daf-2;lgg-3

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Genetic mutants with daf-2, lgg-3 alterations

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

Temperature °C
20
Lifespan (days)
46.6
Lifespan change (compared to wild type)
117.76%
Phenotype
Maternal RNAi of lgg-3 significantly extended lifespan in the daf-2 mutant.
Lifespan comparisons
Double mutant daf-2(e1370);lgg-3(RNAi) has a lifespan of 46.6 days, while single mutant lgg-3(RNAi) has a lifespan of 22.5 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
Synergistic (positive)
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)
40.0
Lifespan change (compared to wild type)
82.65%
Lifespan comparisons
Double mutant daf-2(e1370);lgg-3(RNAi) has a lifespan of 40.0 days, while single mutant lgg-3(RNAi) has a lifespan of 24.7 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
Almost additive (positive)
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: daf-2 lgg-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

175793
lgg-3
View on GenAge (lgg-3)
WBGene00002982

Ubiquitin-like protein ATG12

Locus: CELE_B0336.8

Wormbase description: lgg-3 encodes a hydrophilic protein that is orthologous to Saccharomyces cerevisiae autophagy protein Apg12p; by homology, LGG-3 is predicted to function as a modifier protein required for a protein conjugation system essential for autophagy; in the context of this conjugation system, LGG-3 is predicted to interact with Apg7p and Apg5p homologs (encoded by M7.5 and Y71G12B.12a, respectively) to effect bulk degradation of cytoplasmic components under conditions of starvation or cellular remodeling; free LGG-3 is predicted to localize to the cytoplasm, while LGG-3 conjugated to the Apg5p homolog is predicted to associate with membrane compartments; loss of lgg-3 activity via large-scale RNAi screens results in no obvious developmental or behavioral abnormalities.

Orthologs of daf-2;lgg-3 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Atg12;InR
Mus musculus	Atg12;Insr
Mus musculus	Atg12;Igf1r
Mus musculus	Atg12;Insrr
Mus musculus	Insr;Atg12
Mus musculus	Igf1r;Atg12
Mus musculus	Insrr;Atg12

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 lgg-3 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Atg12
Mus musculus	Atg12