🔬TODAY’S BREAKTHROUGH
Low-dose rapamycin and analogues like everolimus are emerging as some of the most promising geroprotective drugs, with human data now suggesting both benefits and manageable risks.
The Discovery:
The PEARL clinical trial and other smaller human studies analyzed in this review involved intermittent low-dose rapamycin/everolimus over periods of 6–12 months. Results show meaningful improvements in immune function, metabolic biomarkers, and mTOR signaling, with tolerable side effects, offering a strong translational signal for anti-aging use in humans.
The Science:
mTOR (mechanistic target of rapamycin) is a central nutrient-sensing pathway that regulates cell growth, autophagy, and protein synthesis
Rapamycin/stable analogues inhibit mTORC1, promoting cell cleanup, stress resistance, and metabolic improvements
In PEARL, intermittent dosing reduced inflammatory cytokines like IL‑6 (interleukin‑6) and CRP (C-reactive protein), and improved T-cell function, including higher naïve T-cell counts
Metabolic markers (e.g., insulin sensitivity, lipid profiles) shifted toward youthful profiles
Key side effects such as mild mouth ulcers, acne, and elevated lipid levels, were dose-dependent and reversible
Review outlines biomarkers to monitor: mTORC1-specific phosphorylation targets, autophagy markers (LC3-II), and immune-nutritional panels
Your Action:
If you’re considering off-label rapamycin for longevity, start with physician consultation and monitoring. Explore intermittent low-dose protocols used in PEARL. Track CRP, IL‑6, lipid panels, and T-cell subsets regularly. Maintain a balanced diet and exercise, since these optimize mTOR modulation and reduce side effects risk.
Bottom Line:
Low-dose, intermittent rapamycin shows rising evidence as a safe, actionable longevity strategy in humans, but medical oversight and biomarker monitoring are essential.
Source:
Rapamycin/Sirolimus and Its Analogues in Human Aging: Clinical Advances, Mechanisms, and Perspectives, Frontiers in Aging, June 20, 2025
https://www.frontiersin.org/journals/aging/articles/10.3389/fragi.2025.1628187/full
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Disclaimer:
This newsletter is for informational purposes only and does not substitute professional medical advice. Always consult with a healthcare provider before making any changes to your health regimen.