A secreted microRNA disrupts autophagy in distinct tissues of Caenorhabditis elegans upon ageing

Yifei Zhou, Xueqing Wang, Mengjiao Song, Zhidong He, Guizhong Cui, Guangdun Peng, Christoph Dieterich, Adam Antebi, Naihe Jing and Yidong Shen ()
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Yifei Zhou: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Xueqing Wang: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Mengjiao Song: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Zhidong He: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Guizhong Cui: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Guangdun Peng: Chinese Academy of Sciences
Christoph Dieterich: Klaus Tschira Institute for Integrative Computational Cardiology and Department of Internal Medicine III, University Hospital Heidelberg
Adam Antebi: Max Planck Institute for Biology of Ageing
Naihe Jing: University of Chinese Academy of Sciences, Chinese Academy of Sciences
Yidong Shen: University of Chinese Academy of Sciences, Chinese Academy of Sciences

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract Macroautophagy, a key player in protein quality control, is proposed to be systematically impaired in distinct tissues and causes coordinated disruption of protein homeostasis and ageing throughout the body. Although tissue-specific changes in autophagy and ageing have been extensively explored, the mechanism underlying the inter-tissue regulation of autophagy with ageing is poorly understood. Here, we show that a secreted microRNA, mir-83/miR-29, controls the age-related decrease in macroautophagy across tissues in Caenorhabditis elegans. Upregulated in the intestine by hsf-1/HSF1 with age, mir-83 is transported across tissues potentially via extracellular vesicles and disrupts macroautophagy by suppressing CUP-5/MCOLN, a vital autophagy regulator, autonomously in the intestine as well as non-autonomously in body wall muscle. Mutating mir-83 thereby enhances macroautophagy in different tissues, promoting protein homeostasis and longevity. These findings thus identify a microRNA-based mechanism to coordinate the decreasing macroautophagy in various tissues with age.

Date: 2019
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DOI: 10.1038/s41467-019-12821-2

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