Systemic mTOR activation

[mccoy]

Hi all,

we've been discussing in other threads local and systemic mTOR, how mTOR activity may be good in some tissue as muculoskeletal muscles and less good in the system as a whole (except the immune system) and in organs in general.

Also, there is no non-invasive lab analysis which is correlated to mTOr activity. We cannot be sure when mTOR is inhibited or in full activity. Except from some hints maybe.

The following is a very empirical, although conceptually very reasonable observation carried out on myself.

My observations are very simply based upon daily bodyweight measurement and observation at the mirror.

By definition, systemic mTOR activity means a proliferation and growth mode, driven by abundance of nutrients in the system.

A reasonable proxy for systemic mTOR actrivity may be white adipose tissue growth. Conceptually, accumulation of adipose tissue happens when there is a relative abundance of nutrients, so that some of'em are free from immediate biological needs and can be stored.

If we keep the system in a state of realtive inhibition of mTOR (proliferation and growth mode off) that means relative scarcity of nutrients in relation to energy state of the body. No adipose tissue can be accumulate. The overall energy state of the system is read by the mTOR circuit as unfavourable to growth. Masterswitch off.

Now, my daily monitoring of bodyweight reveals a very little increase in the latest 3 weeks. But my mirror observations, plus pinching by fingers reveal that soem adipose tissue has accumulated at the frontal belly. Not much, enough though to reveal a state of abundance of nutrients and energy.

My muscular state is more ro less steady, my muscles grew but not too much, coherently with the level of resistance exercise.

Hypothesizing a lag time of 3 weeks (latest 3 weeks representative of the regimen leading to mTOR activation) this is my cronometer 3 weeks average. The following is what presently activates mTOR in my system. Now, I'll have to downsize calories, protein, or maybe carbs and protein with a moderately low-carb diet, or increase energy expenditure by cardio activity, or doing a fast, or whatever else inhibits mTOR. 100 gr of protein are probably too much, more than the muscles need now and are read like abundance. Calories are also in a slight excess.

The following is also a proof that a vegan regimen can be anabolic. I was skeptic about it but now I have the hard evidence.

Any comments are welcome to this empirical, n=1, very simplified but apparently logic analysis.

 

[mccoy]

Action I took to moderate mTOR activity:

• Valter Longo's FMD
• Reset caloric target  and respect it
• Avoid hunger excesses by training more evenly thruout the week 

[Michael R]

On 9/10/2018 at 12:39 AM, mccoy said:

By definition, systemic mTOR activity means a proliferation and growth mode, driven by abundance of nutrients in the system.

A reasonable proxy for systemic mTOR actrivity may be white adipose tissue growth. Conceptually, accumulation of adipose tissue happens when there is a relative abundance of nutrients, so that some of'em are free from immediate biological needs and can be stored.

No, this really doesn't work: adipose tissue "grows" primarily by socking more TG into existing adipocytes, not by adipocyte proliferation or hypertrophy sensu stricto, and is driven by simple energy excess. (This is even more so in insulin-resistant states and with age). By contrast, mTOR drives cell hypertrophy and proliferation, is decoupled from TG storage in adipocytes, and while it is certainly downregulated by energy deficit, it has a much more complex regulatory regime, including importantly a 'leucine threshold' as a necessary and almost-sufficient condition, as well as a role for methionine.

This decoupling is readily apparent in sarcopenic obesity, and in aging, where body composition gradually shifts to more and more adipose and less and less lean tissue — initially in the face of misleadingly-stable weight, and increasingly with age and in the last 9 years of life one becomes more adipose (and less lean tissue) even in the face of involuntary weight loss.

[mccoy]

OK thanks Michael, so ipertrophy of adipocites suggests an anergy excess which is necessary, but not sufficient, to the upregulation of systemic mTOR.