Longevity FDA-approved medicinePrescription drug

Rapamycin

Sirolimus · Rapamune

Evidence: Approved label. Example dose: finalize with a provider. Not a fact-check stamp.

1-6mg – 5-6 mg Oral weekly

Rapamycin (sirolimus) is a macrolide compound originally isolated from the bacterium Streptomyces hygroscopicus found in soil samples from Easter Island (Rapa Nui) in 1972. It is FDA-approved as an immunosuppressant to prevent organ transplant rejection (brand name Rapamune, approved 1999) and is also used in drug-eluting coronary stents. It works by inhibiting the mechanistic target of rapamycin (mTOR), a kinase that serves as a central regulator of cell growth, metabolism, and aging.

Quick Start

Route

Oral

Start low

1-6mg Oral

Frequency

weekly

Timing

Bioavailability increases with high-fat meal; take consistently (fed or fasted)

❋

Start here. Every protocol below is ordered lowest-first. Begin at the smallest effective dose, hold about a week to assess tolerance, and step up only if needed.

Tiered Protocols · lowest first

Conservative start

1-6mg · Oral · weekly

conservative starter

1-6mg

weekly

Expert

Longevity mTOR Inhibition

5-6 mg · Oral · Weekly

human clinical trial · Mannick et al. 2014 (Sci Transl Med 6:268ra179)

Must be dosed weekly, never daily, to selectively inhibit mTORC1 without heavily suppressing mTORC2. Take with a fatty meal to triple absorption.

5-6 mg

Weekly

◆

How it works

Binds to the intracellular protein FKBP12, forming a complex that inhibits mTOR complex 1 (mTORC1), a master regulator of cell growth, protein synthesis, and autophagy. Inhibition of mTORC1 activates autophagy and reduces cellular senescence.

Upregulates autophagy - the cellular recycling process that clears damaged proteins and organelles - which declines with age and is thought to be a key mechanism behind its lifespan extension effects.

At immunosuppressive doses, also inhibits mTOR complex 2 (mTORC2) with chronic exposure, which affects insulin signaling and lipid metabolism. Intermittent dosing preferentially targets mTORC1 while sparing mTORC2.

What to expect

Early

Days 1–7

Weeks 1-4: Minimal subjective changes. Drug is building tissue levels. Mouth sores possible (usually mild at low doses).

Evidence

HumanPresent

AnimalPresent

In-vitroStrong

Each reference below was re-fetched from its PubMed record, and the quoted sentence was confirmed to appear in that abstract and to support the claim it sits under. Follow any of them to read the source.

Rapamycin and its analogs (everolimus, temsirolimus, ridaforolimus) inhibit the mammalian target of rapamycin (mTOR) kinase by binding to FK506-binding proteins (FKBP) and have a similar chemical structure that only differs in the functional group present at carbon-40.

Rapamycin and its analogs (everolimus, temsirolimus, ridaforolimus) inhibit the mammalian target of rapamycin (mTOR) kinase by binding to FK506-binding proteins (FKBP) and have a similar chemical structure that only differs in the functional group present at carbon-40.

Why Is Rapamycin Not a Rapalog? Gerontology · 2023 · PMID 36617414

Evidence scope. Mechanistic review; does not support the card's intermittent longevity regimen.

Claims we could not support

No abstract we checked supports these for this molecule at this route. That is not the same as saying they are false — it marks where the evidence is missing.

Dose/route: 1-6mg via Oral, weekly. No checked live PubMed abstract supported this complete molecule/formulation/route/dose/frequency combination.

Primary safety claim: Mouth sores / aphthous ulcers (most common, usually dose-dependent). No checked live abstract directly established this as the primary concern for the card's exact formulation and regimen.

Interactions & stacking

Two different questions: what is documented about running these together, and what is documented about drawing them into the same syringe. A good pharmacological partner can still have to be pinned separately.

Documented together

MelatoninAntioxidant and circadian regulator does not interact with mTOR pathway

PregnenoloneNeurosteroid precursor and mTOR inhibitor act through unrelated pathways

NAD+NAD+ supports sirtuin activity and mitochondrial function, complementary to but independent of mTOR inhibition

MOTS-cMitochondrial peptide and mTOR inhibitor both support metabolic health through distinct mechanisms

Keep separate

Thymosin Alpha-1Rapamycin is immunosuppressive at higher doses while TA-1 is immunostimulatory - opposing effects on immune function may reduce efficacy of both

ThymulinRapamycin suppresses T-cell activation via mTOR while thymulin promotes T-cell maturation - conflicting immune signals

ThymopentinmTOR inhibition by rapamycin suppresses T-cell proliferation while thymopentin promotes it - contradictory immune modulation

IGF-1 LR3IGF-1 strongly activates mTOR/PI3K/Akt pathway, directly opposing rapamycin mTOR inhibition

Check any specific pair in the Stack & Interaction Checker, which answers both questions separately. Absence of a documented conflict is not evidence of safety.

Pharmacokinetics

Illustrative plasma concentration · 10 d

Half-life

~62 hours

Peak · Tmax

1-3 hours

Oral

Elimination

~13 days

~5x half-life

Bioavailability

~14%

Oral (significant first-pass metabolism; increased with high-fat meal)

Duration of action

7-10 days

Per dose (mTORC1 inhibition persists beyond plasma clearance; weekly dosing maintains effect)

Clearance

Hepatic (CYP3A4, P-glycoprotein substrate)

Storage. Store at room temperature (20-25C). Protect from light. Oral compound - no reconstitution needed.

Regulatory status

FDA-approved (Rapamune/sirolimus) for renal transplant rejection prevention and lymphangioleiomyomatosis. Use for longevity/aging is off-label. Prescription required.

Put it to work

Calculate, log & track

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Go deeper

The guide & community

The complete Rapamycin walkthrough, real protocol discussion and coaching live inside the BlessUp community on Skool.

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