PT  - JOURNAL ARTICLE
AU  - Marina Ezcurra
AU  - Alexandre Benedetto
AU  - Thanet Sornda
AU  - Ann F. Gilliat
AU  - Catherine Au
AU  - Qifeng Zhang
AU  - Sophie van Schelt
AU  - Alexandra L. Petrache
AU  - Yila de la Guardia
AU  - Shoshana Bar-Nun
AU  - Eleanor Tyler
AU  - Michael J. Wakelam
AU  - David Gems
TI  - Autophagy-dependent gut-to-yolk biomass conversion generates visceral polymorbidity in aging <em>C. elegans</em>
AID  - 10.1101/234419
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 234419
4099  - http://biorxiv.org/content/early/2017/12/15/234419.short
4100  - http://biorxiv.org/content/early/2017/12/15/234419.full
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.