Zero human longevity data around Rapamycin

Recently I got into a small discussion after I saw one claim around that there exists zero human longevity data when it comes to Rapamycin. In this post I will try to summarize the four areas where we have some data in.

  1. First I want to lift the human research data on the mTOR inhibitors, rapalog Everolimus and the mTORC1 inhibitor RTB101, which has shown improvement of the aged immune system and improvement of the response of influenza vaccine (pubmed: 25540326, 29997249, 33977284). This research has been done by the researcher Joan Mannick. In December I interviewed her and this podcast episode will be published this month where you can hear more about this research and what other interesting future steps that will be taken. We also talk about the big setback in her phase 3 trial. One reason why it failed was because the FDA proposed to change the primary endpoint from laboratory-confirmed respiratory tract infections to experienced respiratory symptoms (such as runny nose, sneezing, hoarseness etc). This led to that the quality of the data in phase 3 trial got very messy and subjective. My guess is that if this change in primary endpoint would not have been done then we would have had an mTOR inhibitor in the market today. Now it will take until around 2030 before this probably happens but I’m glad that Joan Mannick has not given up on her pursuit after this big setback. The data behind is too promising for her to just let go of this.

  2. The second thing I would like to highlight is that Rapamycin was FDA approved 1999 and from that date we have many years of safety data on chronic daily high doses taken by organ transplant patients. The dose regime for organ transplants is often around 2-5 mg/daily. In the longevity community the common dose regime is around 6 mg/weekly (pubmed: 37191826). Here are some interesting beneficial findings that have been seen in organ transplant patients: “There are also beneficial side effects in transplant patients, including fewer skin cancers, non-Hodgkin’s lymphomas, viral infections, and reduced cardiac allograft vasculopathy.” (pubmed: 33528569). Important to note is that there are also non-beneficial side effects.

  3. The third data point is that the Rapamycin researcher Matt Kaeberlein published a survey study this year to try to consolidate the N=1 anecdotal data of off-label use around Rapamycin in the longevity community (pubmed: 37191826). More research is needed to verify the results but it gives some interesting indications of both the beneficial and side effect profile of Rapamycin.

  4. Lastly there are also a lot of anecdotal data on places like This data is by no means strong data but its data that can be useful when setting up future research studies. I’m also thankful for this resource and that people are not self-experimenting in silence in their own chambers. I have learned a lot from these people but it’s important to always keep a critical mindset around the data that is shared.

In the near future we will also start to get even more data from other studies. One of them is the PEARL trial which was completed in December and the results will be published this year. If I have missed any other data point please let me know!


I read that exchange on X. You handled it brilliantly. He doesn’t know what he’s missing imo. I’m the one that replied to you that I greatly reduced my cholesterol over the last year while on rapa btw and without drugs. My ldl is still slightly elevated at 106 but down 99 points since December of ‘22 fwiw and all the other numbers are excellent.


The fact that convinces me over any other is that Rapamycin has worked in every single study (Over 64 and counting) in every model organism (yeast, worms, flies, mice, monkeys). The worst result was no change. If it works for every diverse lifeform, it stands to reason it will work for humans as well. My biggest concern is I may get only 1-2 years extra healthy lifespan instead of 15. :wink:

And, subjectively, I feel healthier too. I will be taking Rapamycin until the day I die or there is indisputable evidence that it is bad for me.


I think an important point about Rapamycin is that it is a single tool which assists to improve the function of mitochondria.

There are other tools that can and should be used to do the same thing.

People may not agree with my overall hypothesis about the two main aging pathways (transcription, translation). However, there has to be general agreement that mitochondrial efficiency matters for health and therefore healthspan.

My personal view is that we should get on with it and work out how best to use each of the tools that work towards this objective in the most effective synergistic manner.


Interesting about the improved function of mitochondria. Does there exist any interesting study showing this?


Do you measure your resting lactate levels? That’s probably important to assess mitochondrial efficiency.

I don’t actually. At the moment I am spending some time after Xmas and a period of working to stimulate AMPK and mitochondrial effeciency. This has as far as I can tell pushed up my metabolism such that my RHR and BP have gone up a bit. I am expecting this to come gradually down and it is doing so, but I want to get an outcome from this before having a second go at it.

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This is what the outcome of autophagy (mitophagy) is. More efficient mitochondria as new mitochondria are created.

If you will, I recommend getting a lactate meter used by cyclists etc like Lactate Scout since they require less blood. I bought an el cheapo meter (-30%) which requires more blood which gave me thrombosis of palmar digital vein since I accidentally used too large of a lancet. It went away after some time. Not dangerous though it seemed from my doctor’s opinion.

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Its a thought, however, I would think the level varies during the day depending upon what you are doing. Hence I am not sure what I would learn from it.

You could measure your maximum wattage on an ergometer that sustains a lactate level around 1.7-1.9 mmol/L. That tests your mitochondria in your muscles. Peter stopped with metformin afaik since his patients showed mitochondrial toxcity by reducing their maximum wattage.

People with metabolic syndrome have a w/kg of around 1 w/kg.
Elite atheltes iirc 3 w/kg.

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Sounds a good idea, but I would need to set up the ergometer and get the lactate measurement. As it stands I am happy tracking simple strength exercises and also maximum heart rate. What I am trying to track with this is change - if there is any change.

Anyone know when continuous lactate meters (CLMs) (similar to Dexcom and Abbots CGMs) are coming out or if any has come out?

Abbot was working on one for instance.

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Do you have any recommendation for a concrete and good protocol for doing this?

Choose a wattage on ergometer indoor bike that you can sustain for a long time. Then be ready with the lactate meter, test strip, and right before you go off the bike remove sweat from fingers with soapy water in a bucket and clean with water in another bucket, then test with an appropiate lancet and test strip asap. Lactate clears fast, and there’s lactate in sweat.



Ok. So the idea is to lock my effort at max that I can do for a long time and then test?

For some reason I thought the idea was that I would do multiple lactate measurements and try and figure out at what wattage the lactate breaks out of the range.

Well if you’re below the range for next time you can add X amounts of watts to it and test again.
It’s not useful for deconditioned people as the watt will break out of the range at very low intensities. But it can get a bit useful later.

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Ok, thx. I’ll look into it.

Thank you for this informative post @Krister_Kauppi, and especially for calling my attention to Joan Mannick’s research.