atg-4.1;daf-2

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Genetic mutants with atg-4.1, daf-2 alterations

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

Temperature °C
20
Lifespan (days)
37.3
Lifespan change (compared to wild type)
74.30%
Lifespan comparisons
Double mutant atg-4.1(RNAi);daf-2(e1370) has a lifespan of 37.3 days, while single mutant atg-4.1(RNAi) has a lifespan of 18.5 days, single mutant daf-2(e1370) has a lifespan of 34.6 days and wild type has a lifespan of 21.4 days.
Type of interaction
See methods
Enhancer, opposite lifespan effects
Citation
View abstract
Hashimoto Y et al., 2009, Lifespan extension by suppression of autophagy genes in Caenorhabditis elegans. Genes Cells. 14(6):717-26 19469880 Click here to select all mutants from this PubMed ID in the graph
Abstract
Lifespan is regulated by a complex combination of environmental and genetic factors. Autophagy, which is a bulk degradation system of macromolecules and organelles, has an important role in various biological events. In Caenorhabditis elegans, several autophagy genes have been shown to have a role in promoting longevity, but many other autophagy genes have not been examined for their role in the lifespan regulation. Here we have systematically examined the effect of RNAi suppression of 14 autophagy genes on lifespan. While maternal RNAi of autophagy genes in wild-type worms tended to reduce lifespan, maternal RNAi of each of seven autophagy genes in the insulin/IGF-1 receptor daf-2 mutants extended lifespan. Remarkably, RNAi of unc-51/atg-1, bec-1/atg-6 or atg-9, from young adult, i.e. after development, extended lifespan in both wild-type animals and daf-2 mutants, although RNAi of one or two genes shortened it. Moreover, our analysis suggests that the lifespan extension, which is induced by RNAi of unc-51, bec-1 or atg-9 after development, does not require the transcription factor daf-16, the NAD(+)-dependent protein deacetylase sir-2.1 or the genes related to mitochondrial functions. Collectively, our results suggest that autophagy may not always be beneficial to longevity, but may also function to restrict lifespan in C. elegans.

Temperature °C
20
Lifespan (days)
37.1
Lifespan change (compared to wild type)
69.41%
Lifespan comparisons
Double mutant atg-4.1(RNAi);daf-2(e1370) has a lifespan of 37.1 days, while single mutant atg-4.1(RNAi) has a lifespan of 22.0 days, single mutant daf-2(e1370) has a lifespan of 38.1 days and wild type has a lifespan of 21.9 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Hashimoto Y et al., 2009, Lifespan extension by suppression of autophagy genes in Caenorhabditis elegans. Genes Cells. 14(6):717-26 19469880 Click here to select all mutants from this PubMed ID in the graph
Abstract
Lifespan is regulated by a complex combination of environmental and genetic factors. Autophagy, which is a bulk degradation system of macromolecules and organelles, has an important role in various biological events. In Caenorhabditis elegans, several autophagy genes have been shown to have a role in promoting longevity, but many other autophagy genes have not been examined for their role in the lifespan regulation. Here we have systematically examined the effect of RNAi suppression of 14 autophagy genes on lifespan. While maternal RNAi of autophagy genes in wild-type worms tended to reduce lifespan, maternal RNAi of each of seven autophagy genes in the insulin/IGF-1 receptor daf-2 mutants extended lifespan. Remarkably, RNAi of unc-51/atg-1, bec-1/atg-6 or atg-9, from young adult, i.e. after development, extended lifespan in both wild-type animals and daf-2 mutants, although RNAi of one or two genes shortened it. Moreover, our analysis suggests that the lifespan extension, which is induced by RNAi of unc-51, bec-1 or atg-9 after development, does not require the transcription factor daf-16, the NAD(+)-dependent protein deacetylase sir-2.1 or the genes related to mitochondrial functions. Collectively, our results suggest that autophagy may not always be beneficial to longevity, but may also function to restrict lifespan in C. elegans.

Search genes: atg-4.1 daf-2

Entrez ID
Symbol
GenAge
Wormbase ID

190777
atg-4.1
View on GenAge (atg-4.1)
WBGene00013595

Cysteine protease

Locus: CELE_Y87G2A.3

Wormbase description: atg-4.1 encodes a putative cysteine protease orthologous to the autophagic budding yeast protein Atg4p, and to human ATG4A and ATG4B; ATG-4.1 is paralogous to ATG-4.2 and to human ATG4C (OMIM:611339) and ATG4D (OMIM:611340); ATG-4.1 is expressed from early embryos to adults, in larval and adult intestine, renal gland cells, and neurons; ATG-4.1 exhibits protease activity towards LGG-1; ATG-4.1 localizes to the cytoplasm of most cells during embryogenesis.

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 atg-4.1;daf-2 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Atg4a;InR
Mus musculus	Atg4b;Insr
Mus musculus	Atg4b;Igf1r
Mus musculus	Atg4b;Insrr
Mus musculus	Atg4a;Insr
Mus musculus	Atg4a;Igf1r
Mus musculus	Atg4a;Insrr
Mus musculus	Insr;Atg4b
Mus musculus	Insr;Atg4a
Mus musculus	Igf1r;Atg4b
Mus musculus	Igf1r;Atg4a
Mus musculus	Insrr;Atg4b
Mus musculus	Insrr;Atg4a

Orthologs of atg-4.1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Atg4a
Mus musculus	Atg4b
Mus musculus	Atg4a

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