clk-5;daf-2

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Genetic mutants with clk-5, daf-2 alterations

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

Temperature °C
20
Diet
NGM
Lifespan (days)
34.48
Lifespan change (compared to wild type)
85.18%
Phenotype
clk-5 (qm152) mutations did not increase the life span of daf-2(e1370) worms and thus are non-additive.
Lifespan comparisons
Double mutant clk-5(qm152);daf-2(e1370) has a lifespan of 34.48 days, while single mutant clk-5(qm152) has a lifespan of 20.68 days, single mutant daf-2(e1370) has a lifespan of 37.24 days and wild type has a lifespan of 18.62 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Van Raamsdonk JM et al., 2010, Decreased energy metabolism extends life span in Caenorhabditis elegans without reducing oxidative damage. Genetics. 185(2):559-71 20382831 Click here to select all mutants from this PubMed ID in the graph
Abstract
On the basis of the free radical and rate of living theories of aging, it has been proposed that decreased metabolism leads to increased longevity through a decreased production of reactive oxygen species (ROS). In this article, we examine the relationship between mitochondrial energy metabolism and life span by using the Clk mutants in Caenorhabditis elegans. Clk mutants are characterized by slow physiologic rates, delayed development, and increased life span. This phenotype suggests that increased life span may be achieved by decreasing energy expenditure. To test this hypothesis, we identified six novel Clk mutants in a screen for worms that have slow defecation and slow development and that can be maternally rescued. Interestingly, all 11 Clk mutants have increased life span despite the fact that slow physiologic rates were used as the only screening criterion. Although mitochondrial function is decreased in the Clk mutants, ATP levels are normal or increased, suggesting decreased energy utilization. To determine whether the longevity of the Clk mutants results from decreased production of ROS, we examined sensitivity to oxidative stress and oxidative damage. We found no evidence for systematically increased resistance to oxidative stress or decreased oxidative damage in the Clk mutants despite normal or elevated levels of superoxide dismutases. Overall, our findings suggest that decreased energy metabolism can lead to increased life span without decreased production of ROS.

Search genes: clk-5 daf-2

Symbol
GenAge

clk-5
View on GenAge (clk-5)

No gene information for clk-5

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.

Orthologs of clk-5;daf-2 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of clk-5 in SynergyAge

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Species	Gene

Orthologs of daf-2 in SynergyAge

Show in SynergyAge
Species	Gene
Drosophila melanogaster	InR

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

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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.