NEW PEARL Trial Results: Your Questions Answered on Aging with Rapamycin for Longevity

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Check out the PEARL trial webinar with Dr. Z of AgelessRx, Oliver Medvedik of Genspace, and Matt Kaeberlein:    • PEARL Trial: Results Review with Matt Kaeb...  

Check out the preprint discussing PEARL trial results after one year: https://www.medrxiv.org/content/10.11...

Check out the PEARL trial listing: https://clinicaltrials.gov/study/NCT0...

Check out a blogpost from AgelessRx discussing the PEARL trial: https://agelessrx.com/results-of-the-...

The AgelessRx-sponsored Participatory Evaluation of Aging with Rapamycin for Longevity (PEARL) trial was a 48-week randomized, double-blind, placebo-controlled trial investigating the safety and potential efficacy of different intermittent rapamycin doses for mitigating signs of aging. AgelessRx recently published results after one year of data collection, and hosted a webinar with several experts to review the results and answer follow-up questions.

In this episode, Matt tackles questions that the webinar didn't get to about topics including the challenges of determining optimal dosing, the costs of running well-powered longevity trials, the differences between compounded and generic rapamycin, and the potential value of using functional outcome measures as trial endpoints rather than directly measuring aging reversal.

If you have submitted a question that Matt didn't get to, don't worry—we'll be doing more of these. Comment below or email us at [email protected] with your questions. We read everything.

0:00 Introduction
2:18 PEARL trial background
7:35 Compounded vs generic/commercial rapamycin
9:46 The most effective way to check rapamycin levels in blood
10:37 Appropriate rapamycin dosage for men
13:18 Sexual dimorphism in human longevity
15:57 Which is more important for longevity: RapaAUC (area under the curve) or the peak?
20:37 mRNA delivery for mTOR inhibition
21:42 Matt's thoughts on an 8 weeks on/4 weeks off dosing schedule
25:28 Appropriate target rapamycin blood levels
28:20 Everolimus vs generic rapamycin
33:39 Do any rapalogs seem more promising than others?
36:05 Injectable vs oral rapamycin
37:14 Why don't more clinicians pay attention to rapamycin
39:18 Identifying an appropriate dose for humans
41:13 Grip strength/lung capacity as additional indicators of improvement
42:48 Fasting while taking rapamycin
44:56 Costs of a powerful, long-term rapamycin trial
50:33 Aging vs restoration of function as a clinical trial endpoint
53:39 Wrapping up

Producers: Tara Mei, Nicholas Arapis
Video Editor: Jacob Keliikoa

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Hi, I'm Matt Kaeberlein. I spent the first few decades of my career doing scientific research into the biology of aging, trying to understand the finer details of how humans age in order to facilitate translational interventions that promote healthspan and improve quality of life. Now I want to take some of that knowledge out of the lab and into the hands of people who can really use it.

On this podcast I talk about all things aging and healthspan, from supplements and nutrition to the latest discoveries in longevity research. My goal is to lift the veil on the geroscience and longevity world and help you apply what we know to your own personal health trajectory. I care about quality science and will always be honest about what I don't know. I hope you'll find these episodes helpful!