Entry
Name
Longevity regulating pathway - Equus przewalskii (Przewalski's horse)
Description
Regulation of longevity depends on genetic and environmental factors. Caloric restriction (CR), that is limiting food intake, is recognized in mammals as the best characterized and most reproducible strategy for extending lifespan. Four pathways have been implicated in mediating the CR effect. These are the insulin like growth factor (IGF-1)/insulin signaling pathway, the sirtuin pathway, the adenosine monophosphate (AMP) activated protein kinase (AMPK) pathway and the target of rapamycin (TOR) pathway. The collective response of these pathways to CR is believed to promote cellular fitness and ultimately longevity via activation of autophagy, stress defense mechanisms, and survival pathways while attenuating proinflammatory mediators and cellular growth. Furthermore, there is evidence supporting that life span extension can be achieved with pharmacologic agents that mimic the effects of caloric restriction, such as rapamycin, via mTOR signaling blockade, resveratrol, by activating SIRT1 activity, and metformin, which seems to be a robust stimulator of AMPK activity. As an aging suppressor, Klotho is an important molecule in aging processes and its overexpression results in longevity.
Class
Organismal Systems; Aging
BRITE hierarchy
Pathway map
Ortholog table
Organism
Equus przewalskii (Przewalski's horse) [GN:
epz ]
Gene
103548220 PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
103551868 PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
103561550 PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
103566499 CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048 ]
103564266 CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048 ]
103555399 CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048 ]
103547320 RPTOR; regulatory associated protein of MTOR complex 1 [KO:K07204 ]
103543726 EIF4EBP1; eukaryotic translation initiation factor 4E binding protein 1 [KO:K07205 ]
103565936 EIF4E2; eukaryotic translation initiation factor 4E family member 2 [KO:K03259 ]
103540982 EIF4E1B; eukaryotic translation initiation factor 4E family member 1B [KO:K03259 ]
103541667 ADIPOQ; adiponectin, C1Q and collagen domain containing [KO:K07296 ]
103547870 APPL1; adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1 [KO:K08733 ]
103540717 PRKAB1; protein kinase AMP-activated non-catalytic subunit beta 1 [KO:K07199 ]
103542394 PRKAB2; protein kinase AMP-activated non-catalytic subunit beta 2 [KO:K07199 ]
103552223 PRKAG1; protein kinase AMP-activated non-catalytic subunit gamma 1 [KO:K07200 ]
103567915 PRKAG3; protein kinase AMP-activated non-catalytic subunit gamma 3 [KO:K07200 ]
103554547 PPARG; peroxisome proliferator activated receptor gamma [KO:K08530 ]
Compound
C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference
Authors
Barzilai N, Huffman DM, Muzumdar RH, Bartke A
Title
The critical role of metabolic pathways in aging.
Journal
Reference
Authors
Fontana L, Partridge L, Longo VD
Title
Extending healthy life span--from yeast to humans.
Journal
Reference
Authors
Feng Z, Lin M, Wu R
Title
The Regulation of Aging and Longevity: A New and Complex Role of p53.
Journal
Reference
Authors
Kenyon CJ
Title
The genetics of ageing.
Journal
Reference
Authors
Cheng CW, Adams GB, Perin L, Wei M, Zhou X, Lam BS, Da Sacco S, Mirisola M, Quinn DI, Dorff TB, Kopchick JJ, Longo VD
Title
Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression.
Journal
Reference
Authors
Morris BJ, Willcox DC, Donlon TA, Willcox BJ
Title
FOXO3: A Major Gene for Human Longevity - A Mini-Review.
Journal
Reference
Authors
Pyo JO, Yoo SM, Ahn HH, Nah J, Hong SH, Kam TI, Jung S, Jung YK
Title
Overexpression of Atg5 in mice activates autophagy and extends lifespan.
Journal
Reference
Authors
Madeo F, Zimmermann A, Maiuri MC, Kroemer G
Title
Essential role for autophagy in life span extension.
Journal
Reference
Authors
Passtoors WM, Beekman M, Deelen J, van der Breggen R, Maier AB, Guigas B, Derhovanessian E, van Heemst D, de Craen AJ, Gunn DA, Pawelec G, Slagboom PE
Title
Gene expression analysis of mTOR pathway: association with human longevity.
Journal
Reference
Authors
Markaki M, Tavernarakis N
Title
Metabolic control by target of rapamycin and autophagy during ageing - a mini-review.
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
Ruderman NB, Xu XJ, Nelson L, Cacicedo JM, Saha AK, Lan F, Ido Y
Title
AMPK and SIRT1: a long-standing partnership?
Journal
Reference
Authors
Iwabu M, Yamauchi T, Okada-Iwabu M, Sato K, Nakagawa T, Funata M, Yamaguchi M, Namiki S, Nakayama R, Tabata M, Ogata H, Kubota N, Takamoto I, Hayashi YK, Yamauchi N, Waki H, Fukayama M, Nishino I, Tokuyama K, Ueki K, Oike Y, Ishii S, Hirose K, Shimizu T, Touhara K, Kadowaki T
Title
Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1.
Journal
Reference
Authors
Ramis MR, Esteban S, Miralles A, Tan DX, Reiter RJ
Title
Caloric restriction, resveratrol and melatonin: Role of SIRT1 and implications for aging and related-diseases.
Journal
Reference
Authors
Canto C, Gerhart-Hines Z, Feige JN, Lagouge M, Noriega L, Milne JC, Elliott PJ, Puigserver P, Auwerx J
Title
AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity.
Journal
Reference
Authors
Esmaili S, Xu A, George J
Title
The multifaceted and controversial immunometabolic actions of adiponectin.
Journal
Reference
Authors
Mouchiroud L, Molin L, Dalliere N, Solari F
Title
Life span extension by resveratrol, rapamycin, and metformin: The promise of dietary restriction mimetics for an healthy aging.
Journal
Reference
Authors
Tucci P
Title
Caloric restriction: is mammalian life extension linked to p53?
Journal
Reference
Authors
Budanov AV, Karin M
Title
p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling.
Journal
Reference
Authors
Sopjani M, Rinnerthaler M, Kruja J, Dermaku-Sopjani M
Title
Intracellular signaling of the aging suppressor protein Klotho.
Journal
Reference
Authors
Longo VD, Lieber MR, Vijg J
Title
Turning anti-ageing genes against cancer.
Journal
Related pathway
KO pathway
LinkDB
All DBs