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Activating Autophagy by Aerobic Exercise in Mice
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Exercise activates lysosomal function in the brain through AMPK-SIRT1-TFEB pathway.

Jun Huang1, Xue Wang1, Yi Zhu1

  • 1Department of Pharmacology, Laboratory of Aging and Nervous Diseases (SZS0703), Soochow University School of Pharmaceutical Science, Su Zhou, China.

CNS Neuroscience & Therapeutics
|March 14, 2019
PubMed
Summary

Regular running exercise enhances brain lysosomal function by activating the AMPK-SIRT1-TFEB pathway. This pathway boosts autophagy and lysosome biogenesis, improving cellular waste clearance.

Keywords:
TFEBautophagyexerciselysosomal function

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Exercise Physiology

Background:

  • Lysosomal function is crucial for cellular homeostasis and waste removal.
  • The role of exercise in modulating brain lysosomal pathways remains an active area of research.
  • Understanding the molecular mechanisms underlying exercise-induced lysosomal adaptation is key.

Purpose of the Study:

  • To investigate the impact of running exercise on lysosomal function in the brain.
  • To elucidate the molecular signaling pathways involved in exercise-mediated lysosomal activation.
  • To compare the effects of long-term versus short-term exercise on lysosomal biogenesis.

Main Methods:

  • Establishment of a mouse exercise model involving controlled wheel running.
  • Inhibition of SIRT1 activity using the EX527 compound.
  • Assessment of protein levels via Western blot and immunofluorescence.
  • Microscopic examination of lysosome and mitochondria structure using transmission electron microscopy.

Main Results:

  • Exercise promoted nuclear translocation of TFEB (Transcription Factor EB) in the cortex, upregulating autophagy and lysosome-related genes.
  • Running exercise directly activated the autophagy/lysosome system by upregulating the AMPK-SIRT1 signaling pathway.
  • Long-term exercise demonstrated more significant effects on lysosomal biogenesis activation compared to short-term exercise.

Conclusions:

  • Running exercise activates brain lysosomal function via the AMPK-SIRT1-TFEB pathway.
  • This pathway is critical for exercise-induced enhancements in autophagy and lysosomal biogenesis.
  • Exercise offers a promising non-pharmacological strategy for boosting brain lysosomal health.