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.


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.

New introduction variation for the book

When I first put the book How to Live Forever online, it was in order to figure out through split testing how to improve the chapters so they would definitely be read.

The idea was that if 100 people read a page, for example, then I would be able to record three basic stats on that:

  1. number of people that have visited the page
  2. percentage of those people that have then read the page (the test is – did they click the “Read More” button)
  3. percentage of those people that were interested enough that they then wanted to read the next chapter/page in the book (did they click Next Page at the bottom of the article)

The online version of the book does not get enough visitors yet to regularly break that down into meaningful numbers, so there has not been a lot of work yet on this.

The front page (the book’s introduction) just got its first 100 reads, so I decided yesterday to rewrite it it completely so I could have the rewrite and the original up at the same time to do a comparison against each other for the next 100 reads.

To rewrite the page, I didn’t just take each sentence and reword it. Instead, I read through the entire thing, and then wrote an entirely different version that was approximately the same length.

With future revisions, I may just change a few lines here or there, but I can’t be sure at this point that the article is even remotely written the right way, so I thought it would be best to have something written in a different style to test how that goes.

I mentioned three stats that can be easily measured from the page. Increasing those stats is the goal of this endeavour.

Stat 1, page-opens, the number of people that opened the page. This is not affected much by the content of the page itself, so can be ignored when it comes to split testing. I use it merely as a base from which to calculate percentages for the other stats.

Stat 2, full-reads, the number of people that clicked “Read More”. This is affected by the first half of the page, and by the total length of the page. Because the button appears at the half-way point in the page, if the page is very long, there is more to read to get to that point (and vice versa). The content of the first half needs to be high enough that people want to read the rest of the page. An easy split test to do would be to simply reword a few sentences in the first half of the article to see how that affects the full-reads. I may do that when the page-opens reaches 100 again on the introduction.

Stat 3, next-page, the number of people intrigued enough to want to go onto the next chapter. This is affected by the second half of the article. I’m in two minds about this – do I increase by setting up a “cliff-hanger” so the conclusion of the chapter is in the beginning of the next chapter (that’s evil), or do I try to make each article into a stand-alone? An issue with stand-alone articles is that readers may feel so satisfied by the end that they just go away. Well, I guess that’s a conclusion I’m happy with as well.

Here’s what I wrote for the new introduction:

How to Live Forever

When you look for a book on how to live forever, you find that most of the books are religious and/or fiction, or they were lifestyle books with no solid evidence behind their statements. This is not one of those books.

I started writing this book because I wanted to cut through the rubbish and figure out what exactly works and does not work. None of this “just exercise, and eat your vegetables” stuff – I wanted to know exactly how much exercise is necessary, exactly what vegetables.

This book is a collection of histories and research results that state very clearly what we are doing in order to extend our lives towards practical immortality, and how you can improve your own chances today.

What does it mean to live forever?

Literal immortality may be impossible. Even if you eat all of your vegetables and do all of your press-ups, it is still likely that if you were run over by a truck or fell out of an airplane, you might die. Having said that, Quantim Immortality addresses that, but we’ll get to that.

Instead, this book will mostly be working towards an idea of immortality called “negligible senescence”, which means that your body’s aging slows down until it’s just not noticeable. This way you can potentially live for centuries, as long as you avoid open doors on flying airplanes.

For most of human history, the attitude of doctors and scientists towards human life was that you had about 60 years of life and then you simply die of “old age”. It did not occur seriously to people that old age was something that can be studied like a disease and potentially cured.

There have been stories of aging cures, such as Juan Ponce De León’s Fountain Of Youth, or Tír na nÓg, or immortality through vampirism. Those are just stories, but every story told to a child can inspire a spark of “what if?” which may lead that child to look into the possibilities a little further than the previous generations.

Since the 19th century, scientists have made solid advances into finding out what nutrition the body needs, with a lot of horrifying experiments along the way, some of which were performed on animals, criminals and children.

Nutrition, though, is not the entire story. Even with the most perfect nutrition, the human body will still only live for a century or so before it winds down.

We have also found ways of transplanting organs from one body to another, overcoming problems such as blood type differences, and immune systems. In more recent years, artificial organs have been created which can address the lack of transplant donors.

The causes of diseases have been uncovered, and we have moved on from ancient theories such as balances and humours. We understand bacterial and viral infections now, and the importance of clean hands before operations.

Neither nutrition nor transplants will solve aging, though, because aging is not caused by any of those. No matter how many anti-virals or anti-bacterials you take, your body will still continue to age.

And no “alternative medicine” will help either. If it has not been tested and shown to work, then you can’t trust it.

In order to live forever, we must solve aging itself, which is a very difficult thing to do because it is a result of literally decades of chaotic interactions between cells and their DNA.

In recent years, it has become apparent that senescent cells are the main drivers behind aging, and the exact mechanisms by which cells turn senescent have been uncovered. This allows us to then find ways to stop this from happening, or destroy the senescent cells.

Clinical trials on this work have been performed on laboratory animals, showing that some methods (telomere extension, calorie restriction, senescent cell destruction, etc) can give extraordinary boosts to the length of lives, but human trials are just starting out now.

The most important buzzword to watch out for in the next few years is “senolytics” – a class of drug that can target and destroy cells which have converted from normal to senescent (old) cells and are now just hanging around in your body giving out inflamation cytokines that make your body feel like it’s sick all the time.

In this book, by “living forever”, I mean that you will literally not die. By following the guidelines in this book, you should add on a few decades at least to your life, which gives science time to come up with even more extraordinary advances, which I will of course talk about in future editions of this book and on my blog.

We live in amazing times, and I sometimes wonder at the sheer coincidence of it all – that we should be born into times where we are unlocking the secrets of immortality right there in our labs.

Because of the nature of how science works today, those secrets will be available to the common public within years of testing, and we can all have vastly extended lives because of this.

Modern lifestyle and health

Over the weekend, I was at an entrepreneur conference. I wasn’t there to attend any of the talks, but simply because a few of my CoderDojo students were giving talks themselves and a few of my fellow mentors were also involved with the conference, so we moved the entire CoderDojo to the venue (Monaghan Institute) for that weekend.

I spent about two hours answering every question the kids had about 3D printing, and there were a lot. When a child gets interested in something, they can dig really deep down into it and ask the most insightful questions. I had to explain the difference between PLA and ABS, why the bed was heated, how heat-breaks work and why they’re important, what kinds of materials can be printed (basically anything that melts and resolidifies at a predictable temperature) , how multiple-extrusion printers and why /they/ are important (for printing both chocolate and syrup, obviously), etc.

After the class was finished and the kids had mostly gone home except for some stragglers such as my own kids, I got a chance to see some other people’s talks. I got a few minutes of Niall Moyna’s talk on modern technology and health.

It’s unfortunate I didn’t get to stick around for the entire talk, because it is right up the alley of this website and my book, but the essence of what he was saying is that our bodies are “designed” to be active, and yet our technology is designed to keep us inactive.

To illustrate this, he pointed out that when an Australopithecus or Cro-Magnon got up in the morning, they’d better be prepared to run after their breakfast, because the local shop was a few tens of thousand of years away.

He said (and I don’t know the truth of this) that human beings can outrun every other animal on the planet, even if they’re faster, because most animals will need to stop every now and then to pant, while we simply sweat away the heat and keep going.

The point he was making is that we evolved to be active beings.

It has been shown countless times that when we are inactive, we are more likely to die early.

In 1949, Professor Jerry Morris did a study of 31,000 bus conductors and bus drivers and pointed out that bus conductors were 150% more likely per year to die of coronary heart disease. The correlation was because of two noted things: bus conductors are always actively moving and climbing stairs, while bus drivers sit all day and gain weight and fat around their organs.

Modern technology has a tendency of reducing the amount of “work” that we do in order to accomplish goals, which has the side-effect of slowly piling on the pounds on our bodies.

As an example, you are probably sitting while reading this. I’m certainly sitting while writing it.

When you drive your car to a shopping centre, you probably park as close as possible to the entrance. When you go anywhere at all, you try to park as close as possible, because it will reduce the amount of “work” that your body has to do.

Your body has evolved to expect that any energy it stores will be burned off sooner or later, so it doesn’t have a limiter. At no point does your body say “no more – I really can’t store any more of this energy”. Instead, as you eat more and more and don’t burn it off, it converts more and more to fat. All the while, it also makes it harder for you to do the work needed to shift the fat.

Fat is there for the lean times – it’s for the times when you are unable to find food nearby and need to walk miles and possibly days to find it. That scenario is ridiculous in modern days – there are always shops within minutes of any place where you are (in developed countries). But your body doesn’t know that.

Unfortunately, there is no single pill that will solve this.

We do have new methods that can convince the body to burn its fat, converting so-called “white fat” (the normal kind) to “brown fat”, but these methods have not yet been rolled out to the general public, and they only mimic one of the effects of exercise.

Exercise also has an effect on the oxygen intake of the lungs, resting blood pressure, and even happiness. Converting white fat to brown fat is not going to do these things.

It is in every person’s interest to do about 90 minutes of moderate exercise every week. Moderate exercise means something between walking and jogging. Walking up-hill, for example. Doing more than 90 minutes is probably a waste of your energy – you won’t get much more benefit from it, but if you don’t exercise at all, then taking regular walks will almost immediately lower your yearly chance of dying by about 14% and give you an extra 3 years life expectancy.

Modern technology is evolving much faster than the human body, so you need to keep that in mind and try to do more “work” than is necessary. Walk up stairs instead of taking a lift. Park on the far end of the car park. Cycle or walk to work.

The SBSI (Surface-based Body Shape Index) is a good measurement tool for figuring out if your body is “in shape” (literally), as it does a better job than the ABSI and the BMI of correlating body shape to mortality. Use my calculator to figure out your current SBSI, BMI and ABMI, and what you need to do to improve them.

recovering from a spinal injury using stem cells

Earlier this year, a man, Kristopher Boesen, suffered a traumatic injury to the spine when his car slid off the road into a tree and then a telephone pole. He was paralyzed from the neck down.

Luckily, though, he qualified for a clinical experiment, where he was injected with 10,000,000 AST-OPC1 stem cells into the neck. Three months after the treatment, he now has control over the upper body.

There is no guarantee that this treatment will be a total cure, but even the smallest improvement in a spinal injury is a wonderful step forward in the cure for everything.

Previous work on treatment of spinal injuries include bypassing the injured site using electronics, and a possibly spurious “glue” that one doctor intends to use in a notorious body transplant some time soon.

FOXO4-DRI peptide prices for September 2017

There has been no change in the prices of the two suppliers that advertise FOXO4-DRI peptide on their website; Bucky Labs and NovoPro.

(the FOXO4-DRI peptide blocks the FOXO4 gene from interacting with the p53 gene, allowing senescent cells to reach apoptosis and clear themselves up to let younger cells take their place, letting people get a little closer to living forever)

I got a price by email from the guys at YoungShe Chemical – $900 for 50mg. That translates to a price of $540 for 30mg (the FOXO4-DRI dosage I’m aiming for).

That’s still $308.85 more expensive than what was quoted to interested parties at Longecity, who were quoted about $231.15 per 30mg dose, based on a large 1000mg shipment.

Shop July September
Bucky Labs 2265 2265
NovoPro 1756.8 1756.8
YoungShe Chemical 540

It’s still looking cheaper to synthesise this yourself. Until the peptide cost gets down to below about $10 (for 30mg per day), it is still probably a good idea to work on building your own peptide synthesis lab. You’ll save money in the long term, and will learn some really cool science along the way.