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

Zhou, Y.; Wang, X.; Song, M.; He, Z.; Cui, G.; Peng, G.; Dieterich, C.; Antebi, Adam; Jing, N.; Shen, Y.

doi:10.1038/s41467-019-12821-2

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

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Antebi, Adam
Department Antebi - Molecular Genetics of Ageing, Max Planck Institute for Biology of Ageing, Max Planck Society;

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https://www.ncbi.nlm.nih.gov/pubmed/31645592
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Citation

Zhou, Y., Wang, X., Song, M., He, Z., Cui, G., Peng, G., et al. (2019). A secreted microRNA disrupts autophagy in distinct tissues of Caenorhabditis elegans upon ageing. Nat Commun, 10(1), 4827. doi:10.1038/s41467-019-12821-2.

Cite as: https://hdl.handle.net/21.11116/0000-000B-2BA0-0

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.