If you want to find a way to live longer and better,
then one of the best ways to do that is to balance the activation of the mTOR pathway.
And in today’s video, we’ll be talking about what the mTOR pathway is, why that’s such a good idea,
and how to go about accomplishing just that.
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Today, we’re back on the subject of cellular aging, and we’re going to be discussing the mTOR pathway.
I’ll be giving you a definition of what it is and how it got its name.
We’ll be discussing what happens when the activation of the mTOR pathway gets out of balance
and the effect that has on the aging process.
And finally, we’ll go over some great strategies for keeping the mTOR pathway in balance…
and extending your lifespan in the process.
OK, so the term “mTOR” is an acronym that stands for mechanistic target of rapamycin.
It also has been referred to as the mammalian target of rapamycin, and it’s an enzyme that’s encoded by the mTOR gene.
It’s a kinase, and these are enzymes that catalyze the transfer of a phosphate group
from high-energy, phosphate donating molecule to a specific substrate…
which is probably more than you need to know.
Now, the discovery of the mTOR pathway is kinda interesting.
In 1960, an expedition went to Easter Island, known to local inhabitants as Rapa Nui,
with the goal of discovering natural products from plants and soil that had possible therapeutic value.
In 1972, a small molecule from a soil bacterium was discovered to have potent anti fungal activity,
and it was named Rapamycin…paying homage to it’s original source (Rapa Nui)
and it’s activity as an antifungal (mycin).
Early testing revealed that rapamycin also had potent immunosuppressive and anti-cancer activity.
However, the mechanism by which rapamycin worked remained a complete mystery,
until 1994, when an enzyme was discovered that was the target of rapamycin in mammalian tissue.
So now, this enzyme, and the pathway that it activates,
is called the mechanistic, or mammalian, target of rapamycin…or the mTOR pathway.
OK, that’s great…but, what is it? What does it do? And why’s it so important to the aging process?
Whenever there’s plenty of calories and nutrition available, mainly protein and amino acids,
signals go out that tell the body that good times are here, we’ve got plenty of food,
we’re gonna be real active, and that we’re going to need lots of muscle and we’re gonna consume lots of energy.
The mitochondria crank up their working capacity, and ATP production goes up.
Cells divide more, and we poised to growth and repair.
mTOR is the protein that senses this and turns up the heat.
However, when the food supply is reduced and the caloric intake is restricted,
activation of the mTOR pathway is inhibited. But more on that later.
OK, here’s a little bit of science, for you science nerds.
The mTOR pathway is one of four pathways that control the metabolism,
and it controls cell growth, cell proliferation, cel motility, cell survival, protein synthesis, autophagy and transcription.
And the pathway is super complex. Here’s one diagram of all of the different signaling pathways
that make up the mTOR pathway. Here’s another.
This is all way above my pay grade.
OK, so the mTOR pathway includes two distinct complexes: mTOR Complex 1, or mTORC-1 and mTORC2.
The mTOR pathway acts as a central hub, integrating signals from upstream pathways,
including growth factors, such as IFG-1 and IGF-2, insulin and amino acids.
It also plays a role in sensing cellular nutrients, oxygen and energy levels.
So this pathway acts as a molecular switch to regulate cellular growth and proliferation in response to nutrients.
But, having all of this growth and higher energy levels…comes at a price.
Activating the mTOR pathway has both benefits and costs…and so does inhibiting that pathway.
mTOR increases energy production and performance, but it produces junk products in the process.
Now, autophagy, which is the recycling of cellular material,
is the process that breaks down these junk products and recycles them.
But autophagy only kicks in when the mTOR pathway is inhibited.
In other words, the cleaning crew doesn’t come in until after the workday is done.
But here’s the thing: while activating the mTOR pathway is great for growth and energy,
it’s really bad for extending lifespans. Apparently, tissue growth and extended lifespans are mutually exclusive.
You can have one, or the other. But not both. Think of the phrase “Live Fast, Die Young”.
Animals that grow very quickly, like mice, insects and worms, have very short lifespans.
Animals that grow very slowly, like whales and elephants, have very long lifespans.
So big, slow-growing animals live a lot longer than small, very fast-growing animals.
However, within a species, it’s just the opposite. Bigger animals have shorter lifespans than small ones.
An animal that grows larger in the same amount of time will not live as long as an animal that grows less.
Big dogs have drastically shorter lifespans than small dogs.
And the mTOR pathway is the reason why.
Too much mTOR pathway activation can also contribute to a large number of chronic diseases
like cancer, obesity, type 2 diabetes, and neurodegeneration.
Its association with cancer may come because it promotes angiogenesis,
which is the process that forms new blood vessels from pre-existing ones…and this helps cancer to grow.
Inhibiting the mTOR pathway improves insulin sensitivity and promotes autophagy.
Remember, autophagy is only activated when mTOR is inhibited.
There’s another enzyme called AMPK, which is also a kinase.
Activating AMPK both stimulates autophagy and inhibits mTOR.
I did an earlier video on AMPK, and I’ll put a link to that in the description below.
The thing that I didn’t mention in that video is that you can activate either the AMPK pathway,
or the mTOR pathway, but not both.
Activating the AMPK pathway shuts down the mTOR pathway, and kicks autophagy into overdrive.
I want to take a break right here to remind you guys to take part in a conversation and leave a comment.
Do you guys like all the science and technical detail that I tend to put in my videos…
or do you prefer to just get down to the knitty-gritty and want me to stick to just making recommendations.
Leave a comment and let me know.
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I'm shooting in my basement studio instead of on seamless in my dining room.
I like it better, but I'd like to know what you guys think. So, leave a comment and let me know.
OK, so I think we can all agree that if you want to extend your lifespan,
if you want to slow down the aging process,
then you don’t want to activate the mTOR pathway, right?
But how do you do that? Well, one clue is in the name…mechanistic target of rapamycin.
In addition to being a potent anti-fungal, immunosuppressive and anti-cancer drug,
it turns out that the pharmaceutical rapamycin inhibits the mTOR pathway.
It prevents it from activating.
Apparently, the drug is thought to work by making cells think that there aren’t very many nutrients available,
and so they go into survival mode and don’t proliferate as much.
Just as they would during calorie restriction.
In numerous studies, rapamycin has extended lifespans in mice, sometimes by as much as 60%.
In another study with dogs,
rapamycin produced similar cardiovascular benefits in large dogs as those seen in mice.
The same researchers have a second, longer study ongoing,
and it examines the dog’s heart and cognitive health more closely, in the hopes of extending the dog’s life…
and eventually, mankind’s.
But here’s the thing. Not all mTOR activation is bad. Activating the mTOR pathway can do a lot of good.
It’s required to heal wounds. For growing muscles. For more energy.
And as aging adults, we need those things.
As we get older, sarcopenia, or the loss of muscle mass, becomes more and more prevalent.
We need to stave off that loss of muscle mass, we need to grow new muscle, if possible.
We need to consume larger amounts of protein, in order to do just that.
So we need to find a balance between activating and inhibiting the mTOR pathway.
For that reason, I feel that taking something like rapamycin, which inhibits activation full time,
isn’t really the answer. Because sometimes we need to activate the mTOR pathway, particularly as aging adults.
We need to appropriately cycle between periods when the mTOR pathway is activated,
and we’re growing new muscle tissue, we’re healing, and we’re boosting our energy production…
and periods when the mTOR pathway is inhibited and instead, the process of autophagy is activated,
and we’re clearing out toxic cellular waste.
Since the primary activating factor seems to be the presence of excess amino acids,
one of the ways that I’m going to try to balance the inhibition and activation of the mTOR pathway
is through changing my protein intake. Now, admittedly, this is going to be difficult to do,
and I’m not really sure that I’m disciplined enough to pull this off.
So here’s what I’m gonna try and do.
As many of you know, I take a lot of my protein in the form of PerfectAmino.
It’s a form of the 8 essential amino acids needed by humans for tissue growth…like muscle tissue.
It’s protein utilization index is 99%, meaning 99% of it is utilized to synthesize new proteins,
it has 0 calories, and it’s absorbed by the body in 23 minutes.
However, just because it has 0 calories doesn’t mean that it doesn’t activate the mTOR pathway.
It does.
So, on the days that I weightlift, the days that I’m trying to build new muscle and stop sarcopenia,
on those days I’m going to up my intake of PerfectAmino, to 6 scoops of the powder.
Which is equivalent to 30 tablets.
Now, according to the International Society of Sports Nutrition,
the ideal window of time for consuming protein to build muscle mass,
is any time up to 2 hours after your workout.
So I’ll be drinking that shake within 2 hours of the time that I finish my workout.
On the days that I’m not weightlifting, I’ll only take 1-2 scoops.
Since I’m now on a Keto diet, that means that I’m only eating an adequate amount of protein anyway.
Now, I’m having a bit of trouble calculating what an adequate amount of protein is,
since a lot of my protein is coming from PerfectAmino and is non-caloric.
If any of you guys have figured this out, leave me a comment below. I'm struggling with it.
The key here is over-activation.
From what I’ve read, it seems that over-activation is far worse that adequate activation.
So, on the days that I’m not weightlifting, I’m restricting the amount of protein that I consume
and I’m hopefully not over-activating the mTOR pathway.
On the days that I am weightlifting, I’m taking consuming more protein to build new muscle,
but hopefully, I’m still not over-activation the pathway. But even if I am, I’m only doing it when I need it.
One other thing. Although the mTOR pathway is activated in the presence of amino acids,
recent research seems to point to the amino acid methionine as the one the has a primary effect.
Studies have been done that demonstrate that a methionine restricted diet
is effective in inhibiting the activation of the mTOR pathway.
Now, personally, I don’t see myself doing that because methionine is present in most of the proteins that I eat.
Like lean beef, salmon, egg whites, tuna and most nuts…except macadamia nuts.
They’re really low in methionine.
OK, the other way that I’m going to try and balance the inhibition and activation of the mTOR pathway
is by activating autophagy and inhibiting mTOR, and I’ll do this by activating AMPK.
And one of the best ways to do that is by doing high-intensity interval training.
Doing HIIT boosts autophagy and AMPK activation, but not mTOR activation.
So, on those days that I’m weightlifting and trying to boost cellular growth and the mTOR pathway,
I’ll be consuming much more amino acids,
and on those days where I’m trying to inhibit mTOR and boost AMPK activation and autophagy,
I’ll be consuming less amino acids and performing a session of HIIT.
Unfortunately, there’s no way to measure how any of this is working, that I know of.
There’s no way to know when mTOR is activated and when AMPK is activated.
I think I can assume that if I’m increasing strength and muscle mass, then mTOR is being activated…
and if I’m improving my cardiovascular fitness and my mitochondrial health, then AMPK is being activated.
But the only way to know for sure is to check-in in about 10 or 20 years and see how this old body is holding up.
So, for now, I think I’ll stick with this program.
at least until something better comes along as the result of the continuing research into aging.
So, we’ve talked about how the mTOR pathway works
and how destructive it can be to extending the human lifespan.
But we’ve also talked about the many benefits that can be obtained through the activation of the mTOR pathway,
and we’ve talked about the need to balance activating this pathway with activating the AMPK pathway.
And finally, we’ve talked about my own personal strategy for maintaining a balance between the two.
OK, that’s it for me.
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OK, that’s it…I’m done, I’m outta here. See you guys next time. Thanks you so much for watching.