clk-1;hif-1

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Genetic mutants with clk-1, hif-1 alterations

Names of genes are ordered alphabetically. For the order of interventions, please see the specific paper.

Temperature °C
20
Lifespan (days)
16.5
Lifespan change (compared to wild type)
7.84%
Phenotype
RNAi knockdown of hif-1 partially but significantly suppressed the longevity of clk-1(qm30) mutant animals. hif-1 RNAi did not decrease the lifespan of wild-type animals.
Lifespan comparisons
Double mutant clk-1(qm30);hif-1(RNAi) has a lifespan of 16.5 days, while single mutant hif-1(RNAi) has a lifespan of 15.7 days, single mutant clk-1(qm30) has a lifespan of 21.4 days and wild type has a lifespan of 15.3 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Lee SJ et al., 2010, Inhibition of respiration extends C. elegans life span via reactive oxygen species that increase HIF-1 activity. Curr Biol. 20(23):2131-6 21093262 Click here to select all mutants from this PubMed ID in the graph
Abstract
A mild inhibition of mitochondrial respiration extends the life span of many organisms, including yeast, worms, flies, and mice, but the underlying mechanism is unknown. One environmental condition that reduces rates of respiration is hypoxia (low oxygen). Thus, it is possible that mechanisms that sense oxygen play a role in the longevity response to reduced respiration. The hypoxia-inducible factor HIF-1 is a highly conserved transcription factor that activates genes that promote survival during hypoxia. In this study, we show that inhibition of respiration in C. elegans can promote longevity by activating HIF-1. Through genome-wide screening, we found that RNA interference (RNAi) knockdown of many genes encoding respiratory-chain components induced hif-1-dependent transcription. Moreover, HIF-1 was required for the extended life spans of clk-1 and isp-1 mutants, which have reduced rates of respiration. Inhibiting respiration appears to activate HIF-1 by elevating the level of reactive oxygen species (ROS). We found that ROS are increased in respiration mutants and that mild increases in ROS can stimulate HIF-1 to activate gene expression and promote longevity. In this way, HIF-1 appears to link respiratory stress in the mitochondria to a nuclear transcriptional response that promotes longevity.

Temperature °C
20
Lifespan (days)
28.0
Lifespan change (compared to wild type)
54.70%
Phenotype
RNAi knockdown of hif-1 only during adulthood partially suppressed the longevity of clk-1(qm30) mutant animals.
Lifespan comparisons
Double mutant clk-1(qm30);hif-1(RNAi) has a lifespan of 28.0 days, while single mutant hif-1(RNAi) has a lifespan of 16.8 days, single mutant clk-1(qm30) has a lifespan of 33.0 days and wild type has a lifespan of 18.1 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Lee SJ et al., 2010, Inhibition of respiration extends C. elegans life span via reactive oxygen species that increase HIF-1 activity. Curr Biol. 20(23):2131-6 21093262 Click here to select all mutants from this PubMed ID in the graph
Abstract
A mild inhibition of mitochondrial respiration extends the life span of many organisms, including yeast, worms, flies, and mice, but the underlying mechanism is unknown. One environmental condition that reduces rates of respiration is hypoxia (low oxygen). Thus, it is possible that mechanisms that sense oxygen play a role in the longevity response to reduced respiration. The hypoxia-inducible factor HIF-1 is a highly conserved transcription factor that activates genes that promote survival during hypoxia. In this study, we show that inhibition of respiration in C. elegans can promote longevity by activating HIF-1. Through genome-wide screening, we found that RNA interference (RNAi) knockdown of many genes encoding respiratory-chain components induced hif-1-dependent transcription. Moreover, HIF-1 was required for the extended life spans of clk-1 and isp-1 mutants, which have reduced rates of respiration. Inhibiting respiration appears to activate HIF-1 by elevating the level of reactive oxygen species (ROS). We found that ROS are increased in respiration mutants and that mild increases in ROS can stimulate HIF-1 to activate gene expression and promote longevity. In this way, HIF-1 appears to link respiratory stress in the mitochondria to a nuclear transcriptional response that promotes longevity.

Names of genes are ordered alphabetically. For the order of interventions, please see the specific paper.

Temperature °C
20
Lifespan (days)
15.5
Lifespan change (compared to wild type)
-4.91%
Phenotype
hif-1(ia4) loss-of-function mutations decreased the longevity of clk-1(qm30).
Lifespan comparisons
Double mutant clk-1(qm30);hif-1(ia4) has a lifespan of 15.5 days, while single mutant hif-1(ia4) has a lifespan of 17.1 days, single mutant clk-1(qm30) has a lifespan of 24.6 days and wild type has a lifespan of 16.3 days.
Type of interaction
See methods
Antagonistic (negative)
Citation
View abstract
Lee SJ et al., 2010, Inhibition of respiration extends C. elegans life span via reactive oxygen species that increase HIF-1 activity. Curr Biol. 20(23):2131-6 21093262 Click here to select all mutants from this PubMed ID in the graph
Abstract
A mild inhibition of mitochondrial respiration extends the life span of many organisms, including yeast, worms, flies, and mice, but the underlying mechanism is unknown. One environmental condition that reduces rates of respiration is hypoxia (low oxygen). Thus, it is possible that mechanisms that sense oxygen play a role in the longevity response to reduced respiration. The hypoxia-inducible factor HIF-1 is a highly conserved transcription factor that activates genes that promote survival during hypoxia. In this study, we show that inhibition of respiration in C. elegans can promote longevity by activating HIF-1. Through genome-wide screening, we found that RNA interference (RNAi) knockdown of many genes encoding respiratory-chain components induced hif-1-dependent transcription. Moreover, HIF-1 was required for the extended life spans of clk-1 and isp-1 mutants, which have reduced rates of respiration. Inhibiting respiration appears to activate HIF-1 by elevating the level of reactive oxygen species (ROS). We found that ROS are increased in respiration mutants and that mild increases in ROS can stimulate HIF-1 to activate gene expression and promote longevity. In this way, HIF-1 appears to link respiratory stress in the mitochondria to a nuclear transcriptional response that promotes longevity.

Search genes: clk-1 hif-1

Entrez ID
Symbol
GenAge
Wormbase ID

175729
clk-1
View on GenAge (clk-1)
WBGene00000536

5-demethoxyubiquinone hydroxylase, mitochondrial

Locus: CELE_ZC395.2

Wormbase description: clk-1 encodes the C. elegans ortholog of COQ7/CAT5, a highly conserved demethoxyubiquinone (DMQ) hydroxylase that is necessary for the biosynthesis of ubiquinone (coenzyme Q, Q9) from 5-demethoxyubiquinone (DMQ9); in C. elegans, CLK-1 activity is required for normal physiological rates of growth, development, behavior, and aging, as well as for normal brood sizes.

Entrez ID
Symbol
GenAge
Wormbase ID

180359
hif-1
View on GenAge (hif-1)
WBGene00001851

HIF (Hypoxia Inducible Factor) homologa;Hypoxia-inducible factor 1

Locus: CELE_F38A6.3

Wormbase description: hif-1 encodes an ortholog of the mammalian hypoxia-induced factor HIF-1, and is required for survival in hypoxic environments (1% oxygen) that have no effect on wild-type C. elegans.

Orthologs of clk-1;hif-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Clk;COQ7
Mus musculus	Coq7;Epas1
Mus musculus	Coq7;Hif3a
Mus musculus	Coq7;Hif1a
Mus musculus	COQ7;Clk

Orthologs of clk-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	COQ7
Mus musculus	Coq7

Orthologs of hif-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Clk
Mus musculus	Epas1
Mus musculus	Hif3a
Mus musculus	Hif1a