"Human Rapamycin Trials: Measuring Longevity Impacts"

On April 14, 2025, a landmark study titled “Results of a Crowdfunded One-Year Human Rapamycin Trial” was published in Aging by Dr. Sajid Zalzala and a team of researchers. This trial sought to explore the potential life-extending benefits of rapamycin, a drug well-known for its therapeutic properties and significance in the field of longevity.

Crowdfunded Research Bears Fruit

Four years prior to this publication, a crowdfunded initiative significantly surpassed its donation target, drawing considerable interest and support from the public. The increasing fascination with rapamycin can be attributed to its role as a potent inhibitor of the mammalian target of rapamycin (mTOR) (Mannick & Lamming, 2023). Specifically, rapamycin's life-extending effects are associated with mTORC1, while mTORC2, which facilitates cancer growth, is less favorable in the context of aging (Castilho et al., 2009).

Most existing research on rapamycin has predominantly focused on non-human subjects, revealing its ability to extend lifespan in species ranging from mice to monkeys (Harrison et al., 2009); (Colman et al., 2009). Nevertheless, limited extensive human trials have previously been conducted to assess its efficacy on human lifespan and healthspan, primarily being constrained to shorter durations.

Study Design and Methodology

The trial involved a comprehensive design where participants were divided into distinct groups: one receiving 5 mg of rapamycin, another receiving 10 mg, and a control group administered a placebo. Of the total of 114 participants, their average age was approximately 60 years, with only 40 participants being women. This demographic served as an adequate representation to gauge potential gender-based effects. Notably, compounded rapamycin was used for the placebo control to balance the study groups, despite being revealed as approximately one-third less effective than the commercial variant, serolimus (Harinath et al., 2025).

Results and Observations

Across the 48-week duration, the study revealed a mixed bag of findings:

While adverse events were evenly distributed across groups indicating that these doses of rapamycin are generally safe, several specific effects emerged:

• Lean Tissue Mass: Women in the 10 mg group experienced significant increases in lean tissue mass and reported reduced pain levels.
• General Health: The 5 mg group reported benefits for general health across both genders, despite the outnumbered female participants.
• Physical Metrics: No benefits observed on self-reported metrics such as emotional well-being or social interactions.
• Gut Health: Increased markers of gut dysbiosis were noted in males, while females showed trends towards increased intestinal permeability.

Limitations and Future Directions

One of the critical limitations of this study was the reliance on self-reported data, which often poses a challenge in accurately assessing health outcomes. Furthermore, the trial does not provide direct evidence that rapamycin can extend human lifespan, given the absence of statistically significant effects on epigenetic aging.

The authors advocate for conducting larger and longer-term trials to validate the findings. Such future experiments may utilize compounds that specifically target mTORC1 or explore a variety of dosing regimens of rapamycin to unlock further insights into its longevity benefits.

“Despite observed benefits, more research is necessary to draw definitive conclusions regarding the effect of rapamycin on human longevity.” – Dr. Sajid Zalzala, Lead Researcher

Literature Cited

[1] Mannick, J. B., & Lamming, D. W. (2023). Targeting the biology of aging with mTOR inhibitors. Nature Aging, 3(6), 642-660.

[2] Castilho, R. M., et al. (2009). mTOR mediates Wnt-induced epidermal stem cell exhaustion and aging. Cell Stem Cell, 5(3), 279-289.

[3] Harrison, D. E., et al. (2009). Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. NATURE, 460(7253), 392-395.

[4] Colman, R. J., et al. (2009). Caloric restriction delays disease onset and mortality in rhesus monkeys. Science, 325(5937), 201-204.

[5] Mannick, J. B., et al. (2018). TORC1 inhibition enhances immune function and reduces infections in the elderly. Science Translational Medicine, 10(449), eaaq1564.

[6] Harinath, G., et al. (2025). The bioavailability and blood levels of low-dose rapamycin for longevity in real-world cohorts of normative aging individuals. GeroScience, 1-14.