Rapamycin Dosing: Weekly Pulsed Dosing vs. Continuous Low-Dose Inhibition
Should rapamycin for longevity be administered as a single weekly bolus (5-8mg once per week) to maximize peak mTORC1 inhibition while allowing mTORC2 to recover, or does lower continuous micro-dosing provide steadier autophagy?
Position A: Weekly High-Peak Pulsing (5-8mg once/wk)
Camp ADr. Mikhail Blagosklonny (Emeritus)
Cell Cycle & Aging Research Institute
Pulsed dosing is biochemically essential because chronic inhibition disrupts mTOR Complex 2 (mTORC2) assembly, precipitating systemic insulin resistance, dyslipidemia, and impaired T-cell homeostasis. A single weekly pulse achieves high transient tissue penetration (saturating FKBP12-mTORC1), purges senescent phenotypes, and drops below therapeutic trough within 48-72 hours, allowing full immune and metabolic recovery.
Position B: Continuous Micro-Dosing (1-2mg daily)
Camp BDr. Joan Mannick
resTORbio / Life Biosciences
Continuous or frequent low-dose rapalog administration maintains steady partial inhibition of mTORC1 without the peak blood concentration spikes that cause aphthous stomatitis oral ulcers. Phase 2 human clinical trials confirmed that consistent low doses stimulated immune memory and reduced respiratory tract infections in older adults safely without systemic immunosuppression.