The start-ups seeking a cure for old age

Israeli entrepreneur Yuri Milner, from left, Amazon founder Jeff Bezos and Google co-founder Larry Page © Rory Griffiths/FT/AP
Israeli entrepreneur Yuri Milner, from left, Amazon founder Jeff Bezos and Google co-founder Larry Page © Rory Griffiths/FT/AP

When Nir Barzilai specialised in anti-ageing science 30 years ago, it was an act of hope. Now, the Israeli-American scientist believes the world is on the cusp of turning hope into reality, finding transformational drugs that prevent the effects of ageing that used to be viewed as inevitable.

“We are done with hope and promise. We are at the point between having promise and realising it”, says the director of the Institute for Aging Research at New York’s Albert Einstein College of Medicine.

He plans to run a huge flagship trial to test whether a cheap generic diabetes drug — metformin — can extend lifespan by years, after a promising UK study of real world patients.

If regulators approve metformin to target ageing, he believes large pharmaceutical companies and biotechs would jump into the “longevity” field. “Once we prove it, I think it will be an earth-shattering moment for everyone”, he says.

The fantasy of living forever has endured for centuries, from finding renewal in a fountain of youth to gaining immortality from a philosopher’s stone.

Although we are still unable to elude death, we have learnt to forestall it: science has improved life expectancy significantly, initially with more mundane measures such as sewers and vaccines, and then with new drugs to tackle chronic conditions such as heart disease. In the UK, life expectancy at birth almost doubled between 1841 and 2011.

But as many people now spend their last decades in poor health, scientists like Barzilai are on a quest to further increase not just lifespan but also healthspan: the number of healthy years we live.

Longevity researchers reject the hype that they are “curing death” but their vision still has the potential to ease some of the biggest problems of our time: soaring healthcare costs for a population whose health is creaking as it ages, and lacklustre productivity as people become too sick to work.

And yet Barzilai is still searching for money to fund the trial, which could take four or six years and cost $50mn to $75mn. So far, he has $22mn, including $9mn from the US National Institutes of Health. “It is terribly upsetting but we are now on the hunt for the rest of the money”, he says.

Finding the key to prolonging life would benefit us all, but money to fund the search is hard to come by. Healthcare investors typically want to see short-term returns — unlikely, in metformin’s case, since its patent has long expired. Governments, meanwhile, prioritise research into diseases.

Into this gap have stepped tech billionaires including Amazon founder Jeff Bezos, Israeli entrepreneur Yuri Milner, and through Alphabet, Google co-founders Larry Page and Sergey Brin, who are funding new models that aim to combine the best of business and academia without the pressure for short-term returns. Barzilai hopes to pitch to some of this class of investors at an upcoming longevity conference.

The billions being made available to longevity researchers could be a gift to a humanity too distracted by today’s problems to fund a long-term revolution in healthcare. Their interest could be a “win-win”: billionaires tempted by the idea of living ever longer fund a longevity field that would not thrive without them.

But critics worry that if wealthy individuals dominate, future advances could create an elite not of designer babies but of designer elderly. Christopher Wareham, a bioethicist at Utrecht University who studies the ethics of ageing, says advances in longevity science risk widening the gaps between the rich and poor in health, wealth and power, including concerns that dictators could extend their lives.

“Suppose, for example, we had a kind of vaccine for the pandemic of age”, he hypothesised. “This is going to potentially exacerbate all the kinds of existing inequalities that we have . . . The longer you’re around, the more your wealth compounds, and the wealthier you are, the more political influence you have”.

Turning back the biological clock

As the field of longevity research began to expand, scientists convened to ask the most fundamental question: what is ageing? In 2013 an influential group laid out the “nine hallmarks of ageing”, genetic and biochemical processes that lead to impaired function and vulnerability to death.

Eric Verdin, chief executive of the Buck Institute for Research and Aging in California, says scientists have completely changed how they think about ageing, from presuming it was a passive process — if you wait long enough, things fall apart — to learning how to modify it.

Eventually, a breakthrough could simply prevent us reacting to the chronic illnesses that kill. “The biggest risk factor of all diseases is ageing: It is not cholesterol or smoking, it is your age”, he says.

James Peyer, chief executive of Cambrian Biopharma, which incubates and invests in longevity companies, says the “north star” for the field is creating a new generation of preventive drugs, which he believes will have as much impact on human health as vaccines and antibiotics.

Before developing drugs, scientists have to investigate what is happening on a cellular level. One important discovery was that the biological clock on cells can be turned back, using “rejuvenation factors” that create the potential to reverse disease.

Another was that senescent cells build up in older people — ageing, not dividing, but refusing to die — causing health problems. Scientists at the US Mayo Clinic discovered that if you engineer mice so the senescent cells die off, they became healthier and live 20 to 30 per cent longer.

But so far, the majority of these discoveries have been in animals, not humans. “It’s a great time to be a rich mouse. And you could live for a long time as a rich mouse, but I think we want to have human beings that live healthier”, jokes Vijay Pande, general partner at venture capital firm Andreessen Horowitz, which invests in longevity start-up BioAge.

Testing these hypotheses in humans presents huge challenges. It would take too long to wait to see whether humans on a drug live longer. So scientists must find “biomarkers”: signals that track the ageing process to see if it slows.

Researchers also have to contort their trials into the existing regulatory framework, which does not define ageing as a disease. They must target specific diseases, even though some hope the drugs will have broader applications.

While Barzilai thinks metformin has the potential to extend life, his trial will aim to show that the drug delays a basket of diseases, including stroke, heart failure, cancer and dementia, as well as death.

But by far the biggest hurdle is getting enough money to fund large trials, to accelerate this exploration, and find other factors that influence ageing.

Funding ‘engines of discovery’

When Rick Klausner began to raise money for Altos Labs, he created a deck for investors like no other. Instead of coming to potential shareholders with a list of projects and a timetable of milestones, the former director of the US National Cancer Institute hoped they would invest in what he called an “engine of discovery”.

His pitch was that Altos would hire the best minds in the business — including the former GSK chief scientific officer Hal Barron as chief executive — and set them free. Working in a way he hopes will be more collaborative than academia, they will tackle the big problems around rejuvenating cells with the ambition of reversing diseases.

The approach paid off: the company raised $3bn, a life sciences industry record, in a round led by Arch Venture Partners, and reportedly including funds from Bezos and Milner, the cofounder of Mail.Ru and founder of tech investment firm DST Global.

Barron says the money will allow them to fail multiple times in pursuit of their goal: an “incredibly novel way of thinking” about reversing disease. Pursuing such a “complicated, disruptive idea” needs $3bn, he adds.

“If you had a typical $60mn or $100mn investment, it wouldn’t really be thoughtful to try to tackle this problem”, he explains.

Altos, which launched at the start of 2022, is now the best known of the well-funded experiments trying to turbocharge anti-ageing science. The first was Calico Life Sciences, an Alphabet company, founded in 2013, where Barron used to lead research.

Klausner and Barron criticise the academic funding model for creating an environment that doesn’t encourage tackling the biggest questions. Instead of putting pressure on their researchers to publish in the best journals, or placing a premium on being the first author on a paper, they will be judged on whether they are working on the hardest problems.

“It’s an experiment, but I think it is an experiment that’s worth all of us committing the rest of our careers to”, Klausner concluded.

Robert Nelsen, co-founder at Arch Venture Partners, says the company only wanted very long-term investors. His group can hold shares in Altos for 10 to 15 years if necessary, though he believes other investors will see the value long before it lands on a “Holy Grail”.

“If this works, it doesn’t matter if we’ve waited. If you cure disease in my business, you are going to make money”, he says.

Jonathan Lewis, chief business officer at Calico, says a “chunk of funding” from Alphabet, then known as Google, allowed the company to focus on early biology when it launched in 2013.

But since then, it has attracted funding from the pharmaceutical company AbbVie. The partnership has been renewed twice, and Alphabet and AbbVie have now both committed to investing $3.5bn.

The money is significant for the 275-person organisation, but small fry for Alphabet, with its $1.2tn market capitalisation, and AbbVie, at $292bn. Now, Calico has three potential drugs in early clinical trials.

More conventional venture capitalists are entering the field, but they focus on companies that are testing broader principles of anti-ageing science in specific trials that could produce drugs more quickly. However, the step-by-step approach could be slower, and if the first trial fails, a company may suffer, potentially undermining its larger vision.

The ethics of private research

The well-funded new kids on the block have ignited debates about whether governments have their scientific priorities right, and the consequences of shifting more early stage science into private institutions.

Government funding is growing but is still nowhere near matching the investment raised by organisations like Altos. The US National Institutes of Health has an ageing division, but a rise in its budget in the past decade was mainly devoted to Alzheimer’s. The UK has begun to take notice, but the money is spread thinly: the government’s national research funding body, UK Research and Innovation, spent £2mn setting up 11 networks.

James Wilsdon, director of the Research on Research Institute at the University of Sheffield, says public funds need to be directed where they can deliver benefits more immediately.

“The need is great enough as it is, without then taking on much longer term, more speculative questions”, he says.

He added that there is a suspicion that those who stress the need for “long-termism” are actually dressing up their “individual, narcissistic, selfish desires to find ways of extending their own life as long as possible”. “You can paint as much lipstick on a pig as you want, but it is still a pig of an argument for allocating health funding”, he says.

Wareham, the bioethicist, says we need to get away from the “disturbing image of these kinds of vampire-like billionaires, concocting extension potions and experimenting on themselves”, and realise that even if they are self-interested, they can “afford to make a lot of mistakes”, which governments cannot.

Governments are also contributing in less obvious ways. Lewis describes the UK as “prescient” for setting up the UK Biobank, a genetic and health information database of half a million participants. This proved so useful that Calico is helping fund more scans to improve its understanding of how disease progresses in older adults.

Within the field, some envy peers who no longer have to fill out endless funding applications. Lynne Cox, an associate professor at the University of Oxford who specialises in ageing science, spends most of her time “scrambling around for little pots of money”. Even basic resources like pipettes can be in short supply.

She contrasts this with a colleague who recently joined Altos. “He has the freedom to do science the way science should be done”, she says.

Cox has taken funds from Jim Mellon, a British former fund manager who also co-founded Juvenescence, a biotech devoted to longevity, who she describes as a “one of those ideal donors” who does not micromanage.

Others worry that the private companies engaging in early research could restrict access to innovations. While Altos researchers will be free to publish their findings, and Calico declares itself “pro-publishing”, some suspect they are less free than in academia.

The pharmaceutical industry already guards its intellectual property closely, and has been accused of setting drug prices too high. As anti-ageing science gets closer to market, there will be big ethical questions about how fairly treatments are distributed.

Mehmood Khan, chief executive of Hevolution Foundation, a non-profit devoted to longevity research backed by the Saudi royal family that has pledged $1bn a year in investment, says its vision is to “extend healthy lifespan for the benefit of all humanity”, to ensure it doesn’t exacerbate the gap in life expectancy between the rich and poor. He says Hevolution is only funding work that could be “democratised”.

“If this is going to be a gazillion-dollars’ worth of treatment for a handful of people, it is of no interest”, he says.

Altos says it wants to help as many patients with serious medical needs as possible, and is committed to working with the healthcare ecosystem on access and equity.

To speed innovation and encourage wider access, governments have usually been the main contributors to fundamental science, answering essential questions, which do not lead directly to products.

Ronald Kohanski, director of the division of ageing biology at the US National Institute on Aging, says that while in the Renaissance scientists relied on wealthy people’s pockets, in modern times western governments have supported open science.

“Not everybody who was offered the large salaries by Altos went. Some prefer to stay in academia”, he says.

He adds that people with private funding are not subject to the same “compulsion” as those with government money: to ensure their findings are accessible, and that any positive consequences are available to everyone.

“If you’re doing something to make money, you’re going to optimise your profit. That’s capitalism in a nutshell”, he says.

By Hannah Kuchler.

18 comentarios

  1. And just as it is appointed for man to die once, and after that comes judgment,
    Hebrews 9:27

    What every needs is a cure for Sin, and only Jesus can provide that... along with a new glorified immortal body... Only in Christ Jesus...


    1. Take your bronze age philosophy and stick it on your ear, we are so over healthcare via religion, we tried it, it didn't work so well.

      I wonder if the same r3t4rds whom won't get vaccines will fight against this...

      I'm betting they wont.


      1. Thank you kindly for your display of tolerance and impressive display of co-existence based diversity and inclusion dynamics.

        The readership reminds you, the commenter who is a fine example of the embodiment of a certain stereotype/profile, that there are over 3,000,000,000 human beings who are members of your target demographic.

        The behavioral patterns and characteristics which you and those of your ilk ascribe to members of your target demo are a product of your indoctrination and brainwashing. If even .1% actually thought, felt, or behaved the way you have been lead by the nose to believe, then the internet (your god) and the streets would be swamped with them, protesting this and spewing bile at that, you know the this and that, that used to be nobody's business because it was their business... Now it's whatever they teach your 5 year old and his/her/other's response to that indoctrination is none of YOUR business.

        In any case, if you will, or even if you won't, these people are having a discussion amongst themselves, if you do not share their perspective, move on, be tolerant and respectful of the diversity and practice inclusion.

        They have as much right as you or anyone else to provide commentary on whatever they chose.
        But that's what bugs you, gets under your skin like a termite and eats at you. You only want free speech and inclusion and diversity to reflect what you like. That's why you went from adoring Elon Musk to hating him almost overnight and have no idea why.
        Grow up and stop being such a hypocrite.


  2. "For the word of the cross is foolishness to those who are perishing, but to us who are being saved it is the power of God. For it is written:

    'I will destroy the wisdom of the wise,
    And the understanding of those who have understanding, I will confound.'

    Where is the wise person? Where is the scribe? Where is the debater of this age? Has God not made foolish the wisdom of the world? For since in the wisdom of God the world through its wisdom did not come to know God, God was pleased through the foolishness of the message preached to save those who believe. For indeed Jews ask for signs and Greeks search for wisdom; but we preach Christ crucified, to Jews a stumbling block, and to Gentiles foolishness, but to those who are the called, both Jews and Greeks, Christ the power of God and the wisdom of God. For the foolishness of God is wiser than mankind, and the weakness of God is stronger than mankind.

    For consider your calling, brothers and sisters, that there were not many wise according to the flesh, not many mighty, not many noble; but God has chosen the foolish things of the world to shame the wise, and God has chosen the weak things of the world to shame the things which are strong, and the insignificant things of the world and the despised God has chosen, the things that are not, so that He may nullify the things that are, so that no human may boast before God. But it is due to Him that you are in Christ Jesus, who became to us wisdom from God, and righteousness and sanctification, and redemption, so that, just as it is written: 'Let the one who boasts, boast in the Lord.'”

    1 Corinthians 1:18-31


  3. We already have the best pill for mitigating the effects of age: EXERCISE/NUTRITION!
    Eat clean - if man makes it, don't eat it, and get off your lazy ass and exercise.
    Money can't buy discipline, but these rich dolts will never realize their privilege ends with the laws of nature.


    1. There's a ridiculous promotion called the Exodus Effect that promises to give you Methuselah's life expectancy. Rob, you are quite correct about nutrition and exercise. To begin with, "The Exodus Effect" is only the promotion's Bible footage; secondly, the Old Testament uses the lunar--not solar--calendar, so while Methuselah lived like a sea turtle TO 162, the gentleman really lived to 81!


  4. He has made everything beautiful in its time. He has also set eternity in the human heart; yet no one can fathom what God has done from beginning to end.

    Ecclesiastes 3:11


    1. You are right, Juha. Maybe Gretchen Wilson raves about gulping beer rather than champagne (the country song "Redneck Woman"), but beer can fatten you. How should one fight germs, if not with herbs? Chitterlings (PIGS' FEET) like in some toothless, snot-flicking communities? Caramello candy bars? Root beer? Devil Dogs (no, brave Marines, not the kind on covers of "Men's Fitness")? Medical knowledge to the east of the Ural Mountains ISN'T the 17th-century hogwash known as alchemy! Michael Chang was quite a tennis star in the late 1980s, and Nina Davuluri--"dovva-LOORY", a complete knockout--was in 2017 our country's first Hindu Miss America. "Yes, Shirley Temple, have animal crackers in your soup, AS LONG AS IT'S NICKNAMED 'JEWISH PENICILLIN!'"


  5. It's nice to see that there are disciples of Christ out there and know the true problem and solution to death!

    Justa Pilgrim Goin Home


  6. There already is a cure for old age. It's called "death." Everyone alive today on Earth will live forever. You just shed your body, at some point, and continue living.


  7. Where will the extra food come from? We dont feed the people we have. If everybody lives twice as long they will have to create more wars and pandemics to control the population.


    1. Rob, there was also some promotion called Hot Cars, with even a toll-free number: 1-800-HOT-CARS, displaying all these sizzling sports cars supposedly confiscated by cops; and apparently offering the cars for $100. My late father's Consumer Reports explained that these utter apprentices of David Hasselhoff's were about $20,000 and everything selling for $100 HAD BEEN ESSENTIALLY DEMOLISHED AS PART OF A HIGH-RISK OPERATION. "So tell, bud, HOW DID SALLY STRUTHERS' CORRESPONDENCE SCHOOL PREP YOU!"


    2. Relax, Richard! Food is not satisfaction. What about vacations, weekend frivolities, and highly fond holiday memories, or craft projects with excellent neighbors and girlfriends? If one is not sufficiently leery, he can become morbidly obese.


    1. Spence is right. Remember that while Jurassic Park was a borderline replica of Colonial Williamsburg, the dinosaurs were accidentally released. How would you like to be promised romantic getaways to Paris and Rome, or adventure getaways to Athens on some game show; JUST TO BE STUCK WITH TEXAS' PARIS, NEW YORK'S ROME, OR PENNSYLVANIA'S ATHENS!


  8. "While Barzilai thinks metformin has the potential to extend life, his trial will aim to show that the drug delays a basket of diseases, including stroke, heart failure, cancer and dementia, as well as death."

    And going to a low carb, high fat diet like Ketovore or just Carnivore will do the same but better.


    1. You're rather observant, Vernon. I also quite hate to sound anti-Asian but wisely unlike in Japan, we obtain antibiotics only with prescriptions! Dr. Barzilai needs to consider just maybe after some period YOUR BODY DEVELOPS A RESISTANCE. So would anyone rather transform into a sea tortoise living to around 250 years OR CATCH A CONTAMINANT OFF GUARD.


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