hlh-30;tor

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Genetic mutants with hlh-30, tor alterations

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

Temperature °C
20
Diet
OP50
Lifespan (days)
17.8
Lifespan change (compared to wild type)
4.09%
Phenotype
tor RNAi significantly extended the lifespan of WT animals; however, the same treatment failed to prolong the lifespan of hlh-30(tm1978) mutants suggesting that hlh-30 acts downstream of TOR.
Lifespan comparisons
Double mutant hlh-30(RNAi);tor(RNAi) has a lifespan of 17.8 days, while single mutant tor(RNAi) has a lifespan of 21.8 days, single mutant hlh-30(RNAi) has a lifespan of 17.1 days and wild type has a lifespan of 17.1 days.
Type of interaction
See methods
Dependent
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)
17.0
Lifespan change (compared to wild type)
-9.09%
Phenotype
tor RNAi significantly extended the lifespan of WT animals; however, the same treatment failed to prolong the lifespan of hlh-30(tm1978) mutants suggesting that hlh-30 acts downstream of TOR.
Lifespan comparisons
Double mutant hlh-30(RNAi);tor(RNAi) has a lifespan of 17.0 days, while single mutant tor(RNAi) has a lifespan of 24.8 days, single mutant hlh-30(RNAi) has a lifespan of 16.7 days and wild type has a lifespan of 18.7 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)
19.3
Lifespan change (compared to wild type)
-10.65%
Phenotype
tor RNAi significantly extended the lifespan of WT animals; however, the same treatment failed to prolong the lifespan of hlh-30(tm1978) mutants suggesting that hlh-30 acts downstream of TOR.
Lifespan comparisons
Double mutant hlh-30(RNAi);tor(RNAi) has a lifespan of 19.3 days, while single mutant tor(RNAi) has a lifespan of 26.0 days, single mutant hlh-30(RNAi) has a lifespan of 19.5 days and wild type has a lifespan of 21.6 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: hlh-30 tor

Entrez ID
Symbol
GenAge
Wormbase ID

177157
hlh-30
View on GenAge (hlh-30)
WBGene00020930

Helix Loop Helix

Locus: CELE_W02C12.3

Wormbase description: hlh-30 encodes a predicted basic helix-loop-helix (bHLH) transcription factor, one of 42 such genes in the C. elegans genome, it is spliced to give 18 different transcripts; it is orthologous to human microphthalmia-associated transcription factor (HGNC:MITF); loss of hlh-30 activity via RNAi results in reduced fat storage; HLH-30 demonstrates sequence-specific DNA binding for the E box sequence CACGTG and likely binds DNA as a homodimer; expression profiles of hlh-30 mutants indicate that, like its human ortholog, HLH-30 regulates expression of genes involved in metabolism; at least one of the bHLH protein isoforms appears to be important for an infection-specific immune response to M. nematophilum, though the overall induction of this gene following infection was not appreciable (1.3-fold).

Symbol
GenAge

tor
View on GenAge (tor)

No gene information for tor

Orthologs of hlh-30;tor in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of hlh-30 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Mitf
Mus musculus	Tfe3
Mus musculus	Tfeb
Mus musculus	Tfec

Orthologs of tor in SynergyAge

Show in SynergyAge
Species	Gene