flr-4;glp-1

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Genetic mutants with flr-4, glp-1 alterations

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

Temperature °C
20
Diet
OP50; HT139
Lifespan (days)
18.69
Lifespan change (compared to wild type)
33.02%
Lifespan comparisons
Double mutant flr-4(RNAi);glp-1(e2141) has a lifespan of 18.69 days, while single mutant flr-4(RNAi) has a lifespan of 16.51 days, single mutant glp-1(e2141) has a lifespan of 18.65 days and wild type has a lifespan of 14.05 days.
Type of interaction
See methods
Almost additive (positive)
Citation
View abstract
Verma S et al., 2018, A novel gene-diet pair modulates C. elegans aging. PLoS Genet. 14(8):e1007608 30125273 Click here to select all mutants from this PubMed ID in the graph
Abstract
Diet profoundly affects metabolism and incidences of age-related diseases. Animals adapt their physiology to different food-types, modulating complex life-history traits like aging. The molecular mechanisms linking adaptive capacity to diet with aging are less known. We identify FLR-4 kinase as a novel modulator of aging in C. elegans, depending on bacterial diet. FLR-4 functions to prevent differential activation of the p38MAPK pathway in response to diverse food-types, thereby maintaining normal life span. In a kinase-dead flr-4 mutant, E. coli HT115 (K12 strain), but not the standard diet OP50 (B strain), is able to activate p38MAPK, elevate expression of cytoprotective genes through the nuclear hormone receptor NHR-8 and enhance life span. Interestingly, flr-4 and dietary restriction utilize similar pathways for longevity assurance, suggesting cross-talks between cellular modules that respond to diet quality and quantity. Together, our study discovers a new C. elegans gene-diet pair that controls the plasticity of aging.

Search genes: flr-4 glp-1

Entrez ID
Symbol
GenAge
Wormbase ID

181604
flr-4
View on GenAge (flr-4)
WBGene00001468

Serine/threonine-protein kinase flr-4

Locus: CELE_F09B12.6

Wormbase description: flr-4 encodes a predicted Ser/Thr protein kinase that affects sensitivity to fluoride ion, growth, defecation cycle periods, dauer formation; expressed in the intestine, the AUA neurons, the pharyngeal isthmus, and in the excretory canal in larval stages.

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

Orthologs of flr-4;glp-1 in SynergyAge

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Orthologs of flr-4 in SynergyAge

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Orthologs of glp-1 in SynergyAge

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SynergyAge database hosts high-quality, manually curated information about the synergistic and antagonistic lifespan effects of genetic interventions in model organisms, also allowing users to explore the longevity relationships between genes in a visual way.