-: All right, now we're gonna draw up
a cascade of events on how some of this stimuli
to adaptation is occurring with the different parts
within the muscle cell and also outside the muscle cell.
So let's talk about just the very simple thing
of just actually doing some training
that's not super damaging first.
So we have our muscle cell here.
So we have our sarcomeres here
in the individual muscle fiber.
And we're gonna be doing some work here.
I've got my little green mitochondria,
he's gonna be pumping out energy
to fuel this training session.
So I'm going to be going through that,
stimulating some AMPK.
He's gonna have to make the energy
in order for me to be able to switch over.
He's gonna have to make that ATP,
which means somehow I'm going to have to be
getting nutrients in here to do that.
So provided I have some nutrition,
I have some glucose coming in,
and I have enough amino acids available,
we are going to be able to run
some of these hypertrophy processes.
The main one that most people are associating
hypertrophy with is gonna be protein synthesis.
And our energy manager for that is gonna be mTOR,
that thing that kind of goes the opposite of AMPK.
So we trained, didn't do, we just did,
we got enough volume of tension to get some stimulus here.
The way this cascade works is energy balance
gets restored if there are sufficient nutrients.
I'm gonna stimulate mTOR.
MTOR is then going to give permission
for the ribosomes to then start to be active.
And what's gonna happen when we go through this process
is there's going to be some signals sent
from mTOR to the ribosome to say hey,
you guys are gonna start doing some work.
And then there's gonna be a signal to the nucleus
to say hey, we need to transcribe some mRNA
for these ribosomes to read.
So now we're starting to actually get in there,
translate some of that DNA, and then it's gonna
come over here and that ribosome
is gonna transcribe that into amino acids.
So if I have enough, remember that lysosome
where this mTOR thing is gonna sense that
and we're gonna say okay, we have enough stuff,
this guy can actually start making
the proteins that we need, okay?
The reason that, basically this communication
has to happen in tandem, is two things
need to be going at the same time.
One is energy balance needs to happen before any of this.
So if I start, like if I start copying blueprints
but there's no workers to do it, well that's not a good job.
If I hire workers with no plans on
what they're supposed to do, that's not good.
So energy has to happen, energy balance has to happen first,
then I can stimulate these two things.
I can be hiring the workers, getting the plans in order,
and then construction can then occur in terms of
those amino acids being turned over into protein.
So let's say we're going to pick it up a little bit,
we're going to increase the stimulus a little bit more.
So one of the things that's gonna happen
as we produce more tension is we have this sensor.
So there is a line here where the sarcomeres kind of meet.
And we call that the Z line.
And so that's basically, you have your sarcomere,
which is where those little contractile
fibers exist and kind of work.
You've got your actin and myosin
contracting together to shorten.
At the end of each sarcomere where it meets another one,
there is this line where they
are essentially stuck together.
And you have the structure in there
that is tension sensitive.
So as it gets kind of stretched
by the muscles actually contracting,
or the sarcomeres contracting on either side
and stretching that, there's a conformational change
that causes some signaling to occur.
And what that actually does is it works upstream of mTOR.
So you have this stress that's gonna say hey,
we should run some protein synthesis.
Because what that tension is sensing is like,
if I'm giving tension here, that means these
contractile fibers that are doing the work
are probably sustaining some damage.
So the more I do that, and the sort of volume
and intensity both come into play,
so the more tension and the more of that,
the stronger that tension signal is gonna say hey,
we should be turning on protein
synthesis or getting it ready to go.
Because as soon as we have the resources capable,
we're gonna want to repair all this damage
that I'm perceiving is about to happen.
That's a way for my cell to assess
that there's likely gonna be a need for protein synthesis
before inflammation has even come in to occur.
So this is where we can get creative programming
that's like hey, how can I do that
and minimize inflammation or whatever?
We'll look at all the different ways of
kind of edging out certain of these stimuluses later.
So, but remember, without this permission from the energy
status of that cell, all of this is for naught.
Doesn't matter.
Still have to have that.
But provided I am gonna have the nutrition,
I'm already getting kind of like a preemptive,
we're gonna do protein synthesis
as soon as this workout's done.
And energy balance is restored.
But this mitochondria could come in and be like,
no sir, you do not get to do that.
We do not have enough energy.
It's not actually the mitochondria,
but it's the elevated AMPK because the mitochondria
hasn't replaced all of that energy yet.
Or glycogen levels are too low,
we have to get some carbohydrates in there.
Or amino acids are not sufficient.
And that's actually the lysosome is gonna say hey,
mTOR, you can't be active yet,
we don't have the resources to do that.
So keep in mind, all of this still is dependent
on that backbone of having enough nutrition to do it.
So that's preemptive, before we actually get any damage
or at least even know it exists.
So what happens when you actually get the trauma?
So we've got tension there,
but we're doing enough eccentrics,
we're doing enough work at fatigue, whatever it may be,
where we're actually starting to get,
forgive my crude art here, some damages in those sarcomeres.
Okay?
And that damage can happen at the Z line,
it can happen within the contractile tissue.
It can happen both places.
What you will see if you look at muscle
that has been really overloaded
is that you will see trauma at both.
But this Z line, which is a nice straight line,
will actually start to look staggered as it,
like it's really been put under a lot of tension, okay?
So what needs to happen then is wherever this
broken stuff is, that needs to be repaired.
But that starts with it needs to be cleaned up.
All the broken stuff needs to be
completely broken down into usable parts again.
So my immune system is going to come in here
and it is going to resolve that.
It's going to start by breaking down
the tissue to the point where now we can be rebuilding it.
As it's doing that,
those amino acids are gonna get recycled.
They are going to go to that lysosome,
where now mTOR can sense we're having more raw materials.
Okay, so if everything else is in order,
I got this preemptive signal that I would like
mTOR to run when it is appropriate.
I got inflammation coming in and doing its job
of breaking this down, getting those amino acids over.
In the short term, this guy here is going to be blocking
nutrition from the outside saying hey,
let's hold off on getting a bunch of stuff in here
until I've finished breaking this down.
So there's gonna be a little bit of a lag here
in terms of when this mTOR actually gets activated now
because this inflammation process is kind of saying hey,
hold that off, that could interfere with energy production,
it could interfere with amino acid uptake.
Whatever it may be.
It's just gonna be a delay.
Now that may be a delay of minutes to days
depending on how much inflammation you decided to create.
Okay?
Because we have a certain amount of immune cells,
or inflammatory enzymes in our cells in at all times
just kind of doing maintenance cleaning.
So a little bit, no big deal.
A lot of it, especially an excessive amount,
could be potentially very bad in terms of
can I switch over to doing this fast?
But at the same time, when we look at training,
remember there is going to be a
threshold that we do need to hit.
So it's not that, like, inflammation is bad
because it slows things down, it may be a necessary evil
in certain people that have a certain level of adaptations.
So that's gonna happen there, right?
Short term blockage.
But we get some other benefits
from that inflammatory process.
So one of the things we get from inflammation
within a muscle cell is that we
reach exterior to the muscle for help.
And this is one of the best things that you can do
for potentiating muscle growth in the future.
So we have these things called satellite cells,
who are essentially, they're stem cells.
They're blank cells.
They're cells that have all of the ingredients of a cell,
but they're not doing anything.
They haven't been coded to become any type of tissue yet.
They're essentially a clean slate.
And what they can do is they can
come and they can donate that nutrient.
So we talked about this in the myonuclear domain discussion.
So that inflammatory process is that hey,
stuff in here is damaged.
So we would like things from the
satellite cells in order to repair that.
Because we don't always just get
damage to the contractile protein.
Sometimes we get damage to organelles.
Sometimes we get damage to the cell wall.
And that tends to happen more from the
oxidative stress that gets created.
So, but inflammation is inflammation.
Damage is damage.
So regardless of how that damaged occurred,
what's gonna happen is this guy is gonna go and release some
of those local growth factors that we were talking about.
And they are going to reach out to the satellite cells.
And what that's gonna do is it's gonna create two things.
Some of those satellite cells are going to come
and they are gonna donate their contents.
So we get everything.
We get the mitochondria, we get the nucleus, the lysosomes,
the ribosomes, everything that was in that cell
becomes now a part of the muscle cell, okay?
The other thing that you're gonna get
is these guys are going to duplicate, right?
So you actually get a division.
Some satellite cells, so say you have
50 satellite cells and we send the signal, okay?
An appropriate ratio would be half of them
are going to donate and half of them are gonna duplicate.
That way what happens is that pool
of satellite cells stays at 50.
Okay, that's what should happen.
Now this is one of those things where
when you look into the bodybuilding realm
and stuff like that and people are using drugs and stuff,
you can upset that, you could have too many donating
and all of a sudden the satellite pool gets small.
Because how big that pool is is the potential
for how much can be donated to help me recover.
So two things need to happen there.
One is I need to stimulate some of those
satellite cells to donate and then I need to
stimulate the remainder to duplicate.
So that's referred to as proliferation and differentiation.
So when a satellite cell becomes part
of the muscle tissue, it differentiates itself.
So it changes from a satellite cell
to part of the muscle cell.
When we proliferate, that just means they duplicate.
They become just more of themselves.
So both of those things are going to be
happening outside of the muscle tissue.
So this happens, there's these little pockets of these
all over in the body for this very purpose.
Inflammation that most of the time is thought of as
a negative is important for driving this process.
The biggest thing that we get out of that,
I mean one, we get some mitochondria, which is always good.
But from a hypertrophy perspective,
from a potential to do protein synthesis later,
the best thing that we get is we get more nuclei.
So this black guy right here that represents that,
that is one of these nuclei.
So that means we have more DNA.
We have more instructions to build protein.
That means I could potentially have also then more workers.
Because if I have more instructions,
more workers can be working.
If I have more instructions and more workers
and I have more money and more resources,
because I am metabolically conditioned
and I am matching my nutrition to my training stimulus,
I'm getting all the food in at right times,
well now the rate at which I can
do protein synthesis drastically goes up.
So when we're looking at potentiating
the ability to grow a muscle faster,
to be able to recover from more strenuous workouts,
more damaging workouts, a huge aspect is being able
to improve that myonuclear domain and the metabolic level
or metabolic conditioning of that cell.
Whether that be through enzymes or number of mitochondria,
preferably both, now I'm in a position
where my potential is much higher, okay?
So one of the things that we will get
when we have a certain threshold,
instead of the mTOR just saying hey ribosomes, do your job,
what you will actually also do, instead of just decoding
that DNA for the proteins that you're gonna make,
you will also decode protein to make new ribosomes.
So you'll have more ribosomes
and that's how you get the more workers as well.
So having more nucleus increases
my ability to do protein synthesis.
This also increases my ability to replicate more ribosomes.
Now this is a very important process,
this whole satellite cell donation.
So normal cells that only have one nuclei,
like a skin cell for example, when it duplicates,
it can duplicate its nucleus.
So it can just literally become two cells.
Your muscle cells don't ever do that.
They don't duplicate everything and then divide.
The reason being is that in order for that to happen,
that cell actually has to become essentially dysfunctional.
Like, when it's going through that process,
it is no longer contributing to the rest of the body.
Our muscle cells are needed every day for movement, right?
If we could not move, we could not survive.
We could not get food, we could not prevent ourselves
from becoming food or just avoiding just natural danger.
So we always need our muscles
to be functioning in some capacity.
They don't get to take time off to duplicate.
So the only way that you are going to essentially get
quote unquote more muscle cells is we have to get
enough of these nuclei from those satellite cells.
And then when a muscle cell accumulates enough,
if there is enough stress on the system,
this is a complicated thing.
But if there's enough stress in the system,
the myonuclear domain happens,
what a muscle cell will do is it will split.
It will not replicate and divide like a regular cell,
but because it has so many,
if it's accumulated a ton of nuclei,
well it technically has enough that it could become two
and each of those would still have enough nuclei
and enough mitochondria, enough organelles to function.
And then they could then grow and prosper
by taking up more satellite cells in the future
without ever really taking time from being,
or taking time off, per se.
They were still able to contract
and contribute pretty much that entire time.
Basically the only thing that has to happen
is that just a new little layer of cell membrane
just has to form in between and then we get that.
It's referred to as hyperplasia instead of hypertrophy
because the muscle is not actually growing in size.
It's the same sized muscle,
it's just becoming two cells instead of one.
It's just getting cut in half,
it's not actually duplicating its contents.
So, back on track here.
So we have this process going from damage,
inflammation, all right, leads to that satellite
cell signaling where we're getting
differentiation down to the muscle cell.
Donating the contents, proliferation to restore that.
That gives us a net increase in the amount of nuclei I have,
which means now I can make more protein
and I can make more ribosomes which accelerates
my ability to make more protein.
And an important thing, we talked about these ribosomes,
is we have more than just contractile
tissue that's made out of protein.
So this helps these cells recover period,
not just from mechanical damage.
The other source that we were talking about
in terms of signaling here was oxidative stress, right?
And that's gonna come from this guy, right?
So we've got our oxidative stress here.
He is going to cause damage as well, right?
So this guy is going to damage some proteins there,
damage some stuff there, okay?
That same damage is going to have this cascade as well.
So these are going to need to be
cleaned up by the inflammatory process.
Inflammation, inflammation.
Signaling is going to be the same.
The difference being is that when we damage things
from a chemical level, we may not be able
to salvage those amino acids or those fatty acids,
depending on where the damage happens to occur.
So an important thing to understand
with what is being damaged is when we do mechanical damage,
it's mostly going to be this contractile tissue
that takes the blunt of the work or the blunt of the damage.
When we create oxidative stress,
these oxidants can be going all over the place.
They could be damaging the mitochondria,
they could be damaging ribosomes,
the cell wall, the endoplasmic reticulum,
like all of these different things can be getting damaged.
So what needs repaired and what signals are being sent,
while they're still going to reach
out to these satellite cells,
the internal mechanisms of what the inflammatory process
and the immune system is gonna
be doing may very much differ.
So the amount of mTOR stimulation I get from oxidative
stress versus mechanical damage are going to be different.
'Cause from a mechanical damage,
I'm getting that influx of amino acids that's being recycled
whereas with the oxidative I may not be getting as much.
So if you are thinking of what is the most ideal way
to get these satellite cells to donate their contents
to run through that differentiation phase,
is it these very extreme metabolic
oxidatively stressed-based workouts
or is it these very mechanically damaging workouts?
And really, that's going to come down to the individual
and what is gonna be safe for them to train,
what they're going to be capable of training,
what they can nutritionally fuel.
Maybe there's a functional component
that goes along with this on whether or not
they're doing a sport or have an activity that requires
a lot of strength versus a lot of conditioning.
What's their relative trainability
for dealing with oxidative stress?
Are we trying to maybe double dip, getting this and also
some mitochondrial adaptations at the same time?
Different reasons that you would go one way or another.
But all things considered equal,
if my main goal is hypertrophy and everything else was good,
I'm going to get more advantage from the mechanical damage
than I am the oxidative stress in this case
if my sole purpose is getting these satellite cells
there for the hypertrophy only stimulus, okay?
So take all of that into context.
So complicated interactions that are gonna go along
at all of these phases where hey,
this could or could not happen depending on energy.
So satellite cells, guess what?
They need fuel to differentiate
and they need fuel to proliferate, okay?
More to proliferate than to differentiate, right?
So if I create a lot of damage
but don't have enough nutrients, guess what happens?
That satellite is going to get smaller over time,
decreasing my ability to recover from this type of training.
So when we're looking at all of this stuff, just remember
there's a lot of places where this isn't just like,
you do this, magic happens, we get hypertrophy.
There are ways of all of this stuff getting shut off.
So we need to have a healthy inflammatory response,
not an overactive inflammatory response.
And we need to have a healthy way of managing
oxidative stress.
We need to have mitochondria that can function well,
both to eliminate oxidative stress that's excessive
and to be able to produce ATP efficiently
to be able to get my body back in an energetic state
where this whole process can run.
I need to be efficient at getting nutrients into these cells
so that I have the raw building blocks
so that I can have permission to run this process
and then actually have the resources
to carry it out to completion.
And then the damage that I do incur should not exceed
whatever this recovery repair mechanism is.
Because there's a certain amount that you can recover from.
You have a certain number of ribosomes
and a certain number of nuclei today, right?
That is how much,
or what your potential is to recover today.
If you do more damage than that potential,
you will not net extra muscle mass.
If anything, what it's gonna do
is these guys are gonna have to work for longer at best.
And what that's gonna do is it's
gonna decrease your training frequency.
So you're going to spend more time recovering
from this session just to get back to baseline.
Whereas if you were to pick the appropriate amount,
you would have recovered faster, actually made progress
because your recovery would have exceeded the damage.
So your body would have been able to say hey,
let's invest a little bit in our future,
build a little bit more muscle than we had going in.
And then next time, we're able to stimulate that sooner
because we can train with a little bit more frequency.
So more is not better in terms of mechanical damage.
So there is a certain threshold of what we will need
to get all of this stimulus to happen.
But beyond that threshold is not
necessarily always better results.
Now where there is some like, we'll say
proportionate benefit will be like this Z line stuff, right?
There's a certain volume needed for that to happen, okay?
There is going to be a certain amount
of inflammation that needs to occur for this to happen.
But it's not more is better.
Where, as some of these stimuluses, like just the
tension-based but not extremely damaging stuff,
that there's more of a volume threshold.
So you'll take that into context
when we look at are we overloading the eccentric
to accomplish the mechanical damage?
Are we spending more time going to failure
and doing forced reps and things like that
to accomplish that mechanical damage?
Because you create more mechanical damage
when you're closer to failure.
Because what happens is fewer of these muscle fibers
have the ability to keep handling the load,
so it's essentially, as you get tired,
it's essentially like the weight is getting heavier
in terms of the perspective of these individual sarcomeres
because some of them are just exhausted
and can't actually help anymore.
So it's like, the equivalent of you holding a weight
and then letting go with one arm, right?
All of that weight gets transferred to the other arm.
And that's what happens as these sarcomeres start to
fatigue, these muscle cells and fibers start to fatigue,
is it starts putting more stress on the remaining ones
and then that kind of goes cyclical as you go
from contraction to contraction to contraction.
So training more sets to failure
or spending more time near failure total,
more volume total close to failure within a workout
is another way of creating more of that mechanical trauma.
So it's very important to distinguish
that volume of work to the volume
of work that's at a lower threshold.
So and this is where we really get into being
able to dial in the appropriate sets and reps
and stuff for an individual to find that right threshold
for them to get the maximum benefit.