daf-12;pkc-2

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Genetic mutants with daf-12, 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)
23.6
Lifespan comparisons
Double mutant daf-12(rh61rh411);pkc-2(xuEx913) 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 pkc-2

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

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-12;pkc-2 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Hr96;Pkc53E
Mus musculus	Pkc53E;Hr96

Orthologs of daf-12 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Hr96

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.