ENTRY ko04213 Pathway NAME Longevity regulating pathway - multiple species 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 ko04213 Longevity regulating pathway - multiple species ORTHOLOGY K04526 insulin K04527 insulin receptor [EC:2.7.10.1] K05459 insulin-like growth factor 1 K05087 insulin-like growth factor 1 receptor [EC:2.7.10.1] K16172 insulin receptor substrate 1 K07187 insulin receptor substrate 2 K17445 insulin receptor substrate 3 K17446 insulin receptor substrate 4 K02833 GTPase HRas K07827 GTPase KRas K07828 GTPase NRas K00922 phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153] K02649 phosphoinositide-3-kinase regulatory subunit alpha/beta/delta K04456 RAC serine/threonine-protein kinase [EC:2.7.11.1] K08041 adenylate cyclase 1 [EC:4.6.1.1] K08042 adenylate cyclase 2 [EC:4.6.1.1] K08043 adenylate cyclase 3 [EC:4.6.1.1] K08044 adenylate cyclase 4 [EC:4.6.1.1] K08045 adenylate cyclase 5 [EC:4.6.1.1] K08046 adenylate cyclase 6 [EC:4.6.1.1] K08047 adenylate cyclase 7 [EC:4.6.1.1] K08048 adenylate cyclase 8 [EC:4.6.1.1] K08049 adenylate cyclase 9 [EC:4.6.1.1] K04345 protein kinase A [EC:2.7.11.11] K07201 forkhead box protein O1 K09408 forkhead box protein O3 K04564 superoxide dismutase, Fe-Mn family [EC:1.15.1.1] K03781 catalase [EC:1.11.1.6] K08339 autophagy-related protein 5 K07198 5'-AMP-activated protein kinase, catalytic alpha subunit [EC:2.7.11.31] K07199 5'-AMP-activated protein kinase, regulatory beta subunit K07200 5'-AMP-activated protein kinase, regulatory gamma subunit K07203 serine/threonine-protein kinase mTOR [EC:2.7.11.1] K07204 regulatory associated protein of mTOR K16184 proline-rich AKT1 substrate 1 K04688 ribosomal protein S6 kinase beta [EC:2.7.11.1] K11411 NAD-dependent protein deacetylase sirtuin 1 [EC:2.3.1.286] K19805 insulin-like peptide 7 K04565 superoxide dismutase, Cu-Zn family [EC:1.15.1.1] K18644 eukaryotic translation initiation factor 4E binding protein 2 K03283 heat shock 70kDa protein 1/6/8 K09542 crystallin, alpha B K06067 histone deacetylase 1/2 [EC:3.5.1.98] K19764 insulin-like neuropeptide K08035 forkhead box protein A2, hepatocyte nuclear factor 3-beta K19766 heat shock protein Hsp-16.1/Hsp-16.11 K19767 heat shock protein Hsp-16.48/Hsp-16.49 K19768 heat shock protein 12.6 K19769 stress-induced protein 1 K12762 G protein-coupled receptor GPR1 K01768 adenylate cyclase [EC:4.6.1.1] K09468 zinc finger protein MSN2/4 K12767 serine/threonine-protein kinase RIM15 [EC:2.7.11.36] K19798 transcriptional activator/repressor GIS1 K19800 serine/threonine protein kinase SCH9 [EC:2.7.11.1] K03695 ATP-dependent Clp protease ATP-binding subunit ClpB K01440 nicotinamidase [EC:3.5.1.19] K11121 NAD-dependent protein deacetylase SIR2 [EC:2.3.1.286] 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. 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JOURNAL Nat Rev Mol Cell Biol 8:681-91 (2007) DOI:10.1038/nrm2234 REL_PATHWAY ko04068 FoxO signaling pathway ko04150 mTOR signaling pathway ko04151 PI3K-Akt signaling pathway ko04152 AMPK signaling pathway ko04211 Longevity regulating pathway ko04212 Longevity regulating pathway - worm ko04910 Insulin signaling pathway ///