begin name dallepezze2 end name begin reactions reaction1 {1.0}Akt = {1.0}AktpS473 reaction10 {1.0}Mitophagy = {1.0}Nil reaction11 {1.0}FoxO3a = {1.0}FoxO3apS253 reaction12 {1.0}FoxO3apS253 = {1.0}FoxO3a reaction13 {1.0}FoxO3apS253 = {1.0}Nil reaction14 {1.0}$EXTERNAL = {1.0}FoxO3a reaction15 {1.0}$EXTERNAL = {1.0}CDKN1A reaction16 {1.0}CDKN1A = {1.0}Nil reaction17 {1.0}$EXTERNAL = {1.0}CDKN1B reaction18 {1.0}CDKN1B = {1.0}Nil reaction19 {1.0}$EXTERNAL = {1.0}DNAdamage reaction2 {1.0}AktpS473 = {1.0}Akt reaction20 {1.0}$EXTERNAL = {1.0}DNAdamage reaction21 {1.0}DNAdamage = {1.0}Nil reaction22 {1.0}$EXTERNAL = {1.0}ROS reaction23 {1.0}$EXTERNAL = {1.0}ROS reaction24 {1.0}ROS = {1.0}Nil reaction25 {1.0}JNK = {1.0}JNKpT183 reaction26 {1.0}JNKpT183 = {1.0}JNK reaction27 {1.0}$EXTERNAL = {1.0}SAbetagal reaction28 {1.0}$EXTERNAL = {1.0}SAbetagal reaction29 {1.0}SAbetagal = {1.0}$EXTERNAL reaction3 {1.0}AMPK = {1.0}AMPKpT172 reaction30 {1.0}Mitomassturnover = {1.0}Mitomassnew reaction31 {1.0}Mitomassturnover = {1.0}Mitomassnew reaction32 {1.0}Mitomassnew = {1.0}Mitomassturnover reaction33 {1.0}Mitomassold = {1.0}Mitomassturnover reaction34 {1.0}Mitomassnew = {1.0}Mitomassold reaction35 {1.0}$EXTERNAL = {1.0}Mitomembrpotnew reaction36 {1.0}$EXTERNAL = {1.0}Mitomembrpotold reaction37 {1.0}Mitomembrpotnew = {1.0}Nil reaction38 {1.0}Mitomembrpotold = {1.0}Nil reaction39 {1.0}$EXTERNAL = {1.0}IKKbeta reaction4 {1.0}AMPKpT172 = {1.0}AMPK reaction40 {1.0}IKKbeta = {1.0}Nil reaction41 {1.0}mTORC1 = {1.0}mTORC1pS2448 reaction5 {1.0}AMPKpT172 = {1.0}AMPK reaction6 {1.0}mTORC1 = {1.0}mTORC1pS2448 reaction7 {1.0}mTORC1 = {1.0}mTORC1pS2448 reaction8 {1.0}mTORC1pS2448 = {1.0}mTORC1 reaction9 {1.0}$EXTERNAL = {1.0}Mitophagy end reactions begin rate equations reaction1 = Cell*function4reaction11[Akt[t], AktS473phosbyinsulin, Insulin] reaction10 = Cell*function4reaction101[Mitophagy[t], mTORC1pS2448[t], mitophagyinactivbymTORC1pS2448] reaction11 = Cell*function4reaction111[AktpS473[t], FoxO3a[t], FoxO3aphosbyAktpS473] reaction12 = Cell*function4reaction121[FoxO3apS253[t], FoxO3aphosbyJNKpT183, JNKpT183[t]] reaction13 = Cell*FoxO3apS253degrad*FoxO3apS253[t] reaction14 = Cell*function2[FoxO3asynthesis] reaction15 = Cell*function4reaction151[CDKN1AtranscrbyFoxO3anDNAdamage, DNAdamage[t], FoxO3a[t]] reaction16 = Cell*function4reaction161[AktpS473[t], CDKN1A[t], CDKN1AinactivbyAktpS473] reaction17 = Cell*function4reaction171[CDKN1BtranscrbyFoxO3anDNAdamage, DNAdamage[t], FoxO3a[t]] reaction18 = Cell*function4reaction181[AktpS473[t], CDKN1B[t], CDKN1BinactivbyAktpS473] reaction19 = Cell*function4reaction191[DNAdamagedbyirradiation, Irradiation] reaction2 = Cell*function4reaction21[AktpS473[t], AktpS473dephosbymTORC1pS2448, mTORC1pS2448[t]] reaction20 = Cell*function4reaction201[DNAdamagedbyROS, ROS[t]] reaction21 = Cell*DNArepair*DNAdamage[t] reaction22 = Cell*function4reaction221[Mitomembrpotnew[t], ROSprodbyMitomembrpotnew] reaction23 = Cell*function4reaction231[Mitomembrpotold[t], ROSprodbyMitomembrpotold] reaction24 = Cell*ROSturnover*ROS[t] reaction25 = Cell*function4reaction251[JNK[t], JNKactivbyROS, ROS[t]] reaction26 = Cell*JNKpT183inactiv*JNKpT183[t] reaction27 = Cell*function4reaction271[ROS[t], senassbetagalincbyROS] reaction28 = Cell*function4reaction281[Mitophagy[t], senassbetagalincbyMitophagy] reaction29 = Cell*senassbetagaldec*SAbetagal[t] reaction3 = AMPKT172phos*Cell*AMPK[t] reaction30 = Cell*function4reaction301[Mitomassturnover[t], mTORC1pS2448[t], mitobiogenesisbymTORC1pS2448] reaction31 = Cell*function4reaction311[Mitomassturnover[t], mTORC1pS2448[t], mitobiogenesisbyAMPKpT172] reaction32 = Cell*function4reaction321[Mitomassnew[t], Mitophagy[t], mitophagynew] reaction33 = Cell*function4reaction331[Mitomassold[t], Mitophagy[t], mitophagyold] reaction34 = Cell*function4reaction341[CDKN1A[t], Mitomassnew[t], mitodysfunction] reaction35 = Cell*function4reaction351[Mitomassnew[t], mitomembrpotnewinc] reaction36 = Cell*function4reaction361[Mitomassold[t], mitomembrpotoldinc] reaction37 = Cell*mitomembrpotnewdec*Mitomembrpotnew[t] reaction38 = Cell*mitomembrpotolddec*Mitomembrpotold[t] reaction39 = Cell*function4reaction391[IKKbetaactivbyROS, ROS[t]] reaction4 = Cell*function4reaction41[AMPKpT172[t], AMPKpT172dephosbyMitomembrpotnew, Mitomembrpotnew[t]] reaction40 = Cell*IKKbetainactiv*IKKbeta[t] reaction41 = Cell*function4reaction411[AminoAcids, IKKbeta[t], mTORC1[t], mTORC1S2448phosbyAAnIKKbeta] reaction5 = Cell*function4reaction51[AMPKpT172[t], AMPKpT172dephosbyMitomembrpotold, Mitomembrpotold[t]] reaction6 = Cell*function4reaction61[AminoAcids, mTORC1[t], mTORC1S2448phosbyAA] reaction7 = Cell*function4reaction71[AktpS473[t], AminoAcids, mTORC1[t], mTORC1S2448phosbyAAnAktpS473] reaction8 = Cell*function4reaction81[AMPKpT172[t], mTORC1pS2448[t], mTORC1pS2448dephosbyAMPKpT172] reaction9 = Cell*function4reaction91[AMPKpT172[t], FoxO3a[t], mitophagyactivbyFoxO3anAMPKpT172] end rate equations begin parameters AMPKT172phos = 0.355183987378767 AMPKpT172dephosbyMitomembrpotnew = 0.117744691539618 AMPKpT172dephosbyMitomembrpotold = "1.00000000000003e-06" AktS473phosbyinsulin = 0.588783148144923 AktpS473dephosbymTORC1pS2448 = 0.114598191621279 CDKN1AinactivbyAktpS473 = 0.0667971061916905 CDKN1AtranscrbyFoxO3anDNAdamage = 0.0852182335681166 CDKN1BinactivbyAktpS473 = 0.0596841598127919 CDKN1BtranscrbyFoxO3anDNAdamage = 0.0920526565951487 DNAdamagedbyROS = 0.118873655169353 DNAdamagedbyirradiation = 9237.72311545872 DNArepair = 0.325724769122274 FoxO3apS253degrad = 39.4068609318082 FoxO3aphosbyAktpS473 = 6.83511123229576 FoxO3aphosbyJNKpT183 = 0.112877630496044 FoxO3asynthesis = 407.307409980937 IKKbetaactivbyROS = 1.0 IKKbetainactiv = 1.0 JNKactivbyROS = 0.00502329152478409 JNKpT183inactiv = 0.0718429173444438 ROSprodbyMitomembrpotnew = 4.55464788075885 ROSprodbyMitomembrpotold = 772.829490967078 ROSturnover = 3.23082321168464 mTORC1S2448phosbyAA = "1.00008999860285e-06" mTORC1S2448phosbyAAnAktpS473 = 162.471039450073 mTORC1S2448phosbyAAnIKKbeta = "1.00008996727694e-05" mTORC1pS2448dephosbyAMPKpT172 = 191.297262771509 mitobiogenesisbyAMPKpT172 = "5.8915457309741e-05" mitobiogenesisbymTORC1pS2448 = 0.0133620123598202 mitodysfunction = 0.0270695257507146 mitomembrpotnewdec = 1094.58423149719 mitomembrpotnewinc = 9882.02736076158 mitomembrpotolddec = 0.954903499913184 mitomembrpotoldinc = 0.00586017882122243 mitophagyactivbyFoxO3anAMPKpT172 = 1319.84219165251 mitophagyinactivbymTORC1pS2448 = 645.999307230137 mitophagynew = 0.22465992989378 mitophagyold = 0.00122607614891116 scaleAMPKpT172obs = 1.0 scaleAktpS473obs = 1.0 scaleCDKN1Aobs = 1.0 scaleCDKN1Bobs = 1.0 scaleDNAdamagegammaH2AXobs = 1.0 scaleFoxO3apS253obs = 1.0 scaleFoxO3atotalobs = 1.0 scaleJNKpT183obs = 1.0 scaleMitoMassobs = 1.0 scaleMitoMembrPotobs = 1.0 scaleMitophagyobs = 1.0 scaleROSobs = 1.0 scaleSAbetagalobs = 1.0 scalemTORpS2448obs = 1.0 senassbetagaldec = 0.154821166783837 senassbetagalincbyMitophagy = "1.00000000000011e-06" senassbetagalincbyROS = 0.0701139988718817 Cell = 1.0 end parameters begin initial conditions AMPK[0] = AMPKi AMPKpT172[0] = AMPKpT172i Akt[0] = Akti AktpS473[0] = AktpS473i CDKN1A[0] = CDKN1Ai CDKN1B[0] = CDKN1Bi DNAdamage[0] = DNAdamagei FoxO3a[0] = FoxO3ai FoxO3apS253[0] = FoxO3apS253i IKKbeta[0] = IKKbetai JNK[0] = JNKi JNKpT183[0] = JNKpT183i Mitomassnew[0] = Mitomassnewi Mitomassold[0] = Mitomassoldi Mitomassturnover[0] = Mitomassturnoveri Mitomembrpotnew[0] = Mitomembrpotnewi Mitomembrpotold[0] = Mitomembrpotoldi Mitophagy[0] = Mitophagyi Nil[0] = Nili ROS[0] = ROSi SAbetagal[0] = SAbetagali mTORC1[0] = mTORC1i mTORC1pS2448[0] = mTORC1pS2448i end initial conditions begin initial values AMPKi = 10.0 AMPKpT172i = 10.0 Akti = 10.0 AktpS473i = 10.0 CDKN1Ai = 10.0 CDKN1Bi = 10.0 DNAdamagei = 1.0 FoxO3ai = 10.0 FoxO3apS253i = 10.0 IKKbetai = 10.0 JNKi = 25.0 JNKpT183i = 10.0 Mitomassnewi = 1.0 Mitomassoldi = 0.0 Mitomassturnoveri = 25.0 Mitomembrpotnewi = 12.12 Mitomembrpotoldi = 0.0 Mitophagyi = 10.0 Nili = 0.0 ROSi = 10.0 SAbetagali = 0.81 mTORC1i = 10.0 mTORC1pS2448i = 10.0 end initial values begin assignment rules AktpS473obs := scaleAktpS473obs*AktpS473[t] Irradiation := Piecewise[{{0, t < -1}}, Piecewise[{{0, t < 0}}, Piecewise[{{1, t < 0.003472}}, 0]]] AminoAcids := 1 Insulin := 1 DNAdamagegammaH2AXobs := scaleDNAdamagegammaH2AXobs*DNAdamage[t] mTORpS2448obs := scalemTORpS2448obs*mTORC1pS2448[t] FoxO3apS253obs := scaleFoxO3apS253obs*FoxO3apS253[t] AMPKpT172obs := scaleAMPKpT172obs*AMPKpT172[t] MitoMassobs := scaleMitoMassobs*(Mitomassnew[t] + Mitomassold[t]) CDKN1Aobs := scaleCDKN1Aobs*CDKN1A[t] CDKN1Bobs := scaleCDKN1Bobs*CDKN1B[t] MitoMembrPotobs := scaleMitoMembrPotobs*(Mitomembrpotnew[t] + Mitomembrpotold[t]) Mitophagyobs := scaleMitophagyobs*Mitophagy[t] FoxO3atotalobs := scaleFoxO3atotalobs*(FoxO3a[t] + FoxO3apS253[t]) ROSobs := scaleROSobs*ROS[t] JNKpT183obs := scaleJNKpT183obs*JNKpT183[t] SAbetagalobs := scaleSAbetagalobs*SAbetagal[t] end assignment rules begin function definitions function2[v_] := v function4reaction11[Akt_,AktS473phosbyinsulin_,Insulin_] := Akt*AktS473phosbyinsulin*Insulin function4reaction21[AktpS473_,AktpS473dephosbymTORC1pS2448_,mTORC1pS2448_] := AktpS473*AktpS473dephosbymTORC1pS2448*mTORC1pS2448 function4reaction41[AMPKpT172_,AMPKpT172dephosbyMitomembrpotnew_,Mitomembrpotnew_] := AMPKpT172*AMPKpT172dephosbyMitomembrpotnew*Mitomembrpotnew function4reaction61[AminoAcids_,mTORC1_,mTORC1S2448phosbyAA_] := AminoAcids*mTORC1*mTORC1S2448phosbyAA function4reaction81[AMPKpT172_,mTORC1pS2448_,mTORC1pS2448dephosbyAMPKpT172_] := AMPKpT172*mTORC1pS2448*mTORC1pS2448dephosbyAMPKpT172 function4reaction101[Mitophagy_,mTORC1pS2448_,mitophagyinactivbymTORC1pS2448_] := Mitophagy*mitophagyinactivbymTORC1pS2448*mTORC1pS2448 function4reaction111[AktpS473_,FoxO3a_,FoxO3aphosbyAktpS473_] := AktpS473*FoxO3a*FoxO3aphosbyAktpS473 function4reaction151[CDKN1AtranscrbyFoxO3anDNAdamage_,DNAdamage_,FoxO3a_] := CDKN1AtranscrbyFoxO3anDNAdamage*DNAdamage*FoxO3a function4reaction171[CDKN1BtranscrbyFoxO3anDNAdamage_,DNAdamage_,FoxO3a_] := CDKN1BtranscrbyFoxO3anDNAdamage*DNAdamage*FoxO3a function4reaction191[DNAdamagedbyirradiation_,Irradiation_] := DNAdamagedbyirradiation*Irradiation function4reaction201[DNAdamagedbyROS_,ROS_] := DNAdamagedbyROS*ROS function4reaction221[Mitomembrpotnew_,ROSprodbyMitomembrpotnew_] := Mitomembrpotnew*ROSprodbyMitomembrpotnew function4reaction251[JNK_,JNKactivbyROS_,ROS_] := JNK*JNKactivbyROS*ROS function4reaction281[Mitophagy_,senassbetagalincbyMitophagy_] := Mitophagy*senassbetagalincbyMitophagy function4reaction301[Mitomassturnover_,mTORC1pS2448_,mitobiogenesisbymTORC1pS2448_] := mitobiogenesisbymTORC1pS2448*Mitomassturnover*mTORC1pS2448 function4reaction321[Mitomassnew_,Mitophagy_,mitophagynew_] := Mitophagy*mitophagynew*Mitomassnew function4reaction331[Mitomassold_,Mitophagy_,mitophagyold_] := Mitophagy*mitophagyold*Mitomassold function4reaction411[AminoAcids_,IKKbeta_,mTORC1_,mTORC1S2448phosbyAAnIKKbeta_] := AminoAcids*IKKbeta*mTORC1*mTORC1S2448phosbyAAnIKKbeta function4reaction391[IKKbetaactivbyROS_,ROS_] := IKKbetaactivbyROS*ROS function4reaction361[Mitomassold_,mitomembrpotoldinc_] := Mitomassold*mitomembrpotoldinc function4reaction351[Mitomassnew_,mitomembrpotnewinc_] := Mitomassnew*mitomembrpotnewinc function4reaction341[CDKN1A_,Mitomassnew_,mitodysfunction_] := CDKN1A*mitodysfunction*Mitomassnew function4reaction311[Mitomassturnover_,mTORC1pS2448_,mitobiogenesisbyAMPKpT172_] := mitobiogenesisbyAMPKpT172*Mitomassturnover*mTORC1pS2448 function4reaction271[ROS_,senassbetagalincbyROS_] := ROS*senassbetagalincbyROS function4reaction231[Mitomembrpotold_,ROSprodbyMitomembrpotold_] := Mitomembrpotold*ROSprodbyMitomembrpotold function4reaction181[AktpS473_,CDKN1B_,CDKN1BinactivbyAktpS473_] := AktpS473*CDKN1B*CDKN1BinactivbyAktpS473 function4reaction161[AktpS473_,CDKN1A_,CDKN1AinactivbyAktpS473_] := AktpS473*CDKN1A*CDKN1AinactivbyAktpS473 function4reaction121[FoxO3apS253_,FoxO3aphosbyJNKpT183_,JNKpT183_] := FoxO3aphosbyJNKpT183*FoxO3apS253*JNKpT183 function4reaction91[AMPKpT172_,FoxO3a_,mitophagyactivbyFoxO3anAMPKpT172_] := AMPKpT172*FoxO3a*mitophagyactivbyFoxO3anAMPKpT172 function4reaction71[AktpS473_,AminoAcids_,mTORC1_,mTORC1S2448phosbyAAnAktpS473_] := AktpS473*AminoAcids*mTORC1*mTORC1S2448phosbyAAnAktpS473 function4reaction51[AMPKpT172_,AMPKpT172dephosbyMitomembrpotold_,Mitomembrpotold_] := AMPKpT172*AMPKpT172dephosbyMitomembrpotold*Mitomembrpotold end function definitions begin events end events begin process annotations end process annotations begin species annotations Insulin http://identifiers.org/chebi/CHEBI:5931 Nil http://identifiers.org/biomodels.sbo/SBO:0000291 ROS http://identifiers.org/chebi/CHEBI:26523 end species annotations begin units end units