daf-16;sea-2

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Genetic mutants with daf-16, sea-2 alterations

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

Temperature °C
20
Lifespan (days)
12.1
Lifespan change (compared to wild type)
-30.06%
Phenotype
sea-2 mutants have extended lifespan. The long-lived phenotype of sea-2 is suppressed by loss of function of daf-16.
Lifespan comparisons
Double mutant daf-16(mu86);sea-2(bp283) has a lifespan of 12.1 days, while single mutant daf-16(mu86) has a lifespan of 12.7 days, single mutant sea-2(bp283) has a lifespan of 20.1 days and wild type has a lifespan of 17.3 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Huang X et al., 2011, The zinc-finger protein SEA-2 regulates larval developmental timing and adult lifespan in C. elegans. Development. 138(10):2059-68 21471153 Click here to select all mutants from this PubMed ID in the graph
Abstract
Like other biological processes, aging is regulated by genetic pathways. However, it remains largely unknown whether aging is determined by an innate programmed timing mechanism and, if so, how this timer is linked to the mechanisms that control developmental timing. Here, we demonstrate that sea-2, which encodes a zinc-finger protein, controls developmental timing in C. elegans larvae by regulating expression of the heterochronic gene lin-28 at the post-transcriptional level. lin-28 is also essential for the autosomal signal element (ASE) function of sea-2 in X:A signal assessment. We also show that sea-2 modulates aging in adulthood. Loss of function of sea-2 slows the aging process and extends the adult lifespan in a DAF-16/FOXO-dependent manner. Mutation of sea-2 promotes nuclear translocation of DAF-16 and subsequent activation of daf-16 targets. We further demonstrate that insulin/IGF-1 signaling functions in the larval heterochronic circuit. Loss of function of the insulin/IGF-1 receptor gene daf-2, which extends lifespan, also greatly enhances the retarded heterochronic defects in sea-2 mutants. Regulation of developmental timing by daf-2 requires daf-16 activity. Our study provides evidence for intricate interplay between the heterochronic circuit that controls developmental timing in larvae and the timing mechanism that modulates aging in adults.

Search genes: daf-16 sea-2

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

173738
sea-2
View on GenAge (sea-2)
WBGene00004751

Signal Element on Autosome

Locus: CELE_K10G6.3

Wormbase description: sea-2 encodes a zinc finger protein; SEA-2 is an autosomal signal element (ASE) that functions to interpret the X:A chromosomal ratio; in addition, SEA-2 functions autonomously in the intestine to regulate adult lifespan and autonomously in seam cells to regulate larval developmental timing; in regulating lifespan and developmental timing, SEA-2 functions as a post-transcriptional negative regulator of LIN-28, which specifies the L2 larval developmental program; sea-2 also interacts with the daf-2/insulin-IGF-1 signaling pathway to regulate larval developmental timing and adult lifespan; a SEA-2::GFP fusion protein is expressed in a variety of tissues, including seam cells, intestinal cells, pharyngeal muscles and nerve ring neurons, and localizes diffusely to the cytoplasm and the nucleus.

Orthologs of daf-16;sea-2 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 sea-2 in SynergyAge

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Species	Gene