daf-16;nhr-49

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Genetic mutants with daf-16, nhr-49 alterations

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

Temperature °C
20
Diet
OP50
Lifespan (days)
11.8
Lifespan change (compared to wild type)
-41.87%
Lifespan comparisons
Double mutant daf-16(RNAi);nhr-49(OE) has a lifespan of 11.8 days, while single mutant nhr-49(OE) has a lifespan of 21.6 days and wild type has a lifespan of 20.3 days.
Type of interaction
See methods
Contains dependence
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)
17.4
Lifespan change (compared to wild type)
-5.95%
Phenotype
nhr-49 overexpression in daf-16 mutants caused a small additional increment in their longevity.
Lifespan comparisons
Double mutant daf-16(mu86);nhr-49(OE) has a lifespan of 17.4 days, while single mutant daf-16(mu86) has a lifespan of 15.6 days, single mutant nhr-49(OE) has a lifespan of 24.9 days and wild type has a lifespan of 18.5 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: daf-16 nhr-49

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

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 daf-16;nhr-49 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene

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 nhr-49 in SynergyAge

Show in SynergyAge
Species	Gene