An Interview with Jim Mellon, and Update on Juvenescence

This interview with Jim Mellon opens with an update on some of the recent investment activities of Juvenescence, founded last year in order to participate in the enormous market opportunity afforded by the development of the first working rejuvenation therapies. It is in Mellon's self-interest to help educate the world about the size of this market, and draw in other, larger entities that will help to carry his portfolio companies to the finish line. So he is doing just that, and in doing so benefits us all. His advocacy will help all fronts in fundraising for research and development in this field.

That advocacy continues, as it remains the case that the investment community as a whole is slow to wake on the topic of treating aging as a medical condition. The more agile portions of it are starting to move, but the larger interests are still on the sidelines. Yet any viable rejuvenation therapy will be a bigger prospect that any blockbuster drug of the past few decades, and the first of these therapies are already either in development or even arguable available in the case of the first senolytic pharmaceuticals. The target market is every human being over the age of 40, for treatments that will have to be reapplied every so often, indefinitely. There won't be a bigger opportunity for gain until the orbital frontier opens up.

What's making you so optimistic that you and I will live to be 100 or 110?

The first book I wrote about biotech came out at the end of 2012. When the latest book came out, we were looking at just five years of a gap. And in those five years, artificial intelligence - which didn't exist in 2012 - is now very much in the frame for the development of new compounds. A cure for hepatitis C did not exist in 2012. Now, if you've got the money - and even if you don't have the money, because drugs are coming down in price - you can be cured of hepatitis C. Cancer immunotherapy did not exist in 2012, and is fast becoming the standard of care in blood cancers and will ultimately become as important in solid tumors as well, improving cancer survival rates by a dramatic amount. And lastly, most importantly, CRISPR gene editing did not exist in 2012. If you think about what's happened in the last five years, all remarkable technologies, just imagine what's going happen in the next five years.

How do you expect Juvenescence Ltd. will capitalize on this?

We are very early in this land grab. We are very hopeful that we can get at least two or three compounds into the clinic and out of the clinic within the next few years which will have indications beyond longevity, because it's very hard for anyone to say "I can keep you alive for 30 or 40 years" without hanging around to see if it works. I've done a few things in my life, but this is by far the most interesting and exciting. Rather than associating old people with being decrepit, people will be robust for a lot longer and will live a lot longer. I'm not a subscriber to Aubrey de Grey's view that the first person to be 1,000 is alive today. But I do absolutely believe that the first people who will live to be over 150 are amongst us now. That is just quite amazing. It's going to change everything in the world.

Not long ago I interviewed an actuary about how the financial assumptions underlying pensions or life insurance. He pointed out that gains in life expectancy are leveling off.

Every bit of our life expectancy increase in the last century or so has come from environmental factors. Better sanitation, lower infant mortality, better nutrition, less manual labor and therefore less accidents. None of it has occurred from biological change. It's only now that biological change is about to happen. The question then becomes: who benefits, and who doesn't? In the United States, you suffer from tremendous health inequality. New drugs like senolytics or rapalogs are probably going to have 10 years of patent life. Now if we have a long life, 10 years is not that long. So even if those drugs may expensive to begin with and therefore available only to so-called elites, they will in due course become rather like anti-ulcer drugs are today and available to everyone. In the 1980s, anti-ulcer drugs were extremely expensive prescription drugs. Now you can go into Walgreens and buy them for nothing, basically. That will apply to all these drugs.

Link: https://medium.com/neodotlife/juvenescence-jim-mellon-longevity-e9a415dd0569

Comments

this section caught my eyes when reading this last week or the week beforehand: 'I'm not a subscriber to Aubrey de Grey's view that the first person to be 1,000 is alive today. But I do absolutely believe that the first people who will live to be over 150 are amongst us now.'

It'd be interesting to know based on what technological scenario or lack of a technological scenario does Jim Mellon thinks that 1000 is a no-go while 150 is a go. It's kinda hard to say at this point reasonably that at 150 there's going to be a hard limit that will take another 1000+ years to figure out and solve so everybody living alive now is dead by then. I mean nobody really has a clue about hard limits even amongst hardcore scientists and technologists, so imposing them probably serve some other cause like 'being more acceptable to the mainstream' or something. In the meantime, let's just acknowledge to be uncertain about this and stay open. One reason I call my approach Open Lifespan. :)

Posted by: Attila Csordas at June 4th, 2018 7:15 AM

@Attilla Csordas: Open Lifespan, I guess you have coined it? I like it extremely much. Do you have a blog or other with the title?

Posted by: Norse at June 4th, 2018 8:19 AM

My Rx GERD medication cost me $300/month; the cheap stuff did not work. It's bit perplexing since the Rx is just the optically pure (not racemic) version of the same drug. Upping the dose of the racemic version should have achieved the same efficacy, but it did not. My gastroenterologist said that he had other patients that had the same experience and he had no explanation for it. I gave up on PPIs entirely and just toughed it out.
Fortunately probiotics and lots of fiber did work (no more GERD every night, only occasional heartburn), but it took a few weeks.

Posted by: CD at June 4th, 2018 9:39 AM

@Attila - I think Jim Mellon's reluctance to accept that if you have the power to keep people alive and healthy to 150, you have the power to keep them alive indefinitely, is just down to intuitive human reasoning. Most people expect tomorrow to be much like today, because that is a model that is generally right and actually thinking about things in more depth is difficult as it is generally a waste of time for your average hunter gatherer human.

Humans just accept that there are facts of life and inevitable things. Which is why there was such skepticism of the possibility of powered human flight, until it was no longer impossible.

Posted by: Jim at June 4th, 2018 10:16 AM

Hey guys,

I've been studying Jim a LOT this last year. Not just on the longevity front, but also on his track record.

Jim certainly DOES subscribe to the idea that humans can live past 150.

There is a LOT going on when it comes to investment PR. He needs to play the game and not come off like a cook. He prefaces most of his talks saying that this isn't sci-fi and my favorite quote "The science has caught up with the aspiration, we're here now, this is going to be a huge industry. Please take note of it.".

Jim just can't come out and say we'll live to 1000. Be glad he doesn't. He knows the real deal, and he knows what is possible. He's playing it safe to get at the cash.The average human can BARELY seriously grasp living to 120 in good health. It goes against EVERYTHING it means to be human at this point in time. In every talk he gives, he has to remind people that in 1900, average lifespan was 49ish, and its not unreasonable that given the accelerating trends of technology we should expect to see 110-120 over the next 3 decades. That brings us to the 2050's. If his predictions are correct, those of us in our 40's now will be around in the 2090's.

If we are talking about regeneration, age resistant cells and gene editing now.... by 2090? Are you kidding me? At that stage, I'm not entirely sure we'll even be meat-based anymore. The biotech industry has the potential to overtake the size of the auto industry. Think about that for a sec. Cars are EVERYWHERE.

There will be plenty of time to push the numbers up as people live longer/healthier and hopefully, sexier.

Flat out in his book, Jim states if you are reasonably healthy, don't smoke and under the age of 75, you have an excellent chance of living over 100, (Gotta read his stuff guys). Based ONLY on the tech we have today (Rapalogs, Senolytics and the new tech coming out to reduce age related diseases like CART and PCSK9). He flat out acknowledges that once we get gene editing, Stem Cell tech, and iTR, ALL BETS ARE OFF. If you want sources, I'll provide. He states it over and over (And he needs to, this is going to take a LOT for it to sink into peoples brains. We are fundamentally changing what it means to be human).

Ever go looking for money for your own start up? I have. Business plans, revenue projections, the lawyers, the beancounters, the milestone projections, all of them have top be grounded in real tangible methods and ideologies. This is going to require MOUNTAINS of cash, and he's trying to get as much as possible. In fact, there's one talk where he's at the Milken Institute on a panel with the Chairwoman of AARP. She controls something like 3 billion dollars and you can see him licking his chops like a wolf trying to get her on-board and investing. He's doing all he can. Best thing is, he's being taken seriously.

Anyway, enough bloviating. Time for some proof/links.

https://www.youtube.com/watch?v=zkgHPsr0yfk&t=1687s

https://www.youtube.com/watch?v=zbS50yVWkOg&t=1624s

https://www.youtube.com/watch?v=qv2K-QmCDDs&t=28s

More if you want it.

I'm a big fan of Jim. I wish him much success with his new company. For all of us.

Posted by: Mark Borbely at June 4th, 2018 10:56 AM

Hey there, just a 2 cent.

I believe Mr.Melon, 150 years is about the tops of what SENS will give (although combied with other therapies it might change that, albeit unlikely unless the body is entirely replaced from head to toe, while somehow preserving the brain/memories/your identity), it will not be a repeatable thing that (you can repeat it, the error is to think this will bring you back to a young you. Fallacy, that I am near assured of. This biological aging is under epigenetic control, damage reduction doe not stop aging, the element missing from this 'damage is all' picture. Epigenome does not just revert itself because of damage reduction, iPSCs tells us a whole lot about this, before and after reprogramming them to DNAm age 0. There are many unsolved problems that linger/no answer to and why 150 years max is about right. With that said, if it is the best of what's next in the 30-40 coming years, we'll still take it, nothing better so far.

Just a 2 cent.

Posted by: CANanonymity at June 4th, 2018 11:40 AM

On the 150/1000 debate: I do think Mellon really thinks what he says. It's not a PR strategy, simply it's the common reaction from people that don't have enough knowledge/expertise or don't agree with SENS (basically by the same lack of knowledge/expertise). That's also why he puts so much hope on metformin, rapalogs and the like. It's understandable--he is a newcomer and rapalogs etc. is where the mainstream/traditional advocacy lies. Luckily, he is also investing in senolytics (but, again, using the traditional approach of massively searching in compound databases).

Posted by: Antonio at June 4th, 2018 12:36 PM

It is funny that one can talk about reaching the lifespan of 150 in the next couple of decades. The longest proven living person was a tad less than 25. So to get anybody , not average, but ANYBODY at all to live up to 150 will require the oldest person alive (only 112 years) to live to 150, which is 38 years from now. If you discount that estimate that anybody who's 50 years old could potentially live up to 150 ,you have to plan for 100 years of scientific and medical advances. That's too far in the future. An adult person of 1800 could still comprehend the lifestyle of 1900 but probably not all the inventions available then. An adult person of 1900 will not be bale to comprehend our lifestyle, the knowledge and capabilities.

@CANanonymity
>I believe Mr.Melon, 150 years is about the tops of what SENS will give
If a few superlucky people can live up to 122, then why not up to 150?

>Fallacy, that I am near assured of. This biological aging is under epigenetic control, damage reduction doe not stop aging, the element missing from this 'damage is all' picture.
So you are implying that we have an epigenetic death-switch. Than it would be too easy. just find the switch and hack it. Now we might not be able to repair the brain without losing memories or identity. However, with reprogrammed or universally non-rejectable stems cells we could find a way to print and implant any body part(apart from brain memories) in youthfully-equivalent state. So without mastering the memory transfer in 100 years we will have people with young bodies and fading childhood memories. If it is done gradually enough, those "memories" could be reconstructed based on documents, diaries, pictures and video. But let's jump from that bridge when we get to it....

Posted by: cuberat at June 4th, 2018 2:20 PM

@Antonio
>On the 150/1000 debate: I do think Mellon really thinks what he says. It's not a PR strategy, ...don't have enough knowledge/expertise ...

Well, I don't think it is pure ignorance. He might be just too cautious. After all we know that if the humanity doesn't destroy it self or stagnate, the life expectancy will be slowly but steadily increasing with time. It might be a week per calendar year. So it means that in 52 years the life expectancy would grow by one full year, in 520 years it will grow by 10 years, and in 5200 years it would be add full 100 years(the period is really huge, from the first civilization till today). So the question is not if it can be done, but rather when it will be achieved. And if ever we could reach LEV...

>...That's also why he puts so much hope on metformin, rapalogs and the like...

Now adding a week per calendar year would not be exciting enough to warrant huge investment if it doesn't improve the quality of life. Unfortunately, merformin can add only a couple of years and probably because of calorie-restriction mimetic. Or simply because metformin causes gastric issues and makes the people eat less. So it cannot reach the effectiveness of a full-blown CR. Rapalogs reduce the chronic inflammation and can win you another 2-5 yers. But the effects of combining metformin with rapalogs don't seem to compound well. So, with perfect mix of merformin, rapalogs, CR you could expect to increase the average lifespan by 10 years. Same as intermittent fasting and exercise. And we have no proof that fating hermits can live to 150 y.o.

On the other hand, those are low hanging fruits. Senolitics are potentially a game changer , but are more involving. He might be lucky to find something in the existing compounds. However, it probably would be with nasty side effects. After all, we don't witness magical supplements or people looking younger after chemo...

Posted by: cuberat at June 4th, 2018 2:42 PM

Hi cuberat! Thanks for asking. Just a 2 cent,

Exactly, I think that too, if a human reached 122, why not 150, makes sense, it's no so far apart; with that said stats show that mortality is orders of magnitude each subsequent year when reaching 115-120 bracket. We can read about super centenarians who claim being 130 or 140 years - it could be possible, there may have been another Jeanne Calment (122) somewhere whom we never heard of (unlikely but possible (genetics repeat themselves (we have a twin 'clone somewhere), it would have been noticed/historically recorded). Albeit, super centenarian claims are debunked one after another as false (they don't remember their real age or make fake birth documents to spur tourism money/be the Oldest human attraction)), especially the ones claiming to be over 130, all debunked. I'm not saying it's impossible just ultra rare (1 chance on 7 billion people, or less).

122-130 is really a limit that imposes itself, and why no one in history reached 130 (as recorded and true, not an agrandized number made up ... like super centenarian claiming 144 years, dubious. Just a little)).

But, not Our future, 150 will now be a reality for the most genetically gifted (if you have centenarians in your family it is more likely obviously, but not set in stone. Centenarian offsprings live, generally, as long or nearly as long as their centenarian parents (inherited centenarian genetic)). It's a mixture between environment/lifestyle/genetic. But, with age the largest determinant of whether you reach 120 or not 'if doing everything right', is what your parents gave you at birth (genetics).

Just a 2 cent.

Ps: Yes, a sort of epigenetic switch if you will, this clock keeps a tab on the cell's age. There can be a 'time's up', no more time, that is the job of this methylclock. Yes, recent research studies have tried to alter this clock but with underwhelming results akin to every CR study results. We are not out of the woods yet, epigenetic is extremely complex and requires special reprogramming factors etc (Oct, Sox, Nanog, Zincfinger gene/domains, helicase and telomere Shelterin proteins, Yamanaka factors))).

Plus, one study had found very short telomeres in a 115 year old woman (leukocytes, she was experiencing immunoscenescence, thus could die soon from a viral/bacterial disease (many elderly die of pneumonia or other bacterial infection disease because of weaken old immune system)). There are so many stumbling blocks to getting to 150.
Not unfeasable (later) but will still remain rare altogether not common despite biorejuvenation arrival.

Posted by: CANanonymity at June 4th, 2018 3:35 PM

@cuberat "It is funny that one can talk about reaching the lifespan of 150 in the next couple of decades."

That's not what he said. Read it again.

"After all we know that if the humanity doesn't destroy it self or stagnate, the life expectancy will be slowly but steadily increasing with time."

No, we don't know that. LE increase is not something that simply happens or that is guaranteed in any way. It's a product of medical progress, the standars of living, etc.

"Now adding a week per calendar year would not be exciting enough to warrant huge investment if it doesn't improve the quality of life."

You can't have one without the other.

"CR you could expect to increase the average lifespan by 10 years."

The increases in monkeys lifespans are really tiny. I'd be very surprised if it turns out to be more than a couple of years in humans.

Posted by: Antonio at June 4th, 2018 5:16 PM

Just a side note:

To truly understand epigenetics and aging, one must move beyond the conventional molecular biologist definition as it is used to describe covalent chromatin and DNA modifications (i.e. death-switch) and think broader in terms of C.H. Waddington's original "epigenetic landscape".

The concept of an "epigenetic state", which represents a system-level stable state that arises from various hierarchical interactions, is more encompassing of all the factors that need to be controlled in order to turn back biologic time and get beyond where damage removal will ever take us (i.e. aging as just another bio-attractor state like another: embryogeneis, morphogenesis, growth, development, etc.)

This vast "nested architecture" of control systems that sit above our bio-chemical networks, which modulate their function, and more completely represent the integrated causes of disease, degeneration, and aging include:

- bio-mechanical networks - i.e. forces of mechano-transduction, sheer stresses, friction

- hydro-dynamic networks - i.e. reaction diffusion dynamics of the intra-cellular space, water-gel transitions, visco-elasticity of interstitial fluids

- bio-kinetic networks - i.e. differential sedimentation, differential adhesion; biochemical oscillation / multi-stability of biochemical states

- bio-dynamic networks - i.e. cell-tissue fields of corrosion, contusion, retension, dilation, detraction, etc.

- bio-electric networks - i.e. membrane potentials of cells, tissues, organs, and body segments

- bio-magnetic networks - i.e. DNA resonance recognition; para-magnetic properties of metal ions / polyanions / electretes; radical pair mechanisms

- microbiome / virome - 100 trillion organisms living on, in or among / symbiogenically as a part of us

- bio-semiotic / bio-holon networks - i.e. induced phenotypic plasticity

- psycho-biologic - having to do with the increasing amount of evidence in the neuroscience literature on how thoughts, can impact "downstream" physical and chemical manifestations, and the brain, its respective signals, and its connection to the many other systems within the human body (endocrine, lymphatic, etc.) can stimulate alterations to our organs, tissues, cells, and even the level of DNA

- cosmo-biologic - how major "cosmic level" factors affect us too, from gravity (see recent information on the gene expression changes in astronauts in the international space station), to the earth's natural electromagnetic field, to time itself (see the field evolving field of chrono-biology)

Homeotaxic Networks - Non-hierarchical, peripheral automaticity - in groups of cells

These factors all need to be considered in any LEV approach

Posted by: Ira S. Pastor at June 4th, 2018 6:57 PM

@Antonio
>That's not what he said. Read it again.
Yeah he said that the first person to reach 150 is probably alive today. So if you take a newborn it leaves some 149 years till the deadline .

>LE increase is not something that simply happens or that is guaranteed in any way. It's a product of medical progress, the standars of living, etc

For the last few thousand years there was slow yet steady improvement in living standards and medical knowledge, with since big reverses from time to time. If the last choir of hundred years are not something exceptional there will be some imprudents on the cure le future. Another interesting development is that by the virtue of delaying childbirths the humanity is referring a pro-longevity selection pressure on the population. That alone over the course of many generations could increase the life expectancy. Of course there is no guarantee but there is a reasonable expectation for the trend to continue.

>The increases in monkeys lifespans are really tiny. I'd be very surprised if it turns out to be more than a couple of years in humans.

Probably not increasing the maximum lifespan but for sure could improve the average life expectancy, especially withe the current obesity epidemy

Of course, here we are hoping for much faster improvements. And for sure Mellon is expecting to see some improvements relatively soon, otherwise he wouldn't be investing in such treatments...

Posted by: Cuberat at June 4th, 2018 7:02 PM

@Cuberat

"For the last few thousand years there was slow yet steady improvement in living standards and medical knowledge"

Nope, it mainly ocurred in the last 200 years or so. Before that, life expectancy variation was mostly flat.

"Another interesting development is that by the virtue of delaying childbirths the humanity is referring a pro-longevity selection pressure on the population."

No, most deaths already happen well past reproductive age.

"Probably not increasing the maximum lifespan but for sure could improve the average life expectancy, especially withe the current obesity epidemy"

I was comparing CR practitioners lifespan to that of non-CR healthy individuals, not obese individuals.

Posted by: Antonio at June 4th, 2018 7:33 PM

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