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Science 5 September 2003:
Vol. 301. no. 5638, pp. 1387 - 1391
DOI: 10.1126/science.1087782
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Reports

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

Alicia Meléndez,1 Zsolt Tallóczy,1 Matthew Seaman,2 Eeva-Liisa Eskelinen,3 David H. Hall,4 Beth Levine1*

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.

1 Department of Medicine, Columbia University College of Physicians & Surgeons, 630 West 168th Street, New York, NY 10032, USA.
2 Department of Clinical Biochemistry, Cambridge Institute for Medical Research, Addenbrookes Hospital, Cambridge, CB2 2XY, UK.
3 Institute of Biochemistry, University of Kiel, D-24098 Kiel, Germany.
4 Center for C. elegans Anatomy, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

* To whom correspondence should be addressed. E-mail: levine{at}cancercenter.columbia.edu

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