Entry
Name
Longevity regulating pathway - multiple species - Loxodonta africana (African savanna elephant)
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
BRITE hierarchy
Pathway map
lav04213 Longevity regulating pathway - multiple species
Ortholog table
Organism
Loxodonta africana (African savanna elephant) [GN:
lav ]
Gene
100660353 LOW QUALITY PROTEIN: insulin receptor substrate 1-like [KO:K17445 ]
100667324 IRS4; LOW QUALITY PROTEIN: insulin receptor substrate 4 [KO:K17446 ]
100657948 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
100658340 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
100666266 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
100653731 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
100665045 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
100675496 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
100665273 PRKAB2; 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199 ]
100676546 PRKAB1; 5'-AMP-activated protein kinase subunit beta-1 [KO:K07199 ]
100669727 PRKAG1; 5'-AMP-activated protein kinase subunit gamma-1 isoform X2 [KO:K07200 ]
100675348 PRKAG3; 5'-AMP-activated protein kinase subunit gamma-3 [KO:K07200 ]
100672035 PRKAG2; 5'-AMP-activated protein kinase subunit gamma-2 [KO:K07200 ]
100671084 EIF4EBP2; eukaryotic translation initiation factor 4E-binding protein 2 [KO:K18644 ]
100656420 HSPA6; LOW QUALITY PROTEIN: heat shock 70 kDa protein 6 [KO:K03283 ]
100670717 FOXA2; LOW QUALITY PROTEIN: hepatocyte nuclear factor 3-beta [KO:K08035 ]
100673715 CLPB; caseinolytic peptidase B protein homolog isoform X1 [KO:K03695 ]
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 pathway
KO pathway
LinkDB
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