KEGG   PATHWAY: tmu04213
Entry
tmu04213                    Pathway                                
Name
Longevity regulating pathway - multiple species - Trichechus manatus latirostris (Florida manatee)
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
tmu04213  Longevity regulating pathway - multiple species
tmu04213

Organism
Trichechus manatus latirostris (Florida manatee) [GN:tmu]
Gene
101346705  insulin [KO:K04526]
101360415  insulin receptor [KO:K04527] [EC:2.7.10.1]
101361934  insulin-like growth factor I isoform X1 [KO:K05459]
101355333  insulin-like growth factor 1 receptor [KO:K05087] [EC:2.7.10.1]
101356151  insulin receptor substrate 1 [KO:K16172]
101345051  insulin receptor substrate 2 [KO:K07187]
101362072  insulin receptor substrate 1-like [KO:K17445]
101350401  insulin receptor substrate 4 isoform X1 [KO:K17446]
101342804  GTPase HRas isoform X2 [KO:K02833]
101347525  GTPase KRas isoform X3 [KO:K07827]
101344230  GTPase NRas isoform X1 [KO:K07828]
101358678  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101346849  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101359658  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
101351035  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
101343804  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101347746  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101360493  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101356099  RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101350197  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101354868  adenylate cyclase type 1 [KO:K08041] [EC:4.6.1.1]
101360334  adenylate cyclase type 2 [KO:K08042] [EC:4.6.1.1]
101349290  adenylate cyclase type 3 [KO:K08043] [EC:4.6.1.1]
101350438  adenylate cyclase type 4 [KO:K08044] [EC:4.6.1.1]
101346041  adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
101349243  adenylate cyclase type 6 [KO:K08046] [EC:4.6.1.1]
101341715  adenylate cyclase type 7 isoform X1 [KO:K08047] [EC:4.6.1.1]
101350704  adenylate cyclase type 8 isoform X1 [KO:K08048] [EC:4.6.1.1]
101344705  adenylate cyclase type 9 [KO:K08049] [EC:4.6.1.1]
101342638  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
101348995  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
101340503  LOW QUALITY PROTEIN: forkhead box protein O1 [KO:K07201]
101354741  forkhead box protein O3 [KO:K09408]
101345412  superoxide dismutase [Mn], mitochondrial [KO:K04564] [EC:1.15.1.1]
105756103  superoxide dismutase [Mn], mitochondrial-like [KO:K04564] [EC:1.15.1.1]
101361987  catalase [KO:K03781] [EC:1.11.1.6]
101351212  autophagy protein 5 isoform X3 [KO:K08339]
101346784  5'-AMP-activated protein kinase catalytic subunit alpha-1 [KO:K07198] [EC:2.7.11.31]
101360368  5'-AMP-activated protein kinase catalytic subunit alpha-2 isoform X1 [KO:K07198] [EC:2.7.11.31]
101356476  5'-AMP-activated protein kinase subunit beta-2 isoform X2 [KO:K07199]
101361359  5'-AMP-activated protein kinase subunit beta-1 isoform X2 [KO:K07199]
101341480  5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200]
101352672  5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200]
101349182  5'-AMP-activated protein kinase subunit gamma-2 isoform X2 [KO:K07200]
101343808  serine/threonine-protein kinase mTOR [KO:K07203] [EC:2.7.11.1]
101343081  LOW QUALITY PROTEIN: regulatory-associated protein of mTOR [KO:K07204]
101345300  LOW QUALITY PROTEIN: proline-rich AKT1 substrate 1 [KO:K16184]
101343535  ribosomal protein S6 kinase beta-2 isoform X1 [KO:K04688] [EC:2.7.11.1]
101354510  ribosomal protein S6 kinase beta-1 isoform X1 [KO:K04688] [EC:2.7.11.1]
101342951  NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
101341738  LOW QUALITY PROTEIN: superoxide dismutase [Cu-Zn]-like [KO:K04565] [EC:1.15.1.1]
101358349  superoxide dismutase [Cu-Zn] [KO:K04565] [EC:1.15.1.1]
101355477  eukaryotic translation initiation factor 4E-binding protein 2 [KO:K18644]
101348660  heat shock 70 kDa protein 1-like [KO:K03283]
101354728  heat shock cognate 71 kDa protein [KO:K03283]
101351001  heat shock 70 kDa protein 6 [KO:K03283]
101356837  LOW QUALITY PROTEIN: heat shock 70 kDa protein-like [KO:K03283]
101356536  LOW QUALITY PROTEIN: heat shock cognate 71 kDa protein-like [KO:K03283]
101348919  heat shock 70 kDa protein 1 [KO:K03283]
101357110  heat shock 70 kDa protein 1 [KO:K03283]
101345815  alpha-crystallin B chain [KO:K09542]
101342476  histone deacetylase 2 isoform X1 [KO:K06067] [EC:3.5.1.98]
101357779  histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
101354174  hepatocyte nuclear factor 3-beta [KO:K08035]
101351345  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
tmu04068  FoxO signaling pathway
tmu04150  mTOR signaling pathway
tmu04151  PI3K-Akt signaling pathway
tmu04152  AMPK signaling pathway
tmu04211  Longevity regulating pathway
tmu04910  Insulin signaling pathway
KO pathway
ko04213   
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