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

Marina Ezcurra; Alexandre Benedetto; Thanet Sornda; Ann F Gilliat; Catherine Au; Qifeng Zhang; Sophie van Schelt; Alexandra L Petrache; Hongyuan Wang; Yila de la Guardia; Shoshana Bar-Nun; Eleanor Tyler; Michael J Wakelam; David Gems

doi:10.1016/j.cub.2018.06.035

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

Curr Biol. 2018 Aug 20;28(16):2544-2556.e5. doi: 10.1016/j.cub.2018.06.035. Epub 2018 Aug 9.

Authors

Affiliations

¹ Institute of Healthy Ageing and Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, UK; School of Biological and Chemical Sciences, Queen Mary University of London, London E1 4NS, UK.
² Institute of Healthy Ageing and Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, UK; Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster LA1 4YW, UK.
³ Institute of Healthy Ageing and Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, UK; Department of Biochemistry, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand.
⁴ Institute of Healthy Ageing and Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, UK.
⁵ The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
⁶ The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Tel-Aviv, Israel.
⁷ Institute of Healthy Ageing and Department of Genetics, Evolution and Environment, University College London, London WC1E 6BT, UK. Electronic address: [email protected].

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).

Keywords: C. elegans; aging; atrophy; autophagy; insulin/IGF-1 signaling; intestine; pathology; steatosis; vitellogenin; yolk.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aging / physiology*
Animals
Autophagy / physiology*
Caenorhabditis elegans / physiology*
Egg Yolk / metabolism*
Intestines / physiology*
Signal Transduction
Vitellogenesis / physiology*

Grants and funding

Wellcome Trust/United Kingdom