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Neuronal Autophagy

Neuronal Autophagy

Charge up your brain with autophagy

Are you looking to avoid Alzheimer’s?

Sounds like a pretty silly question if you ask me. Of course. Who wouldn’t want that? But if you really want tangible brain health, then you must look at the implications of autophagy.

Autophagy is the recycling system of the body.[1] In the absence of food, your body triggers certain pathways to recycle all of the junk in your body. Your body needs energy, so where does it get it from when you don’t eat? That’s right – one of the ways your body keeps on going through starvation is by breaking down degraded parts of the cell for use.

Autophagy is the mechanism by which we keep ourselves young. It destroys the harmful parts of the cell that cause damage. It picks all the bad fruit off the tree. This may play a much bigger role in keeping ourselves healthy than we ever thought.

 

Autophagy keeps our brains young


However, there used to be a lot of debate around the world about its role in brain health. Can it really be used to protect neurons and brain cells from damage? The brain has been thought to be “metabolically protected” so that recycling does not occur.

See, although autophagy is protective, it is still objectively “destructive” as far as your body is concerned. That is why researchers have thought for a long time that autophagy does not occur in the brain. It can’t help. But is that really true?

Although this study is several years old, it brings light to the question of our bodies healing themselves. It turns out that this one pathway is not just useful for certain parts of the body, but rather for all parts of the body, including the brain. You were designed to be able to heal yourself – you just need the right course of action.

Summary

As I stated above, scientists used to think that autophagy does not occur in the brain. However, a group of researchers California set out to test this theory. They took lab mice and induced autophagy in them through 1 or 2 day fasts. By not eating, these rats were able to down-regulate their mTOR signaling pathways, which triggers autophagy.[2]

What they found was pretty amazing. From their experiments they were able to determine that autophagy does occur in the brain. And not only does it occur, it cleans house with the force like that of a disaster response crew. It can also occur in subjects in as little as 24 hours. This weeks research article is all about that,[3] so get ready and feel free to follow along as I describe the most important facts. [Click here for the file.]

Alirezaei M, Kemball CC, Flynn CT, Wood MR, Whitton L, Kiosses WB. (2010). Short-term fasting induces profound neuronal autophagy. Autophagy 6(6): 702-710.


Here are some of most important facts I gathered from reading:

  • Autophagy does occur in neurons of the brain.
    • It is not just limited to one kind of neuron – but it appears as if this therapy works for all kind of brain cells.
  • Autophagy is induced to a great extent even after just 24 hours of fasting.
  • Autophagy may be the “new” treatment for Alzheimer’s disease.
    • Still, drugs are being developed with the same end in mind.

The experiment

First of all, this study was done on mice, which means this is not a perfect translation to humans. But despite that fact, it is still pretty dang close, and there are human applications for this that have been proven elsewhere. They took two groups of mice: one was restricted food for 24 and 48 hours, and the other had no food restriction.

 

Research done on mice to confirm autophagy in the brain


They confirmed their methods were valid when they found similar autophagy markers in the liver as previous literature had reported at the time. So the point is that their experimental methods were up to par, and we can trust they conducted this in the best way possible.

Not only did they find autophagy occurring in the liver, but they found it at just 24 hours of food restriction. They also found the same thing in the neurons when they looked at the brain. That is pretty cool. You don’t need to go on a several day fast to induce autophagy – just skip a day of eating! That’s it.

Anyway, they conducted all of their tests and showed through special microscopy that autophagosomes were present. They were present in abundance after 24 hours, and then even more plentiful after 48 hours (when compared to the non-food-restricted mice). Yes, all of this confirmed their hypothesis that autophagy does occur in the brain. Awesome.

But they did not just look at one type of brain cell for this. They moved from cortical neurons to Purkinje cells to test their hypothesis further. Don’t worry about those names. The point is that they checked autophagy in 2 different type of brain cells to confirm their findings.

Implications of autophagy

Okay, so you might understand that cleansing occurs in your brain. Big whoop. But trust me, this is certainly something you should care about. When you inhibit autophagy from occurring in your brain, it leads to neuro-degenerative disease like Alzheimer’s, Parkinson’s, and Huntington’s diseases.[3]

If you are not encouraging the practice of cleaning out your brain and nerve cells, then you will eventually fall apart. Autophagy keeps us young and keeps us functioning smoothly. Imagine that in your brain! Don’t you want a well oiled machine running the show?

 

Autophagy for brain health!


Combine this with a ketogenic diet, and you are in heaven. A ketogenic diet mimics the life-lengthening effects of calorie restriction already.[4] Imagine in you also had the pathway to further neuroprotection from autophagy. You would be unstoppable! And it turns out it is much easier to eat less and fast when you are on a high fat diet. You are less hungry and are more adapted to a food-restricted environment.

Okay, so food restriction is one method of inducing autophagy in your body. This primarily happens through fasting, but are there other ways to do this? Maybe in the near future there will be, but for right now, we know it to only come about from fasting. But let’s have a look at the possibilities.

Ways to get into autophagy

The best way to get into a state of autophagy is to avoid eating for an entire day. When you don’t eat, you lowering your mTOR signaling and induce the autophagic pathway. Autophagosomes come into your cell to destroy the bad parts and use them as food. All pieces eventually go down to meet their doom at the lysosome which is the “trash can” of the cell. Right, so you get to that point by not eating.

However, there may be another way to get into autophagy in the near future. Researchers have been looking for some time at developing drugs that can trigger this same effect – and this week’s article touches on that. By shutting certain things off and turning certain things on through drug delivery, we may be able to kick off autophagy without starving.

 

Drugs as the solution for autophagy?


I do not like this idea as much. It seems like too many people are focused on finding a drug fix for everything. Just take a pill and everything works out, right? But sadly, that does not even really “fix” the problem. I have nothing against trying to make autophagy easier for people, but why does it always have to go back to the giant pharmaceutical companies?

I am still keeping an open mind to this kind of stuff though because who knows all of its applications. Maybe the drug will be able to make autophagy happen without side-effects and in a cost effective manner. We will see. I try to remain as objective and unbiased as possible – I like to wait for all the evidence to come in.

But still, something doesn’t seem quite right about developing a drug around this. All you have to do is not eat!! Why do they need to complicate it with drugs? Fasting is always going to be cheaper, safer, and more reliable than drugs will ever be.

Summary

  • Autophagy does occur in neurons of the brain.
    • It is not just limited to one kind of neuron – but it appears as if this therapy works for all kind of brain cells.
  • Autophagy is induced to a great extent even after just 24 hours of fasting.
  • Autophagy may be the “new” treatment for Alzheimer’s disease.
    • Still, drugs are being developed with the same end in mind.

References:

[1] Klionsky DJ, Emr SD. (2000). Autophagy as a Regulated Pathway of Cellular Degradation. Science 290(5497): 1717-1721.

[2] Kim J, Kundu M, Viollet B, Guan KL. (2011). AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nature Cell Biology 13: 132-141

[3] Alirezaei M, Kemball CC, Flynn CT, Wood MR, Whitton L, Kiosses WB. (2010). Short-term fasting induces profound neuronal autophagy. Autophagy 6(6): 702-710.

[4] Veech RL, Bradshaw PC, Clarke K, Curtis W, Pawlosky R, King MT. (2017). Ketone Bodies Mimic the Life Span Extending Properties of Caloric RestrictionInternational Union of Biochemistry and Molecular Biology: Life 69(5): 305-314.

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