age-1;cst-1

There is no network for this step.

Fullscreen mode

Hide graph

Legend

Genetic mutants with age-1, cst-1 alterations

Names of genes are ordered alphabetically. For the order of interventions, please see the specific paper.

Lifespan (days)
21.1
Lifespan change (compared to wild type)
29.45%
Phenotype
CST knockdown reduced life span to a similar extent in both N2 and DAF-2-deficient daf-2(e1368) C. elegans as well as in both age-1(hx546) and N2 nematodes
Lifespan comparisons
Double mutant age-1(hx546);cst-1(RNAi) has a lifespan of 21.1 days, while single mutant age-1(hx546) has a lifespan of 24.8 days and wild type has a lifespan of 16.3 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Lehtinen MK et al., 2006, A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span. Cell. 125(5):987-1001 16751106 Click here to select all mutants from this PubMed ID in the graph
Abstract
Oxidative stress influences cell survival and homeostasis, but the mechanisms underlying the biological effects of oxidative stress remain to be elucidated. Here, we demonstrate that the protein kinase MST1 mediates oxidative-stress-induced cell death in primary mammalian neurons by directly activating the FOXO transcription factors. MST1 phosphorylates FOXO proteins at a conserved site within the forkhead domain that disrupts their interaction with 14-3-3 proteins, promotes FOXO nuclear translocation, and thereby induces cell death in neurons. We also extend the MST-FOXO signaling link to nematodes. Knockdown of the C. elegans MST1 ortholog CST-1 shortens life span and accelerates tissue aging, while overexpression of cst-1 promotes life span and delays aging. The cst-1-induced life-span extension occurs in a daf-16-dependent manner. The identification of the FOXO transcription factors as major and evolutionarily conserved targets of MST1 suggests that MST kinases play important roles in diverse biological processes including cellular responses to oxidative stress and longevity.

Search genes: age-1 cst-1

Entrez ID
Symbol
GenAge
Wormbase ID

174762
age-1
View on GenAge (age-1)
WBGene00000090

Phosphatidylinositol 3-kinase age-1;hypothetical protein

Locus: CELE_B0334.8

Wormbase description: age-1 encodes the C. elegans ortholog of the phosphoinositide 3-kinase (PI3K) p110 catalytic subunit; AGE-1, supplied maternally and embryonically, is a central component of the C. elegans insulin-like signaling pathway, lying downstream of the DAF-2/insulin receptor and upstream of both the PDK-1 and AKT-1/AKT-2 kinases and the DAF-16 forkhead type transcription factor, whose negative regulation is the key output of the insulin signaling pathway; in accordance with its role in insulin signaling, AGE-1 activity is required for regulation of metabolism, life span, dauer formation, stress resistance, salt chemotaxis learning, fertility, and embryonic development; although the age-1 expression pattern has not yet been reported, ectopic expression studies indicate that pan-neuronal age-1 expression is sufficient to rescue life-span defects, while neuronal, intestinal, or muscle expression can partially rescue dauer formation, and neuronal or muscle expression can rescue metabolic defects.

Entrez ID
Symbol
GenAge
Wormbase ID

180708
cst-1
View on GenAge (cst-1)
WBGene00017472

Serine/threonine-protein kinase cst-1 37kDa subunit

Locus: CELE_F14H12.4

Wormbase description: cst-1 encodes one of two C. elegans protein kinases orthologous to the MST (mammalian Ste20-like) kinases and Drosophila Hippo; CST-1 appears to play a role in the responses to oxidative stress and determination of adult lifespan; in regulating stress response and lifespan, CST-1 functions upstream of the DAF-16/FOXO transcription factor; CST-1 physically interacts with RSF-1, the C. elegans homolog of the Ras-association domain family protein 1.

Orthologs of age-1;cst-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	hpo;Pi3K92E
Mus musculus	Pik3cd;Stk3
Mus musculus	Pik3cd;Stk4
Mus musculus	Pik3ca;Stk3
Mus musculus	Pik3ca;Stk4
Mus musculus	Pik3cb;Stk3
Mus musculus	Pik3cb;Stk4
Mus musculus	Pik3cg;Stk3
Mus musculus	Pik3cg;Stk4

Orthologs of age-1 in SynergyAge

Show in SynergyAge
Species	Gene
Drosophila melanogaster	Pi3K92E

Not in SynergyAge
Species	Gene
Mus musculus	Pik3cd
Mus musculus	Pik3ca
Mus musculus	Pik3cb
Mus musculus	Pik3cg

Orthologs of cst-1 in SynergyAge

Show in SynergyAge
Species	Gene

About

SynergyAge database hosts high-quality, manually curated information about the synergistic and antagonistic lifespan effects of genetic interventions in model organisms, also allowing users to explore the longevity relationships between genes in a visual way.