pkc-2;trpa-1

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Genetic mutants with pkc-2, trpa-1 alterations

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

Temperature °C
15
Diet
NGM
Lifespan (days)
22.81
Lifespan change (compared to wild type)
-16.08%
Phenotype
The short-lived phenotype of pkc-2; trpa-1double mutant at low temperatures is similar to that of trpa-1 and pkc-2 single mutants, showing that the effect of these two genes on lifespan is not additive. This provides additional evidence that TRPA-1 and PKC-2 act in the same pathway.
Lifespan comparisons
Double mutant pkc-2(ok328);trpa-1(ok999) has a lifespan of 22.81 days, while single mutant pkc-2(ok328) has a lifespan of 22.81 days, single mutant trpa-1(ok999) has a lifespan of 23.75 days and wild type has a lifespan of 27.18 days.
Type of interaction
See methods
Dependent
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)
16.0
Lifespan change (compared to wild type)
-20.00%
Phenotype
The short-lived phenotype of pkc-2; trpa-1double mutant is similar to that of trpa-1 and pkc-2 single mutants, showing that the effect of these two genes on lifespan is not additive. This provides additional evidence that TRPA-1 and PKC-2 act in the same pathway.
Lifespan comparisons
Double mutant pkc-2(ok328);trpa-1(ok999) has a lifespan of 16.0 days, while single mutant pkc-2(ok328) has a lifespan of 17.5 days, single mutant trpa-1(ok999) has a lifespan of 17.0 days and wild type has a lifespan of 20.0 days.
Type of interaction
See methods
Almost additive (negative)
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
25
Diet
NGM
Lifespan (days)
13.95
Lifespan change (compared to wild type)
-2.92%
Phenotype
The short-lived phenotype of pkc-2; trpa-1double mutant is similar to that of trpa-1 and pkc-2 single mutants, showing that the effect of these two genes on lifespan is not additive. This provides additional evidence that TRPA-1 and PKC-2 act in the same pathway.
Lifespan comparisons
Double mutant pkc-2(ok328);trpa-1(ok999) has a lifespan of 13.95 days, while single mutant pkc-2(ok328) has a lifespan of 13.95 days, single mutant trpa-1(ok999) has a lifespan of 15.2 days and wild type has a lifespan of 14.37 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)
19.7
Phenotype
Loss of pkc-2 fully suppresses the long-lived phenotype of trpa-1 transgenic worms.
Lifespan comparisons
Double mutant pkc-2(ok328);trpa-1(xuEx601) has a lifespan of 19.7 days, while single mutant trpa-1(xuEx601) has a lifespan of 23.9 days and single mutant pkc-2(ok328) has a lifespan of 19.2 days.
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)
18.7
Phenotype
Loss of pkc-2 fully suppresses the long-lived phenotype of trpa-1 transgenic worms.
Lifespan comparisons
Double mutant pkc-2(ok328);trpa-1(xuEx601) has a lifespan of 18.7 days, while single mutant trpa-1(xuEx601) has a lifespan of 21.6 days and single mutant pkc-2(ok328) has a lifespan of 18.5 days.
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)
19.3
Phenotype
Loss of pkc-2 fully suppresses the long-lived phenotype of trpa-1 transgenic worms.
Lifespan comparisons
Double mutant pkc-2(ok328);trpa-1(xuEx619) has a lifespan of 19.3 days, while single mutant trpa-1(xuEx619) has a lifespan of 22.1 days and single mutant pkc-2(ok328) has a lifespan of 18.5 days.
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)
25.33
Lifespan change (compared to wild type)
35.74%
Phenotype
pkc-2 transgene can fully suppress the short-lived phenotype of trpa-1 mutant worms, consistent with the model that PKC-2 acts downstream of TRPA-1.
Lifespan comparisons
Double mutant pkc-2(xuEx913);trpa-1(ok999) has a lifespan of 25.33 days, while single mutant pkc-2(xuEx913) has a lifespan of 25.33 days, single mutant trpa-1(ok999) has a lifespan of 17.3 days and wild type has a lifespan of 18.66 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: pkc-2 trpa-1

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.

Entrez ID
Symbol
GenAge
Wormbase ID

178118
trpa-1
View on GenAge (trpa-1)
WBGene00007801

TRPA cation channel homolog;Transient receptor potential cation channel subfamily A member 1 homolog

Locus: CELE_C29E6.2

Wormbase description: trpa-1 encodes a transient receptor potential (TRP) ion channel orthologous to the vertebrate and Drosophila TRPA1 channels; in C. elegans, trpa-1 activity is required for specific mechanosensory behaviors such as nose-touch avoidance and touch-mediated foraging; when expressed in mammalian cells, TRPA-1 exhibits channel activity in response to mechanical stimulation; TRPA-1::GFP reporters are expressed in a number of different cell types including sensory neurons, muscle, and epithelial cells.

Orthologs of pkc-2;trpa-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Pkc53E;TrpA1
Mus musculus	Prkca;Trpa1
Mus musculus	Prkcg;Trpa1
Mus musculus	Prkcb;Trpa1

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

Orthologs of trpa-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	TrpA1
Mus musculus	Trpa1