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?
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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.
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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.
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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.
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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.
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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
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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.
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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.
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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.
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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?
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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.
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For the thymus regeneration potential, I dont see why it wouldnt be the case in human. Especially since we have an effect as “immune reset”. So for now personally I will use 6mg rapamune per 6 weeks or once a month.
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I am also switching from weekly to monthly Rapamycin dosing. The last time I had blood drawn, my white cell count was low. I assume the T cell count CD4 or whatever was also low.
I wonder if there would be any value in a group of us testing CD4 a year from now after following a strict Rapamycin dosage schedule. This is routinely tested in HIV patients, but we might determine a bit about Rapamycin dosing. We would need a weekly group, every other week group, and a monthly group. We might also have high and low dose people in each group. A good age adjusted CD4 hints that the thymus is working well.
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As I have stated previously let this place be a registry. We all feed the data, biomarkers, labs and regimen. Let AI do the rest! Or, may be let AI take the guided lead!
I am sure there are database experts in here besides healthcare ppl.
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" low-dose rapamycin (1 mg/kg per day for three days)"
Huh? 1mg/kg constitutes a low dose?
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So the fact that females were one commonly excluded means that it henceforth okay to exclude males?
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@msmccor100, sorry if my comment was confusing.
I wasn’t trying to take a stance on the current state of gender equality in science. However, I was trying to tease my forum friend. FYI, the kissy face emoji often denotes playfulness.
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These are rodent medicine numbers.
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Yes - and 1mg/kg IP injection is actually on the lower dosing schedule for the mammals. Here is the range:
- Mouse — 20 mg/kg/day i.p. (daily) in Nf1 mutant mice. Dose–response study measured blood/brain levels and pathway readouts at 0, 2, 5, and 20 mg/kg/day i.p.; 20 mg/kg/day suppressed AKT activation that rebounded at 5 mg/kg/day.
- Mouse — 8 mg/kg/day i.p. (daily) in Ndufs4−/− mitochondrial disease model. Repeated i.p. 8 mg/kg/day improved survival and disease metrics; same group details PK/PD and weight effects.
- Mouse — 8 mg/kg i.p. schedules (M–F or weekly) in Tsc2 tumor models. Compared 8 mg/kg i.p. regimens: M–F for 4 weeks, weekly, and hybrids; all injection routes.
- Mouse — 10 mg/kg i.p. (single-day) in BTBR behavioral model. Single 10 mg/kg i.p. dose used to test sociability/stereotypy outcomes.
- Rat — 10 mg/kg i.p. (single dose) in metabolic/behavior study. 10 mg/kg i.p. rapamycin administered to rats; outcomes measured days to weeks later.
- Rat — 20 mg/kg i.v. (single bolus) acute-tox comparison. Head-to-head acute-tox study gave rats a single 20 mg/kg intravenous dose of sirolimus; survival, hematology, organ histology assessed at 5 and 14 days.
Takeaway
- The highest repeated injection dose in mice I can document is 20 mg/kg/day i.p. (Nf1 model).
- Frequently used “high” repeated dosing is 8 mg/kg/day i.p. in disease models (e.g., Ndufs4−/−).
- In rats, clearly reported injections include 10 mg/kg i.p. (single dose) and 20 mg/kg i.v. (single bolus) in acute-tox work.
Here are the highest documented injection doses of Rapamycin (sirolimus) in mammals, route = injection only, with direct links:
• Mouse — 20 mg/kg/day i.p. (5 days/week × 2 weeks) in an NF1-mutant glioma model.
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC3857701/ 
• Mouse — 8 mg/kg/day i.p. (daily) in the Ndufs4−/− mitochondrial disease (Leigh Syndrome) model.
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC4055856/ 
• Mouse — 8 mg/kg/day i.p. (daily) more broadly referenced in dosing-response/lifespan review.
Link: https://pmc.ncbi.nlm.nih.gov/articles/PMC8190242/ 
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Sorry, I’m slow.
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