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Updated: Jun 12, 2026
08:44
Activating Autophagy by Aerobic Exercise in Mice
Published on: February 3, 2017
Short-term fasting induces profound neuronal autophagy.
Mehrdad Alirezaei1, Christopher C Kemball, Claudia T Flynn
1Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, USA.
Autophagy
|June 11, 2010
Summary
Short-term fasting significantly increases neuronal autophagy, a key process for brain health. This finding challenges the long-held belief that the brain is unaffected by fasting and suggests a simple method to promote neuroprotection.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Autophagy is a critical cellular process for maintaining homeostasis, and its disruption is linked to neurodegeneration.
- Upregulating neuronal autophagy is a therapeutic target for neurodegenerative diseases.
- It was previously believed that the brain does not respond to autophagy induction via food restriction.
Purpose of the Study:
- To re-evaluate the dogma that the brain is metabolically privileged and unaffected by food restriction.
- To develop and validate a novel in vivo method for detecting and characterizing autophagosomes in neurons.
- To investigate the effect of short-term fasting on neuronal autophagy.
Main Methods:
- Development of a novel in vivo approach to detect, enumerate, and characterize autophagosomes.
- Validation of the method in the livers of food-restricted mice.
- Application of the method to identify autophagosomes in cortical neurons and Purkinje cells, and assessment of mTOR activity via phosphorylated S6 ribosomal protein levels.
- Confirmation of autophagosome abundance using transmission electron microscopy.
Main Results:
- The novel method successfully identified and characterized autophagosomes in vivo.
- Short-term fasting led to a significant upregulation of neuronal autophagy in cortical neurons and Purkinje cells.
- Fasting reduced neuronal mTOR activity, indicated by decreased levels of phosphorylated S6 ribosomal protein in Purkinje cells.
- Increased autophagosome abundance in Purkinje cells was confirmed by electron microscopy.
Conclusions:
- The brain does respond to short-term fasting with increased autophagy.
- Neuronal autophagy can be upregulated by sporadic fasting, challenging previous assumptions.
- Sporadic fasting may offer a simple, safe, and cost-effective strategy to promote potentially therapeutic neuronal responses.
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