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C. Elegans Eats Its Own Intestine to Make Yolk: A Cause of Senescent Polymorbidity

53 Pages Posted: 8 Apr 2018 Sneak Peek Status: Under Review

See all articles by Marina Ezcurra

Marina Ezcurra

University College London - Institute of Healthy Ageing; Queen Mary University of London - School of Biological and Chemical Sciences

Alexandre Benedetto

University College London - Institute of Healthy Ageing; Lancaster University - Division of Biomedical and Life Sciences

Thanet Sornda

University College London - Institute of Healthy Ageing

Ann F. Gilliat

University College London - Institute of Healthy Ageing

Catherine Au

University College London - Institute of Healthy Ageing

Qifeng Zhang

The Babraham Institute

Sophie van Schelt

University College London - Institute of Healthy Ageing

Alexandra L. Petrache

University College London - Institute of Healthy Ageing

Yila de la Guardia

University College London - Institute of Healthy Ageing

Shoshana Bar-Nun

University College London - Institute of Healthy Ageing

Eleanor Tyler

University College London - Institute of Healthy Ageing

Michael J. Wakelam

The Babraham Institute

David Gems

University College London - Institute of Healthy Ageing

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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 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): autophagymediated 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.

Suggested Citation

Ezcurra, Marina and Benedetto, Alexandre and Sornda, Thanet and Gilliat, Ann F. and Au, Catherine and Zhang, Qifeng and Schelt, Sophie van and Petrache, Alexandra L. and de la Guardia, Yila and Bar-Nun, Shoshana and Tyler, Eleanor and Wakelam, Michael J. and Gems, David, C. Elegans Eats Its Own Intestine to Make Yolk: A Cause of Senescent Polymorbidity (2018). Available at SSRN: https://ssrn.com/abstract=3155672 or http://dx.doi.org/10.2139/ssrn.3155672
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Marina Ezcurra

University College London - Institute of Healthy Ageing

United Kingdom

Queen Mary University of London - School of Biological and Chemical Sciences

London
United Kingdom

Alexandre Benedetto

University College London - Institute of Healthy Ageing

United Kingdom

Lancaster University - Division of Biomedical and Life Sciences

Lancaster
United Kingdom

Thanet Sornda

University College London - Institute of Healthy Ageing

United Kingdom

Ann F. Gilliat

University College London - Institute of Healthy Ageing

United Kingdom

Catherine Au

University College London - Institute of Healthy Ageing

United Kingdom

Qifeng Zhang

The Babraham Institute

Babraham Hall House
Babraham Research Campus
Babraham, Cambridge, England CB22 3AT
United Kingdom

Sophie van Schelt

University College London - Institute of Healthy Ageing

United Kingdom

Alexandra L. Petrache

University College London - Institute of Healthy Ageing

United Kingdom

Yila De la Guardia

University College London - Institute of Healthy Ageing

United Kingdom

Shoshana Bar-Nun

University College London - Institute of Healthy Ageing

United Kingdom

Eleanor Tyler

University College London - Institute of Healthy Ageing

United Kingdom

Michael J. Wakelam

The Babraham Institute

Babraham Hall House
Babraham Research Campus
Babraham, Cambridge, England CB22 3AT
United Kingdom

David Gems (Contact Author)

University College London - Institute of Healthy Ageing ( email )

United Kingdom

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