Last month, entrepreneur and venture capitalist Bryan Johnson released a Youtube video detailing his trip to Prospera, Honduras to receive follistatin gene therapy from the Minicircle Gene Therapy clinic. Bryan describes Minicircle's gene therapy as "a pioneering technology with the potential to improve muscle and strength, slow the speed of aging, and many more benefits".

In this episode, Matt reacts in real time to his first watch of Bryan's video and responds to Nick's questions about various topics that come up along the way. He provides a primer on gene therapy and its potential as a longevity intervention, discusses the clinical evidence for follistatin's effects on humans and model organisms, and goes through several things one might want to consider when deciding whether to partake in a new therapy. He also gives his honest take on "offshore medicine"—medicine performed in countries that lack the regulatory oversight of the United States Food and Drug Administration—and discusses potential mechanisms for safely offering experimental therapies in the United States.

Follistatin is a glycoprotein that functions as a potent inhibitor of several members of the TGF-beta superfamily, particularly activin and myostatin. It is involved in various physiological processes, including muscle growth and development, reproduction, and inflammation. By binding to these proteins, follistatin prevents them from interacting with their receptors, thereby regulating their activity.
Minicircle Gene Therapy https://minicircle.io

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!

Minicircle Gene Therapy

Here's Minicircle's website if you'd like to check out the company's claims, follistatin primer, and more for yourself. The website includes the company's answer to "will this turn me into a superhuman?".

What is Gene Therapy?

This is a quick primer on gene therapy that the United States Food & Drug Administration has released. It covers potential mechanisms for manipulating gene expression in humans as well as some of the products currently available to do so.

Plasmid delivery of follistatin gene therapy safely improves body composition and lowers extrinsic epigenetic age in sex- and age-diverse adult human subjects

This paper, sponsored by Minicircle Gene Therapy, presents the results of a clinical trial demonstrating the efficacy of follistatin gene therapy on body composition and extrinsic epigenetic age in humans. Mean lean mass increased by 1.96 lbs, with a maximum increase of 12.15 lbs, and mean body fat reduction was 0.87 percent. The study reported mild trends in inflammatory markers, glucose metabolism, and cholesterol, none of which were significant. Participants did not experience severe adverse effects related to the therapy.

New intranasal and injectable gene therapy for healthy life extension

Matt mentions this paper in the podcast as a piece of research that has received some criticism for several reasons, among them a small sample size of mice in each treatment group. This study tested the efficacy and safety of a viral vector for delivering telomerase reverse transcriptase and follistatin gene therapy, and found lifespan extension effects for both therapies of 41.4 percent and 32.5 percent respectively. The paper also describes other observed effects of one or both gene therapies, including telomere length increases in some tissues, improvements in hair loss and texture, weight loss prevention, improved motor coordination, and preserved mitochondrial integrity.

Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice

A senolytic is an agent that selectively clears senescent cells. This paper describes vaccination as a potential delivery agent for a senolytic, enabling delivery to specific sites and the avoidance of off-target effects. The researchers suggest that a vaccination targeted at glycoprotein nonmetastatic melanoma protein B (GPNMB), a protein that is enriched in senescent cells, increases mouse lifespan and improves various aging-associated phenotypes such as atherogenesis.