aak-2;mdt-15

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Genetic mutants with aak-2, mdt-15 alterations

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

Temperature °C
25
Diet
NGM
Lifespan (days)
12.2
Lifespan change (compared to wild type)
-39.90%
Lifespan comparisons
Double mutant aak-2(ok524);mdt-15(RNAi) has a lifespan of 12.2 days, while single mutant mdt-15(RNAi) has a lifespan of 16.7 days, single mutant aak-2(ok524) has a lifespan of 17.1 days and wild type has a lifespan of 20.3 days.
Type of interaction
See methods
Synergistic (negative)
Citation
View abstract
Rogers AN et al., 2011, Life span extension via eIF4G inhibition is mediated by posttranscriptional remodeling of stress response gene expression in C. elegans. Cell Metab. 14(1):55-66 21723504 Click here to select all mutants from this PubMed ID in the graph
Abstract
Reducing protein synthesis slows growth and development but can increase adult life span. We demonstrate that knockdown of eukaryotic translation initiation factor 4G (eIF4G), which is downregulated during starvation and dauer state, results in differential translation of genes important for growth and longevity in C. elegans. Genome-wide mRNA translation state analysis showed that inhibition of IFG-1, the C. elegans ortholog of eIF4G, results in a relative increase in ribosomal loading and translation of stress response genes. Some of these genes are required for life span extension when IFG-1 is inhibited. Furthermore, enhanced ribosomal loading of certain mRNAs upon IFG-1 inhibition was correlated with increased mRNA length. This association was supported by changes in the proteome assayed via quantitative mass spectrometry. Our results suggest that IFG-1 mediates the antagonistic effects on growth and somatic maintenance by regulating mRNA translation of particular mRNAs based, in part, on transcript length.

Search genes: aak-2 mdt-15

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

175817
mdt-15
View on GenAge (mdt-15)
WBGene00007016

Mediator of RNA polymerase II transcription subunit 15

Locus: CELE_R12B2.5

Wormbase description: mdt-15 encodes, by alternative splicing, two isoforms of a Mediator subunit orthologous to human MED15; together with NHR-49 and SBP-1, MDT-15 is required for normal fat accumulation, for expression of fatty acid (FA) desaturase genes (fat-5, fat-6, and fat-7), for normal levels of mono- and polyunsaturated FAs (PUFAs), and for viability, fecundity, mobility, and normally long lifespan; several of these phenotypes can be at least partially suppressed by supplying PUFAs in the food medium; in part through NHR-49, MDT-15 participates in basal and fasting-induced transcription of numerous other metabolic genes, such as gei-7 and acs-2; independently of NHR-49 and SBP-1, MDT-15 ensures appropriate transcriptional response and survival in response to toxins and heavy metals by inducing select detoxification genes encoding such as cdr-1, cyp-35C1, gst-5, mtl-1, mtl-2, ugt-1, ugt-8, and others; mdt-15 is expressed at constant levels from embryos to adulthood, in several head neurons and intestine; MDT-15 binds NHR-49 and NHR-64 in yeast two-hybrid assays, and SBP-1 in GST pull-down assays.

Orthologs of aak-2;mdt-15 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of aak-2 in SynergyAge

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Species	Gene

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

Orthologs of mdt-15 in SynergyAge

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Species	Gene

About

SynergyAge database hosts high-quality, manually curated information about the synergistic and antagonistic lifespan effects of genetic interventions in model organisms, also allowing users to explore the longevity relationships between genes in a visual way.