The starvation hormone, fibroblast growth factor-21, extends lifespan in mice

7/31/2019 The starvation hormone, fibroblast growth factor-21, extends lifespan in mice

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4Nivdr~jih~ g Vbdrjdcgmge|- Yhlqirsl~| g îds Sgy~buis~irh Jinlcdm Cih~ir-Ndmmds- Yhl~in S~d~is; ?Nivdr~jih~ g Cmlhlcdm Sclihcis- Yhlqirsl~| g îdsSgy~buis~irh Jinlcdm Cih~ir- Ndmmds- Yhl~in S~d~is; 3B|vg~bdmdjlc _isidrcb-Yhlqirsl~| g îds Sgy~buis~irh Jinlcdm Cih~ir- Ndmmds- Yhl~in S~d~is; >Nivdr~jih~g Vbdrjdcgmge|- Bgudrn Byebis Jinlcdm Lhs~l~y~i- Yhlqirsl~| g îdsSgy~buis~irh Jinlcdm Cih~ir- Ndmmds- Yhl~in S~d~is; 9Dnqdhcin Ljdelhe _isidrcbCih~ir- Yhlqirsl~| g îds Sgy~buis~irh Jinlcdm Cih~ir- Ndmmds- Yhl~in S~d~is;1

Eihi Ivrisslgh Mdogrd~gr|- Bgudrn Byebis Jinlcdm Lhs~l~y~i- Sdmk Lhs~l~y~i grOlgmgelcdm S~ynlis- Sdh Nlieg- Yhl~in S~d~is; 5Nivdr~jih~s g Jgmicymdr Olgmge| dhnVbdrjdcgmge|- Yhlqirsl~| g îds Sgy~buis~irh Jinlcdm Cih~ir- Ndmmds- Yhl~in S~d~is

Dos~rdc~ Alorgomds~ ergu~b dc~gr*?4 "AEA?4, ls d bgrjghi sicri~in o| ~bi mlqir nyrlhe ds~lhe~bd~ imlcl~s nlqirsi dsvic~s g ~bi dndv~lqi s~drqd~lgh risvghsi( Djghe l~s iic~s- AEA?4 lhnycis

bivd~lc d~~| dcln glnd~lgh dhn ki~geihisls- lhcridsis lhsymlh sihsl~lql~|- omgcks sgjd~lc ergu~b dhn

cdysis oghi mgss( Biri ui sbgu ~bd~ ~rdhseihlc gqirivrisslgh g AEA?4 jdrkinm| i~ihns

mlisvdh lh jlci ul~bgy~ rinyclhe ggn lh~dki gr dic~lhe jdrkirs g HDN+ ji~dogmlsj gr DJV

klhdsi dhn j^G_ slehdmlhe( rdhscrlv~gjlc dhdm|sls syeeis~s ~bd~ AEA?4 dc~s vrljdrlm| o| omyh~lhe

~bi ergu~b bgrjghi'lhsymlh*mlki ergu~b dc~gr*4 slehdmlhe vd~bud| lh mlqir( bisi ahnlhes rdlsi ~bi

vgsslolml~| ~bd~ AEA?4 cdh oi ysin ~g i~ihn mlisvdh lh g~bir sviclis(NGL0 46(599>'iMli(66619(664

Lh~rgnyc~lghCdmgrlc ris~rlc~lgh ul~bgy~ jdmhy~rl~lgh ls d vrgqih jidhs g lhblol~lhe delhe lh sviclis rdhelhe rgj

ugrjs ~g hghbyjdh vrljd~is "Jdsgrg- ?669; Olsbgv dhn Eydrih~i- ?665; Kih|gh- ?646,( ^bi

iic~ g cdmgrlc ris~rlc~lgh gh mgheiql~| dvvidrs ~g oi jinld~in o| jym~lvmi hy~rlih~*sihslhe vd~bud|s

lhcmynlhe ~bgsi lhqgmqlhe lhsymlh dhn lhsymlh*mlki ergu~b dc~gr "LEA*4,- ~drei~ g rdvdj|clh "^G_,- DJV

klhdsi dhn slr~ylhs( Vbdrjdcgmgelc dhn'gr eihi~lc jdhlvymd~lgh g ~bisi vd~bud|s lhcridsis mgheiql~|

~g qdr|lhe nieriis- syeeis~lhe ~bi idslolml~| g nryes ~bd~ lhcridsi mlisvdh lh ~bi dosihci g cdmgrlc

ris~rlc~lgh "Olsbgv dhn Eydrih~i- ?665; Kih|gh- ?646; Odrplmdl i~ dm(- ?64?,(

Alorgomds~ ergu~b dc~gr*?4 "AEA?4, ls dh d~|vlcdm AEA ~bd~ yhc~lghs ds dh ihngcrlhi bgrjghi"Vg~~bgaa i~ dm(- ?64?,( Lh jlci- AEA?4 ls s~rghem| lhnycin lh mlqir lh risvghsi ~g vrgmghein ds~s

~brgyeb d virglsgji vrgmlird~gr*dc~lqd~in riciv~gr *nivihnih~ jicbdhlsj( AEA?4 lh ~yrh imlcl~s

nlqirsi dsvic~s g ~bi dndv~lqi s~drqd~lgh risvghsi( Djghe ~bisi- AEA?4 lhcridsis lhsymlh sihsl~lql~|

dhn cdysis d cgrrisvghnlhe nicridsi lh odsdm lhsymlh cghcih~rd~lghs; AEA?4 lhcridsis bivd~lc d~~|

dcln glnd~lgh- ki~geihisls dhn emycghigeihisls; dhn- AEA?4 sihsl~lpis jlci ~g ~grvgr- d bloirhd~lgh

mlki s~d~i g rinycin ogn| ~ijvird~yri dhn vb|slcdm dc~lql~| "Vg~~bgaa i~ dm(- ?64?,( AEA?4 dmsg omgcks

sgjd~lc ergu~b o| cdyslhe EB risls~dhci- d vbihgjihgh dssgcld~in ul~b s~drqd~lgh( ^rdhseihlc "ê

jlci gqirivrisslhe AEA?4 dri jdrkinm| sjdmmir ~bdh ulmn*~|vi jlci dhn bdqi d cgrrisvghnlhe

nicridsi lh clrcymd~lhe LEA*4 cghcih~rd~lghs nisvl~i bdqlhe imiqd~in ergu~b bgrjghi "EB, miqims

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http://elife.elifesciences.org/http://dx.doi.org/10.7554/elife.00065http://dx.doi.org/10.7554/elife.00065.001http://creativecommons.org/licenses/by/3.0/http://creativecommons.org/licenses/by/3.0/http://creativecommons.org/licenses/by/3.0/http://creativecommons.org/licenses/by/3.0/http://dx.doi.org/10.7554/elife.00065.001http://dx.doi.org/10.7554/elife.00065http://creativecommons.org/licenses/by/3.0/http://www.elifesciences.org/the-journal/open-access/http://elife.elifesciences.org/


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3/14

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_isidrcb dr~lcmi

vircih~ d~ dhn midh jdss "Aleyri 4I-A,( Dccgrnlhem|- vmdsjd miv~lh miqims uiri hg~ slehlcdh~m|

cbdhein lh AEA?4*ê jlci "^domi 4,( Vmdsjd dnlvghic~lh cghcih~rd~lghs uiri slehlcdh~m| blebir lh

jdmi AEA?4*ê jlci "^domi 4,- ul~b lhcridsis lh og~b ~bi jghgjirlc dhn jgri dc~lqi gmlegjirlc

grjs "Aleyri 4E,( biri uds hg slehlcdh~ cbdhei lh il~bir ~bi ~g~dm djgyh~ gr ~bi nlirih~ grjs g

dnlvghic~lh lh ijdmis "^domi 4- Aleyri 4E,( Vmdsjd ki~ghi ogn| miqims uiri slehlcdh~m| blebir lh

ijdmi oy~ hg~ jdmi AEA?4*ê jlci " domi 4,( Bivd~lc ~rlem|irlni cghcih~rd~lghs uiri mguir lh ijdmi

oy~ hg~ jdmi AEA?4*ê jlci " domi 4,( Vmdsjd dhn bivd~lc cbgmis~irgm cghcih~rd~lghs uiri yhcbdhein

lh AEA?4*ê jlci "^domi 4,( Ds ivic~in "Uil i~ dm(- ?64?,- AEA?4*ê jlci bdn rinycin oghi jdss

"Aleyri 4B,(Ui hi~ idjlhin emycgsi bgjigs~dsls lh gmnir jlci( Yhnir > br ds~in cghnl~lghs- vmdsjd emy*

cgsi cghcih~rd~lghs uiri mguir lh og~b jdmi dhn ijdmi AEA?4*ê jlci- ublmi vmdsjd lhsymlh cghcih

~rd~lghs uiri slehlcdh~m| mguir lh jdmi AEA?4*ê jlci "^domi 4,( Vmdsjd LEA*4 cghcih~rd~lghs uiri

dmsg mguir lh og~b jdmi dhn ijdmi AEA?4*ê jlci- ul~b ~bi nicridsi vdr~lcymdrm| s~rlklhe lh ijdmis

"^domi 4,( Lh grdm emycgsi ~gmirdhci ~is~s nghi lh jlci ds~in gr 41 br- ~biri uds hg nlirihci lh

emycgsi icyrslgh oi~uiih ulmn*~|vi dhn AEA?4*ê jlci- oy~ ~bi AEA?4*ê jlci bdn slehlcdh~m|

mguir lhsymlh miqims lh risvghsi ~g ~bi emycgsi cbdmmihei "Aleyri ?D,( Lh lhsymlh ~gmirdhci ~is~s nghi lh

jdmi jlci ds~in gr > br- vmdsjd emycgsi cghcih~rd~lghs nicridsin jgri lh AEA?4*ê jlci ~bdh lh

ulmn*~|vi jlci "Aleyri ?O,(

^bisi nd~d syeeis~in ~bd~ ~bi AEA?4*ê jlci bdqi lhcridsin lhsymlh sihsl~lql~|( ^g dnnriss ~bls

nlric~m|- b|virlhsymlhijlc*iyem|cijlc cmdjv ivirljih~s uiri virgrjin( ^bi igeihgys emycgsi

lhyslgh rd~i ritylrin ~g jdlh~dlh iyem|cijld yhnir cmdjv cghnl~lghs uds jdrkinm| blebir lh AEA?4*ê

jlci ~bdh lh ulmn*~|vi jlci- nijghs~rd~lhe ihbdhcin ubgmi*ogn| lhsymlh sihsl~lql~| "Aleyri ?C,

Emycgsi ~rdcir klhi~lc dhdm|sls riqidmin ~bd~ lhsymlh*s~ljymd~in syvvrisslgh g bivd~lc emycgsi

vrgnyc~lgh dhn dc~lqd~lgh g ubgmi*ogn| emycgsi nlsvgsdm uiri slehlcdh~m| erid~ir lh AEA?4*ê jlci

~bdh lh ulmn*~|vi jlci "Aleyri ?N,( Cmdjv lhsymlh miqims uiri sljlmdr oi~uiih ulmn*~|vi dhn AEA?4*ê

jlci "5(6?(6 dhn 2(3?(3 he'jM- risvic~lqim|; hg~ slehlcdh~m| nlirih~,( gei~bir- ~bisi nd~d nij

ghs~rd~i ~bd~ emycgsi ~gmirdhci dhn ubgmi*ogn| lhsymlh sihsl~lql~| dri nrdjd~lcdmm| lhcridsin lh

AEA?4*ê jlci(

Elqih ~bi iic~s g mghe*~irj AEA?4 ivgsyri gh cdrogb|nrd~i dhn mlvln vdrdji~irs- isvicldmm|

lhsymlh dhn LEA*4 cghcih~rd~lghs- ui jidsyrin ~bi mlisvdh g AEA?4*ê jlci( Mgheiql~| uds slehl

cdh~m| i~ihnin lh AEA?4*ê jlci cgjvdrin ~g ulmn*~|vi ml~~irjd~is "bdpdrn rd~lg:6(?? [6(49- 6(3>Z

v:?(5i4?,- ul~b d 31) lhcridsi lh ~bi jinldh syrqlqdm ~lji gr AEA?4*ê jlci "Aleyri 3D,( Dm~bgyeb

~biri uds hg nlirihci lh mgheiql~| oi~uiih jdmi dhn ijdmi ulmn*~|vi jlci- ~bi nlirihci lh mlisvdh

oi~uiih jdmi dhn ijdmi AEA?4*ê jlci uds s~d~ls~lcdmm| slehlcdh~ "bdpdrn rd~lg:?(>? [4(35- >(?1Zv:6(66?3, "Aleyri 3O-C,( Cg vrgvgr~lghdm*bdpdrns rierisslgh dhdm|sls sbgus ~bd~ AEA?4 rinycin ~bi

rlsk g nid~b o| 19) lh jdmis "bdpdrn rd~lg:6(39 [6(?6- 6(16Z- v:6(66645, dhn 22) lh ijdmis "bdpdrn

rd~lg:6(4? [6(69> jgh~bs g dei(

Slhci AEA?4 ls lhnycin o| ds~lhe dhn imlcl~s nlqirsi dsvic~s g ~bi dndv~lqi s~drqd~lgh risvghsi

ui idjlhin ubi~bir cbrghlc AEA?4 ivgsyri jljlcs hy~rlih~ nivrlqd~lgh ul~b risvic~ ~g cbdheis lh

eihi ivrisslgh( Cgjvribihslqi ~rdhscrlv~gji dhdm|sls uds virgrjin o| jlcrgdrrd| yslhe _HD

rgj mlqir- eds~rgchijlys jyscmi dhn ivlnln|jdm ubl~i dnlvgsi ~lssyi g ulmn*~|vi dhn AEA?4*ê jlci

dhn jlci syoìc~in ~g il~bir cdmgrlc ris~rlc~lgh gr d ?> br ds~( Yslhe d dmsi nlscgqir| rd~i =6(46 dhn

gmn cbdhei 8? ds crl~irld- ui gyhn ~bd~ ivrisslgh g 33- 2 dhn ?? eihis uds cbdhein lh mlqir- jyscmi

dhn dnlvgsi g AEA?4*ê jlci- risvic~lqim| "Aleyri >D,( Jdh| jgri eihis uiri rieymd~in o| cdmgrlc

ris~rlc~lgh gr ds~lhe ~bdh o| ~bi AEA?4 ~rdhseihi lh dmm ~brii ~lssyis( Ds ivic~in- Aea?4 uds s~rghem|lhnycin lh mlqir o| ds~lhe( Syrvrlslhem|- bguiqir- Aea?4 uds hg~ lhnycin o| ~bi cdmgrlc ris~rlc~lgh riel

jih "Aleyri >O,( Mlkiulsi- ~biri uds hg lhcridsi lh vmdsjd AEA?4 cghcih~rd~lghs lh risvghsi ~g

cdmgrlc ris~rlc~lgh "nd~d hg~ sbguh,( Ublmi ~bi jgmicymdr odsls gr ~bls nlirih~ldm rieymd~lgh gAea?4

o| ds~lhe dhn cdmgrlc ris~rlc~lgh ls hg~ |i~ khguh- ~bisi nd~d lhnlcd~i ~bd~ AEA?4 ls hg~ dh ihnge

ihgys jinld~gr g ~bi cdmgrlc ris~rlc~lgh risvghsi( Hg~dom|- 36 g ~bi 33 eihis ul~b cbdhein ivris

slgh lh mlqir g AEA?4*ê jlci uiri dmsg rieymd~in o| cdmgrlc ris~rlc~lgh- ublmi ?6 g ~bisi eihis uiri

rieymd~in o| ds~lhe "Aleyri >O,( Ileb~ g ~bi eihis ul~b dm~irin ivrisslgh lh mlqir g AEA?4*ê jlci

"blebmleb~in lh rin lh Aleyri >O; sii Nlscysslgh, dri sljlmdrm| rieymd~in lh mghe*mlqin nudr jlci

"Sulhnimm- ?665,( Lh cgh~rds~- ~biri uds ml~~mi gqirmdv lh eihis rieymd~in o| AEA?4 dhn il~bir cdmgrlc
http://dx.doi.org/10.7554/elife.00065http://dx.doi.org/10.7554/elife.00065


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Pbdhe i~ dm( iMlai ?64?;40i66619( NGL0 46(599>'iMlai(66619 > ga 4>

_isidrcb dr~lcmi

Aleyri 4( Ji~dogmlc vdrdji~irs lh delhe ulmn~|vi dhn AEA?4~rdhseihlc jlci( "D, Aggn lh~dki- "O, vb|slcdm

dc~lql~|- lhcmynlhe ~g~dm bgrlpgh~dm dhn djoymd~gr| dc~lql~|- "C, risvlrd~gr| icbdhei rd~lg "QCG?'QG?, dhn "N, g|eih

cghsyjv~lgh "QG?, nd~d gr 36jgh~bgmn jdmi ulmn~|vi "U^, dhn AEA?4~rdhseihlc "ê, jlci "h:1'ergyv, bgysin

slhem| lh ji~dogmlc cdeis( Agr "N,- ~bi drid yhnir ~bi cyrqi "DYC, nd~d dri sbguh lh ~bi rleb~ vdhim( "I, Ogn|

uileb~s g jdmi dhn ijdmi jlci jidsyrin d~ 1- 4? dhn ?1 jgh~bs( Jidsyrijih~s uiri nghi gh dmm syrqlqlhe jlci

lh ~bi cgbgr~s "h:?59>'ergyv,( "A, Ad~ dhn midh jdss vircih~deis uiri jidsyrin lh ?1jgh~bgmn jlci "h:91'ergyv,( "E, Dnlvghic~lh gmlegjir grjs- lhcmynlhe bleb jgmicymdr uileb~ "BJU,- jinlyj jgmicymdr uileb~

"JJU, dhn mgu jgmicymdr uileb~ "MJU, grjs- uiri jidsyrin lh vmdsjd rgj ?1 ~g ?5jgh~bgmn jdmi dhn

ijdmi U^ dhn AEA?4ê jlci( _ivrisih~d~lqi uis~irh omg~s yslhe vmdsjd rgj slhemi dhljdms dri sbguh ~gei~bi

ul~b ~bi rd~lgs g ~bi nlirih~ dnlvghic~lh grjs lh AEA?4ê dhn U^ vmdsjd "h:>'ergyv,( "B, Tydh~lacd~lgh g

~rdoicymdr oghi qgmyji o| C^ dhdm|sls yslhe ~loldi rgj 33 ~g 39jgh~bgmn jdmi U^ dhn AEA?4ê jlci

"h:>9'ergyv,( Dmm nd~d dri vrisih~in ds ~bi jidh SIJ(

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http://dx.doi.org/10.7554/elife.00065http://dx.doi.org/10.7554/elife.00065.003http://dx.doi.org/10.7554/elife.00065.003http://dx.doi.org/10.7554/elife.00065


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_isidrcb dr~lcmi

ris~rlc~lgh gr ds~lhe lh jyscmi gr dnlvgsi( ^bisi nd~d syeeis~ ~bd~ AEA?4 jd| i~ihn mlisvdh o|

rieymd~lhe d sjdmm syosi~ g eihis dmsg rieymd~in o| cdmgrlc ris~rlc~lgh lh mlqir(

Lhcridsis lh DJV klhdsi dhn slr~ylh dc~lql~| dhn nicridsis lh j^G_ dc~lql~| dri dssgcld~in ul~b

lhcridsin mgheiql~| "Olsbgv dhn Eydrih~i- ?665; Kih|gh- ?646,( g oielh ~g dssiss ubi~bir ~bisi

vd~bud|s dri dic~in o| AEA?4- ui jidsyrin vbgsvbgr|md~in dhn ~g~dm miqims g DJV klhdsi dhn

~bi j^G_ ~drei~s S1 dhn >I*OV4lh mlqir- jyscmi dhn dnlvgsi ~lssyi g jdmi dhn ijdmi ulmn*~|vi dhn

AEA?4*ê jlci( Ui dmsg ni~irjlhin jl~gcbghnrldm NHD cgh~ih~ lh mlqir ds d nguhs~ridj jidsyri

g DJV klhdsi dc~lql~|( Vbgsvbg*DJV klhdsi miqims uiri hg~ lhcridsin lh ~lssyis rgj AEA?4*ê jlci

"Aleyri 9DC,( Cghsls~ih~ ul~b ~bisi nd~d- jl~gcbghnrldm NHD cgh~ih~ uds yhcbdhein lh mlqi

"Aleyri 9N,( Ublmi Vbgsvbg*S1 dhn vbgsvbg*>I*OV4 miqims uiri nicridsin lh jyscmi g jdmi

AEA?4*ê jlci "Aleyri 9O,- ~bi| uiri yhcbdhein lh jyscmi g mgheir*mlqin AEA?4*ê ijdmis gr lh

mlqir gr dnlvgsi rgj il~bir si "Aleyri 9DC,( Ui dmsg nln hg~ gosirqi lhcridsis lh HDN+ cghcih

~rd~lghs "Aleyri 9I, gr ~bi j_HD miqims g Slr~ylhs 45 "nd~d hg~ sbguh, lh mlqir g AEA?4*ê jlci

syeeis~lhe ~bd~ slr~ylh dc~lql~| ls yhmlkim| ~g oi lhcridsin( ^dkih ~gei~bir- ~bisi nd~d syeeis~ ~bd~

AEA?4 jd| lhcridsi mgheiql~| ~brgyeb d jicbdhlsj lhnivihnih~ g ~bi DJV klhdsi- j^G_ dhn

slr~ylh vd~bud|s(

NlscysslghLh ~bls rivgr~- ui nijghs~rd~i ~bd~ cbrghlc ivgsyri g jlci ~g ~bi s~drqd~lgh bgrjghi- AEA?4

lhcridsis jinldh syrqlqdm ~lji o| x36) dhn x>6) lh jdmis dhn ijdmis- risvic~lqim|- ul~bgy~ nicrids

lhe ggn lh~dki( bi lhcridsi lh mlisvdh i~ihslgh ls cgjvdrdomi ~g ~bd~ dcbliqin o| cdmgrlc ris~rlc~lgh

"^yr~yrrg i~ dm(- 4(4>4(6< 6(99 >(264(2? 5(>1?(2< 6(>5

rlem|cirlnis "je'nM, 59(4>(?(656(?6 6(54 >(9?6(?? >(9>6(43 6(

Jidsyrijih~s uiri jdni yslhe ?1?5jgh~bgmn jlci "h:>9 jlci'ergyv,(

*> br ds~lhe nd~d(

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_isidrcb dr~lcmi

Aleyri ?( AEA?4~rdhseihlc jlci bdqi lhcridsin lhsymlh sihsl~lql~|( ?1?5jgh~bgmn ulmn~|vi "U^, dhn AEA?4

~rdhseihlc "ê, jdmi dhn ijdmi jlci "h:9'ergyv, uiri syoìc~in ~g "D, grdm emycgsi ~gmirdhci ~is~s gr "O, lhsymlh

~gmirdhci ~is~s( Vmdsjd emycgsi dhn lhsymlh miqims uiri jidsyrin ds lhnlcd~in( Tydh~lacd~lgh g ~bi drid yhnir ~bi

cyrqi "DYC, ls sbguh lh ~bi vdhims ~g ~bi rleb~( "C- N, B|virlhsymlhijlciyem|cijlc cmdjv s~ynlis uiri virgrjin

gh 1 ~g 2jgh~bgmn jdmi U^ dhn AEA?4ê jlci "h:1'ergyv,( Lhsymlh uds lhysin d~ ? jY'ke'jlh dhn "C, omggn

emycgsi "yvvir vdhim, uds cmdjvin d~ 4?6 je'nM nyrlhe ~bi s~idn|s~d~i virlgn "~:446496 jlh, yslhe d qdrldomi

emycgsi lhyslgh rd~i "mguir vdhim,( ^bi emycgsi lhyslgh rd~i lh AEA?4ê jlci ls s~d~ls~lcdmm| nlirih~ "v=6(69,

rgj U^ jlci d~ dmm vglh~s d~ir ~:6 jlh( "N, _d~is g bivd~lc emycgsi vrgnyc~lgh "yvvir vdhim, dhn ubgmiogn|

emycgsi nlsvgsdm "mguir vdhim, lh U^ "h:1, dhn AEA?4ê "h:3, jlci nyrlhe ~bi odsdm dhn s~idn|s~d~i virlgns g

~bi cmdjv(

NGL0 46(599>'iMli(66619(669


7/14



_isidrcb dr~lcmi

jlci- sycb ds lhcridsin dnlvgsl~| lh EB riciv~gr*khgckgy~ jlci "Jds~irhdk i~ dm(- ?64?,- dri hg~ricdvl~ymd~in lh AEA?4*^e jlci(

Lh jlcrgdrrd| s~ynlis- AEA?4 jgnymd~in jgri eihis lh mlqir ~bdh lh il~bir jyscmi gr dnlvgsi

Lh~iris~lhem|- hidrm| dmm g ~bisi bivd~lc eihis "36 g 33, uiri sljlmdrm| rieymd~in o| cdmgrlc ris~rlc~lgh

d vrgqih ji~bgn g i~ihnlhe mlisvdh lh jlci dhn g~bir sviclis "Jdsgrg- ?669; Olsbgv dhn

Eydrih~i- ?665; Kih|gh- ?646,( Lh cgh~rds~- ~biri uds ml~~mi gr hg gqirmdv lh ~bi eihis rieymd~in o|

AEA?4 dhn cdmgrlc ris~rlc~lgh lh jyscmi gr dnlvgsi( D rijdrkdomi risym~ g gyr s~ynlis ls ~bd~ AEA?4

lhcridsin mgheiql~| ~g d sljlmdr i~ih~ ds cdmgrlc ris~rlc~lgh ublmi rieymd~lhe d jycb sjdmmir si~ g

eihis lh mlqir( ^bisi nd~d syeeis~ ~bd~ AEA?4 jd| i~ihn mlisvdh o| dc~lhe ds d simic~lqi cdmgrlc

ris~rlc~lgh jlji~lc lh mlqir( Dh ljvgr~dh~ cdqid~- bguiqir- ls ~bd~ ~biri jd| oi cbdheis lh g~bir ~lssyis

Aleyri 3( AEA?4 i~ihns mlisvdh( "DC, KdvmdhJi|ir syrqlqdm cyrqis gr ulmn~|vi "U^, dhn AEA?4~rdhseihlc

"^e, jlci dri sbguh( "D, Cgjolhin jdmi dhn ijdmi nd~d; "O, jdmi nd~d; "C, ijdmi nd~d( "N, Jinldh syrqlqdm ~lji

"d~ 96~b vircih~lmi, dhn jdljyj mlisvdh "d~


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_isidrcb dr~lcmi

gr vgs~*~rdhscrlv~lghdm cbdheis ~bd~ uiri jlssin lh ~bls dhdm|sls( Ui hg~i ~bd~ cdmgrlc ris~rlc~lgh

nln hg~ lhcridsi clrcymd~lhe AEA?4 miqims- lhnlcd~lhe ~bd~ ihngeihgys AEA?4 ngis hg~ jinld~i ~bi

mgheiql~| iic~s g cdmgrlc ris~rlc~lgh(

Yslhe jlcrgdrrd| dhdm|sls- Sulhnimm "?665,vriqlgysm| nihin d si~ g >3 cdhnlnd~i mgheiql~| eihis

odsin yvgh ~bilr sljlmdr rieymd~lgh lh nlirih~ nudr jgysi s~rdlhs gr oi~uiih nudr s~rdlhs dhn

cdmgrlc ris~rlc~lgh( Ileb~ g ~bisi eihis "Ajg3- Leadms- Bis1- Dmds?- C|v>d4?o- Jyv>- Sirvlhd4?Bsn3o9, dri djghe ~bgsi cg*rieymd~in o| AEA?4 dhn cdmgrlc ris~rlc~lgh lh mlqir lh gyr cyrrih~ s~yn|

dhn gyr g~birs "Lea4- Leaov4- Sgcs?dhn Jyv3, uiri vriqlgysm| sbguh o| jgri sihsl~lqi tydh~l~d~lqi

ridm*~lji VC_ ~g oi rieymd~in lh mlqir g AEA?4*ê jlci "Lhdedkl i~ dm(- ?662,( S~rlklhem|- ?1 g ~bi 33

eihis rieymd~in o| AEA?4 lh mlqir uiri vriqlgysm| sbguh ~g oi rieymd~in lh d sljlmdr jdhhir lh jlci

mdcklhe S^D^9 dc~lql~| "Odrcmd| i~ dm(- ?644,( ^bys- AEA?4 jd| lhcridsi mgheiql~| o| syvvrisslhe ~bi

EB slehdmlhe dls lh mlqir lh d jdhhir sljlmdr ~g ~bd~ g cdmgrlc ris~rlc~lgh( Lh~iris~lhem|- EB lhnycis

AEA?4 lh mlqir ~brgyeb d S^D^9*nivihnih~ jicbdhlsj "Odrcmd| i~ dm(- ?644; Cbih i~ dm(- ?644

\y i~ dm(- ?64?,( ^bls rieymd~gr| rimd~lghsblv oi~uiih EB dhn AEA?4 ls m lkim| ~g oi ljvgr~dh~ lh cgh

~rgmmlhe EB dc~lql~| dhn cggrnlhd~lhe ihire| bgjigs~dsls nyrlhe s~drqd~lgh(

Aleyri >( Eihis rieymd~in o| AEA?4 dhn cdmgrlc ris~rlc~lgh gqirmdv lh mlqir( "D, Qihh nlderdjs sbgulhe gqirmdv g

eihis slehlacdh~m| rieymd~in lh mlqir- jyscmi dhn dnlvgsi ~lssyi g AEA?4~rdhseihlc "ê, qs ulmn~|vi "U^, jlci

"AN_=6(46- 8~uggmn rieymd~lgh, cgjvdrin ~g ~bi sdji eihi ivrisslgh dhdm|sls lh cdmgrlcdmm| ris~rlc~in "C_, qs dn

mlol~yj "DM, gr ds~in qs DM jlci( "O, Bid~ jdv g eihis slehlacdh~m| rieymd~in lh mlqir g AEA?4ê qs U^

"AN_=6(46- 8~uggmn rieymd~lgh, cgjvdrin ~g ivrisslgh g ~bi sdji mlqir eihi si~ rieymd~in o| ds~lhe gr C_(

Jlcrgdrrd| dhdm|sls uds virgrjin yslhe mlqir- ivlnln|jdm ubl~i dnlvgsi ~lssyi dhn eds~rgchijlys jyscmi rgj

ulmn~|vi dhn AEA?4ê jdmi jlci dhn jdmi C95OM'1@ jlci syoìc~in ~g 16) cdmgrlc ris~rlc~lgh gr ? uiiks gr d

?> br ds~( Dmm jlci ysin lh ~bisi s~ynlis uiri 3 jgh~bs gmn d~ ~bi ihn g ~bi s~yn|(

NGL0 46(599>'iMli(66619(665


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Pbdhe i~ dm( iMlai ?64?;40i66619( NGL0 46(599>'iMlai(66619 < ga 4>

_isidrcb dr~lcmi

^bi dolml~| ~g lhcridsi mlisvdh dnns ~g d ergulhe mls~ g g~bir oihicldm iic~s ~bd~ vbdrjdcgmgelc

dnjlhls~rd~lgh g AEA?4 bds lh jdjjdms- lhcmynlhe lhsymlh sihsl~lpd~lgh- hgrjdmlpd~lgh g em|cijld

dhn rinycin ogn| uileb~ lh goisi dhljdms "Vg~~bgaa i~ dm(- ?64?,( bisi d~~rloy~is bdqi jdni AEA?4

dh lh~rleylhe ~birdviy~lc ~drei~( Lh cgh~rds~ ~g ~bisi vgsl~lqi iic~s- bguiqir- ui vriqlgysm| sbguin

~bd~ |gyheir "=2*jgh~b*gmn, AEA?4*ê jlci dhn dnym~ jlci dnjlhls~irin ricgjolhdh~ AEA?4 g

4> nd|s bdqi rinycin oghi jdss "Uil i~ dm(- ?64?,( Lh gyr cyrrih~ s~yn|- sljlmdr rinyc~lghs lh oghi

jdss uiri siih lh gmnir jlci( ^bi AEA?4*nivihnih~ nicridsi lh oghi jdss ls cdysin lh vdr~ o| dh

lhcridsi lh ~bi nlirih~ld~lgh g jdrrgu dnlvgc|~is dhn cgrrisvghnlhe nicridsi lh gs~igomds~

nlirih~ld~lgh "Uil i~ dm(- ?64?,( Lh dnnl~lgh- AEA?4 lhblol~s EB dc~lgh nlric~m| d~ ~bi ergu~b vmd~i

"Uy i~ dm(- ?64?,- dhn mghe*mlqin VDVV*D*khgckgy~ jlci bdqi d nicridsi lh oghi jlhirdm nihsl~|" dhhir i~ dm(- ?662,- syeeis~lhe ~bd~ cbdheis lh EB'LEA*4 slehdmlhe dri dmsg mlkim| ~g oi lhqgmqin lh

AEA?4*lhnycin nicridsis lh oghi jdss( Ublmi l~ rijdlhs ~g oi ni~irjlhin ubi~bir AEA?4 cdysis

oghi mgss lh byjdhs- l~ ls mlkim| ~bd~ ~bls dnqirsi iic~ ulmm bdqi ~g oi gqircgji l AEA?4 ls ~g oi ysin

cmlhlcdmm| ~g cgjod~ delhe(

Lh syjjdr|- ui sbgu ~bd~ cbrghlc ivgsyri ~g AEA?4- d hd~yrdmm|*gccyrrlhe bgrjghi dhn vg~ih~

lhsymlh sihsl~lpir- jdrkinm| i~ihns mlisvdh lh jlci ~brgyeb d jicbdhlsj ~bd~ jd| lhqgmqi syvvrisslgh

g ~bi EB'LEA*4 slehdmlhe dls lh mlqir( _iedrnlhe g~bir bgrjghis ~bd~ lhayihci mlisvdh- ui hg~i ~bd~

~bi i~rdcimmymdr ngjdlh g Kmg~bg- d jijordhi vrg~ilh ~bd~ rieymd~is vbgsvbd~i ji~dogmlsj dhn

sirqis ds d cg*riciv~gr gr AEA?3 oy~ hg~ AEA?4- cdh oi cmidqin ~g |limn d clrcymd~lhe viv~lni ~bd~

Aleyri 9( Iqdmyd~lgh g jdrkirs g DJV klhdsi- j^G_ dhn slr~ylh vd~bud| dc~lql~| lh AEA?4ê jlci( Vbgsvbgr|md~in miqims g DJV klhdsi- S1- dhn

>IOV4 lh "D, mlqir- "O, eds~rgchijlys jyscmi- dhn "C, ivlnln|jdm ubl~i dnlvgsi ~lssyi; "N, jl~gcbghnrldm NHD cgh~ih~ dhn "I, HDN+ cghcih~rd~lghs lh

mlqir g ?1?2jgh~bgmn jdmi dhn ijdmi ulmn~|vi "U^, dhn AEA?4~rdhseihlc "ê, jlci "h:>'ergyv iciv~ gr ijdmi dnlvgsi ~lssyi- ubiri h:?'

ergyv; dmm nd~d dri vrisih~in ds ~bi jidh SIJ; *v=6(69,(

NGL0 46(599>'iMli(66619(662


10/14



_isidrcb dr~lcmi

omgcks lhsymlh dhn LEA*4 slehdmlhe( bls bgrjghdm dc~lql~| jd| cgh~rloy~i ~g Kmg~bgs mlisvdh*i~ihnlhe

iic~ lh jlci "Kyrgsy i~ dm(- ?669,( Bguiqir- yhmlki AEA?4- Kmg~bg cdysis lhsymlh risls~dhci- ublcb

jd| mljl~ l~s y~lml~| ds d ~birdviy~lc deih~( Ui cghcmyni ~bd~ AEA?4 cgymn vg~ih~ldmm| oi ysin ds d

bgrjghi ~birdv| ~g i~ihn mlisvdh lh jdjjdms(

Jd~irldms dhn ji~bgns

Dhljdm ivirljih~s

AEA?4*^e jlci dhn ulmn*~|vi ml~~irjd~is "Lhdedkl i~ dm(- ?665, uiri jdlh~dlhin gh C95Om'1@ odckergyhn lh d sviclc*vd~bgeih*rii dclml~| ul~b 4?04? mleb~0ndrk c|cmi- dhn in ?


11/14



_isidrcb dr~lcmi

emycgsi ~yrhgqir( Omggn sdjvmis uiri go~dlhin rgj ~bi cy~ ~dlm d~ ~:49 dhn 9 jlh gr ~bi jidsyri

jih~ g odsdm omggn emycgsi "Dmvbd^_DK emycgji~ir- Doog~~- Cblcdeg- LM,( D~ ~:6 jlh- d vrljin

cgh~lhygys lhyslgh g lhsymlh "1 jY + ?(6jY'ke'jlh; Byjymlh, uds s~dr~in ~g lhnyci b|virlhsymlhijld

dhn ~bi [3*3BZemycgsi lhyslgh rd~i uds ngyomin "6(4 Cl'jlh, ~g jlhljlpi dm~ird~lghs lh sviclc dc~lql~|

Omggn emycgsi uds jidsyrin iqir| 46 jlh ~birid~ir- ublmi 96) ni~rgsi uds lhysin d~ d qdrldomi

rd~i ~g jdlh~dlh ~drei~ em|cijlc miqims d~ 4?6 je'nM( Emycgsi ~yrhgqir uds cdmcymd~in nyrlhe ~bi odsd

"~:49 ~g 9 jlh, dhn s~idn|*s~d~i "~:446496 jlh, virlgns g ~bi cmdjv yslhe S~iimis s~idn|*s~d~i

ityd~lgh "S~iimi i~ dm(- 46 ul~b Cgjvmi~i vrg~idsi lhblol~gr cgck~dlm "_gcbi nldehgs~lcs,

36 je g ubgmi mlqir m|sd~i uds risgmqin gh d SNS*vgm|dcr|mdjlni eims dhn imic~rg~rdhsirrin ~g d

VQNA jijordhi "Djirsbdj,( ^bi jijordhi uds ~bih b|orlnlpin ul~b dh~lognlis dedlhs~ ~g~d

DJVK- vbgsvbg*DJVK "^45?,- ~g~dm S1 dhn vbgsvbg*S1 "S?>6'?>>, "Cimm Slehdmlhe, dhn ~g~dm dhn

vbgsvbg*>I*OV4 "^56, "Cimm Slehdmlhe,( Vrg~ilh uds ni~ic~in o| cbijlmyjlhiscihci "ICM kl~Djirsbdj,( _isym~s uiri tydh~lin o| nihsl~gji~r| yslhe Ljdei@ Sg~udri "HLB,(

Jl~gcbghnrldm NHD cgh~ih~Eihgjlc NHD uds lsgmd~in rgj mlqir yslhe d NHids| Omggn dhn ^lssyi kl~ "Tldeih,( ^bi jl~gcbgh*

nrldm eihi CGR*4 uds jidsyrin o| tydh~l~d~lqi ridm*~lji VC_ ul~b *emgolh ysin ds d cgh~rgm ds

niscrloin "Sdblh i~ dm(- ?644,(

HDN+ jidsyrijih~sArgpih mlqir ~lssyis uiri i~rdc~in dhn HDN+ miqims uiri jidsyrin yslhe BVMC ds niscrloin "_djsi|

i~ dm(- ?66


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Pbdhe i~ dm( iMlai ?64?;40i66619( NGL0 46(599>'iMlai(66619 4? ga 4>

_isidrcb dr~lcmi

Dccisslgh hyjoirs^bi jlcrgdrrd| nd~d bdqi oiih nivgsl~in lh ~bi HCOL Eihi Ivrisslgh Gjhloys ul~b dccisslgh

hyjoir ESI3


13/14



_isidrcb dr~lcmi

_iirihcisD|dmd @I- Ordc| NV- JcEylhhiss GV- Udssirjdh NB( ?661( Cghslnird~lghs lh ~bi nisleh g b|virlhsymlhijlc*

iyem|cijlc cmdjvs lh ~bi cghsclgys jgysi( Nldoi~is990 3


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Pbdhe i~ dm( iMlai ?64?;40i66619( NGL0 46(599>'iMlai(66619 4> ga 4>

_isidrcb dr~lcmi

Jdsgrg I@( ?669( Gqirqliu g cdmgrlc ris~rlc~lgh dhn deilhe( Jicb Deilhe Niq4?10

The starvation hormone, fibroblast growth factor-21, extends lifespan in mice

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Transcript of The starvation hormone, fibroblast growth factor-21, extends lifespan in mice