ctl-1;ctl-2;ctl-3;sod-2

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Genetic mutants with ctl-1, ctl-2, ctl-3, sod-2 alterations

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

Temperature °C
20
Lifespan (days)
23.8
Lifespan comparisons
Quadruple mutant ctl-1(wuIs151);ctl-2(wuIs151);ctl-3(wuIs151);sod-2(wuIs156) has a lifespan of 23.8 days, while single mutant sod-2(wuIs156) has a lifespan of 23.9 days and triple mutant ctl-1(wuIs151);ctl-2(wuIs151);ctl-3(wuIs151) has a lifespan of 20.7 days.
Citation
View abstract
Cabreiro F et al., 2011, Increased life span from overexpression of superoxide dismutase in Caenorhabditis elegans is not caused by decreased oxidative damage. Free Radic Biol Med. 51(8):1575-82 21839827 Click here to select all mutants from this PubMed ID in the graph
Abstract
The superoxide free radical (O(2)(•-)) has been viewed as a likely major contributor to aging. If this is correct, then superoxide dismutase (SOD), which removes O(2)(•-), should contribute to longevity assurance. In Caenorhabditis elegans, overexpression (OE) of the major cytosolic Cu/Zn-SOD, sod-1, increases life span. But is this increase caused by enhanced antioxidant defense? sod-1 OE did not reduce measures of lipid oxidation or glycation and actually increased levels of protein oxidation. The effect of sod-1 OE on life span was dependent on the DAF-16/FoxO transcription factor (TF) and, partially, on the heat shock TF HSF-1. Similarly, overexpression of sod-2 (major mitochondrial Mn-SOD) resulted in life-span extension that was daf-16 dependent. sod-1 OE increased steady-state hydrogen peroxide (H(2)O(2)) levels in vivo. However, co-overexpression of catalase did not suppress the life-span extension, arguing against H(2)O(2) as a cause of longevity. sod-1 OE increased hsp-4 expression, suggesting increased endoplasmic reticulum (ER) stress. Moreover, longevity was partially suppressed by inactivation of ire-1 and xbp-1, mediators of the ER stress response. This suggests that high levels of SOD-1 protein may challenge protein-folding homeostasis, triggering a daf-16- and hsf-1-dependent stress response that extends life span. These findings imply that SOD overexpression increases C. elegans life span, not by removal of O(2)(•-), but instead by activating longevity-promoting transcription factors.

Temperature °C
20
Lifespan (days)
20.8
Lifespan comparisons
Quadruple mutant ctl-1(wuIs151);ctl-2(wuIs151);ctl-3(wuIs151);sod-2(wuIs156) has a lifespan of 20.8 days, while single mutant sod-2(wuIs156) has a lifespan of 19.5 days and triple mutant ctl-1(wuIs151);ctl-2(wuIs151);ctl-3(wuIs151) has a lifespan of 15.2 days.
Citation
View abstract
Cabreiro F et al., 2011, Increased life span from overexpression of superoxide dismutase in Caenorhabditis elegans is not caused by decreased oxidative damage. Free Radic Biol Med. 51(8):1575-82 21839827 Click here to select all mutants from this PubMed ID in the graph
Abstract
The superoxide free radical (O(2)(•-)) has been viewed as a likely major contributor to aging. If this is correct, then superoxide dismutase (SOD), which removes O(2)(•-), should contribute to longevity assurance. In Caenorhabditis elegans, overexpression (OE) of the major cytosolic Cu/Zn-SOD, sod-1, increases life span. But is this increase caused by enhanced antioxidant defense? sod-1 OE did not reduce measures of lipid oxidation or glycation and actually increased levels of protein oxidation. The effect of sod-1 OE on life span was dependent on the DAF-16/FoxO transcription factor (TF) and, partially, on the heat shock TF HSF-1. Similarly, overexpression of sod-2 (major mitochondrial Mn-SOD) resulted in life-span extension that was daf-16 dependent. sod-1 OE increased steady-state hydrogen peroxide (H(2)O(2)) levels in vivo. However, co-overexpression of catalase did not suppress the life-span extension, arguing against H(2)O(2) as a cause of longevity. sod-1 OE increased hsp-4 expression, suggesting increased endoplasmic reticulum (ER) stress. Moreover, longevity was partially suppressed by inactivation of ire-1 and xbp-1, mediators of the ER stress response. This suggests that high levels of SOD-1 protein may challenge protein-folding homeostasis, triggering a daf-16- and hsf-1-dependent stress response that extends life span. These findings imply that SOD overexpression increases C. elegans life span, not by removal of O(2)(•-), but instead by activating longevity-promoting transcription factors.

Search genes: ctl-1 ctl-2 ctl-3 sod-2 ctl-1;ctl-2;ctl-3;sod-2

Entrez ID
Symbol
GenAge
Wormbase ID

259738
ctl-1
View on GenAge (ctl-1)
WBGene00000830

Catalase-2

Locus: CELE_Y54G11A.6

Wormbase description: ctl-1 encodes one of three C. elegans catalases; CTL-1 exhibits catalase activity in vitro, and thus likely functions in vivo as an antioxidant enzyme that protects cells from reactive oxygen species; ctl-1 activity contributes to the extended lifespan seen in daf-2 mutant animals; in addition, ctl-1 expression is negatively regulated by DAF-2-mediated insulin signaling; as CTL-1 does not possess a C-terminal peroxisomal targeting signal (PTS), it is predicted to be a cytosolic catalase.

Entrez ID
Symbol
GenAge
Wormbase ID

175085
ctl-2
View on GenAge (ctl-2)
WBGene00000831

Peroxisomal catalase 1

Locus: CELE_Y54G11A.5

Wormbase description: ctl-2 encodes one of three C. elegans catalases; CTL-2 exhibits catalase and peroxidase activity in vitro, and thus likely functions in vivo as an antioxidant enzyme that protects cells from reactive oxygen species; ctl-2 activity is required for normal lifespan as well as for the extended lifespan seen in daf-2 mutant animals; in addition, ctl-2 is required for normal egg-laying capacity and for normal peroxisomal morphology; immunoelectron microscopy indicates that CTL-2 is found mainly in the peroxisomes of intestinal epithelial cells; ctl-2 expression is negatively regulated by DAF-2-mediated insulin signaling.

Entrez ID
Symbol
GenAge
Wormbase ID

175086
ctl-3
View on GenAge (ctl-3)
WBGene00013220

Catalase

Locus: CELE_Y54G11A.13

Wormbase description: ctl-3 encodes one of three C. elegans catalases; CTL-3 is predicted to function as an antioxidant enzyme that protects cells from reactive oxygen species; a ctl-3 promoter gfp fusion construct is expressed in pharyngeal muscles and neuronal cell bodies; loss of ctl-3 activity via RNAi results in no obvious abnormalities.

Entrez ID
Symbol
GenAge
Wormbase ID

172632
sod-2
View on GenAge (sod-2)
WBGene00004931

Superoxide dismutase [Mn] 1, mitochondrial

Locus: CELE_F10D11.1

Wormbase description: sod-2 encodes a iron/manganese superoxide dismutase, predicted to be mitochondrial, that might defend against oxidative stress and promote normal lifespan; sod-2 mRNA levels are diminished by mutation of daf-16, and heterologously expressed SOD-2 in E. coli protects against methyl viologen-induced oxidative stress.

Orthologs of ctl-1;ctl-2;ctl-3;sod-2 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Cat;Cat;Cat;Sod2
Drosophila melanogaster	Cat;Cat;CG9314;Sod2
Drosophila melanogaster	Cat;CG9314;CG9314;Sod2
Drosophila melanogaster	CG9314;CG9314;CG9314;Sod2
Mus musculus	Cat;Cat;Cat;Sod2

Orthologs of ctl-1 in SynergyAge

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Species	Gene

Orthologs of ctl-2 in SynergyAge

Show in SynergyAge
Species	Gene

Orthologs of ctl-3 in SynergyAge

Show in SynergyAge
Species	Gene

Orthologs of sod-2 in SynergyAge

Show in SynergyAge
Species	Gene
Drosophila melanogaster	Sod2

Not in SynergyAge
Species	Gene
Mus musculus	Sod2