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.

As we've mentioned before, we read every comment on our social media and Youtube channels and often learn a lot from your questions and feedback. For this episode, we collected comments you left containing questions about rapamycin. Many of the questions focus on rapamycin dosing, diet and exercise changes while taking rapamycin, and potential side effects. We also appreciated your curiosity about the state of rapamycin research, evidence for benefit in different model organisms, and the nuances of experimental conditions in rapamycin studies. Keep the questions coming!

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.

Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice

Many of those interested in rapamycin have questions about what the optimum rapamycin dosing regime looks like. While there is not yet any conclusive evidence suggesting an ideal dose for humans, researchers have demonstrated dosing regimes that work in mice. This study found that a single three-month rapamycin regimen increased life expectancy in middle-aged mice without overt detrimental side effects. It also shows some of the positive effects rapamycin has on mouse life- and healthspan.

Rapamycin fed late in life extends lifespan in genetically heterogeneous mice

This study found that rapamycin improved mouse survival by 14% and 9% for females and males respectively, even when rapamycin feeding began late in life. The authors propose several mechanisms by which rapamycin might delay aging, including modulation of nutrient dynamics and cellular stress resistance.

272 ‒ Rapamycin: potential longevity benefits, surge in popularity, unanswered questions, and more

In this episode of the Peter Attia Drive podcast, Matt joins physician Peter Attia and Institute of Organic Chemistry and Biochemistry senior group leader David Sabatini to talk about the discovery of rapamycin, its first uses in humans, the mTOR pathway, potential mechanisms by which rapamycin might influence human longevity, recent studies of the effects of rapamycin in model organisms, potential side effects, and more.

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.