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Research output: Contribution to Journal/Magazine › Journal article
Research output: Contribution to Journal/Magazine › Journal article
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TY - JOUR
T1 - Autophagy-dependent gut-to-yolk biomass conversion generates visceral polymorbidity in aging C. elegans
AU - Ezcurra, Marina
AU - Benedetto, Alexandre
AU - Sornda, Thanet
AU - Gilliat, Ann
AU - Au, Catherine
AU - Zhang, Qifeng
AU - van Schelt, Sophie
AU - Petrache, Alexandra L
AU - de la Guardia, Yila
AU - Bar-Nun, Shoshana
AU - Tyler, Eleonor
AU - Wakelam, Michael J
AU - Gems, David
PY - 2017/12/15
Y1 - 2017/12/15
N2 - 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.
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.
U2 - 10.1101/234419
DO - 10.1101/234419
M3 - Journal article
JO - Biorxiv
JF - Biorxiv
ER -