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.

When will we be able to live forever

Based on the rate at which medicine is evolving, the answer to this question is a resounding “Now!”

Almost every disease has a cure or a cure-in-testing, and aging is just one of those diseases.

In the book How To Live Forever, I wrote four sections on ways that we already know to slow or even reverse aging, including telomere extension, senolytics such as FOXO4-DRI or UBX0101, calorie restriction, and increasing NAD+.

Of the four, three of them are in human trial at the moment, and the fourth has already been shown to reduce the incidence of tumours in humans.

Telomere extension has already been shown by Elizabeth Parrish to increase telomere length by 9%. This equates to about 10-15 years of life extension. This year, it was shown that telomere extension treatment in progeria sufferers results in decreased inflammation and decreased ╬▓-galactosidase almost immediately after treatment. Because humans live so long, it is hard to know for sure if live extension works. Progeria is basically a disease that increases the speed of aging in humans – if you can slow or cure progeria, there’s a good chance you’ve also made huge steps towards curing aging itself.

Senolytics are drugs that kill senescent cells – cells that have stopped replicating and producing new young cells, but which also refuse to die. Instead, they stick around spewing out inflammation proteins and causing other nearby cells to also go senescent, resulting in more and more of your cell population becoming old and useless. Senolytics such as FOXO4-DRI or UBX0101 work by covering the part of the FOXO4 gene which is stopping the cell from dying, thus forcing the cell into apoptosis (cell death), making room for new young cells.

Calorie restriction is shown in lab animals to reduce the incidence of tumours (cancers), and leading to longer (up to 50% longer!) lives as a consequence.

And finally, NAD+ is a catalyst which helps the mitochondria of your cells to work with oxygen to produce energy. In older people, the amount of NAD+ in your cells reduces, making it harder for the cell to produce energy, and sometimes resulting in DNA-replication errors. To increase NAD+ in your cells, you can either inject NAD+ directly, or ingest NMN (a precursor molecule that turns into NAD+ in the body).

There are a lot of other methods of living forever, but these are the big four at the moment.

Progress on the workshop/lab

I mentioned last month that I’m starting work building a lab for (eventually!) protein synthesis of FOXO4-DRI to reduce senescent cell build-up and NMN to promote NAD+ production in cells, etc. There’s no point writing a book on how to live forever if you’re not going to get working on the answers yourself!

Because I’m working completely on my own, and have no experience in construction, this is taking longer than I thought!

I have the foundation 95% completed now. The structural parts (the load-bearing bits) are completed. I just need to fill in some gaps in the foundation wall, then add some plastic damp proof coursing between the wall and the wood of the workshop floor, then I can start on the frame of the thing.

The plan with this is to start off with some simple things – a 3D printer and some electronics, and use those as a base from which to build up a proper lab, one tool at a time, building as many as possible from scratch.

Critics might say (and they do…) that the only way to do good work is with good tools, but they appear to forget that everything we see today was built from the ground up using nothing much more than a rock hitting another rock. You use bad tools to make better tools. I am doing the same.

I was asked why I didn’t just get some people in to do the building for me. Partly, it’s cost, but it’s mostly because I want the satisfaction of knowing exactly where every nail and knothole is, and I want to design every aspect of the building to my own specifications.

I have had to learn a lot along the way so far – how to do mortaring, how to drain an accidental pool (siphoning through a hose. muddy water doesn’t taste nice ­čśë ), how water travels through concrete.

I’m still learning some things, like how to connect two pieces of wood together. Nails and nail plates appear to be the solution.

This weekend, I start on the frame of the build. I think that will go up very quickly.

longevity escape velocity

The main part of this website is the book, “how to live forever“, and even as it was written, I kept changing my mind about what the “thrust” of the thing was – is it simply a list of diseases? Is there a central premise? Does a step-by-step instruction set even exist?

I believe that I have the premise now (and will need to rewrite parts of the book now…), which is based around “longevity escape velocity” (note to self: good chapter name)

In the past hundred years, life expectancy at birth has increased in parts of the world from about 64.75 years in 1928, to 89.5 years today. The “life expectancy at birth” is the age at which actuarial calculations predict that humans will die, based on current conditions and past performance.

64.75 to 89.5 is an increase of about 25 years in one century. 25 extra years that a person might live.

While that sounds like a lot (25 years is almost half again of 60 years), it’s not enough to guarantee immortality.

Even if we repeat the trick this century, and tack on an extra 25.25 years to the expected 89.5 years (that a person in Monaco might expect to live), we still have an expected age at death of only 114.75.

As I pointed out in that previous post, though, life expectancy predictions are usually pessimistic, because they rely on the technology of the time, and cannot predict accurately what the future will bring.

The biggest change that we have made in the last few years is one that has not yet filtered down to the world’s clinics – instead of treating old age as a simple winding down and inevitable end to the body, we are now beginning to treat it as a disease that can be treated and cured.

The full “cure” for old age is not likely to appear for a very long time, but that does not matter, as we can concentrate on the more accessible “longevity escape velocity” as a near-term goal.

So what does “longevity escape velocity” mean?

Let’s say that every year, we discover how to let the average person live an extra half year, the current average age of death is 80, and you are 40. How long do you think it will be before you die (on average)? When you are 80 the average age of death will be 100. When you’re 100, the average age of death will be 110. When 110, 115. When 115, 117.5. On average, people will still die by 120, despite the progress.

This is because half a year is /less than/ one year.

But let’s say we discovered how to add on 1.5 years to the average lifespan every year, the current average age of death is 80, and you are 40.

When you are 80, the average expected age of death will be 120. When you are 120, it will be 210. Instead of being almost guaranteed dead at 120, you are now middle-aged!

Even if we have not discovered a total and final cure for old age, if you are 120 and have an extra 90 years to live /at that moment/, you are almost certain to find yet another way to push back that final curtain further, even if it’s not forever.

We are already discovering how to do these things.

The current accepted biological limit to human life is 126 years, because of something called the “Hayflick” limit, which is caused by telomeres shortening on DNA every time it replicates itself. But we have already found ways to lengthen this. Elizabeth Parrish, CEO of BioViva, became the first person to extend telomeres, extending her own by 9%, which equates to between 14 and 20 years extra, bringing her potential lifespan up to 140+ years.

It might even be possible to repeat the same treatment, so she has potentially worked around the Hayflick limit permanently.

This gives us all an extra few years of life to work on whatever the next issue is.

Aging is caused by a lot of different things happening to the cells of the body. Telomere shortening is just one.

Another is that your mitochondria lose the ability to absorb oxygen and convert it to energy as the years go on. By fixing this, we gain another few years. David Sinclair’s research with NAD+ addresses this issue.

Then there are senescent cells – cells which have reached their “end of life”, and yet stick around, taking up space that would be better used by younger cells, and giving out inflammation proteins. We can now selectively kill these cells with FOXO4-DRI and UBX0101 drugs.

All of these are treatments that add on multiple years to your life. And these have all been announced only in the last five years.

It might not be possible to predict the future accurately, but I’m fairly sure it will be a long one!

maximum lifespan of a human

Last year (October 2016), a number of scientists pronounced that humans can not live longer than 115 years old.

This, despite the fact that a French woman, Jeanne Calment, died aged 122.

The problem arose because these scientists based their pronouncement on existing data, not factoring in the fact that we have never in the history of medicine applied ourselves to solving aging itself, but rather to solving the health issues that arise as side effects of aging.

This is similar in a way to stating that the highest point a person could ever touch on a wall is about 2.5 meters above ground, totally ignoring that we can invent stools or ladders.

Aging is only recently being recognised as a disease, and the fundamental causes of it are still being identified.

One reason we have an apparent limit on longevity is that genes have a “half-life” of sorts, where they can only divide a certain maximum number of times before they refuse to divide anymore. This limit is called the “Hayflick limit” after the person who noticed it.

The reason that genes won’t divide forever is that the ends of them, the telomeres, get shorter each time a division happens, and eventually they are so short that another division might cause a loss of functional code, so the cells notice this and refuse to divide anymore, going into senescence mode.

There are two treatments which can solve this issue.

Firstly, there is a treatment which has been demonstrated to lengthen the telomeres. If this treatment is repeated each ten-fifteen years, the telomeres should stay long indefinitely.

Second, you can kill the already-senescent cells by blocking the FOXO4 protein using a FOXO4-DRI (a FOXO4 peptide whose amino acid sequence has been reversed). This allows the senescent cells to die off, letting the body replace them with fresher cells.

And to help the DNA replicate more correctly, probably reducing the frequency that telomere treatment would be needed, you can increase the NAD+ in your cells by using NMN supplements.

People in the past never had access to those treatments, so it is understandable that there was an apparent limit to lifespan, but there really is no excuse – a scientist should never make an absolute claim like that which can so easily be shown to be false.

image source

Niacin dosage for high cholesterol

The recommended daily dosage of niacin is 16mg (males) or 14mg (females), with a maximum dosage of 35mg, beyond which you end up with a niacin flush. Niacin flushes are not dangerous, but they can be uncomfortable.

Niacin is a precursor for (it turns into) nicotinamide mononucleotide (NMN), which in turn is a precursor for nicotinamide adenine dinucleotide (NAD), which helps your DNA repair itself.

The nutritional need for niacin was first noted in 1937, 100 years after its first discovery, after a long chase for the cause and cure of Pellegra in the US.

Studies found that high-dosage niacin can reduce high cholesterol levels (hypercholesterolemia). The niacin dosage for high cholesterol is 1-6 grams of niacin daily, starting from a lower 100mg per day and increasing steadily. This is best done using a slow-release supplement, which will reduce the “hit” that the body receives, thus lowering the effect of the niacin flush.

High dosages of niacin cause liver damage, with symptoms of jaundice, itching, nausea, vomiting and fatigue. However, the damage is usually mild, and will stop as soon as the niacin overdosage is stopped.

Live Forever – the blog

This short article is an introduction to what I’m trying to achieve here, and how.

I started writing a book on how to live forever a few years ago, but never got much beyond the first few pages.

It’s becoming more and more probable that the first person to live to two hundred has already been born, so I wanted to create a book that would describe the current state of research, and ideas on how we can achieve full immortality (not just life extension)/

I have enough content in the book now that I can start putting together a website for it.

My idea is that by putting the entire content of the book online, I can use split-testing to try make it better, by carefully analysing what pages of the book lead to people moving onto the next page, etc.

With the book, I am trying to be as factual as possible about everything, with references for everything that might be contentious.

For the most part,┬áthe book’s content is general knowledge – don’t smoke, avoid obesity, exercise – but there is a lot of stuff that people don’t know about, and that sounds really crazy (for want of a better word!) at first hearing.

You’ve probably never heard of NAD+, FOXO4 peptides, or telomere lengthening, for example.

These are properly researched methods to┬ákeep your┬ábody’s cells young. You will have heard, for example, that red wine is good for you because of something called Resveretrol. Well, David Sinclair, the scientist behind that research went on to research something else called NAD. It turns out there is very solid evidence that this extends life in mice, and there are human trials that suggest the same thing. Of course, we live longer than mice, so we won’t be certain of this for a long time, but the evidence is strong enough that Sinclair and his team take the NMN supplement themselves (which increases NAD in your cells).

On the crazy side, I’ve also written about Quantum Immortality – the idea that you cannot die, because there are infinite universes and there will always be at least one in which you (or an exact clone, right down to the memories) will wake up tomorrow – which is not really as mad as it sounds. Especially if you compare it with some ideas that various religions state as fact.