aakg-4;rsks-1

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Genetic mutants with aakg-4, rsks-1 alterations

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

Temperature °C
25
Lifespan (days)
15.0
Lifespan change (compared to wild type)
10.29%
Lifespan comparisons
Double mutant aakg-4(RNAi);rsks-1(ok1255) has a lifespan of 15.0 days, while single mutant rsks-1(ok1255) has a lifespan of 15.2 days, single mutant aakg-4(RNAi) has a lifespan of 12.9 days and wild type has a lifespan of 13.6 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Chen D et al., 2013, Germline signaling mediates the synergistically prolonged longevity produced by double mutations in daf-2 and rsks-1 in C. elegans. Cell Rep. 5(6):1600-10 24332851 Click here to select all mutants from this PubMed ID in the graph
Abstract
Inhibition of DAF-2 (insulin-like growth factor 1 [IGF-1] receptor) or RSKS-1 (S6K), key molecules in the insulin/IGF-1 signaling (IIS) and target of rapamycin (TOR) pathways, respectively, extend lifespan in Caenorhabditis elegans. However, it has not been clear how and in which tissues they interact with each other to modulate longevity. Here, we demonstrate that a combination of mutations in daf-2 and rsks-1 produces a nearly 5-fold increase in longevity that is much greater than the sum of single mutations. This synergistic lifespan extension requires positive feedback regulation of DAF-16 (FOXO) via the AMP-activated protein kinase (AMPK) complex. Furthermore, we identify germline as the key tissue for this synergistic longevity. Moreover, germline-specific inhibition of rsks-1 activates DAF-16 in the intestine. Together, our findings highlight the importance of the germline in the significantly increased longevity produced by daf-2 rsks-1, which has important implications for interactions between the two major conserved longevity pathways in more complex organisms.

Temperature °C
25
Lifespan (days)
13.2
Lifespan change (compared to wild type)
3.12%
Lifespan comparisons
Double mutant aakg-4(RNAi);rsks-1(ok1255) has a lifespan of 13.2 days, while single mutant rsks-1(ok1255) has a lifespan of 14.5 days, single mutant aakg-4(RNAi) has a lifespan of 12.9 days and wild type has a lifespan of 12.8 days.
Type of interaction
See methods
Dependent
Citation
View abstract
Chen D et al., 2013, Germline signaling mediates the synergistically prolonged longevity produced by double mutations in daf-2 and rsks-1 in C. elegans. Cell Rep. 5(6):1600-10 24332851 Click here to select all mutants from this PubMed ID in the graph
Abstract
Inhibition of DAF-2 (insulin-like growth factor 1 [IGF-1] receptor) or RSKS-1 (S6K), key molecules in the insulin/IGF-1 signaling (IIS) and target of rapamycin (TOR) pathways, respectively, extend lifespan in Caenorhabditis elegans. However, it has not been clear how and in which tissues they interact with each other to modulate longevity. Here, we demonstrate that a combination of mutations in daf-2 and rsks-1 produces a nearly 5-fold increase in longevity that is much greater than the sum of single mutations. This synergistic lifespan extension requires positive feedback regulation of DAF-16 (FOXO) via the AMP-activated protein kinase (AMPK) complex. Furthermore, we identify germline as the key tissue for this synergistic longevity. Moreover, germline-specific inhibition of rsks-1 activates DAF-16 in the intestine. Together, our findings highlight the importance of the germline in the significantly increased longevity produced by daf-2 rsks-1, which has important implications for interactions between the two major conserved longevity pathways in more complex organisms.

Search genes: aakg-4 rsks-1

Entrez ID
Symbol
GenAge
Wormbase ID

187928
aakg-4
View on GenAge (aakg-4)
WBGene00020135

AMP-Activated protein Kinase Gamma subunit

Locus: CELE_T01B6.3

Wormbase description: aakg-4 encodes one of five C. elegans AMP kinase (AMPK) gamma regulatory subunits.

Entrez ID
Symbol
GenAge
Wormbase ID

176554
rsks-1
View on GenAge (rsks-1)
WBGene00012929

Ribosomal protein S6 kinase beta

Locus: CELE_Y47D3A.16

Wormbase description: rsks-1 encodes a putative ribosomal protein S6 kinase (S6K) required additively with IFG-1 for normally high levels of protein synthesis, and for normally short lifespan; RSKS-1's effect on lifespan is independent of DAF-16, ISP-1, and SIR-2.1, and does not correlate with juglone resistance, but does correlate with abnormally high resistance to starvation and (perhaps) thermotolerance; RSKS-1 is required for normal juglone resistance, as well as normally rapid growth and normal brood sizes; RSKS-1 is expressed in E-lineage embryonic cells, and in pharyngeal and hypodermal cells of larvae and adults; RSKS-1 is orthologous to human RPS6KB1 (OMIM:608938) and RPS6KB2 (OMIM:608939).

Orthologs of aakg-4;rsks-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of aakg-4 in SynergyAge

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Species	Gene

Orthologs of rsks-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	S6k
Mus musculus	Rps6kb1
Mus musculus	Rps6kb2