You asked, we listened. Ever since the February 2024 launch of our series "The R-Files", a series of episodes about all things rapamycin, we've received a ton of questions about this compound and how it works in the context of aging and longevity. We went through every comment you left on Youtube, Twitter, and LinkedIn to compile a list of your questions about combining interventions, optimizing rapamycin dosing, limitations in applying findings from mice and medical studies to off-label human usage of rapamycin and other supplements, and so much more.

Keep the questions coming—if there are more, we'll address them in a future AMA episode.

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.

Distinct and additive effects of calorie restriction and rapamycin in aging skeletal muscle

This study addresses the question of how much the effects of rapamycin recapitulate the effects of caloric restriction by profiling gene expression signatures and markers of muscle quality in mice undergoing caloric restriction and rapamycin treatment. The researchers found that rapamycin and caloric restriction likely act via mechanisms that are likely non-overlapping and complementary in mouse skeletal muscle.

Effect of caloric restriction and rapamycin on ovarian aging in mice

This study found that caloric restriction and rapamycin exert similar effects on ovarian aging in mice. Both interventions preserve the number of primordial follicles—immature egg cells at the earliest stage of ovarian follicle development—to a similar degree. Effects on metabolism differed, however: caloric restriction mice demonstrated lower weight gain and visceral fat as well as increased insulin sensitivity, while rapamycin-treated mice did not.

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.