So I was out working out of the gym last week and YouTube flipped up a video on
Autophagy. I was a little bit surprised. I usually end up talking about Autophagy
with most of my cardiovascular prevention patients but you can usually
see it - sort of like a "Yeah, I've heard of it but I don't know what that means" so
again, I was surprised (very pleasantly) that it's now hitting the YouTube
vocabulary. This doc is Dr. Boz. She's got a great YouTube channel community
focusing on low-carb and fasting. it turns out just a few years ago she was
an old style internist - didn't know anything about either of those topics
until her mother got very ill, she ended up studying these and she and her mother
got into low carb and fasting and had a significant positive impact on her
health. Now the rest of her family's into it. She's got a large community doing it.
Anybody that spends any time on internet and health related topics usually ends
up seeing some of the usual suspects -Joe Mercola, Erik Berg. I found that (sure
enough) Erik Berg has a video on autophagy and he's got a lot of the
concepts right. Autophagy - I'll explain. We'll go into the details
of what that means in a few minutes but it's garbage recycling - just like he says there.
I'm gonna go - I'm gonna describe a Nobel Prize that I think created a lot
of the recent awareness. It was Nobel Prize for medicine in 2016. It was for autophagy
Some work a fella (named) Yoshinori Osumi did, but I'll cover that
and then I'll talk about a great reviewer article in the New England
Journal which goes a little bit more into the detail and gives some good
pictures. Everybody loves pictures - makes it
easier to understand what's going on but before we do - just a brief introduction:
My name is Ford brewer F-O-R-D Brewer B-R-E-W-E-R. I started off as an ER doc in the
panhandle of Florida but got frustrated very quickly because the vast majority
of things that people - that bring people into the ER are things that should have
been prevented. I decided to go get more training. There weren't a lot of places
in the country that trained in preventive medicine. Most of its just
focusing on a cure. I went to Hopkins, ended up running the program and still
am loving doing prevention. This channel is a - is a way of sharing prevention with
anybody that's interested and giving - hopefully, arming you with the
information that you need to impact your own health. Of course, you need a -
You often need a doc to help but when you start talking about prevention, the vast
majority of these issues - you don't need a doc to do. So anyway, back to Autophagy
and the 2016 Nobel Prize. the winner was - for medicine, the winner
was Yoshinori Ohsumi and the the work that he did started in the early 90s and
went mostly through the 90s, so he got his Nobel Prize 20 years later. He was
working - he started his work with baker's yeast. He first identified the genes
essential for Autophagy, then the enzymes and went on to elucidate
the mechanisms in yeast and then showed that there's similar machinery and
processes and mechanisms within ourselves so this led to a new paradigm
in our understanding of how cells recycle junk, worn-out mit-
anything from worn-out mitochondria to viruses that have invaded us to torn bits of
protein. So cancers, neurological diseases and, as some people like Brad Bale and
Amy Dineen and some others have been saying for decades, also cardiovascular
disease. All of these things are very much related to to cleaning up junk in
our cells. So, how can that be? Well again, we'll get a little bit more into detail
on this. This is one of the first - I'm just gonna go through the pictures for
the most part on that New England Journal article and I'll give you a
link to that article under the video. This is first - this goes into the process
and again as you start looking at it, it's very, very helpful. The first part is
called an autophagosome or a phagophore. its vesicle elongation, in other
words, there's a - there's a phagophore. this is a little pocket here in the cell
This green thing is a mitochondria that's broken. It's not working very well
The cell recognizes that and this phagophore begins to encircle it. Then it
completely engulfs it. at that point, it's called a mature autophagosome. again
"Auto" - meaning self; "phage" - meaning to eat; and "some" - meaning a body. So a body used
to eat the part of itself within the cell. Now, lysosome - remember "some" means a
little body. "Lyso" means to split. So you've got the damaged mitochondria
isolated in autophagosome, then you combine it with a lysosome. Now, how do
the lysosomes releases enzymes which digest the defective, beaten up, worn-out
broken mitochondria and, again, that's what lysosomes are - are basically pockets
of enzymes which are used to digest trash material. So you put that lysosome
with the enzymes - the digestive enzymes together with the autophagosome with
the junk in it and it begins - the digestive enzymes begin to digest and
end up digesting the junk. That junk is then reused after it's been digested
by the cell to rebuild new organelles. Now, I'm not going to go into this very
deeply. It's difficult to see but there's just a couple of components here that
help you begin to think about some of the lifestyle issues that we've been -
we've been hearing a lot about recently. Let me just read a couple of things:
nutrients signals modulated signaling process depending on mammalian - the
target rapamycin mTOR. You've heard that a lot. AMPK you've heard a lot. now what
you have - and here's another thing that you've heard: insulin has a negative
impact on this process: fasting, starvation
Here you see (that) starvation and rapamycin increase this process. So, again, you see
this mentioned multiple times in this article how starvation or fasting
increases autophagy and how insulin decreases autophagy. Again, so now you're
beginning to connect the dots. Cardiovascular disease like many other
diseases of aging tends to be a disease where you get a
lot of buildup of junk in the cells because
as we develop insulin resistance, you get higher and higher levels of basal
insulin and that basal insulin just slows down and stops the autophagy
process. In addition, being overweight, we start getting into a vicious spiral of
gaining weight. Our blood sugar is too high, our insulin gets too high and stays too
high trying to push that blood sugar down and, again, in multiple ways we're
not - we're not stimulating autophagy. Now, what does autophagy got to
do with this? This shows the impact of autophagy on several different types of
diseases. Infectious diseases is the first and easiest to show and (I recopy
this a little bit larger so you can see it) the one down at the bottom is showing
infectious disease. Xenophages. "xeno"- means outside so
these are viruses and bacteria that have been caught and engulfed into an autophagosome
and then the lysosomes have been combined with this autophagosome
to digest the bacteria and viruses. So again, these are some of the things that
autophagy does with infectious diseases - up here with cancer, again
similar process. You get cell death, chemo sensitization, and tumor suppression.
- suppression. In other words, you kill cancer cells. I'll just give you a brief
{pardon the skin there) but you see, I've got basal cells and I've been using a
medication which stimulates the inflammation process and autophagy
again, that's this process going on with cancer. I'll do another video on that - it
actually makes the point that inflammation is not always bad.
Sometimes, you need inflammation to kill cancer cells. Now (but that's not what
this video is about) this video is connecting that - it's showing some of the
visual processes associated with autophagy and what they have to do with
plaque, cardiovascular disease... Unfortunately, the bottom of this is cut
off but this lower left-hand corner talks about vascular disease, plaque
stabilization, regulation and proliferation. As you see here, this is
an arterial - an artery on cross-section. Down in the bottom, they've got a plaque
Now, what's this apoptosis? Actually, apoptosis
is cell death. Well, what does cell death got to do with this? If the
inflammatory process that we're talking about is mast cells going in and
polymorphs - the two types of cells that we know that will eat plaque, then you
can get a cell death. These cells can get too busy, too active. The lysosomes
actually pop within the cell and there's too many of them and kill the cell
itself. That results in hot liquid plaque. So, again I hope this helps to connect
some of the dots between our immune system attacking our plaque and the
role of autophagy. Autophagy is very - it's critical to getting rid of plaque
stabilizing it, but if we have too much of it going on too quickly, it can cause
danger by apoptosis - killing cells. I hope
this has been helpful. I'm not going to go into some of the other details in
this review article. there's a lot of diseases which we've discovered which
are related to problems with autophagy - inflammatory diseases, Crohn's disease,
actually Parkinson's disease, Paget's disease, ulcerative colitis - again, if
you've made it this far thank you very much for your interest