Entry Name Longevity regulating pathway - Enhydra lutris kenyoni (northern sea otter)
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; AgingBRITE hierarchy
Pathway map Ortholog table Organism Enhydra lutris kenyoni (northern sea otter) [GN:
elk ]
Gene 111155003 LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
111154641 phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
111143470 phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
111155224 phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
111143790 phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
111147575 cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
111142901 cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450 ]
111151973 cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048 ]
111150050 cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048 ]
111138943 cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048 ]
111161856 cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048 ]
111152366 cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049 ]
111144538 eukaryotic translation initiation factor 4E-binding protein 1 [KO:K07205 ]
111146502 eukaryotic translation initiation factor 4E type 1B-like [KO:K03259 ]
111146503 eukaryotic translation initiation factor 4E type 1B-like [KO:K03259 ]
111157179 eukaryotic translation initiation factor 4E isoform X1 [KO:K03259 ]
111150366 eukaryotic translation initiation factor 4E type 2 isoform X1 [KO:K03259 ]
111162051 5'-AMP-activated protein kinase subunit beta-2 isoform X1 [KO:K07199 ]
111142413 5'-AMP-activated protein kinase subunit gamma-3 isoform X1 [KO:K07200 ]
111154394 LOW QUALITY PROTEIN: 5'-AMP-activated protein kinase subunit gamma-2 [KO:K07200 ]
111157789 5'-AMP-activated protein kinase subunit gamma-1 isoform X1 [KO:K07200 ]
111149050 peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform X1 [KO:K07202 ]
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 KO pathway LinkDB All DBs
