daf-2;isp-1

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Genetic mutants with daf-2, isp-1 alterations

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

Temperature °C
25
Diet
NGM
Lifespan (days)
41.1
Lifespan change (compared to wild type)
102.46%
Lifespan comparisons
Double mutant daf-2(RNAi);isp-1(gm150) has a lifespan of 41.1 days, while single mutant daf-2(RNAi) has a lifespan of 30.6 days, single mutant isp-1(gm150) has a lifespan of 29.3 days and wild type has a lifespan of 20.3 days.
Type of interaction
See methods
Synergistic (positive)
Citation
View abstract
Rogers AN et al., 2011, Life span extension via eIF4G inhibition is mediated by posttranscriptional remodeling of stress response gene expression in C. elegans. Cell Metab. 14(1):55-66 21723504 Click here to select all mutants from this PubMed ID in the graph
Abstract
Reducing protein synthesis slows growth and development but can increase adult life span. We demonstrate that knockdown of eukaryotic translation initiation factor 4G (eIF4G), which is downregulated during starvation and dauer state, results in differential translation of genes important for growth and longevity in C. elegans. Genome-wide mRNA translation state analysis showed that inhibition of IFG-1, the C. elegans ortholog of eIF4G, results in a relative increase in ribosomal loading and translation of stress response genes. Some of these genes are required for life span extension when IFG-1 is inhibited. Furthermore, enhanced ribosomal loading of certain mRNAs upon IFG-1 inhibition was correlated with increased mRNA length. This association was supported by changes in the proteome assayed via quantitative mass spectrometry. Our results suggest that IFG-1 mediates the antagonistic effects on growth and somatic maintenance by regulating mRNA translation of particular mRNAs based, in part, on transcript length.

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

Temperature °C
20
Diet
NGM
Lifespan (days)
40.15
Lifespan comparisons
Double mutant daf-2(RNAi);isp-1(qm150) has a lifespan of 40.15 days, while single mutant isp-1(qm150) has a lifespan of 30.21 days.
Citation
View abstract
Khan MH et al., 2013, TAF-4 is required for the life extension of isp-1, clk-1 and tpk-1 Mit mutants. Aging (Albany NY). 5(10):741-58 24107417 Click here to select all mutants from this PubMed ID in the graph
Abstract
While numerous life-extending manipulations have been discovered in the nematode Caenorhabditis elegans, one that remains most enigmatic is disruption of oxidative phosphorylation. In order to unravel how such an ostensibly deleterious manipulation can extend lifespan, we sought to identify the ensemble of nuclear transcription factors that are activated in response to defective mitochondrial electron transport chain (ETC) function. Using a feeding RNAi approach, we targeted over 400 transcription factors and identified 15 that, when reduced in function, reproducibly and differentially altered the development, stress response, and/or fecundity of isp-1(qm150) Mit mutants relative to wild-type animals. Seven of these transcription factors--AHA-1, CEH-18, HIF-1, JUN-1, NHR-27, NHR-49 and the CREB homolog-1 (CRH-1)-interacting protein TAF-4--were also essential for isp-1 life extension. When we tested the involvement of these seven transcription factors in the life extension of two other Mit mutants, namely clk-1(qm30) and tpk-1(qm162), TAF-4 and HIF-1 were consistently required. Our findings suggest that the Mit phenotype is under the control of multiple transcriptional responses, and that TAF-4 and HIF-1 may be part of a general signaling axis that specifies Mit mutant life extension.

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

Temperature °C
20
Lifespan (days)
42.3
Lifespan change (compared to wild type)
115.82%
Phenotype
The effects of daf-2(e1370) and isp-1(qm150) on life span are almost identical in magnitude but are not additive as the double mutants live only marginally longer than either of the single mutants. Although there is a slight increase in the life span of the double mutants, it is only a fraction of what their life span would be if the two mutations were increasing life span independently.
Lifespan comparisons
Double mutant daf-2(e1370);isp-1(qm150) has a lifespan of 42.3 days, while single mutant isp-1(qm150) has a lifespan of 33.0 days, single mutant daf-2(e1370) has a lifespan of 36.3 days and wild type has a lifespan of 19.6 days.
Type of interaction
See methods
Almost additive (positive)
Citation
View abstract
Feng J et al., 2001, Mitochondrial electron transport is a key determinant of life span in Caenorhabditis elegans. Dev Cell. 1(5):633-44 11709184 Click here to select all mutants from this PubMed ID in the graph
Abstract
Increased protection from reactive oxygen species (ROS) is believed to increase life span. However, it has not been clearly demonstrated that endogenous ROS production actually limits normal life span. We have identified a mutation in the Caenorhabditis elegans iron sulfur protein (isp-1) of mitochondrial complex III, which results in low oxygen consumption, decreased sensitivity to ROS, and increased life span. Furthermore, combining isp-1(qm150) with a mutation (daf-2) that increases resistance to ROS does not result in any significant further increase in adult life span. These findings indicate that both isp-1 and daf-2 mutations increase life span by lowering oxidative stress and result in the maximum life span increase that can be produced in this way.

Search genes: daf-2 isp-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.

Entrez ID
Symbol
GenAge
Wormbase ID

177609
isp-1
View on GenAge (isp-1)
WBGene00002162

Cytochrome b-c1 complex subunit Rieske, mitochondrial

Locus: CELE_F42G8.12

Wormbase description: isp-1 encodes a Rieske iron sulphur protein (ISP) which is a subunit of the mitochondrial complex III in the mitochondrial membrane; the subunits are highly conserved in all mitochondria and aerobic bacteria; mitochondrial complex III catalyses electron transport from ubiquinol to cytochrome c; isp-1 mutants show low oxygen consumption, a decreased sensitivity to reactive oxygen species and increased lifespan suggesting that mitochondrial electron transport is a key factor affecting life span; isp-1 affects the rates of physiological processes like reproduction and development and also affects behavior.

Orthologs of daf-2;isp-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Insr;Uqcrfs1
Mus musculus	Igf1r;Uqcrfs1
Mus musculus	Insrr;Uqcrfs1
Mus musculus	Uqcrfs1;Insr
Mus musculus	Uqcrfs1;Igf1r
Mus musculus	Uqcrfs1;Insrr

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 isp-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Uqcrfs1