daf-2;maoc-1

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Genetic mutants with daf-2, maoc-1 alterations

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

Temperature °C
25
Lifespan (days)
29.2
Lifespan comparisons
Double mutant daf-2(e1370);maoc-1(RNAi) has a lifespan of 29.2 days, while single mutant daf-2(e1370) has a lifespan of 27.0 days.
Citation
View abstract
Hansen M et al., 2005, New genes tied to endocrine, metabolic, and dietary regulation of lifespan from a Caenorhabditis elegans genomic RNAi screen. PLoS Genet. 1(1):119-28 16103914 Click here to select all mutants from this PubMed ID in the graph
Abstract
Most of our knowledge about the regulation of aging comes from mutants originally isolated for other phenotypes. To ask whether our current view of aging has been affected by selection bias, and to deepen our understanding of known longevity pathways, we screened a genomic Caenorhabditis elegans RNAi library for clones that extend lifespan. We identified 23 new longevity genes affecting signal transduction, the stress response, gene expression, and metabolism and assigned these genes to specific longevity pathways. Our most important findings are (i) that dietary restriction extends C. elegans' lifespan by down-regulating expression of key genes, including a gene required for methylation of many macromolecules, (ii) that integrin signaling is likely to play a general, evolutionarily conserved role in lifespan regulation, and (iii) that specific lipophilic hormones may influence lifespan in a DAF-16/FOXO-dependent fashion. Surprisingly, of the new genes that have conserved sequence domains, only one could not be associated with a known longevity pathway. Thus, our current view of the genetics of aging has probably not been distorted substantially by selection bias.

Search genes: daf-2 maoc-1

Entrez ID
Symbol
GenAge
Wormbase ID

175410
daf-2
View on GenAge (daf-2)
WBGene00000898

Insulin-like receptor subunit beta;Receptor protein-tyrosine kinase;hypothetical protein

Locus: CELE_Y55D5A.5

Wormbase description: daf-2 encodes a receptor tyrosine kinase that is the C. elegans insulin/IGF receptor ortholog; DAF-2 activity is required for a number of processes in C. elegans, including embryonic and larval development, formation of the developmentally arrested dauer larval stage (diapause), larval developmental timing, adult longevity, reproduction, fat storage, salt chemotaxis learning, and stress resistance, including response to high temperature, oxidative stress, and bacterial infection; DAF-2 signals through a conserved PI 3-kinase pathway to negatively regulate the activity of DAF-16, a Forkhead-related transcription factor, by inducing its phosphorylation and nuclear exclusion; in addition, DAF-2 negatively regulates the nuclear localization, and hence transcriptional activity, of SKN-1 in intestinal nuclei; amongst the 38 predicted insulin-like molecules in C. elegans, genetic and microarray analyses suggest that at least DAF-28, INS-1, and INS-7 are likely DAF-2 ligands; genetic mosaic and tissue-specific promoter studies indicate that daf-2 can function cell nonautonomously and within multiple cell types to influence dauer formation and adult lifespan, likely by regulating the production of secondary endocrine signals that coordinate growth and longevity throughout the animal; temporal analysis of daf-2 function indicates that daf-2 regulates lifespan, reproduction, and diapause independently, at distinct times during the animal's life cycle.

Entrez ID
Symbol
GenAge
Wormbase ID

174181
maoc-1
View on GenAge (maoc-1)
WBGene00017123

MAO-C-like dehydratase domain

Locus: CELE_E04F6.3

Wormbase description: maoc-1 encodes an ortholog of human HSD17B4 (OMIM:601860, mutated in D-bifunctional protein deficiency); MAOC-1 contains a MaoC-like domain found in diverse enzymes (HSD17B4, peroxisomal hydratase-dehydrogenase-epimerase, and the fatty acid synthase beta subunit) and by homology, is predicted to function in peroxisomal fatty acid beta-oxidation; loss of maoc-1 activity via RNAi results in lifespan extension, increased fat content, and an increased susceptibility to pathogens.

Orthologs of daf-2;maoc-1 in SynergyAge

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Species	Gene

Not in SynergyAge
Species	Gene

Orthologs of daf-2 in SynergyAge

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Species	Gene
Drosophila melanogaster	InR

Not in SynergyAge
Species	Gene
Mus musculus	Insr
Mus musculus	Igf1r
Mus musculus	Insrr

Orthologs of maoc-1 in SynergyAge

Show in SynergyAge
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.