aak-2;rsks-1

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Genetic mutants with aak-2, rsks-1 alterations

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

Temperature °C
25
Lifespan (days)
9.7
Lifespan change (compared to wild type)
-24.22%
Lifespan comparisons
Double mutant aak-2(ok524);rsks-1(ok1255) has a lifespan of 9.7 days, while single mutant rsks-1(ok1255) has a lifespan of 14.7 days, single mutant aak-2(ok524) has a lifespan of 10.2 days and wild type has a lifespan of 12.8 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
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)
9.0
Lifespan change (compared to wild type)
-30.77%
Lifespan comparisons
Double mutant aak-2(ok524);rsks-1(ok1255) has a lifespan of 9.0 days, while single mutant rsks-1(ok1255) has a lifespan of 15.2 days, single mutant aak-2(ok524) has a lifespan of 11.3 days and wild type has a lifespan of 13.0 days.
Type of interaction
See methods
Enhancer, opposite lifespan effects
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.

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

Temperature °C
20
Diet
HT115
Lifespan (days)
16.31
Lifespan change (compared to wild type)
-20.90%
Phenotype
The aak-2(ok524) null allele fully suppressed rsks-1 mutant longevity. This effect is likely to be specific since several other modes of C. elegans longevity are not aak-2 dependent.
Lifespan comparisons
Double mutant aak-2(ok524);rsks-1(pk1255) has a lifespan of 16.31 days, while single mutant rsks-1(pk1255) has a lifespan of 23.09 days, single mutant aak-2(ok524) has a lifespan of 16.72 days and wild type has a lifespan of 20.62 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Selman C et al., 2009, Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science. 326(5949):140-4 19797661 Click here to select all mutants from this PubMed ID in the graph
Abstract
Caloric restriction (CR) protects against aging and disease, but the mechanisms by which this affects mammalian life span are unclear. We show in mice that deletion of ribosomal S6 protein kinase 1 (S6K1), a component of the nutrient-responsive mTOR (mammalian target of rapamycin) signaling pathway, led to increased life span and resistance to age-related pathologies, such as bone, immune, and motor dysfunction and loss of insulin sensitivity. Deletion of S6K1 induced gene expression patterns similar to those seen in CR or with pharmacological activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK), a conserved regulator of the metabolic response to CR. Our results demonstrate that S6K1 influences healthy mammalian life-span and suggest that therapeutic manipulation of S6K1 and AMPK might mimic CR and could provide broad protection against diseases of aging.

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

Temperature °C
22.5
Diet
NGM
Lifespan (days)
17.9
Lifespan change (compared to wild type)
1.13%
Phenotype
The long lifespan of rsks-1(tm1714) mutants was suppressed by aak-2(ok524) mutation.
Lifespan comparisons
Double mutant aak-2(ok524);rsks-1(tm1714) has a lifespan of 17.9 days, while single mutant aak-2(ok524) has a lifespan of 16.3 days, single mutant rsks-1(tm1714) has a lifespan of 22.0 days and wild type has a lifespan of 17.7 days.
Type of interaction
See methods
Opposite lifespan effects of single mutants
Citation
View abstract
Seo K et al., 2013, Heat shock factor 1 mediates the longevity conferred by inhibition of TOR and insulin/IGF-1 signaling pathways in C. elegans. Aging Cell. 12(6):1073-81 23879233 Click here to select all mutants from this PubMed ID in the graph
Abstract
Target of rapamycin (TOR) signaling is an evolutionarily well-conserved pathway that regulates various physiologic processes, including aging and metabolism. One of the key downstream components of TOR signaling is ribosomal protein S6 kinase (S6K) whose inhibition extends the lifespan of yeast, Caenorhabditis elegans, Drosophila, and mice. Here, we demonstrate that the activation of heat shock factor 1 (HSF-1), a crucial longevity transcription factor known to act downstream of the insulin/IGF-1 signaling (IIS) pathway, mediates the prolonged lifespan conferred by mutations in C. elegans S6K (rsks-1). We found that hsf-1 is required for the longevity caused by down-regulation of components in TOR signaling pathways, including TOR and S6K. The induction of a small heat-shock protein hsp-16, a transcriptional target of HSF-1, mediates the long lifespan of rsks-1 mutants. Moreover, we show that synergistic activation of HSF-1 is required for the further enhanced longevity caused by simultaneous down-regulation of TOR and IIS pathways. Our findings suggest that HSF-1 acts as an essential longevity factor that intersects both IIS and TOR signaling pathways.

Temperature °C
22.5
Diet
NGM
Lifespan (days)
12.8
Lifespan change (compared to wild type)
-28.09%
Phenotype
The long lifespan of rsks-1(tm1714) mutants was suppressed by aak-2(ok524) mutation.
Lifespan comparisons
Double mutant aak-2(ok524);rsks-1(tm1714) has a lifespan of 12.8 days, while single mutant aak-2(ok524) has a lifespan of 14.5 days, single mutant rsks-1(tm1714) has a lifespan of 18.0 days and wild type has a lifespan of 17.8 days.
Type of interaction
See methods
Enhancer, opposite lifespan effects
Citation
View abstract
Seo K et al., 2013, Heat shock factor 1 mediates the longevity conferred by inhibition of TOR and insulin/IGF-1 signaling pathways in C. elegans. Aging Cell. 12(6):1073-81 23879233 Click here to select all mutants from this PubMed ID in the graph
Abstract
Target of rapamycin (TOR) signaling is an evolutionarily well-conserved pathway that regulates various physiologic processes, including aging and metabolism. One of the key downstream components of TOR signaling is ribosomal protein S6 kinase (S6K) whose inhibition extends the lifespan of yeast, Caenorhabditis elegans, Drosophila, and mice. Here, we demonstrate that the activation of heat shock factor 1 (HSF-1), a crucial longevity transcription factor known to act downstream of the insulin/IGF-1 signaling (IIS) pathway, mediates the prolonged lifespan conferred by mutations in C. elegans S6K (rsks-1). We found that hsf-1 is required for the longevity caused by down-regulation of components in TOR signaling pathways, including TOR and S6K. The induction of a small heat-shock protein hsp-16, a transcriptional target of HSF-1, mediates the long lifespan of rsks-1 mutants. Moreover, we show that synergistic activation of HSF-1 is required for the further enhanced longevity caused by simultaneous down-regulation of TOR and IIS pathways. Our findings suggest that HSF-1 acts as an essential longevity factor that intersects both IIS and TOR signaling pathways.

Search genes: aak-2 rsks-1

Entrez ID
Symbol
GenAge
Wormbase ID

181727
aak-2
View on GenAge (aak-2)
WBGene00020142

5'-AMP-activated protein kinase catalytic subunit alpha-2

Locus: CELE_T01C8.1

Wormbase description: aak-2 encodes one of two C. elegans homologs of the catalytic alpha subunit of AMP-activated protein kinases (AMPKs); in C. elegans, aak-2 functions downstream of environmental stressors, energy level signals (AMP:ATP ratio), and daf-2-mediated insulin signaling to positively regulate adult lifespan; in regulating lifespan, aak-2 likely acts in parallel with daf-16/FOXO; aak-2 activity is also required for dauer formation in daf-2 mutant animals at high temperature in a manner independent of the AMP:ATP ratio; in the germline, aak-2 functions downstream of daf-2 and daf-7, and in parallel to par-4 and aak-1, to negatively regulate germline proliferation during dauer development; in vitro, AAK-2 exhibits AMP-enhanced kinase activity against a known AMPK substrate, the SAMS peptide.

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 aak-2;rsks-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	AMPKalpha;S6k
Mus musculus	Prkaa1;Rps6kb1
Mus musculus	Prkaa1;Rps6kb2
Mus musculus	Prkaa2;Rps6kb1
Mus musculus	Prkaa2;Rps6kb2
Mus musculus	Rps6kb1;Prkaa1
Mus musculus	Rps6kb1;Prkaa2
Mus musculus	Rps6kb2;Prkaa1
Mus musculus	Rps6kb2;Prkaa2

Orthologs of aak-2 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	AMPKalpha
Mus musculus	Prkaa1
Mus musculus	Prkaa2

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