daf-12;trpa-1

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Genetic mutants with daf-12, 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)
23.6
Lifespan comparisons
Double mutant daf-12(rh61rh411);trpa-1(xuEx601) has a lifespan of 23.6 days, while single mutant daf-12(rh61rh411) has a lifespan of 20.8 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.

Search genes: daf-12 trpa-1

Entrez ID
Symbol
GenAge
Wormbase ID

181263
daf-12
View on GenAge (daf-12)
WBGene00000908

Nuclear hormone receptor family member daf-12

Locus: CELE_F11A1.3

Wormbase description: daf-12 encodes a member of the steroid hormone receptor superfamily that is homologous to human VITAMIN D RECEPTOR (VDR; OMIM:601769, mutated in vitamin D-resistant rickets); daf-12 affects dauer formation downstream of the TGF- and insulin signaling pathways, and affects gonad-dependent adult longevity together with DAF-16, chemosensory signal transduction, and distal tip cell migration and hypodermal and intestinal cell lineages during the L3 larval stage; DAF-12 is expressed in the nucleus and in most cells; daf-12 expression in lateral seam cells is negatively regulated by the let-7 miRNA.

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 daf-12;trpa-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Hr96;TrpA1
Mus musculus	TrpA1;Hr96

Orthologs of daf-12 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Hr96

Orthologs of trpa-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	TrpA1
Mus musculus	Trpa1

About

SynergyAge database hosts high-quality, manually curated information about the synergistic and antagonistic lifespan effects of genetic interventions in model organisms, also allowing users to explore the longevity relationships between genes in a visual way.