glp-1;vha-16

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Genetic mutants with glp-1, vha-16 alterations

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

Temperature °C
25
Diet
OP50
Lifespan (days)
14.16
Phenotype
RNAi-mediated inhibition of the lysosomal gene vha-16substantially reduced the long lifespan of glp-1(e2141) mutants supporting the notion that a subset of HLH-30-regulated genes, with functions relevant to autophagy, may contribute to lifespan extension.
Lifespan comparisons
Double mutant glp-1(e2141);vha-16(RNAi) has a lifespan of 14.16 days, while single mutant vha-16(RNAi) has a lifespan of 14.16 days, single mutant glp-1(e2141) has a lifespan of 21.11 days and wild type has a lifespan of 14.16 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
25
Diet
OP50
Lifespan (days)
13.8
Lifespan change (compared to wild type)
-21.14%
Phenotype
RNAi-mediated inhibition of the lysosomal gene vha-16substantially reduced the long lifespan of glp-1(e2141) mutants supporting the notion that a subset of HLH-30-regulated genes, with functions relevant to autophagy, may contribute to lifespan extension.
Lifespan comparisons
Double mutant glp-1(e2141);vha-16(RNAi) has a lifespan of 13.8 days, while single mutant vha-16(RNAi) has a lifespan of 15.6 days, single mutant glp-1(e2141) has a lifespan of 25.9 days and wild type has a lifespan of 17.5 days.
Type of interaction
See methods
Enhancer, opposite lifespan effects
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
25
Diet
OP50
Lifespan (days)
14.8
Lifespan change (compared to wild type)
-11.90%
Phenotype
RNAi-mediated inhibition of the lysosomal gene vha-16substantially reduced the long lifespan of glp-1(e2141) mutants supporting the notion that a subset of HLH-30-regulated genes, with functions relevant to autophagy, may contribute to lifespan extension.
Lifespan comparisons
Double mutant glp-1(e2141);vha-16(RNAi) has a lifespan of 14.8 days, while single mutant vha-16(RNAi) has a lifespan of 14.1 days, single mutant glp-1(e2141) has a lifespan of 24.8 days and wild type has a lifespan of 16.8 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
25
Diet
OP50
Lifespan (days)
15.0
Lifespan change (compared to wild type)
-6.83%
Phenotype
RNAi-mediated inhibition of the lysosomal gene vha-16substantially reduced the long lifespan of glp-1(e2141) mutants supporting the notion that a subset of HLH-30-regulated genes, with functions relevant to autophagy, may contribute to lifespan extension.
Lifespan comparisons
Double mutant glp-1(e2141);vha-16(RNAi) has a lifespan of 15.0 days, while single mutant vha-16(RNAi) has a lifespan of 14.6 days, single mutant glp-1(e2141) has a lifespan of 22.0 days and wild type has a lifespan of 16.1 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: glp-1 vha-16

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

172134
vha-16
View on GenAge (vha-16)
WBGene00016258

V-type proton ATPase subunit

Locus: CELE_C30F8.2

Wormbase description: vha-16 encodes an an ortholog of subunit d of the membrane-bound (V0) domain of vacuolar proton-translocating ATPase (V-ATPase); VHA-16 is predicted to mechanically anchor the V-ATPase cytosolic rotor (stalk) to the membrane, while also providing a hub for the V-ATPase transmembrane rotor; vha-16 is expressed in diverse tissues (e.g., excretory cell, pharynx, intestine, hypodermis, and neurons).

Orthologs of glp-1;vha-16 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of glp-1 in SynergyAge

Show in SynergyAge
Species	Gene

Orthologs of vha-16 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	VhaAC39-1
Mus musculus	Atp6v0d1