KEGG   PATHWAY: fca04213
Entry
fca04213                    Pathway                                
Name
Longevity regulating pathway - multiple species - Felis catus (domestic cat)
Description
Aging is a complex process of accumulation of molecular, cellular, and organ damage, leading to loss of function and increased vulnerability to disease and death. Despite the complexity of aging, recent work has shown that dietary restriction (DR) and genetic down-regulation of nutrient-sensing pathways, namely IIS (insulin/insulin-like growth factor signalling) and TOR (target-of- rapamycin) can substantially increase healthy life span of laboratory model organisms. These nutrient signaling pathways are conserved in various organisms. In worms, flies, and mammals, DR reduces signalling through IIS/TOR pathways, deactivating the PI3K/Akt/TOR intracellular signalling cascade and consequently activating the antiaging FOXO family transcription factor(s). In yeast, the effects of DR on life- span extension are associated with reduced activities of the TOR/Sch9 and Ras/PKA pathways and require the serine-threonine kinase Rim15 and transcription factors Gis1 and Msn2/4. These transcription factors (FOXO, DAF-16, Gis1, and Msn2/4) transactivate genes involved in resistance to oxidative stress, energy metabolism, DNA damage repair, glucose metabolism, autophagy and protection of proteins by chaperones.
Class
Organismal Systems; Aging
Pathway map
fca04213  Longevity regulating pathway - multiple species
fca04213

Organism
Felis catus (domestic cat) [GN:fca]
Gene
493804  INS; insulin precursor [KO:K04526]
100127108  INSR; insulin receptor isoform X1 [KO:K04527] [EC:2.7.10.1]
101101237  IGF1; insulin-like growth factor I isoform X3 [KO:K05459]
100500937  IGF1R; insulin-like growth factor 1 receptor isoform X1 [KO:K05087] [EC:2.7.10.1]
101087257  IRS1; insulin receptor substrate 1 [KO:K16172]
101095791  IRS2; insulin receptor substrate 2 [KO:K07187]
101100432  insulin receptor substrate 1-like isoform X2 [KO:K17445]
101093251  IRS4; insulin receptor substrate 4 [KO:K17446]
751103  HRAS; GTPase HRas isoform X1 [KO:K02833]
751104  KRAS; GTPase KRas isoform X2 [KO:K07827]
751105  NRAS; GTPase NRas [KO:K07828]
101094274  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
101091892  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
101097413  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100271864  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
101093286  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
101093586  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101087931  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101092818  AKT3; RAC-gamma serine/threonine-protein kinase isoform X4 [KO:K04456] [EC:2.7.11.1]
100499544  AKT2; RAC-beta serine/threonine-protein kinase isoform X4 [KO:K04456] [EC:2.7.11.1]
101101375  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
101094327  ADCY2; adenylate cyclase type 2 isoform X1 [KO:K08042] [EC:4.6.1.1]
101088157  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
101097735  ADCY4; adenylate cyclase type 4 isoform X1 [KO:K08044] [EC:4.6.1.1]
101100749  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
101091211  ADCY6; adenylate cyclase type 6 isoform X2 [KO:K08046] [EC:4.6.1.1]
101094148  ADCY7; adenylate cyclase type 7 isoform X2 [KO:K08047] [EC:4.6.1.1]
101087555  ADCY8; adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
101095942  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
101090494  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X3 [KO:K04345] [EC:2.7.11.11]
101095353  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101096628  FOXO1; forkhead box protein O1 [KO:K07201]
101081548  FOXO3; forkhead box protein O3 [KO:K09408]
101096985  SOD2; superoxide dismutase [Mn], mitochondrial [KO:K04564] [EC:1.15.1.1]
101093891  CAT; catalase [KO:K03781] [EC:1.11.1.6]
101092114  ATG5; autophagy protein 5 isoform X1 [KO:K08339]
101096000  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
101095885  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X3 [KO:K07198] [EC:2.7.11.31]
101094051  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
101092284  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X3 [KO:K07199]
101094684  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X2 [KO:K07200]
101092204  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 isoform X3 [KO:K07200]
101100119  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform X1 [KO:K07200]
101098152  MTOR; serine/threonine-protein kinase mTOR isoform X3 [KO:K07203] [EC:2.7.11.1]
101086862  RPTOR; regulatory-associated protein of mTOR isoform X1 [KO:K07204]
101100932  AKT1S1; proline-rich AKT1 substrate 1 isoform X1 [KO:K16184]
101091812  RPS6KB2; ribosomal protein S6 kinase beta-2 isoform X3 [KO:K04688] [EC:2.7.11.1]
101092561  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X2 [KO:K04688] [EC:2.7.11.1]
101087610  SIRT1; NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
101091804  SOD1; superoxide dismutase [Cu-Zn] [KO:K04565] [EC:1.15.1.1]
101089258  LOW QUALITY PROTEIN: superoxide dismutase [Cu-Zn]-like [KO:K04565] [EC:1.15.1.1]
101099906  EIF4EBP2; eukaryotic translation initiation factor 4E-binding protein 2 [KO:K18644]
105260573  heat shock 70 kDa protein 1 [KO:K03283]
101091022  heat shock 70 kDa protein 1-like [KO:K03283]
101087422  HSPA8; heat shock cognate 71 kDa protein [KO:K03283]
101080710  LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein-like [KO:K03283]
101099237  LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein-like [KO:K03283]
101092640  CRYAB; alpha-crystallin B chain [KO:K09542]
101088165  HDAC2; histone deacetylase 2 isoform X1 [KO:K06067] [EC:3.5.1.98]
101099228  HDAC1; histone deacetylase 1 isoform X3 [KO:K06067] [EC:3.5.1.98]
101085112  FOXA2; hepatocyte nuclear factor 3-beta isoform X1 [KO:K08035]
101083619  CLPB; caseinolytic peptidase B protein homolog isoform X1 [KO:K03695]
Compound
C00575  3',5'-Cyclic AMP
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
  Authors
Fontana L, Partridge L, Longo VD
  Title
Extending healthy life span--from yeast to humans.
  Journal
Science 328:321-6 (2010)
DOI:10.1126/science.1172539
Reference
  Authors
Parrella E, Longo VD
  Title
Insulin/IGF-I and related signaling pathways regulate aging in nondividing cells: from yeast to the mammalian brain.
  Journal
ScientificWorldJournal 10:161-77 (2010)
DOI:10.1100/tsw.2010.8
Reference
  Authors
Santos J, Leitao-Correia F, Sousa MJ, Leao C
  Title
Dietary Restriction and Nutrient Balance in Aging.
  Journal
Oxid Med Cell Longev 2016:4010357 (2016)
DOI:10.1155/2016/4010357
Reference
  Authors
Longo VD, Lieber MR, Vijg J
  Title
Turning anti-ageing genes against cancer.
  Journal
Nat Rev Mol Cell Biol 9:903-10 (2008)
DOI:10.1038/nrm2526
Reference
  Authors
Longo VD, Mitteldorf J, Skulachev VP
  Title
Programmed and altruistic ageing.
  Journal
Nat Rev Genet 6:866-72 (2005)
DOI:10.1038/nrg1706
Reference
  Authors
Longo VD, Finch CE
  Title
Evolutionary medicine: from dwarf model systems to healthy centenarians?
  Journal
Science 299:1342-6 (2003)
DOI:10.1126/science.1077991
Reference
  Authors
Mirzaei H, Suarez JA, Longo VD
  Title
Protein and amino acid restriction, aging and disease: from yeast to humans.
  Journal
Trends Endocrinol Metab 25:558-66 (2014)
DOI:10.1016/j.tem.2014.07.002
Reference
  Authors
Kenyon CJ
  Title
The genetics of ageing.
  Journal
Nature 464:504-12 (2010)
DOI:10.1038/nature08980
Reference
  Authors
Longo VD, Fontana L
  Title
Calorie restriction and cancer prevention: metabolic and molecular mechanisms.
  Journal
Trends Pharmacol Sci 31:89-98 (2010)
DOI:10.1016/j.tips.2009.11.004
Reference
  Authors
Longo VD, Fabrizio P
  Title
Chronological aging in Saccharomyces cerevisiae.
  Journal
Subcell Biochem 57:101-21 (2012)
DOI:10.1007/978-94-007-2561-4_5
Reference
  Authors
Bitto A, Wang AM, Bennett CF, Kaeberlein M
  Title
Biochemical Genetic Pathways that Modulate Aging in Multiple Species.
  Journal
Cold Spring Harb Perspect Med 5:a025114 (2015)
DOI:10.1101/cshperspect.a025114
Reference
  Authors
Mair W, Dillin A
  Title
Aging and survival: the genetics of life span extension by dietary restriction.
  Journal
Annu Rev Biochem 77:727-54 (2008)
DOI:10.1146/annurev.biochem.77.061206.171059
Reference
  Authors
Dali-Youcef N, Lagouge M, Froelich S, Koehl C, Schoonjans K, Auwerx J
  Title
Sirtuins: the 'magnificent seven', function, metabolism and longevity.
  Journal
Ann Med 39:335-45 (2007)
DOI:10.1080/07853890701408194
Reference
  Authors
Rizki G, Iwata TN, Li J, Riedel CG, Picard CL, Jan M, Murphy CT, Lee SS
  Title
The evolutionarily conserved longevity determinants HCF-1 and SIR-2.1/SIRT1 collaborate to regulate DAF-16/FOXO.
  Journal
PLoS Genet 7:e1002235 (2011)
DOI:10.1371/journal.pgen.1002235
Reference
  Authors
Lee SH, Min KJ
  Title
Caloric restriction and its mimetics.
  Journal
BMB Rep 46:181-7 (2013)
DOI:10.5483/BMBRep.2013.46.4.033
Reference
  Authors
Bordone L, Guarente L
  Title
Calorie restriction, SIRT1 and metabolism: understanding longevity.
  Journal
Nat Rev Mol Cell Biol 6:298-305 (2005)
DOI:10.1038/nrm1616
Reference
  Authors
Canto C, Auwerx J
  Title
Calorie restriction: is AMPK a key sensor and effector?
  Journal
Physiology (Bethesda) 26:214-24 (2011)
DOI:10.1152/physiol.00010.2011
Reference
  Authors
Barbieri M, Bonafe M, Franceschi C, Paolisso G
  Title
Insulin/IGF-I-signaling pathway: an evolutionarily conserved mechanism of longevity from yeast to humans.
  Journal
Am J Physiol Endocrinol Metab 285:E1064-71 (2003)
DOI:10.1152/ajpendo.00296.2003
Reference
  Authors
Russell SJ, Kahn CR
  Title
Endocrine regulation of ageing.
  Journal
Nat Rev Mol Cell Biol 8:681-91 (2007)
DOI:10.1038/nrm2234
Related
pathway
fca04068  FoxO signaling pathway
fca04150  mTOR signaling pathway
fca04151  PI3K-Akt signaling pathway
fca04152  AMPK signaling pathway
fca04211  Longevity regulating pathway
fca04910  Insulin signaling pathway
KO pathway
ko04213   
LinkDB

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