Autophagy Genes Are Essential for Dauer Development and Life-Span Extension in C. elegans

Abstract

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.

Genes that may modulate longevity in C. elegans in both dauer larvae and long-lived daf-2 adults

“…Autophagy has been highlighted as an important aging-related process in C. elegans (Melendez et al, 2003). Perhaps because of low tag counts, we did not find autophagy-related genes among those showing statistically significant expression changes in long-lived nematodes.…”

The pleiotropic role of autophagy: from protein metabolism to bactericide

“…There is possible genetic evidence. Melendez et al 24 demonstrated that beclin-1 (Atg6) is required for the life-span extension observed in a worm mutant lacking the insulin signaling gene daf2. Although the effects of knocking down other atg genes were not demonstrated, these data suggest that autophagy could be an important process regulating longevity.…”

“…10,49 Finally, dauer formation is abnormal in Caenorhabditis elegans autophagy mutants. 24 Although these phenotypes seem to be diverse, all of them are closely related to nutrient status and starvation. For example, sporulation, fruiting body formation, and dauer formation are typical starvation responses.…”

Evidence for only two independent pathways for decreasing senescence in Caenorhabditis elegans

“…Although free radicals have been correlated with senescence, in both mice and worms, there is increasing evidence that they may not be the causative agent (Doonan et al 2008;Ran et al 2007;Van Raamsdonk and Hekimi 2009;Van Remmen et al 2003;Yen et al 2009). The target of rapamycin pathway, which may also link DR and insulin/IGF signaling, regulates autophagy, and this is important for both DR and insulin/IGF mediated longevity (Hansen et al 2008;Kaeberlein et al 2005;Kapahi et al 2004;Melendez et al 2003).…”