pha-4;pkc-2

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Genetic mutants with pha-4, 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)
17.24
Lifespan change (compared to wild type)
-19.33%
Lifespan comparisons
Double mutant pha-4(RNAi);pkc-2(xuEx913) has a lifespan of 17.24 days, while single mutant pha-4(RNAi) has a lifespan of 14.13 days and wild type has a lifespan of 21.37 days.
Type of interaction
See methods
Contains dependence
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: pha-4 pkc-2

Entrez ID
Symbol
GenAge
Wormbase ID

180357
pha-4
View on GenAge (pha-4)
WBGene00004013

Defective pharyngeal development protein 4

Locus: CELE_F38A6.1

Wormbase description: pha-4 encodes a FoxA transcription factor; during embryonic development, PHA-4 functions as an organ identity gene whose activity is necessary and sufficient for development of the pharynx/foregut; in addition, PHA-4 plays a key role in regulation of diet-restriction-induced longevity in adult animals; PHA-4 expression begins early in embryogenesis and is seen in pharyngeal and intestinal cells (foregut and midgut); PHA-4 is also expressed later in the developing somatic gonad.

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 pha-4;pkc-2 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	FoxK;Pkc53E
Mus musculus	Pkc53E;FoxK

Orthologs of pha-4 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	FoxK

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

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.