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 β-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 😉 ), 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!

what is the maximum lifespan of the human body?

It’s amusing to watch people predict things and then see their predictions fall flat almost before the words leave their mouths.

In 1928, Louis Dublin used US life tables to predict an “ultimate figure of 64.75“, saying that it was impossible for a human to live longer than that without the intervention of “radical innovations or fantastic evolutionary change in our physiological make-up, such as we have no reason to assume”.

He was not aware that at that very moment, non-Māori women of New Zealand had a life expectancy of 74.9 years – more than 10 years more than Dublin thought was possible (see Life Expectancy table here).

8 years later, in 1936, Dublin worked with Alfred Lotka on a reassessment, taking New Zealand’s data into account, and predicted a new limit, 69.93. in 1941, only five years later, women in Iceland broke that limit

Undeterred, he tried again, predicting a life expectancy limit of 70.8 years in 1941. Only five years later it was reported that women were reaching into their 80s in Norway.

The error with this kind of prediction, which people keep on doing over and over, is that it is based on information available on how long we lived in the past, but doesn’t take into account that we are always discovering new ways to live longer.

In 1990, S. Jay Olshansky predicted that “it seems highly unlikely that life expectancy at birth will exceed the age of 85“. In 2002, the life expectancy of Japanese females at birth was 85.2 years.

The country with the current highest life expectancy at birth is Monaco, with an expected life expectancy of 89.5 years.

It should be noted that “life expectancy” is not a limit on mortality. It doesn’t state for a fact, that people will not live longer than that. All it says is that this is the age at which most people are expected to die. There will be outliers that live well beyond that, and accidents where people die before that.

But, the fact that the number keeps on increasing, no matter what the experts say, shows that the human race is (very) gradually winning the fight against mortality.

More recent limits are based not on the past indicators of how long people have lived, but on limitations imposed on the human body by biology itself.

A recent prediction is that the biological limit for human longevity is 126 years old, based on the Hayflick limit, which limits how long a human cell can keep replicating itself, because the telomeres at the end of the DNA shorten each time, until the cells stop replicating and go into senescent mode instead.

But, there is now a treatment that can lengthen telomeres, showing that yet again, the naysayers who put limits on what is possible, are consistently low-reaching. And even for those cells that have passed their Hayflick limits, we have senolytics designed for killing senescent cells.

The future is optimistic. We are pushing our mortality further and further into the future. Read more about how we are learning to solve these problems in my book on how to live forever.

FOXO4 DRI prices (July 2017)

I’ve removed a few entries from the table of prices I was tracking, because they were not DRI peptides.

If you are buying in bulk, it would be cheaper to synthesise, as discovered by some people at Longecity, who were quoted about $231.15 per 30mg dose, as long as you’re willing to fork out nearly $8000 to buy a 1000mg shipment.

The off-the-shelf prices are coming down quickly, month by month, as you can see, with NovoPro being the first lab to provide 30mg for less than $2000 (down from more than twice the price only two months ago!)

Shop May June July
Bucky Labs 2460 2265
NovoPro 4060.2 2144.6 1756.8

Hopefully next month, there will be more labs providing FOXO4 DRI off-the-shelf.

It’s still very expensive, but I’m certain that as demand ramps up, the prices will drop.

If you are aware of any lab that sells FOXO4 D-Retro-Inverso(DRI) peptide please comment below so I can add them to the list

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

FOXO4-DRI price updates

It’s only been two weeks since I last checked the price of 30mg of FOXO4-DRI (the FOXO4 peptide), and already there are huge changes in the prices.

Shop May June
Novus Biologicals €85,800 €85,800
Merck €10,755 €43,020
Bucky Labs $2,460
NovoPro $4,060.20 $2,144.60
MyBioSource $1,830 $1,830

Bucky Labs is new to the list. The only other place I could find to buy FOXO4-DRI was at a shop that asks that you contact them for prices. That always says to me “you can’t afford it, and we don’t want to sell it to you anyway”.

I’m still puzzled at the huge difference in prices here. Maybe I’m reading their websites wrong and these are actually different products? If so, please comment below to help me understand.

Note: FOXO4, not FOX04. The only number in there is 4. The “FOX” is short for FOrkhead boX, and there are variations of the final part from FOXA1 to FOXR2 and all letters in between. FOXO4 is the 4th member of the FOXO subclass.

FOXO4 peptide prices

When I checked last, the price for a full human dosage of FOXO4-DRI (used to kill senescent cells) was $3000 per day, based on the first reply here.

I expect that the price will go down as people discover it, with the various drugs companies fighting each other to catch the market. I’m going to periodically check to see how the prices reduce, and when it gets into a range I’m comfortable with (definitely not $3000 per day!), I will test it myself.

Current prices for 30mg are:
€85,800 at NovusBio
€10,755
$4,060.20 at Novoprolabs
$1,830.00 at MyBioSource (and 6 free USB drives for some reason…)

I don’t understand why the prices are so wildly different.

At this moment, I think it would be cheaper to pay your way through college and then buy the lab equipment and synthesise it yourself. The FOXO4 peptide’s amino sequence is described in the patent, but I don’t think patents restrict you from doing things as long as you don’t benefit commercially from them.

foxo4 human trial (not plural)

There is at least one person trialling the FOXO4 peptide (albeit informally), and blogging about his experiences while taking it. I’ve added him to my list of feeds – looking forward to his progress!

I’d love to know where he’s getting his stash from, but I’m sure he’d prefer not to say, in case the producer gets in trouble (FOXO4-DRI has still not been approved for human trials). [update: he’s in the business, so didn’t need to go through commercial channels]

FOXO4 is a gene that, in senescent cells, uses the p53 gene to stop the cell from splitting further, but also stops it from dying (apoptosis).

Recent research shows that if the FOXO4 gene is blocked using FOXO4-DRI (a kind of peptide), then senescent cells will kill themselves, and the body can recover by growing new younger cells to replace them.

Killing senescent cells is necessary, because if you don’t, then they accumulate over time, eventually being the only kind of cells that you have.

Nutrition chapters, and FOXO4 peptides

This week, I started working on the Nutrition chapters. I read a fascinating 1791 book by George Fordyce titled A Treatise on the Digestion of Food. In it, he proved that calcium is a nutritional need for chickens in order that hens could lay eggs.

He also weirdly was able to prove that goldfish can survive for weeks on end in distilled water with no food. I haven’t taken the time yet to figure out how he got that wrong, but I’m pretty sure he did!

I’ve been searching to see if I can find cheap sources for FOXO4 peptides, but the lowest price is still about $85 for 50μg.