daf-16;lin-14

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Genetic mutants with daf-16, lin-14 alterations

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

Temperature °C
25
Lifespan (days)
8.4
Lifespan change (compared to wild type)
-5.62%
Phenotype
The life-span extension conferred by the lin-14(n179)lf mutation is abolished with daf-16(RNAi)
Lifespan comparisons
Double mutant daf-16(RNAi);lin-14(n179) has a lifespan of 8.4 days, while single mutant lin-14(n179) has a lifespan of 11.9 days and wild type has a lifespan of 8.9 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Boehm M, Slack F, 2005, A developmental timing microRNA and its target regulate life span in C. elegans. Science. 310(5756):1954-7 16373574 Click here to select all mutants from this PubMed ID in the graph
Abstract
The microRNA lin-4 and its target, the putative transcription factor lin-14, control the timing of larval development in Caenorhabditis elegans. Here, we report that lin-4 and lin-14 also regulate life span in the adult. Reducing the activity of lin-4 shortened life span and accelerated tissue aging, whereas overexpressing lin-4 or reducing the activity of lin-14 extended life span. Lifespan extension conferred by a reduction in lin-14 was dependent on the DAF-16 and HSF-1 transcription factors, suggesting that the lin-4-lin-14 pair affects life span through the insulin/insulin-like growth factor-1 pathway. This work reveals a role for microRNAs and developmental timing genes in life-span regulation.

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

Temperature °C
15
Lifespan (days)
16.7
Lifespan change (compared to wild type)
-22.69%
Phenotype
lin-14(RNAi) is unable to extend the life span of daf-16(mu86) or daf-2(e1370)lf mutants as compared with these strains grown on mock RNAi at 15°C.
Lifespan comparisons
Double mutant daf-16(mu86);lin-14(RNAi) has a lifespan of 16.7 days, while single mutant daf-16(mu86) has a lifespan of 16.4 days, single mutant lin-14(RNAi) has a lifespan of 25.1 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
Boehm M, Slack F, 2005, A developmental timing microRNA and its target regulate life span in C. elegans. Science. 310(5756):1954-7 16373574 Click here to select all mutants from this PubMed ID in the graph
Abstract
The microRNA lin-4 and its target, the putative transcription factor lin-14, control the timing of larval development in Caenorhabditis elegans. Here, we report that lin-4 and lin-14 also regulate life span in the adult. Reducing the activity of lin-4 shortened life span and accelerated tissue aging, whereas overexpressing lin-4 or reducing the activity of lin-14 extended life span. Lifespan extension conferred by a reduction in lin-14 was dependent on the DAF-16 and HSF-1 transcription factors, suggesting that the lin-4-lin-14 pair affects life span through the insulin/insulin-like growth factor-1 pathway. This work reveals a role for microRNAs and developmental timing genes in life-span regulation.

Search genes: daf-16 lin-14

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

181337
lin-14
View on GenAge (lin-14)
WBGene00003003

Protein lin-14

Locus: CELE_T25C12.1

Wormbase description: lin-14 encodes a novel protein whose activity is required for specifying the division timings of a specific group of cells during postembryonic development; lin-14 loss-of-function mutations result in the premature appearance of later larval lineages, while gain-of-function mutations result in reiteration of L1 larval stages lineages; in addition, lin-14 acts as a positive regulator of AVM, PVM, and FLP touch cell development; in regulating developmental timing, lin-14 acts, in part, by positively regulating the activity of lin-28, which encodes a cytoplasmic protein also required for proper developmental timing; at hatching, LIN-14 is detected in the nuclei of blast cells and neurons; later, from the late L1 to adult stages, LIN-14 levels are negatively regulated by translational repression mediated by lin-4, a 22-nt small temporal RNA (stRNA) that is complementary to sequences in the lin-14 3' UTR.

Orthologs of daf-16;lin-14 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of daf-16 in SynergyAge

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Species	Gene

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

Orthologs of lin-14 in SynergyAge

Show in SynergyAge
Species	Gene