C. elegans Eats Its Own Intestine to Make Yolk Leading to Multiple Senescent Pathologies

Ezcurra, Marina and Benedetto, Alexandre and Sornda, Thanet and Gilliat, Ann F and Au, Catherine and Zhang, Qifeng and van Schelt, Sophie and Petrache, Alexandra L and Wang, Hongyuan and de la Guardia, Yila and Bar-Nun, Shoshana and Tyler, Eleanor and Wakelam, Michael J and Gems, David (2018) C. elegans Eats Its Own Intestine to Make Yolk Leading to Multiple Senescent Pathologies. Current Biology, 28 (16). 2544-2556.e5. ISSN 0960-9822

Abstract

Aging (senescence) is characterized by the development of numerous pathologies, some of which limit lifespan. Key to understanding aging is discovery of the mechanisms (etiologies) that cause senescent pathology. In C. elegans, a major senescent pathology of unknown etiology is atrophy of its principal metabolic organ, the intestine. Here we identify a cause of not only this pathology but also of yolky lipid accumulation and redistribution (a form of senescent obesity): autophagy-mediated conversion of intestinal biomass into yolk. Inhibiting intestinal autophagy or vitellogenesis rescues both visceral pathologies and can also extend lifespan. This defines a disease syndrome leading to multimorbidity and contributing to late-life mortality. Activation of gut-to-yolk biomass conversion by insulin/IGF-1 signaling (IIS) promotes reproduction and senescence. This illustrates how major, IIS-promoted senescent pathologies in C. elegans can originate not from damage accumulation but from direct effects of futile, continued action of a wild-type biological program (vitellogenesis).