akt-1;daf-16

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Genetic mutants with akt-1, daf-16 alterations

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

Temperature °C
20
Diet
OP50
Lifespan (days)
15.3
Lifespan change (compared to wild type)
-39.04%
Lifespan comparisons
Double mutant akt-1(mg306);daf-16(mu86) has a lifespan of 15.3 days, while single mutant akt-1(mg306) has a lifespan of 30.0 days and wild type has a lifespan of 25.1 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Chen AT et al., 2013, Effects of Caenorhabditis elegans sgk-1 mutations on lifespan, stress resistance, and DAF-16/FoxO regulation. Aging Cell. 12(5):932-40 23786484 Click here to select all mutants from this PubMed ID in the graph
Abstract
The AGC family serine-threonine kinases Akt and Sgk are similar in primary amino acid sequence and in vitro substrate specificity, and both kinases are thought to directly phosphorylate and inhibit FoxO transcription factors. In the nematode Caenorhabditis elegans, it is well established that AKT-1 controls dauer arrest and lifespan by regulating the subcellular localization of the FoxO transcription factor DAF-16. SGK-1 is thought to act similarly to AKT-1 in lifespan control by phosphorylating and inhibiting the nuclear translocation of DAF-16/FoxO. Using sgk-1 null and gain-of-function mutants, we now provide multiple lines of evidence indicating that AKT-1 and SGK-1 influence C. elegans lifespan, stress resistance, and DAF-16/FoxO activity in fundamentally different ways. Whereas AKT-1 shortens lifespan, SGK-1 promotes longevity in a DAF-16-/FoxO-dependent manner. In contrast to AKT-1, which reduces resistance to multiple stresses, SGK-1 promotes resistance to oxidative stress and ultraviolet radiation but inhibits thermotolerance. Analysis of several DAF-16/FoxO target genes that are repressed by AKT-1 reveals that SGK-1 represses a subset of these genes while having little influence on the expression of others. Accordingly, unlike AKT-1, which promotes the cytoplasmic sequestration of DAF-16/FoxO, SGK-1 does not influence DAF-16/FoxO subcellular localization. Thus, in spite of their similar in vitro substrate specificities, Akt and Sgk influence longevity, stress resistance, and FoxO activity through distinct mechanisms in vivo. Our findings highlight the need for a re-evaluation of current paradigms of FoxO regulation by Sgk.

Temperature °C
20
Diet
OP50
Lifespan (days)
13.5
Lifespan change (compared to wild type)
-34.78%
Lifespan comparisons
Double mutant akt-1(mg306);daf-16(mu86) has a lifespan of 13.5 days, while single mutant akt-1(mg306) has a lifespan of 32.2 days and wild type has a lifespan of 20.7 days.
Type of interaction
See methods
Contains dependence
Citation
View abstract
Chen AT et al., 2013, Effects of Caenorhabditis elegans sgk-1 mutations on lifespan, stress resistance, and DAF-16/FoxO regulation. Aging Cell. 12(5):932-40 23786484 Click here to select all mutants from this PubMed ID in the graph
Abstract
The AGC family serine-threonine kinases Akt and Sgk are similar in primary amino acid sequence and in vitro substrate specificity, and both kinases are thought to directly phosphorylate and inhibit FoxO transcription factors. In the nematode Caenorhabditis elegans, it is well established that AKT-1 controls dauer arrest and lifespan by regulating the subcellular localization of the FoxO transcription factor DAF-16. SGK-1 is thought to act similarly to AKT-1 in lifespan control by phosphorylating and inhibiting the nuclear translocation of DAF-16/FoxO. Using sgk-1 null and gain-of-function mutants, we now provide multiple lines of evidence indicating that AKT-1 and SGK-1 influence C. elegans lifespan, stress resistance, and DAF-16/FoxO activity in fundamentally different ways. Whereas AKT-1 shortens lifespan, SGK-1 promotes longevity in a DAF-16-/FoxO-dependent manner. In contrast to AKT-1, which reduces resistance to multiple stresses, SGK-1 promotes resistance to oxidative stress and ultraviolet radiation but inhibits thermotolerance. Analysis of several DAF-16/FoxO target genes that are repressed by AKT-1 reveals that SGK-1 represses a subset of these genes while having little influence on the expression of others. Accordingly, unlike AKT-1, which promotes the cytoplasmic sequestration of DAF-16/FoxO, SGK-1 does not influence DAF-16/FoxO subcellular localization. Thus, in spite of their similar in vitro substrate specificities, Akt and Sgk influence longevity, stress resistance, and FoxO activity through distinct mechanisms in vivo. Our findings highlight the need for a re-evaluation of current paradigms of FoxO regulation by Sgk.

Search genes: akt-1 daf-16

Entrez ID
Symbol
GenAge
Wormbase ID

179424
akt-1
View on GenAge (akt-1)
WBGene00000102

Serine/threonine-protein kinase akt-1

Locus: CELE_C12D8.10

Wormbase description: akt-1 encodes an ortholog of the serine/threonine kinase Akt/PKB; akt-1 genetically interacts with the insulin signaling pathway and functions to regulate such processes as dauer larval development and salt chemotaxis learning; AKT-1 binds calmodulin in vitro in a calcium-dependent manner; an AKT-1::GFP fusion protein is widely expressed beginning in late stage embryos and continuing through adulthood; expression is seen in head, tail, and dorsal and ventral cord neurons, with additional expression seen in other cells including those of the pharynx, hypodermis, intestine, and spermatheca; two alleles of akt-1 (sa573 and sa700) have a Daf-c mutant phenotype at 27 degrees C (Hid phenotype).

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.

Orthologs of akt-1;daf-16 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Akt1;Foxo6
Mus musculus	Akt1;Foxo1
Mus musculus	Akt1;Foxo4
Mus musculus	Akt1;Foxo3
Mus musculus	Akt2;Foxo6
Mus musculus	Akt2;Foxo1
Mus musculus	Akt2;Foxo4
Mus musculus	Akt2;Foxo3
Mus musculus	Akt3;Foxo6
Mus musculus	Akt3;Foxo1
Mus musculus	Akt3;Foxo4
Mus musculus	Akt3;Foxo3

Orthologs of akt-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Akt1
Mus musculus	Akt1
Mus musculus	Akt2
Mus musculus	Akt3

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