The PEARL trial investigates the effects of low-dose rapamycin on healthy aging, focusing on safety and potential benefits in a normative aging population.

This year-long, placebo-controlled study involved 114 participants aged 50 to 85, who were randomized into groups receiving placebo, 5 mg/week, or 10 mg/week of compounded rapamycin for 48 weeks.

The trial confirmed a favorable safety profile, with adverse events comparable to placebo, although gastrointestinal disturbances were slightly more common in treatment groups.

The primary endpoint of reducing visceral adiposity was not statistically significant; however, secondary results showed a significant increase in lean tissue mass among women taking 10 mg/week of rapamycin.

Women also reported reductions in pain and improvements in subjective quality-of-life measures, particularly in the 5 mg cohort, indicating potential sex-specific benefits of treatment.

The findings suggest that further research should focus on refining dosing strategies and exploring the benefits of rapamycin specifically for post-menopausal women and other high-risk populations.

Compounded rapamycin demonstrated approximately 66% lower bioavailability than commercial formulations, suggesting that even low doses may have effects.

Dr. Sajad Zalzala highlighted the trial as a significant step in applying geroscience to clinical practice, emphasizing the importance of ongoing research in this area.

The PEARL trial adds to the growing literature on mTOR modulation and its potential roles in enhancing healthspan, raising questions about optimal dosing and target populations for future studies.