Fight Aging!

Today's question: are we at the point at which it make sense to run a great many short human trials of potential interventions to slow or reverse aging? The answer tends to be quite conditional on the details. If the trials cost little, meaning that they can run for a year or less, and involve low-cost assays conducted before and after, then exploration sounds more viable. If the potential interventions have sizable, reliable effects in mice, then that makes it more attractive to devote funding to the project. Testing senolytics such as the dasatinib and quercetin combination in old human volunteers, with assessments of epigenetic age and blood markers of inflammation and disease, for example. There is no reason to leave that entirely to the Mayo Clinic, as they certainly won't be covering all of the bases any time soon. The wheels of the formal clinical trial system turn very slowly.

Use of the immunosuppressant drug rapamycin is a reliable way to slow aging in mice, with data that is far better than that for metformin. It triggers some of the mTOR related pathways that are involved in the calorie restriction response. The outcomes in mice are not as impressive as those for senolytics, but at some cost, testing rapamycin against potential biomarkers of aging makes sense. Biomarkers based on blood samples are becoming quite cheap. Volunteer organizations can run viable, useful studies of a few hundred volunteers at a tiny fraction of the millions of dollars it would cost a major institution to conduct the same work. And so Lifespan.io is doing just that. They have crushed down the cost of a rapamycin trial of 200 people or so, and are looking to raise $75,000 to perform the minimum version of that trial. I encourage you to take a look at this project: we'll be seeing a lot more of this sort of thing, as the community grows and more people ask why there is a lack of human data for existing approaches and biomarkers.

Pearl: Participatory Evaluation of Aging with Rapamycin for Longevity

The medicine rapamycin has been shown to extend the healthspan of all organisms it has been tested on - mice, warms, yeast - for decades, and yet to date there has been no trial to sufficiently demonstrate safety and proper dosing for this purpose in humans. It is now time for this to change. With your help, we will be conducting a large clinical trial named Participatory Evaluation (of) Aging (with) Rapamycin (for) Longevity Study, or PEARL, to find out. This will be the first study to see if Rapamycin works as well in humans as it does in mice (for longevity).

Rapamycin works through the mTOR signaling pathway, one of the master regulators of cell metabolism and a key controller of autophagy (recycling in cells). Basically, it tells our cells to switch from growth to repair, and to clean out all the garbage. Not only that, but the quality of the proteins our cells produce increases, which means that there is less garbage in the first place. What all this amounts to is improved health and lengthened life for worms, flies and mice - now it's our turn!

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 PI 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.