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Updated: Jan 27, 2026

Activating Autophagy by Aerobic Exercise in Mice
Published on: February 3, 2017
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.
Aim:
To study the effects of exercise on lysosomal functions.
Methods:
Mouse exercise model was established and wheel running was scheduled as 18 rpm (14:00-17:00), 5 d/wk, for 8 weeks. Mice were injected EX527 to inhibit SIRT1 activity. The protein level was assayed with Western blot and immunofluorescence histochemistry. The transmission electron microscopic examination was used to show the structure of lysosome and mitochondria.
Results:
Exercise promoted the nuclear translocation of TFEB in the cortex which upregulated the transcription of genes associated with autophagy and lysosome. Exercise directly activated autophagy/lysosome system via up-regulating of AMPK-SIRT1 signaling. The SIRT1 inhibitor EX527 decreased TFEB regulated gene transcription but had little effect on the nuclear translocation of TFEB. In addition, long-term exercise showed more significant effects on activation of lysosomes biogenesis compared with the short-term exercise and trehalose, a classical autophagy activator in the mTOR-independent pathway.
Conclusion:
Running exercise activates lysosomal function in the brain through AMPK-SIRT1-TFEB pathway.
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