akt-2;trpa-1

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Genetic mutants with akt-2, 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)
28.78
Lifespan change (compared to wild type)
58.31%
Phenotype
trpa-1 transgene can further extend the lifespan of akt-2 mutant worms.
Lifespan comparisons
Double mutant akt-2(ok393);trpa-1(xuEx601) has a lifespan of 28.78 days, while single mutant trpa-1(xuEx601) has a lifespan of 24.54 days, single mutant akt-2(ok393) has a lifespan of 25.75 days and wild type has a lifespan of 18.18 days.
Type of interaction
See methods
Almost additive (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.

Search genes: akt-2 trpa-1

Entrez ID
Symbol
GenAge
Wormbase ID

181524
akt-2
View on GenAge (akt-2)
WBGene00000103

Serine/threonine-protein kinase akt-2

Locus: CELE_F28H6.1

Wormbase description: akt-2 encodes a homolog of the serine/threonine kinase Akt/PKB, AKT-2, that is required for progression through the dauer stage of development and for the negative regulation of adult lifespan; inactivation of akt-2 causes animals to arrest constitutively at the dauer stage, while having an increased life span; widely expressed, AKT-2 is activated by the phospholipid products of phosphoinositide 3-kinase AGE-1/PI3K and by PDK-1, a homolog of vertebrate 3-phosphoinositide-dependent kinase-1 (PDK-1) Normal akt-2 (and akt-1) activity is required for excess pdk-1 activity to suppress the dauer-arrest phenotype of age-1, indicating that the 3-phosphoinositide-dependent kinase-1 homolog PDK-1 transduces signals from AGE-1 to AKT-2 (and AKT-1); conversely, the akt-2 loss-of-function phenotype is suppressed by daf-16 null mutations, indicating that the Fork head transcription factor DAF-16 is downstream of AKT-2 (and AKT-1), and that AKT-1 and AKT-2 act primarily to antagonize DAF-16.

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 akt-2;trpa-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Akt1;TrpA1
Mus musculus	Akt1;Trpa1
Mus musculus	Akt2;Trpa1
Mus musculus	Akt3;Trpa1

Orthologs of akt-2 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 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.