Macrolide mTOR inhibitor; not a peptide

Rapamycin (sirolimus)

aka Sirolimus · Rapamune

Evidence grade
Grade C: Preliminary human data
for longevity / healthy ageing (off-label, low intermittent dosing)
User score too few reports (9) needs ≥ 10 reports
US FDA Approved for transplant & LAM only checked 2026-11-13
WADA 2026 Not named no clearance either · checked 2026-11-13
EU Rapamune authorized for specified adult renal-transplant use and sporadic LAM with moderate disease or declining lung function; not authorized for longevity. · checked 2026-11-13

Grade note: revised from F to C on independent review. No human trial has tested lifespan.

Goals: Longevity Compare with another peptide →

User reports

approximate — combined from two independent Reddit reads

Men 45–60

0 men aged 45–60

No reports in this group yet.

All men

0 men

No reports in this group yet.

Everyone

9 people

small sample · n = 9

Outcome mixed 5 of 9 · negative 3 of 9 · positive 1 of 9

Benefits fat loss 1 of 9 · focus / cognition 1 of 9 · hair 1 of 9 · immune 1 of 9 · inflammation 1 of 9

Side effects other 7 of 9 · acne 1 of 9 · fatigue 1 of 9 · flushing 1 of 9 · more hunger 1 of 9

Stopped 0 of 9 Used with other compounds 1 of 9

User reports are anecdata, not evidence: self-selected, unverified, often combined with other compounds.

In their words

  • “Mild mouth sores four times during a period of a year.”

  • “I've also found it easier to start and complete tasks lately”

  • “A month after Rapamycin, I dropped 9 lbs from 230 to 220.”

  • “I've been on Rapamycin for about a month for Longevity”

Read summaries and method notes

Read 1. No user could be verified as a man aged 45–60 in the coded longevity sample; one 49-year-old reported using rapamycin, but did not explicitly state sex. Among eight coded self-reporters, some described changes in inflammation, infections, weight, task completion, or hair pigmentation, but these were subjective observations rather than evidence of longer lifespan. Recurring adverse reports concerned mouth or throat ulcers, altered blood lipids, flushing, and increased hunger. Immediate effects were generally subtle, whereas some accounts covered six months to more than a year of use. Longevity self-experimentation was kept separate from treatment for long COVID or chronic fatigue, and the evidence remains too limited to demonstrate a longevity benefit in humans.

Read 2. Only two (r/cfs) threads were accessible; one valid self-report overall — strong adverse reactions to rapamycin (negative). A partner's 6-week titration to 4 mg was excluded as second-hand. This reflects chronic-fatigue use, not healthy longevity use in older men; r/Rapamycin threads could not be retrieved.

Note 1. Rapamycin is sirolimus, not a peptide, but is retained because the requested batch includes it. Explicit treatment reports for long COVID and CFS were excluded from longevity outcome counts. The 49-year-old author did not state sex and was not included in all_men. Other side effects include mouth or throat ulcers, lipid or glucose changes, and miscellaneous symptoms. Considering discontinuation was not coded as actual discontinuation. A weekly dose with grapefruit was a user-reported exposure, not a recommended practice.

Note 2. Only 2 r/cfs threads were accessible, in translated snippets; a partner report was excluded. No verbatim English quotes were available.

Each read counted people independently. Overlap between the two reads is estimated from shared threads and removed; counts are approximate. How we count.

Summary

Macrolide compound (not technically a peptide). MW: ~914 Da. mTOR inhibitor. Originally isolated from Streptomyces hygroscopicus (Easter Island soil, 1972). FDA-approved for transplant immunosuppression and LAM.

Proposed mechanism

Rapamycin inhibits mTOR (mechanistic target of rapamycin) — the master cellular growth/nutrient sensor:

  1. mTORC1 inhibition (primary) — suppresses cell growth, protein synthesis, and anabolic signaling. Activates autophagy (cellular cleanup of damaged components)
  2. Autophagy and lifespan — lifespan extension has been demonstrated in specific experimental regimens in species including yeast, worms, flies and mice; “gold standard,” “most robustly validated mechanism” and “every organism tested” overstate what individual experiments establish, and animal survival does not prove human longevity benefit
  3. Immune remodeling — the 2014 vaccine-response study used everolimus (RAD001), and the 2018 infection study used other mTOR inhibitors including a RAD001/BEZ235 combination; they do not prove that low-dose sirolimus enhances immunity. A small 2026 rapamycin study reported immune-cell biomarkers, not established infection prevention or lifespan extension
  4. Senescent cell modulation — reduces SASP (senescence-associated secretory phenotype) output without killing senescent cells directly
  5. At high/chronic doses: immunosuppression (transplant use), metabolic side effects (glucose intolerance, dyslipidemia)

The dose paradox: Continuous transplant dosing and intermittent experimental longevity dosing differ, but categorical reassurance that low-dose intermittent rapamycin enhances immunity is unsupported. Weekly sirolimus did not add functional benefit in RAPA-EX-01 and does not eliminate infection risk.

Safety

  • Serious infection and malignancy warnings
  • Mouth ulcers, edema, lipid abnormalities and cytopenias
  • Impaired wound healing and noninfectious pneumonitis
  • Fetal toxicity and fertility effects
  • CYP3A4/P-gp interactions; grapefruit and live-vaccine precautions
  • Weekly regimens do not eliminate infection risk

From labels, regulators and trials. No signal in small studies ≠ safe.

Evidence C longevity / healthy ageing (off-label, low intermittent dosing)

Changed F to C. No human trial has tested lifespan. The two healthy-ageing RCTs are small and exploratory: PEARL (114 completers) missed its visceral-fat primary endpoint but reported secondary signals; RAPA-EX-01 (40 people, 13 weeks) found no added benefit to exercise and possibly a small detriment. Two small early trials with null primaries is 'small, early, unconfirmed' (C), not a failed programme: nothing adequately powered has tested the claim, and the animal lifespan data remain strong. F is reserved here for a failed pivotal trial of the marketed use (AOD-9604). The approved transplant and LAM uses are unrelated and do not count.

Human trials · 3

  1. PMID 40188830202548-week double-blind placebo-controlled RCT; n is analyzed completers, with 11 additional discontinuations excluded 114 people

    Generally healthy adults aged 50-85

    Primary visceral-fat endpoint negative (p=0.942); exploratory female subgroup signals and no clear overall adverse-event imbalance.

  2. PMID 41985884202613-week double-blind placebo-controlled RCT 40 people

    Sedentary adults aged 65-85 undertaking home exercise

    No added functional benefit; 99 versus 63 adverse events and one possibly drug-related pneumonia event. Source

  3. PMID 21410393201112-month double-blind placebo-controlled RCT followed by observation 89 people

    Lymphangioleiomyomatosis with moderate lung impairment

    Stabilized FEV1 during treatment relative to decline on placebo; evidence is disease-specific. Source

Bar length = trial size on a log scale.

Dose ranges

Reported ranges from labels and studies, with context. Not a recommendation.

  • clinical trial
    5 or 10 mg compounded oral rapamycin once weekly for 48 weeks in PEARL; formulation exposure differed from standard tablets Source on a non-primary host — not linked
  • clinical trial
    6 mg oral sirolimus once weekly for 13 weeks with exercise in RAPA-EX-01 Source
  • approved label
    LAM: initial 2 mg orally daily, adjusted to trough concentrations of 5-15 ng/mL Source

Editorial ratings EDITORIAL

Editors’ judgement, 0–5. Opinion, not data; separate from grade and user score.

Not rated yet.

Sources

  1. pubmed.ncbi.nlm.nih.gov/41985884/
  2. pubmed.ncbi.nlm.nih.gov/21410393/
  3. dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3275b824-3f82-4151-2ab2-0036a9ba0acc
  4. wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf
  5. ema.europa.eu/en/medicines/human/EPAR/rapamune
  6. pmc.ncbi.nlm.nih.gov/articles/PMC12074816/
  7. pmc.ncbi.nlm.nih.gov/articles/PMC12074816
  8. pubmed.ncbi.nlm.nih.gov/41524558/
  9. pmc.ncbi.nlm.nih.gov/articles/PMC12794675/
  10. pubmed.ncbi.nlm.nih.gov/25540326/
  11. pubmed.ncbi.nlm.nih.gov/29997249/
  12. pubmed.ncbi.nlm.nih.gov/33977284/
  13. ema.europa.eu/en/medicines/human/epar/rapamune
  14. fda.gov/advisory-committees/advisory-committee-calendar/july-23-24-2026-meeting-pharmacy-c

Reddit threads read · 8

3 further sources on commercial or non-primary hosts not listed.

Research checked 2026-11-13.