This week, we’re writing about one of our favorite articles mentioned in our recent member’s only autophagy talk!  In this study, researchers disproved the previous belief that fasting-induced autophagy was unable to reach the brain.  They then analyzed some of the incredible neuroprotective powers of autophagy!

Published in August 2010 in the journal Autophagy. The full article is freely available online here: Short-term fasting induces profound neuronal autophagy

Autophagy Background Information:

• Autophagy is a homeostatic mechanism in which cell components are degraded and recycled to be reused
  • A homeostatic mechanism is a process that works to keep the body in a stable and consistent state in order for it to function properly
• It has been described as a key defense mechanism to protect against:
  • Malignancy (abnormal and uncontrollable cell growth)
  • Infection
  • Neurodegeneration (loss of function and/or structure in the nervous system)

The Gap in Autophagy Research:

• So far, research has struggled to actively observe the process of autophagy in intact organs and tissues
• Food restriction has been shown to induce autophagy in many organs and tissues but had not been detected in the brain even after long periods of fasting
  • Originally believed that the brain was “metabolically privileged” or in other words that it needed a stronger signal than nutrient deprivation to enter autophagy

Autophagy in Intact Organs and Tissues:

• Microscopy identified autophagosomes in the livers of food-restricted mice 
  • Autophagosome: organelle that plays a key role in autophagy by delivering cellular components to the lysosome for degradation
  • Seen as early as 24 hours after fasting began and then more abundantly after 48 hours
  • This is likely caused by either an increase in the production of autophagosomes or a reduction in autophagosome fusion with lysosomes
• Autophagosomes were also observed in neurons of normal-fed mice, with increased abundance after short-term food restriction
• Other neurons, known as Purkinje cells, in food-restricted mice contained greater numbers of autophagosomes and showed reduced mTOR function
  • mTOR (mechanistic target of rapamycin) is a negative regulator of autophagy, meaning that when mTOR is turned off, autophagy is turned on

Significance and Clinical Relevance:

• This article is the first to demonstrate that short-term fasting can induce a dramatic upregulation of autophagy in various cells in the nervous system
• Also found that autophagy pathways vary somewhat between cell type
  • Consistent with the theory that autophagy mechanisms vary as a result of adaptations to cellular needs
• If disruption of autophagy causes neurodegenerative disease, it is posisble that the opposite is also true: that upregulation of autophagy has a neuroprotective effect
  • This might indicat a method of improving neuronal functioning through intermittent fasting due to upregulation of autophagy

Other Fasting Flamingo Autophagy Resources: 

• Intermittent fasting, a possible priming tool for host defense against SARS-CoV-2 infection: Crosstalk among calorie restriction, autophagy and immune response
  • In this article, researchers discuss the possible connections between the pathways associated with intermittent fasting, autophagy, and SARS-CoV-2 infection.  
• The Switch with James Clement- Ignite Your Metabolism with Intermittent Fasting & Keto
  • In this video, Reena Jadhav interviews author James Clement and discusses the metabolic benefits of intermittent fasting.  Specifically, they analyze some of the concepts present in Clement’s book, “The Switch,” which discusses the importance of the metabolic switch mTOR. 
• Can autophagy (and fasting) naturally shed excess skin following weight loss? 
  • Is what you’ve heard true? Can autophagy help you naturally shed excess skin after weight loss?

Want to learn more? Here are some of the references cited by this article:

• Autophagy fights disease through cellular self-digestion
• Eating the enemy within: autophagy in infectious diseases
• Autophagy, amyloidogenesis and Alzheimer disease

Need more background information on autophagy? Believe it or not, Wikipedia is a great starting place when learning about new scientific concepts! Just make sure to check the sources and follow up anything that interests you with more research.  

Autophagy Wikipedia.