Worms lacking the autophagy gene bec-1 lost the lifespan-extending benefit of reduced insulin-like signaling - autophagy is mechanistically required for longevity, not just correlated.
| Evidence tier | C Animal in vivo |
| Study type | 4 - Animal Study |
| Model system | Caenorhabditis elegans |
| Journal | Science |
| Year | 2003 |
| Peer reviewed | Yes |
| Source | DOI 10.1126/science.1087782 · PMID 12958363 |
Both dauer formation (a stage of developmental arrest) and adult life-span in Caenorhabditis elegans are negatively regulated by insulin-like signaling, but little is known about cellular pathways that mediate these processes. Autophagy, through the sequestration and delivery of cargo to the lysosomes, is the major route for degrading long-lived proteins and cytoplasmic organelles in eukaryotic cells. Using nematodes with a loss-of-function mutation in the insulin-like signaling pathway, we show that bec-1, the C. elegans ortholog of the yeast and mammalian autophagy gene APG6/VPS30/beclin1, is essential for normal dauer morphogenesis and life-span extension. Dauer formation is associated with increased autophagy and also requires C. elegans orthologs of the yeast autophagy genes APG1, APG7, APG8, and AUT10. Thus, autophagy is a cellular pathway essential for dauer development and life-span extension in C. elegans.
| Intervention | Genetic (autophagy-gene RNAi) |
| Target | Autophagy / insulin-IGF (daf-2) |
| Model | C. elegans |
| Effect | Autophagy genes are essential for dauer development and for lifespan extension in insulin/IGF (daf-2) mutants |