cmk-1;trpa-1

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Genetic mutants with cmk-1, trpa-1 alterations

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

Temperature °C
20
Diet
NGM
Lifespan (days)
24.28
Lifespan change (compared to wild type)
58.18%
Phenotype
trpa-1 transgene can further extend the lifespan of cmk-1mutant worms.
Lifespan comparisons
Double mutant cmk-1(oy21);trpa-1(xuEx601) has a lifespan of 24.28 days, while single mutant trpa-1(xuEx601) has a lifespan of 22.85 days, single mutant cmk-1(oy21) has a lifespan of 16.42 days and wild type has a lifespan of 15.35 days.
Type of interaction
See methods
Synergistic (positive)
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)
22.85
Lifespan change (compared to wild type)
48.86%
Phenotype
trpa-1 transgene can further extend the lifespan of cmk-1mutant worms.
Lifespan comparisons
Double mutant cmk-1(oy21);trpa-1(xuEx619) has a lifespan of 22.85 days, while single mutant trpa-1(xuEx619) has a lifespan of 23.92 days, single mutant cmk-1(oy21) has a lifespan of 16.42 days and wild type has a lifespan of 15.35 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.

Search genes: cmk-1 trpa-1

Entrez ID
Symbol
GenAge
Wormbase ID

176989
cmk-1
View on GenAge (cmk-1)
WBGene00000553

Calcium/calmodulin-dependent protein kinase type 1

Locus: CELE_K07A9.2

Wormbase description: cmk-1 encodes a Ca+2/calmodulin-dependent protein kinase I (CaMK1); CMK-1 activity is required, cell autonomously and downstream of the cyclic nucleotide-gated channel TAX-4, for several aspects of AFD thermosensory neuron differentiation, including expression of the gcy-8 guanylyl cyclase and nhr-38 nuclear hormone receptor genes and morphology of the AFD sensory endings; cmk-1 activity is thus also required for normal thermosensory behavior; when expressed in COS-7 cells, CMK-1 and CKK-1 positively regulate the transcriptional activity of endogenous CREB; a cmk-1::gfp reporter is expressed in head sensory and interneurons as well as in the ventral nerve cord; expression is seen specifically in the neurons of the thermosensory circuit, AFD, AIY, and AIZ; in the AFD neurons, CMK-1 localizes exclusively to the cytoplasm, however when expressed in COS-7 cells, CMK-1 is seen in the nucleus.

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 cmk-1;trpa-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	CaMKI;TrpA1
Mus musculus	Camk1d;Trpa1
Mus musculus	Camk1;Trpa1
Mus musculus	Pnck;Trpa1

Orthologs of cmk-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	CaMKI
Mus musculus	Camk1d
Mus musculus	Camk1
Mus musculus	Pnck

Orthologs of trpa-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	TrpA1
Mus musculus	Trpa1