daf-16;oga-1

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Genetic mutants with daf-16, oga-1 alterations

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

Temperature °C
20
Diet
NGM; OP50
Lifespan (days)
14.8
Lifespan change (compared to wild type)
-6.92%
Phenotype
Lifespan extension in the oga-1 mutant is DAF-16-dependent, as seen in the reduced lifespan of the oga-1(ok1207); daf-16(mu86) double mutant relative to the oga-1(ok1207) single mutant.
Lifespan comparisons
Double mutant daf-16(mu86);oga-1(ok1207) has a lifespan of 14.8 days, while single mutant daf-16(mu86) has a lifespan of 14.3 days, single mutant oga-1(ok1207) has a lifespan of 20.9 days and wild type has a lifespan of 15.9 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Rahman MM et al., 2010, Intracellular protein glycosylation modulates insulin mediated lifespan in C.elegans. Aging (Albany NY). 2(10):678-90 20952811 Click here to select all mutants from this PubMed ID in the graph
Abstract
O-linked-β-N-acetylglucosamine (O-GlcNAc) modification is a regulatory, nuclear and cytoplasmic post-translational glycosylation of proteins associated with age-related diseases such as Alzheimer's, Parkinson's, and type II diabetes. Global elevation of O-GlcNAc levels on intracellular proteins can induce insulin resistance, the hallmark of type II diabetes, in mammalian systems. InC. elegans, attenuation of the insulin-like signal transduction pathway increases adult lifespan of the nematode. We demonstrate that the O-GlcNAc cycling enzymes OGT and OGA, which add and remove O-GlcNAc respectively, modulate lifespan in C. elegans. Median adult lifespan is increased in an oga-1 deletion strain while median adult life span is decreased upon ogt-1 deletion. The O-GlcNAc-mediated effect on nematode lifespan is dependent on the FoxO transcription factor DAF-16. DAF-16 is a key factor in the insulin-like signal transduction pathway to regulate reproductive development, lifespan, stress tolerance, and dauer formation in C. elegans. Our data indicates that O-GlcNAc cycling selectively influences only a subset of DAF-16 mediated phenotypes, including lifespan and oxidative stress resistance. We performed an affinity purification of O-GlcNAc-modified proteins and observed that a high percentage of these proteins are regulated by insulin signaling and/or impact insulin pathway functional outcomes, suggesting that the O-GlcNAc modification may control downstream effectors to modulate insulin pathway mediated cellular processes.

Search genes: daf-16 oga-1

Entrez ID
Symbol
GenAge
Wormbase ID

172981
daf-16
View on GenAge (daf-16)
WBGene00000912

Forkhead box protein O;hypothetical protein

Locus: CELE_R13H8.1

Wormbase description: daf-16 encodes the sole C. elegans forkhead box O (FOXO) homologue; DAF-16 functions as a transcription factor that acts in the insulin/IGF-1-mediated signaling (IIS) pathway that regulates dauer formation, longevity, fat metabolism, stress response, and innate immunity; DAF-16 regulates these various processes through isoform-specific expression, isoform-specific regulation by different AKT kinases, and differential regulation of target genes; DAF-16 can interact with the CBP-1 transcription cofactor in vitro, and interacts genetically with other genes in the insulin signaling and with daf-12, which encodes a nuclear hormone receptor; DAF-16 is activated in response to DNA damage during development and co-regulated by EGL-27, alleviates DNA-damage-induced developmental arrest by inducing DAF-16-associated element (DAE)-regulated genes; DAF-16 is broadly expressed but displays isoform-specific tissue enrichment; DAF-16 localizes to both the cytoplasm and the nucleus, with the ratio between the two an important regulator of function.

Entrez ID
Symbol
GenAge
Wormbase ID

181164
oga-1
View on GenAge (oga-1)
WBGene00020596

O-GlcNAc selective N-Acetyl-beta-D-glucosaminidase (O-GlcNAcase)

Locus: CELE_T20B5.3

Wormbase description: oga-1 encodes an ortholog of mammalian O-linked N-acetylglucosamine (O-GlcNAc)-selective N-acetyl-beta-D-glucosaminidase (O-GlcNAcase); a polymorphism of OGA-1's human ortholog MGEA5 is associated with type 2 diabetes, and OGA-1 appears to be required for fine-tuning of insulin signalling; oga-1(ok1207) mutants are viable and fertile but accumulate O-GlcNAc on nuclear pores and other proteins, while showing S/T-phosphorylation of proteins, increased GSK-3beta activity, excess glycogen and trehalose, and decreased lipid storage; oga-1(ok1207) mutations enhance the Daf-c phenotype of daf-2(e1370ts) alleles even under conditions where oga-1(ok1207) alone diminishes dauer formation.

Orthologs of daf-16;oga-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Foxo6;Mgea5
Mus musculus	Foxo1;Mgea5
Mus musculus	Foxo4;Mgea5
Mus musculus	Foxo3;Mgea5
Mus musculus	Mgea5;Foxo6
Mus musculus	Mgea5;Foxo1
Mus musculus	Mgea5;Foxo4
Mus musculus	Mgea5;Foxo3

Orthologs of daf-16 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Foxo6
Mus musculus	Foxo1
Mus musculus	Foxo4
Mus musculus	Foxo3

Orthologs of oga-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Oga
Mus musculus	Mgea5