daf-16;sir-2.1;unc-51

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Genetic mutants with daf-16, sir-2.1, unc-51 alterations

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

Temperature °C
20
Lifespan (days)
12.7
Lifespan comparisons
Triple mutant daf-16(mgDf50);sir-2.1(ok434);unc-51(RNAi) has a lifespan of 12.7 days, while double mutant daf-16(mgDf50);sir-2.1(ok434) has a lifespan of 11.9 days.
Citation
View abstract
Hashimoto Y et al., 2009, Lifespan extension by suppression of autophagy genes in Caenorhabditis elegans. Genes Cells. 14(6):717-26 19469880 Click here to select all mutants from this PubMed ID in the graph
Abstract
Lifespan is regulated by a complex combination of environmental and genetic factors. Autophagy, which is a bulk degradation system of macromolecules and organelles, has an important role in various biological events. In Caenorhabditis elegans, several autophagy genes have been shown to have a role in promoting longevity, but many other autophagy genes have not been examined for their role in the lifespan regulation. Here we have systematically examined the effect of RNAi suppression of 14 autophagy genes on lifespan. While maternal RNAi of autophagy genes in wild-type worms tended to reduce lifespan, maternal RNAi of each of seven autophagy genes in the insulin/IGF-1 receptor daf-2 mutants extended lifespan. Remarkably, RNAi of unc-51/atg-1, bec-1/atg-6 or atg-9, from young adult, i.e. after development, extended lifespan in both wild-type animals and daf-2 mutants, although RNAi of one or two genes shortened it. Moreover, our analysis suggests that the lifespan extension, which is induced by RNAi of unc-51, bec-1 or atg-9 after development, does not require the transcription factor daf-16, the NAD(+)-dependent protein deacetylase sir-2.1 or the genes related to mitochondrial functions. Collectively, our results suggest that autophagy may not always be beneficial to longevity, but may also function to restrict lifespan in C. elegans.

Search genes: daf-16 sir-2.1 unc-51 daf-16;sir-2.1;unc-51

Entrez ID
Symbol
GenAge
Wormbase ID

172981
daf-16
View on GenAge (daf-16)
WBGene00000912

Forkhead box protein O;hypothetical protein

Locus: CELE_R13H8.1

Wormbase description: daf-16 encodes the sole C. elegans forkhead box O (FOXO) homologue; DAF-16 functions as a transcription factor that acts in the insulin/IGF-1-mediated signaling (IIS) pathway that regulates dauer formation, longevity, fat metabolism, stress response, and innate immunity; DAF-16 regulates these various processes through isoform-specific expression, isoform-specific regulation by different AKT kinases, and differential regulation of target genes; DAF-16 can interact with the CBP-1 transcription cofactor in vitro, and interacts genetically with other genes in the insulin signaling and with daf-12, which encodes a nuclear hormone receptor; DAF-16 is activated in response to DNA damage during development and co-regulated by EGL-27, alleviates DNA-damage-induced developmental arrest by inducing DAF-16-associated element (DAE)-regulated genes; DAF-16 is broadly expressed but displays isoform-specific tissue enrichment; DAF-16 localizes to both the cytoplasm and the nucleus, with the ratio between the two an important regulator of function.

Entrez ID
Symbol
GenAge
Wormbase ID

177924
sir-2.1
View on GenAge (sir-2.1)
WBGene00004800

NAD-dependent protein deacetylase sir-2.1;yeast SIR related

Locus: CELE_R11A8.4

Wormbase description: sir-2.1 encodes an NAD-dependent protein deacetylase with similarity to Saccharomyces cerevisiae Sir2p and mammalian SIRT1.

Entrez ID
Symbol
GenAge
Wormbase ID

180311
unc-51
View on GenAge (unc-51)
WBGene00006786

Serine/threonine-protein kinase unc-51

Locus: CELE_Y60A3A.1

Wormbase description: unc-51 encodes a serine/threonine protein kinase orthologous to Saccharomyces cerevisiae autophagy protein Atg1p and the vertebrate ULK proteins; unc-51 is required for axon outgrowth along the anterior-posterior axis and sex myoblast migration; in regulating axon outgrowth, UNC-51 functions together with the VAB-8 kinesin-like protein and UNC-14, both of which physically interact with, and are phosphorylated by, UNC-51, and with the UNC-5 Netrin receptor, whose subcellular localization in neurons is regulated by UNC-51 and UNC-14; in addition, UNC-51 is required for normal dauer morphogenesis of daf-2 mutant animals; UNC-51 is expressed in all C. elegans neurons and in body wall and pharyngeal muscles; in neurons, an UNC-51::GFP fusion protein shows punctate cytoplasmic localization in axons and cell bodies and partial co-localization with UNC-14 and UNC-5.

Orthologs of daf-16;sir-2.1;unc-51 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Foxo6;Sirt1;Ulk1
Mus musculus	Foxo6;Sirt1;Ulk2
Mus musculus	Foxo1;Sirt1;Ulk1
Mus musculus	Foxo1;Sirt1;Ulk2
Mus musculus	Foxo4;Sirt1;Ulk1
Mus musculus	Foxo4;Sirt1;Ulk2
Mus musculus	Foxo3;Sirt1;Ulk1
Mus musculus	Foxo3;Sirt1;Ulk2
Mus musculus	Ulk1;Sirt1;Foxo6
Mus musculus	Ulk1;Sirt1;Foxo1
Mus musculus	Ulk1;Sirt1;Foxo4
Mus musculus	Ulk1;Sirt1;Foxo3
Mus musculus	Ulk2;Sirt1;Foxo6
Mus musculus	Ulk2;Sirt1;Foxo1
Mus musculus	Ulk2;Sirt1;Foxo4
Mus musculus	Ulk2;Sirt1;Foxo3

Orthologs of daf-16 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Foxo6
Mus musculus	Foxo1
Mus musculus	Foxo4
Mus musculus	Foxo3

Orthologs of sir-2.1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Mus musculus	Sirt1

Orthologs of unc-51 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Atg1
Mus musculus	Ulk1
Mus musculus	Ulk2