daf-2;elt-3

There is no network for this step.

Fullscreen mode

Hide graph

Legend

Genetic mutants with daf-2, elt-3 alterations

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

Temperature °C
20
Diet
HT115
Lifespan (days)
22.7
Lifespan change (compared to wild type)
59.86%
Lifespan comparisons
Double mutant daf-2(RNAi);elt-3(vp1) has a lifespan of 22.7 days, while single mutant daf-2(RNAi) has a lifespan of 24.5 days, single mutant elt-3(vp1) has a lifespan of 12.6 days and wild type has a lifespan of 14.2 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
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.

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

Temperature °C
20
Diet
HT115
Lifespan (days)
17.5
Lifespan change (compared to wild type)
19.86%
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);elt-3(RNAi) has a lifespan of 17.5 days, while single mutant elt-3(RNAi) has a lifespan of 15.2 days, single mutant daf-2(e1370) has a lifespan of 28.5 days and wild type has a lifespan of 14.6 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)
14.7
Lifespan change (compared to wild type)
0.68%
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);elt-3(RNAi) has a lifespan of 14.7 days, while single mutant elt-3(RNAi) has a lifespan of 12.8 days, single mutant daf-2(e1370) has a lifespan of 30.7 days and wild type has a lifespan of 14.6 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
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)
24.0
Lifespan change (compared to wild type)
80.45%
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);elt-3(RNAi) has a lifespan of 24.0 days, while single mutant elt-3(RNAi) has a lifespan of 12.4 days, single mutant daf-2(e1370) has a lifespan of 33.9 days and wild type has a lifespan of 13.3 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
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.

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

Temperature °C
20
Diet
HT115
Lifespan (days)
20.0
Lifespan change (compared to wild type)
10.50%
Phenotype
elt-3(vp1) suppresses the longevity phenotype of both daf-2(e1370) and daf-2(RNAi) animals
Lifespan comparisons
Double mutant daf-2(e1370);elt-3(vp1) has a lifespan of 20.0 days, while single mutant elt-3(vp1) has a lifespan of 15.1 days, single mutant daf-2(e1370) has a lifespan of 30.3 days and wild type has a lifespan of 18.1 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
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
Lifespan (days)
38.33
Lifespan change (compared to wild type)
91.65%
Phenotype
No evidence that the elt-3(vp1) mutation is able to reverse the lifespan extension induced by the daf-2(e1370) mutation.
Lifespan comparisons
Double mutant daf-2(e1370);elt-3(vp1) has a lifespan of 38.33 days, while single mutant elt-3(vp1) has a lifespan of 17.0 days, single mutant daf-2(e1370) has a lifespan of 38.33 days and wild type has a lifespan of 20.0 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Tonsaker T et al., 2012, Re-evaluating the role of ELT-3 in a GATA transcription factor circuit proposed to guide aging in C. elegans. Mech Ageing Dev. 133(1):50-3 22001047 Click here to select all mutants from this PubMed ID in the graph
Abstract
Budovskaya et al. (Cell. 134, 291-303, 2008) have proposed that the ELT-3 GATA factor regulates somatic aging genes, including those expressed in the intestine, and participates in a transcription factor circuit that "guides Caenorhabditis elegans aging". We have re-investigated two key features of this proposal: (i) expression of elt-3 in the C. elegans adult intestine where the majority of somatic aging genes are expressed, and; (ii) the ability of elt-3 loss-of-function to revert the extended lifespan of daf-2(e1370) mutants. We find that: (i) in agreement with our previously published results, ELT-3 expression is largely hypodermal and is not expressed at significant levels in the adult C. elegans intestine, and; (ii) the elt-3(vp1) zinc-finger deletion mutant does not significantly influence the extended lifespan of daf-2(e1370) mutants. We thus suggest that the role of ELT-3 in C. elegans aging should be re-evaluated.

Search genes: daf-2 elt-3

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

181503
elt-3
View on GenAge (elt-3)
WBGene00001251

Erythroid-Like Transcription factor family

Locus: CELE_K02B9.4

Wormbase description: elt-3 gene encodes a GATA transcription factor; during embryogenesis, ELT-3 appears to act downstream of ELT-1, also a GATA transcription factor, in a redundant pathway controlling hypodermal cell differentiation; ELT-3 is also required for positive regulation of transcription of nlp-29, which encodes an antimicrobial peptide, in response to fungal infection and gpdh-1 in response to salt stress; in addition, ELT-3 may also play a role in regulating adult lifespan; ELT-3 is expressed in all of the major hypodermal cells except the lateral seam cells and localizes to the nucleus; elt-3 expression in the hypodermis is positively regulated by ELT-1 and negatively regulated by ELT-5 and ELT-6.

Orthologs of daf-2;elt-3 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 elt-3 in SynergyAge

Show in SynergyAge
Species	Gene