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Thanks, John. I felt like a got a real education on mTOR.
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Great presentation. I found Dr Loh’s level of detail on the mtor system informative and clearly stated.
Given that Rapa puts mtor in the G1 phase and thus enables autophagy, I continue to be concerned by what brings it “prematurely” out of the beneficial G1 phase, other than time and the diminishing effective dose level of Rapa. My concern is to avoid negatively reducing the benefits of Rapa. I think there are a lot of questions about dosing, timeframes, the beneficial, or otherwise, nature of certain foods, drugs, supplements, (protein / amino acids) and other activities like exercise, sleep, etc.
We’ve all guessed at an appropriate rapa dosing, timeframes, associated stacks and protocols but I am not convinced that I have it right.
I know John has an innovative approach, protocol and supplement regime.
I try to play down the middle erring on caution. 6mg, 7 day cycle for 4 weeks then 3 weeks off. I avoid foods and supplements that are known to interfere with Rapa for the first three days after dosing.
BTW I was blissfully ignorant on mtorc3, as it relates to cancer!
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The presentation was very informative and humbling as well. It definitely made me to realize how little I know.
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I think the key point is that there is a lot that “the experts” don’t yet know.
What I find is that individuals often understand in great detail part of the subject, but have little knowledge of the whole subject.
What I learnt from yesterday was the key role of mTOR inhibition in slowing down or stopping cell division. The very immediate effect of this relates to lymphocytes, but more generally it is relevant and gives some idea of the ideal upper boundary of mTOR inhibition. (or more precisely supports cycling it)
Anecdotal reports from other members of the forum particularly @Agetron indicates that there is a sensible upper boundary to mTOR inhibition, but we now are clearer on what the mechanism might be that affects this (cell division).
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Which supplements are these? Thank you!
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I know Curcumin and Berberine are thought to interfere with Rapa (both ways), but I think this is mainly a thing for the digestion rather than something that requires 3 days of avoidance.
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Since I am 74, “older age” is one of the key filters through which I view information/evidence. In this presentation the evidence that Rapamycin shortened life in telemerase-deficient mice rang a bell. And it resonated with another bit of evidence that said that Rapamycin could be harmful with respect to neuro degeneration IF the organism was already experiencing (age-driven) performance degradation in the lysosome. Also there have been questions about the benefits or wisdom of prolonged fasting in older people, and that calorie restriction has a relatively higher benefit in younger people. (Correct me please if I am wrong about any of this).
I am developing an impression that strategies that push toward catabolism may not be that good for older people especially if they are already thin but basically metabolically healthy.
The presenter here, Vivyanne Loh, was so helpful in reminding that the systems are complex, and vary with the individual organism. For all that she knows, I am cautioned that there is still so much more we don’t know.
Would welcome thoughts about all these interventions, if you are old.
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I am 64. You would need to make your own decision as to whether I count as being “old”.
I don’t think the telomerase issue was relevant, but that was more because I think the expression of hTERT links to when cells divide. Rapamcyin holds back cell division per se.
The balance between catabolism and anabolism is key.
I was of the view that younger people (perhaps from 25 onwards) might have a benefit from Rapamycin perhaps once or twice a year.
I accept I am biased because I have been supportive of longer periods between Rapamycin dosage and this is therefore not a new position, but I really think people need to switch between anabolic and catabolic when older as well as when younger.
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Creatine, Urolithin A and any Fatty Acids ie DHA, EPA or C:15.
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I wonder how those interfere with Rapamycin?
Almost all of the compounds that I mentioned have a direct effect on mtor regulation. Or the other closely associated systems intimated by Dr Loh in her presentation. There’s decent research assessing all of them and much of it can be found on this site. RapAdmin has posted some of this above.
My initial interest on supplementation was related to athletic performance and body repair, rather than healthy longevity. Creatine is one of the best studied and trusted compounds for sports performance and muscle repair. There’s reasonable potential for creatine to interfere with the Rapa regulated cycle.
As I’ve mentioned, I am quite conservative with mixing too many supplements that may risk undesirable side-effects or outcomes.
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