The R-Files is a series of episodes about rapamycin, a naturally occurring compound originally discovered in soil samples from Easter Island, also known as Rapa Nui (hence the drug's name). Rapamycin belongs to a class of drugs called macrolides and has potent immunosuppressive and anti-proliferative effects. The drug has garnered attention for its potential anti-aging properties and has attracted research interest for its ability to extend lifespan and delay age-related diseases in various model organisms, including yeast and mice.

In the third episode of the R-Files, Matt, who studied rapamycin for over a decade of his career, talks about a recent study evaluating the benefits and side effects of taking rapamycin off-label—that is, for a purpose other than that for which the drug gained FDA approval. Physicians can prescribe any FDA-approved drug off-label as long as they believe it will be beneficial for the patient. Matt discusses noteworthy potential side effects of rapamycin use, the experiences of study participants who took rapamycin, and why off-label rapamycin use is not widespread despite considerable evidence for life- and healthspan benefits in laboratory animals.

Check out the links below for further information and/or reading about some of the things we discussed in this podcast episode. Note that we do not necessarily endorse or agree with the content of these readings, but present them as supplementary material that may deepen your understanding of the topic after you listen to our podcast. This list is in no way exhaustive, but it’s a good start!

Rapamycin News

Many of our podcast listeners are interested in questions about rapamycin dosing, how to get a prescription for rapamycin, and how rapamycin might interact with other supplements or drugs. This website is a great resource for getting more clarity on some of these questions, as well as for hearing about others' experiences with rapamycin and other longevity medications.

Evaluation of off-label rapamycin use to promote healthspan in 333 adults

Matt and colleagues, including Optispan Chief Medical Officer George Haddad, collected self-reported data from over 300 adults with a history of off-label rapamycin use to capture data about the drug's potential side effects. The only side effect that was significantly more prevalent in rapamycin users compared to non-users was the presence of mouth sores, and several side effects typically associated with rapamycin use such as eye pain and anxiety occurred less frequently in rapamycin users than in non-users.

Rapamycin and aging: Dosage, side effects, and success stories | Matt Kaeberlein

Matt discusses rapamycin on this podcast with Stanford Prevention Research Center lecturer Lucia Aronica. He makes several anecdotal observations about rapamycin, including that most people don’t seem to experience observable side effects on a weekly 3-6 mg dose. Side effects that seem real, he notes, are mouth sores and higher triglycerides. He also discusses differences in side effects observed in biohackers versus organ transplant patients taking rapamycin.

Rapamycin in aging and disease: maximizing efficacy while minimizing side effects

This article argues for several important considerations in future studies of rapamycin for successful translation to human use, including sex-dependent impacts on biological outcomes, the impact of short-term rapamycin treatment on a variety of healthspan metrics, the best regimen for extracting maximum benefits from rapamycin treatment while minimizing adverse effects, and more.

mTOR Inhibition: From Aging to Autism and Beyond

In this paper, Matt reviews the effects of mammalian target of rapamycin (mTOR) inhibitors on age-related disease and decline as well as on non-aging-related diseases such as tuberous sclerosis complex and epilepsy. He describes the side effects of chronic mTOR inhibition in mice, which include hyperlipidemia, insulin resistance, enhanced cataract formation and male sterility; as well as the adverse effects of mTOR inhibitors used in the clinic, which include mouth ulcers, diarrhea and nausea, hyperlipidemia, and infection.