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All peptides
mTOR inhibitor (NOT a peptide)

Rapamycin

Also known as: Sirolimus, Rapamune, Macrocyclic lactone — 31-carbon macrolide

Tier 1 — Human RCTReviewed 2026-05-05

Approved immunosuppressant for transplant; the canonical mTOR inhibitor. Off-label longevity dosing (5–8 mg weekly) is widely community-practiced; PEARL Phase 2 (2024) is the largest healthy-adult RCT and was equivocal.

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Overview

Rapamycin (sirolimus, Rapamune) is a small-molecule macrocyclic lactone — not a peptide — that inhibits mTORC1 signaling. It is included in this 'peptide companion' library for the same reason as NAD+ and glutathione: longevity-clinic and self-experimenter communities routinely stack it with peptide regimens, and competitor apps quietly include it without disclosing it isn't a peptide. Its clinical pedigree is excellent for its approved use (kidney-transplant rejection prophylaxis since 1999) and for tuberous sclerosis complex. The longevity application — once-weekly dosing of 5–8 mg in healthy adults to mimic the lifespan-extension findings in mice — is community practice rather than approved use. The PEARL Phase 2 trial (Mannick / AgelessRx, 2024-2025 readouts) is the largest healthy-adult RCT on intermittent rapamycin and gave equivocal results.

Mechanism

Binds FKBP12, and the rapamycin–FKBP12 complex binds and inhibits mTORC1 (mechanistic target of rapamycin complex 1). mTORC1 is a master integrator of nutrient, growth-factor, and energy signaling — inhibiting it shifts cells from anabolic/growth modes toward autophagy and stress resistance. Chronic / continuous dosing also affects mTORC2 (insulin-signaling axis), which underlies several of the metabolic side effects (hyperglycemia, dyslipidemia). Intermittent (weekly) low-dose schedules are designed to preferentially hit mTORC1 while sparing mTORC2.

Evidence by indication

We classify each indication separately. The same peptide can be Tier 1 for one use and Tier 4 for another. Tiers reflect the published literature, not the strength of community framing.

Kidney transplant rejection prophylaxis

Tier 1high confidence

FDA-approved since 1999 (Rapamune). Multiple Phase 3 trials demonstrated efficacy as part of immunosuppression regimens. This is the foundational clinical evidence base.

Kahan BD et al. 2000

Tuberous sclerosis complex (subependymal giant cell astrocytoma, lymphangioleiomyomatosis)

Tier 1high confidence

FDA-approved for these TSC manifestations based on clinical evidence in subgroups; everolimus (close analog) shares the indication.

No primary citations are anchored to this indication — the tier reflects the absence of usable literature, not a missing reference.

Healthy human longevity / 'lifespan extension' off-label

Tier 3high confidence

Mouse Interventions Testing Program established lifespan extension in multiple genetic backgrounds — the most reproducible longevity intervention in rodents. PEARL Phase 2 RCT (n≈122) in healthy adults reported some functional improvements but mixed primary outcomes. Tier 3 reflects strong preclinical + emerging but underpowered human RCT evidence.

AgelessRx / Mannick JB et al. et al. 2024

Immune-system rejuvenation in older adults

Tier 3medium confidence

Mannick 2014 and subsequent work showed mTOR inhibitors (RAD001/everolimus and rapamycin) can improve influenza-vaccine responses in older adults — an immune-rejuvenation signal. Tier 3 reflects translational human work that has not converted into approved indication.

Mannick JB et al. 2014

General anti-aging in healthy adults

Tier 3high confidence

Mechanistically the strongest case in this library for any small molecule. PEARL provides the first dedicated healthy-adult RCT data. The story is interesting; the data is not yet definitive.

AgelessRx / Mannick JB et al. et al. 2024

Studied dose ranges

The ranges below come from published trial protocols where available, and from documented self-experimenter consensus where the literature does not include human dose-finding work. The notes flag which is which.

1,000–8,000 mcgonce weekly (longevity off-label) or once daily (transplant) · oral

Longevity off-label dosing is typically 5–8 mg orally once weekly (5,000–8,000 mcg/week). Transplant dosing is daily (2–10 mg/day) and titrated to whole-blood trough level. The off-label longevity dose schedule is community practice — not what the drug was approved for.

Contraindications

  • Active infection (rapamycin is immunosuppressive, even at intermittent doses)
  • Active malignancy where the immune system is part of tumor surveillance
  • Pregnancy and breastfeeding (teratogenic risk)
  • Major surgery within ~2 weeks (impaired wound healing — a real, recurring side effect)
  • Uncontrolled hypercholesterolemia or hypertriglyceridemia (rapamycin worsens both)
  • Severe hepatic impairment
  • Concurrent use with strong CYP3A4 inhibitors / inducers without dose adjustment
  • Live vaccines (efficacy may be reduced; some live vaccines are contraindicated)

Reported side effects

  • Oral aphthous ulcers / mouth sores (the most common dose-limiting side effect of intermittent dosing)
  • Impaired wound healing (clinically meaningful; users typically pause before/after surgery or dental work)
  • Hyperlipidemia — elevated LDL and triglycerides (more pronounced with daily than weekly dosing)
  • Hyperglycemia / mild insulin resistance
  • Increased infection risk — herpes reactivation, sinusitis, UTI
  • Edema, including peripheral and pulmonary
  • Thrombocytopenia, anemia, neutropenia (cytopenias)
  • Proteinuria
  • Acneiform rash
  • Pneumonitis (rare, can be life-threatening; requires immediate evaluation)

Reconstitution & storage

Oral tablet or oral solution — no reconstitution. Generic sirolimus is widely available through pharmacy channels with a prescription.

Storage. Tablets: room temperature per label. Solution: refrigerate 2–8 °C; once opened, follow label timing.

Open the peptide calculator → to compute exact draw volumes for your specific vial and BAC water choice.

Editorial note

DRAFT — pending Wayne's review. Rapamycin is the canonical 'longevity small molecule' and not a peptide — the class field says so explicitly to prevent user confusion (same convention as NAD+). Editorial position: respect the Tier 1 transplant indication, give honest Tier 3 framing to the longevity application (it is the strongest small-molecule longevity candidate, but PEARL is one Phase 2 trial), and never under-disclose the mouth-ulcer / wound-healing / immunosuppressive side-effect profile. The community 'low-dose intermittent' framing does mitigate side effects somewhat but does not eliminate them.

Citations

  1. [1]
    Efficacy of sirolimus compared with azathioprine for reduction of acute renal allograft rejection: a randomised multicentre study
    Kahan BD · Lancet · 2000 · PMID 10872008
    Foundational Phase 3 transplant trial — anchor for the FDA-approved indication.
    View source
  2. [2]
    mTOR inhibition improves immune function in the elderly
    Mannick JB, Del Giudice G, Lattanzi M, et al. · Science Translational Medicine · 2014 · PMID 25540326
    Translational evidence that mTOR inhibition improves vaccine response in older adults — anchor for immune-rejuvenation indication.
    View source
  3. [3]
    PEARL: Participatory Evaluation of Aging with Rapamycin for Longevity (Phase 2 RCT readouts, 2024-2025)
    AgelessRx / Mannick JB et al. · Aging Cell / preprint readouts · 2024
    Largest healthy-adult RCT of intermittent rapamycin to date; mixed-positive readouts. Anchor for Tier 3 longevity indication.
    View source