daf-2;sod-4

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Genetic mutants with daf-2, sod-4 alterations

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

Temperature °C
20
Lifespan (days)
63.7
Lifespan change (compared to wild type)
180.62%
Phenotype
The sod-4 deletion had little effect on the lifespan under the wild-type background but slightly extended the lifespan under the daf-2(e1370) background
Lifespan comparisons
Double mutant daf-2(e1370);sod-4(gk101) has a lifespan of 63.7 days, while single mutant daf-2(e1370) has a lifespan of 45.7 days, single mutant sod-4(gk101) has a lifespan of 21.9 days and wild type has a lifespan of 22.7 days.
Type of interaction
See methods
Enhancer, opposite lifespan effects
Citation
View abstract
Honda Y et al., 2008, Modulation of longevity and diapause by redox regulation mechanisms under the insulin-like signaling control in Caenorhabditis elegans. Exp Gerontol. 43(6):520-9 18406553 Click here to select all mutants from this PubMed ID in the graph
Abstract
In Caenorhabditis elegans, the downregulation of insulin-like signaling induces lifespan extension (Age) and the constitutive formation of dauer larvae (Daf-c). This also causes resistance to oxidative stress (Oxr) and other stress stimuli and enhances the expression of many stress-defense-related enzymes such as Mn superoxide dismutase (SOD) that functions to remove reactive oxygen species in mitochondria. To elucidate the roles of the two isoforms of MnSOD, SOD-2 and SOD-3, in the Age, Daf-c and Oxr phenotypes, we investigated the effects of a gene knockout of MnSODs on them in the daf-2 (insulin-like receptor) mutants that lower insulin-like signaling. In our current report, we demonstrate that double deletions of two MnSOD genes induce oxidative-stress sensitivity and thus ablate Oxr, but do not abolish Age in the daf-2 mutant background. This indicates that Oxr is not the underlying cause of Age and that oxidative stress is not necessarily a limiting factor for longevity. Interestingly, deletions in the sod-2 and sod-3 genes suppressed and stimulated, respectively, both Age and Daf-c. In addition, the sod-2/sod-3 double deletions stimulated these phenotypes in a similar manner to the sod-3 deletion, suggesting that the regulatory pathway consists of two MnSOD isoforms. Furthermore, hyperoxic and hypoxic conditions affected Daf-c in the MnSOD-deleted daf-2 mutants. We thus conclude that the MnSOD systems in C. elegans fine-tune the insulin-like-signaling based regulation of both longevity and dauer formation by acting not as antioxidants but as physiological-redox-signaling modulators.

Search genes: daf-2 sod-4

Entrez ID
Symbol
GenAge
Wormbase ID

175410
daf-2
View on GenAge (daf-2)
WBGene00000898

Insulin-like receptor subunit beta;Receptor protein-tyrosine kinase;hypothetical protein

Locus: CELE_Y55D5A.5

Wormbase description: daf-2 encodes a receptor tyrosine kinase that is the C. elegans insulin/IGF receptor ortholog; DAF-2 activity is required for a number of processes in C. elegans, including embryonic and larval development, formation of the developmentally arrested dauer larval stage (diapause), larval developmental timing, adult longevity, reproduction, fat storage, salt chemotaxis learning, and stress resistance, including response to high temperature, oxidative stress, and bacterial infection; DAF-2 signals through a conserved PI 3-kinase pathway to negatively regulate the activity of DAF-16, a Forkhead-related transcription factor, by inducing its phosphorylation and nuclear exclusion; in addition, DAF-2 negatively regulates the nuclear localization, and hence transcriptional activity, of SKN-1 in intestinal nuclei; amongst the 38 predicted insulin-like molecules in C. elegans, genetic and microarray analyses suggest that at least DAF-28, INS-1, and INS-7 are likely DAF-2 ligands; genetic mosaic and tissue-specific promoter studies indicate that daf-2 can function cell nonautonomously and within multiple cell types to influence dauer formation and adult lifespan, likely by regulating the production of secondary endocrine signals that coordinate growth and longevity throughout the animal; temporal analysis of daf-2 function indicates that daf-2 regulates lifespan, reproduction, and diapause independently, at distinct times during the animal's life cycle.

Entrez ID
Symbol
GenAge
Wormbase ID

176336
sod-4
View on GenAge (sod-4)
WBGene00004933

Extracellular superoxide dismutase [Cu-Zn];Superoxide dismutase [Cu-Zn]

Locus: CELE_F55H2.1

Wormbase description: sod-4 encodes an extracellular Cu2+/Zn2+ superoxide dismutase (SOD) that is one of five C. elegans SOD enzymes; genetic analyses indicates that sod-4 is required for redox regulation of a number of processes including axon pathfinding in the PVQ interneurons, insulin/IGF-1 signaling, and vulval development; large-scale expression studies indicate that sod-4 is expressed in the nervous system, intestine, and rectal gland cells; sod-4 transcripts are significantly upregulated in dauers.

Orthologs of daf-2;sod-4 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of daf-2 in SynergyAge

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Species	Gene
Drosophila melanogaster	InR

Not in SynergyAge
Species	Gene
Mus musculus	Insr
Mus musculus	Igf1r
Mus musculus	Insrr

Orthologs of sod-4 in SynergyAge

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Species	Gene