daf-16;pkc-2

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Genetic mutants with daf-16, pkc-2 alterations

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

Temperature °C
20
Diet
NGM
Lifespan (days)
14.6
Lifespan change (compared to wild type)
-26.26%
Phenotype
Overexpression of pkc-2 cDNA extends lifespan, which can be fully suppressed by loss of daf-16.
Lifespan comparisons
Double mutant daf-16(mgDf47);pkc-2(xuEx913) has a lifespan of 14.6 days, while single mutant pkc-2(xuEx913) has a lifespan of 27.1 days, single mutant daf-16(mgDf47) has a lifespan of 14.8 days and wild type has a lifespan of 19.8 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Xiao R et al., 2013, A genetic program promotes C. elegans longevity at cold temperatures via a thermosensitive TRP channel. Cell. 152(4):806-17 23415228 Click here to select all mutants from this PubMed ID in the graph
Abstract
Both poikilotherms and homeotherms live longer at lower body temperatures, highlighting a general role of temperature reduction in lifespan extension. However, the underlying mechanisms remain unclear. One prominent model is that cold temperatures reduce the rate of chemical reactions, thereby slowing the rate of aging. This view suggests that cold-dependent lifespan extension is simply a passive thermodynamic process. Here, we challenge this view in C. elegans by showing that genetic programs actively promote longevity at cold temperatures. We find that TRPA-1, a cold-sensitive TRP channel, detects temperature drop in the environment to extend lifespan. This effect requires cold-induced, TRPA-1-mediated calcium influx and a calcium-sensitive PKC that signals to the transcription factor DAF-16/FOXO. Human TRPA1 can functionally substitute for worm TRPA-1 in promoting longevity. Our results reveal a previously unrecognized function for TRP channels, link calcium signaling to longevity, and, importantly, demonstrate that genetic programs contribute to lifespan extension at cold temperatures.

Temperature °C
20
Diet
NGM
Lifespan (days)
17.2
Lifespan change (compared to wild type)
-13.57%
Phenotype
Overexpression of pkc-2 cDNA extends lifespan, which can be fully suppressed by loss of daf-16.
Lifespan comparisons
Double mutant daf-16(mgDf47);pkc-2(xuEx913) has a lifespan of 17.2 days, while single mutant pkc-2(xuEx913) has a lifespan of 23.4 days, single mutant daf-16(mgDf47) has a lifespan of 17.1 days and wild type has a lifespan of 19.9 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Xiao R et al., 2013, A genetic program promotes C. elegans longevity at cold temperatures via a thermosensitive TRP channel. Cell. 152(4):806-17 23415228 Click here to select all mutants from this PubMed ID in the graph
Abstract
Both poikilotherms and homeotherms live longer at lower body temperatures, highlighting a general role of temperature reduction in lifespan extension. However, the underlying mechanisms remain unclear. One prominent model is that cold temperatures reduce the rate of chemical reactions, thereby slowing the rate of aging. This view suggests that cold-dependent lifespan extension is simply a passive thermodynamic process. Here, we challenge this view in C. elegans by showing that genetic programs actively promote longevity at cold temperatures. We find that TRPA-1, a cold-sensitive TRP channel, detects temperature drop in the environment to extend lifespan. This effect requires cold-induced, TRPA-1-mediated calcium influx and a calcium-sensitive PKC that signals to the transcription factor DAF-16/FOXO. Human TRPA1 can functionally substitute for worm TRPA-1 in promoting longevity. Our results reveal a previously unrecognized function for TRP channels, link calcium signaling to longevity, and, importantly, demonstrate that genetic programs contribute to lifespan extension at cold temperatures.

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

Temperature °C
20
Diet
NGM
Lifespan (days)
15.1
Lifespan change (compared to wild type)
-23.74%
Phenotype
Overexpression of pkc-2 cDNA extends lifespan, which can be fully suppressed by loss of daf-16.
Lifespan comparisons
Double mutant daf-16(mgDf47);pkc-2(xuEx916) has a lifespan of 15.1 days, while single mutant pkc-2(xuEx916) has a lifespan of 25.0 days, single mutant daf-16(mgDf47) has a lifespan of 14.8 days and wild type has a lifespan of 19.8 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Xiao R et al., 2013, A genetic program promotes C. elegans longevity at cold temperatures via a thermosensitive TRP channel. Cell. 152(4):806-17 23415228 Click here to select all mutants from this PubMed ID in the graph
Abstract
Both poikilotherms and homeotherms live longer at lower body temperatures, highlighting a general role of temperature reduction in lifespan extension. However, the underlying mechanisms remain unclear. One prominent model is that cold temperatures reduce the rate of chemical reactions, thereby slowing the rate of aging. This view suggests that cold-dependent lifespan extension is simply a passive thermodynamic process. Here, we challenge this view in C. elegans by showing that genetic programs actively promote longevity at cold temperatures. We find that TRPA-1, a cold-sensitive TRP channel, detects temperature drop in the environment to extend lifespan. This effect requires cold-induced, TRPA-1-mediated calcium influx and a calcium-sensitive PKC that signals to the transcription factor DAF-16/FOXO. Human TRPA1 can functionally substitute for worm TRPA-1 in promoting longevity. Our results reveal a previously unrecognized function for TRP channels, link calcium signaling to longevity, and, importantly, demonstrate that genetic programs contribute to lifespan extension at cold temperatures.

Temperature °C
20
Diet
NGM
Lifespan (days)
16.7
Lifespan change (compared to wild type)
-16.08%
Phenotype
Overexpression of pkc-2 cDNA extends lifespan, which can be fully suppressed by loss of daf-16.
Lifespan comparisons
Double mutant daf-16(mgDf47);pkc-2(xuEx916) has a lifespan of 16.7 days, while single mutant pkc-2(xuEx916) has a lifespan of 22.7 days, single mutant daf-16(mgDf47) has a lifespan of 17.1 days and wild type has a lifespan of 19.9 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Xiao R et al., 2013, A genetic program promotes C. elegans longevity at cold temperatures via a thermosensitive TRP channel. Cell. 152(4):806-17 23415228 Click here to select all mutants from this PubMed ID in the graph
Abstract
Both poikilotherms and homeotherms live longer at lower body temperatures, highlighting a general role of temperature reduction in lifespan extension. However, the underlying mechanisms remain unclear. One prominent model is that cold temperatures reduce the rate of chemical reactions, thereby slowing the rate of aging. This view suggests that cold-dependent lifespan extension is simply a passive thermodynamic process. Here, we challenge this view in C. elegans by showing that genetic programs actively promote longevity at cold temperatures. We find that TRPA-1, a cold-sensitive TRP channel, detects temperature drop in the environment to extend lifespan. This effect requires cold-induced, TRPA-1-mediated calcium influx and a calcium-sensitive PKC that signals to the transcription factor DAF-16/FOXO. Human TRPA1 can functionally substitute for worm TRPA-1 in promoting longevity. Our results reveal a previously unrecognized function for TRP channels, link calcium signaling to longevity, and, importantly, demonstrate that genetic programs contribute to lifespan extension at cold temperatures.

Search genes: daf-16 pkc-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

181166
pkc-2
View on GenAge (pkc-2)
WBGene00004033

Protein kinase C;Protein kinase C-like 2

Locus: CELE_E01H11.1

Wormbase description: pkc-2 encodes protein kinases similar to the classical protein kinase C family of Ca2+/diacylglycerol-stimulated kinases; when expressed in insect cells, one PKC-2 isoform exhibits Ca2+-dependent serine phosphorylation; PKC-2 isoforms are expressed in neurons, the intestine, muscles cells, and the somatic distal gonad, including the spermatheca; in neurons, PKC-2 localizes to the cell body and to neuronal processes; PKC-2 is expressed at low levels in embryos, with expression increasing 10-fold during the L1 larval stage, and then continuing at lower levels throughout post-embryonic development; fractionation experiments indicate that in young adults and mid-L1 and L2 larvae, PKC-2 isoforms are nearly evenly distributed between the cytosol and organelles and/or the cytoskeleton; in egg-laying adults, approximately 70% of PKC-2 is found in the cytosol.

Orthologs of daf-16;pkc-2 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Foxo6;Prkca
Mus musculus	Foxo6;Prkcg
Mus musculus	Foxo6;Prkcb
Mus musculus	Foxo1;Prkca
Mus musculus	Foxo1;Prkcg
Mus musculus	Foxo1;Prkcb
Mus musculus	Foxo4;Prkca
Mus musculus	Foxo4;Prkcg
Mus musculus	Foxo4;Prkcb
Mus musculus	Foxo3;Prkca
Mus musculus	Foxo3;Prkcg
Mus musculus	Foxo3;Prkcb
Mus musculus	Prkca;Foxo6
Mus musculus	Prkca;Foxo1
Mus musculus	Prkca;Foxo4
Mus musculus	Prkca;Foxo3
Mus musculus	Prkcg;Foxo6
Mus musculus	Prkcg;Foxo1
Mus musculus	Prkcg;Foxo4
Mus musculus	Prkcg;Foxo3
Mus musculus	Prkcb;Foxo6
Mus musculus	Prkcb;Foxo1
Mus musculus	Prkcb;Foxo4
Mus musculus	Prkcb;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 pkc-2 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Pkc53E
Mus musculus	Prkca
Mus musculus	Prkcg
Mus musculus	Prkcb