daf-16;fasn-1

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Genetic mutants with daf-16, fasn-1 alterations

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

Temperature °C
25
Diet
NGM
Lifespan (days)
12.1
Lifespan change (compared to wild type)
-40.39%
Lifespan comparisons
Double mutant daf-16(mu86);fasn-1(RNAi) has a lifespan of 12.1 days, while single mutant fasn-1(RNAi) has a lifespan of 17.9 days, single mutant daf-16(mu86) has a lifespan of 13.1 days and wild type has a lifespan of 20.3 days.
Type of interaction
See methods
Almost additive (negative)
Citation
View abstract
Rogers AN et al., 2011, Life span extension via eIF4G inhibition is mediated by posttranscriptional remodeling of stress response gene expression in C. elegans. Cell Metab. 14(1):55-66 21723504 Click here to select all mutants from this PubMed ID in the graph
Abstract
Reducing protein synthesis slows growth and development but can increase adult life span. We demonstrate that knockdown of eukaryotic translation initiation factor 4G (eIF4G), which is downregulated during starvation and dauer state, results in differential translation of genes important for growth and longevity in C. elegans. Genome-wide mRNA translation state analysis showed that inhibition of IFG-1, the C. elegans ortholog of eIF4G, results in a relative increase in ribosomal loading and translation of stress response genes. Some of these genes are required for life span extension when IFG-1 is inhibited. Furthermore, enhanced ribosomal loading of certain mRNAs upon IFG-1 inhibition was correlated with increased mRNA length. This association was supported by changes in the proteome assayed via quantitative mass spectrometry. Our results suggest that IFG-1 mediates the antagonistic effects on growth and somatic maintenance by regulating mRNA translation of particular mRNAs based, in part, on transcript length.

Search genes: daf-16 fasn-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

172715
fasn-1
View on GenAge (fasn-1)
WBGene00009342

Fatty Acid SyNthase

Locus: CELE_F32H2.5

Wormbase description: fasn-1 encodes a fatty acid synthase, orthologous to human FASN (OMIM:600212); CEP-1 is required for fully normal fasn-1 expression in vivo; CEP-1 drives transcription of luciferase reporters whose promoters contains either of two putative CEP-1 binding sites (FAS-T1 and FAS-T2) found in the fasn-1 gene, and this activity is partially lost by mutation of conserved CEP-1 residues (R298 or H310); in humans, the CEP-1 ortholog isoforms TAp73alpha and deltaNp63alpha bind the human FASN gene, suggesting that FASN genes might be a conserved direct target of p53-like proteins in metazoa; fasn-1 transcription is moderately activated (2 to 4-fold) in L1 or L2 larvae starved for 12 hours, but is not so activated in later larvae or adults.

Orthologs of daf-16;fasn-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Fasn;Foxo6
Mus musculus	Fasn;Foxo1
Mus musculus	Fasn;Foxo4
Mus musculus	Fasn;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 fasn-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	FASN1
Drosophila melanogaster	FASN2
Mus musculus	Fasn

About

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.