RT Journal Article SR Electronic T1 Autophagy-dependent gut-to-yolk biomass conversion generates visceral polymorbidity in aging C. elegans JF bioRxiv FD Cold Spring Harbor Laboratory SP 234419 DO 10.1101/234419 A1 Marina Ezcurra A1 Alexandre Benedetto A1 Thanet Sornda A1 Ann F. Gilliat A1 Catherine Au A1 Qifeng Zhang A1 Sophie van Schelt A1 Alexandra L. Petrache A1 Yila de la Guardia A1 Shoshana Bar-Nun A1 Eleanor Tyler A1 Michael J. Wakelam A1 David Gems YR 2017 UL http://biorxiv.org/content/early/2017/12/15/234419.abstract AB 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 Caenorhabditis 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 polymorbidity 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 continued action of a wild-type function (vitellogenesis), consistent with the recently proposed hyperfunction theory of aging.