Anti-aging Dilemma: Yuav Ua Li Cas Rov Qab Kho Kho Kho lossis Rov Kho Lub Software?

Hu rau: jerry.he@wecistanche.com

Ancha Baranova'.2* thiab James D. Willett*

'Center for the Study of Chronc Metaboic Diseases, School of Systems Bidlogy, Gearge Mason Uriversity, Farfax, VA USA, 2 Research Center for Medical Genetics, Mosoow, Russia

Keywords: metabolome, SEUs, kev hloov, Turing tshuab, hypercomputation

"Cov lus piv txwv muaj txoj hauv kev los tuav qhov tseeb tshaj plaws hauv qhov tsawg kawg nkaus."

-Orson Scott Card, Alvin Journeyman

Cistanche muaj cov nyhuv anti-aging

Txij li thaum nws tseem ntxov, tus nqi ntawm kev txiav txim siab ntawm tib neeg DNA tau pom feem ntau hauv kev rho tawm cov kab lus uas khiav cov hlwb uas tsim lub cev. Hauv kev nkag siab zoo sib xws, cov lus no tau muab tso rau hauv DNA thiab tau muab sau ua cov txheej txheem ntawm tes ntawm RNAs, qee qhov tau muab txhais ua cov protein, tom qab ntawd hloov nrog ntau yam kev txhais lus ntxiv rau cov suab thaj. lipids thiab lwm yam moieties. Qhov kev sib txuas ntawm cov xwm txheej nyuaj no yog qhov nyuaj ntxiv los ntawm ntau txheej txheej possi-bilities rau cov kev hloov kho tau tso cai ntawm txhua kauj ruam-epigenetics rau DNA, kho rau RNAs thiab qhov tsis ntev los no pom tshwm sim ntawm non-template polypeptide extension tso cai los ntawm ribosomes (Shen li al., 2015). Nws zoo nkaus li tias thaum saib tag nrho, DNA, thiab tag nrho cov lus sib txuas nrog DNA, tsis zoo li daim ntawv qhia, lossis txawm tias muaj cov lus qhia meej, tab sis yog cov ntawv tsis zoo lossis cov ntawv sau uas sau ntawv. tag nrho thiab tag nrho ntawm ambiguities.

Txawm li cas los xij, cia peb nyiag los ntawm feem ntau ntawm "omics" thiab saib cov txheej txheem me me hu ua metabolites, thiab kev qhuab qhia ntawm Metabolomics uas tshawb nrhiav qhov tseeb hauv qab ntawm cov txheej txheem ntau yam ntawm cov cell nyob. Nws yog ib qho tsim nyog yuav tsum nco ntsoov tias, mus rau ib qho kev txiav txim siab me ntsis, lub xov tooj ntawm tes yuav zam qhov kev poob ntawm cov noob los yog kev hloov pauv hauv qib RNAs lossis txawm tias qhov tseem ceeb tshaj plaws ntawm cov protein, txawm tias me ntsis deregulation ntawm cov qib ntawm qee qhov me me metabolites. coj mus rau tam sim ntawd thiab kev puas tsuaj loj. Cov poov tshuaj ion thiab ATP tuaj yeem siv los ua cov piv txwv ntawm cov molecules me tshaj plaws uas muaj peev xwm ua rau muaj kev cuam tshuam cov lus teb. Raws li peb suav, tsuas yog 0.5 feem pua ​​​​nce hauv tag nrho cov ntsiab lus ntawm cov poov tshuaj chlo-ride, ib qho ntawm cov electrolytes feem ntau hauv tib neeg lub cev, ua rau lub plawv nres tam sim ntawd. Cov txiaj ntsig ntawm qhov depletion ntawm ATP tuaj yeem tshwm sim raws li ntau yam kab mob, nrog rau lawv lub sijhawm hloov pauv mus rau qhov hnyav ntawm qhov tsis xws luag.Kev laus, tshwj xeeb, yog txuam nrog kev poob qis hauv kev ua haujlwm ntawm oxidative phosphorylation thiab nce qhov kev pheej hmoo ntawm kev tshwm sim pathologies. Tau kawg, muaj lwm cov molecules me me, tej zaum tsis zoo li ATP, tab sis tseem indispens-muaj peev xwm thiab irreplaceable. Hauv particular, cov metabolites muab tau los ntawm cov amino acid tryptophan muaj peev xwm ua rau muaj kev hloov pauv loj ntawm kev ua haujlwm thoob plaws hauv lub cev. Feem ntau cuam tshuam rau lub ntsiab lus ntawm qhov kev sib tham no, cov kev hloov pauv hauv metabolic profles raug suav tias yog cov tsav tsheb rau cov kab mob pathogene-sis ntawm cov hnub nyoog cuam tshuam, suav nrog Alzheimer's kab mob (Tacutu et al, 2010; Demetrius and Driver, 2013; Jia et al., 2014; Obre thiab Rossignol, 2015). Nws kuj tseem ceeb heev uas cov metabolites tsis muaj ntau npaum li kev kawm ntau hom proteins thiab RNAs. Yog li, lub ntiaj teb ntawm metabolites yog qhov yooj yim heev kom nkag siab ntau dua li lub ntiaj teb nyuaj dhau ntawm lwm lub npe nrov "omics." Lub ntsiab lus tom kawg yog qhov tseem ceeb heev, vim tias nws muaj peev xwm ua tau rau kev siv lub zog txo qis-ist mus kom ze yam tsis tau poob rau hauv kev mob. fitting los yog over-fitting ntawm tus qauv hauv qab, ib qho kev paub zoo perpetual qhov chaw ntawm entrapment.

Cia peb sib piv cov nyob (thiabkev laus) ntawm tes, nrog nws qhov kawg "omics"-txheej txheej ntawm cov khoom sib txuas, rau cov khoos phis tawj niaj hnub. Khoos phis tawj kho vajtse yog ib phau ntawm cov khoom siv sib txuas ntawm lub cev siv hauv lossis nrog koj lub tshuab. Ib qho ntawm cov khoom no tuaj yeem hnav nws tus kheej tawm thiab tuag; txawm li cas los xij,

nyob rau hauv industrially-tsim computers, muaj ntau yam redundant circuits incorporated nyob rau hauv txhaum-tolerant los yog multi-modular redundancy designs muab kev tiv thaiv txaus tiv thaiv thiaj li hu ua "softerrors." Tab sis dab tsi yog qhov yuam kev zoo li no? Qhov tseeb, cov no tsis yog ib qho piv txwv nrog "software glitches." Cov kev ua yuam kev mos feem ntau raug suav hais tias yog "kev ntxhov siab ib leeg" (SEU), qhov kev hloov pauv ntawm lub xeev tshwm sim los ntawm ions lossis hluav taws xob sib nqus hluav taws xob tawm tsam qhov rhiab ntawm lub tshuab hluav taws xob microelectronic, feem ntau yog ib chav tsev uas khaws cia. Qhov feem ntau ua rau "qhov yuam kev tsis zoo" yog qhov cuam tshuam ncaj qha ntawm cov kab hluav taws xob los ntawm cosmic particles sib tsoo nrog cov atoms hauv cov huab cua, tsim cov cascades los yog da dej ntawm neutrons thiab pro- tons (Ziegler thiab Lanford, 1979)-analogous rau qhov tshwm sim ntawm ib kev hloov pauv. Muaj txawm tias ib qho qauv rau kev suav ntawm qhov kev ua yuam kev uas feem ntau qhia tau tias muaj ntau qhov kev ua tsis tiav-hauv-lub sijhawm (aka tus nqi hloov pauv) (Li et al., 2007). Ib yam li cov kab ke nyob, cov khoos phis tawj tuaj yeem yog thiab tsim los txhawm rau txheeb xyuas SEUs thiab rov qab tau zoo, yog los ntawm kev kho qhov yuam kev yav tom ntej uas suav nrog cov lej rov ua yuam kev-kho rau hauv txhua qhov tso zis, lossis los ntawm kev kho qhov yuam kev rov qab uas kuaj pom SEU siv "sentinel "

(lossis parity) cov khoom, thiab, yog tias xav tau, rov sau cov ntaub ntawv siv qhov thaub qab. Hauv lub ntiaj teb DNA, ob qho tib si ntawm cov haujlwm no raug tua los ntawm DNA kho tshuab. Zoo ib yam li cov txheej txheem rov ua dua tshiab x-ing SEUs, cov txheej txheem kho DNA tsis tu ncua tau muab tso rau hauv cov txheej txheem qub tsim, txawm nyob hauv vivo lossis hauv silico. Yog li, ob qho tib si DNA thiab cov molecules ncaj qha nkag los ntawm DNA, piv txwv li, RNA thiab cov proteins, yog cov khoom siv ntawm lub neej.

Cov lus nug txog lab daus las yog: "Cov khoom siv dab tsi ua rau lub cell nyob hauv software?" Hauv qab no peb yuav sim ua ib rooj plaub rau cov zej zog ntawm cov me me molecules extant nyob rau hauv lub metabolome li cov software Cheebtsam uas khiav lub cell nyob. Tseeb, metabolites yog universal, thiab kuj interchangeable ntawm cellular hom. Thaum kawg, ATP tsuas yog ATP xwb; Nws yog qhov nyuaj rau xav txog tias ATP tuaj yeem hloov mus rau lwm yam. Yog li, cov metabolites yuav zoo li cov lus qhia (software), uas tuaj yeem khiav ntawm ib lossis lwm hom khoom siv - piv txwv li, ib qho molecule ntawm ATP muab rho tawm los ntawm tus kab mob tapeworm yuav tau hais txog cov kev xav tau ntawm tes thiab ua haujlwm tib yam li. uas muab rho tawm los ntawm tib neeg cell. Nyob rau hauv lub cell, ib txheej ntawm metabolites, txhua tus nrog nws cov koom haum hauv zos concentrations thiab, tejzaum nws, lawv cov piv txwv yuav ua tau raws li "net regulator" directing tag nrho cov qauv ntawm transcription, txhais, thiab ntxiv kev hloov kho ntawm cov lus encoded nyob rau hauv DNA. Qhov tseem ceeb, cov ntsiab lus ntawm cov metabolites tuaj yeem hloov kho sab nraud, los ntawm kev ntxiv ncaj qha lossis kev tswj hwm ntawm soluble enzyme inhibitors lossis co-factors. Nrog rau qhov ntawd, zoo ib yam li khoos phis tawj software, "net regulation" uas tswj hwm los ntawm cellular metabolome tuaj yeem rov qab mus rau qhov chaw pib. Nyob rau hauv cov ntaub ntawv ntawmkev laus, lub neej ntawd hom yuav sib raug rau ib lossis lwm lub sijhawm dhau los ntawm kev ua neej nyob, lossis "hnub nyoog" lub xeev ntawm kev ua neej nyob. Raws li ib tug ntawm peb tau pom yav dhau los, metabolic proles yog robust, reproducible ntiv tes ntawm tag nrho cov kab mob pheno-typic xeev nyob rau hauv lub nematode, Caenorhabditis elegans, yog reecting ob lub neej theem sib txawv thiab ib puag ncig modulations (Willett li al., 2010; Sudama. , 2013). Tej zaum nws yog ntau tshaj qhov xwm txheej uas Sydney Brenner, tus thawj coj ntawm kev siv C. elegans ua tus qauv pob tshab rau ntau yam kev tshawb fawb, suav nrogkev lauskev tshawb fawb, tsis ntev los no tau taw qhia txog qhov tseem ceeb ntawm bio-logical ntawm suav nrog cov lus nug ntawm cov ntaub ntawv mus rau qhov kev kawm nyob mus ib txhis ntawm qhov teeb meem thiab lub zog (Brenner, 2012).

Tsis ntseeg, tag nrho cov saum toj no tsis muaj dab tsi ntau tshaj li cov piv txwv. Txawm li cas los xij, cov kev sib piv no yuav pab tau kom nkag siab txog qhov teeb meem nyob mus ib txhis ntawmkev lausraws li lub mundane crackdown ntawm lub rooj saum lub computer. Thaum lub desktop tab tom pib ua tsis tiav peb los ntawm kev ua kom qeeb lossis khov thav ntawv, peb rov pib dua nws lossis, ua qhov kawg, rov nruab nws cov software ua haujlwm. Nco ntsoov tias lub tswv yim ntawm kev tsim kho dua tshiab lossis lwm yam txhawb nqa cov khoom siv kho vajtse kom lawv tsis tshua muaj kev cuam tshuam rau SEUs, lossis kev hloov pauv, nyob rau hauv rooj plaub ntawm lub desktop zoo li absurd. Ib yam li ntawd, raws li ib tug countermeasure raukev laus, peb yuav tsum tsom ntsoov rau cov ntsiab lus uas yooj yim xable, los yog hloov tau-tus

Cov qauv metabolic zoo li tus neeg sib tw tsim nyog rau kev txhawb siab los yog kev txhawb siab (Muradian, 2013). Obviously, txoj kev ntawm kev xav no txhais tau tiaskev laustsis yog ib qho cuab yeej tseem ceeb ntawm kev ua neej nyob, tab sis yog lub sij hawm cuam tshuam nrog kev lwj, thiab ib qho los yog lwm txoj hauv kev yuav raug tsim los txhawm rau txhim kho cov txheej txheem no, nyob rau hauv txoj kev uas zoo ib yam li kev kho tus kab mob. .

Hauv lwm lo lus, cov duab piv txwv muab rau kev cia siab tias cov khoom siv software ntawm lub tshuab muaj sia, cov metabolism, tuaj yeem hloov kho kom rov pib dua. Qhov tseeb, qhov sib piv ntawm lub ntiaj teb lub computer thiab lub ntiaj teb ntawm kev nyob (thiabkev laus) yam khoom muaj ntau. Txij li thaum pib ntawm kev tshawb fawb niaj hnub no, physics thiab nws qhov txuas ntxiv, chemistry, tau raug suav tias yog lub hauv paus ntawm biology. Hauv digital physics, tag nrho cov kev cai lij choj paub txog physics muaj qhov tshwm sim uas yog theoretically xam tau ntawm lub khoos phis tawj dig-ital, thiab yog li ntawd lub ntiaj teb nws tus kheej yuav tsum suav tau rau ntawm lub tshuab Turing classical, ib qho khoom siv tswv yim uas tswj cov cim ntawm ib daim kab xev raws li ib tug rooj ntawm txoj cai (Turing, 1936). Qhov tseeb tseem ceeb uas tau teev tseg saum toj no yog hu ua Lub Koom Txoos Strong–Turing thesis (Copeland, 1996). Muaj feem xyuam rau biology, cov txheej txheem nyob yog ib feem ntawm Turing Universe; yog li ntawd, tag nrho cov muaj sia nyob yog Turing computers thiab, yog li ntawd, yog cov ntsiab lus ntawm biological determinism nyob rau hauv lub widest kev txiav txim zoo.

Thaum muab ob lub hauv paus rau cov ntaub ntawv tshawb fawb innite piav txog ntau yam kev nkag siab txog kev siv tshuab rau hauv "kev tswj hwm" xov tooj ntawm tes thiab muab kev cia siab rau kev nkag siab qhov kawg ntawm kev ua neej nyob, peb yuav tsum lees paub tias cov physics tsis yog qhov niaj hnub tshaj plaws, tsis yog tus sawv cev ntxim nyiam tshaj plaws ntawm lub qab ntuj khwb. Muaj qee qhov kev sib tham dav dav, piv txwv li, hais tias Lub Ntiaj Teb yog ib lub khoos phis tawj uas muaj peev xwm ua tsis tau rov ua dua (Siegelmann, 1995; Copeland thiab Proudfoot, 1999).

Qhov tseem ceeb, txawm tias lub ntiaj teb tag nrho yuav raug piv rau lub khoos phis tawj hypercomputer, nws muaj peev xwm hais tias nws qhov chaw, piv txwv li, cov kab ke nyob, yuav nyob twj ywm hauv thaj tsam Turing. Ntawm no peb xav ntxiv rau qhov kev sib cav tsis ntev los no uas ua rau cov ntaub ntawv ntawm kev ua neej nyob dhau ntawm Turing cov cai (Mal- donado thiab Gomez Cruz, 2015) los ntawm kev xa mus rau Turing- unsolvable halting teeb meem. Ib qho tsis muaj peev xwm txheeb xyuas qhov nres lossis, hauv lwm lo lus, los txiav txim siab los ntawm cov lus piav qhia ntawm lub khoos phis tawj arbitrary thiab cov tswv yim seb qhov kev zov me nyuam yuav khiav, lossis txuas ntxiv mus mus ib txhis, yog qhov tshwj xeeb kos rau hauv Turing tsim (Jack Copeland, 2004). Ntawm no peb postulate tias, rau txoj kev nyob, kev tuag yog sib npaug rau ib tug nres. Txij li thaum nyob rau hauv cov kab ke nyob ib leeg tuaj yeem tshawb pom thiab kwv yees kev tuag nrog qhov tseeb, peb yuav tsum lees txais tsis yog-recursive hypercomputation ua ib qho tseem ceeb hauv paus ntsiab lus ntawm biology.

Cov ntaub ntawv

Brenner, S. (2012). Keeb kwm ntawm science. Lub kiv puag ncig nyob rau hauv lub neej sciences. Science 338, 1427–1428. doi: 10.1126/science.1232919 ib

Copeland, BJ (1996). "Lub koom txoos-turing thesis," hauv Stanford Encyclopaedia of Philosophy, ed E. Zalta. Muaj nyob online ntawm: http://plato.stanford.edu/

Copeland, BJ, thiab Proudfoot, D. (1999). Alan Turing lub tswv yim tsis nco qab hauv computer science. Sci. Am. 280, 76–81 : kuv. doi: 10.1038/scienticamerican0499-98 Demetrius, LA, thiab Tsav Tsheb, J. (2013). Alzheimer's raws li tus kab mob metabolic.

Biogerontology 14, 641–649. doi: 10.1007/s10522-013-9479-7

Jack Copeland, B. (2004). Qhov Tseem Ceeb Turing: Seminal Writings in Computing, Logic, Philosophy, Artificial Intelligence, thiab Artificial Life plus The Secrets of Enigma. Oxford: Clarendon Xovxwm; Oxford University Press. ISBN: 0-19- 825079-7.

Jia, G., Aroor, AR, Whaley-Connell, AT, and Sowers, JR (2014). Fructose thiab uric acid: puas muaj lub luag haujlwm hauv kev ua haujlwm endothelial? Curr. Hypertens. Ntawv Nkauj 16:434. doi: 10.1007/s11906-014-0434-z

Li, X., Shen, K., Huang, MC, and Chu, LA (2007). "Memory softerror measurement on production systems," in Proceeding of 2007 USENIX Annual Technical Conference (Santa Clara, CA), 275–280.

Maldonado, CE, and Gomez Cruz, NA (2015). Biological hypercomputation: qhov teeb meem tshawb fawb tshiab hauv txoj kev xav nyuaj. Kev nyuaj siab 20, 8–18. doi: 10.1002/cplx.21535

Muradian, K. (2013). "Pull thiab thawb rov qab" cov ntsiab lus ntawm kev ua neej ntev thiab kev ncua ntev. Biogerontology 14, 687–691. doi: 10.1007/s10522-013-9472-1

Obre, E., and Rossignol, R. (2015). Cov tswv yim tshiab hauv bioenergetics thiab kev tshawb fawb qog noj ntshav: metabolic yooj, coupling, symbiosis, hloov, oxidative qog, metabolic remodeling, signaling, thiab bioenergetic kho. Int. J. Biochem. Cell Bio. 59 Ib., 167–181. doi: 10.1016/j.biocel.2014.12.008

Shen, PS, Park, J., Qin, Y., Li, X., Parsawar, K., Larson, MH, et al. (2015). Protein synthesis. Rqc2p thiab 60S ribosomal subunits mediate mRNA-ywj siab

Kev lees paub

Cov kws sau ntawv tau ua tsaug rau qhov kev txhawb nqa dav dav los ntawm College of Science, George Mason University, thiab los ntawm Human Proteome Scientific Program ntawm Tsoom Fwv Teb Chaws Lub Koom Haum Saib Xyuas Kev Tshawb Fawb, Russia.

elongation ntawm nascent chains. Science 347, 75–78. doi: 10.1126/kev. 1259724 ib

Siegelmann, HT (1995). Kev suav dhau ntawm Turing txwv. Science 268, 545–548. doi: 10.1126/science.268.5210.545 ib.

Sudama, G., Zhang, J., Isbister, J., thiab Willett, JD (2013). Metabolic proling nyob rau hauv Caenorhabditis elegans muab txoj hauv kev tsis ncaj ncees rau kev tshawb xyuas ntawm kev siv tshuaj ntau npaum li cas ntawm cov hlau lead toxicity. Metabolomics 9, 189–201. doi: 10.1007/s11306- 012-0438-0

Tacutu, R., Budovsky, A., Wolfson, M., thiab Fraifeld, VE (2010). MicroRNA- tswj kev sib txuas ntawm cov protein-protein sib txuas: lawv yuav pab tau li cas hauv kev tshawb nrhiav cov hom phiaj ntev? Rejuvenation Res. 13, 373–377, ib. doi: 10.1089/rej.2009.0980

Turing, A. (1936). Ntawm cov lej suav nrog, nrog rau daim ntawv thov rau entschei- dungsproblem. Proc. Lod. lej. Soc. 42, 230–265 : kuv.

Willett, JD, Podugu, N., Sudama, G., Kopecky, JJ, and Isbister, J. (2010). Kev siv cov kev ntxhov siab txias rau hnub nyoog fractionate Caenorhabditis elegans: cov txheej txheem yooj yim pheej yig. J. Gerontol. Ib Biol. Sci. Med. Sci. 65:457–467. doi: 10.1093/gerona/glq036

Ziegler, JF, thiab Lanford, WA (1979). Eect ntawm cosmic rays ntawm lub computer nco. Science 206, 776–788. doi: 10.1126/science.206.4420.776 ib.

Conict of Interest Statement: Cov kws sau ntawv tshaj tawm tias qhov kev tshawb fawb tau ua thaum tsis muaj kev lag luam lossis kev sib raug zoo ntawm nyiaj txiag uas tuaj yeem txhais tau tias muaj peev xwm ua rau muaj kev txaus siab.