NEW PEARL Trial Results: Your Questions Answered on Aging with Rapamycin for Longevity | 66 - AMA #5
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 on the Youtube video or email us at optispanpodcast@gmail.com with your questions. We read everything.
Safety and efficacy of rapamycin on healthspan metrics after one year: PEARL Trial Results
This preprint describes the results of the 12-month double-blinded, randomized, placebo-controlled PEARL trial Matt discusses in this episode. 114 individuals between the ages of 50 and 85 received 5 mg or 10 mg of compounded rapamycin per week, or a placebo. The preprint reports that rapamycin is safe and well-tolerated as well as some intriguing potential benefits of rapamycin, though more work is necessary to more definitively determine rapamycin's effects, if any, on human healthspan.
Results of the PEARL Trial: An Expert Analysis
AgelessRx, the company that led the PEARL trial, wrote this blogpost summarizing the background behind the PEARL trial, how the researchers carried the trial out, and the trial's results. The post notes that the PEARL trial results alone are insufficient to determine concrete benefits of rapamycin use in humans.
This preprint, also from AgelessRx and colleagues, discusses the bioavailability of compounded rapamycin. Bioavailability refers to the proportion of a drug that enters the bloodstream when introduced into the body and is available to have an active effect. It is a key measure for understanding how much of the administered drug actually reaches its target site of action, and thus for determining the correct dosage of a medication to ensure it has the intended therapeutic effect.
TORC1 inhibition enhances immune function and reduces infections in the elderly
This paper investigated the effects of rapamycin treatment on elderly humans. It found that six weeks of treatment with a rapamycin derivative improved vaccination response and decreased infection rates in healthy people over 65, with minimal adverse effects.
A novel rapamycin analog is highly selective for mTORC1 in vivo
According to this paper, the rapalog (rapamycin analog) DL001 has 40 times the mTORC1 specificity of rapamycin, and inhibits mTORC1 without significant side effects on glucose homeostasis, lipid metabolism, or the immune system. The paper does not present data on the longevity or healthspan effects of this rapalog.
