mTOR Signaling & Growth (Mammalian Target of Rapamycin)

kennycro@@aol.com

Level 6 Valued Member
Cliff Notes of mTOR Signaling & Growth (Mammalian Target of Rapamycin)
Podcast https://hvmn.com/podcast/mtor-signaling-&-cell-growth-ft-dr-keith-barr-ep-109

The first 36 minutes of the podcast is about mTOR.


1) mTOR signals and promotes muscle growth.

a) Exercise triggers mTOR, muscle growth.

b) Leucine (amino acid) in the right amount promotes muscle growth via mTOR.

c) Leucine elicits mTOR in a different way than Exercise.

d) "...If you only have one, you only get part of the response."

c) Exercise with the right amount of Leucine elicits a synergistic (additive) effect; Kenny's metaphoric analogy, 2 + 2 + 5!

2) AMP-k, Activated Protein Kinase

a) AMP-k inhibits mTOR

b) Low glucose, Fasting and the Ketogenic Diet activate AMP-k.

3) Increasing Life Span

a) Low Carbohydrate Diets increase Life Span 6%

b) Ketogenic Diet increase Life Span 13%

c) "...The increase in lifespan the result of the ability to inhibit baseline mTOR activity."

d) "mTOR is really important for cancer growth."

e) "...What happens as we begin to age, ... Baseline inflammation goes up. ...What the ketogenic diet does, it keeps the baseline down."

3) Maintaining Low mTOR Baseline For Health

Extrapolated information from the podcast...

a) Chronic elevation of mTOR promotes heath issues.

b) Low Carbohydrate Diets, Fasting and the Ketogenic Diet maintain a low mTOR Baseline; promote health.

4) Acute Elevation of mTOR For Strength/Increasing Muscle mass

a) Acute/short spikes of mTOR increase Strength/Muscle Mass.

b) Exercise specifically "Targets" the activation of mTOR to the muscles worked. Leucine or Leucine rich proteins consumed are shuttle directly to the muscles trained.

c) When Leucine or a Leucine rich proteins are consumed without Exercise; Leucine has a "Global Growth Effect". Growth of all cells are promoted, like cancer

6) Increasing Some Muscle Mass While Decreasing Other Muscle Mass For Sports

1) British "Sky City" Cycling's Program

a) ..."They want to get rid of the upper body. They want to maintain legs, because that increases power to weight ratio."

b) "...Give them a very low caloric diet. ...Have them take all of their calories in around their exercise, ...give them all calories that are gonna be leucine rich proteins, so that it's gonna be targeted to the muscle that we want to maintain. ...They maintained leg strength, leg size, in an individual who had a 3 to 4 kilo loss in upper body mass. So you waste the upper body mass, because you don't need it, and then you maintain the lower body mass by using the exercise as a way to target the nutrients."

"...You target by using exercise as a targeting device."

"...If I do an exercise session, and I take it (Leucine) right afterwards, and I've got lots of blood flow going to the muscles they just worked, what you've basically done is you've taken an envelope that you've put into the mail, and you've put an address on it. So same nutrients, same supplement, but now by using blood flow that I've done, I've targeted to the muscles I want to target by using exercise, now everything that I just took in is going to go to the place that I want it to go."

"It's the same thing that Lance Armstrong did during his cancer rehab. So, he was getting chemotherapy, he was taking in calories, and he was cycling through this. So as he was cycling, he had been a triathlete, he had been a guy with big upper body, big back, big shoulders. And then as he's cycling with chemotherapy, the chemotherapy and the nutrients are all getting targeted to his muscles of his legs, so he maintains. The chemotherapy targeted him and he lost a huge amount of upper body mass. And it was a lot of muscle mass that he lost. And so that increases power to weight ratio and gave them this great advantage."

7) Nutrient Timing Window For Leucine/mTOR

...It's not that there's a window where you have to get in within a certain amount of time. Because the window is quite big and it's quite open.

Kenny Croxdale
 
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Al Ciampa

Level 8 Valued Member
Certified Instructor
Cliff Note of mTOR Signaling & Growth (Mammalian Target of Rapamycin)
Podcast https://hvmn.com/podcast/mtor-signaling-&-cell-growth-ft-dr-keith-barr-ep-109

The first 36 minutes of the podcast is about mTOR.


1) mTOR signals and promotes muscle growth.

a) Exercise triggers mTOR, muscle growth.

b) Leucine (amino acid) in the right amount promotes muscle growth via mTOR.

c) Leucine elicits mTOR in a different way than Exercise.

d) "...If you only have one, you only get part of the response."

c) Exercise with the right amount of Leucine elicits a synergistic (additive) effect; Kenny's metaphoric analogy, 2 + 2 + 5!

2) AMP-k, Activated Protein Kinase

a) AMP-k inhibits mTOR

b) Low glucose, Fasting and the Ketogenic Diet activate AMP-k.

3) Increasing Life Span

a) Low Carbohydrate Diets increase Life Span 6%

b) Ketogenic Diet increase Life Span 13%

c) "...The increase in lifespan the result of the ability to inhibit baseline mTOR activity."

d) "mTOR is really important for cancer growth."

e) "...What happens as we begin to age, ... Baseline inflammation goes up. ...What the ketogenic diet does, it keeps the baseline down."

3) Maintaining Low mTOR Baseline For Health

Extrapolated information from the podcast...

a) Chronic elevation of mTOR promotes heath issues.

b) Low Carbohydrate Diets, Fasting and the Ketogenic Diet maintain a low mTOR Baseline; promote health.

4) Acute Elevation of mTOR For Strength/Increasing Muscle mass

a) Acute/short spikes of mTOR increase Strength/Muscle Mass.

b) Exercise specifically "Targets" the activation of mTOR to the muscles worked. Leucine or Leucine rich proteins consumed are shuttle directly to the muscles trained.

c) When Leucine or a Leucine rich proteins are consumed without Exercise; Leucine has a "Global Growth Effect". Growth of all cells are promoted, like cancer

6) Increasing Some Muscle Mass While Decreasing Other Muscle Mass For Sports

1) British "Sky City" Cycling's Program

a) ..."They want to get rid of the upper body. They want to maintain legs, because that increases power to weight ratio."

b) "...Give them a very low caloric diet. ...Have them take all of their calories in around their exercise, ...give them all calories that are gonna be leucine rich proteins, so that it's gonna be targeted to the muscle that we want to maintain. ...They maintained leg strength, leg size, in an individual who had a 3 to 4 kilo loss in upper body mass. So you waste the upper body mass, because you don't need it, and then you maintain the lower body mass by using the exercise as a way to target the nutrients."

"...You target by using exercise as a targeting device."

"...If I do an exercise session, and I take it (Leucine) right afterwards, and I've got lots of blood flow going to the muscles they just worked, what you've basically done is you've taken an envelope that you've put into the mail, and you've put an address on it. So same nutrients, same supplement, but now by using blood flow that I've done, I've targeted to the muscles I want to target by using exercise, now everything that I just took in is going to go to the place that I want it to go."

"It's the same thing that Lance Armstrong did during his cancer rehab. So, he was getting chemotherapy, he was taking in calories, and he was cycling through this. So as he was cycling, he had been a triathlete, he had been a guy with big upper body, big back, big shoulders. And then as he's cycling with chemotherapy, the chemotherapy and the nutrients are all getting targeted to his muscles of his legs, so he maintains. The chemotherapy targeted him and he lost a huge amount of upper body mass. And it was a lot of muscle mass that he lost. And so that increases power to weight ratio and gave them this great advantage."

7) Nutrient Timing Window For Leucine/mTOR

...It's not that there's a window where you have to get in within a certain amount of time. Because the window is quite big and it's quite open.

Kenny Croxdale
Great write up, Kenny. mTOR is Peter Attia’s hobby also.
 

HUNTER1313

Level 6 Valued Member
So.....
1 c, if us heavy construction workers hauling heavy stuff around all day take some leucine during the day is good?
2, but we can't 1 c as it may promote cancer and affect our lifespan.
4 c, if we do take leucine since pretty much every muscle is being worked at any given time, it will be a "global growth effect"
6 b, so we want some leucine/protein while we're working to maintain the muscles we're using which is obviously the ones used daily and repeatedly. Pretty much whole body.
7, so we don't have to worry so much during the work day, as long as we get a whopping protein/leucine meal or two at the end of the day
 

HUNTER1313

Level 6 Valued Member
For instance, I have a shake on the way home from work with some bcaa, creatine, glutamine, greens powder, and some hydrolyzed collagen. Then have supper anywhere from half an hour to an hour later. Supper usually starts with a salad, then is whatever. I wash it down with a protein shake. Between supper and bed I may snack on some mixed nuts or a protein bar or some cheese.
I forgot to mention, during the day it's water, carbonated mineral water, and coffee.
 

kennycro@@aol.com

Level 6 Valued Member
So...

mTOR is a very complex mechanism. The notes provide a snap shot of the information.

Perhaps Al or Snowman add more.

The following is based on my overview of it and research from other individual on it.

2, but we can't 1 c as it may promote cancer and affect our lifespan.
Manipulating mTOR

My perspective is that you want to manipulate mTOR as a means of maintain or increasing muscle mass and strength while minimizing health issues (like promoting cancer) or decreasing life span.

1) Targeting Muscle

Per Barr, Exercise specifically "Targets" the activation of mTOR to the muscles worked. Leucine or Leucine rich proteins consumed are shuttled directly to the muscles trained.

One of the interesting side notes on this was how Bikers and Runners "Targeted" Leg Muscle Growth with this method.

Bikers and Runners use the reverse method as a means of decreasing Upper Body Muscle Mass, limited upper body training and not consuming a Leucine rich protein afterward; starving the upper body muscle mass.

2) Refractory Period

Dr Layne Norton determined that Muscle Protein Synthesis (via mTOR) is most effective when a protein Leucine rich meal is consumed every 4 - 6 hours; the traditional bodybuilding protocol of eating every three hours is less effective.

3) Three Meals Per Day

This falls in line with the Refractory Period of eating, every 4 - 6 hours. Thus, you end up with three brief mTOR spikes during the day for building or maintaining muscle mass.

The three meals that briefly spike mTOR are followed by in the remaining part of the day when no food is consumed.

AMP-k, Activated Protein Kinase

A drop in mTOR, triggers AMP-k. AMP-k is associated with an increase in life span and other heath benefits.

Thus, when eating is limited to two or three meals a day, the AMP-k Baseline is maintained during the majority of a 24 hour day; which is what you want.

4 c, if we do take leucine since pretty much every muscle is being worked at any given time, it will be a "global growth effect"
Global Effect

When it come to maintaining and/or increasing muscle mass, Targeting mTOR though exercise allows you to maintain control to a greater degree.

6 b, so we want some leucine/protein while we're working to maintain the muscles we're using which is obviously the ones used daily and repeatedly. Pretty much whole body.
The Right Amount of Leucine

Yea, you want a the right amount of Leucine rich protein at the right time to elicit the greatest effect.

7, so we don't have to worry so much during the work day, as long as we get a whopping protein/leucine meal or two at the end of the day
Three Meals A Day

Dr Donald Layman determined one of reasons most individual lose muscle mass each year is because they aren't consuming enough quality protein at breakfast and lunch to turn on mTOR; to maintain muscle mass.

Layman found that the only meal they consumed with the right amount of quality protein to turn on mTOR was dinner.

So, getting "a whopping protein/leucine meal...at the end of the day" isn't the best option.

Based Norton's Refractory Period, I am not sure how you squeeze in two meals at the end of the day.

Kenny Croxdale
 
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Sean M

Level 6 Valued Member
@kennycro@@aol.com Thanks again for your research. I didn’t know I wanted to know all this, but it’s fascinating.

I’m struck by the fact that the standard American diet/lifestyle is the worst of both these aspects:
  • Little strength training (and sarcopenia in middle and old age)
  • Eating all day - the longevity phase of this cycle is minimized
  • Not eating enough protein - and what protein that is consumed is not shuttled where it could be most helpful (muscles) because we don’t give it a reason to do so (e.g. resistance training)
 

HUNTER1313

Level 6 Valued Member
So if we want to fast, our best bet is to use the leangains model where we could make three to four servings of protein every four to six hours work. Or Iron Addicts modified warrior diet where he had three to four servings of protein during the day and a main meal at night.
 

North Coast Miller

Level 7 Valued Member
This would seem to lend support for a "protein window" following exercise, at least for leucine rich proteins.

I wondered how competitive bikers attained such large upper/lower muscle imbalance.
 

offwidth

Level 9 Valued Member
Yes. But even then you'll find that the sprinters will most likely have a little bit more 'up top' than your climbers and GC riders.

And it's important.... because you have to carry your own engine...
 

LukeV

Level 6 Valued Member
If you're consuming the correct amount of Leucine over three spaced meals daily, do you still derive a hypertrophy benefit from consuming additional BCAAs post exercise?

And also does anyone know whether alcohol effects mTOR?
 
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Snowman

Level 6 Valued Member
So...

mTOR is a very complex mechanism. The notes provide a snap shot of the information.

Perhaps Al or Snowman add more.

The following is based on my overview of it and research from other individual on it.
I'd say it's a good write up. I haven't spent much time digging into mTOR, and don't have a whole lot to add, except a general principle regarding growth factors. It's always going to be a matter of stimulating enough, but not too much. Rarely is any signaling system in the body constant; these things tend to be cyclic, with spikes and troughs of hormonal/genetic/enzymatic activity. Optimization then becomes a matter of getting the "right" number of peaks and troughs, and ensuring that the peaks are high enough and the troughs are low enough. @kennycro@@aol.com has given a good summary of how to do this with mTOR. The same considerations can be made with HGH, insulin, testosterone, estrogen, etc, although that doesn't mean you need to think specifically about each of those. If you are optimizing one growth factor, you're probably optimizing a few of them, as tends to happen in a system.

I'll also add, just to address the few sarcopenic test-tube experts that yell "mTOR and cancer, mTOR and cancer!"....mTOR activation does not cause cancer. Generally speaking, growth factors do not cause cancer. They help cancer grow faster. Because they're growth factors, and that's what they do. Don't take steroids and eat a bunch of protein if you have cancer, mmkaaay. That being said, there is no such thing as a cancer that is caused by excess mTOR activation. Your chances of getting cancer are the same regardless of what you do with mTOR, and frankly, if you're training and recovering intelligently, you're probably reducing your risk of cancer due to improved immune system function.
 

wespom9

Level 6 Valued Member
Certified Instructor
Just came in here to tell everyone to listen to Peter Attia but it's already been mentioned!
 

Tobias Wissmueller

Level 6 Valued Member
1) Targeting Muscle

Per Barr, Exercise specifically "Targets" the activation of mTOR to the muscles worked. Leucine or Leucine rich proteins consumed are shuttled directly to the muscles trained.

One of the interesting side notes on this was how Bikers and Runners "Targeted" Leg Muscle Growth with this method.

Bikers and Runners use the reverse method as a means of decreasing Upper Body Muscle Mass, limited upper body training and not consuming a Leucine rich protein afterward; starving the upper body muscle mass.
@kennycro@@aol.com @Al Ciampa @Snowman

A few thoughts am trying to wrap my head around, not really related to our cause of strength training here, but quite a serious one ...

Consider patients with a mutation in PIK3CA in specific cells / regions which leads to cancerous overgrowth syndromes, especially CLOVES syndrome.

Let's assume the PIK3CA mutation is exclusively in adipose or bone tissue, e.g. the hands and / or arms, feet, ...

Could the activation of the mTOR pathway to these tissues be reduced by kind of "redirecting" it to e.g. muscle cells that are stimulated by strength training?

Can mTOR be "depleted" in a certain timeframe and will it be "replenished"?
 

kennycro@@aol.com

Level 6 Valued Member
Rarely is any signaling system in the body constant; these things tend to be cyclic, with spikes and troughs of hormonal/genetic/enzymatic activity. Optimization then becomes a matter of getting the "right" number of peaks and troughs, and ensuring that the peaks are high enough and the troughs are low enough.
Cyclical

Great point. mTOR and AMP-k are cyclical, working in conjunction with each other. There is a somewhat of a See Saw effect. When one is up, the other is down and vise versa, as most things in life; night and day, etc.

Optimization

One of the keys is, as Snowman stated, "getting the right number of peaks". I'd paraphrase that to "Creating" the right number of peaks". Making it happen.

mTOR Example

Performing a training session that triggers mTOR combined with a post workout meal/snack of a Leucine rich protein that magnifies the mTOR anabolic effect.

That followed by not eating a meal for 4 - 6 hours. This allows mTOR to return to Baseline. It also ensure Muscle Protein Synthesis (The Refractory Period) is optimized, promoting muscle recovery/growth.

Number of Peaks

Dr Donald Layman's presentation indicated that three meals a day with the right amount of Leucine was effective. Increasing your meal to four times a day or decreasing them to two times a day might work, as well.

AMP-k

As someone said, mTOR amount to having a party. AMP-k job is to clean up after the party.

The article below posted by North Carolina Miller provides some good information...

All About mTOR + Natural mTOR Inhibitors & Activators - SelfHacked


Take Home Message: For health and longevity, we’d want systemic mTOR levels to be low most of the time, with bouts of activation.

mTOR activation does not cause cancer. ...there is no such thing as a cancer that is caused by excess mTOR activation. Your chances of getting cancer are the same regardless of what you do with mTOR, and frankly, if you're training and recovering intelligently, you're probably reducing your risk of cancer due to improved immune system function.
Another great point.

Kenny Croxdale
 

HUNTER1313

Level 6 Valued Member
All the talk about "exercise " triggering mtor, but what about us construction workers? We exercise all day. For instance, I hauled heavy bars and stuff all day the other day. Wouldn't that trigger motor and keep it elevated all day?
 

HUNTER1313

Level 6 Valued Member
I get I probably should have some protein during the day, but how am I to create these peaks and valleys when all I do is haul and carry heavy stuff? I work harder at work than I do in the gym.
 
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