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

Nat Commun. 2019 Oct 23;10(1):4827. doi: 10.1038/s41467-019-12821-2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics*
  • Animals
  • Autophagy / genetics
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Extracellular Vesicles / metabolism
  • Intestinal Mucosa / metabolism
  • Intestines
  • Macroautophagy / genetics*
  • Membrane Proteins / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Muscles / metabolism
  • Transcription Factors / metabolism

Substances

  • CUP-5 protein, C elegans
  • Caenorhabditis elegans Proteins
  • MIRN83 microRNA, C elegans
  • Membrane Proteins
  • MicroRNAs
  • Transcription Factors
  • heat shock factor-1, C elegans