Hey Rob,
Yes, I am doing rapamycin and HGH. At 9 months on HGH and 4 years 3 months on rapamycin.
After the Kaeberlein and Fahy Optispan interview… I was with Matt on rapamycin shouldn’t be an issue on the thymus. Given this latest paper on mice and the thymus… rapamycin does great work.
Probably why Joan Mannick’s human trial worked on the immune system.
actually I continue to warn here that it is NOT what people are doing here. Once a week does not allow the thymus to recover and people are probably shriking more their thymus. I also know it was shown like that in studies. What works is the intense short term treatment followed by a long recovery
Thanks Tom,
I see what you mean… especially in view of the paper… it is the equivalent of a human year later post dosing that the improvement occurs.
Just hesitant to stop rapamycin for all the other good stuff it does for me based on Bio-markers. My inflammation is very low and Methylation DNA is also 15 years younger.
I will see if I can get a thymus measurement and T- cell generation reading in January with my other testing.
Might be why Attia is taking a break.
N=1: My thymus is fine, and I have been taking weekly high-dose rapamycin for years.
Human intermittent/weekly studies show no thymic harm signal.
“In mice, the higher the dose, the longer lifespan [6, 12, 35, 43]. Therefore, in humans, the highest dose that does not yet cause unacceptable side effects (maximal tolerated dose) may be optimal for longevity. If (unacceptable) side effects develop, the dose should be decreased. In other words, anti-aging doses are maximal doses without side effects in a particular person [34]. Then anti-aging doses are individual and side-effect-free by definition.”
“Rapamycin transiently slows thymocyte proliferation by inhibiting mTORC1; with continuous drug levels, this can shrink the thymic cortex in mice. With intermittent (weekly) dosing, drug is cleared for several half-lives between doses, allowing normal thymic cycling and avoiding sustained suppression—consistent with the reversibility seen in animal models and the lack of harm signals in human weekly studies.”
Bottom line
“The specific claim that once-weekly 5–29 mg rapamycin damages the thymus is not supported by current evidence. Signals of thymic involution come from daily exposure models and are reversible; human weekly protocols (5–10 mg/week studied so far) show no evidence of thymic damage and rapalogs have even enhanced immune responsiveness in older adults.”
From your summary I can see the thymus over-regenerated to ~130% of baseline mass within 14 days. Can someone with access to the full paper also share the thymus measurements from day 3 of the regeneration phase?
After converting time periods for mice to humans I think that (day 3 mouse) data would be more relevant to most of our intermittent dosing schedules compared to 14 days after mouse withdrawal.
The full paper is included in this thread - above these posts. Just scroll up and you’ll find it.
Here is what ChatGPT 5 suggests is the human equivalent dosing:
Use the standard Km factors (mouse = 3, human = 37):
HED (mg/kg) = 1 × (3/37) ≈ 0.081 mg/kg/day.
Per-day HED by body weight:
If you copy the mouse schedule literally, that’s ~5–7 mg/day for 3 days in a 60–80 kg adult (systemic-equivalent, notaccounting for route).
Because the human half-life is long, three daily mouse injections don’t map 1:1 to three daily human oral doses. After a single human oral dose, levels persist for several days.
Reasonable human analogs people use to approximate the pattern (not exact AUC):
This is a pharmacologic approximation, not medical advice. Individual PK varies (CYP3A4, P-gp, food effect), so clinicians often start lower and titrate to target troughs/exposure if they’re aiming for a research-grade match.
While I know its not sensible or recommended, I’m just curious about what the equivalent systemic exposure dose would be from the BSA-scaled 5–7 mg/day using oral tablets, you’d theoretically need a much higher oral dose (because F is low). What is that theoretical higher dose calculated to be?
If you want to match the systemic exposure of the BSA-scaled i.p. dose (~5–7 mg/day reaching the bloodstream), then the oral dose must be divided by oral bioavailability (F). Using typical sirolimus F ≈ 10–20% (huge person-to-person spread), the math is:
Required oral dose = systemic target ÷ F
If you want finer granularity given published variability:
So the theoretical oral range to mimic 5–7 mg/day systemic is roughly 25–70 mg/day, with most people landing around 33–47 mg/day if you assume F ≈ 15%.
Two reality checks (not advice, just pharmacokinetics):
But purely on the math you asked for: ~25–70 mg oral sirolimus per day for three days would be the theoretical exposure-matching band for the BSA-scaled 5–7 mg/day i.p. equivalent.
Huge fail right there. No idea why peer reviewers didn’t ask that.
Unfortunately I can’t get too excited, other than this is an interesting phenomenon/observation.
If this study pans out we have a great biomarker to look at. The thymus can be evaluated by imaging right? Longevity studies take a long time—even in mice. But a study of various doses and dose intervals in dogs or marmosets might only take a couple of months to give important results on the thymus. It should not be necessary to sacrifice the animals either,
We don’t know the ideal dose or dose interval of Rapamycin for treating sarcopenia. My guess is that the magic happens during the trough period. When mtor signaling has been restored, normal growth also resumes.
Seems to mean we would have to stop taking rapamycin for 2-4 weeks to let the thymus regenerate. Then, if we started again, would it shrink?
This is the most interesting news in a while!
Fahy’s thymus rejuvenation is one of the main interesting therapies besides rapa right now, and thymic degeneration is one of the main risks to using rapa.
We are missing some crucial data to interpret this, I think:
Evidence that rapa extends lifespan in mice used continuous dosing, not this protocol. Does the protocol here extend mice lifespan, and does the thymus also regenerate with continuous dosing used in past lifespan trials? Which is to say: are lifespan benefits in spite of, or because of, or aside from, this thymus effect?
What happens in humans? This seems short enough time period to feasibly trial and measure, as opposed to mortality or lifespan.
I recall someone mentioning Brad Stanfield saying there may be an indication that less frequent rapa dosing (1x / 6 weeks) may be best, based on his data that is not yet published.
To be honest, I took this as an indication that there were not much results in the study, or even that rapa could be seeming bad for humans based on the data so less frequent is less bad. But this thread may provide an interesting alternative explanation - allowing thymic rejuvenation. Eager to see his data.
The recent article: Thymic Regeneration in Female mice Following Short-term Rapamycin administration got me thinking about Dr. Fahy’s Thymus TRIIM Trials. Needed to PM the best source for this – Longevity Rock Star Matt Kaeberlein.
Hey Matt and Tammi -
I know you both are a very busy as researcher and support, you are highly trusted in your work, which would make the demand on your time exceedingly high. Forgive me asking - but I think you might have a gut feeling on this important topic relating to rapamycin and thymus. In view of your interview with Dr. Greg Fahy - he states he thinks rapamycin could be detrimental to the thymus. A new report shows rapamycin might do on its own - what Dr. Fahy is doing with HGH. But, post the rapamycin dosing regimen a long pause is needed (based on my converting mice days to human months).
Do you have a hunch? I realize it is one paper and my question deals with translation from mice to humans - and it’s a Chinese study. LOL
I have been on HGH since January 2025 (after researching thymus regeneration with my personal physician) and on rapamycin no breaks since August 2021. Any thoughts - concerns on the thymus?
mkaeberlein Longevity Researcher & Expert
It’s a really interesting question. My intuition is that the “involution” seen in the mice here is a bit different than the age-associated involution we see in people. Rapa will decrease cell size but typically not cell number and shouldn’t affect composition. Dose is also quite different here, compared to off-label dosing regimens. It’s an educated guess, but I don’t think you would be doing any real harm to your thymus taking rapamycin continuously, although you might be temporarily reducing size.
Of course, most people taking rapamycin off-label already have undergone true thymic involution, so that’s probably not significant at that point. As you may know, I personally cycle rapamycin, typically staying on for 3 months or so at a time. If you are taking HGH to reverse thymic involution, I’d consider taking a break from rapamycin for a few months and monitoring thymic size and function if possible. I don’t think you need to do any sort of time conversion from mice to humans for this, since the kinetics of effects of rapa on inflammation/cell size seem to be pretty much the same (days to weeks) in humans and mice.
Overall, my guess is that if you’re going to see a bump in thymic regeneration, 3 months off rapa is a long enough to see it. Of course, it may not even be necessary to take time off rapa to see this… wish we had more data!
Feel free to share the response publicly.
I was also thinking a little about the Fehy studies. I wonder if perhaps all the benefits Fahy is seeing (with rHGH, DHEA and Metformin) could actually less than what he’d see just using rapamycin. Seems like a comparison study needs to be done.
That’s the bit I’m struggling with. It would seem to argue for a more intense/pulsed strategy. Which is actually where I seem to have settled. I’m essentially 3 months on, 3 months off. If the rebound is greater than the suppression then there should be a ratcheting upwards.
And I wonder if adding HGH (or a secretagogue) during ‘rapamycin off’ would be an effective strategy to boost the ratchet.
Fahy may be announcing his new 90 day protocol soon… which would fit quite nicely
So I’m wondering given what MK said in his response to your question if it might be beneficial for you to stop the Rapa now until that January blood work up to let the HGH really give a boost to your thymus.
Think of it as now taking the brakes off for the last couple of months.
I’d be mightily surprised if you noticed loss of Rapa benefits for two months. (Even if you did that would be an interesting data point for you and I’m sure you’d get the benefits straight back again after a few weeks).
Would be interested to know what you decide to do.
Hey Roberto… 
That is exactly what I plan… no rapamycin until the end of January… basically 3 full months.
Contiuing HGH… at 3.3 iu daily and then end of January 2026 doing a full thymus scan and new T-cell numbers reading… DEXA bone density and fat- adipose tissue reading, Coronary Calcium Scan, GlycanAge Inflammation score, and DNA methylation reading. With a full blood panel review.
Start off the new year with a full work up.
My medical university is changing health insurance, so I can do all of these tests at once with the new provider. I just checked with them.
We need to be very skeptical and cautious when using mice as a model for human organ/tissue regeneration. Mice can quickly heal very large wounds, can regenerate amputated digits, regrow damaged cartilage, and exhibit a host of regenerative capacities that humans do not possess.
What this study actually shows is that high-dose rapamycin damages the thymus (something seen in numerous older studies in mice and primates), but that mice then mount a regenerative response that increases thymic mass beyond baseline.
We don’t know if humans respond in a similar way. It is entirely possible, even likely, that we don’t exhibit a similar regenerative response, and that high-dose rapamycin is toxic to thymocytes without stimulating regrowth.
With that said, I doubt that the low dose intermittent dosing that most people are using will atrophy the thymus the way that high doses do in mice. But higher doses or continuous doses likely would. I highly doubt that rapamycin is a route towards thymic regeneration in humans.
Yes - we always need to be cautious. At the same time the record for rapamycin at improving function of aging organs has been demonstrated in many different studies, and has shown cardiac benefits in dogs too.
See this thread for past related studies: Can Rapamycin repair your organs and therefore reverse aging?
Sure. I’m not speaking to benefits observed in other tissues, only the purported stimulation of thymic regeneration.
I’m convinced of the value of rapamycin for many other longevity purposes, just not thymic regeneration for the reasons mentioned.