glp-1;hlh-30

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Genetic mutants with glp-1, hlh-30 alterations

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

Temperature °C
20
Diet
OP50
Lifespan (days)
17.7
Lifespan change (compared to wild type)
22.92%
Phenotype
glp-1(e2141); hlh-30(tm1978) double mutants to have mean lifespans similar to hlh-30(tm1978) single mutants.
Lifespan comparisons
Double mutant glp-1(e2141);hlh-30(tm1978) has a lifespan of 17.7 days, while single mutant glp-1(e2141) has a lifespan of 17.7 days, single mutant hlh-30(tm1978) has a lifespan of 15.7 days and wild type has a lifespan of 14.4 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)
16.7
Lifespan change (compared to wild type)
4.38%
Phenotype
glp-1(e2141); hlh-30(tm1978) double mutants to have mean lifespans similar to hlh-30(tm1978) single mutants.
Lifespan comparisons
Double mutant glp-1(e2141);hlh-30(tm1978) has a lifespan of 16.7 days, while single mutant glp-1(e2141) has a lifespan of 19.8 days, single mutant hlh-30(tm1978) has a lifespan of 16.0 days and wild type has a lifespan of 16.0 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)
17.6
Lifespan change (compared to wild type)
-8.33%
Phenotype
glp-1(e2141); hlh-30(tm1978) double mutants to have mean lifespans similar to hlh-30(tm1978) single mutants.
Lifespan comparisons
Double mutant glp-1(e2141);hlh-30(tm1978) has a lifespan of 17.6 days, while single mutant glp-1(e2141) has a lifespan of 34.7 days, single mutant hlh-30(tm1978) has a lifespan of 20.5 days and wild type has a lifespan of 19.2 days.
Type of interaction
See methods
Antagonistic (negative)
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)
16.6
Lifespan change (compared to wild type)
-5.68%
Phenotype
glp-1(e2141); hlh-30(tm1978) double mutants to have mean lifespans similar to hlh-30(tm1978) single mutants.
Lifespan comparisons
Double mutant glp-1(e2141);hlh-30(tm1978) has a lifespan of 16.6 days, while single mutant glp-1(e2141) has a lifespan of 23.8 days, single mutant hlh-30(tm1978) has a lifespan of 18.8 days and wild type has a lifespan of 17.6 days.
Type of interaction
See methods
Antagonistic (negative)
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: glp-1 hlh-30

Entrez ID
Symbol
GenAge
Wormbase ID

176286
glp-1
View on GenAge (glp-1)
WBGene00001609

Protein glp-1

Locus: CELE_F02A9.6

Wormbase description: glp-1 encodes an N-glycosylated transmembrane protein that, along with LIN-12, comprises one of two C. elegans members of the LIN-12/Notch family of receptors; from the N- to the C-terminus, GLP-1 is characterized by ten extracellular EGF-like repeats, three LIN-12/Notch repeats, a CC-linker, a transmembrane domain, a RAM domain, six intracellular ankyrin repeats, and a PEST sequence; in C. elegans, GLP-1 activity is required for cell fate specification in germline and somatic tissues; in the germline, GLP-1, acting as a receptor for the DSL family ligand LAG-2, is essential for mitotic proliferation of germ cells and maintenance of germline stem cells; in somatic tissues, maternally provided GLP-1, acting as a receptor for the DSL family ligand APX-1, is required for inductive interactions that specify the fates of certain embryonic blastomeres; GLP-1 is also required for some later embryonic cell fate decisions, and in these decisions its activity is functionally redundant with that of LIN-12; GLP-1 expression is regulated temporally and spatially via translational control, as GLP-1 mRNA, present ubiquitously in the germline and embryo, yields detectable protein solely in lateral, interior, and endomembranes of distal, mitotic germ cells, and then predominantly in the AB blastomere and its descendants in the early embryo; proper spatial translation of glp-1 mRNA in the embryo is dependent upon genes such as the par genes, that are required for normal anterior-posterior asymmetry in the early embryo; signaling through GLP-1 controls the activity of the downstream Notch pathway components LAG-3 and LAG-1, the latter being predicted to function as part of a transcriptional feedback mechanism that positively regulates GLP-1 expression; signaling through the DNA-binding protein LAG-1 is believed to involve a direct interaction between LAG-1 and the GLP-1 RAM and ankyrin domains

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).

Orthologs of glp-1;hlh-30 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of glp-1 in SynergyAge

Show 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