The booming longevity & healthspan boosting industry
September 3rd, 2019
Juvenescence, a company focussed on healthy longevity and rejuvenation, recently raised $100m to further build its portfolio of companies focussed on extending human healthspan. With prior money raised this brings the total raised by Juvenescence to some $160m. Another company, Life Biosciences, Boston Headquartered, also building a portfolio of longevity focussed companies, has raised over $75m to date. Both companies have been formed in the last few years and are said to have achieved valuations of $500m or greater, and the likeable and smart Juvenescence team have people that have previously made a lot of money for others in biotech/ pharma industry. Not yet at Samumed valuations but on their way.
So why the interest and rapid valuation ramp ups?
People have been chasing the elixir of youth or immortality for millenia and yet none have achieved it. However until recently they never had scientific equipment or techniques that could examine individual cells in the human body, rapidly and cheaply sequence the nuclear or mitochondrial genome, examine DNA methylation & epigenetics and proteins and so on, produce many therapies that actually worked, or have such hugely powerful computers or easily usable programming languages and libraries using AI systems allowing analyses that could never before be done by humans…
Lifespan is currently capped…
Extending lifespan, currently capped at about 115 years old (however oldest person is purported to have died at 122) is still many decades away, but various organisms have already been “modified” to increase lifespan by tenfold by genetic and other changes or regimes, giving clues to what could be possible with humans. Some organisms eg jellyfish are effectively immortal, Bowhead whales live to over 200 years old, some can fully regenerate after injury eg Axolotls, and so on- all useful clues from nature. Aubrey de Grey, the intelligent ex Cambridge University scientist focussed on aging and a prominent figure in the longevity field, has gone on record saying that he believes that the first person to live to 1,000 years old has already been born. Just to be clear, many people currently do not want to live beyond 100 or so years old, as they see people like this as decrepit, in poor health, maybe wheelchair bound or with limited mobility, and often with diminished mental faculties. What Aubrey and other researchers are at first focussed on is having people live well in to their 100’s yet have the appearance, physique and mental faculties of a healthy person in their 40s’ or fifties..
With several big problem diseases starting to have big impact in their sixties..
As people move in to their sixties the big five disease incidence rises exponentially... the big five being cardiovascular disease; cancer; type 2 diabetes; kidney disease; and neurodegenerative disease (which includes Alzheimers and dementia) - and then sarcopenia- ie frailty, in the 80’s. Approaching three quarters of people will have one or more of these diseases by the time they are in to their 60’s. However some people get these diseases over 20 years later than others, so the first goal is to move the occurrence of these diseases back by over 20 years, so if you focus on these then the 80/20 rule applies here, you have the biggest ever beneficial effect on humanity, reducing pain and suffering for over 1 billion people, and also save the healthcare system and taxpayer huge amounts of money.
But the explosion of new technologies is changing everything..
There have been a number of technological advances that are now allowing a deep understanding of why people age, at the molecular and cellular level. There have been huge advances in the OMICS- Genomics, methylomics; epigenomics; proteomics; metabolomics, connectomics, and so on, and artificial intelligence is now starting to reach a stage where it can be truly helpful in analysing what is found and proposing new therapies and small molecules to influence certain target pathways.
Just like mass use antibiotics first used widely in 1944 helped save millions, in the 2010’s we have had huge advances and an explosion in new technologies that are producing many incremental but also step change advances in science.
These include:
Single cell and next generation sequencing: technology introduced in the last few years now allows scientists to see inside the workings of a single cell, cell by cell. This will allow better analysis of each cell type and its components and discovery of targets that can be manipulated by new molecules & therapies or structures. Illumina, Oxford Nanopore, 10x genomics are but a few of the leaders in this space.
Gene therapies & delivery vectors & CRISPR/CAS9: allows the deletion and insertion of sections of the DNA/the genome, however delivery issues and potential risks from double strand breaks has slowed the implementation of this huge potential technology, where it is only fairly recently being used in humans. Delivery vectors can be problematic where AAV or lentiviruses are more commonly used but some newer ones are also emerging. Some are looking at altering the epigenome or DNA methylation which does not require the double strand breaks;
Multiple new / improved modalities: Stem cell uses, antibodies, scaffolds, peptides etc are all expanding rapidly.
Artificial Intelligence: Computer power is now sufficiently cheap and powerful enough to analyse huge datasets, now providing analyses that would have been impossible for humans to do. And many new AI techniques and massive coding libraries are now available to the ever burgeoning army of coders in python and other AI languages to permit ever faster development of AI tools.
Given that once something is discovered / hypothesized as important, to get it in to humans as a therapy can take some 10 to 15 years, and cost hundreds of millions or billions… Once a target to affect a disease state is established, then the scientist must find a compound/ small molecule to influence the target, test it in a petri dish, then animals- probably mice, then get the regulatory authorities- the FDA or EMA etc to allow the scientist to try it in humans (get an IND- Investigational New Drug) approval, try it in humans (Phase 1) and if safe then try it in more humans (phase 2, does it work/ efficacy) then lots of humans- phase 3, and if it works then the FDA approves it for sale to patients. This takes a long time and costs a huge amount, and many potential drugs fail at various stages… only a small percentage make it…
And key pathways for aging have been identified and focused on…
In 2013 Cell Magazine published a paper, The hallmarks of Aging (Carlos Lopez-Otin / Kroemer) subsequently updated, that identified 9 Hallmarks that drove the aging of the human body.. from genomic instability, telomere attrition, epigenetic alterations; protein homeostasis; deregulated nutrient sensing; mitochondrial dysfunction; cellular senescence; stem cell exhaustion, and altered intracellular communication, and underlying pathways associated with these hallmarks. Aubrey de Grey proposed a 7 classification system, much of it overlapping, which also offers a pretty comprehensive classification of the hallmarks of aging.
The 9 Hallmarks of Aging:
James Peyer, co-founder of Cambrian Biopharma, one of the three most experienced longevity industry portfolio focussed CEOs, with proven experience, updated this in 2019, with a hallmarks chart, as shown:
Peyers updates seem to merge some of Aubrey de Greys factors and indications with the Lopez-Otin hallmarks, with Peyers enhancements, and seem to be better thought out and better able to be matched to the big 5 (and other) diseases.
With “anti aging” drugs currently being trialled in humans..
The leading candidate to be first to end up in humans is focussed on senescent cells (p53/MDM2 pathway focus), a senolytics focus. Unity Biotech, NASDAQ listed,(NASDAQ: UBX) is in Phase 1 trials, and the first area of focus is knee osteoarthritis. But once proven safe to use in humans the range of indications (specific diseases) could be expanded. (Many cells are supposed to die at certain times ie apoptosis, but some do not, and become “zombie cells” and hang around and poison their cellular neighbours, causing diseases / problems..). There are a huge number of other biotech startups focussed on each of the 9 Hallmarks. However as aging diseases are multifactorial, it is not a straightforward problem. Mind you, sequencing the human genome was not straightforward, and that was accomplished.
And some drugs are believed to increase healthspan and currently being taken by healthy humans…
The big one is metformin, a Type 2 diabetes drug, that reduces glucose in the blood, important for diabetics. It has been in humans since the 50’s, and many in the anti aging crowd are taking it. It is OTC is some places, eg Spain, a few euros gets you 50 850mg tablets, and prescription only in other places.
Another is Rapamycin, which is used as an FDA approved drug for, inter alia, suppressing the immune system after an organ transplant and prevent organ rejection. It appears to increase lifespan in animals by some 30%, but with humans taking it “off label” (ie using it for something that it is not “approved” to be prescribed for). It appears to be focussed on influencing MTORC1, but dosing levels and titrating (when it is taken at what level) is very important and not yet well understood. For some phenotypes once a week works well. Every day administration appears to also affect MTORC2 which can have very negative side effects. So side effects can be dangerous.
NMN/NAD/NR. More and more people are taking NMN or NR, precursors to NAD- and some are taking NAD directly. It is said to provide tremendous energy boosts - making them much younger- and other benefits for many.
There are a number of other compounds people are taking but the big ones currently are those mentioned above.
But lifestyle can be amongst the most important drivers for many..
And lifestyle changes… eg sleep, diet, exercise, light, dealing with stress; circadian rhythms, microbiome, sense of community and purpose, environment and so on also have a huge effect on human healthspan, (as toxins and environment can play a big role- if you live next to a pollution dense highway or factory or eat lots of pesticide laden food for example one needs to pay attention...) different things working differently on different people. This is something to cover another time.
But one thing is important to note… as is said, health is the most biological manifestation of compounding.. with the drive in the longevity sphere to prevent, slow, stop or reverse the compounding... getting sick may then be largely optional.. This will be driving a trillion dollar industry within the not too distant future, very welcome news for over 1 billion people, and part of what will continue to drive the momentum behind companies such as Juvenescence.
