodeli ye-progeria esebenzisa amaseli ihlanganisa lowo mbuzo wocwaningo ogxile kakhulu. Imiphumela yezimonyo neyokusetshenziswa esikhumbeni ingeyokubuyekezwa okuhlukile kobufakazi bokunakekelwa kwesikhumba.
Izitebhisi zobufakazi: into ephilayo, umphumela wokugcina, nesikhathi
Funda lezi zitebhisi uye phansi ubheke embuzweni wokuphila kwabantu isikhathi eside. Ukuhlobana kakhulu nalowo mbuzo akuqinisekisi umphumela omuhle. Umugqa ngamunye usho lokho okwabonwa ngempela.
| Izinga lobufakazi nocwaningo | Imodeli nokuchayeka | Isikhathi | Umphumela wokugcina nencazelo |
|---|---|---|---|
| 1. Ukuguga kwamaseli ngenxa yokuhlukana okuphindaphindiwe | Ama-fibroblast abantu ohlobo lwe-IMR90; i-methylene blue oketshezini lokukhulisa amaseli uma kuqhathaniswa namaseli akhuliswa ngaphandle kwayo | Ukuchayeka okuqhubekayo, amaseli edluliselwa oketshezini olusha masonto onke kuze kube yilapho eguga | Ukuphindeka kabili kwenani lamaseli nezilinganiso zama-mitochondria; ukunwetshwa kwesikhathi amaseli aqhubeka anda ngaso |
| 1. Izinguquko zamaseli ezihlobene nesifo | Ama-fibroblast ajwayelekile nawe-progeria; ukuchayeka ku-100 nM ekukhulisweni kwamaseli uma kuqhathaniswa noketshezi oluthwala into ehlolwayo kuphela esivivinyweni sokukhula esicashuniwe | Ukukhula kwalandelelwa amasonto angu-12; ukuhlolwa okukhethiwe kwama-mitochondria nama-nucleus emasontweni angu-5–8 | Ukukhula nokwakheka kwamaseli; awukho umphumela wokugcina wokulinganisa ukusinda kweziguli |
| 2. Ukusinda kwesilwane esiphelele | Amagundane eduna nensikazi ohlobo lwe-UM-HET3; i-methylene blue hydrate ekudleni uma kuqhathaniswa nokudla kweqembu lokuqhathanisa | Kusukela ezinyangeni ezingu-4 ubudala kuqhubeke nokulandelela sonke isikhathi sokuphila | Ayikho inzuzo ebalulekile ngokwezibalo esikhathini sokuphila esimaphakathi lapho idatha ihlanganisiwe; isikhathi sokuphila ku-percentile yama-90 kwabesifazane sakhuphuka ngo-6% |
| 3. Ingxenye yokusebenza ehlobene nokuguga | Amagundane ensikazi ohlobo lwe-C57BL/6J anezinyanga ezingu-18; i-methylene blue emanzini okuphuza uma kuqhathaniswa namanzi ajwayelekile | Izinyanga ezingu-6 noma ezingu-12 | I-micro-CT yamathambo; akukho ukuvikelwa ekulahlekelweni amathambo okuhlobene nobudala |
| 4. Isivivinyo sesikhathi esifushane kubantu | Abantu abadala abangu-26 abanempilo; ukunikezwa i-methylene blue ngomlomo kanye uma kuqhathaniswa ne-placebo | Ukuhlolwa ngaphambi kokunikezwa nangehora elingu-1 ngemva kokunikezwa | Ukusebenza kobuchopho okuhlobene nomsebenzi nokusebenza kwenkumbulo; akukho ukulinganiswa kwesikhathi sokuphila noma isikhathi eside sokuphila okunempilo |
Ukugxila kwento nezindlela zokuyinikeza kuchaza izivivinyo. Akunikezi uhlelo lokusebenzisa olwenza abantu baphile isikhathi eside. Ikakhulukazi, ukufaka ikhemikhali ngokuqondile oketshezini lokukhulisa amaseli kweqa ukumuncwa, ukusatshalaliswa, nokukhishwa kwayo emzimbeni ophelele. Umtapo wocwaningo uhlela izifundo ngokwale mininingwane yokwakhiwa kwazo.
Kungani umphumela wamagundane udinga izilinganiso ezimbili zesikhathi sokuphila
Ucwaningo lwe-Interventions Testing Program olwenziwa ezindaweni ezintathu lwasebenzisa amagundane ahlukahlukene ngokofuzo. Izindlela zalo zicacisa i-methylene blue hydrate engu-28 mg ngekhilogremu yokudla; isigaba semiphumela sibika u-27 mg/kg wokudla. Kokubili kuchaza ukugxila kwento ekudleni, hhayi amamiligremu ngekhilogremu yesisindo somzimba.
Amajika okusinda ahlanganisiwe awazange athuthuke kakhulu ngokwezibalo kunoma yibuphi ubulili. Nokho, kwensikazi, isikhathi sokuphila ku-percentile yama-90 sakhuphuka sisuka ezinsukwini ezingu-1,072 saya kwezingu-1,138, cishe ngo-6%, nge-P = .004. Abacwaningi abazange babheke imiphumela iyonke njengeyanele ukusekela indlela ephumelelayo yokulwa nokuguga ezingeni lokuchayeka elahlolwa.
Isikhathi sokuphila esimaphakathi siyiminyaka yobudala lapho ingxenye yeqembu isifile. Isikhathi sokuphila ku-percentile yama-90 sichaza ingxenye yabaphila isikhathi eside kakhulu, lapho cishe u-90% usufile. Lapha, “isikhathi sokuphila esiphezulu” sibhekisela kuleso silinganiso esisekelwe ku-percentile, hhayi eminyakeni yobudala yesilwane esisodwa esephule irekhodi. Indlela yokungenelela ingathinta ingxenye eyodwa yokusatshalaliswa kwezikhathi zokusinda ngaphandle kokuthuthukisa iphuzu layo eliphakathi. Umphumela otholwe ezilwaneni zensikazi kuphela nawo awukwazi ukufakazela inzuzo kwabesifazane.
Isikhathi sokuphila okunempilo kufanele sihlolwe ngokwehlukana
Isivivinyo sokuguga kwamathambo sango-2024 sibonisa ukuthi kungani indlela yokusebenza inganele. Nakuba kwakunesizathu sokugxila ekungasebenzini kahle kwama-mitochondria, i-methylene blue ayizange ivimbele ukulahlekelwa amathambo kumagundane ensikazi agugile ayeyithola emanzini okuphuza. Esinye isivivinyo ephepheni elifanayo naso asitholanga ukuvikelwa kwamathambo ngokuyinikeza ekudleni kumagundane ahlukahlukene ngokofuzo.
Lokhu akufakazeli ukuthi yonke imiphumela yokusebenza engase ibe khona ayithinteki. Kodwa kubonisa ukuthi umphumela omuhle emaselini akhuliswe elabhorethri awunakuthathwa njengobufakazi bokuvikela isitho esigugayo. Ukubuyekezwa kobufakazi bokuguga kwamathambo kuhlola ngokuningiliziwe le nkinga yokudlulisela imiphumela ocwaningweni iye emzimbeni.
Okungafakazelwa ukuhlolwa kwabantu nemibiko yomuntu siqu
Ucwaningo lokuthwebula izithombe kubantu olwabela amaqembu ngokungahleliwe lwahlola ukusabela kwesikhathi esifushane ngemva kokunikezwa ngomlomo. Alukwazi ukuphendula ukuthi ukuchayeka okuphindaphindiwe kuyalondoloza yini ukuzimela, kuvimbela izifo ezihlobene nobudala, noma kwandisa ukusinda phakathi neminyaka. Umuthi ungaba nomphumela wesikhathi esifushane olinganisekayo ngaphandle kokuthuthukisa noma yimuphi waleyo miphumela.
Ukucabanga okufanayo kuyasebenza ekuhlolweni kweminyaka yezinto eziphilayo. Ngisho noma isikolo sehla ngemva kokuba othile eqale ukusebenzisa i-methylene blue, lokho kubonwa kufakazela ushintsho esikolweni. Ukubonisa inzuzo ekusindeni kudinga ubufakazi bokuthi indlela yokungenelela ithuthukisa ukusinda, noma isilinganiso esimelela ukusinda esiqinisekiswe ngokuqinile ngalokho kwelashwa nakulelo qembu labantu. Isikolo esibikezela ubungozi kubantu abahlukahlukene asibonisi ngokuzenzakalelayo ukuthi ukushintsha leso sikolo kushintsha lobo bungozi.
Imibiko yomuntu siqu yokusebenzisa izindlela eziningi zokungenelela inenye inkinga. Uma umuntu eshintsha ukudla, ukuvivinya umzimba, ukulala, izithasiselo eziningana, ne-methylene blue ngesikhathi esisodwa, ukuthuthuka okulandelayo akukwazi ukuhlukanisa umnikelo we-methylene blue. Ukuhlolwa okuphindaphindiwe nokubika imiphumela ekhethiwe kuphela kungaphinde kuhlanekezele isithombe. Imibiko enjalo ingaveza imibuzo yocwaningo, kodwa ayikwazi ukubala iminyaka ezuziwe.
Lokhu kusho ukuthini esinqumweni sokuphila isikhathi eside
Imiphumela etholakalayo isekela ucwaningo olwengeziwe, hhayi umthamo noma uhlelo oluqinisekisiwe lokwandisa isikhathi sokuphila. Ukusebenzisa iminyaka ngenjongo yokuvikela kungadinga ubufakazi mayelana nemiphumela emibi enqwabelanayo kanye nezinzuzo. Ilebula lamanje lomkhiqizo ojovwayo libhala ukusebenzisana okubi kakhulu okuthinta i-serotonin nokwenqatshelwa kokusetshenziswa uma kunokuntuleka kwe-G6PD ngenxa yobungozi bokubhubha kwamangqamuzana abomvu egazi. Aliqinisekisi ukusetshenziswa isikhathi eside ngomlomo ngenjongo yokubhekana nokuguga.
Ngaphambi kokucabanga ukuyisebenzisa wena, buyekeza imiphumela engemihle nezimo lapho kungafanele isetshenziswe khona bese uxoxa nochwepheshe wezempilo ngomkhiqizo oqondile nangohlu lwemithi oyisebenzisayo. Ukuze uhlole isimangalo sokuphila isikhathi eside, funa imininingwane yento ephilayo eyacwaningwa, indlela yokuyinikeza, isikhathi sokuchayeka, lokho okuqhathaniswe nakho, nomphumela wokugcina owalinganiswa ngempela. Uma umphumela wokugcina uwukukhula kwamaseli noma isikolo sokuhlolwa, isimangalo kufanele sihlale simayelana nokukhula kwamaseli noma leso sikolo sokuhlolwa.