daf-9;pkc-2

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Genetic mutants with daf-9, 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)
22.37
Lifespan comparisons
Double mutant daf-9(rh50);pkc-2(xuEx913) has a lifespan of 22.37 days, while single mutant daf-9(rh50) has a lifespan of 11.58 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-9 pkc-2

Entrez ID
Symbol
GenAge
Wormbase ID

180889
daf-9
View on GenAge (daf-9)
WBGene00000905

Cytochrome P450 daf-9

Locus: CELE_T13C5.1

Wormbase description: daf-9 encodes a cytochrome P450 of the CYP2 subfamily that by homology is predicted to function as a steroidogenic or fatty acid hydroxylase; DAF-9 likely functions cell nonautonomously in hypodermal and neuronal cells to produce, for the DAF-12 nuclear receptor, a lipophilic hormone whose presence is necessary for bypassing entry into the alternative L3/dauer larval stage and promoting reproductive development; in regulating dauer formation, daf-9 acts downstream of the DAF-2/insulin/IGF receptor and the DAF-7/TGFbeta ligand, suggesting that at least two of the signaling pathways that control dauer formation converge, in part, upon daf-9; in addition, daf-9 activity is required for gonadal cell migration; a DAF-9::GFP fusion is expressed in the XXXL/R head cells at all developmental stages, in hypodermal cells from the L2 to L4 larval stages, and in the spermatheca of adult hermaphrodites.

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 daf-9;pkc-2 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of daf-9 in SynergyAge

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Species	Gene

Orthologs of pkc-2 in SynergyAge

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Species	Gene

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

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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.