glp-1;nhr-49

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Genetic mutants with glp-1, nhr-49 alterations

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

Temperature °C
20
Lifespan (days)
35.3
Lifespan change (compared to wild type)
63.43%
Lifespan comparisons
Double mutant glp-1(e2141ts);nhr-49(OE) has a lifespan of 35.3 days, while single mutant glp-1(e2141ts) has a lifespan of 31.0 days and wild type has a lifespan of 21.6 days.
Type of interaction
See methods
Partially known monotony. Positive epistasis
Citation
View abstract
Ratnappan R et al., 2014, Germline signals deploy NHR-49 to modulate fatty-acid β-oxidation and desaturation in somatic tissues of C. elegans. PLoS Genet. 10(12):e1004829 25474470 Click here to select all mutants from this PubMed ID in the graph
Abstract
In C. elegans, removal of the germline extends lifespan significantly. We demonstrate that the nuclear hormone receptor, NHR-49, enables the response to this physiological change by increasing the expression of genes involved in mitochondrial β-oxidation and fatty-acid desaturation. The coordinated augmentation of these processes is critical for germline-less animals to maintain their lipid stores and to sustain de novo fat synthesis during adulthood. Following germline ablation, NHR-49 is up-regulated in somatic cells by the conserved longevity determinants DAF-16/FOXO and TCER-1/TCERG1. Accordingly, NHR-49 overexpression in fertile animals extends their lifespan modestly. In fertile adults, nhr-49 expression is DAF-16/FOXO and TCER-1/TCERG1 independent although its depletion causes age-related lipid abnormalities. Our data provide molecular insights into how reproductive stimuli are integrated into global metabolic changes to alter the lifespan of the animal. They suggest that NHR-49 may facilitate the adaptation to loss of reproductive potential through synchronized enhancement of fatty-acid oxidation and desaturation, thus breaking down some fats ordained for reproduction and orchestrating a lipid profile conducive for somatic maintenance and longevity.

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

Temperature °C
20
Lifespan (days)
14.1
Lifespan change (compared to wild type)
-34.72%
Lifespan comparisons
Double mutant glp-1(e2141ts);nhr-49(nr2041) has a lifespan of 14.1 days, while single mutant glp-1(e2141ts) has a lifespan of 31.0 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
Ratnappan R et al., 2014, Germline signals deploy NHR-49 to modulate fatty-acid β-oxidation and desaturation in somatic tissues of C. elegans. PLoS Genet. 10(12):e1004829 25474470 Click here to select all mutants from this PubMed ID in the graph
Abstract
In C. elegans, removal of the germline extends lifespan significantly. We demonstrate that the nuclear hormone receptor, NHR-49, enables the response to this physiological change by increasing the expression of genes involved in mitochondrial β-oxidation and fatty-acid desaturation. The coordinated augmentation of these processes is critical for germline-less animals to maintain their lipid stores and to sustain de novo fat synthesis during adulthood. Following germline ablation, NHR-49 is up-regulated in somatic cells by the conserved longevity determinants DAF-16/FOXO and TCER-1/TCERG1. Accordingly, NHR-49 overexpression in fertile animals extends their lifespan modestly. In fertile adults, nhr-49 expression is DAF-16/FOXO and TCER-1/TCERG1 independent although its depletion causes age-related lipid abnormalities. Our data provide molecular insights into how reproductive stimuli are integrated into global metabolic changes to alter the lifespan of the animal. They suggest that NHR-49 may facilitate the adaptation to loss of reproductive potential through synchronized enhancement of fatty-acid oxidation and desaturation, thus breaking down some fats ordained for reproduction and orchestrating a lipid profile conducive for somatic maintenance and longevity.

Search genes: glp-1 nhr-49

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

172839
nhr-49
View on GenAge (nhr-49)
WBGene00003639

Nuclear Hormone Receptor family;Nuclear hormone receptor family member nhr-49

Locus: CELE_K10C3.6

Wormbase description: nhr-49 encodes a nuclear hormone receptor (NHR) related to the mammalian HNF4 (hepatocyte nuclear factor 4) family of NHRs; nhr-49 functions as a key regulator of fat metabolism and lifespan by regulating induction of beta-oxidation genes upon food deprivation and activation of stearoyl-CoA desaturase in fed animals, respectively; NHR-49 activates transcription in conjunction with the MDT-15 mediator subunit with which it physically interacts.

Orthologs of glp-1;nhr-49 in SynergyAge

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Orthologs of glp-1 in SynergyAge

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Orthologs of nhr-49 in SynergyAge

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