The summer before she started her neuroscience degree at the University of Texas, Celine Halioua interned at a clinic in Germany, working with patients who had age-related brain cancer. She formed a bond with one of them. “He had a large, bushy moustache and a permanent smile – the picture of a kind father,” she told me. “My German was not great, and neither was his English, but what struck me was his kindness – despite the fact he was there to discuss his terminal diagnosis.”
Halioua was shadowing a doctor, and found it hard to grasp that nothing could be done for this patient. “I always thought that doctors were magical – that if you put the effort in, you’d be able to fix it. The realisation that you can’t made me feel that we don’t have free will.”
She resolved to find that fix: not a cure for cancer, but an end to ageing itself. Now, at only 27, Halioua is a leading light in the relatively new field of anti-ageing biotech. “I’m confident we’ll have an ageing drug by the time it’s relevant for me,” she told me. She estimated that time as “within a decade”, and aims to dominate the market before then. “Transparently, my goal is to build the ageing pharma company – there will be many. The ageing field will one day be larger than the cancer field.” Halioua described ageing as “deviation from optimal biological function”. “Optimal” is subjective, of course: Olympic gymnasts peak at a much younger age than Olympic sprinters. “Old” is easier to define: Halioua described it as “when the physical body gets in the way of the thing that you want to do”.
Halioua’s speech was so rapid that the internet connection from her office in San Francisco could barely keep up. She looked every inch the digital nomad in her black T-shirt and AirPods: part biogerontologist, part CEO, part Gen Z-er. Halioua’s mother is Moroccan and her father German; she was born in Texas but studied in Sweden, Germany and the UK, and dropped out of her PhD at Oxford University and began to work for the venture capitalist Laura Deming, now 27, at the California-based Longevity Fund, a firm that invests in anti-ageing businesses. Halioua launched her own start-up in 2020.
The quest for eternal youth may not be new, but it is now bankrolled by some of the wealthiest individuals and corporations on Earth. PayPal co-founder Peter Thiel and Oracle’s Larry Ellison are among the many billionaires who are investing. Google founders Sergey Brin and Larry Page helped launch Calico, a Google subsidiary focused on combating ageing, in 2013. Amazon founder Jeff Bezos is in the game: not long after touching down from his maiden space flight in July, he was reported to have invested an undisclosed sum in Russian billionaire Yuri Milner’s Altos Labs, which will have a research base in Cambridge, UK (most anti-ageing start-ups are in the US). It is estimated that the industry will be worth $610bn by 2025.
The field shouldn’t be confused with the kooky subculture of “life extensionism”, whereby the determined and ascetic experiment with severe calorie restriction, intensely calibrated exercise and cocktails of daily supplements in a bid to extend a life that is arguably not worth living. Instead, anti- ageing science works at the level of gene therapy, cell hacking and reconstituting human blood; the medical treatments at its heart are based on “bleeding edge” science and aimed at the mass market. Some focus on biological reprogramming: adding proteins known as Yamanaka factors to cells, causing them to revert to a previous state. Others look at genomic instability or the way DNA damage that accumulates over time might be repaired.
The entrepreneurs in this fledgling field are determined that the end of ageing will come via therapies approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The elixir of youth won’t be a single drug, but a regimen of treatments that knock out different hallmarks of ageing and allow us to get older without losing our bodies and minds. We will still die: there will be accidents as well as diseases unrelated to age (children still get fatal cancers, after all). But death will become increasingly remote, and no longer preceded by years of inevitable decline.
Its advocates argue that, once ageing is cured, the financial, medical, societal and emotional burden of taking care of the elderly will disappear. But have these entrepreneurs thought about what a post-ageing world would look like? And if they have, would anyone want to live there?
As it stands, a drug will only get regulatory approval if it is marketed as a treatment for age-related diseases – such as arthritis, cataracts and macular degeneration, diabetes, certain cancers, dementia and Parkinson’s – rather than ageing in its own right. This, then, is where the science is focused. The thinking is that, if the ageing processes that underlie those diseases are treated, other rejuvenation benefits can be smuggled in.
Based in San Francisco, Unity Biotechnology is developing a class of anti-ageing drugs called senolytics. These work by eradicating senescent cells – those that have stopped dividing and then gather in the body, spewing out factors that harm the surrounding tissue. “It’s a completely new way both of thinking about a disease and targeting it,” Anrivan Ghosh, Unity’s CEO, told me. “Senolytics reprogramme the tissue. They raise the possibility that I can restore a previous state that a tissue or a body was in.” It was first thing in the morning for Ghosh (we were speaking over Zoom), but he was fizzing with enthusiasm. He is 57 but looks younger, with a neat goatee and hair that is only flecked with grey.
Senolytic drugs are designed to be taken prophylactically, during what Ghosh refers to as a “window of time” when senescent cells are known to accumulate (this varies in different parts of the body). He was keen to tell me about Unity’s ongoing clinical trial in people with age-related eye disease – the first evidence of a senolytic treatment working, he said. Twelve patients with severe vision loss due to macular degeneration or diabetic macular oedema (two of the major causes of age-related blindness) had been put on a course of Unity’s lead senolytic. “One of the patients could not see any letters on an eye chart, even with her glasses on, from four metres away. Everything she once needed help with, she can now do independently. The majority of those patients showed an improvement.
“I would have been happy if they just maintained their vision,” Ghosh said. “It raises the possibility that you may somehow be able to reverse trajectory and restore a better state. That’s another level.”
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Unity was an early success story, with Peter Thiel and Jeff Bezos signing up as seed investors. People like Thiel and Bezos aren’t interested in financing the kind of incremental gains a next-generation medicine might offer, Ghosh told me. “They are drawn to the idea of being able to do something that changes the way we think about disease, that changes the way we live.” Over time, Unity’s funding has come increasingly from bigger, more mainstream investors.
Promising paradigm change can be a risky business. Unity was valued at $700m at its initial public offering in May 2018, but shares fell by more than 60 per cent in August 2020 after its flagship product, a senolytic treatment for osteoarthritis of the knee that had worked on mice, was shown to have no greater effect than a placebo in human trials. “It tells you something about the translational gap in that case – sometimes the animal studies do not replicate in the human case,” Ghosh said. “There will be many bumps before we have success.”
Up to 30 biotech companies around the world are developing senolytic drugs. British biogerontologist and computational biologist Andrew Steele, who wrote Ageless: The New Science of Getting Older Without Getting Old (2020) after studying ageing in nematode worms and a stint at the Francis Crick Institute in London, told me he thought we were “two or three years” away from having the first senolytics in the clinic for specific conditions. “It could be within a decade that we’re using these things preventatively.” Like most other advocates, Steele was ambitious about the timeframe, given the relatively small number of human trials.
Ageing isn’t officially defined as a disease, which is a problem for the biotech companies, Steele explained. “It’s currently very difficult to get a drug approved because it isn’t an indication in the pharmaceutical industry. That means there’s no way to say, ‘I’ve reversed or slowed someone’s ageing.’” But he remained optimistic. “We’re in a position, unique in human and scientific history, where we’ve finally got a handle on the processes. Unless you’re very old or very, very unwell, there’s going to be an anti-ageing drug in time for you.”
For Steele, who is 36, this can’t come soon enough. “We have been completely ignoring the single largest cause of death, human disease and suffering,” he told me. “I don’t think barbaric is too strong a word. Being old steals your independence: it’s what puts you at risk of all kinds of things – not just the internal stuff like cancer and heart disease, but external threats like falls, infectious disease.”
Steele told me about some 24-month-old mice (around 70 in human years) he had observed in a lab while researching his book. After a dose of senolytics, the mice thrived. “They get less cancer, fewer cataracts, fewer heart problems, they are fitter and less frail,” he said. “They’re cognitively younger as well. And they have better fur, thicker, plumper skin, less grey hair – they just look fantastic.”
Celine Halioua doesn’t have to worry about the translational gap between mice and humans. She left the world of longevity venture capital in 2019 to become founder and CEO of Loyal, a biotech start-up dedicated to extending dog lifespan. It aims not simply to stretch the length of time a dog can live – anything from an extra six months to three years, depending on the breed – but to ensure that those months and years are healthy. (Halioua herself is a devoted dog owner, and lists her husky, Wolfie, as the company’s “chief evangelist” on the Loyal website.) But dogs are just the beginning. “We’re planning to take what we learn in dogs to help pet parents and non-pet parents live longer, too,” she told me.
Dogs develop the same age-related diseases as we do, Halioua explained, at approximately the same point in their life-span (the exception being heart disease, “because they don’t eat a lot of McDonald’s or whatever”). Their fur loses pigment and goes grey, just like their owners’ hair. They share an environment with us, and “environmental factors are huge in ageing”. It’s also possible to see whether an intervention is working much sooner in dogs than in humans: “You can do a preventative measure when they’re two or three, and you’ll know by six or seven, probably sooner, whether the intervention did or did not do the thing.” Dogs will make the pathway to regulatory approval smoother, Halioua believes. “If something can work in a complex species like a dog, that isn’t super-inbred like a mouse, it’s a more robust justification to pursue that in people.”
Significantly, dogs have devoted owners who are prepared to pay over the odds – though Halioua said she was determined not to exploit that devotion. “It is important to me to price our products so that they are accessible for the majority of dog owners. The final cost will depend on the materials but, order of magnitude – tens, not hundreds, of dollars a month.”
The first of two Loyal drugs in development targets cellular mechanism and glucose metabolism in large- and giant-breed dogs. Due to a quirk of animal husbandry, the larger the dog, the shorter its lifespan. “A Great Dane might live seven to nine years on average, while a Chihuahua might live 16 to 18. That’s weird. You normally don’t see a times-two differential in lifespan within the same species – you don’t see it in people of varying heights.” This, Halioua explained, was due to “an antagonistic pleiotropic effect: the thing that caused the dog to grow big quickly has a negative impact on lifespan”.
The second drug targets metabolic fitness in dogs of any breed and size, in order to replicate the same effect on lifespan that calorie restriction does in mice. “This will be better for late-in-life intervention. Of course, prevention is optimal, but there are people who already have grey-faced dogs and we wanted to have something for them.” Trials are due to begin next year.
Other anti-ageing therapies have emerged from more gruesome animal experimentation. The biotech company Elevian, founded in Silicon Valley but now based in Boston, began 15 years ago after Harvard professor of regenerative biology Amy Wagers stitched live mice together, fusing the circulatory systems of old and young specimens, in a process called parabiosis. The mice lived fused together for four weeks before their organs were removed and studied. Elevian’s CEO and co-founder, Mark Allen, described an experiment that sounded like Frankenstein and Dracula combined: “The old mice exposed to young blood grow biologically younger by many different measures, and the young mice exposed to old blood grow older.”
A 51-year old medical doctor turned tech entrepreneur, Allen told me he had read about Wagers’ work and thought it might be turned into a therapy. “But it’s not an easy thing to translate. In the parabiosis model, the old animals are getting a continuous transfusion of young blood, 24/7, for four weeks. You can’t really have a blood boy tied to you,” he said, with a dark grin.
The Harvard team identified the recombinant protein GDF11, the critical factor circulating in blood that appears to be behind the rejuvenating effect. “Just injecting GDF11 once daily was able to reproduce many of the different effects,” Allen said. “I fell in love with this work because of the breadth of effect.” He reeled off a list of diseases that GDF11 might combat: emphysema, cardiovascular disease, fatty liver disease and potentially some cancers.
Still, Elevian had to choose one specific indication they could tell regulators they were targeting, and decided its best bet was stroke: “the worst possible disease that we could treat for the shortest possible duration, and see clinically meaningful effects”, Allen said. Stroke is the second biggest cause of death worldwide and a leading cause of long-term disability; the few treatments that currently exist need to be given within a few hours after a stroke if they are to be effective.
Allen said animal trials were looking positive. “When we give GDF11 after a stroke, it significantly improves sensory motor function recovery. And we can give it late – we can start it 24 hours or later when no other treatments exist. Our primary focus today is taking it into clinical trials.” For Allen, this would be the start of something more ground-breaking. “Part of the game is getting it to market as soon as possible – and then beginning to expand its indication.”
The entrepreneurs I speak to might be taking different paths to eternal youth, but they agree on one thing: ultimately, ageing will be cured. None wants to hazard a guess at how long people will live – there may be some yet unknown physical side effect that we discover in our 200s – but they believe the only obstacle to an infinite human lifespan is our inability to imagine what that might look like. This means that the potential negative effects can only be raised delicately. “The ageing process causes two thirds of death globally,” Steele reminded me. “Any objection you want to come up with to say we shouldn’t do something about it has to be larger than that.”
But Paul Root Wolpe, 64, director of the centre for ethics at Emory University in Georgia in the USA (and a former senior bioethicist at Nasa), told me that a world without ageing would be “an economic disaster”. The argument some advocates make for its enormous social benefits is “a misdirection”, he said. “I find their arguments extremely naive, sociologically unsupportable, and most importantly, deeply narcissistic. I’ve never heard a single plausible argument of how radical life extension would benefit society – only an egocentric desire not to die. The truth is, they want to stop ageing. They want to live healthily to 150.”
In Wolpe’s view, anti-ageing scientists and entrepreneurs minimise or ignore the profound implications of significantly increasing the human lifespan. “The International Monetary Fund has stated that an ageing population in Japan has led to a vanishing labour force, higher demands for social services, a shrinking tax pool, greater wealth disparities – and that’s just from living what is currently our lifespan. If we increase it, all of those things would increase exponentially.”
But in the future envisaged by the biotech start-ups, we would work into our hundreds: an elderly population would still be a labour force. Wolpe had little patience for this idea. “That is a profoundly elite perspective. Do you really think that the longshoreman, the hard labourer, the person who works as a clerk in a store, at the age of 65 is going to say, ‘Great! I get to work for another 50 years!’ It’s absurd. Polls show that large percentages of people hate their job. Elitists who work entirely with their brains are a small minority of the human population. They have a very blinkered point of view.” It was no coincidence that Silicon Valley’s tech billionaires were early investors, Wolpe said. “This is one of the great scientific, intellectual areas to conquer. These people have already conquered the world in new ways. They are the first group to touch the lives of hundreds of millions, if not billions, of people. They have so much cash, and they don’t know what to do with it.”
The political ramifications of an indefinite lifespan are equally huge, Wolpe argued. The elderly vote at much higher rates than the young, and, in America at least, the highest echelons of power have become the preserve of the over-70s. Politically, young people will be squeezed, and the fresh ideas they bring to politics and innovation more generally will be suppressed.
“Do you think that if the last generation or the generation before that lived to 100 or 150, there would be gay marriage, diversity inclusion movements, #MeToo?” Wolpe said. “The vast majority of the great innovations of the last 50 years were created by young people. A life well-lived hands its torch to the next generation. It doesn’t try to override them for its own narcissistic needs.”
Overpopulation and the climate crisis are other obvious counter-arguments. If death becomes rare, and humans remain at optimal health, how soon will the world run out of space and resources? Won’t humans die from starvation and natural disasters instead?
“This is not a technology in isolation,” Allen argued when I put this to him. “We’re figuring out how to have cleaner energy, how to have food that is healthier and less polluting, how to live more peacefully, how to travel into space. There is not a real estate problem here on Earth if we live better.” It’s an argument typical of Silicon Valley optimism: the solution is always more tech.
“I’m sanguine about overpopulation,” Steele told me. “If we had to work a little bit harder to solve things like climate change, resource use, land use and all those things that I’m genuinely concerned about, I’d happily do so if it meant suddenly no one was dying of cancer or Alzheimer’s.”
Both Steele and Halioua dismissed the idea that indefinite fertility would lead to a population crisis, seeing it instead as an opportunity for a fairer world. Halioua pointed out that, if women want to have children, they are currently forced to make compromises at a critical time in their careers. “I’m going to be in my thirties soon, theoretically the ideal age to have kids, and I’m not going to want kids at that age – hopefully I will still be building Loyal. That’s a societal pressure that men don’t have. [This] will free up 50 per cent of the population who inevitably have to take the hit.”
Already, the wealthy live longer: men in the most deprived areas of England can expect to lead lives nearly a decade shorter than those in the wealthiest parts. Anti-ageing drugs will surely amplify these inequalities, when only the individuals and nations that can afford them can buy ever longer life-spans. Halioua said she had factored these concerns into her development plans: “The ideal ageing drug is going to be like a statin, in terms of not being expensive.” Steele added that this was a long game: expensive drugs have patents that expire after 20 years, after which generic drugs can be made at a fraction of the cost. “I’m not saying it’s right, but it’s normal for rich people in the West, and then everyone in the West, and then poorer countries to benefit from various kinds of medical intervention.”
I asked the anti-ageing entrepreneurs about Wolpe’s point – that longer lives will increase intergenerational inequalities. In a future where people keep their minds and bodies, never losing their edge, how will the young ever compete in the workplace?
“That kind of thinking assumes that if people were to live in good health for a very long period of time they would want to continue to do the same things,” Ghosh said. “I know I would not want to do drug discovery for the next 30 years. I have a bazillion other things I’d like to do, and I would happily let other people take this role.”
Halioua took the question personally. “With Loyal, there are plenty of people who are double my age, in their 40s and 50s, completely cognisant, who have been working in ageing a long time, and didn’t have the idea or desire to build this company,” she said. Experienced people come with baggage and biases. “Being naive has actually been one of my best traits,” she said. In other words, the young will still wield their advantages.
Allen was the only anti-ageing advocate I spoke to who entertained any ethical discomfort. “The biggest thing that concerns me is despots, dictators,” he said. “They die over time. With this, they might be able to live.”
Even if we believe the claims these proponents of eternal youth make – that the planet can cope, that societies will be no more unequal – one problem remains: death. Its proximity directly affects our appetite for risk, making clinical trials into new vaccines possible, and encouraging billionaires to go into space. In a future where death occurs only as a result of rare disease, suicide or tragic accident, will we become paralysed by the fear of it?
For the first time, Halioua didn’t have an answer. “I don’t know,” she replied, after a long pause. “I would argue that this is already a huge latent paralysis in the average human. Maybe it will get better. I don’t see a world where we start becoming extra- terrified of car accidents, but maybe we will.” Her face brightened: she had an idea. “Maybe Tesla needs to get all their self-driving cars on the market and market it this way – ‘Number One Cause of Death Eliminated By Tesla!’” There it was again: the answer to a problem created by technology is… more technology. The future looked bright once more – and endless.
Jenny Kleeman is the author of “Sex Robots and Vegan Meat: Adventures at the Frontier of Birth, Food, Sex and Death” (Picador)
This article appears in the 13 Oct 2021 issue of the New Statesman, Perfect Storm