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Updated: May 15, 2025

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Adipose-derived small extracellular vesicle miR-146a-5p targets Fbx32 to regulate mitochondrial autophagy and delay

Mengran Qin1,2,3,4, Yan Wang1,2,3, Zihan Wang5

  • 1Tianjin Hospital, Tianjin University, Tianjin, 300211, China.

Journal of Nanobiotechnology
|April 11, 2025
PubMed

Insights

MicroRNA-146a-5p from adipose tissue extracellular vesicles delays muscle aging by enhancing mitochondrial autophagy and targeting Fbx32. This discovery offers new therapeutic strategies for age-related muscle disorders.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Gerontology

Background:

  • Skeletal muscle aging is characterized by atrophy, impaired regeneration, and reduced function.
  • Mitochondrial dysfunction and altered autophagy contribute significantly to muscle aging.
  • Small extracellular vesicles (sEVs) are emerging as key mediators of intercellular communication.

Purpose of the Study:

  • To investigate the role of miR-146a-5p, delivered via adipose tissue-derived sEVs, in regulating mitochondrial autophagy and delaying skeletal muscle aging.
  • To elucidate the molecular mechanisms by which miR-146a-5p influences myoblast function and skeletal muscle health.

Main Methods:

  • In vitro studies using C2C12 myoblasts treated with miR-146a-5p mimics and inhibitors.
  • In vivo studies using aged mice treated with miR-146a-5p-enriched sEVs.
  • Analysis of mitochondrial autophagy, apoptosis, ROS levels, ATP production, and gene expression.
  • Investigation of the Fbx32/FoxO3 signaling pathway.

Main Results:

  • miR-146a-5p mimics reduced apoptosis, autophagy, and ROS, while increasing ATP production in C2C12 cells.
  • miR-146a-5p-enriched sEVs alleviated skeletal muscle atrophy in aged mice, promoting muscle fiber growth and repair.
  • miR-146a-5p targets Fbx32, modulating mitochondrial autophagy and the FoxO3 pathway, leading to reduced apoptosis and ROS, and increased ATP.

Conclusions:

  • Adipose tissue-derived miR-146a-5p delivered via sEVs plays a critical role in delaying skeletal muscle aging.
  • The miR-146a-5p/Fbx32/FoxO3 axis is a key regulator of mitochondrial autophagy, apoptosis, and differentiation in myoblasts.
  • This study identifies a novel therapeutic target for combating age-related muscle decline and related disorders.
Keywords:
AgingFbx32Mitochondrial autophagymiR-146a-5psEV

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