If the terms "rapamycin," "mTOR," and "autophagy" aren't familiar to you already, hang
on this before you tune us out. This has got some practical implications
if you want to live a long healthy life. In fact, what I'm doing. This is part
3 in a series on the book "Lifespan" by David Sinclair.
I had several requests from viewers like Jon Touch Oh who asked me to review this
and I've had a blast. It's a long book. It covers... it's encyclopedic in length in
terms of covering the major topics in longevity. One of the reasons I'm
enjoying it so much is I've done videos on most of these topics. For example,
rapamycin. Rapamycin was discovered on the island of Rapa Nui. Most of us don't
remember Rapa Nui, but you do remember Easter Island. It's the islands that have
the hundreds of statues of stone faces. Rapamycin is also known as sirolimus.
The biochemists classified it as a macrolide. You may not remember that but
if you've had involvement with medicine, you know that they are a macrolide
antibiotics. It's already being used as an immunosuppressant. It's used in stent
coatings as well as kidney transplants. It comes from a bug that was... in fact, a
bacteria that were found on the island of Rapa Nui and hasn't been found, it wasn't
found anywhere else. Streptomyces hygroscopicus. That's
Streptomycin hygroscopicus. Don't get too wrapped up in that. It inhibits
mTOR. Remember what mTOR stands for? Mammalian target of rapamycin. And you
may or may not remember, I've done several videos on this fellow.
His name is David Sabatini. He's right next door to David Sinclair at Harvard.
He's over at MIT. He's the one that discovered mTOR. And there's been a
huge amount of research growing out of that now. Why is that mTOR has a lot to
do with controlling catabolism versus anabolism and catabolism, autophagy?
Anabolism is building up, growing, and you see things like anabolic steroids
involved with that. So does that help you maybe connect the dots on why men tend
to have inflammation and cardiovascular disease and positive calcium scores
earlier than women? So there's a lot of work in that area. I also did a
separate video on autophagy. This was from a recent New England Journal
article which was just going into the depth of the mechanisms around autophagy.
You may remember autophagy is where the cell is doing recycling. So let's get
deep in that for just a second. First, you have initiation using a sequence for which
we look autophagy just means to eat. We're going to hold off on that for a
second and look at how this phagophore is growing around this dead organelle and
that organelle is it's like an organ in the body except it's within the cell. So
it's a very tiny component. If you look more deeply, you can recognize this is
the dead mitochondria that this vesicle is wrapping around. As it continues to
wrap around it, it closes up. And now then it's called autophagosome. Autophagosome,
"auto" meaning self; "phago" meaning eating. And some meaning by it's a
recycling body that's within the cell, the cytoplasm of the cell, which is
basically the suit within the cell wall and that's a material out of phases own
those then combined with what's called a lysosome. "Lyso" means to split, and again
"some" means body. So you've got these enzymes within the lysosomes. They
combine with the autophagosome to form an autolysosome. A lot of Greek words
or Latin words you really don't need to know about. But the process
itself I think is very very helpful. And then what happened? What happens is that
these enzymes from the lysosome dissolve the old dead tissue, in this case, an old
dead mitochondria. Mitochondrion then use that for energy and building blocks for
the future, for other new cell parts. Now when we've got things like insulin, too
much insulin, or insulin-like growth factor as you see here up at the top, you
get too much those tend to stop this autophagy process. So if you look at this
slide, this slide is basically to help us connect the dots
with other things that you may have heard of, like insulin-like IGF, insulin
like growth factor, AMPK. You may remember AMPK helps drive
some of these processes autophagy vs. anabolic processes.
AMPK, by the way, you may remember and Sinclair mentions in the book. AMPK is
stimulated by metformin. Sinclair by the way thinks that that is the total
longevity mechanism for metformin. We'll talk about metformin and longevity as he
did but we'll do that in another video on this series.
Remember concepts of energy depletion and starvation are fasting. Again those
help drive this autophagy process. Remember rapamycin? Rapamycin again helps
direct this process. So again, hopefully this helps you connect some dots
that you may have heard in some other videos and thank you for your interest.
So I'm very excited to announce we now have a membership page. Now, what is that?
That's the one place where you can go and access all of our digital products.
It starts off with a few free things, like a lot of infographics which help
you understand the basics of insulin resistance, cardiovascular inflammation,
and other key concepts on how to prevent heart attack and stroke. The next free
item is the intro and first chapter of the book that we're writing on plaque and
the standards of medicine just aren't doing very well right now in terms of
the number one killer and disabler. Plaque, we don't do a good job of
measuring it, we don't do a good job of monitoring it, and there are better ways.
So that's what this book is all about. Again, go in, and get a free look at the
intro and in the first chapter. And if you've purchased the cardiovascular
inflammation and IR courses, thank you so much for doing that. You purchased those
at a time before we had them totally cleaned up and we've cleaned them up now
and they're available for you right there on the membership page. Hit the
link below, register and go in, and take look. Look forward to seeing you there.
Thank you.