MOTs-C and mTOR (C1/C2) inhibition… could someone please explain this to me like I’m five years old?

[Aikman56]

I’m interested in utilizing MOTs-C during my offseason. As @luki7788 has noted, it is preferred by many to use MOTS-c during the high-androgen, high-food phase because of its positive effects and because it can reduce oxidative stress that comes from heavy loading on the body.

But then I remembered reading somewhere that it can inhibit mTOR. So I did some digging to try to figure this out and went down the rabbit hole of mTORC1 signaling, particularly in T cells, acting as a negative regulator, but red that it can activate mTORC2 in muscle cells.

THEN I read that mTORC1 is the master regulator of skeletal muscle mass, promoting protein synthesis and muscle fiber hypertrophy in response to mechanical load (exercise) and amino acids (especially leucine).

So is it inhibiting THAT? And then I found a study indicating MOTs-C reduces my statin and reduces muscle atrophy signaling…

So that’s where my confusion lies. Is the mTORC1 in muscle cells or T-cells? And is the MOTs-C negatively impacting the mTOR that regulates hypertrophy? I feel like I’m picking up some contradictory information…

Or maybe I’ve just completely lost my mind and I’m misinterpreting the data!

Whatever the case, I would love someone more well-versed in this than myself to speak on it. Thanks!

 

[bbxtreme]

I’m interested in utilizing MOTs-C during my offseason. As @luki7788 has noted, it is preferred by many to use MOTS-c during the high-androgen, high-food phase because of its positive effects and because it can reduce oxidative stress that comes from heavy loading on the body.

But then I remembered reading somewhere that it can inhibit mTOR. So I did some digging to try to figure this out and went down the rabbit hole of mTORC1 signaling, particularly in T cells, acting as a negative regulator, but red that it can activate mTORC2 in muscle cells.

THEN I read that mTORC1 is the master regulator of skeletal muscle mass, promoting protein synthesis and muscle fiber hypertrophy in response to mechanical load (exercise) and amino acids (especially leucine).

So is it inhibiting THAT? And then I found a study indicating MOTs-C reduces my statin and reduces muscle atrophy signaling…

So that’s where my confusion lies. Is the mTORC1 in muscle cells or T-cells? And is the MOTs-C negatively impacting the mTOR that regulates hypertrophy? I feel like I’m picking up some contradictory information…

Or maybe I’ve just completely lost my mind and I’m misinterpreting the data!

Whatever the case, I would love someone more well-versed in this than myself to speak on it. Thanks!

MOTS-C does not meaningfully inhibit mTORC1 in skeletal muscle in a way that would blunt hypertrophy.

If anything, the net effect during high-androgen, high-calorie phases is neutral-to-positive, because it:

• Improves mitochondrial efficiency
• Reduces ROS & metabolic stress
• Improves insulin sensitivity
• Reduces muscle atrophy signaling
• May activate AMPK without suppressing mTORC1 after training and feeding

The mTOR inhibition concerns mostly come from immune-cell studies (T-cells), not muscle tissue.

However, I think SS31 may be more in line with what you’re looking for:

SS-31 is the more hypertrophy-friendly peptide.

Why?

• Directly improves mitochondrial efficiency
• Reduces ROS buildup from high training loads
• Helps preserve satellite cell function
• Zero impact on AMPK → doesn’t compete with mTOR
• Reduces apoptosis caused by tren & high systemic inflammation

Think of SS-31 as mitochondrial insurance during brutal off-season phases.

 

[TheOtherOne55]

Agree with @bbxtreme here. MOTs biggest benefit is its ability to help with insulin sensitivity. It’s like taking EQ because you want an appetite increase. While yes, u can get that, there are many other more beneficial reasons to take it. Yes, reduction of oxidative stress is a positive but if you’re looking for a “clean up” peptide like that, go for SS-31.

 

[Sectør]

I’m interested in utilizing MOTs-C during my offseason. As @luki7788 has noted, it is preferred by many to use MOTS-c during the high-androgen, high-food phase because of its positive effects and because it can reduce oxidative stress that comes from heavy loading on the body.

But then I remembered reading somewhere that it can inhibit mTOR. So I did some digging to try to figure this out and went down the rabbit hole of mTORC1 signaling, particularly in T cells, acting as a negative regulator, but red that it can activate mTORC2 in muscle cells.

THEN I read that mTORC1 is the master regulator of skeletal muscle mass, promoting protein synthesis and muscle fiber hypertrophy in response to mechanical load (exercise) and amino acids (especially leucine).

So is it inhibiting THAT? And then I found a study indicating MOTs-C reduces my statin and reduces muscle atrophy signaling…

So that’s where my confusion lies. Is the mTORC1 in muscle cells or T-cells? And is the MOTs-C negatively impacting the mTOR that regulates hypertrophy? I feel like I’m picking up some contradictory information…

Or maybe I’ve just completely lost my mind and I’m misinterpreting the data!

Whatever the case, I would love someone more well-versed in this than myself to speak on it. Thanks!

My understanding of it is that your body basically has two switches. In its simplified form:
1) AMPK - fat burning mode
2) mTOR = muscle building mode

And your body switches between the two based on a number of factors. In the case of Mots-c —it does active the AMPK pathway which can slightly suppress mTOR signaling, but it doesn’t do this long enough to really keep mTOR suppressed for long periods of times (it’s a temporary effect). It would only really be an issue if AMPK was chronically activated all day and you had all day mTOR suppression, which we don’t see happen.

Training, carbs, protein, AAS all increase mTOR signaling—so essentially after a hard training session you slam some food, and your body will be right back into a growth and recovery (mTOR) state that will override any AMPK activation.

I think that’s also why a lot of people reccomend using mots-c fasted when you first wake up so you can utilize some of the AMPK state, then later in the day transition more into a recovery/growth MTOR state (especially after training)

Can be useful in a bulk like others said for keeping insulin sensitivity high and oxidative stress lower, while also improving nutrient partitioning and limiting fat gain. Could potentially aid in recomping in a surplus too?

^^ atleast that’s the way I understand it.

 

[Aikman56]

MOTS-C does not meaningfully inhibit mTORC1 in skeletal muscle in a way that would blunt hypertrophy.

If anything, the net effect during high-androgen, high-calorie phases is neutral-to-positive, because it:

• Improves mitochondrial efficiency
• Reduces ROS & metabolic stress
• Improves insulin sensitivity
• Reduces muscle atrophy signaling
• May activate AMPK without suppressing mTORC1 after training and feeding

The mTOR inhibition concerns mostly come from immune-cell studies (T-cells), not muscle tissue.

However, I think SS31 may be more in line with what you’re looking for:

SS-31 is the more hypertrophy-friendly peptide.

Why?

• Directly improves mitochondrial efficiency
• Reduces ROS buildup from high training loads
• Helps preserve satellite cell function
• Zero impact on AMPK → doesn’t compete with mTOR
• Reduces apoptosis caused by tren & high systemic inflammation

Think of SS-31 as mitochondrial insurance during brutal off-season phases.

As always, that’s a ton of great information… Much appreciated!

So if I do go with SS31, the dosage is that I have seen are around 200 mg daily sub Q… Does that sound about right?

Also, regarding MOTs-C, have you seen any evidence indicating myostatin suppression? I meant to link this study above…

MOTS-c reduces myostatin and muscle atrophy signaling - PMC

Keywords: FOXO1, high-fat diet, MOTS-c, muscle atrophy, myostatin

pmc.ncbi.nlm.nih.gov

 

[Aikman56]

My understanding of it is that your body basically has two switches. In its simplified form:
1) AMPK - fat burning mode
2) mTOR = muscle building mode

And your body switches between the two based on a number of factors. In the case of Mots-c —it does active the AMPK pathway which can slightly suppress mTOR signaling, but it doesn’t do this long enough to really keep mTOR suppressed for long periods of times (it’s a temporary effect). It would only really be an issue if AMPK was chronically activated all day and you had all day mTOR suppression, which we don’t see happen.

Training, carbs, protein, AAS all increase mTOR signaling—so essentially after a hard training session you slam some food, and your body will be right back into a growth and recovery (mTOR) state that will override any AMPK activation.

I think that’s also why a lot of people reccomend using mots-c fasted when you first wake up so you can utilize some of the AMPK state, then later in the day transition more into a recovery/growth MTOR state (especially after training)

Can be useful in a bulk like others said for keeping insulin sensitivity high and oxidative stress lower, while also improving nutrient partitioning and limiting fat gain. Could potentially aid in recomping in a surplus too?

^^ atleast that’s the way I understand it.

That makes perfect sense… Thanks for your input, much appreciated!

 

[bbxtreme]

As always, that’s a ton of great information… Much appreciated!

So if I do go with SS31, the dosage is that I have seen are around 200 mg daily sub Q… Does that sound about right?

Also, regarding MOTs-C, have you seen any evidence indicating myostatin suppression? I meant to link this study above…

MOTS-c reduces myostatin and muscle atrophy signaling - PMC

Keywords: FOXO1, high-fat diet, MOTS-c, muscle atrophy, myostatin

pmc.ncbi.nlm.nih.gov

That’s a cool study. I had not seen it yet.

If the animal & cellular data translate to humans (big “if”), then using MOTS-c might impart lead to Reduced expression of myostatin, meaning less muscle wasting signaling, perhaps better maintenance of muscle integrity under metabolic stress or aging.

At the end of the day my current stance is that if I want to have better BG then I use Mots-C. If I want mitonchondria repair and something that cleans up my labs (or keeps them clean), I use SS31.

1-2.5mg per day would be ideal dosing for SS31. Anything more and you’ll probably get some headaches in terms of side effects.

 

[Aikman56]

That’s a cool study. I had not seen it yet.

If the animal & cellular data translate to humans (big “if”), then using MOTS-c might impart lead to Reduced expression of myostatin, meaning less muscle wasting signaling, perhaps better maintenance of muscle integrity under metabolic stress or aging.

At the end of the day my current stance is that if I want to have better BG then I use Mots-C. If I want mitonchondria repair and something that cleans up my labs (or keeps them clean), I use SS31.

1-2.5mg per day would be ideal dosing for SS31. Anything more and you’ll probably get some headaches in terms of side effects.

OK, that’s awesome. Thank you. And last question, I promise… I feel like I read somewhere you talking about cycling SS–31. Am I remembering that correctly? Would you use it every day or specific training days? How many weeks at a time?

OK, that’s all, I promise!

 

[bbxtreme]

OK, that’s awesome. Thank you. And last question, I promise… I feel like I read somewhere you talking about cycling SS–31. Am I remembering that correctly? Would you use it every day or specific training days? How many weeks at a time?

OK, that’s all, I promise!

Run it 6-8 weeks at a time on all days around 2.5mg (or less). That can be done during a health phase or if on a heavy cycle while using tren.

After those 6-8 weeks you could move into Mots-c for that same period of time. That’s how many of the top coaches and guys are using each compound or the combination currently.

 

[luki7788]

If I’m honest, from everything I found about SS-31, the doses most people recommend online are basically useless. In human studies, the peptide was tested at much higher doses, usually around 10–40 mg, and often given through IV infusions
So doses like 2 mg per day will probably do almost nothing if they do anything at all.
That’s just my opinion, based on what was actually done in real human studies.

This peptide was even supposed to be approved by the FDA at one point. They didn’t approve it in the end, but it was very close to becoming an actual drug.

 

[Aikman56]

Run it 6-8 weeks at a time on all days around 2.5mg (or less). That can be done during a health phase or if on a heavy cycle while using tren.

After those 6-8 weeks you could move into Mots-c for that same period of time. That’s how many of the top coaches and guys are using each compound or the combination currently.

Thank you again. As always, your help is greatly appreciated!

 

[Cerberus777]

My understanding of it is that your body basically has two switches. In its simplified form:
1) AMPK - fat burning mode
2) mTOR = muscle building mode

And your body switches between the two based on a number of factors. In the case of Mots-c —it does active the AMPK pathway which can slightly suppress mTOR signaling, but it doesn’t do this long enough to really keep mTOR suppressed for long periods of times (it’s a temporary effect). It would only really be an issue if AMPK was chronically activated all day and you had all day mTOR suppression, which we don’t see happen.

Training, carbs, protein, AAS all increase mTOR signaling—so essentially after a hard training session you slam some food, and your body will be right back into a growth and recovery (mTOR) state that will override any AMPK activation.

I think that’s also why a lot of people reccomend using mots-c fasted when you first wake up so you can utilize some of the AMPK state, then later in the day transition more into a recovery/growth MTOR state (especially after training)

Can be useful in a bulk like others said for keeping insulin sensitivity high and oxidative stress lower, while also improving nutrient partitioning and limiting fat gain. Could potentially aid in recomping in a surplus too?

^^ atleast that’s the way I understand it.

This is correct on paper. But IRL if you're on gear and calorie surplus. You're bouncing bsck and forth a lot. So in theory you can build while keeping excess inflammation down, burn fat and stay leaner, and insulin sensitivity higher. While having more endurance.