NMN treatment for Friedrich’s Ataxia

I was looking for updates on human trials for NMN (nicotinamide mononucleotide) when I noticed this.

NMN is one of a group of chemicals which is being looked at for their anti-senescence or senolytic properties. In NMN’s case, it helps to increase NAD+ in mitochondria, making it easier for older cells to generate energy to replicate correctly.

It turns out that NMN can also work with the SIRT3 protein to increase the presence of frataxin, which is a protein used in mitochondria and important for heart function.

People that have the disease Friedrich’s Ataxia have a mutation in their DNA which leads to reduced expression of frataxin in their mitochondria. Later in life, this leads to a list of issues, such as scoliosis, diabetes, heart disorders.

In mouse tests, it was shown that mice that had their frataxin-producing genes completely turned off were restored to good heart health after being treated with NMN.

cure for acute myeloid leukemia

In the 9th October edition of Cancer Cell, a paper was released which announced the first molecule that directly attacks just cancer cells (not healthy cells) and pushes them into apoptosis (cell suicide).

Titled “Direct Activation of BAX1 by BTSA1 Overcomes Apoptosis Resistance in Acute Myeloid Leukemia“, the paper describes how the molecule, BTSA1, binds strongly to the activation sites on BAX, which is a protein in cells that triggers apoptosis, increasing the chance that the cell will be able to die properly.

You can think of this like a human messenger trying to send a message to someone (the damaged cell sending a message to itself to self-destruct), and a load of bullies constantly harassing the messenger, tripping her up and standing in her way (the cancer cell’s anti-apoptic proteins bind to the messenger protein). BTSA1 in this case is a strong security guard that travels with the messenger, pushing the bullies out of the way to let her send her message.

In normal cells, when it is time for a cell to die – for example, the telomeres are too short, or damage to the DNA is detected – messages are sent to the BAX protein to tell it to turn on cell suicide mode.

In some cancers, though, Acute Myeloid Leukemia (AML) in this instance, a number of “anti-apoptic” proteins are produced which bind to BAX, so it can’t send its message to start the apoptosis.

In this study, Evripidis Gavathiotis was able to find a molecule which binds stronger to BAX than the AML anti-apoptic proteins do, letting them do their job.

Most importantly, this increase in the strength of the BAX messages only affects those cells that are already trying to commit suicide (the cancer cells)- normal cells are left alone.

In mouse studies, some mice were given AML, and some of those then given the new molecule. Those that received the treatment survived weeks longer than those that did not, with 43% of the treated mice still alive three weeks after the control mice had died and no sign of AML in them.

Even though this treatment was specifically tested on just AML, it is possible that it affects other cancers as well. Dr Gavathiotis has been asked to repeat the test using other cancers to see if this is true.

Recently, the CAR-T cell therapy for cancer was announced which was able to kill cancer cells after some therapy such that a year later 64% of the patients were still in remission. With BTSA1, the chances look even better.

New chapter – good and bad habits

I recently read through a few hundred research papers to find references to “all cause mortality”, looking for studies done on various habits, in order to see what are the best habits to have in order to increase your lifespan.

I’ve converted the list into a chapter in my book (“How to Live Forever“) – a practical list of habits to take up or avoid. I think I did a good job of it!

The online version is here.

The items in the list are proven – I have links to the research papers right next to each point, and did my best to avoid any studies that had ridiculously low numbers in them (for example, a study of 5 people won’t get in the list, but there are a few where the cohort is larger than 100,000).

The list only contains common habits and practical tips. There is nothing in there about Quantum Immortality, for example, because that’s not a habit (and no-one really knows is quantum immortality real anyway). There’s also nothing in there about senolytics, because even though senolytics have a very profound ability to affect your lifespan, they’re not commonly available enough that you can make them into a habit.

Rewriting the Senescent Cells chapter

I rewrote the Senescent Cells chapter of my book (How to Live Forever), reducing the focus on FOXO4-DRI, and including details about alternatives such as UBX0101, Navitoclax and Quercetin.

The latter two have already passed human safety trials, but are designed primarily as cancer treatments. They do have senolytic properties, but those are not as strong as the actions that the FOXO4-DRI peptide and UBX0101 have.

The rewritten chapter is about twice as long as the original, but I think it’s written better. The original chapter is more terse and factual, while the new version is more conversational. It includes the same information (and more), but is much easier to read.

At the end of the chapter, I explained that even though the drugs themselves might be very expensive, the most important of them (in my opinion), can probably be synthesised at home, if you put some time and effort into it.

FOXO4-DRI is a patented drug, meaning that the creators wanted to protect who could sell it. In order to do this, they needed to describe it in full, which they did in the patent application. This included the protein sequence.

Patenting something is done to exclude others from selling or importing the patented device. Patents can also exclude people from making or using the device, but if there is no profit made, and the self-use of the device does no harm to the inventor’s business, it is extremely unlikely that any action would be taken. And even if action would be taken, it would be a mere “stop doing that” from the courts.

Personally, I’m firmly on the side of people creating and using what they create – especially if it involves saving your own life – so I’m building a workshop/lab in order to create drugs such as FOXO4-DRI for my own use.

So far, I have the frame of the lab built, and I’ve bought and calibrated a 3D printer for designing and building the lab equipment itself. I’ll probably write a second book explaining all that when I’m at a sufficiently advanced stage. I’ve just paid for the mechanical and chemical parts for a dehumidifier, which I’ll need to design because there are no 3D-printed desiccant-wheel dehumidifiers already in existence that I know of.

Anyway – next week, I’ll rewrite another chapter. The chapter on fixing DNA replication with NAD+ looks like it might be the next highest in popularity, so it gets a rewrite.

Rewriting the Senescent Cells chapter

Last week, I rewrote the How to Live Forever book’s introduction chapter so I had two different copies. This lets me display one or the other randomly to each visitor to the website, letting me figure out through visitor interactions which chapter catches the attention more and is easier to read.

This week, after resetting the Introduction’s stats, I checked and the next-most popular page was “killing senescent cells with the FOXO4 DRI peptide”, so I’ll rewrite that this week.

The first thing I did was to rename it “Senescent Cells”, since the focus should really be on the problem, senescence, instead of the solution, senolytics. When I first wrote the chapter, the only senolytic that people were talking about was FOXO4-DRI, but since then, others such as UBX0101 and Navitoclax have been mentioned as well. There are about 25 or so senolytics in trial in various clinics. So, I renamed the chapter to be more about what senolytics are for, and not to be about a specific one.

When I rewrote the Introduction chapter, I basically just read the original, then paraphrased it. This was okay to do because the introduction is just a general overview – it doesn’t have a lot of details in it.

When rewriting every other chapter, though, more care needs to be taken. Every sentence has something to say, so I need to make sure that the rewrite includes everything that the original had.

The first rewrite will be a rough draft paraphrase, just like last week’s rewrite. But then I’ll go through carefully and make sure that I included everything written in the original, and finally will try to find new information to talk about, since the focus is no longer on the DRI peptide, but is now on senescent cells themselves.

This should be easy enough, because there are new human trials and new drugs that have come to light since I wrote the original.

I had another idea as well, which is to illustrate the concepts in cartoon form. This will let me explain visually some of the ideas that are hard to explain with words. Of course, I can’t draw, so this may take some redraws to get it right.

Because senolytics such as the FOXO4-DRI peptides are not currently available even to clinics, I will also include some information such as where to buy senolytics.

Is true immortality possible

Is immortality real? Is the concept of it even realistic? What about quantum immortality – doesn’t that make it real? Is quantum immortality real?

“Immortality” is a tricky word, because it leads to some awkward questions. Let’s imagine it means that “you will live forever”, well then we need to define what “you” means.

“You” are the sum of your histories. Let’s say you get hit in the head and you lose most of your memories, and change from the happy person you are into a grouchy paranoid violent mess. That is still “you”, based on the sum of your histories, but if you were to compare the two people, you would not call them the same.

Unfortunately, quantum immortality does not guarantee that it is the current “you” that will live forever. In fact, it’s also very possible that your current you is simply not suited to live forever anyway.

Why?

Anne Rice’s books “Interview With The Vampire” and “The Vampire Lestat” are about two vampires who have different ways of dealing with living forever.

Louis is an 18th century man who does not grow with the times. His way to deal with advancements such as cars, radio, computers, is to retreat away from society into a house where he can surround himself with what he is familiar with.

Lestat, though, moves with the times. He accepts that he cannot change the world, so should change himself instead.

Even within the span of a normal human’s lifetime, you can see Louis’ mindset affecting people. The joke is that only young people can deal with new technologies because they are born into them. Of course, those young people are eventually surrounded by technologies that they were not born into, and the cycle continues.

In order to live even two centuries, you must keep up with modern technologies and society. This changes you. The “you” in a century may be a completely unrecognisable person from the “you” today.

This means that “you” cannot live forever.

However, this is not a bad thing – “you” are not even the “you” that existed just a minute ago. Your thoughts evolve, your memories fade, your personality adapts to changing needs.

The only way to stay exactly the same person is to freeze yourself in time. And if you do that, then you are not living.

For quantum immortality, old age is just a step towards renewal. You will discover something in new technology that fascinates you and gives you a “rebirth”.

This will change who “you” are, but it will be a good change, because the old you was about to die a boring old death stuck in the past.