Entry Name Longevity regulating pathway - multiple species - Homo sapiens (human)
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; AgingBRITE hierarchy
Pathway map hsa04213 Longevity regulating pathway - multiple species
Drug D11811 Tofersen (JAN/USAN/INN)
Organism Homo sapiens (human) [GN:
hsa ]
Gene 1410 CRYAB; alpha-crystallin B chain isoform 1 [KO:K09542 ]
1979 EIF4EBP2; eukaryotic translation initiation factor 4E-binding protein 2 [KO:K18644 ]
208 AKT2; RAC-beta serine/threonine-protein kinase isoform 1 [KO:K04456 ] [EC:2.7.11.1 ]
2309 FOXO3; forkhead box protein O3 isoform 1 [KO:K09408 ]
3170 FOXA2; hepatocyte nuclear factor 3-beta isoform 2 [KO:K08035 ]
3303 HSPA1A; heat shock 70 kDa protein 1A [KO:K03283 ]
3304 HSPA1B; heat shock 70 kDa protein 1B [KO:K03283 ]
3305 HSPA1L; heat shock 70 kDa protein 1-like [KO:K03283 ]
3310 HSPA6; heat shock 70 kDa protein 6 [KO:K03283 ]
3312 HSPA8; heat shock cognate 71 kDa protein isoform 1 [KO:K03283 ]
3479 IGF1; insulin-like growth factor 1 isoform 3 preproprotein [KO:K05459 ]
3480 IGF1R; insulin-like growth factor 1 receptor isoform 1 precursor [KO:K05087 ] [EC:2.7.10.1 ]
3667 IRS1; insulin receptor substrate 1 [KO:K16172 ]
51422 PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 isoform a [KO:K07200 ]
5290 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
5291 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform 1 [KO:K00922 ] [EC:2.7.1.153 ]
5293 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform 1 [KO:K00922 ] [EC:2.7.1.153 ]
5295 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform 1 [KO:K02649 ]
5296 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
53632 PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200 ]
5562 PRKAA1; 5'-AMP-activated protein kinase catalytic subunit alpha-1 isoform 1 [KO:K07198 ] [EC:2.7.11.31 ]
5563 PRKAA2; 5'-AMP-activated protein kinase catalytic subunit alpha-2 [KO:K07198 ] [EC:2.7.11.31 ]
5564 PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199 ]
5565 PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 [KO:K07199 ]
5566 PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform Calpha1 [KO:K04345 ] [EC:2.7.11.11 ]
5567 PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform 2 [KO:K04345 ] [EC:2.7.11.11 ]
5571 PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform 1 [KO:K07200 ]
57521 RPTOR; regulatory-associated protein of mTOR isoform 1 [KO:K07204 ]
6648 SOD2; superoxide dismutase [Mn], mitochondrial isoform A precursor [KO:K04564 ] [EC:1.15.1.1 ]
81570 CLPB; mitochondrial disaggregase isoform 1 [KO:K03695 ]
84335 AKT1S1; proline-rich AKT1 substrate 1 isoform b [KO:K16184 ]
8471 IRS4; insulin receptor substrate 4 isoform 1 [KO:K17446 ]
8503 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform 1 [KO:K02649 ]
8660 IRS2; insulin receptor substrate 2 [KO:K07187 ]
9474 ATG5; autophagy protein 5 isoform a [KO:K08339 ]
Compound C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference Authors Fontana L, Partridge L, Longo VD
Title Extending healthy life span--from yeast to humans.
Journal 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 Reference Authors Santos J, Leitao-Correia F, Sousa MJ, Leao C
Title Dietary Restriction and Nutrient Balance in Aging.
Journal Reference Authors Longo VD, Lieber MR, Vijg J
Title Turning anti-ageing genes against cancer.
Journal Reference Authors Longo VD, Mitteldorf J, Skulachev VP
Title Programmed and altruistic ageing.
Journal Reference Authors Longo VD, Finch CE
Title Evolutionary medicine: from dwarf model systems to healthy centenarians?
Journal Reference Authors Mirzaei H, Suarez JA, Longo VD
Title Protein and amino acid restriction, aging and disease: from yeast to humans.
Journal Reference Authors Kenyon CJ
Title The genetics of ageing.
Journal Reference Authors Longo VD, Fontana L
Title Calorie restriction and cancer prevention: metabolic and molecular mechanisms.
Journal Reference Authors Longo VD, Fabrizio P
Title Chronological aging in Saccharomyces cerevisiae.
Journal Reference Authors Bitto A, Wang AM, Bennett CF, Kaeberlein M
Title Biochemical Genetic Pathways that Modulate Aging in Multiple Species.
Journal Reference Authors Mair W, Dillin A
Title Aging and survival: the genetics of life span extension by dietary restriction.
Journal 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 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 Reference Authors Lee SH, Min KJ
Title Caloric restriction and its mimetics.
Journal Reference Authors Bordone L, Guarente L
Title Calorie restriction, SIRT1 and metabolism: understanding longevity.
Journal Reference Authors Canto C, Auwerx J
Title Calorie restriction: is AMPK a key sensor and effector?
Journal 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 Reference Authors Russell SJ, Kahn CR
Title Endocrine regulation of ageing.
Journal Related KO pathway
