Investment Strategist Jim Mellon Considers the Near Future of Longevity Science

Investment in the development of rejuvenation therapies represents an enormous opportunity for profit; these are products for which every adult human being much over the age of 30 is a potential customer at some price point. That is larger than near every existing industry, either within or outside the field of medicine, even given that customers will only purchase such a therapy once every few years, for clearance of metabolic waste, or even just once, for treatments like the SENS approach of allotopic expression of mitochondrial genes. Among the first successful companies in this space, some will grow to become among the largest in the world: I'd wager that the Ford or Microsoft of rejuvenation will be a lot larger than the actual Ford of automobiles or Microsoft of personal computing.

The field of human rejuvenation is also possibly the greatest opportunity for arbitrage ever seen, if we take the most general meaning of that term. The vast majority of people, whether investment professionals or not, greatly undervalue present efforts aimed at the production of rejuvenation biotechnology. They do not have the interest and insight to distinguish between the nonsense of the "anti-aging" marketplace of past years, marginal calorie restriction mimetic drugs, and approaches that target and repair the causes of aging. Only the last of those is capable in principle of producing large and reliable gains in human healthy lifespan, turning back the consequences of aging. The handful of people who do appreciate the possibilities still have a few years to establish positions and invest at a comparatively cheap price before this marketplace becomes a free for all.

It is definitely in our favor for that free for all to happen sooner rather than later, since it will bring a great deal more money to bear on the problem of human aging - a field that is still the poor relation in the medical sciences, looked down upon and given little funding. I suspect it will require senescent cell clearance to reach clinics and be used in hundreds of humans with reliable and public results for that to happen, however. Nonetheless, all fforts to speed matters along are a good thing, and so it is a pleasing to see a strategist like Jim Mellon earnestly advising his peers to enter this space for all the reasons I have given above. The second half of the video here is more concerned with aging, longevity, and rejuvenation therapies than the first half; if you skip ahead to a slide on opinion makers and another on longevity companies, you'll see some names you recognize - including Oisin Biotechnologies, SENS, and the Methuselah Foundation. It is good to hear the voice of an influential group that has performed enough due diligence to appreciate the useful end of the longevity science community, and understand its potential.

Jim Mellon | Main Stage | Master Investor Show 2017

Renowned UK investor and entrepreneur Jim Mellon gives his keynote talk at Master Investor Show 2017. Presenting to a packed-out audience, Jim focuses on longevity as the next 'money fountain' and subject of his forthcoming book, Juvenescence. His engaging, impassionate speech also covers the latest macroeconomic developments and prospects in the U.S. and Europe, and the future trends that could provide returns for investors.

Mann Bioinvest

We believe that over the coming decade the life science sector will be leading one of the most meaningful periods of scientific discovery and advancement. This period of development has been underpinned by two seminal moments - the discovery of the structure of DNA and the sequencing of the human genome; the latter occurring nearly 50 years after the former. Subsequent breakthroughs stemming from the discovery of DNA will give new hope to those with certain diseases who relatively recently would have had none. These breakthroughs are coinciding with a period in which the world's population is undergoing the most ubiquitous and rapid aging in its history. This, we believe, will lead to the life science sector gaining new prominence and that the biggest successes in the sector will ultimately dwarf the likes of Apple, Exxon and BHP that are the current colossi of the stock market.

Comments

I think this technological area might be on the verge of the hype phase.

I'm still wondering if necessary breakthroughs in the area of stem cells and cancer treatments are near, with a revolution in the next 5 to 15 years, or much more difficult only arriving decades from now?

William Bain's words also haunt me when he pointed out that we may just think these areas are the hardest because we are actually working on them, the proximity phalacy, and that the other areas rather than being easy will be equally difficult.

"[Lipofuscin clearance] is probably one of the easier of the proposed technologies: we do not know where to start with (to take another example) repairing mitochondrial defects with somatic cell gene therapy. For this project, Aubrey's biggest concern is one related to the capacity of the mitochondrial protein import system. This I think is falling for the proximity fallacy e the problem we know seems the most important, we ignore the ones in the distance (past and future) and so over-estimate the value of overcoming today's problem [5]. Yes, there is no fundamental law of physics that says you cannot do it, and this was the conclusion of the reviews that Aubrey has carried out of the various SENS components, performed by basic scientists, that allow him to conclude that we are ready to implement these ideas. But at a practical level we do not have the technology today that can even point the way to how it can be achieved. For this level of gene therapy, it is not Steam Engine Time."

Steam Engine Time: A review of ending ageing by Aubrey de Grey

Posted by: Jim at April 4th, 2017 1:18 PM

I'd assessed lipofuscin clearance as one of the harder parts of SENS. Well, easier to start, as the SRF has, but hard to complete to a usefully comprehensive degree given the large number of compounds involved, each of which requires its own development project, and the comparative lack of specific knowledge regarding the impact of most of these compounds on aging.

Allotopic expression at least has the merit of having only 13 distinct projects involved rather than some much larger number.

Posted by: Reason at April 4th, 2017 1:23 PM

Lipofuscin can potentially be solved by encouraging cell division as the burden is halved with each division. This is the view of stem cell researchers I have talked to. The issue is non or slow dividing cells as far as I can see. Many ways to skin a cat lets get this done!

Posted by: Steve Hill at April 4th, 2017 2:01 PM

This still does not ensure medical treatment official acceptance/testing notwithstanding any amount of money/ investment/ endorsement as the public is protected/ cosseted/ deprived of meaningful access. Only specialized 'regions', protected by otherwise 'interested' parties such as at a government level in a non-G7 environment could spawn such a large industry that requires so much clinical vetting and support (even private), such as:
http://marginalrevolution.com/marginalrevolution/2017/04/china-creates-sez-medical-tourism.html

Posted by: Jer at April 4th, 2017 2:08 PM

Seems like they're on the right track.

@Steve Hill Where exactly does the lipofuscin go once you promote mitosis? Aren't you just loading up your macrophages with it after they sweep up the dead cells? Doesn't seem like a valid option to me. Not unless they do something for the aging macrophage populations as well.

Posted by: Anonymoose at April 4th, 2017 3:43 PM

Well, 9 years after Bain's words, and with very low funding, we have cleared 3 genes out of 13. It doesn't seem that it was at a point were "we do not have the technology today that can even point the way to how it can be achieved."

Posted by: Antonio at April 4th, 2017 4:05 PM

About the presentation, it mixes together very dispare things: SENS, the Hallmarks, metformin, CR, genetic modifications, personalized medicine, lifestyle... but overall, at a high level, I note some very positive and unexpected things:

- a focus on damage repair therapies and non-programmed theories of aging

- aiming high (extending already born people's lifespan to 1000 years instead of 120 or 150 years)

- very short timeframes (big life extension in the next decade)

Posted by: Antonio at April 4th, 2017 5:16 PM

It seems like most of the opportunity for profit will go to venture capitalists and small time investors like myself will be left behind, which is a bit frustrating after having been an early supporter. Yes aging may finally be cured but I wouldn't mind having both youth and wealth!

Posted by: Corbin at April 4th, 2017 5:22 PM

While I'm glad the field has seen a nice and somewhat recent influx of money and general attention, I'm still not sold that there will really be acceptance for any of this from the general public, let alone regulators and/or 'bioethicists'. Especially prominent ones like Kass, Fukuyama, Zoloth, etc, etc. It always boils down to "imagine the Peter Thiel's living forever, while everyone else dies. Inequality!". Look no further than the comments section of any aging article. So we'll see. Maybe medical tourism will be the initial answer, if companies are willing to work outside of FDA oversight. Jer's link is pretty interesting. I did not know that was a thing.

Posted by: Ham at April 4th, 2017 5:51 PM

Hey !

IT'S good to aim high, if you don't reach the moon you'll be dancing among the starts (at least). I don't think a 1000 years will be reached anytime soon. But reaching 150 is possible.

It could be possible to see substantial life gain in the next decade but I remain cautiously optimistic because we've been deceived and let down quite often in the past, and this story/history repeats itself.

Just like when he said :

''This period of development has been underpinned by two seminal moments - the discovery of the structure of DNA and the sequencing of the human genome; the latter occurring nearly 50 years after the former'' ...the latter part...is very very Latter -Later-Later 'Latter...50 years later (the latter) after the former, I'm not suppose to feel happy about this- had he said, 5 years after I would be. I don't know about you but us living people don't have 50 years to wait for the next big thing. Many here will not be alive in 50y.

9 years time for 3 genes out of 13 for allotopic expression is quite impressive because of the extreme difficulty though we can do it despite tech limitations. On the other hand, it does
not mean that it will be easier or faster for the remaining 10 ones... If it took 9 years for 3, we may be in for about 30 more years of waiting to see mitochondrial allotopic expression done (all things equal).

Cell cycle dilution of lipofuscin. Even if we accelerate cell division, lipofuscin still accumulates because most of these dividing cells do not use sufficient telomerase as a replicative immortality mechanism (Except immune cells and sexual germ cells), the rest they don't use it; as such, the proteasome will fail and lipofuscin will take over. It was shown in laboratory that cells that were replicatively immortal by hTERT or ALT did not accumulate any lipofuscin (meaning their proteasomic/autophagic/mitophagic/endosomic/ macrophagic/lysosophagic mecanisms are kept intact).

''Free for All''...it will not be...simple as that (not at first at least). It's expensive therapeutical technology used in the future's given rejuvenation therapies.
Again, mostly rich people who will benefit. I wager at leart 25 years before it's somewhat 'acceptable' in price tag. ultra-Rich people may get it 5-10 years before you.

''It always boils down to "imagine the Peter Thiel's living forever, while everyone else dies. Inequality!". Look no further than the comments section of any aging article''

Very true. That's a big problem. But it's because it's ingrained and people won't buy it until - it's made and tested (tangibly). Then their opinions will (supsiciously and suddenly, but not so surprisingly) change.

''Maybe medical tourism will be the initial answer, if companies are willing to work outside of FDA oversight''

Yes, it seems the only answer, and you will have to pay dearly to 'get there' and 'to get it'...not in your home country...one more problem :
costly, unavailable and is 'bs' from everyone's idea....not exactly easy to 'sell it' to people..

Lipofuscin and junk ends up in autophagic compartments (Autophagic vacuoles, endosomes) like the lysosome where there is docking by LAMP and Chaperones (HSPs Heat Shock Proteins). With time the lysosomal mass enlarges (full of junk, like lipofuscin which is composed of damaged DNA, peroxidized fatty acids/phospholipids from the membranes, carbonyls, aldhehydes like MDA (malondialdehyde) or also called TBARS (thiobarbituric substance),
and tons more stuff mixed-in the gunk).

SENS should look up north-east at what Canadians scientists have done here with nanorobots/-acting-like-bacterias against cancerous hypoxic-zones of tumors (to avoid hard chemotherapy) at the Montreal Polytechnique University's Nanorobotics Laboratory
for an idea about how to do it and get some inspiration (lipofuscin removal with nanotech) :

"These legions of nanorobotic agents were actually composed of more than 100 million flagellated bacteria -
and therefore self-propelled - and loaded with drugs that moved by taking the most direct path between the
drug's injection point and the area of the body to cure ...
To move around, bacteria used by Professor Martel's team rely on two natural systems. A kind of compass created by the synthesis of a chain of magnetic nanoparticles allows them to move in the direction of a magnetic field, while a sensor measuring oxygen concentration enables them to reach and remain in the tumour's active regions. By harnessing these two transportation systems and by exposing the bacteria to a computer-controlled magnetic field,

***researchers showed that these bacteria could perfectly replicate artificial nanorobots of the future designed for this kind of task.***

"This innovative use of nanotransporters will have an impact not only on creating more advanced engineering concepts and original intervention methods,
but it also throws the door wide open to the synthesis of new vehicles for therapeutic, imaging and diagnostic agents,"

"Approximately 70 drug-loaded nanoliposomes were attached to each MC-1 cell.
Our results suggest that harnessing swarms of microorganisms exhibiting magneto-aerotactic
behaviour can significantly improve the therapeutic index of various nanocarriers in tumour hypoxic regions."

This could very well be used, similarly, for lipofuscin clearance (rather than tumor cell clearance or senescent cell clearance, anyway this technique applies to every cell or detritus), magnetic field-targeted bacterias, or the bacterias'enzymes that degrade lipofuscin
encapsulated in nano-liposomes ('the bacterias' enzymes bomb') directly towards lipofuscin in the lysosomes. Let's forget about nanorobots for now,
we're still far from them being in real use. Controlled-Bacterias will do a better job for now it seems. SENS should take it/learn from this study and work on the bacterias' lipofuscin-destroying enzymes, and the Bacterias Themselves - as the Carriers of their own liposome-filled enzymes load.

1-http://www.polymtl.ca/salle-de-presse/en/newsreleases/legions-nanorobots-target-cancerous-tumours-precision

The nanobacterias study :

Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions
2-http://www.nature.com/nnano/journal/v11/n11/full/nnano.2016.137.html

Posted by: CANanonymity at April 4th, 2017 7:39 PM

Which of the SENS principles is working on the bone loss problem?

Posted by: RS at April 4th, 2017 7:51 PM

HI RS !

Bone loss/osteoporosis is dependent on bone minerality and mineral intake (that's because minerals are incorporated to bone to become
less hollow/more dense; like calcium and magnesium; not only that, but also because they produce ions that our cells respond to and
affects their activities/processes (like for ex calcium ions are direct antagonists of mag ions, one constricts arteries the other dilates;
both alter the redox and greatly affect bones too (especially calcium/calcification - and also, magnesium; magnesium is lost from bone
with oxidative bad-food diet that disrupts the redox. Bone magnesium is even more important than calcium, because it is said that it
solidies the density (like certain compartments of the bone have mag pockets, while others have calcium; with age this precious pocket is
replaced with calcium - a very bad thing. Since bones are a combination of minerals and there is a precise % of these minerals - they determine
the BMD (bone mineral density) and thus bone health (and also the bones' marrow stem cells activivity/thus indirectly the immune system).

As for which SENS therapy would prevent bone loss, I would wager (just my less informed 'Wild Guess' 2 cent)
RepleniSENS, MitoSENS, ApoptoSENS, GlycoSENS, AmyloSENS, LysoSENS... does that make sense ?

RepleniSENS because of cell loss/bone cell loss; it would favor bone cell creation/replacement though that's not assured. It could help somehow for sure.
Bone cell number atrophy could thus be partially reversed.

MitoSENS because bone cell's mitochondrias can have big mutations/deletions in older age, this would ease some of these mutations
that accelerate bone mineral density loss/skeleteal fragility. Mitochondrial mutations, oftenly, end-up creating problems in the ETC
(Electron Transport Chain) where Complex I-V reside in the IMM (inner mitochondrial membrane), these energy complexes are the crux
of the mitochondria 'OXPHOS (Oxidative Phosphorylation/ATP) energy-making' process in humans (although there is alternate ETC like AOX (Alternative Oxidase that disengages/uncouples ETC
electron passage by bypassing Complex IV Cyctochrome C Oxidase, the 'respiration' complex)). Once mutations make problems in the mitochondria's
ETC - then energy throughput is generally affected : the mitochodrais produce less ATP; this in turn 'starves' the cell from inside; making
it feable and weak - and dying - rather then energized. This would weaken bone cells and thus, accelerate bone BMD loss/osteoporose inflammation.

ApoptoSENS because targeted ablation of senescent cells will reduce the bone's inflammatory load of senescent-cells that secrete SAPS
and not exactly helping the bone. Causing inflammation (TNF, p53...) ni the bones; thus, osteoporosis/bone loss BMD.

GlycoSENS because the ECM (Exctracellular Maxtric) does become become very stiff...so of course if you are capable of removing
the crap in it, it Does help. Like better cartilage/bone cartilage by GlycoSENS, breaking down AGEs (advanced glycation end products inside cartilage/bone ECM)
. Removal of Cross-links glucosepane in the cartilage. Reducing glycated hemoglobin HbA1c, thus better blood coming towards bones, less inflammation
for bones cell/more oxygenated.

AmyloSENS because extra-cellular aggregates like plaques dont' help either; in bones it might be a differeny process - although this seems
more towards Amyloids and such..it does aim at Transthyreetin, so if could aim other types of extra-cellular aggregates present outside bone cells.
Calcium ultra-calcification aggregates could be possible.

LysoSENS because intra-cellular aggreates like Lipofuscin that reduces the life of a bone cell in its lysosomes (which it is bound by),
and other intra-cellular aggregates (like ceroid, drusen, A2E, oxidized end-products, tons of fun gunk...). Removing that will make
more vigorous bone cells = solid bones = prevention of bone loss/osteoporosis.

Just my 2 cent.

Posted by: CANanonymity at April 4th, 2017 11:45 PM

> Not unless they do something for the aging macrophage populations as well.

What about taking them out of the body bit by bit? The body will replace them.
If they're in the bloodstream use dialysis. For those in the lymphatic system use a needle to take them out.

> Maybe medical tourism will be the initial answer, if companies are willing to work outside of FDA oversight.

Or do what the Open Longevity initiative does: Put up a webpage, find enough patients for a specific treatment then camouflage the treatment as a clinical trial and away they go.

For the patients this is a better solution, because it's cheaper and the risk is lower as side effects show up earlier with more patients. And they have a 50% chance of getting into the control group, in which case they would get the treatment a bit later but it's tested. Last but not least they have full control over the procedure.

Posted by: Matthias F at April 5th, 2017 12:09 AM

CANanonymity thank you for your answer, old people get shorter and their face structure change due to bone loss, we will have to not only stop it but reverse it too.

Posted by: RS at April 5th, 2017 6:17 AM

I wonder what research Jim Mellon will invest in.

Posted by: Antonio at April 6th, 2017 3:28 PM

Would it be possible to receive a copy of the charts used by Mr Mellon in his lecture in London in January titled "The Age of Longevity?

Posted by: Lord Thomas d Conrad, Ph.D. at July 14th, 2017 9:50 AM

Post a comment; thoughtful, considered opinions are valued. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.