It is possible in principle to organize low-cost human trials capable of providing potentially interesting data; much of the cost of formal clinical trials is unrelated to the essentials. The Lifespan.io staff and volunteers have demonstrated this point by successfully raising the modest amount needed to run a 200 person study of the impact of rapamycin use on aging-related biomarkers of health. Rapamycin inhibits mTOR, both the mTORC1 and mTORC2 protein complexes, which have different effects on metabolism. mTOR signaling is involved in the beneficial response to calorie restriction and upregulation of the cellular maintenance process of autophagy, and its inhibition extends healthy longevity in short-lived species such as mice.
The immunosuppressive effects of rapamycin, and a consensus that mTORC2 inhibition is probably undesirable, have led the research community to focus on building specific inhibitors of mTORC1, which are at various stages of clinical development. The the benefits to be obtained from the use of mTOR inhibitors are likely modest, less than those resulting from the actual practice of calorie restriction, but it is certainly the case that more human data is better than less human data. Further, the Lifespan.io study provides a good blueprint for later organizers who may wish to conduct low cost trials for more meaningful interventions, such as the established senolytic combination of dasatinib and quercetin.
Today is a doubly important day: it marks the final day of the PEARL campaign and it is a celebration of another victory for the life extension community. PEARL smashed its initial fundraising goal and sailed through its two stretch goals, raising just under $183k thanks to the generous support of the community. The Participatory Evaluation (of) Aging (with) Rapamycin (for) Longevity Study, or PEARL, will launch the first large-scale placebo-controlled clinical trial to determine the effects of rapamycin on human aging. The principal investigator is Dr. James P. Watson based at UCLA.
The PEARL trial will follow up to 200 participants over 12 months testing four different rapamycin dosing regimens. It will be double-blind, randomized, placebo-controlled and registered with clinicaltrials.gov. The principal investigator is Dr. James P Watson at UCLA, who was also a principle investigator for the famous TRIIM trial. To ensure safety the participants' blood will be regularly monitored and side effects noted.
A battery of tests and measurements will be taken, both after 6 and 12 months. These will include autonomic health tests, blood tests, body composition tests, fecal microbiome testing, immune and inflammation health tests, methylation age clock testing, and skeletal muscle tests. With your help we will find out if and how well rapamycin works to combat human aging. And, armed with a positive result, we will finally be able to help slow down onset of age related damage for you and those who you love and care about.