enriched in mannoheptulose as a calorie r estriction mimetic · t err rab iologicals , ll c* ww w...

51
. D . h P , m a r g n I . K d l a n o D l a n o i t i r t u N , r o s s e f o r P g n i g A d n a e c n e i c s o r u e N y r o t a r o b a L n o t g n i n n e P r e t n e C h c r a e s e R l a c i d e m o i B m e t s y S y t i s r e v i n U e t a t S a n a i s i u o L a n a i s i u o L , e g u o R n o t a B , A S U , t n a t l u s n o C : S E R U S O L C S I D ; e l b m a G & r o t c o r P , r e d l o h e r a h S e c n e i c S o r e G , . c n I c n I . t c a r t x E o d a c o v A n a f o t n e m p o l e v e D n i d e h c i r n E e s o l u t p e h o n n a M a s a n o i t c i r t s e R e i r o l a C c i t e m i M

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Page 1: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

.D.hP ,margnI .K dlanoD lanoitirtuN ,rosseforP gnigA dna ecneicsorueN yrotarobaL

notgninneP retneC hcraeseR lacidemoiBmetsyS ytisrevinU etatS anaisiuoL

anaisiuoL ,eguoR notaB , ASU

,tnatlusnoC :SERUSOLCSID ;elbmaG & rotcorP ,redloherahS ecneicSoreG , .cnI cnI .

tcartxE odacovA na fo tnempoleveD ni dehcirnE esolutpehonnaM a sa

noitcirtseR eirolaC citemiM

Page 2: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

noitseuQ giB ehT

2

Page 3: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

!oN ti wols nac ew ,tuB

.tib doog a nwod 3

Page 4: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

:elpicnirP gnidiuGnoN ,tsuboR tsoM eht si noitcirtseR eirolaC - snaeM citeneG

dna napsefiL esaercnI ot napshtlaeH .

4

Page 5: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

shtnom ni EGA

morf detpadA hcurdnieW 9791 ,.la te

sromuT - lortnoCsromuT - RC

sa noitcirtseR eirolaC fo noitartsnomeD tsuboR

detalupinaM eb naC gnigA woH .

5

Page 6: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

RC fo serutaeF rojaMega fo tesno deyaled dna ecnedicni decudeR -

,recnac ,esaesid traeh gnidulcni ,sesaesid detalersesaesid evitarenegedoruen dna ,setebaid

decuder ,noitcnuf enummi devorpmI dna ,ecnatsiser sserts desaercni ,noitammalfni

efil ni retal ecnamrofrep laroivaheb retteb

6

Page 7: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

RC yrev sahstceffe tsubor

no dna napsefilnapshtlaeh .

? ?

Page 8: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

seidutS RC namuH dednuF AIN

retneC hcraeseR lacidemoiB notgninnePytisrevinU notgnihsaW

ytisrevinU stfuT

fo stceffE mreT gnoL eht fo tnemssessA evisneherpmoC ehT)EIRELAC( ygrenE fo ekatnI gnicudeR

8

Page 9: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

won saw xR RC eht fi nevE:noitseuq eht sgeb ti ,niatrec

od uoy dluoC ti?tnemnorivne hcir eirolac ruo ni

hsifwarC delioB hsiftaC deirF gnidduP daerB

enisiuC anaisiuoL

Page 10: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

noitseuQ evitanretlA ehT

poleved ew naC taht stnemtaert gniga wols gnikcimim yb eht laicifeneb fo stceffe htlaeh

noitcirtser eirolac gnitae ni egnahc a gniriuqer tuohtiw ?stibah

01

Page 11: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

,naciremA cifitneicS 42 :782 - 2002 ,92

11

Page 12: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

ehT fo tpecnoC RC scitemiM si decudortnI

itnA fo lanruoJ - 723 :1 enicideM gnigA - 8991 ,733

RC fo stceffe cilobatem niatrec cimiM edivorp dna syawhtap esnopser sserts etavitcA

noitcetorp ssertsekatni doof ecuder yltnacifingis ton oD

dna ytivegnol ecudorP napshtlaeh RC fo stceffeega fo noitcuder gnidulcni - esaesid detaler

,DVC( setebaid ,recnac .)

Page 13: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

2- GD

ygetartS : 2 esU - esoculgyxoed sa fo rotibihni evititepmoc a

ralullec msilobatem esoculg

2- esoculgyxoed

2- 6 esoculgyxoed - etahpsohp

2- esotcurf esoculgyxoed -6- etahpsohp

PTA

esaremosi esoculgohpsohP

esoculGretropsnarT

Page 14: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

evitavonnI ygetartS)sisylocylg( msilobatem esoculg tegraT

lleC

esoculg

!teid a no llec eht tup ,tceffe nI

41

Page 15: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

seidutS tnedoR ni stceffE GD2 fo yrammuS

erusserp doolb dna ,etar traeh ,erutarepmet ydob decudeRslevel nilusni amsalp decudeR

slevel esoculg amsalp ni noitcuder tsedom ro oNthgiew ydob dna ekatni doof ni noitcuder tsedom decudorP

yticixot laroivaheb tnerappa on daH tsniaga detcetorP yticixototicxe yb ciniak dica

yticixot PTPM tsniaga detcetorPekorts cimehcsi tsniaga detcetorP

detalugerpU 87PRG ;07PSH niarbdetalugerpU FNDB

ezis dna tesno romut decudeRYTICIXOT CAIDRAC DECUDORP TUB

Page 16: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

setisbeW hcetoiB fo hcraeseR ni degagnE seinapmoC noitcirtseR eirolaC no scitemiM

* tekraM eht no stcudorP htiW________________________________________________________________

emaN ynapmoC etisbeW________________________________________________________________

slacituecamrahP rekramoiB mth.emoh/lmth/moc.cnirekramoib.wwwnegonorhC negonorhc.www - moc.cni

rexilE slacituecamrahP moc.mrahprixile.wwwnirixilE *noitaroproC moc.nirixile.www

*hcraeseR avoNoreG moc.avonoreg.wwwyrevocsidoiB uzarI ten.yrevocsidoibuzari.www

*nonevuJ moc.nonevuj.www seigolonhceT neGefiL moc.hcetnegefil.www

*noitadnuoF noisnetxE efiL gro.fel.wwwslacituecamrahP sirtriS moc.amrahpsirtris.www

slacigoloiBarrreT *CLL , gro.eneganeb.wwwamrahParreT .cnI , moc.arretamrahp.www

Page 17: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

eirolaC noitcirtseR alumroF citemiM sedulcni lortarevser , eneblitsoretp ,nitecreuq dees eparg , slonehpylop ,

ot tcartxe aet kcalb dna neve edivorp noisserpxe eneg murtceps redaorb

.dnuopmoc lanoitirtun eno ni troppus ot nwohs neeb evah stneirtun esehT ni stceffe emas eht fo ynam etareneg

,noitcirtser cirolac sa ydob eht yrateid tnacifingis tuohtiw

pleh yeht ,ralucitrap nI .noitacifidom elbarovaf s’noitcirtser cirolac cimim

eht ecneulfni taht seneg no tcapmi .ssecorp gniga

71

noitcirtseR eirolaC scitemiM eradetekram gnieb yltnerruc

Page 18: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

noitcirtseR eirolaC etadidnaC scitemiMetadidnaC noitcA fo edoM

lortarevseR eneg 1TRIS etavitcAniutriS )sCATS( sdnuopmoC gnitavitcA etavitcA 1TRIS eneg

nimrofteM rezitisnes rotpecer nilusnInidanaxE ( editanaxe nogaculG ) - ekil p rotaludom editpe

nitcenopidA enikopiLnicymapaR ROTm tsinogatna

etatecaolaxO etaidemretni elcyc dica cirtiCetarticyxordyH stibihnI etarticosi esayl )noitisoped taf(edisomenmyG stibiihnI noitprosba esoculg

etatecaodoI enietsyc stibihnI esaditipep )esoculg ecuder(2- esoculgyxoed rotibihni citylocylg

esolutpehonnaM rotibihni citylocylg

Page 19: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

sirtriS ™slacituecamrahP si )TRIS :QADSAN( lacituecamrahpoib a yllaro ,yrateirporp gnipoleved dna gnirevocsid no desucof ynapmoc sesaesid taert ot laitnetop eht htiw sgurd elucelom llams ,elbaliava 2 epyT sa hcus sesaesid cilobatem gnidulcni ,gniga htiw detaicossa

.setebaiD niatrec cimim ot dengised era setadidnac gurd ruO a gniriuqer tuohtiw ,noitcirtser eirolac fo stceffe htlaeh laicifeneb

,stibah gnitae ni egnahc fo noitavitca yb sniutris yltnecer a , ehT .ssecorp gniga eht lortnoc taht semyzne fo ssalc derevocsid

.sttesuhcassaM ,egdirbmaC ni era sretrauqdaeh s'ynapmoc

Page 20: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

lortarevseR itna( nixelaotyhp cilonehpylop a si - .)dnuopmoc lagnuf.eneblits fo evitavired a ,dioneblis a si tI

Page 21: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

?maertsnwoD rO

?maertspu gnikooL

12

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:HM esolutpehonnaM

sisylocylG yawhtaP

22

Page 23: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

morf devired ragus A sa odacova epirnu

citemim RC a

esolutpehonnam

8.040.611.1)%( HM

5.58.012.12)%( taF

4.214.88.0)%( hsA

9.48.21.1)%( nietorP

2 tcartxE1 tcartxEodacovA ssaH

8.040.611.1)%( HM

5.58.012.12)%( taF

4.214.88.0)%( hsA

9.48.21.1)%( nietorP

2 tcartxE1 tcartxEodacovA ssaH odacovA saaH

Page 24: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

syaD ni egA

desaercnI snoitartnecnoc owt ta sperp odacova edurc def seilf tiurf fo lavivrus.)021=n( .thgiew yb

0

02

04

06

08

001

021

4 8 21 61 02 42 82 23 43 83 24 44 84 25 450

02

04

06

08

001

021

4 8 21 61 02 42 82 23 43 83 24 44 84 25 45

skeew ni egA

lortnoC

%5.0

%0.2

lavivruS tnecreP

noitaraperP odacovA edurC I sesaercn L napsefi

ylF tiurF eht ni

Page 25: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

amsalP teid lortnoc def ecim .sv tcartxe vA htiw detnemelppus teid def ecim J6/LB75C elam ni HM

0

5

01

51

02

52

03

53

NOC tcartxE vA tcartxE vA NOC

lm/g

m noitartnecnoC

HM

tcartxE vA NOC

era eciM nehw doolB eht otni debrosbA si HM

tcartxE odacovA deF

Page 26: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

.4 erugiF def ecim .sv tcartxe vA htiw detnemelppus teid def ecim J6/LB75C elam ni HM amsalPteid lortnoc

0

5

01

51

02

52

03

53

NOC tcartxE vA tcartxE vA NOC

lm/g

m noitartnecnoC

HM

tcartxE vA NOC

.E .tcartxe vA htiw teid def ecim ni noitprosba HM ssaM elam ni HM amsalp elbarusaem dewohs sisylana cipocsortceps

%61( tcartxe vA gniniatnoc teid a no om 9 gniwollof ecim J6/LB75C .gk/gm 0071 yletamixorppa fo esod HM a dedivorp taht )HM

( )4 erugiF .

fo ytivitcA esanikoxeH IIelcsuM esuoM ni

- EvA EvA+540.0

050.0

550.0

060.0

560.0

puorG teiD

)lm/

U( ytivitcA

Page 27: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

.5 erugiF

B . :esoculg doolB tnacifingisnilusni - noitcuder decudni

)8=n( tcartxe vA htiw

.A :thgiew ydoB htiw tceffe tnacifingis on

.)03=n( tcartxe vA

lortnoC

vA

040506070809001011021

0 51 03 06 09nim ni emiT

Ld/gm esoculG

05

015102

5203

5304

smarg

lortnoC

vA

teiD no shtnoM1 3 5 7

A

B

Page 28: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

selameF & selaM

0 001 002 003 004 005 006 007 008 009 00010010203040506070809001011

HINMFE

evilA syaD

lavivrus tnecreP

selaM

0 001 002 003 004 005 006 007 008 009 00010010203040506070809001011

HINMFE

evilA syaD

lavivrus tnecreP

selameF

0 001 002 003 004 005 006 007 008 009 00010010203040506070809001011

HINMFE

evilA syaD

lavivrus tnecreP

MFE HIN naideM 686 245

lamixaM 529 088 1162..0<P )knar-gol( llarevO

MFE HIN naideM 326 784

lamixaM 278 )evila 2( 529 2323.0<P )knar gol( llarevO

MFE HIN naideM 217 216

lamixaM 458 5780077.0<P )knar-gol( llarevO

60-4-21 EVILA LLITSselaM HIN 0

MFE 2selameF HIN 0

MFE 0

fo napsefiL naideM ni esaercnI tnacifingiS* 011 syad

tnacifingiS oN sceffE napsefiL mumixaM no

dehcirne HM fo tceffE XvA napsefiL noecim JeH3C elamef ni

03=n ;gk/gm 0071

gk/gm 051~ esoD tnelaviuqE namuH

Page 29: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

thgieW ydoB

51025203530454055506

yaM-2yaM-32

nuJ-31

luJ-4luJ-52

)%52( guA-51

)%57 ro 05( peS-5

)%57 ro 05( peS-62

tcO-71

voN-7voN-82

ceD-91

naJ-9naJ-03

esuoM/s

marG

lortnoC

HM+lortnoC

FH

HM+FH

hctiwS HM/FH

ni niaG thgieW ydoB no tcartxE odacovA fo stceffE ateiD - ledoM ytisebO decudnI

elaM( J6/LB75C )eciM

63 03 42 81 21 6 0

teiD no skeeW

)detarutasnu %06(

Page 30: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

yawhtap gnilangis nilusni eht sretla tcartxe vA ni HMsllec elcsum ni — gnaW .Z dna ulafeC .W morf atad

Page 31: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

sllec elcsum 6L ni noitadixo dica yttaf sesaercni tcartxe vA ni HM

gnaW .Z dna ulafeC .W morf ataD

Page 32: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

trohS fo yrammuS - gnisU seidutS esuoM mreTHM - tcartxE odacovA dehcirnE

stceffe esrevda on ,detarelot lleWekatni doof no stceffe oN

ytivitisnes nilusni devorpmIesoculg ni esaercni oN

itnA - stceffe ytisebosdipil doolb decudeR

itnA - stceffe s’remiehzlA

gnisU seidutS lleC ortiV nI fo yrammuSHM - tcartxE odacovA dehcirnE

RC lareves detceffA - syawhtap gnilangis detaler)KPMA( gnilangis nilusni)1TRIS( sesnopser sserts

1CGP( noitarefilorp lairdnohcotimnoitadixo dica yttaf

Page 33: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

enil lleC lortnoC HM - detaert noitibihni htworg %

thgieW romuT

amonicrac noloc namuh 251 93 23 51 97amonicrac reddalb namuh 6.4 4.0 6.1 3.0 56

amonicrac tar 534 38 663 85 61

( HM :etoN esolutpehonnam 31 n( star ot deretsinimda ) - noitcejni PI aiv )puorg rep 71( gk/gm 0071 .syad 5 rof )

star ni htworg romut tibihni HM fo snoitcejni PI

Page 34: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

HM eht fo noitaulavE - dehcirnEXvA sgoD ni

)sreveirteR rodarbaL(

G&P htiw noitaroballoc nI( eraCteP )

Page 35: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction
Page 36: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

sgod ni slevel nilusni gnitsaf tcartxe vA gniniatnoc teid fo tceffE

0

52

05

57

001

521

0 41 82 65

)lortnoC fo %( nilusnI

noC

lortnoC gk/gm1WB

gk/gm2WB

gk/gm02WB

*

vA

* *

slevel nilusni gnitsaf secuder tcartxe vAsgod ni

xoF dna sreveirteR rodarbaL gnuoY( )6=n ,sreirreT

NOCA Xv

Page 37: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

gk/gm 0 gk/gm 2 gk/gm 5

dlO

05

015102

520353

0454

0 5.0 0.1 5.1 0.2 5.2 0.3 5.3 0.4

tsoP emiT - )rH( gnideeF

tludA

0

5

01

51

02

52

03

0 5.0 0.1 5.1 0.2 5.2 0.3 5.3 0.4

SREVEIRTER RODARBAL

/UIµ( nilusnI

Lm

)

50.0<P ba

0

5

01

51

02

52

03

53

04

0 2 5

a

ba

b

gk/gm HM

/UIµ( nilusnI nae

ML

m)

NILUSNI NAEM — BAL DLO

sbaL ni esnopseR nilusnI amsalPlaeM a gniwolloF

RY 4~RY 21~

Page 38: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

noitammalfni cimetsySegA fo noitaunettA - PRC ni esaercnI detaleR

nietorP evitcaeR-C

0

5

01

51

02

52

0 6 21 81 42 03 63 24 45

tseT no htnoM

L/gm

abunakuE HM + abunakuE

50.<P01.<P

7 8 9 01 11egA naeM

lortnoC XvA

83

Page 39: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

93

gnoL morf gnigremE stluseR - fo ydutS mreT( tcartxE odacovA XvA ni teiD )HM gk/gm 2 :

sreveirteR yrotarobaLegA - ssam ydob nael ni enilced detaler

)AXED yb derusaem( def sgod ni detaunetta si XvA teid)ledom stceffe dexim(

teiD NOC

XvA )42=n( teiD

raeY s no ydutS

Page 40: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

)rewop( htgnerts elcsuM HM XvA ega sgod sa htgnerts elcsum secnahne

sgod regnuoY )sry 7 ot 5 :ega(stta

W ,htgnertS elcsuM

0 8 11 41 71 02 32 62 92 23TSET NO HTNOM

50.<P01.<P

0

001

002

003

004

005

006

sgod redlO )sry 11 ot 9 :ega(

`

sttaW ,htgnertS elcsu

M

0 22 52 82 13 43 73 04 34 64YDUTS NO HTNOM

0

001

002

003

004

005

006

00750.<P

abunakuE HM + abunakuE XvAlortnoC

04

)ledom stceffe dexim(

Page 41: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

HM gnisU seidutS goD fo yrammuS - dehcirnEtcartxE odacovA

stceffe esrevda on ,)gk/gm 2( detarelot lleWsraey lareves revo gnidnetxe gnideef htiw

gnoL - ytefas dewohs yduts ygolocixot mretekatni doof no stceffe oN

ytivitisnes nilusni devorpmIecnarelot esoculg devorpmI

noitammalfni fo srekram decudeRsserts evitadixo fo srekram decudeRecnamrofrep dna htgnerts devorpmI

14

Page 42: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

esolutpehonnaM :egatnavdA gnizamA s’odacovA

a si erehT lacituecartun !ereh ni meg

24

Page 43: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

noitcarf suoeuqa eht ni dehcirne sodacova epirnu fo tcartxe deredwop A2 fo esod tegrat a htiw )XVA( HM gniniatnoc - .gk/gm 02

A esuaceb SARG sa delebal eb dna PMG rednu derutcafunam eb dluoc tcudorp fo .doof a morf noitavired sti

a sa mrof eluspac a ni tcudorp siht tekram nac eW tnemelppus htlaeh lareneg a sa ro doof lacidem ni ytivitisnes nilusni gnivorpmi drawot detcerid

citebaiderp tcudorp eht tekram nac ew ro/dna ,stneitap B2B enibmoc ot .smialc htlaeh suoirav htiw stnemelppus htlaeh rieht rof stneidergni rehto htiw

eht gnicudorp rof sdohtem eht evah ew ,G&P yb noitcudorp tcudorp no desaB yllacificeps ,esirpretne laicremmoc a yb elacs ssam a no XVA nimeK htiw

51 morf HM fo sdleiy - .%04 fo puorg tnenimorp a htiw pihsnoitaler esolc a tliub evah ew ,noitidda nI

era ew rehtegot dna ,stsirutlucitroh dna sreworg odacova ainrofilaC HM fo sdohtem evitceffe tsoc dna tneiciffe erom gnirolpxe yltnerruc

esaercni nac taht sravitluc repaehc ,rehto derevocsid evah eW .noitcudorp3 ot pu dleiy HM - .odacova epirnu thgiew yb %4

W htiw gnidnatsrednu fo mudnaromem a evah e xamartuN gnimrifnoc sbaL .tem era airetirc ytefas niatrec ecno tcudorp a gnirutcafunam ni tseretni rieht

tcudorP laitinI desoporP

34

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?tekraM eht si ohW

eW yub ohw snosrep fo gnitegrat tenretni htiw ,llams ffo trats nacitna ylralucitrap ,stnemelppus htlaeh - .stnemelppus gniga

”htlaeh cilobatem“ ni detseretni esoht tegrat nac ew ,tnemelppus a sAitna“ dna - .stnemelppus gniga

itna ,htlaeh gnilles seinapmoc tegrat nac ew ,tcudorp B2B a sA -itna dna ,citebaid - .stnemelppus gniga

revo tegrat dluow ew ,doof lacidem a sA - ro thgiew citebaiderp .stluda cirtaidep egral a si ereht eveileb ew yllautneve ,doof lacidem a sA

ta nerdlihc rof tekram - setebaid dna ytisebo rof ksir — yletinifed dluow.mialc siht rof lairt lacinilc doog a deen

44

Page 45: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

stcatnoC laicnaniF/ssenisuB tnerruC

stcudorp tep fo tnempoleved rof tnemeergA esneciL tnetaP :G&P ,snoitacilppa tcudorp namuh ot sthgir lla SG nevig sah G&P :etoN tub

weN fo noitisiuqca 2102 fo esuaceb detseretni sniamer a ,retpahC.ynapmoc tnemelppus

xamartuN : stnemelppus tnioj fo retekram dna rerutcafunam rojaMnimeK : stneidergni doof fo reilppus dna rerutcafunam rojaM

tsafideM : ynapmoc noitirtun teid rojaMeMuN : tratS - ynapmoc sdoof lacidem pu

scigoloibarreT : tratS - RC fo retekram dna rerutcafunam pu scitemim :s’C4 tratS - gnirutcafunam no desucof hcetoib pu esolutpehonnam morf

stcudorp odacova :dnuF anaisiuoL ehT anaisiuoL - puorg CV desucof

ecruoS :latipaC puorg tnemtsevni legnA/CV lacoL54

Page 46: Enriched in Mannoheptulose as a Calorie R estriction Mimetic · T err raB iologicals , LL C* ww w .benagene.o rg T err aPharma , I nc. ww w .pharmater r a.com. Calorie Restriction

segnellahC ssenisuB

poleveD nalp tixe gnidulcni nalp ssenisub etelpmoc a eruceS gnidnuf eruceS ssenisub a rentrap

noitisop PI nehtgnerts dna yfidiloSFRBP ro CRBP yb noitisop pihsrenwo/elor no ediceD

segnellahC tcudorP

stsoc tnemerucorp ni kcol dna ylppus fo niahc eruceSsnalp noitcudorp eruces dna tcudorp fo epyt no ediceD

yrassecen fi enilno ffo trats nac…nalp gnitekram poleveD

laicnaniF segnellahC

rof dedeen sdnuF evloser ot seiduts lacinilcerp gnitcudnoc esod dna yticificeps noitca fo

roF yduts yticixot dna KP namuh gnitcudnoc roF ycaciffe namuh gnitcudnoc slairt

segnellahC ssenisuB tnerruC

64

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snoitisoP tnetaP

ecneicSoreG elpitlum sah sa delif snoitacilppa PI eht rof tnetap SU detnarg eno dna G&P htiw srentrap

doof tep ( noitacilppa )954,666,7 . erehT seitrap rehto ot detnarg stnetap rehto era

taht leef ew tub ,HM fo snoitacilppa emos gnidrager ni detnarg dna rof deilppa eb nac stnetap lanoitidda

.secaps rehto lareves eW dna sgnilif PI wen rof saedi fo rebmun a evah

tnempoleved tcudorp dna ygolonhcet lanoitidda .

74

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slairT lacinilC

lairT ytefaS/gnisoD :1 ydutS

,esebo yhtlaeh 8 :stcejbuS citebaidnon slaudividni12 sega ;selamef 4 ;selam 4( - 03 :IMB ;sry 14 - )53

XvA gk/gm 02,2,0 etamitse ot sesod gnitalacse ni eluspaC :yrevileD1 ta - slavretni keew

:stniopdnE ,)AXED( noitisopmoc ,ssam ydobygolotameh ,CBC ,C1A ,sdipil ,nilusni ,esoculg amsalp

eriannoitseuq yteitas dna ekatni doof

84

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slairT lacinilClairT ytefaS/ycaciffE :2 ydutS

,esebo yhtlaeh 23 :stcejbuS citebaidnon slaudividni12 sega ;selamef 61 ;selam 61( - 52 :IMB ;sry 15 - )03

elbuoD :ngiseD - 6 ,dellortnoc obecalp ,dnilb - stnemerusaeM ;yduts kw3 ,enilesab ta edam - 6 ,kw - kw

XvA )1 ydutS fo stluser morf denimreted( esod eno ni eluspaC :yrevileDtaeh( eluspac obecalp dna - detavitcani XvA ro ecno dereviled )

kw 6 rof )denimreted eb ot( yliad eciwt

:stniopdnE ,)AXED( noitisopmoc ,ssam ydobygolotameh ,CBC ,C1A ,sdipil ,nilusni ,esoculg amsalp

eriannoitseuq yteitas dna ekatni doof ot skeew 6 dna enilesab ta erudecorp pmalc esoculg

ytivitisnes nilusni erusaem94

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tnemelppus a teG ,tekram ot daor eht no doof lacidem ro ediced neht nwo rieht ni edulcni ot seinapmoc rehto ot XVA eht tekram ot rehtehw

itlum - .stcudorp tneidergni

wolloF - no pu taht stcudorp larutan rehto htiw XVA fo serutxim euqinu.PI lanoitidda edivorp dluow dna ycaciffe sti ecnahne thgim

foorp a sa XVA eht deweiv syawla evah eW - fo - ,elpicnirp zértne eht otni emocni ro tnemtsevni tneiciffus nevig ,revewoh ;tekram citemim RC

fo noitcudorp no saedi evah ew ,hcnual XVA lufsseccus a no desab.yalp lacituecamrahp a edivorp dluoc taht srotibihni citylocylg citehtnys

ygetarts tixe eht ,hcnual dna tnempoleved tcudorp lufsseccus dnoyeB lanoitirtun a ylekil ,reyub a dnif ot eb dluohs nalp ssenisub yna rof

.ynapmoc tnemelppus

snoitceriD erutuF

05

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erehw os ,yakO og ew nac ?ereh morf

15