qns-1;rrf-3

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Genetic mutants with qns-1, rrf-3 alterations

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

Temperature °C
20
Diet
NGM; OP52
Lifespan (days)
14.4
Lifespan comparisons
Double mutant qns-1(RNAi);rrf-3(pk1426) has a lifespan of 14.4 days, while single mutant rrf-3(pk1426) has a lifespan of 20.5 days.
Citation
View abstract
Mouchiroud L et al., 2013, The NAD(+)/Sirtuin Pathway Modulates Longevity through Activation of Mitochondrial UPR and FOXO Signaling. Cell. 154(2):430-41 23870130 Click here to select all mutants from this PubMed ID in the graph
Abstract
NAD(+) is an important cofactor regulating metabolic homeostasis and a rate-limiting substrate for sirtuin deacylases. We show that NAD(+) levels are reduced in aged mice and Caenorhabditis elegans and that decreasing NAD(+) levels results in a further reduction in worm lifespan. Conversely, genetic or pharmacological restoration of NAD(+) prevents age-associated metabolic decline and promotes longevity in worms. These effects are dependent upon the protein deacetylase sir-2.1 and involve the induction of mitonuclear protein imbalance as well as activation of stress signaling via the mitochondrial unfolded protein response (UPR(mt)) and the nuclear translocation and activation of FOXO transcription factor DAF-16. Our data suggest that augmenting mitochondrial stress signaling through the modulation of NAD(+) levels may be a target to improve mitochondrial function and prevent or treat age-associated decline.

Search genes: qns-1 rrf-3

Entrez ID
Symbol
GenAge
Wormbase ID

177900
qns-1
View on GenAge (qns-1)
WBGene00007698

Glutamine-dependent NAD(+) synthetase;glutamine(Q)-dependent NAD(+) Synthase

Locus: CELE_C24F3.4

Wormbase description: qns-1 encodes an NAD+ synthase orthologous to human NAD synthetase 1 (HGNC:NADSYN1); by homology, QNS-1 is predicted to catalyze the final step in NAD+ synthesis; loss of qns-1 activity via RNAi results in reduced NAD+ levels and shortened adult lifespan.

Entrez ID
Symbol
GenAge
Wormbase ID

174315
rrf-3
View on GenAge (rrf-3)
WBGene00004510

RNA-dependent RNA polymerase Family

Locus: CELE_F10B5.7

Wormbase description: rrf-3 encodes an RNA-directed RNA polymerase (RdRP) homolog that inhibits somatic RNAi, and thus promotes activity of repeated genes (e.g., multicopy transgenic arrays); the effect of RRF-3 on RNAi is opposite to that of RRF-1 (which stimulates somatic RNAi), which might arise from competition by RRF-3 with RRF-1 or EGO-1 in RNAi formation; rrf-3(allele) or rrf-3(allele2) mutants are hypersensitive to somatic RNAi, and conversely suppress the activity of an integrated rol6 (su1006) transgene.

Orthologs of qns-1;rrf-3 in SynergyAge

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Orthologs of qns-1 in SynergyAge

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Orthologs of rrf-3 in SynergyAge

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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.