atg-18;daf-2

There is no network for this step.

Fullscreen mode

Hide graph

Legend

Genetic mutants with atg-18, daf-2 alterations

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

Temperature °C
20
Lifespan (days)
23.8
Lifespan change (compared to wild type)
11.21%
Lifespan comparisons
Double mutant atg-18(RNAi);daf-2(e1370) has a lifespan of 23.8 days, while single mutant atg-18(RNAi) has a lifespan of 12.1 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
Opposite lifespan effects of single mutants
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)
38.9
Lifespan change (compared to wild type)
77.63%
Lifespan comparisons
Double mutant atg-18(RNAi);daf-2(e1370) has a lifespan of 38.9 days, while single mutant atg-18(RNAi) has a lifespan of 17.6 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
Opposite lifespan effects of single mutants
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-18 daf-2

Entrez ID
Symbol
GenAge
Wormbase ID

179246
atg-18
View on GenAge (atg-18)
WBGene00018294

AuTophaGy (yeast Atg homolog)

Locus: CELE_F41E6.13

Wormbase description: atg-18 encodes, by alternative splicing, two isoforms of a WD40 repeat-containing protein orthologous to the autophagic budding yeast protein Atg18p, and to human WIPI1 (OMIM:609224) and WIPI2 (OMIM:609225); ATG-18 activity is essential for normal dauer morphogenesis and autophagy in daf-2 mutant animals; ATG-18 is expressed in larval and adult pharynx, bodywall muscle, hypodermis, seam cells, and neurons, and in larval intestine; in mass RNAi assays, ATG-18 is required for normally rapid growth, and is weakly required for the viability of cup-5(ar465) mutants.

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-18;daf-2 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Atg18b;InR
Drosophila melanogaster	Atg18a;InR
Mus musculus	Insr;Wipi2
Mus musculus	Igf1r;Wipi2
Mus musculus	Insrr;Wipi2
Mus musculus	Insr;Wipi1
Mus musculus	Igf1r;Wipi1
Mus musculus	Insrr;Wipi1
Mus musculus	InR;Atg18b
Mus musculus	InR;Atg18a

Orthologs of atg-18 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Atg18b
Drosophila melanogaster	Atg18a
Mus musculus	Wipi2
Mus musculus	Wipi1

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