Biting tongue hard not to hit send on my snarky comment about the poor neglected white straight man being left out of science 
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Agreed, go back 10-20 years and pretty much ALL animal studies were only in males.
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Another promising result in rodent medicine. Looking forward to follow-up studies in humans.
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it is VERY interesting. Especially, it would make the basic 6mg once a week protocol totally obsolete. We would need more dose, maybe over a week, and then stop for a long time to all the thymus regenerate fully ?
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1 day for mice equals a week for humans, assuming of course that the mice in the trial were injected once a day.
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Yes… mice age 30 years to 1 human year.
I thought the same thing on this study initially. Treated 3 days… hardly a start…but that is equivalent to 3 human months.
14 days later retest after stopping is a year and 2 months.
When I do my full blood work this January. … and total body scans for everything… I will decide if I need to tweak my protocol based on results.
So Jason, are you still taking the Rapa whilst doing this HGH experiment?
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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.
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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
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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.
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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.
- Rapalog everolimus (low dose) improved influenza vaccine responses and lowered PD-1 on T cells in elderly adults—the opposite of a “damaged thymus” phenotype. Thymic injury was not reported. PubMed
- Trials using once-weekly sirolimus (e.g., 5–10 mg/week for 13–48 weeks) were designed to assess safety and healthspan metrics; protocols and early reports do not identify thymic toxicity as a concern or observed signal. (Registered protocols and reports.)
“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.”
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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.
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The full paper is included in this thread - above these posts. Just scroll up and you’ll find it.
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Here is what ChatGPT 5 suggests is the human equivalent dosing:
What the mice got
- Dose & schedule: 1 mg/kg/day, intraperitoneal (i.p.), for 3 consecutive days.
- That’s a parenteral regimen with near-complete systemic delivery.
Simple body-surface–area (BSA) scaling → Human-Equivalent Dose (HED)
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:
- 60 kg: ~4.9 mg/day
- 70 kg: ~5.7 mg/day
- 80 kg: ~6.5 mg/day
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).
Route matters (i.p. vs. oral)
- Mice received i.p. (high systemic availability).
- Humans take oral sirolimus/rapamycin , which has low and variable bioavailability (~10–20%) and a long human half-life (~60 h) .
- If you tried to match systemic exposure from the BSA-scaled 5–7 mg/day using oral tablets, you’d theoretically need a much higher oral dose (because F is low). That quickly exceeds customary clinical “longevity” pulses and isn’t sensible.
Timing equivalence (the practical bit)
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):
- Single-pulse approach (most conservative)
- ~6 mg once orally (70 kg reference).
- Rationale: matches the BSA-scaled daily amount, and the human half-life lets it cover several days of exposure without stacking daily doses.
- Split-pulse (closer to “3-day” feel, but still reasonable)
- ~6 mg on Day 0, ~4 mg on Day 2.
- Keeps total exposure modest while stretching the signal over ~3–5 days thanks to slow decay.
- Literal BSA schedule (rarely advisable)
- ~5–7 mg/day for 3 consecutive days.
- This stacks on a 60-hour half-life and will overshoot in many people. It’s closer to the mouse pattern but not to real-world PK prudence.
Bottom line
- Mathematical HED: ~0.081 mg/kg/day ⇒ ~5–7 mg/day for 3 days (60–80 kg adult).
- Translation with PK reality: prefer one pulse (~6 mg) or split pulse (6 mg then 4 mg 48 h later) rather than three consecutive daily oral doses.
- Observe effects over ~2 weeks (the mouse study watched 14 days post-course).
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.
My New Prompt after this last one:
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?
CGPT5 Response:
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
- F = 10%: 5 mg ÷ 0.10 = 50 mg/day 7 mg ÷ 0.10 = 70 mg/day
- F = 15%: 5 mg ÷ 0.15 ≈ 33 mg/day 7 mg ÷ 0.15 ≈ 47 mg/day
- F = 20%: 5 mg ÷ 0.20 = 25 mg/day 7 mg ÷ 0.20 = 35 mg/day
If you want finer granularity given published variability:
- F = 12%: 5/0.12 ≈ 41.7 mg/day ; 7/0.12 ≈ 58.3 mg/day
- F = 18%: 5/0.18 ≈ 27.8 mg/day ; 7/0.18 ≈ 38.9 mg/day
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):
- Stacking: Human half-life ≈ 60 h. Daily dosing for 3 days accumulates, so exposure will overshoot the same “per-day” systemic target unless you space doses.
- F is unstable: CYP3A4/P-gp interactions, fed vs. fasted state, and tablet vs. solution can swing AUC by >2×. That’s why literal translation from i.p. mice to oral humans is inherently noisy.
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.
Related Reading:
- Higher Dose Rapamycin - some initial results
- Second High Dose of Rapamycin topic for results
- High Dose Rapamycin + MTOR Rebound Experiment
- One User Trying Very High Doses of Rapamycin, and Negative Adverse Events / Results
- Ultra-high Dose Rapamycin Case Report 500 -1000 mg Rapamune (video)
- Why is it possible for mice to take high rapamycin doses daily?
- Why People Get Diarrhea When Taking High Doses of Rapamycin
- One Week Rapamycin High Dose Test for My Dog; Schedule and Results
- Intramuscular (IM) + Intranasal (IN) Rapamycin - A new paradigm for human longevity translation
- Attempted suicide by rapamycin (but was fine) - Case Report (103mg dosing)
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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.
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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.
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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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