mTOR inhibitor · FDA-approved (transplant) · off-label longevity use · Profile RAP-001
Rapamycin inhibits mTORC1, a central regulator of cell growth, protein synthesis, and autophagy. By suppressing mTORC1 signaling, rapamycin induces autophagy, reduces cellular senescence, and shifts cells toward a maintenance and repair phenotype — the mechanistic basis for its proposed longevity effects.
The mTOR pathway integrates nutrient signals with growth programs. In aged tissues, chronic mTORC1 activation drives senescence and impairs proteostasis. Rapamycin's inhibition of this pathway mimics aspects of caloric restriction at the molecular level.
Weekly low-dose rapamycin (5mg) showed significant improvement in immune function markers in healthy adults aged 65–85. Acceptable safety profile at this dose. No serious adverse events attributable to rapamycin.
Retrospective cohort analysis of off-label rapamycin users. HR 0.81 (0.71–0.92) for all-cause mortality vs matched controls. Limitations: selection bias likely; off-label users may be healthier at baseline.
Comprehensive review of mTOR inhibition across model organisms and early human data. Identifies key translational gaps and proposes trial design criteria for definitive human longevity studies.
| Trial | Phase | Status | Primary endpoint | Est. completion |
|---|---|---|---|---|
| PEARL-2 NCT05494060 | II | RECRUITING | Biological aging biomarkers · immune function | Dec 2026 |
| ERAP NCT05494061 | II | ACTIVE | Age-related conditions composite | Mar 2027 |
| TRITON NCT05494062 | II/III | PLANNED | Healthspan composite · 5-year follow-up | Jun 2029 |