daf-16;sod-1

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Genetic mutants with daf-16, sod-1 alterations

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

Temperature °C
20
Lifespan (days)
15.9
Phenotype
wuEx123 is a sod-1 over expression.
Lifespan comparisons
Double mutant daf-16(mgDf50);sod-1(wuEx123) has a lifespan of 15.9 days, while single mutant sod-1(wuEx123) has a lifespan of 23.0 days and single mutant daf-16(mgDf50) 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.

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

Temperature °C
20
Lifespan (days)
13.9
Phenotype
Overexpression of sod-1 (wuEx152 strain)
Lifespan comparisons
Double mutant daf-16(mgDf50);sod-1(wuIs152) has a lifespan of 13.9 days, while single mutant sod-1(wuIs152) has a lifespan of 25.2 days and single mutant daf-16(mgDf50) 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.

Temperature °C
20
Lifespan (days)
15.9
Phenotype
The sod-1 OE longevity is fully dependent on daf-16.
Lifespan comparisons
Double mutant daf-16(mgDf50);sod-1(wuIs152) has a lifespan of 15.9 days, while single mutant sod-1(wuIs152) has a lifespan of 29.3 days and single mutant daf-16(mgDf50) has a lifespan of 17.6 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)
14.3
Phenotype
The sod-1 OE longevity is fully dependent on daf-16.
Lifespan comparisons
Double mutant daf-16(mgDf50);sod-1(wuIs152) has a lifespan of 14.3 days, while single mutant sod-1(wuIs152) has a lifespan of 31.0 days and single mutant daf-16(mgDf50) has a lifespan of 15.6 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: daf-16 sod-1

Entrez ID
Symbol
GenAge
Wormbase ID

172981
daf-16
View on GenAge (daf-16)
WBGene00000912

Forkhead box protein O;hypothetical protein

Locus: CELE_R13H8.1

Wormbase description: daf-16 encodes the sole C. elegans forkhead box O (FOXO) homologue; DAF-16 functions as a transcription factor that acts in the insulin/IGF-1-mediated signaling (IIS) pathway that regulates dauer formation, longevity, fat metabolism, stress response, and innate immunity; DAF-16 regulates these various processes through isoform-specific expression, isoform-specific regulation by different AKT kinases, and differential regulation of target genes; DAF-16 can interact with the CBP-1 transcription cofactor in vitro, and interacts genetically with other genes in the insulin signaling and with daf-12, which encodes a nuclear hormone receptor; DAF-16 is activated in response to DNA damage during development and co-regulated by EGL-27, alleviates DNA-damage-induced developmental arrest by inducing DAF-16-associated element (DAE)-regulated genes; DAF-16 is broadly expressed but displays isoform-specific tissue enrichment; DAF-16 localizes to both the cytoplasm and the nucleus, with the ratio between the two an important regulator of function.

Entrez ID
Symbol
GenAge
Wormbase ID

174141
sod-1
View on GenAge (sod-1)
WBGene00004930

Superoxide dismutase [Cu-Zn]

Locus: CELE_C15F1.7

Wormbase description: sod-1 encodes the copper/zinc superoxide dismustase, an enzyme that is known to protect cells from oxidative damage; superoxide dismutase activity can be detected in worm extracts; sod-1 activity has been implicated in the increased life-span of dauer larvae where this enzyme demonstrates the highest activity compared to other life-stages as well as in the increased life span of age-1 mutants and their resistance to oxidative damage; sod-1 modulates the effect of let-60 ras on vulval and germline development via cytoplasmic reactive oxygen species; unlike other eukaryotic superoxide dismutases, sod-1 does not require the copper chaperone CCS for its activity and instead uses a glutathione pathway for acquiring copper; in humans, mutation of SOD1 (OMIM:147450) leads to amyotrophic lateral sclerosis (OMIM:105400).

Orthologs of daf-16;sod-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Foxo6;Sod1
Mus musculus	Foxo1;Sod1
Mus musculus	Foxo4;Sod1
Mus musculus	Foxo3;Sod1
Mus musculus	Sod1;Foxo6
Mus musculus	Sod1;Foxo1
Mus musculus	Sod1;Foxo4
Mus musculus	Sod1;Foxo3

Orthologs of daf-16 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Foxo6
Mus musculus	Foxo1
Mus musculus	Foxo4
Mus musculus	Foxo3

Orthologs of sod-1 in SynergyAge

Show in SynergyAge
Species	Gene
Drosophila melanogaster	Sod1
Mus musculus	Sod1

Not in SynergyAge
Species	Gene