bec-1;clk-1

There is no network for this step.

Fullscreen mode

Hide graph

Legend

Genetic mutants with bec-1, clk-1 alterations

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

Temperature °C
20
Lifespan (days)
26.7
Lifespan comparisons
Double mutant bec-1(RNAi);clk-1(e2519) has a lifespan of 26.7 days, while single mutant clk-1(e2519) has a lifespan of 21.6 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.

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

Temperature °C
20
Diet
OP50
Lifespan (days)
25.6
Lifespan comparisons
Double mutant bec-1(RNAi);clk-1(qm30) has a lifespan of 25.6 days, while single mutant clk-1(qm30) has a lifespan of 23.9 days.
Citation
View abstract
Hansen M et al., 2008, A role for autophagy in the extension of lifespan by dietary restriction in C. elegans. PLoS Genet. 4(2):e24 18282106 Click here to select all mutants from this PubMed ID in the graph
Abstract
In many organisms, dietary restriction appears to extend lifespan, at least in part, by down-regulating the nutrient-sensor TOR (Target Of Rapamycin). TOR inhibition elicits autophagy, the large-scale recycling of cytoplasmic macromolecules and organelles. In this study, we asked whether autophagy might contribute to the lifespan extension induced by dietary restriction in C. elegans. We find that dietary restriction and TOR inhibition produce an autophagic phenotype and that inhibiting genes required for autophagy prevents dietary restriction and TOR inhibition from extending lifespan. The longevity response to dietary restriction in C. elegans requires the PHA-4 transcription factor. We find that the autophagic response to dietary restriction also requires PHA-4 activity, indicating that autophagy is a transcriptionally regulated response to food limitation. In spite of the rejuvenating effect that autophagy is predicted to have on cells, our findings suggest that autophagy is not sufficient to extend lifespan. Long-lived daf-2 insulin/IGF-1 receptor mutants require both autophagy and the transcription factor DAF-16/FOXO for their longevity, but we find that autophagy takes place in the absence of DAF-16. Perhaps autophagy is not sufficient for lifespan extension because although it provides raw material for new macromolecular synthesis, DAF-16/FOXO must program the cells to recycle this raw material into cell-protective longevity proteins.

Temperature °C
20
Diet
OP50
Lifespan (days)
23.5
Lifespan comparisons
Double mutant bec-1(RNAi);clk-1(qm30) has a lifespan of 23.5 days, while single mutant clk-1(qm30) has a lifespan of 24.2 days.
Citation
View abstract
Hansen M et al., 2008, A role for autophagy in the extension of lifespan by dietary restriction in C. elegans. PLoS Genet. 4(2):e24 18282106 Click here to select all mutants from this PubMed ID in the graph
Abstract
In many organisms, dietary restriction appears to extend lifespan, at least in part, by down-regulating the nutrient-sensor TOR (Target Of Rapamycin). TOR inhibition elicits autophagy, the large-scale recycling of cytoplasmic macromolecules and organelles. In this study, we asked whether autophagy might contribute to the lifespan extension induced by dietary restriction in C. elegans. We find that dietary restriction and TOR inhibition produce an autophagic phenotype and that inhibiting genes required for autophagy prevents dietary restriction and TOR inhibition from extending lifespan. The longevity response to dietary restriction in C. elegans requires the PHA-4 transcription factor. We find that the autophagic response to dietary restriction also requires PHA-4 activity, indicating that autophagy is a transcriptionally regulated response to food limitation. In spite of the rejuvenating effect that autophagy is predicted to have on cells, our findings suggest that autophagy is not sufficient to extend lifespan. Long-lived daf-2 insulin/IGF-1 receptor mutants require both autophagy and the transcription factor DAF-16/FOXO for their longevity, but we find that autophagy takes place in the absence of DAF-16. Perhaps autophagy is not sufficient for lifespan extension because although it provides raw material for new macromolecular synthesis, DAF-16/FOXO must program the cells to recycle this raw material into cell-protective longevity proteins.

Temperature °C
20
Diet
OP50
Lifespan (days)
22.5
Lifespan comparisons
Double mutant bec-1(RNAi);clk-1(qm30) has a lifespan of 22.5 days, while single mutant clk-1(qm30) has a lifespan of 23.9 days.
Citation
View abstract
Hansen M et al., 2008, A role for autophagy in the extension of lifespan by dietary restriction in C. elegans. PLoS Genet. 4(2):e24 18282106 Click here to select all mutants from this PubMed ID in the graph
Abstract
In many organisms, dietary restriction appears to extend lifespan, at least in part, by down-regulating the nutrient-sensor TOR (Target Of Rapamycin). TOR inhibition elicits autophagy, the large-scale recycling of cytoplasmic macromolecules and organelles. In this study, we asked whether autophagy might contribute to the lifespan extension induced by dietary restriction in C. elegans. We find that dietary restriction and TOR inhibition produce an autophagic phenotype and that inhibiting genes required for autophagy prevents dietary restriction and TOR inhibition from extending lifespan. The longevity response to dietary restriction in C. elegans requires the PHA-4 transcription factor. We find that the autophagic response to dietary restriction also requires PHA-4 activity, indicating that autophagy is a transcriptionally regulated response to food limitation. In spite of the rejuvenating effect that autophagy is predicted to have on cells, our findings suggest that autophagy is not sufficient to extend lifespan. Long-lived daf-2 insulin/IGF-1 receptor mutants require both autophagy and the transcription factor DAF-16/FOXO for their longevity, but we find that autophagy takes place in the absence of DAF-16. Perhaps autophagy is not sufficient for lifespan extension because although it provides raw material for new macromolecular synthesis, DAF-16/FOXO must program the cells to recycle this raw material into cell-protective longevity proteins.

Search genes: bec-1 clk-1

Entrez ID
Symbol
GenAge
Wormbase ID

177345
bec-1
View on GenAge (bec-1)
WBGene00000247

Beclin homolog

Locus: CELE_T19E7.3

Wormbase description: bec-1 encodes a coiled-coil protein orthologous to the yeast and mammalian autophagy proteins Atg6/Vps30/Beclin1; by homology, BEC-1 may be part of a Class III phosphatidylinositol 3-kinase complex that plays a role in localizing autophagy proteins to preautophagosomal structures and overexpression of C. elegans bec-1 in S. cerevisiae APG6/VPS30 mutants can rescue associated autophagy defects; bec-1 is also required for regulation of endocytic retrograde transport; in C. elegans, bec-1 activity is required for normal dauer morphogenesis and survival of dauer larvae, as well as for adult life span extension of daf-2(e1370) mutants at 15 degrees; in addition, bec-1(RNAi) indicates a role for bec-1 in normal growth rates, movement, and vulval morphogenesis; a bec-1::GFP reporter fusion is expressed in the hypodermis, intestine, nervous system, pharynx, and reproductive organs, all tissues that are remodeled during dauer larval development.

Entrez ID
Symbol
GenAge
Wormbase ID

175729
clk-1
View on GenAge (clk-1)
WBGene00000536

5-demethoxyubiquinone hydroxylase, mitochondrial

Locus: CELE_ZC395.2

Wormbase description: clk-1 encodes the C. elegans ortholog of COQ7/CAT5, a highly conserved demethoxyubiquinone (DMQ) hydroxylase that is necessary for the biosynthesis of ubiquinone (coenzyme Q, Q9) from 5-demethoxyubiquinone (DMQ9); in C. elegans, CLK-1 activity is required for normal physiological rates of growth, development, behavior, and aging, as well as for normal brood sizes.

Orthologs of bec-1;clk-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Atg6;COQ7
Mus musculus	Becn1;Coq7

Orthologs of bec-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	Atg6
Mus musculus	Becn1

Orthologs of clk-1 in SynergyAge

Show in SynergyAge
Species	Gene

Not in SynergyAge
Species	Gene
Drosophila melanogaster	COQ7
Mus musculus	Coq7