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Hi all, I'm starting this thread which is another offshoot of my mTOR obsession. I find this protein more fascinating than ever. It has been described as an ON/OFF switch, but actually it's more like a DIMMER. It can be downregulated, emanating a soft, pale light (activity) whereas it can be upregulated, providing a bright light. In scientific terms, it's activity is measured by the phoshorylation ratio (phosphorylated/unphosphorylated mTOR proteins) in every single organ/tissue. Chronical downregulation or upregulation can be bad and result in sickness or degenerative or neoplastic disease. Whereas a wise tweaking of such a metabolic dimmer can result in more healthspan and longevity. In the central nervous system (CNS) a fair level of mTOR activity is believed to mantain neurogenesis and prevent cognitive impairment. I'm going to post some literature and some practical consideration upon the literature. We've seen that we can upregulate mTOR in skeletal muscles by exercise thru the mechanoreceptors signal and make muscles grow, or preventing them from atrophying. We've seen that we can upregulate mTOR in the BAT tissue by cold exposure thru the norepinephrine receptors signal, making BAT increase in mass and reaping the beneficial results. How can we upregulate mTOR in the CNS?

A recent interview with Brian Delaney with information on: Benefits of vegan over animal diet regarding mTor Calorie restriction in its various forms mTor considerations with hormone replacement Brian's work and role in the Age Reversal Network

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.

A new, excellent stemtalk interview to the eminent cellular biologist David Sabatini, the one who discovered the mTOR pathway. Some myths are shattered by this interview. In particular,: Sabatini answers: there is no evidence at all. If we feed an excess of amminoacids to the system, mTOR activity will reach a maximum threshold and the excess nutrients will be excreted. The max threshold is not such to cause cancer, whereas mutation of GTpases, the intermediate sensing protein, may take mTOR activity to pathological high levels such as to cause cancer. So, the high quantities of protein eaten by Atkins dieters or by bodybuilders would jconstitute a simple waste and just be excreted. Whereas the benefits of calorie restriction and methionine restriction are probably, according to Sabatini, related to the triggering of autophagy. by mTOR inhibition and the subsequent homecleaning. Excess fo autophagy can be very detrimental in that when the last cellular ribosome and mytocondia are digested there is a point of no return, cellular functions are lost. Another very interesting issue: the insulin signal governs mTOR in skeletal muscles, the nutrients signal governs liver mTOR. Actually, some competitive bodybuilders will inject themselves with insuline to amplify muscle growth. Literature says otherwise but Sabatini is a candidate to the Nobel prize and the one who knows most about mTOR. Some of the above prompted a readjustment of my conceptual model of mTOR, such as: Role of carbs (energy substrate) in muscle growth, their 'fueling' the proteins would mean fueling the insulin signal which activates mTOR in such a way to maximize protein efficiency. In a few words the belief that not so many protein are needed in the presence of significant carbs would be supported by Sabatini More protein would be useful only insofar as they feed the insulin signal directly and by gluconeogenesis (eating more protein while dieting or cutting notoriously spares loss of muscle tissue). Carbs optimization rather than protein optimization would be needed to promote muscle growth (I remember Sergio Oliva, historical winner of 3 Mr Olympia, suggesting fresh fruit to increase in muscle mass) Keto diets good to loose weight but also cause loose of muscle mass (as testified by bodybuilders), because of substantial drop in the insulin signal. Low carb-Low protein classic keto diet especially causes a decrease in muscle mass, since the insulin signal is killed by very littel glucose and very little protein (which also stimulates insulin plus cannot activate in this case gluconeogenesis due to the low amounts). The Rosedale diet is an example of this. I've followed that for a couple of months, notwithstnding exercise I lost muscle mass AND adipose tissue. By this conceptual model, Valter Longo's suggestion to moderate protein would not be so meaningful, barring the avoidance of other detrimental effects (such as inflammation, which is probably a real one, especially with animal protein). Valter Longo's longevity diet would not have huge effects aside the ones coming from a healthy diet with a low glycaemic index and moderate nutrients. Whereas the FMD would promote autophagy by the substantial decrease in the insulin +protein signals.