Rapamycin: longevity benefits, surge in popularity, unanswered questions, and more

Featuring: David Sabatini, M.D., Ph.D. and Matt Kaeberlein, Ph.D

See Video of the podcast here: https://www.youtube.com/watch?v=O67pvKxio10

"[Rapamycin] is the most robust and reproducible drug that we know about today for impacting not only longevity, but to the extent that we can measure various metrics of healthspan in complex animals, rapamycin also seems to positively impact pretty much every aspect of health span that we measure. ” —Matt Kaeberlein


Looking forward to this one!

How many people that hate “influencers” are going to still watch this? lol.

Someone should create /post a transcription of the entire podcast.

This podcast is OUTSTANDING!


What are the Key takeaways?

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Yes, please someone summarize! I can’t stand to sit for a 3 hour hit movie, let alone a podcast of something that is just going to rehash what has already been discussed in this forum.


Worked my way through the 3 hours. Worth the time. Great video. Should be required watching for anyone interested in longevity. Might change a few things based on info.


Don’t be lazy. :grin: Summarize it. Actually, is there anything new that hasn’t been discussed extensively in the forum threads? If so please share. I admire your fortitude for watching a 3 hour video on YouTube for anything.


@KarlT Please summarize it for the good of the community. Thanks in advance!

I’ sure he forgot it all the minute the clip ended. Unless I keep notes, I’d forget it in no time :smile:

Dr Attila’s website has extensive notes on the talk.

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Ok I summarize for you guys:

  1. What the hell has happened to Peter Atia. I last watched him about 6 months ago, and the dude just aged 20 years in six months. Would be interesting to know what the hell he is taking or doing that did this to him
  2. Next thing i got is the Mat dude seems like a cool no BS type of guy
  3. the rest same as everything you have ever known/heard about RAPA- nothing new.

Jokes aside, one thing they are saying that RAPA does inhibit mtor2 also and that is relatively speaking a bd thing, but nevertheless the mechanism how this is happening is not clear, and may still not affect on longevity. Now, this was really new, and maybe a bit of bad news, but they said it is not complete and they don’t know exactly how it is affecting the longevity.

  • What I also got is that the dose should be pretty high to mimic the study in rodents, so more validation for me to continue my 10mg with EVOO and GFJ

Thanks, that is about what I expected. If there is actually something new, it will show up in this forum almost immediately.

Nothing new but Matt has mentioned:

  1. seeing “survival benefit” in his dog group (to answer the Q if there would be a negative lifespan).
  2. currently weekly dose is 0.15 mg/kg for his dogs
  3. So if the person is 60 kg then he would be on a 9mg weekly dose (someone double check).
  4. Overall, he is “under-dosing”.
  5. Matt: there is “structural rejuvenation of the ovaries” in the reproductive study with rapamycin (data presented privately thus far).
  6. After watching it, the conclusion is nobody knows. So I think I will go with how my body feels and be guided by regular blood tests of biomarkers but not serum levels.

Texas weather and with all the extreme “rucking” is my guess, but yeah he does not look great it also could be the lighting.
I always thought Attia had been over-training himself for too long (starting from his teenage years).


I’m in discussion with the author of this rapamycin rejuvenating ovaries paper (its in process) who is in Korea. The paper reviewers asked for more experiments to be performed, so its been delayed. I’ll ping him again in a few months…


Can you send over a good contact person who I could interview when the study is completed :pray:


The discussion of rapamycin’s effect on the brain was interesting. I almost spit out my coffee when David casually mentioned synthesizing an antibody to mtor. I have watched too many sci fi movies. That seems like a great way to wipe out all life on earth.


Well yes that was interesting, but more interesting part was the fact that they seem to agree that in small doses is perhaps futile to even do RAPA. I can ATTEST to that. I tried various doses from 3-10mg’s,(all with EVOO and GFJ) and surprise, surprise, the dose that i feel best is 10mg +EVOO and GFJ. Even though it is up in the air (as to the dosing and frequency) and these dudes being docs were careful not to throw any specific numbers out there, it was clear that for real benefits to be had you better load up your truck man.


Attempt to summarize:

I think everyone, especially anyone new to longevity, should listen to this talk. Rare opportunity to hear two of the true experts in Rapamycin. Only a few people on this forum that might not benefit from this talk.

Obvious this is my interpretation of what they said. Others may interpret differently.

Rapamycin best substance currently available for longevity and health span. “Airtight case” for mtor relationship to longevity.
Rapa works via inhibition of mTORC. Active mTORC is anabolic. Inhibition of mTORC is catabolic.

Side effect profile, especially for intermittent dosing of Rapa not well defined.
Data on Rapa dosing is remarkably inadequate. Best amount, timing, age to start all unknown. Dr K has requested funding for this and NIH rejected.
Rapa, in mouse model, clearly works even when started later in life.

Rapa positive effects generally attributed to blocking mTORC1 activity.

Rapa binds to FKBP and then binds to mTOR.
mTOR bound to RPTOR is mTORC1
MTOR bound to RICTOR is mTORC2
mTORC complexes interacts with hundreds of other proteins
Rapa binds to mTORC1 and inhibits mTORC1 function, although likely not completely.
Rapa does not inhibit mTORC2, but rather interferes with the synthesis of mTORC2.
Important because once mTORC2 is formed, Rapa doesn’t affect it. Apparently you only need 10-15% of mTORC2 function to keep things running.

The exact mechanism by which Rapa extends lifespan is not known. Primarily because of mTORC1 inhibition but mTORC2 could be involved and process very complex.
Dr K not convinced that all benefits are due to mTORC1, and that all side effects are due to mTORC2 inhibition.

MTORC is a nutrient sensor. Activated by nutrients.
Amino acids, especially Leucine and Arginine stimulate mTORC1. Strong bond between Leucine and mTORC1.
Since Rapa is catabolic, unclear why it does not cause sarcopenia. Maybe by also stopping inflammation.

mTORC1 and mTORC2 in all cells in large amounts.
Distribution of Rapa into different tissues not well known.
May take higher dose or longer exposure to get Rapa into CNS.
Crossing blood brain barrier may not be required to have positive impact on brain. Others signaling may occur.

Everolimus remarkably similar molecule to Rapa.

Rapamycin is an immune modulator, not an immunosuppressant and with intermittent dosing is an immune rejuvenator.

Rapamycin impacts all 12 hallmarks of aging, changes the epigenome, causes autophagy, and reduces inflammation.
Autophagy likely Rapa most important mechanism, although anti inflammatory effects may be just as important.
No great biomarkers for autophagy.

High degree of similar genetic impact on longevity across different species. Dr K. Feels this indicates that testing on worms and mice is useful.

They did discuss Dr K’s questionnaire study of Rapa users, the dog study, and fertility, but those have been discussed elsewhere.


Thanks for the synopsis.

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