Sirolimus Rx dosage: what the human and mouse data show

Last updated 2026-07-27

What dose of sirolimus do people actually use for longevity?

Nobody has a validated answer, and anyone who tells you otherwise is selling something. What circulates online and in some physician practices is a once-weekly dose somewhere between 1mg and 10mg, taken as a single pulse rather than the daily dosing used in transplant medicine. The logic borrows from the PEARL trial (Participatory Evaluation of Aging with Rapamycin for Longevity), a small crowdfunded human study out of AKG Longevity/led by researchers including Joan Mannick's prior work informing the design, which tested 5mg and 10mg once-weekly doses against placebo in adults over roughly 48-52 weeks ^[1]. PEARL was not a lifespan trial. It looked at bone density, frailty measures, and patient-reported outcomes in healthy older adults, and it was underpowered and short. The published results (Kaeberlein lab, University of Washington, in Aging journal) reported that participants receiving rapamycin group-wise had no significant difference in bone mineral density and mixed, largely non-significant results on secondary measures, though the trial supported feasibility and safety of intermittent dosing in this population ^[1]. So when you see a 6mg weekly dose or a 5mg-then-10mg titration schedule referenced by longevity clinics, that dosing choice traces back to PEARL's protocol design and to transplant-derived pharmacokinetics, not to any demonstrated life-extension effect in humans. If you want the actual math behind converting a target blood level or weekly total into a specific tablet or reconstituted dose, that is a separate calculation problem, and a Sirolimus Rx dosage calculator exists for working through the arithmetic; it does not substitute for physician oversight.

Is sirolimus the same thing as rapamycin?

Yes. Sirolimus and rapamycin are the same molecule (chemical name sirolimus; rapamycin is the older name derived from Rapa Nui, Easter Island, where the soil bacterium Streptomyces hygroscopicus that produces it was first isolated in the 1970s) ^[2]. Sirolimus is the generic drug name used on FDA labeling; "rapamycin" persists in scientific literature and longevity discussion out of habit and history. Brand-name formulations include Rapamune (oral sirolimus, approved by the FDA in 1999 for prophylaxis of organ rejection in kidney transplant patients age 13 and older) ^[3], and newer albumin-bound formulations, Fyarro (for malignant perivascular epithelioid cell tumor) and Hyftor (topical, for facial angiofibromas in tuberous sclerosis complex) ^[4][5]. None of these approvals cover aging, longevity, or lifespan extension. Every longevity use of sirolimus in humans today is off-label, full stop.

What does the mouse lifespan data actually show?

This is where the evidence is genuinely strong, and it's the reason sirolimus gets taken seriously at all in longevity circles. The National Institute on Aging's Interventions Testing Program (ITP), running since 2004 across three test sites (Jackson Laboratory, University of Michigan, University of Texas Health San Antonio), has tested rapamycin in genetically heterogeneous mice at multiple doses and starting ages ^[6]. The headline results: rapamycin started at 9 months of age extended median lifespan by about 23% in males and 26% in females in the ITP's 2011 cohort report (Harrison et al., Nature) ^[7]. Later cohorts starting rapamycin later in life (20 months) still showed extension, roughly 9-14% depending on sex and dose, suggesting benefit even when treatment starts late in the animal's life ^[6]. Effects have been dose-dependent and, notably, more pronounced in females at lower doses in some cohorts, a sex difference nobody fully understands yet. This is the strongest, most replicated pharmacological lifespan-extension finding in mammalian aging research. But it is mouse data, generated with continuous or near-continuous feeding-based dosing in animals with lifespans of two to three years, not weekly injections in humans living eight decades. Translating an ITP mouse dose to a human equivalent dose is not a simple weight-based scaling; mouse and human mTOR pharmacokinetics, feeding patterns, and metabolic rates differ enough that any human dose claim derived from ITP numbers is an extrapolation, not a translation.

Why is there still no completed human lifespan trial?

Because a human lifespan trial for a drug like sirolimus would take decades and enormous cost, and no funder has committed to running one to completion. A trial powered to detect a mortality difference in humans would need thousands of participants followed for many years, plausibly a decade or more, given human lifespans and the noise in all-cause mortality data. What exists instead are short surrogate-endpoint studies. Besides PEARL, there's a 2019 trial (Mannick et al., published in Lancet's eBioMedicine and earlier Science Translational Medicine work) testing low-dose mTOR inhibitor combinations (not sirolimus alone, but rapalogs like RTB101) in elderly adults, which found reduced incidence of respiratory tract infections over a winter season, a proxy for immune aging, not a lifespan or mortality endpoint . A separate small study looked at topical/oral sirolimus effects on skin aging markers in a handful of participants . None of this constitutes proof that sirolimus extends human lifespan. The honest statement, repeated because it needs repeating every time this topic comes up, is: strong mouse data, no completed human lifespan trial, off-label everything in between.

What is the typical dosing schedule (daily vs weekly)?

Transplant dosing (the only FDA-approved use) is daily: Rapamune's label specifies a loading dose followed by daily maintenance dosing adjusted to trough blood levels, typically targeted between 5-15 ng/mL depending on the transplant regimen and concomitant drugs ^[3]. This daily dosing is designed to maintain continuous immunosuppression, which is the whole point after an organ transplant. Off-label longevity protocols almost universally use intermittent, once-weekly pulse dosing instead, a strategy popularized by Kaeberlein and colleagues based on animal data suggesting that intermittent mTOR inhibition captures much of the benefit while allowing immune function to recover between doses . The theory is plausible pharmacologically (sirolimus has a long half-life, discussed in more detail in Sirolimus Rx half life), but the once-weekly human longevity schedule has not itself been validated against any hard outcome beyond PEARL's short, mostly-null secondary endpoints. Some protocols use a biweekly or every-10-day schedule instead, and cycling on and off over months is common practice among prescribers, discussed further under Sirolimus Rx cycle length. None of these schedules have head-to-head human data comparing them against each other for any aging-related outcome.

What are the real risks and side effects at longevity doses?

Mouth ulcers (stomatitis) are the most commonly reported side effect even at low, intermittent longevity doses, showing up in a meaningful fraction of PEARL participants and widely reported anecdotally in off-label use ^[1]. They're usually manageable, sometimes dose-limiting, and one of the more concrete signs that a dose is high enough to be doing something pharmacologically. Immunosuppression is the risk that matters most and gets underplayed. Sirolimus is an immunosuppressant; that is its FDA-approved mechanism of action, used deliberately to prevent transplant rejection. Even at lower, pulsed longevity doses, it suppresses parts of adaptive immune signaling through mTOR inhibition, and the RTB101 trial data suggesting reduced respiratory infections cuts both ways: mTOR inhibition changed immune response, and it is not guaranteed that every immune change is beneficial, especially around vaccination timing or active infection. Anyone on a longevity dosing schedule should not be taking it during acute illness, and vaccine timing (particularly live vaccines) deserves case-by-case coordination with a prescriber. Metabolic effects are the third real concern. Sirolimus's package insert documents dyslipidemia (elevated triglycerides and cholesterol) and new-onset hyperglycemia as adverse effects in transplant populations on daily dosing ^[3]. Whether intermittent low-dose weekly use carries meaningfully lower metabolic risk is plausible but not proven; lipid panels and fasting glucose are reasonable things to monitor periodically if someone is using it long-term off-label. Other known effects in transplant literature include impaired wound healing, elevated risk of certain infections, and rare but serious pulmonary toxicity (interstitial lung disease), all documented at the daily therapeutic doses used in transplant medicine rather than at low weekly pulses, but they set the outer bound of what this drug class can do to a body ^[3].

How do longevity doses compare to transplant doses?

The gap between an FDA-labeled transplant dose and a typical off-label longevity dose is large, and it's worth seeing side by side. | Use case | Typical dose | Schedule | Approved use? |

How is the dose adjusted for body weight or blood levels?

In transplant medicine, dosing is titrated to a measured trough blood level (5-15 ng/mL typically, drawn via a validated immunoassay or LC-MS/MS method) rather than fixed by weight alone, per the Rapamune label's monitoring guidance ^[3]. This is precision medicine forced by a narrow therapeutic window and serious consequences (rejection on one side, toxicity on the other). Off-label longevity dosing rarely uses this level of monitoring. Some prescribers check periodic trough levels to confirm the drug is being absorbed and cleared as expected, and to catch outliers, but there's no established target range for longevity use the way there is for transplant. A prescriber choosing 6mg weekly for a 70kg adult and 6mg weekly for a 100kg adult isn't following a validated weight-based formula; they're picking a starting point from precedent and adjusting based on side effects (mouth ulcers, GI upset) rather than a proven biomarker. This is one more way the off-label longevity use diverges from the FDA-approved use: the approved use has rules; the longevity use has judgment calls.

What does a typical off-label protocol look like in practice?

Most protocols people discuss follow a similar shape, though the specific numbers are prescriber-dependent and not standardized by any guideline body: a starting dose (often lower, like 1mg or 2mg weekly, or a compounded liquid dose reconstituted at home), a step-up over some weeks if tolerated, periodic bloodwork (lipid panel, fasting glucose, occasionally a trough sirolimus level and CBC), and ongoing monitoring for mouth ulcers or other side effects. Home-administered compounded or injectable formulations require correct reconstitution and storage; details on that process are covered separately in how to reconstitute Sirolimus Rx, and injection technique and site rotation in Sirolimus Rx how to inject and Sirolimus Rx injection sites. None of these logistics questions should be attempted without a prescriber who is actually reviewing bloodwork and adjusting the plan; sirolimus has real drug interactions (notably CYP3A4 substrates, grapefruit juice, and certain antifungals materially raise blood levels) documented in the FDA label ^[3], and self-directed dosing without monitoring is how people end up with a level far outside anything ever studied.

Should I start sirolimus for longevity and at what dose?

That decision belongs with a physician who has reviewed your bloodwork, medical history, and current medications, not with a dosage chart on a website. What can be said honestly: the mouse data supporting rapamycin as a lifespan-extension compound is some of the most replicated pharmacological aging data that exists (roughly 9-26% median lifespan extension across NIA ITP cohorts depending on sex, dose, and start age) ^[6][7]. What can also be said honestly: there is no completed human trial showing sirolimus extends human lifespan or delays a hard clinical endpoint like all-cause mortality, and every weekly-dose protocol in circulation is an extrapolation from short surrogate-endpoint studies and transplant pharmacology, not a validated longevity dose. The route that makes sense if you're going to pursue this off-label is provider-reviewed: bloodwork before starting, a prescriber who adjusts based on your labs and side effects rather than a fixed internet protocol, and a pharmacy that actually handles the fulfillment correctly. Sirolimus Rx works with a provider-reviewed process and names its fulfilling pharmacy partner rather than compounding or dispensing anything itself; that structure (real oversight, real pharmacy, transparent sourcing) is the baseline worth expecting from anyone offering this off-label. Nobody should be buying sirolimus from an unverified online source without labs and a prescriber attached to it.

Frequently asked questions

What is the standard longevity dose of sirolimus?

There is no standard, validated longevity dose. Off-label protocols in circulation range roughly from 1mg to 10mg once weekly, a schedule borrowed from the PEARL trial's 5mg/10mg weekly design ^[1], not from any completed lifespan study. Doses are typically adjusted by a prescriber based on side effects and periodic bloodwork rather than a fixed formula.

Is rapamycin the same as sirolimus?

Yes, they are the same molecule. Sirolimus is the generic drug name on FDA labeling (Rapamune); rapamycin is the original name from the compound's discovery in soil bacteria on Rapa Nui (Easter Island) in the 1970s ^[2]. The terms are used interchangeably in scientific and longevity literature.

Has a human lifespan trial for sirolimus ever been completed?

No. No completed trial has measured sirolimus's effect on human lifespan or all-cause mortality. Existing human studies, like PEARL (bone density, frailty measures) ^[1] and the RTB101 respiratory infection trial ^[8], used short surrogate endpoints over less than a year, not survival data over a meaningful fraction of a human lifespan.

How much does rapamycin extend lifespan in mice?

NIA Interventions Testing Program data showed median lifespan extension of roughly 23% in males and 26% in females when rapamycin was started at 9 months of age, with smaller but still significant extensions (about 9-14%) when started later, around 20 months ^[6][7]. This is mouse data across multiple genetically diverse cohorts, not a human result.

Is sirolimus dosing daily or weekly for longevity use?

Off-label longevity protocols almost always use weekly (sometimes biweekly) pulse dosing, unlike the daily dosing used in FDA-approved transplant medicine ^[3]. The intermittent schedule is meant to allow immune recovery between doses, a strategy with some supporting mouse data but no validated human outcome trial behind the specific weekly schedule.

What are the biggest risks of low-dose sirolimus?

The three most documented real risks are mouth ulcers (stomatitis, common even at low doses) ^[1], immunosuppression (sirolimus's core FDA-approved mechanism, relevant during infections or around vaccination) ^[3], and metabolic effects like elevated triglycerides, cholesterol, or blood glucose, documented in transplant-dose data ^[3] and plausible but less studied at lower intermittent doses.

Is sirolimus FDA-approved for anti-aging or longevity?

No. Sirolimus is FDA-approved only for kidney transplant rejection prophylaxis (Rapamune, approved 1999) ^[3], and in other formulations for a rare tumor (Fyarro) ^[4] and facial angiofibromas in tuberous sclerosis complex (Hyftor) ^[5]. Any use for aging, longevity, or lifespan extension is entirely off-label.

What blood level should sirolimus be monitored at for longevity use?

There is no established target trough level for longevity use, unlike the 5-15 ng/mL range used in transplant dosing per the Rapamune label ^[3]. Some prescribers check periodic levels to confirm absorption and clearance, but the target range is a clinical judgment call, not a validated standard.

Can I take sirolimus with grapefruit juice or other medications?

No, grapefruit juice should be avoided; it inhibits CYP3A4 metabolism and can raise sirolimus blood levels substantially, per the FDA label's drug interaction warnings ^[3]. Certain antifungals, macrolide antibiotics, and other CYP3A4 inhibitors or inducers also meaningfully change sirolimus levels and require prescriber review before combining.

How long is a typical sirolimus longevity cycle?

There is no standardized cycle length; protocols vary by prescriber. Some run continuous weekly dosing for months with periodic labs, others use defined on/off cycles. The PEARL trial ran its weekly dosing protocol for about 48 to 52 weeks ^[1], which is one of the only structured duration references available, though it wasn't testing an on/off cycle.

Why do people use weekly pulse dosing instead of daily dosing for longevity?

The theory, based on animal and pharmacokinetic reasoning popularized by researchers like Matt Kaeberlein, is that intermittent high-dose pulses may inhibit mTOR signaling in a way that captures anti-aging benefits while allowing immune function to recover between doses ^[10]. This has plausibility but has not been validated against any hard human aging or mortality outcome.

Does sirolimus cause immunosuppression at low longevity doses?

Sirolimus's core FDA-approved mechanism is immunosuppression, used deliberately in transplant patients ^[3]. At lower, intermittent longevity doses the degree of immune suppression is less than continuous daily transplant dosing, but it is not zero, and prescribers generally advise against dosing during active infections and recommend coordinating vaccine timing.

Sources

1. Kaeberlein Lab / Aging (journal), PEARL trial results: PEARL trial tested 5mg and 10mg once-weekly sirolimus in older adults over about 48 weeks, with mouth ulcers as a common side effect and no significant bone density benefit
2. FDA, Hyftor approval: Hyftor (topical sirolimus) is FDA-approved for facial angiofibroma associated with tuberous sclerosis complex
3. National Institute on Aging, Interventions Testing Program: The NIA Interventions Testing Program has tested rapamycin across multiple sites and doses in genetically heterogeneous mice since 2004
4. Harrison et al., Nature 2009 / ITP rapamycin lifespan findings: Rapamycin extended median lifespan in genetically heterogeneous mice even when started late in life, in the original ITP rapamycin cohort report
5. Mannick et al., Lancet Healthy Longevity/eBioMedicine, RTB101 trial: Low-dose mTOR inhibitor treatment (RTB101) reduced incidence of respiratory tract infections in elderly adults over a winter season
6. PubMed, topical sirolimus skin aging pilot study: A small pilot study evaluated topical sirolimus effects on skin aging markers in human participants
7. Kaeberlein, npj Aging and Mechanisms of Disease, intermittent rapamycin dosing rationale: Intermittent dosing strategies for rapamycin are proposed to separate benefits on aging from continuous immunosuppressive effects