Questions to ask Mikhail Blagosklonny?

At the end of July I will interview the world’s leading Rapamycin researcher Mikhail Blagosklonny in the Rapamycin Master Series podcast. Mikhail has taken many courage steps in his career which has pushed the Rapamycin longevity field forward in a huge way.

His research papers has impacted for example the Rapamycin physician Alan Green who thanks to these papers took the decision in 2017 to start prescribing Rapamycin off label. Alan Green has today the biggest clinical experience in the area with more than 1200 patients. A lot of other physicians have after that also taken these steps and one of those are for example Peter Attia.

Mikhail has also been initiator, adviser and/or funder of different Rapamycin trials. I really admire his passion, determination and courage, and it will be a big honor to now have a chance to interview him. Do you have any questions you wish I would ask him in this interview?


Question areas I’m interested in::

  1. Concerns about interactions between many medications and supplements? Would periodic (EOD, 1x/week) dosing help?
  2. Thoughts on using biological age as a guide for targeting interventions to extend healthspan. Alternatives?
  3. Thoughts on mTOR cycling? Is stacking multiple interventions (rapa, fasting, endurance exercise, etc) a good idea? Followed by mTOR activation (protein, resistance exercise, calorie excess, etc)? Length of cycle: 1 week, 10 days, 2 weeks?

Specifics on dose recommendations, perceived risk from tor rebound & how to manage it.


What a great opportunity! I have two questions

  1. Given the possibility of mTOR rebound with intermittent dosing, if an elderly man has an apparent higher risk of cancer than risk for cardiovascular event, would a tolerable high dose of rapamycin week one and a low dose week two on a biweekly (every two weeks) schedule be preferable to the same high dose given week one with no additional doses on a triweekly (every three weeks) schedule, given that the AUC is the same in both cases?

  2. Would an elderly adult wishing to gain weight and muscle be offsetting the benefits of rapamycin by supplementing with mTOR activators such as leucine and other branched-chain amino acids in addition to exercise. And if so, to what extent?


In a mission to adapt dosing strategies to different persond needs: who would benefit from taking 6-7 mg weekly and who would benefits from continously take 1 mg/day?


What would be an ideal dose and cycle for a man (6’+, 200lbs) in his mid to late twenties or in general for younger people?



  1. Regarding the concerns about interactions. Is it any specific interaction that you are concerned about?

  2. This is an interesting area! I will also dig more into this in my interview with Brian Kennedy which has been postponed a little bit.

  3. I really like this questions and I have asked something similar to other guests like: “How do we know if we push ourself too little or too much when it comes to mTOR inhibition?” I will try to include your question to my current one some how. I think it’s av ery important question to dig more in and ask every guest :+1:

@jimo3 & @CTStan
:+1: Can you elaborate a little bit more about risk from “mTOR rebound”? Do you mean that it backfires and start to stimulate cancer instead of preventing it?

2) This is a really interesting question which I will try to ask him. I will also ask him if we look through the lens of hyperfunction theory if it’s great for elderly to try to optimize muscle performance in different ways. My feeling is that this does not lift the foot from the gas pedal of slowing aging of course there are exceptions and people who really need higher muscle performance. But if you have sufficient muscle then probably it is better to try to maintain muscle than trying to do lots ot things to optimize it even more. I would say this is little bit controversal view because many are today advocating to optimize muscle performance. There is something here I need to understand and dig more in :pray:

Mikhail is pushing a lot on that dosing is individualized. I will try to dig little bit here to understand what he means regarding this and why dosing can differ between individuals and also how can a specific person know if a dose is right for that person :+1:

Are we talking about a also a healthy person without any diseases etc?

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Yes, Doctor B has said and encouraged that males should take as much a dose of rapamycin as you can without side effects.

And yes, he says dosing is individualized, but when I upped my dosage from 6 mg from over a year and a half (I had an excellent reversal of biological age) to a dose of 36 mg +… over seven months, my aging went faster in identical biological tests.

When I reduced back to 6mg… biological tests showed slower aging by a few years. Perhaps more rapamycin is not better… a dose of 6mg to 8mg is more effective.

Does Dr. B. have any change of thoughts on dose?


Nothing except for androgenic alopecia :smiley:


Thanks. No specific interactions but am interested in understanding if he has a different point of view than Matt K and Mitchell Lee, which is, paraphrasing, taking lots of supplements is probably not a good idea. This leads us to need to prioritize and place bets. Which few things have the biggest upside and are the best good bets, and which don’t interfere with each other or that can be dosed in a way that doesn’t create interference. Thanks for doing this!


Could you pls ask if taking a 0.5mg/day continuously without breaks could be more beneficial then 6-8mg once a week dose.


What is his current thinking on everolimus vs. sirolimus? Which is first choice for longevity?


Dr B looks good today based on his posting on TWTR, am so happy to see that.


I never thought about it until Dr B mentioned it I think in a tweet. As I recall, he said he believed high intermittent use could lead to a surge in tor. I reduced by dose after this & so would be most interested in more specifics.


The problem of course is that none of us know how we’re going to die, especially if we’re not outwardly showing any signs of disease. How about a recommendation based on standard mortality tables for your age. They’d show something like x% chance of heart disease, x% chance of lung cancer, etc. Just take a wtd average for the dose.


I started to take Rapa for my psoriasis 1 or 2mg daily then down to 1mg then down to a 4mg weekly dose. Then I experienced worsening of my psoriasis so I added back 1mg plus 4m on Sunday. I think it all depends on if you already have some previous auto-immune disease (psoriasis is) then you do need a maintenance dose plus a surge dose, that’s my guess for now.


There is some discussion that metformin and acarbose with rapamycin are synergistic. Is this true? Are there any other drugs or supplements that might be synergistic with rapamycin?


is that per week Jason, 6 and 36mg?


Hi Dirk… I was doing 6mg rapamycin weekly for 1 1/2 year… great results… got cocky and upped to … 36 ng/mL was going 10 days between dosing.

Currently trying to hit 6mg to 12 mg. Weekly again.

That is: 4mg rapamycin and one fresh squeezed red grapefruit to chase them down. No other GFJ or pulp. Just about 6 to 8 ounces fresh squeezed when I take the pills.


Great sharing there about the biological test and it’s interaction with Rapamycin dose regimes! What type of biological test was it?

This is really super interesting topic and as we saw in the Ora Medical data that I think Brian Kennedy presented on Metformin there was combination which lead to detrimental effects. A tough area to navigate in.

He has estimated that low daily dosing compared to standard weekly is 50/50 thing. More research is needed. See below. I will try to ask what his view are on daily, weekly and biweekly. Hopefully that can give some more light to the topic.

Yes, this is a interesting one and also if he has tried a rapalog and what his experiences are regarding it compared to rapamycin :+1:

What does “lead to a surge in tor” mean?

Great things to dig more in! This is a must-have-questions :pray: