Isingeniso se-athikili:

I-NAD+ ibalulekile ekwakhiweni kwamandla emzimbeni kanye nokulawulwa kwezinqubo ezibalulekile zamaselula.Nakhu ukuthi kungani kubaluleke kangaka, ukuthi kwatholakala kanjani, nokuthi ungakuthola kanjani okwengeziwe.

Inamandla Kanjani I-NAD+

Vula noma iyiphi incwadi yebhayoloji futhi uzofunda nge-NAD+, emele i-nicotinamide adenine dinucleotide.Kuyi-coenzyme ebalulekile etholakala kuwo wonke amangqamuzana emzimbeni wakho ebandakanyeka kumakhulu ezinqubo ze-metabolic njengamandla amaselula kanye nempilo ye-mitochondrial.I-NAD+ iyasebenza kanzima kumaseli abantu nezinye izilwane ezincelisayo, imvubelo namagciwane, ngisho nezitshalo.

Ososayensi bazi nge-NAD+ kusukela yaqala ukutholwa ngo-1906, futhi kusukela lapho ukuqonda kwethu ngokubaluleka kwayo kuqhubekile nokuvela.Isibonelo, i-NAD+ precursor niacin ibambe iqhaza ekwehliseni i-pellagra, isifo esibulalayo esahlupha i-America eningizimu ngeminyaka yawo-1900.Ososayensi ngaleso sikhathi bahlonze ukuthi ubisi nemvubelo, kokubili okuqukethe izandulela ze-NAD+, kwadambisa izimpawu.Ngokuhamba kwesikhathi ososayensi bahlonze izandulela ezimbalwa ze-NAD+ - okuhlanganisa i-nicotinic acid, i-nicotinamide, ne-nicotinamide riboside, phakathi kokunye - ezisebenzisa izindlela zemvelo eziholela ku-NAD+.Cabanga ngamazandulela e-NAD+ njengemizila ehlukene ongayithatha ukuze ufike endaweni oya kuyo.Zonke izindlela zikuyisa endaweni efanayo kodwa ngezindlela ezahlukene zokuthutha.

Muva nje, i-NAD+ isiphenduke i-molecule eyigugu ocwaningweni lwesayensi ngenxa yendima yayo eyinhloko emisebenzini yebhayoloji.Umphakathi wesayensi ubucwaninga ukuthi i-NAD+ ihlobana kanjani nezinzuzo eziphawulekayo ezilwaneni eziqhubeka nokugqugquzela abacwaningi ukuthi bahumushele lokhu okutholakele kubantu.Ngakho-ke i-NAD+ idlala kanjani indima ebaluleke kangaka?Ngamafuphi, i-coenzyme noma i-molecule "yomsizi", ebophezela kwamanye ama-enzyme ukusiza ukubangela ukusabela ezingeni lamangqamuzana.

Kepha umzimba awunakho ukuhlinzekwa okungapheli kwe-NAD+.Eqinisweni, empeleni liyehla ngokuya ngeminyaka.Umlando wocwaningo lwe-NAD+, nokusungulwa kwayo kwakamuva emphakathini wesayensi, uvule amasango ezikhukhula ukuze ososayensi baphenye ngokugcina amazinga e-NAD+ kanye nokuthola i-NAD+ eyengeziwe.

Uyini umlando we-NAD+?

I-NAD+ yaqala ukuhlonzwa uSir Arthur Harden noWilliam John Young ngo-1906 lapho laba ababili behlose ukuqonda kangcono ukuvutshelwa - lapho imvubelo igaya ushukela futhi yakhe utshwala ne-CO2.Kuthathe cishe iminyaka engama-20 ukuqashelwa okwengeziwe kwe-NAD+, lapho u-Harden abelana ngomklomelo we-Nobel we-Chemistry wango-1929 noHans von Euler-Chelpin ngomsebenzi wabo wokuvutshelwa.U-Euler-Chelpin ukhombe ukuthi ukwakheka kwe-NAD+ kwenziwa ngama-nucleotide amabili, izingqimba zokwakha ama-nucleic acid, akha i-DNA.Ukuthola ukuthi ukuvutshelwa, inqubo ye-metabolic, kuncike ku-NAD+ kwafanekisela lokho manje esikwaziyo nge-NAD+ edlala indima ebalulekile ezinqubweni ze-metabolic kubantu.

U-Euler-Chelpin, enkulumweni yakhe yoMklomelo kaNobel ka-1930, wabiza i-NAD+ ngokuthi i-cosymase, eyake yabizwa kanjalo, eveza ubungqabavu bayo."Isizathu sokwenza kwethu umsebenzi omningi kangaka ekuhlanzeni nasekunqumeni umthethosisekelo walesi sici," esho, "i-cosymase ingesinye sezishoshovu ezisakazeke kakhulu futhi ezibaluleke kakhulu empilweni yezitshalo nezilwane."

U-Otto Heinrich Warburg - owaziwa "ngomphumela we-Warburg" - waqhubekisela phambili isayensi ngeminyaka yawo-1930s, ucwaningo oluqhubeka luchaza i-NAD+ edlala indima ekuphenduleni kwe-metabolic.Ngo-1931, osokhemisi u-Conrad A. Elvehjem kanye no-CK Koehn bahlonza ukuthi i-nicotinic acid, eyandulela i-NAD+, yayiyisici sokunciphisa i-pellagra.UDokotela Wezempilo Yomphakathi wase-United States uJoseph Goldberger phambilini wayekhombe ukuthi lesi sifo esibulalayo sasixhunywe kokuthile okungekho ekudleni, wabe esebiza i-PPF ngokuthi "isici sokuvimbela i-pellagra."UGoldberger ushone ngaphambi kokutholakala kokugcina ukuthi kwakuyi-nicotinic acid, kodwa iminikelo yakhe yaholela ekutholakaleni, okuphinde kwazisa umthetho ogcina ugunyaza ukuthi kuqiniswe ufulawa nelayisi emhlabeni wonke.

Eminyakeni eyishumi eyalandela, u-Arthur Kornberg, kamuva owawina uMklomelo KaNobel ngokubonisa indlela i-DNA ne-RNA ezakheka ngayo, kwatholakala i-NAD synthetase, i-enzyme eyenza i-NAD+.Lolu cwaningo luphawule ukuqala kokuqonda amabhlokhi wokwakha we-NAD+.Ngo-1958, ososayensi uJack Preiss noPhilip Handler bachaza lokho manje okwaziwa ngokuthi i-Preiss-Handler pathway.Indlela ikhombisa ukuthi i-nicotinic acid - uhlobo olufanayo lukavithamini B3 olwasiza ukwelapha i-pellagra - iba yi-NAD+.Lokhu kusize ososayensi baqonde kabanzi indima ye-NAD+ ekudleni.U-Handler kamuva wathola iNdondo Kazwelonke Yesayensi kuMongameli u-Ronald Reagan, owacaphuna “amagalelo avelele ka-Handler ocwaningweni lwe-biomedical…eqhubekisela phambili isimo sesayensi yaseMelika.”

Nakuba ososayensi manje base bebonile ukubaluleka kwe-NAD+, bebengakatholi umthelela wayo oyinkimbinkimbi ezingeni lamaselula.Ubuchwepheshe obuzayo ocwaningweni lwesayensi kuhlanganiswe nokuqashelwa okuphelele kokubaluleka kwe-coenzyme ekugcineni kukhuthaze ososayensi ukuthi baqhubeke nokutadisha i-molecule.

Isebenza kanjani i-NAD+ emzimbeni?

I-NAD+ isebenza njengebhasi elihambayo, idlulisela ama-electron esuka kwelinye i-molecule iye kwelinye ngaphakathi kwamaseli ukuze enze zonke izinhlobo zokusabela nezinqubo.Ngozakwabo wamangqamuzana, i-NADH, le ngqamuzana ebalulekile ibamba iqhaza ekuphenduleni okuhlukahlukene kwe-metabolic ekhiqiza amandla amangqamuzana ethu.Ngaphandle kwamazinga e-NAD+ anele, amaseli ethu ngeke akwazi ukukhiqiza amandla ukuze aphile futhi enze imisebenzi yawo.Eminye imisebenzi ye-NAD+ ifaka phakathi ukulawula isigqi sethu se-circadian, esilawula umjikelezo wokulala/ukuvuka komzimba wethu.

Njengoba sikhula, amazinga e-NAD+ ayehla, ephakamisa imithelela ebalulekile ekusebenzeni kwe-metabolic kanye nezifo ezihlobene nobudala.Umonakalo we-DNA uyanqwabelana kanye namabhola eqhwa ngokuguga.

Kwenzekani uma amazinga e-NAD+ encishiswa?

Ucwaningo oluningi lukhombisa amazinga ancishisiwe e-NAD+ ezimeni ezinomsoco eziphazamisekile, njengokukhuluphala nokuguga.Ukwehliswa kwamazinga e-NAD+ kungaholela ezinkingeni nge-metabolism.Lezi zinkinga zingadala ukuphazamiseka, okuhlanganisa ukukhuluphala kanye nokumelana ne-insulin.Ukukhuluphala ngokweqile kubangela isifo sikashukela kanye nomfutho wegazi ophakeme.

Ukuphazamiseka kwe-metabolic okubangelwa izinga eliphansi le-NAD+ lehla.Umfutho wegazi ophakeme kanye nokunye ukwehla kokusebenza kwenhliziyo kungathumela amagagasi okucindezela alimazayo ebuchosheni okungase kuholele ekukhubazekeni kwengqondo.

Ukukhomba i-NAD+ metabolism wukungenelela okunomsoco okusebenzayo ekuvikeleni ngokumelene ne-metabolic nezinye izifo ezihlobene nobudala.Amaqembu amaningana enze izifundo ezikhombisa ukuthi ukwengezela ngama-boosters e-NAD+ kuthuthukisa ukumelana ne-insulin ekukhuluphaleni.Kumamodeli egundane ezifo ezihlobene nobudala, ukugcwalisa nge-NAD+ booster kuthuthukisa izimpawu zezifo.Lokhu kuphakamisa amazinga ancishisiwe e-NAD+ ngobudala angase abe nomthelela ekuqalekeni kwezifo ezihlobene nobudala.

Ukuvimbela ukwehla kwe-NAD+ kunikeza isu elithembisayo lokulwa nokuphazamiseka kwemetabolism ngeminyaka.Njengoba amazinga e-NAD+ ehla ngokukhula, lokhu kungaholela ekwehliseni ukulungiswa kwe-DNA, impendulo yengcindezi yamaselula, kanye nokulawulwa kokusebenza kwamandla.

Izinzuzo ezingaba khona

I-NAD+ ibalulekile ekunakekeleni uhlobo lwe-mitochondrial kanye nokulawulwa kofuzo mayelana nokuguga.Kodwa-ke, izinga le-NAD + emzimbeni wethu lehla kakhulu ngokuya ngeminyaka.“Njengoba sikhula, silahlekelwa yi-NAD+.Lapho usuhlanganisa iminyaka engu-50, usuke usunengxenye yezinga owake waba nalo lapho uneminyaka engu-20,” kusho uDavid Sinclair waseHarvard University engxoxweni.

Ucwaningo luye lwabonisa ukwehla kwe-molecule ehlotshaniswa nezifo ezihlobene neminyaka ehlanganisa ukuguga okusheshayo, ukuphazamiseka kwe-metabolic, isifo senhliziyo, kanye ne-neurodegeneration.Amazinga aphansi e-NAD+ ahlotshaniswa nesifo esihlobene neminyaka ngenxa yokusebenza kancane kwemetabolism.Kodwa ukugcwalisa amazinga e-NAD+ kwethule imiphumela elwa nokuguga kumamodeli ezilwane, okubonisa imiphumela ethembisayo ekubuyiseleni emuva izifo ezihlobene nobudala, okwandisa ubude bempilo kanye nempilo.

Ukuguga

Aziwa ngokuthi “abaqaphi bezakhi zofuzo,” ama-sirtuin ayizakhi zofuzo ezivikela izinto eziphilayo, ezitshalweni kuya ezilwaneni ezincelisayo, ekuwohlokeni nasezifweni.Lapho izakhi zofuzo zizwa ukuthi umzimba ungaphansi kokucindezeleka ngokomzimba, njengokuzivocavoca noma ukulamba, kuthumela amasosha ukuba avikele umzimba.Ama-Sirtuin agcina ubuqotho be-genome, akhuthaza ukulungiswa kwe-DNA futhi abonise izici ezihlobene nokuguga ezilwaneni eziyimodeli njengokukhula kwesikhathi sokuphila.

I-NAD+ inguphethiloli oshayela ufuzo ukuthi lusebenze.Kepha njengemoto ayikwazi ukushayela ngaphandle kukaphethiloli wayo, ama-sirtuin adinga i-NAD +.Imiphumela evela ocwaningweni ikhombisa ukuthi ukukhuphula izinga le-NAD+ emzimbeni kwenza ama-sirtuin asebenze futhi kwandisa isikhathi sokuphila kumvubelo, izikelemu namagundane.Yize ukugcwalisa kabusha kwe-NAD+ kukhombisa imiphumela ethembisayo kumamodeli ezilwane, ososayensi basatadisha ukuthi le miphumela ingahumusha kanjani kubantu.

Ukusebenza kwemisipha

Njengendlu yamandla yomzimba, umsebenzi we-mitochondrial ubalulekile ekusebenzeni kwethu kokuzivocavoca.I-NAD+ ingenye yezikhiye zokugcina i-mitochondria enempilo kanye nokuphuma kwamandla okuzinzile.

Ukwenyusa amazinga e-NAD+ emisipha kungathuthukisa i-mitochondria nokuqina kumagundane.Olunye ucwaningo luphinde lubonise ukuthi amagundane athatha ama-booster e-NAD+ ayacile futhi angagijima aqhubekele phambili ku-treadmill, ekhombisa umthamo wokuzivocavoca ophakeme.Izilwane esezikhulile ezinezinga eliphakeme le-NAD+ zidlula ontanga yazo.

Izinkinga ze-metabolic

Njengoba iWorld Health Organization (WHO) imemezele njengobhubhane, ukukhuluphala ngokweqile kungesinye sezifo ezivame kakhulu emphakathini wanamuhla.Ukukhuluphala ngokweqile kungaholela kwezinye izifo ze-metabolic ezifana nesifo sikashukela, esabulala abantu abayizigidi ezingu-1.6 emhlabeni wonke ngo-2016.

Ukuguga nokudla okunamafutha amaningi kunciphisa izinga le-NAD+ emzimbeni.Ucwaningo lukhombisile ukuthi ukuthatha ama-booster e-NAD+ kungadambisa ukuzuza kwesisindo okuhambisana nokudla nokuhambisana neminyaka kumagundane futhi kuthuthukise amandla awo okuzivocavoca, ngisho nasemagundaneni amadala.Olunye ucwaningo lwaze lwawuhlehlisa umphumela wesifo sikashukela kumagundane esifazane, lubonisa amasu amasha okulwa nokuphazamiseka kwe-metabolic.

Umsebenzi wenhliziyo

Ukunwebeka kwemithambo kusebenza njengesivimbeli phakathi kwamagagasi okucindezela athunyelwa ukushaya kwenhliziyo.Kodwa imithambo iyaqina njengoba siguga, okubangela umfutho wegazi ophakeme, izici eziyingozi kakhulu zesifo senhliziyo nemithambo yegazi.Umuntu oyedwa ubulawa isifo senhliziyo njalo ngemizuzwana engu-37 e-United States iyodwa, kubika i-CDC.

Umfutho wegazi ophakeme ungabangela inhliziyo ukuba ibe nkulu futhi kuvaleke imithambo eholela ekushayweni.Ukuthuthukisa amazinga e-NAD+ kunikeza isivikelo enhliziyweni, kuthuthukise imisebenzi yenhliziyo.Emagundaneni, ama-booster e-NAD+ agcwalise amazinga e-NAD+ enhliziyweni ukuze afinyelele emazingeni ayisisekelo futhi avimbele ukulimala kwenhliziyo okubangelwa ukushoda kokugeleza kwegazi.Olunye ucwaningo lubonise ukuthi ama-booster e-NAD+ angavikela amagundane ekwandeni kwenhliziyo okungavamile.

Ingabe i-NAD+ iyasikhulisa isikhathi sokuphila?

Yebo, liyakwenza.Ukube ubuyigundane.Ukwandisa i-NAD+ ngama-booster, njenge-NMN ne-NR, kunganweba ubude bempilo kanye nempilo kumagundane.

Amazinga e-NAD+ anyusiwe anikeza umthelela onesizotha ngokwandisa isikhathi sokuphila kumagundane.Besebenzisa isandulela se-NAD+, i-NR, ososayensi bathola ocwaningweni olushicilelwe kuIsayensi, 2016, ukwesekwa kwe-NR kwandisa isikhathi sokuphila samagundane cishe ngamaphesenti amahlanu.

Amazinga e-NAD+ athuthukisiwe aphinde anikeze isivikelo ezifweni ezihlukahlukene ezihlobene nobudala.Ukuvikelwa ezifweni ezihlobene neminyaka kusho ukuphila impilo enempilo isikhathi eside, okwandisa impilo.

Eqinisweni, abanye ososayensi abalwa nokuguga abanjengoSinclair babheka imiphumela ocwaningweni lwezilwane ngempumelelo yokuthi bona ngokwabo, bathatha ama-booster e-NAD+.Kodwa-ke, abanye ososayensi abafana noFelipe Sierra wesikhungo sikazwelonke sokuguga e-NIH abacabangi ukuthi umuthi usulungile.“Okubalulekile wukuthi angizami noma iyiphi yalezi zinto.Kungani ngingakwenzi?Ngoba angilona igundane,” usho kanje.

Emagundaneni, ukufuna “umthombo wobusha” kwakungase kuphele.Nokho, kubantu, ososayensi bayavuma ukuthi asikakafiki lapho.Izivivinyo zomtholampilo ze-NMN ne-NR kubantu zinganikeza imiphumela eminyakeni embalwa ezayo.

Ikusasa le-NAD+

Njengoba "i-silver wave" ingena, isixazululo sezifo ezingelapheki ezihambisana neminyaka yokususa umthwalo wezempilo nomnotho siyaphuthuma.Ososayensi kungenzeka bathole isisombululo esingaba khona: NAD+.

Ebizwa ngokuthi “i-molecule eyisimangaliso” yekhono lokubuyisela nokugcina impilo yamaselula, i-NAD+ ibonise amandla ahlukahlukene ekwelapheni izifo zenhliziyo, isifo sikashukela, i-Alzheimer's, kanye nokukhuluphala kumamodeli ezilwane.Kodwa-ke, ukuqonda ukuthi izifundo ezilwaneni zingahumushela kanjani kubantu isinyathelo esilandelayo sososayensi sokuqinisekisa ukuphepha nokusebenza ngempumelelo kwe-molecule.

Ososayensi bahlose ukuqonda ngokugcwele indlela ye-biochemical ye-molecule kanye nocwaningo lwe-NAD+ metabolism luyaqhubeka.Imininingwane yomshini we-molecule ingase yembule imfihlo yokuletha isayensi yokulwa nokuguga isuka ebhentshini iye eceleni kombhede.