Gene therapies currently available

Of course!

The survival curve here is my main interest https://www.pnas.org/doi/10.1073/pnas.2121499119

I remain interested in understanding mechanisms. I think I have some understanding of the mechanism of aging which this does not directly hit. Still if you want to try it I would be interested in knowing the outcome.

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I think when it comes to gene therapies, I’ll be a ‘settler’ rather than a ‘pioneer’, I’d imagine it’s a lot easier to stop taking a medicine that doesn’t agree with you, than to reverse a gene therapy gone wrong.

That doesn’t mean I’m not rooting :mega: for those you are willing to undergo gene therapy

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Sure - but nobody is claiming it will increase lifespan, I don’t think, from the current treatment. The iteration that Mini Circle is doing is only lasting for a number of months, they claim.

I believe any significant increase in lifespan with Follistatin is via transgenic knock-in mice, where there is over-expression of the gene in all cells of the body because they start with embryonic stem cells, make the gene modification, then grow the mouse.

An injection therapy is only going to get very limited transfection, so will be much less effective, I believe.

I think the primary benefit of the folistatin injection by MiniCircle is increased strength for a period of time. See here for more info: Bryan Johnson's Longevity Protocol - Your Thoughts? - #479 by RapAdmin

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Bryan Johnson

This therapy ranks 7th among lifespan studies, extending mouse lifespan by 30%.

Data from my first longevity gene therapy: 160% increase in follistatin levels. Achieving our target objective. This therapy ranks 7th among lifespan studies, extending mouse lifespan by 30%. Goals: . epigenetic age reduction . monitoring dozen+ organs for possible improvements . improved muscle volume and strength . reduced speed of aging
Developed by [https://minicircle.io]

twitter.com/bryan_johnson/status/1730290432305930689

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Good to see. It will be interesting to see how long these shots last.

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I checked out Minicircle recently, mostly because Bryan Johnson tried it. Here are links to a small study they did on subjects that tried out the follistatin plasmids, and the info sheet they sent me about the procedure- hope the links work. Ultimately, I decided against it because the effect was leaner, more muscular bodies (which I mostly have already) with a massive reduction of epigenetic age. Not sure which epigenetic test they used. I was hoping for a telomere length increase, but that didn’t happen. I’ll probably do it in a year or two if nothing better comes along. One interesting thing about their treatment is that it is reversible with a dose of a specific antibiotic.

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Here Jim - I just put the file into the post:

FST_MiniCircle_v1.2 (1).pdf (600.4 KB)

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Do you know if they have or will publish the paper in a peer-reviewed journal?

That would be important for many reasons.

I believe any significant increase in lifespan with Follistatin is via transgenic knock-in mice, where there is over-expression of the gene in all cells of the body because they start with embryonic stem cells, make the gene modification, then grow the mouse.

This isn’t the case for BioViva’s CMV vector that was used to deliver follistatin or TERT. With this vector, serum TERT levels returned to baseline about 25 days after administration. It could also be administered intranasally, and this increased follistatin expression in various tissues (brain, heart, kidney, liver lung muscle).

BioViva’s CEO Elizabeth Parrish has reportedly taken multiple rounds of the TERT therapy, although I believe it was using AAV vector.

Yes - Minicircle is using plasmids, and while the AAV vector is the most commonly used vector today, it has issues, as our resident gene therapy expert posted here: Bryan Johnson's Longevity Protocol - Your Thoughts? - #794 by 59vw

We don’t have the perfect vector yet… everything is a trade off, safety/proven effectiveness, persistence, random integration issues, etc.

Agreed. Don’t know, but they put a lot of effort into the paper. I would bet they’ve submitted it somewhere.

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Saw this discussion of the follistatin gene therapy using plasmids, sounds like the evidence suggests it will only last up to 6 months…

Source: https://x.com/alexkesin/status/1755489954187382993?s=20

From this thread where a guy reports on his treatment: https://x.com/alexkesin/status/1755489952387990007?s=20

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BJ botoxes his penis. Must be legit.

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Apparently Jeff likes it…

It seems he was pretty unfit before… so any decent diet or workout is going to help…

Source: https://twitter.com/farbood

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And Peter Thiel and Sam Altman invested in it…:

It’s certainly no accident that Minicircle opened its first gene therapy clinic in Próspera, which is formally administered as a Zone for Employment and Economic Development (ZEDE) in Honduras. A bustling private enclave on the tropical island of Roatán, Próspera has pulled in investment from Peter Thiel and Marc Andreessen and is managed by an international group of libertarians (although they reject this label, claiming instead to champion a nonideological manifesto of freedom and prosperity).

It’s a philosophy that appears to resonate with biohackers as well as tech titans. Thiel, who has pumped millions into longevity research and has said the possibility of injecting himself with the blood of young people is “really interesting,” has also invested directly in Minicircle

OpenAI CEO Sam Altman has also confirmed to MIT Technology Review that he has plowed $250,000 into the startup.

It ultimately aims to democratize access to gene therapies, with an emphasis on discovering the right nucleic cocktail to promote longevity.

The follistatin gene therapy increases muscle mass in animals. It doubles bone density and halves body fat, the cardiovascular system is rapidly improved, the animals live longer, and they’re healthier,” claimed Davis. In fact, his and his associates’ ad hoc human experiments with follistatin are what served as the impetus to start Minicircle: “We’ve seen some very interesting effects,” he said.

Minicircle is taking something of a different tack. The startup, which is registered in Delaware, aims to fuse elements of the traditional drug testing path with the ethos of “biohackers”—medical mavericks who proudly dabble in self-experimentation and have long hailed the promise of DIY gene therapies.

The eccentricities don’t end there. Minicircle’s trials are going ahead in Próspera, an aspiring libertarian paradise born from controversial legislation that has allowed international businesses to carve off bits of Honduras and establish their own micronations. It’s a radical experiment that is allowing a private company to take on the role of the state. While much attention has been paid to the charter city’s use of Bitcoin as legal tender, the partnership with Minicircle is an important milestone toward another goal—becoming a hotbed of medical innovation and a future hub of medical tourism.

At least one prominent scientist sees a potential upside to growth in the biohacking space: George Church, a professor of genetics at Harvard Medical School who has previously consulted on biohacking endeavors, tells me he welcomes the evolution of biohacking self-experimentation into full-blown clinical trials. He isn’t familiar with Minicircle’s work specifically, but he says of the general premise, “As long as nothing goes wrong, it could herald a revolution in cost reduction.”

But Harper says he hasn’t heard anything related to Minicircle’s more outlandish claims that follistatin gene therapy decreases chronic inflammation and body fat, boosts DNA repair, and promotes age reversal. Robert Kotin, a gene therapy expert and professor of microbiology and physiological systems at the University of Massachusetts Medical School, echoes Harper’s skepticism: “If I wanted to make a fountain-of-youth drug, I don’t think it would be follistatin.”

But human studies using the minicircle technique have so far failed to deliver DNA to the nucleus of the cell in a way that is clinically relevant, safe, and therapeutic, says one of its creators, Mark Kay, a Stanford University professor of genetics (although he notes that the method has found some success in vaccines). From what he could find out on Minicircle’s website, Kay doesn’t understand why the startup would succeed where others have failed. “Where’s the novelty in any of their technology?” he asks. “How is it different?”

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Interesting. Not sure if this is ready for humans. But they are hopefully coming out with a paper soon and note that Prof Steve Horvarth retweeted



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What do you think about telomerase therapy ? It looks much more sexy than follistatin to me

A good article on new gene therapy delivery technology (vectors) that are finally starting to take hold. These non-viral vectors have been showing promise for the past 15 or 20 years but are finally making some real headway in the field.

In this subseries, we focus specifically on gene therapies. We explore the current treatments and examine the advances poised to transform healthcare. Each article in this collection delves into a different aspect of gene therapy’s role within the larger narrative of Regenerative Medicine. This piece continues s a miniseries on gene therapy vectors and their significance. Specifically, this piece begins with a two-part story on nonviral methods and vectors of gene therapy.

For comparison, viral vectors are the primary means of delivery today:

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