" Evidence indicates that non-responsiveness to mTORC1 inhibition results from the release of negative feedback loops whereby pro-survival pathways upstream of mTOR are activated, such as the activation of Akt (termed ‘Akt rebound’). To investigate these feedback loops in more detail Carracedo and colleagues analysed tumour biopsy samples from patients with metastatic breast or colon cancer or melanoma enrolled in a phase I trial of the rapamycin derivative RAD001. They found that tumours from all patients treated with a high weekly dose exhibited increased activation of extracellular signal-regulated kinase (Erk; indicative of mitogen-activated protein kinase (MAPK) pathway activation), whereas those treated with a low daily dose did not."
The rebound effect on mTor I think is what has allowed many users to gain muscle even better than while not on rapamycin.
Theoretically that could be the case but I doubt it. The increase in mTORC1 between doses would have to be greater than the decrease in mTORC1 during dosing for the overall effect to be an increase in mTORC1 and increased anabolism. I think that’s highly unlikely. If there is some significant rebound, I think the mTORC1 level is on average lower with rapamycin. If it were not then the animal studies most likely wouldn’t show the benefits they do. Also anecdotally, while rapamycin doesn’t seem to be decreasing the ability of people to gain muscle, it isn’t improving it either. Any small perceived increase in the ability to gain muscle I would think are attributed partially to decreased inflammation in older people on rapamycin, which in turn allows them to train harder, which then leads to slightly improved results.
In any case. I’m not particularly concerned about the potential rebound effects of rapamycin. Any rebound appears to be either too small to be of major importance or to not matter much in the end for longevity. If that were not the case then we wouldn’t be seeing life span benefits in mice.
I’ll let you know- I took a vacay from Rapa due to low MCV and increased RDW which have now stabilized. I am doubling down on strength training + protein =feel great! Not saying Rapa made me feel bad but I definitely feel a pump at the gym and more energy being off this month! Fasting, zone 2 exercise, ketogenic, (timing of more protein), sleep, supplements getting great results! Is Rapa the longevity elixir which will provide 5 years more of lifespan? Perhaps. Its a journey!
I agree… you might not gain muscle… if anything for me, I am more shredded - but much stronger…no fat or marbelized muscles. In my 3-years of use, my muscle size has been consistent and considered large by peers who don’t workout.
Gains with rapamycin are in strength… not growth/size for me.
I am glad to be stable at 65 years - when most people at my age are losing both muscle size and strength.
No size change (increae or decrease) after the initial shredding of fat to my current size. Pic from last night at gym.
I do 1 hour 15 minutes of muscle resistance… a total body workout (arms, chest, legs) every other day. I just started taking 1 tablespoon of Taurine in my morning coffee this week.
