ddr-2;sams-1

There is no network for this step.

Fullscreen mode

Hide graph

Legend

Genetic mutants with ddr-2, sams-1 alterations

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

Temperature °C
20
Lifespan (days)
19.08
Lifespan change (compared to wild type)
10.80%
Phenotype
Inhibition of sams-1 by RNAi does not extend the lifespan of EQ19 (drr-2 over-expression) significantly, while inhibition of sams-1 extends the lifespan of wild-type animals, suggesting a common mechanism that mediates the lifespan effects of eIF4H/drr-2 and sams-1.
Lifespan comparisons
Double mutant ddr-2(OE);sams-1(RNAi) has a lifespan of 19.08 days, while single mutant sams-1(RNAi) has a lifespan of 24.55 days, single mutant ddr-2(OE) has a lifespan of 17.14 days and wild type has a lifespan of 17.22 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Ching TT et al., 2010, drr-2 encodes an eIF4H that acts downstream of TOR in diet-restriction-induced longevity of C. elegans. Aging Cell. 9(4):545-57 20456299 Click here to select all mutants from this PubMed ID in the graph
Abstract
Dietary restriction (DR) results in a robust increase in lifespan while maintaining the physiology of much younger animals in a wide range of species. Here, we examine the role of drr-2, a DR-responsive gene recently identified, in determining the longevity of Caenorhabditis elegans. Inhibition of drr-2 has been shown to increase longevity. However, the molecular mechanisms by which drr-2 influences longevity remain unknown. We report here that drr-2 encodes an ortholog of human eukaryotic translation initiation factor 4H (eIF4H), whose function is to mediate the initiation step of mRNA translation. The molecular function of DRR-2 is validated by the association of DRR-2 with polysomes and by the decreased rate of protein synthesis observed in drr-2 knockdown animals. Previous studies have also suggested that DR might trigger a regulated reduction in drr-2 expression to initiate its longevity response. By examining the effect of increasing drr-2 expression on DR animals, we find that drr-2 is essential for a large portion of the longevity response to DR. The nutrient-sensing target of rapamycin (TOR) pathway has been shown to mediate the longevity effects of DR in C. elegans. Results from our genetic analyses suggest that eIF4H/DRR-2 functions downstream of TOR, but in parallel to the S6K/PHA-4 pathway to mediate the lifespan effects of DR. Together, our findings reveal an important role for eIF4H/drr-2 in the TOR-mediated longevity responses to DR.

Temperature °C
20
Lifespan (days)
17.51
Lifespan change (compared to wild type)
5.74%
Phenotype
Inhibition of sams-1 by RNAi does not extend the lifespan of EQ19 (drr-2 over-expression) significantly, while inhibition of sams-1 extends the lifespan of wild-type animals, suggesting a common mechanism that mediates the lifespan effects of eIF4H/drr-2 and sams-1.
Lifespan comparisons
Double mutant ddr-2(OE);sams-1(RNAi) has a lifespan of 17.51 days, while single mutant sams-1(RNAi) has a lifespan of 21.73 days, single mutant ddr-2(OE) has a lifespan of 17.06 days and wild type has a lifespan of 16.56 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Ching TT et al., 2010, drr-2 encodes an eIF4H that acts downstream of TOR in diet-restriction-induced longevity of C. elegans. Aging Cell. 9(4):545-57 20456299 Click here to select all mutants from this PubMed ID in the graph
Abstract
Dietary restriction (DR) results in a robust increase in lifespan while maintaining the physiology of much younger animals in a wide range of species. Here, we examine the role of drr-2, a DR-responsive gene recently identified, in determining the longevity of Caenorhabditis elegans. Inhibition of drr-2 has been shown to increase longevity. However, the molecular mechanisms by which drr-2 influences longevity remain unknown. We report here that drr-2 encodes an ortholog of human eukaryotic translation initiation factor 4H (eIF4H), whose function is to mediate the initiation step of mRNA translation. The molecular function of DRR-2 is validated by the association of DRR-2 with polysomes and by the decreased rate of protein synthesis observed in drr-2 knockdown animals. Previous studies have also suggested that DR might trigger a regulated reduction in drr-2 expression to initiate its longevity response. By examining the effect of increasing drr-2 expression on DR animals, we find that drr-2 is essential for a large portion of the longevity response to DR. The nutrient-sensing target of rapamycin (TOR) pathway has been shown to mediate the longevity effects of DR in C. elegans. Results from our genetic analyses suggest that eIF4H/DRR-2 functions downstream of TOR, but in parallel to the S6K/PHA-4 pathway to mediate the lifespan effects of DR. Together, our findings reveal an important role for eIF4H/drr-2 in the TOR-mediated longevity responses to DR.

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

Temperature °C
20
Lifespan (days)
20.58
Lifespan change (compared to wild type)
18.21%
Phenotype
Inhibition of eIF4H/drr-2 consistently extends the lifespan of wild-type animals and animals over-expressing sams-1 (EQ2). Taken together, these results strongly imply that eIF4H/drr-2 may act downstream of both rab-10 and sams-1 and its activity might be essential for RAB-10 and SAMS-1 to mediate the longevity effects of DR.
Lifespan comparisons
Double mutant ddr-2(RNAi);sams-1(OE) has a lifespan of 20.58 days, while single mutant ddr-2(RNAi) has a lifespan of 21.17 days, single mutant sams-1(OE) has a lifespan of 16.1 days and wild type has a lifespan of 17.41 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Ching TT et al., 2010, drr-2 encodes an eIF4H that acts downstream of TOR in diet-restriction-induced longevity of C. elegans. Aging Cell. 9(4):545-57 20456299 Click here to select all mutants from this PubMed ID in the graph
Abstract
Dietary restriction (DR) results in a robust increase in lifespan while maintaining the physiology of much younger animals in a wide range of species. Here, we examine the role of drr-2, a DR-responsive gene recently identified, in determining the longevity of Caenorhabditis elegans. Inhibition of drr-2 has been shown to increase longevity. However, the molecular mechanisms by which drr-2 influences longevity remain unknown. We report here that drr-2 encodes an ortholog of human eukaryotic translation initiation factor 4H (eIF4H), whose function is to mediate the initiation step of mRNA translation. The molecular function of DRR-2 is validated by the association of DRR-2 with polysomes and by the decreased rate of protein synthesis observed in drr-2 knockdown animals. Previous studies have also suggested that DR might trigger a regulated reduction in drr-2 expression to initiate its longevity response. By examining the effect of increasing drr-2 expression on DR animals, we find that drr-2 is essential for a large portion of the longevity response to DR. The nutrient-sensing target of rapamycin (TOR) pathway has been shown to mediate the longevity effects of DR in C. elegans. Results from our genetic analyses suggest that eIF4H/DRR-2 functions downstream of TOR, but in parallel to the S6K/PHA-4 pathway to mediate the lifespan effects of DR. Together, our findings reveal an important role for eIF4H/drr-2 in the TOR-mediated longevity responses to DR.

Temperature °C
20
Lifespan (days)
20.33
Lifespan change (compared to wild type)
10.25%
Phenotype
Inhibition of eIF4H/drr-2 consistently extends the lifespan of wild-type animals and animals over-expressing sams-1 (EQ2). Taken together, these results strongly imply that eIF4H/drr-2 may act downstream of both rab-10 and sams-1 and its activity might be essential for RAB-10 and SAMS-1 to mediate the longevity effects of DR.
Lifespan comparisons
Double mutant ddr-2(RNAi);sams-1(OE) has a lifespan of 20.33 days, while single mutant ddr-2(RNAi) has a lifespan of 20.44 days, single mutant sams-1(OE) has a lifespan of 17.33 days and wild type has a lifespan of 18.44 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Ching TT et al., 2010, drr-2 encodes an eIF4H that acts downstream of TOR in diet-restriction-induced longevity of C. elegans. Aging Cell. 9(4):545-57 20456299 Click here to select all mutants from this PubMed ID in the graph
Abstract
Dietary restriction (DR) results in a robust increase in lifespan while maintaining the physiology of much younger animals in a wide range of species. Here, we examine the role of drr-2, a DR-responsive gene recently identified, in determining the longevity of Caenorhabditis elegans. Inhibition of drr-2 has been shown to increase longevity. However, the molecular mechanisms by which drr-2 influences longevity remain unknown. We report here that drr-2 encodes an ortholog of human eukaryotic translation initiation factor 4H (eIF4H), whose function is to mediate the initiation step of mRNA translation. The molecular function of DRR-2 is validated by the association of DRR-2 with polysomes and by the decreased rate of protein synthesis observed in drr-2 knockdown animals. Previous studies have also suggested that DR might trigger a regulated reduction in drr-2 expression to initiate its longevity response. By examining the effect of increasing drr-2 expression on DR animals, we find that drr-2 is essential for a large portion of the longevity response to DR. The nutrient-sensing target of rapamycin (TOR) pathway has been shown to mediate the longevity effects of DR in C. elegans. Results from our genetic analyses suggest that eIF4H/DRR-2 functions downstream of TOR, but in parallel to the S6K/PHA-4 pathway to mediate the lifespan effects of DR. Together, our findings reveal an important role for eIF4H/drr-2 in the TOR-mediated longevity responses to DR.

Temperature °C
20
Lifespan (days)
20.8
Lifespan change (compared to wild type)
-4.06%
Phenotype
Inhibition of eIF4H/drr-2 consistently extends the lifespan of wild-type animals and animals over-expressing sams-1 (EQ2). Taken together, these results strongly imply that eIF4H/drr-2 may act downstream of both rab-10 and sams-1 and its activity might be essential for RAB-10 and SAMS-1 to mediate the longevity effects of DR.
Lifespan comparisons
Double mutant ddr-2(RNAi);sams-1(OE) has a lifespan of 20.8 days, while single mutant ddr-2(RNAi) has a lifespan of 25.2 days, single mutant sams-1(OE) has a lifespan of 17.83 days and wild type has a lifespan of 21.68 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Ching TT et al., 2010, drr-2 encodes an eIF4H that acts downstream of TOR in diet-restriction-induced longevity of C. elegans. Aging Cell. 9(4):545-57 20456299 Click here to select all mutants from this PubMed ID in the graph
Abstract
Dietary restriction (DR) results in a robust increase in lifespan while maintaining the physiology of much younger animals in a wide range of species. Here, we examine the role of drr-2, a DR-responsive gene recently identified, in determining the longevity of Caenorhabditis elegans. Inhibition of drr-2 has been shown to increase longevity. However, the molecular mechanisms by which drr-2 influences longevity remain unknown. We report here that drr-2 encodes an ortholog of human eukaryotic translation initiation factor 4H (eIF4H), whose function is to mediate the initiation step of mRNA translation. The molecular function of DRR-2 is validated by the association of DRR-2 with polysomes and by the decreased rate of protein synthesis observed in drr-2 knockdown animals. Previous studies have also suggested that DR might trigger a regulated reduction in drr-2 expression to initiate its longevity response. By examining the effect of increasing drr-2 expression on DR animals, we find that drr-2 is essential for a large portion of the longevity response to DR. The nutrient-sensing target of rapamycin (TOR) pathway has been shown to mediate the longevity effects of DR in C. elegans. Results from our genetic analyses suggest that eIF4H/DRR-2 functions downstream of TOR, but in parallel to the S6K/PHA-4 pathway to mediate the lifespan effects of DR. Together, our findings reveal an important role for eIF4H/drr-2 in the TOR-mediated longevity responses to DR.

Search genes: ddr-2 sams-1

Entrez ID
Symbol
GenAge
Wormbase ID

180622
ddr-2
View on GenAge (ddr-2)
WBGene00017381

Discoidin domain-containing receptor tyrosine kinase B

Locus: CELE_F11D5.3

Wormbase description: F11D5.3 encodes a putative tyrosine kinase homologous to human RS1 (OMIM:312700, mutated in juvenile X-linked retinoschisis).

Entrez ID
Symbol
GenAge
Wormbase ID

181370
sams-1
View on GenAge (sams-1)
WBGene00008205

Probable S-adenosylmethionine synthase 1

Locus: CELE_C49F5.1

Wormbase description: sams-1 encodes an S-adenosyl methionine synthetase; by homology, SAMS-1 is predicted to function as a methyl-group donor in many biochemical reactions; sams-1 expression levels are negatively regulated by dietary restriction (as seen in eat-2 mutant animals), suggesting that increased lifespan due to dietary restriction is due, in part, to reducing the activity of key metabolic enzymes; loss of sams-1 via RNAi can extend adult lifespan.

Orthologs of ddr-2;sams-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Ddr1;Mat2a
Mus musculus	Ddr1;Mat1a
Mus musculus	Ddr2;Mat2a
Mus musculus	Ddr2;Mat1a
Mus musculus	Mat2a;Ddr1
Mus musculus	Mat2a;Ddr2
Mus musculus	Mat1a;Ddr1
Mus musculus	Mat1a;Ddr2

Orthologs of ddr-2 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Ddr1
Mus musculus	Ddr2

Orthologs of sams-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Sam-S
Mus musculus	Mat2a
Mus musculus	Mat1a