KEGG   PATHWAY: pcoo04213
Entry
pcoo04213                   Pathway                                
Name
Longevity regulating pathway - multiple species - Puma concolor (puma)
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
pcoo04213  Longevity regulating pathway - multiple species
pcoo04213

Organism
Puma concolor (puma) [GN:pcoo]
Gene
112852904  INSR; insulin receptor [KO:K04527] [EC:2.7.10.1]
112863499  IGF1; insulin-like growth factor I isoform X1 [KO:K05459]
112855479  IGF1R; insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
112859926  insulin receptor substrate 1-like [KO:K17445]
112871206  IRS4; insulin receptor substrate 4 [KO:K17446]
112868012  KRAS; GTPase KRas isoform X1 [KO:K07827]
112848478  NRAS; GTPase NRas [KO:K07828]
112849397  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
112849524  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
112848856  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
112861619  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
112868847  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
112863208  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
112851313  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
112859788  ADCY1; adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
112860207  ADCY2; adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
112864041  ADCY3; adenylate cyclase type 3 isoform X1 [KO:K08043] [EC:4.6.1.1]
112855238  ADCY4; adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
112849881  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
112867731  ADCY6; adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
112857348  ADCY7; adenylate cyclase type 7 [KO:K08047] [EC:4.6.1.1]
112859389  ADCY8; adenylate cyclase type 8 [KO:K08048] [EC:4.6.1.1]
112853291  ADCY9; adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
112852313  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
112871920  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
112860838  FOXO1; forkhead box protein O1 [KO:K07201]
112862093  FOXO3; forkhead box protein O3 [KO:K09408]
112862357  SOD2; superoxide dismutase [Mn], mitochondrial [KO:K04564] [EC:1.15.1.1]
112865557  CAT; catalase [KO:K03781] [EC:1.11.1.6]
112862046  ATG5; autophagy protein 5 [KO:K08339]
112871770  PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198] [EC:2.7.11.31]
112861156  PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform X1 [KO:K07198] [EC:2.7.11.31]
112869010  PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199]
112870095  PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199]
112866705  PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 [KO:K07200]
112867041  PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200]
112867175  PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
112848905  MTOR; serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
112850817  AKT1S1; proline-rich AKT1 substrate 1 [KO:K16184]
112852203  RPS6KB1; ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
112854631  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
112849351  SOD1; superoxide dismutase [Cu-Zn] [KO:K04565] [EC:1.15.1.1]
112854390  EIF4EBP2; eukaryotic translation initiation factor 4E-binding protein 2 [KO:K18644]
112865282  HSPA8; LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein [KO:K03283]
112853784  heat shock 70 kDa protein 1-like [KO:K03283]
112853785  heat shock 70 kDa protein 1-like [KO:K03283]
112864906  CRYAB; alpha-crystallin B chain [KO:K09542]
112868534  HDAC1; histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
112862527  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
112869208  FOXA2; hepatocyte nuclear factor 3-beta [KO:K08035]
112865206  CLPB; caseinolytic peptidase B protein homolog isoform X1 [KO:K03695]
Compound
C00575  3',5'-Cyclic AMP
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
PMID:20395504
  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
PMID:20098959
  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
PMID:26682004
  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
PMID:18946478
  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
PMID:16304601
  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
PMID:12610293
  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
PMID:25153840
  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
PMID:20336132
  Authors
Kenyon CJ
  Title
The genetics of ageing.
  Journal
Nature 464:504-12 (2010)
DOI:10.1038/nature08980
Reference
PMID:20097433
  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
PMID:22094419
  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
PMID:26525455
  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
PMID:18373439
  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
PMID:17701476
  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
PMID:21909281
  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
PMID:23615258
  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
PMID:15768047
  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
PMID:21841070
  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
PMID:14534077
  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
PMID:17684529
  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
pcoo04068  FoxO signaling pathway
pcoo04150  mTOR signaling pathway
pcoo04151  PI3K-Akt signaling pathway
pcoo04152  AMPK signaling pathway
pcoo04211  Longevity regulating pathway
pcoo04910  Insulin signaling pathway
KO pathway
ko04213   
LinkDB

DBGET integrated database retrieval system