Who wants to live forever?

The song “Who Wants to Live Forever” was composed for the movie Highlander by the British rock band Queen and inspiration came from the scene where Connor Macleod, an Immortal, takes his dying wife Heather in his arms at the time of her death. Connor being an Immortal is immune to every disease so he stopped aging, meaning he can live forever and die only when he is beheaded. But while everything in the life of Connor — and other Immortals scattered around the world — ran “smoothly” suddenly something unexpected happened: Connor fell in love with a mortal that eventually died as she got old. Connor can’t stop grieving for her, eternally. Before him the same fate was suffered also by the greek gods and deities, that unable to escape the powerful arrows of God Eros fell in love with mortals, always with catastrophic results in the end. Biological immortality is in fact a characteristic considered to be attributed only to very few and a debate on whether “immortality is a good or a bad thing” has been around for thousands of years.

Biological immortality (organisms do not age) is a state in which the rate of mortality from senescence is stable or decreasing, thus decoupling it from chronological age, and it is claimed that various unicellular and multicellular species (including some vertebrates) have achieved this state (bacteria, yeast, hydra, jellyfish, lobsters, planarian flatworms). As to modern humans the closest we have to biological immortality or eternal youth are the communities of the centenerians that can be found around the world in the so called Blue Zones. The Blue Zones (Okinawa, Japan; Sardinia, Italy; Nicola, Costa Rica; Icaria, Greece and Loma Linda, California) are regions of the world where people (“naturally induced” centenarians) live healthier and longer lives than others . But when it comes to “technically induced” centenarians, well some of the craziest attempts to reach immortality or eternal youth by humans have been so far the following:

The man who injected himself with extracts from the testicles of guinea pigs and dogs, The monks who mummify themselves to death in the hopes of achieving immortality, People who are being cryogenically frozen after death, hoping one day that they will be properly unfreezed and revitalised, Qin Shi Huang who tried to become immortal by drinking mercury (Chinese alchemists spent centuries formulating elixirs of life with toxic mercury, gold, sulfur and plants; as a matter of fact the formula for gunpowder was originally an attempted elixir of immortality…), Gilgamesh, the tragic figure symbolizing man’s vain but endless drive for fame, glory, and immortality, The scientists who believe studying box jellyfish (has incredible regenerative powers) is the key to immortality, Strange people who drink a potion made with menstrual blood or use it as a face mask to stay young (menstrual blood-derived stem cells, MenSCs), The famous blood countess Bathory who did whatever necessary to get younger people’s blood and then she bathed in their blood to retain her youth, Rich people who are infusing themselves with the blood of young people, And people who want to have embalm and preserve their brain and upload their “consciousness” into an android (digital brain) — whatever consciousness means of course — while choosing for a body among a collection of robots.

Considering now that stories relative to the various elixirs of youth have always existed from ancient times, that implies that immortality and eternal youth have tormented our consciousness since the first human witnessed death and realized his or her own eventual demise. So, the obvious answer to Freddie Mercury’s question “Who wants to live forever? ” is definitely “A lot of people want to live for ever”!

But before we start ordering a Starbucks® cold brew coffee with fresh blood or a sushi burrito with sprinkles of testicular extract or ordering from Amazon or Alibaba a 3D printed human organ, the first thing will be to understand how to learn to navigate the blurring lines between reality, science fiction and fantasy in the digital storytelling about immortality. And most importantly understand that the key to immortality is probably living a life worth living and worth remembering of. And undoubtedly a life worth living, is a life where the longevity industry — the study of aging with the ultimate aim of delaying its diverse diseases — will play a predominant role when coupled with scientific pragmatism. So, while caloric restriction, moderate exercise and using (not abusing) some drugs and supplements and nextgen apps, is more of an intuitive and logical way for achieving eternal youth, that is not the case for other methods. For example the Count Dracula Approach was firmly denounced by the FDA, as a result the startup Ambrosia — offering $8000 “shots” of fresh blood — was closed down (after all people can die from poop transplant not to mention infected blood). While for genetic manipulation, regenerative medicine and 3D printed organs it might take years — under our current scientific and regulatory framework — for us to understand what really is going on. Hopefully, in the meantime by staying away from microplastics (oxidative damage) in our food chain while enjoying a blood pancake or a blood sausage might be a wiser road to longevity and prolonged youth.

Longevity Industry and Startups

The longevity industry — once considered an expensive eccentricity of the ultra rich — has grown in the past 4 years from a neglected and underfunded domain of R&D into what is now claimed a trillion-dollar industry, spanning thousands of active companies across almost every continent.

Longevity’s industry four distinct segments/sectors and top startups are:

I) GEROSCIENCE R&D (Science of Aging)

The first segment of the longevity industry is Geroscience R&D, that aims to treat the root causes of aging and is all about: regenerative medicine, rejuvenation biotechnology, gene therapy, nutraceuticals, geroprotectors and of course basic research on biology of aging.

Lessons about the danger of unchecked innovation: Frankenstein

Before going through some of the top startups active in geroscience we should remember that Frankenstein or The Modern Prometheus, was a young scientist who created a hideous sapient creature in an unorthodox scientific experiment. So, before we decide for a gene therapy let’s keep in mind that what we thought before as junk DNA, is not junk at all! And before we devour stem cells, nutraceuticals and geroprotectors, let’s keep in mind that we really don’t know everything that is happening inside a cell or a body, especially when it comes to signalling pathways. Put it differently, unchecked innovation can create monsters but is also true that we learn from our mistakes.

Geroscience Top Startups:

AgeX Therapeutics (AGE) is using the potential of pluripotent stem cells (vascular progenitors, brown adipocytes) all in preclinical phase, to produce any cell or tissue the body needs to repair. Unity Biotechnology (UBX) targets senescent cells (the so called zombie cells), which are cells that have stopped dividing but accumulate in tissues and organs, causing inflammation and other problems as we age. The company is in a phase 2 clinical trial with a drug candidate to treat osteoarthritis of the knee and results are expected in the second half of 2020.

Celularity, harvests stem cells from postpartum placentas and with over twelve pre-clinical stem cell and new drug trials in progress claims to regenerate damaged tissue, produce whole organs and augment immunity. Samumed is developing small-molecule drugs that “modulate Wnt activity” to treat osteoarthritis and Alzheimer’s disease. Elevian, rather than steal the blood of young people as other vampire startups are trying to do, has identified blood factors (GDF11) that appears responsible for the benefits of young’s people blood. So they developing drugs that target GDF11 to treat a number of age-related diseases. Life Biosciences, a startup composed of five “daughter” companies: Senolytic Therapeutics goes after the same “zombie” cells as Unity Biotechnology, while Selphagy Therapeutics is attempting to restore autophagy in people with metabolic diseases that are characterized by an abnormal build-up of various toxic materials in the body’s cells. Mitobridge is discovering and developing novel therapeutics that improve mitochondrial functions. Gensight Biologics, a biopharma company focused on discovering and developing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders, reported on October 2019 positive proof of GS010 DNA transfer from one eye to the other eye following unilateral intravitreal injection of primates.

There are hundreds other companies working on various forms of regenerative medicine and here are some to keep an eye on: Humacyte, was the first company to receive an FDA Regenerative Medicine Designation and has products in both pre-clinical investigations and in clinical trials (proprietary technology to “grow” human acellular vessels). BlueRock Therapeutics pipeline aims to restore dopamine-producing neurons and thus regenerate that capacity in victims of Parkinson’s disease. OxStem’s approach is to awaken the stem cells that already exist in the patient and induce them to repair tissues damaged by disease or injury. Ichor Therapeutics is researching senolytics (drugs to combat senescent cells). Osiris Therapeutics Inc. (OSIR) researches, develops, manufactures and commercializes regenerative medicine products intended to improve the health and lives of patients and lower overall healthcare costs. Unlike many early-stage pharma companies, Osiris is actually turning a profit from this.

T.A. Sciences claims to have developed a pill to increase the activity of an enzyme (telomerase) that increases telomere length. Prellis Biologics is using 3D holographic printing – the fastest high-resolution printing technology on the planet they say – to grow human tissues and cells. According to the company, “standard bioprinting cannot produce transplantable organs and tissues because it fails to match the resolution necessary for function.”

resTORbio (TORC) a spinout from Novartis, is attempting to commercialize a drug platform that inhibits an age-signaling pathway known as mTOR pathway (TORC1 protein) which research suggests could prolong lifespan, enhance immune function, ameliorate heart failure, enhance memory and mobility. resTORbio expects top-line data in mid-2020. Rapamycin Holdings, a life sciences company that has changed its name to Emtora Biosciences, is also trying to inhibit the age-signaling pathway mTOR. ERapa its new formulation of the drug rapamycin — which was initially developed as an immunosuppressant to prevent organ transplant rejection at a high dose — it is now believed that a low dose might rejuvenate humans. Rapamycin, rapalogs and other small molecules have been used for ages in single and double treatments in cancer therapy, and while not always succesfull for cancer treatment, it was evident — at least in nude mice — that some of these small molecules would rejuvenate mice.

The second longevity sector is:

II) P4 or the four “P” MEDICINE (Personalised, Precision, Preventive and Participatory)

The first and second “P” in P4 medicine stand for personalised (diagnostics, biomarker analysis, prognostics, in vivo and in silico drug design) and precision, which refers to the drugs and treatments that will be designed and applied using individually-tailored methods. The third “P” in P4 medicine is about prevention and a shift away from reactionary treatment and towards optimized disease prevention long before the underlying pathology develops into actual chronic disease. The fourth “P” in P4 medicine stands for participatory, which refers to the increasingly active role that patients are taking in managing their own health.

Insilico Medicine (the face of AI drug discovery in cancer, Parkinson’s, Alzheimer’s, sarcopenia and geroprotector discovery) is a personalised in silico drug design company founded in 2014. Recently has raised $37 million in Series B funding to commercialize its validated generative chemistry and target identification technology for drug development. ISM has also developed a drug discovery and repurposing platform that they refer to as GeroScope that evaluates differences in signaling between “young” and “old cells and tissues and simulates the activity of thousands of known drugs and drugs combinations and assigning geroscores.

Human Longevity Inc is also a personalised and preventive health company, using AI and genome sequencing. Its product, Health Nucleus, involves applying machine learning to provide personalised health assessments from a person’s DNA sequence, as well as a battery of tests that include a whole-body MRI. They want to create a preventive healthcare model that can take baseline measurements of healthy individuals — with its large sequencing, 7-Tesla ultra-high-field magnetic resonance imaging (MRI) and molecular profiling capabilities — and monitor these individuals for life (every 6–12 months), in order to predict and prevent different pathologies. Sounds intelligent, intersting but expensive for now. The company had been valued initially as high as $1.6 billion but in 2018 HLI’s worth dropped by 80%.

Detail of the Sala dei Giganti in the Palazzo del Te, Mantua, c. 1530, Giulio Romano

Dispute among Giants in Human Longevity Inc: the company was initially founded by Craig Venter, Robert Harir and Peter Diamandis and they wanted to become the largest human genome sequencing center in the world. But in 2018 Human Longevity filed a lawsuit against its co-founder and former CEO, J. Craig Venter, on grounds of leaking information to competitors and using the company’s computer and e-mail to tap investors and poach employees after being terminated as CEO. Prior to the case, HLI has also reportedly terminated multiple senior executives. But the federal judge has denied Human Longevity Inc.’s request for a temporary restraining order against the J. Craig Venter Institute, which HLI claims has stolen its trade secrets. Anyway in this interesting chat, David Karow, MD, PhD, President and Chief Innovation Officer at HLI, talks to Howard Krein, MD, PhD, Chief Medical Officer of StartUp Health.

Direct competitor of Human Longevity is Alphabet’s secretive anti-aging startup Calico. Larry Page described Calico as a company focused on health, well-being and longevity. Calico’s stated goal is to harness advanced technologies to increase our understanding of the biology that controls lifespan in order to devise interventions that enable people to lead longer and healthier lives. In an announcement Calico revealed one of its in development drugs related to a class of compounds called P7C3s, which appear to protect nerve cells in the brain from dying by activating an enzyme called nicotinamide phosphoribosyltransferase that inhibits cell death. While Calico remains secretive, its alliance with AbbVie shows Calico is serious about developing marketable products to tackle major diseases in a reasonable timeframe.

Grail Inc, is a startup that wants to cure most cancers by a new diagnostics that will detect tumours at an early stage when they can be successfully treated. Grail plans to use high intensity DNA sequencing to probe and screen blood samples for genetic materials and biomarkers secreted by hidden tumours, which will require a massive amount of data processing and storage and Amazon can help.

Juvenescence, is a UK company advancing multiple anti-aging treatments co-founded by Jim Mellon. Juvenescence wants to establish a network of companies working in areas related to longevity and forming alliances with AI startups while investing in biotechs and licensing assets. Juvenescence has looked beyond traditional biotech venture capitalists for sizable chunks of its money and let’s look at their portfolio: 1) direct investor behind Insilico Medicine, 2) joint ventures called Generate Pharmaceuticals, BHB Therapeutics, Napa Therapeutics, NetraMark and FoxBio, and 3) launching or supporting AgeX Therapeutics, LyGenesis, Souvien Therapeutics and BYOMass.

The third lonevity sector is:

III) THE AGETECH MARKET

The third segment of the Longevity industry is AgeTech, which broadly refers to all IT and digital technologies (nextgen mobile apps and fintech for the elderly) that help to maintain greater functionality into older age, and that improve quality of life using non-medical means. This segment also includes advanced and progressive forms of social care (novel retirement plans), as well as products and services that help to preserve neuroplasticity into older ages (entertainment for the elderly, continuing education, cognitive enhancement). AgeTech can not slow down biological aging, but it can improve the quality of life, enhance psychological well being, mental functioning and neuroplasticity, and increasing levels of independence and social activity. And who knows, maybe in the future we might notice an IT placebo effect from using these IT gadgets…, after all “belief is a powerful drug”.

Alexa Amazon has been identified as one of the Agetechs to watch which may become a key platform for independent living for many seniors. TrueLink, LiveWell and PensionBee are examples at the intersection of Fin-Tech and Age-Tech, offering retirement and other financial services products oriented around the needs of older adults. BrainHQ offers online mental exercises to promote memory and brain health. In robotics associated with aging we have Intuition Robotics and Ageless Innovations. Companies tackling the future of care, are Honor and Sense.ly. The five promising European agetech startups serving the elderly are: No Isolation, Birdie, Nectarine Health, cettefamille, SuperCarers. AgeTech to follow in 2019 are: Nesterly, Soundmind, GrownUp, Papa Technologies, Tomorrow Ideas, Inc and Leeo.

Longevity United is a data Longevity-focused consumer-oriented mobile app marketplace and ecosystem fueled by the Longevity crypto token that has just established a joint venture with Eterly Inc. Eterly is the world’s first longevity-focused HealthTech mobile app backed by real science. By leveraging AI, blockchain and the marketplace ecosystem being developed by Longevity United, they plan to make an immediate and lasting impact on extending healthy longevity.

And finally the last and fourth sector of longevity is:

IV) LONGEVITY ADVANCING FINANCIAL INDUSTRY

The fourth sector of the Longevity Industry is the Longevity Financial Industry, which encompasses all the activities and efforts of large financial institutions to neutralize the economic issues of aging population (silver tsunami), manifest the opportunities of Healthy Longevity, and enter new markets of AgeTech and WealthTech relating to the one billion people on retirement globally. In the coming years, this sector will become dominated by: Longevity index fund, longevity hedge fund, longevity stock exchange, agetech bank, longevity derivatives and longevity trust.