daf-2;egr-1

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Genetic mutants with daf-2, egr-1 alterations

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

Temperature °C
25
Lifespan (days)
23.6
Lifespan change (compared to wild type)
60.54%
Phenotype
Fifty-seven gene inactivations (corresponding to 55 RNAi clones) more dramatically shortened the life span of daf-2 animals compared with daf-2;daf-16, but still shortened the life span of daf-2;daf-16 animals, suggesting that they function in a parallel/converging pathway to insulin/IGF1 signaling
Lifespan comparisons
Double mutant daf-2(e1370);egr-1(RNAi) has a lifespan of 23.6 days, while single mutant daf-2(e1370) has a lifespan of 36.7 days, single mutant egr-1(RNAi) has a lifespan of 11.1 days and wild type has a lifespan of 14.7 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Samuelson AV et al., 2007, Gene activities that mediate increased life span of C. elegans insulin-like signaling mutants. Genes Dev. 21(22):2976-94 18006689 Click here to select all mutants from this PubMed ID in the graph
Abstract
Genetic and RNA interference (RNAi) screens for life span regulatory genes have revealed that the daf-2 insulin-like signaling pathway plays a major role in Caenorhabditis elegans longevity. This pathway converges on the DAF-16 transcription factor and may regulate life span by controlling the expression of a large number of genes, including free-radical detoxifying genes, stress resistance genes, and pathogen resistance genes. We conducted a genome-wide RNAi screen to identify genes necessary for the extended life span of daf-2 mutants and identified approximately 200 gene inactivations that shorten daf-2 life span. Some of these gene inactivations dramatically shorten daf-2 mutant life span but less dramatically shorten daf-2; daf-16 mutant or wild-type life span. Molecular and behavioral markers for normal aging and for extended life span in low insulin/IGF1 (insulin-like growth factor 1) signaling were assayed to distinguish accelerated aging from general sickness and to examine age-related phenotypes. Detailed demographic analysis, molecular markers of aging, and insulin signaling mutant test strains were used to filter progeric gene inactivations for specific acceleration of aging. Highly represented in the genes that mediate life span extension in the daf-2 mutant are components of endocytotic trafficking of membrane proteins to lysosomes. These gene inactivations disrupt the increased expression of the DAF-16 downstream gene superoxide dismutase sod-3 in a daf-2 mutant, suggesting trafficking between the insulin-like receptor and DAF-16. The activities of these genes may normally decline during aging.

Temperature °C
20
Diet
HT115
Lifespan (days)
20.1
Lifespan change (compared to wild type)
24.84%
Phenotype
If a GATA transcription factor functions specifically to extend life span rather than shorten it, then RNAi treatment may suppress the longevity of a long-lived mutant such as daf-2(e1370) without causing nonspecific early lethality of wild-type worms. Of the ten GATA transcription factor genes, we found that RNAi treatment of three (elt-3, egr-1, and egl-27) behave in this way in multiple independent life span experiments
Lifespan comparisons
Double mutant daf-2(e1370);egr-1(RNAi) has a lifespan of 20.1 days, while single mutant egr-1(RNAi) has a lifespan of 16.9 days, single mutant daf-2(e1370) has a lifespan of 24.1 days and wild type has a lifespan of 16.1 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Budovskaya YV et al., 2008, An elt-3/elt-5/elt-6 GATA transcription circuit guides aging in C. elegans. Cell. 134(2):291-303 18662544 Click here to select all mutants from this PubMed ID in the graph
Abstract
To define the C. elegans aging process at the molecular level, we used DNA microarray experiments to identify a set of 1294 age-regulated genes and found that the GATA transcription factors ELT-3, ELT-5, and ELT-6 are responsible for age regulation of a large fraction of these genes. Expression of elt-5 and elt-6 increases during normal aging, and both of these GATA factors repress expression of elt-3, which shows a corresponding decrease in expression in old worms. elt-3 regulates a large number of downstream genes that change expression in old age, including ugt-9, col-144, and sod-3. elt-5(RNAi) and elt-6(RNAi) worms have extended longevity, indicating that elt-3, elt-5, and elt-6 play an important functional role in the aging process. These results identify a transcriptional circuit that guides the rapid aging process in C. elegans and indicate that this circuit is driven by drift of developmental pathways rather than accumulation of damage.

Temperature °C
20
Diet
HT115
Lifespan (days)
22.0
Lifespan change (compared to wild type)
41.94%
Phenotype
If a GATA transcription factor functions specifically to extend life span rather than shorten it, then RNAi treatment may suppress the longevity of a long-lived mutant such as daf-2(e1370) without causing nonspecific early lethality of wild-type worms. Of the ten GATA transcription factor genes, we found that RNAi treatment of three (elt-3, egr-1, and egl-27) behave in this way in multiple independent life span experiments
Lifespan comparisons
Double mutant daf-2(e1370);egr-1(RNAi) has a lifespan of 22.0 days, while single mutant egr-1(RNAi) has a lifespan of 17.9 days, single mutant daf-2(e1370) has a lifespan of 29.6 days and wild type has a lifespan of 15.5 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Budovskaya YV et al., 2008, An elt-3/elt-5/elt-6 GATA transcription circuit guides aging in C. elegans. Cell. 134(2):291-303 18662544 Click here to select all mutants from this PubMed ID in the graph
Abstract
To define the C. elegans aging process at the molecular level, we used DNA microarray experiments to identify a set of 1294 age-regulated genes and found that the GATA transcription factors ELT-3, ELT-5, and ELT-6 are responsible for age regulation of a large fraction of these genes. Expression of elt-5 and elt-6 increases during normal aging, and both of these GATA factors repress expression of elt-3, which shows a corresponding decrease in expression in old worms. elt-3 regulates a large number of downstream genes that change expression in old age, including ugt-9, col-144, and sod-3. elt-5(RNAi) and elt-6(RNAi) worms have extended longevity, indicating that elt-3, elt-5, and elt-6 play an important functional role in the aging process. These results identify a transcriptional circuit that guides the rapid aging process in C. elegans and indicate that this circuit is driven by drift of developmental pathways rather than accumulation of damage.

Search genes: daf-2 egr-1

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.

Symbol
GenAge

egr-1
View on GenAge (egr-1)

No gene information for egr-1

Orthologs of daf-2;egr-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
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

Orthologs of egr-1 in SynergyAge

Show in SynergyAge
Species	Gene