The mentioned E5 plasma fraction has seemingly led to a new lifespan record for Sprague Dawley rats.

"The female lifespan study, in which E5 is being tested on elderly female rats, is still ongoing because of an extraordinary fact: one of the treated rats, named "Sima", is still alive at 44 months of age. Sprague Dawley rats have a lifespan of 24 to 36 months, with specimens reaching 42 months according to some sources. So Sima, with the help of E5, is extending the limits of the maximum lifespan of Sprague Dawley rats.

The study began in February 2021, when E5 started being injected in 8 female rats every 90 days, with another 8 female rats in the control group. Over time, all the rats in the untreated group died, and in the E5-treated group, all but Sima died. Additionally, Sima has not received any E5 for the last 6 months which may indicate that the benefits of the therapy can become long lasting. She hasn’t lost eyesight, hasn’t developed skin canker sores, hasn’t lost motor function or developed bald patches.

Overall, the treated rats lived longer than the control ones, but it won't be possible to know exactly how much longer on average until Sima dies."

Interesting article on new promise for "rejuvenation" therapies (once the realm of science fiction).

Last paragraph puts its finger on one of the reasons progress is so slow:

> The most promising avenue for rejuvenation (IMO) is not attracting research attention because it cannot attract venture capital; it can’t attract venture capital because there is no attractive business model; and there is no business model because of the structure of our patent law.

Would that really dissuade a Musk/Bezos/Gates from investing in it? Our society is flush with billionaires and a procedure that restored youth would be worth 1000X a money making investment to them.

How do you know they're not investing in it? If they are would it be worth their trying to make money on it or would they consider it worth more if they kept it to themselves?

You can't 1000x investment if there is no barrier to entry for competition.

They're saying a treatment that can actually reverse aging and prolong lifespan is worth 1000x more than money, especially to someone who already has more money than they can possibly spend in a (currently expected) lifetime.

There are other barriers than patents. First mover advantage, brand name recognition, first to achieve low cost, strategic partnerships, etc.

It's not just (or even predominantly) patent law: if there is no explicit or implicit agreement for FDA to approve some treatments that modulate ageing (to even become a possibility, this category of indications should be created) and for the healthcare provider complex (insurers, governments, clinics) to provide said treatments to the public, there is no prospective market.

Until there is a coordinated push to align our regulatory and medical systems with this challenge, the status quo will remain frozen.

Will a few remaining decades be enough for the metaphorical ice to crack?

> Meanwhile, the four questions I listed above are not being addressed. Patent law is working against us, since Katcher’s E5 patent is for a process of extraction. If a subset of active ingredients is identified and the minimal set of rejuvenating proteins becomes known, his patent becomes worthless. Naturally occurring proteins cannot be patented.

> This is the maddening influence of capitalism and intellectual property law on anti-aging science. The most promising avenue for rejuvenation (IMO) is not attracting research attention because it cannot attract venture capital; it can’t attract venture capital because there is no attractive business model; and there is no business model because of the structure of our patent law.

This is common in pharma patent law. At an earlier company we made some progress on a treatment for a fairly common disease, but it looked like any compounding pharmacy could make it. So we abandoned that path and went in a different direction that was protectable (and more effective, true). The inverse is the case as well: had the less effective treatment been available, it might not have been worth developing something that could help even more people, because those that needed the better treatment would not be enough to justify development.

But the situation is not as clear as stated by the author. First of all, much of the work is basic research, and that is mostly funded by governments and charities. Second of all, even if you've identified a mechanism of action, developing a feasible in vivo way to trigger that action, figuring out how to manufacture it at scale, and getting it approved can provide many patent opportunities. When people complain "why are drugs expensive when the government pays for it" they miss the point: "government" developed the transistor,* it was private companies that developed the IC and the microprocessor. The situation with drugs is analogous.

* Yes the transistor was invented at Bell Labs, but Bell Labs only existed due to the structure of the government's consent decree for the Bell telephone company, and when that decree was lifted Bell Labs suffered a precipitous decline. Anyway, it's just an analogy.

>Katcher’s E5 patent is for a process of extraction. If a subset of active ingredients is identified and the minimal set of rejuvenating proteins becomes known, his patent becomes worthless. Naturally occurring proteins cannot be patented.

This is not legal advice, but I firmly disagree with these statements. Individual naturally occurring proteins cannot be patented, but: A method of treating aging by administering the individual protein can be patented. A specific combination (subset) of naturally occurring proteins that is otherwise not really found together in nature in an isolated manner, is likely patentable A highly concentrated extract (or other means of making the particular combination) that is not found in nature is patentable A method of making the combination is likely patentable. A compound that begins as a naturally occuring protein, but is modified in some way for therapeutic efficacy (pegylation, truncation, fusion, etc.) is patentable A formulation suitable for administration (with buffers, stabilizers, etc.) is patentable.

There are many inventions that go into making a therapeutic. Yes the compound itself provides the cleanest and most valuable patent protection, but natural products can be protected.

Then there is regulatory exclusivity, which can be an entirely different ball of wax that does not necessarily have anything to do with patents at all.

> Individual naturally occurring proteins cannot be patented, but: A method of treating aging by administering the individual protein can be patented.

An easy way to think of this for people not in the field: you can't patent titanium, but you can (well, once could have) patent the idea of a bicycle crank made of titanium.

Why can't it attract venture capital if the possible outcome is worth more than what money can buy, regardless of any argument about competition?

Are VCs only interested in wealth that is in excess of other people's wealth?

The idea that aging research is being stifled by patent law (or any other mechanism) is ridiculous. Aging and neurodegenerative disease already receive an exorbitant amount of funding from the government (see: the NIA). The aging billionaire class is also more than happy to fund aging research that works for them (see: Altos Labs as the most recent example, The SENS Research Foundation, and tech life sciences offshoots like Calico). The argument that you "can't patent naturally occurring proteins" may be technically true, but there are plenty of ways around this which often improve the performance of the native proteins as therapeutics (see: insulin, among many others).

"Leapfrogging ahead of these research institutes with a practical demonstration has been Harold Katcher. Katcher’s method is proprietary."

Wow, a proprietary method that outdoes decades of scientific research? Haven't heard that one before. I understand that there has been little progress in this space, but that's because no one knows what causes aging (or if it can be halted at all). There's no single smoking gun, and there is likely no single easy solution. I also understand that our scientific institutions aren't perfect–and that the big ship of science can sometimes take a while to turn away from a tantalizing hypotheses, like the amyloid hypothesis-but that doesn't mean that you should trust Harold Katcher instead.

Presumably, longer proteins require more splicing, so impaired RNA splicing could account for a deficit of longer proteins as we age.

Why is this "presumably true"? Intuitively, impaired splicing would produce longer proteins, because introns aren't excised as effectively. Even this take is far too simplistic–there are innumerate feedback and control mechanisms involved in mRNA splicing. I'm sure the author has a better grasp on molecular biology than this hot take suggests based on his credentials, but the treatment of this topic by the author is concerning.

As an aside, wow, that preprint spent over three years in review, and the figures and text are way different. A lot of work and stress must have gone into it.

I suspect that the impaired splicing leads to a multitude of premature stop codons and stretches of RNA that don't lend themselves well to transcription and/or translation. Longer proteins, have more introns and are therefore more likely to suffer from this issue, at least that is my guess.

NAD seems to have some rejuvenation effect. It's a refined vitamin b component.

If only it was cheap enough to take regularly...

It's cheap from China ^^