Is immunosuppressive, antifungal and anti-inflammatory effect connected to mTOR inhibition?

I want to understand the biological pathways how things work. I’m starting to think that maybe it’s not directly the mTOR inhibition that cause the immunosuppressive, antifungal and anti-inflammatory effect when it comes to rapamycin. I wonder if it’s not more linked to the AMPK activation when mTOR is inhibited. mTOR and AMPK have a strong relation so if you inhibit mTOR than it creates better conditions for AMPK to increase and vice versa.

Very simplistic view of the pathway

Rapamycin > mTOR ↓ > AMPK ↑ = Immunosuppressive ↑ + Antifungal ↑ + Anti-inflammatory ↑

The pathway is important to understand because then we better understand how other interventions also work. For example, today it’s not only rapamycin that has immunosuppressive, antifungal and/or anti-inflammatory effect.

Two other intervention is for example extended fasting or calorie restriction. This two has been connected to immunosuppressive and anti-inflammatory effect. I have never read anything about that these two interventions should have antifungal. Do someone know if they have this effect?

The pathway for these interventions can be simplistic illustrated like this. The mTOR inhibition is usually not as big as when compared to rapamycin.

Fasting or calorie restriction > mTOR ↓ > AMPK ↑ = Immunosuppressive ↑ + antifungal ↑ + anti-inflammatory ↑

Now to the interesting part. If we look at coconut oil or MCT oil then these are usually said to have antifungal and anti-inflammatory effect. Here the pathway would look more like the above. Of course the mTOR pathway will also be lowered because of the AMPK increases.

Coconut oil or MCT oil > AMPK ↑ = Antifungal ↑ + Anti-inflammatory ↑

Can it be that both coconut oil and MCT oil has some immunosuppressive effect? My quess it most likely is so. If someone finds any study or something that supports or not support this post a comment in this thread.

I found this very old study saying that diets high in polyunsaturated fat have higher immunosuppressive effect than diets high in saturated fat.

“diets high in polyunsaturated fat, relative to diets high in saturated fat, are more immunosuppressive and are better promotors of tumorigenesis.”
Source: Lipids and immune function - PubMed

So when it comes to coconut oil and MCT oil then these contains primarily of saturated fat. So it probably looks like there is some kind of similiar pathway and my quess is that everything regarding the immunosuppressive, antifungal and anti-inflammatory effects are more connected to the AMPK activation.

Lets look at something else for example garlic. I seems like it has both antifungal and anti-inflammatory effects but does it have immunosuppressive effect? I quickly looked around and found this study.

“Under certain conditions garlic extract may act as immunosuppressive for downregulation of pro-inflammatory responses.”
Source: Antileishmanial and Immunomodulatory Activity of Allium sativum (Garlic): A Review - PubMed

So here the pathway looks like this.

Garlic > AMPK ↑ = Immunosuppressive ↑ + antifungal ↑ + anti-inflammatory ↑

When people say that rapamycin is dangerous because it has immunosuppressive effects then also garlic, cocunut oil and other AMPK activators are also dangerous because they use the same pathway.

Now to the verry interesting question. Now that we digged little bit in to the pathways can it be that you could get similiar lifespan benefits as rapamycin with other AMPK activators. For example if we just find the right dose when it comes to garlic extracts we most likely could mimic the effects of rapamycin.

This goes also back little bit into one of my earlier threads here in the forum were I pointed out that it’s more important to look at the overall dose of mTOR inhibition than just the dose of rapamycin (The total dose (regime) of mTOR inhibition vs Rapamycin dose regime). Because one person can for example practice fasting, calorie restriction and take rapamycin and one other person is just taking rapamycin. Very simplistic conclusion is that the first person probably will generally need to take little bit less rapamycin than the second for the similiar effect on lifespan.

This thread has opened my eyes to also take in consideration the overall AMPK actication dosage.

PS. Sorry about the long thread but I felt it is a important topic to raise.

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@Krister_Kauppi

Great to see people that are passionate and enjoy the processes of figuring stuff out! I am sure there are some answers in the variations of diet that seem to enhance longevity with mTOR modulation - Okinawan Diet?

Understanding what specifically aging does to disrupt “normal” or more youthful modulation of mTOR would help as well. This can help with approach, dose and what may be good co-treatments with Rapa to get best response.

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The big puzzle is a challenge thing to set in place so it’s good to be humble in this process. And as you say the more we start to understand what disrupt “normal” aging etc we can be better in hacking the biological organism we live in so that it better serves our life goals.

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@Krister_Kauppi

I totally agree!

I appreciate and try to live by the “humble” component that you suggest. Its hard to let go of Ego that is attached to the emotion of wanting to be right or easily offended, but the only way forward.

My feeling is that we are just a the beginning of mTOR’s role in aging. Understanding what ideal modulation looks like by reproducible metrics would be a start. Long term human studies are good for future generations, but of little value to those whose expiration date will have past.

My personal goal would be to pursue objectives that allow me a higher standard of physical and mental quality than the natural progression. If I live to 120 - great, but would take being a 90 year old that was able run, travel, teach / learn and contribute.

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You can certainly live to 90 and be physically and mentally active without taking rapamycin.

IMO: Exercise and maintaining a healthy BMI will certainly extend your health span.
The number one reason for sarcopenia is that people just stop exercising as much as they get older and lead sedentary lifestyles.

I was shopping at my local supermarket this morning and thought: Most of the people I am seeing will not live to be as old as I am now. The obesity crisis is out of control.

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I fully agree that keeping up the healthspan is the most important thing when it comes to longevity and it would be really great to have a quality in life as you point out :pray:

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True, I see that rapamycin can help out in this journey and be a nice complement to exercise and healthy BMI by increasing the probability that we get to 90 and have a good quality in life :heart: