atg-18;rsks-1

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Genetic mutants with atg-18, rsks-1 alterations

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

Temperature °C
20
Diet
OP50
Lifespan (days)
17.22
Lifespan comparisons
Double mutant atg-18(RNAi);rsks-1(sv31) has a lifespan of 17.22 days, while single mutant atg-18(RNAi) has a lifespan of 16.66 days, single mutant rsks-1(sv31) has a lifespan of 20.83 days and wild type has a lifespan of 17.22 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Lapierre LR et al., 2013;4:2267., The TFEB orthologue HLH-30 regulates autophagy and modulates longevity in Caenorhabditis elegans. Nat Commun. 4:2267 23925298 Click here to select all mutants from this PubMed ID in the graph
Abstract
Autophagy is a cellular recycling process that has an important anti-aging role, but the underlying molecular mechanism is not well understood. The mammalian transcription factor EB (TFEB) was recently shown to regulate multiple genes in the autophagy process. Here we show that the predicted TFEB orthologue HLH-30 regulates autophagy in Caenorhabditis elegans and, in addition, has a key role in lifespan determination. We demonstrate that hlh-30 is essential for the extended lifespan of Caenorhabditis elegans in six mechanistically distinct longevity models, and overexpression of HLH-30 extends lifespan. Nuclear localization of HLH-30 is increased in all six Caenorhabditis elegans models and, notably, nuclear TFEB levels are augmented in the livers of mice subjected to dietary restriction, a known longevity-extending regimen. Collectively, our results demonstrate a conserved role for HLH-30 and TFEB in autophagy, and possibly longevity, and identify HLH-30 as a uniquely important transcription factor for lifespan modulation in Caenorhabditis elegans.

Temperature °C
20
Diet
OP50
Lifespan (days)
18.4
Lifespan change (compared to wild type)
2.79%
Lifespan comparisons
Double mutant atg-18(RNAi);rsks-1(sv31) has a lifespan of 18.4 days, while single mutant atg-18(RNAi) has a lifespan of 16.8 days, single mutant rsks-1(sv31) has a lifespan of 21.5 days and wild type has a lifespan of 17.9 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Lapierre LR et al., 2013;4:2267., The TFEB orthologue HLH-30 regulates autophagy and modulates longevity in Caenorhabditis elegans. Nat Commun. 4:2267 23925298 Click here to select all mutants from this PubMed ID in the graph
Abstract
Autophagy is a cellular recycling process that has an important anti-aging role, but the underlying molecular mechanism is not well understood. The mammalian transcription factor EB (TFEB) was recently shown to regulate multiple genes in the autophagy process. Here we show that the predicted TFEB orthologue HLH-30 regulates autophagy in Caenorhabditis elegans and, in addition, has a key role in lifespan determination. We demonstrate that hlh-30 is essential for the extended lifespan of Caenorhabditis elegans in six mechanistically distinct longevity models, and overexpression of HLH-30 extends lifespan. Nuclear localization of HLH-30 is increased in all six Caenorhabditis elegans models and, notably, nuclear TFEB levels are augmented in the livers of mice subjected to dietary restriction, a known longevity-extending regimen. Collectively, our results demonstrate a conserved role for HLH-30 and TFEB in autophagy, and possibly longevity, and identify HLH-30 as a uniquely important transcription factor for lifespan modulation in Caenorhabditis elegans.

Temperature °C
20
Diet
OP50
Lifespan (days)
16.5
Lifespan change (compared to wild type)
-4.62%
Lifespan comparisons
Double mutant atg-18(RNAi);rsks-1(sv31) has a lifespan of 16.5 days, while single mutant atg-18(RNAi) has a lifespan of 14.4 days, single mutant rsks-1(sv31) has a lifespan of 21.4 days and wild type has a lifespan of 17.3 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Lapierre LR et al., 2013;4:2267., The TFEB orthologue HLH-30 regulates autophagy and modulates longevity in Caenorhabditis elegans. Nat Commun. 4:2267 23925298 Click here to select all mutants from this PubMed ID in the graph
Abstract
Autophagy is a cellular recycling process that has an important anti-aging role, but the underlying molecular mechanism is not well understood. The mammalian transcription factor EB (TFEB) was recently shown to regulate multiple genes in the autophagy process. Here we show that the predicted TFEB orthologue HLH-30 regulates autophagy in Caenorhabditis elegans and, in addition, has a key role in lifespan determination. We demonstrate that hlh-30 is essential for the extended lifespan of Caenorhabditis elegans in six mechanistically distinct longevity models, and overexpression of HLH-30 extends lifespan. Nuclear localization of HLH-30 is increased in all six Caenorhabditis elegans models and, notably, nuclear TFEB levels are augmented in the livers of mice subjected to dietary restriction, a known longevity-extending regimen. Collectively, our results demonstrate a conserved role for HLH-30 and TFEB in autophagy, and possibly longevity, and identify HLH-30 as a uniquely important transcription factor for lifespan modulation in Caenorhabditis elegans.

Temperature °C
20
Diet
OP50
Lifespan (days)
16.0
Lifespan change (compared to wild type)
3.90%
Lifespan comparisons
Double mutant atg-18(RNAi);rsks-1(sv31) has a lifespan of 16.0 days, while single mutant atg-18(RNAi) has a lifespan of 13.0 days, single mutant rsks-1(sv31) has a lifespan of 20.8 days and wild type has a lifespan of 15.4 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Lapierre LR et al., 2013;4:2267., The TFEB orthologue HLH-30 regulates autophagy and modulates longevity in Caenorhabditis elegans. Nat Commun. 4:2267 23925298 Click here to select all mutants from this PubMed ID in the graph
Abstract
Autophagy is a cellular recycling process that has an important anti-aging role, but the underlying molecular mechanism is not well understood. The mammalian transcription factor EB (TFEB) was recently shown to regulate multiple genes in the autophagy process. Here we show that the predicted TFEB orthologue HLH-30 regulates autophagy in Caenorhabditis elegans and, in addition, has a key role in lifespan determination. We demonstrate that hlh-30 is essential for the extended lifespan of Caenorhabditis elegans in six mechanistically distinct longevity models, and overexpression of HLH-30 extends lifespan. Nuclear localization of HLH-30 is increased in all six Caenorhabditis elegans models and, notably, nuclear TFEB levels are augmented in the livers of mice subjected to dietary restriction, a known longevity-extending regimen. Collectively, our results demonstrate a conserved role for HLH-30 and TFEB in autophagy, and possibly longevity, and identify HLH-30 as a uniquely important transcription factor for lifespan modulation in Caenorhabditis elegans.

Search genes: atg-18 rsks-1

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

176554
rsks-1
View on GenAge (rsks-1)
WBGene00012929

Ribosomal protein S6 kinase beta

Locus: CELE_Y47D3A.16

Wormbase description: rsks-1 encodes a putative ribosomal protein S6 kinase (S6K) required additively with IFG-1 for normally high levels of protein synthesis, and for normally short lifespan; RSKS-1's effect on lifespan is independent of DAF-16, ISP-1, and SIR-2.1, and does not correlate with juglone resistance, but does correlate with abnormally high resistance to starvation and (perhaps) thermotolerance; RSKS-1 is required for normal juglone resistance, as well as normally rapid growth and normal brood sizes; RSKS-1 is expressed in E-lineage embryonic cells, and in pharyngeal and hypodermal cells of larvae and adults; RSKS-1 is orthologous to human RPS6KB1 (OMIM:608938) and RPS6KB2 (OMIM:608939).

Orthologs of atg-18;rsks-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Atg18b;S6k
Drosophila melanogaster	Atg18a;S6k
Mus musculus	Rps6kb1;Wipi2
Mus musculus	Rps6kb2;Wipi2
Mus musculus	Rps6kb1;Wipi1
Mus musculus	Rps6kb2;Wipi1
Mus musculus	S6k;Atg18b
Mus musculus	S6k;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 rsks-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	S6k
Mus musculus	Rps6kb1
Mus musculus	Rps6kb2