If they could turn back time: How tech billionaires are trying to reverse the ageing process

It is not the first time Silicon Valley billionaires have thrown their wealth at the ageing problem. 

In the summer of 2019, months before the word “coronavirus” entered the daily discourse, Diljeet Gill was double-checking data from his latest experiment. 

He was investigating what happens when old human skin cells are “reprogrammed” — a process used in labs around the world to turn adult cells (heart, brain, muscle, and the like) — into stem cells, the body’s equivalent of a blank slate.

Gill, a PhD student at the Babraham Institute near Cambridge, had stopped the reprogramming process midway to see how the cells responded.

Sure of his findings, he took them to his supervisor Wolf Reik, a leading authority in epigenetics. 

What Gill’s work showed was remarkable: The aged skin had become more youthful — and by no small margin. Tests found that the cells behaved as if they were 25 years younger. 

“That was the real 'wow' moment for me,” says Reik. “I fell off my chair three times.” 

A lot has happened since then. 

Last summer, Reik resigned as the director of the Babraham Institute to lead a new UK institute being built by Altos Labs, a contender for the most flush startup in history. 

Backed by Silicon Valley billionaires to the tune of $3bn (€2.6bn), Altos has signed up a dream team of scientists — Gill and numerous Nobel laureates among them. 

They will start work in the spring at two labs in the US and one in Britain, with substantial input from researchers in Japan. 

Their aim is to rejuvenate human cells, not with an eye on immortality — as some reports have claimed — but to stave off the diseases of old age that inexorably drive us to the grave.

It is not the first time Silicon Valley billionaires have thrown their wealth at the ageing problem. 

In 2013, Google launched Calico — the California Life Company — with its own high-profile hires. 

With $1bn to burn, the secretive firm began studying mice, which have an average lifespan of six years, and naked mole rats, which, with a lifespan of 30 years, appear to have traded good looks for longevity.

The company aims to map the ageing process and extend healthy lifespan, but has yet to produce any products.

Not that this has dampened Silicon Valley’s expectations. 

In a microcosm shaped by Big Tech, ageing is framed as code to be hacked, with death merely another problem to be solved. 

Peter Thiel, co-founder of PayPal and the big-data analysis firm Palantir, has poured millions into anti-ageing research, notably the Methuselah Foundation, a non-profit that aims to make “90 the new 50 by 2030”.

Peter Thiel.

Thiel has claimed it will be possible to “reverse all human ailments in the same way that we can fix the bugs of a computer program. Death will eventually be reduced from a mystery to a solvable problem”. 

Thiel, who hopes to live to 120, is one of the more adventurous advocates of anti-ageing therapies. 

One that caught his eye — although it is unclear if he has tried it — stems from a series of macabre experiments that found the muscles, brains, and organs of old mice were partially rejuvenated when they shared the blood of a young animal (the younger animals, in return, appeared to age).

Scientists are still trying to establish which blood components are behind the effect, with a view to slowing dementia and other age‑related diseases. 

But that didn’t stop a number of US firms from offering transfusions of young blood for thousands of dollars — until the US Food and Drug Administration intervened, warning consumers that there was “no proven clinical benefit”.

Another approach that has pulled in private funders aims to flush worn cells from the body. When cells are damaged — for instance, by toxins or radiation — they can switch into a zombie-like state known as senescence. 

The process has benefits: Senescence can shut down cells with mangled DNA and prevent them from becoming tumours. But senescent cells cause trouble, too: They accumulate in our bodies like junk and release substances that ramp up inflammation. This, in turn, drives diseases of old age.

Thiel believes it will be possible to "reverse all human ailments in the same way that we can fix the bugs of a computer program". 

In 2016, a Silicon Valley startup called Unity Biotechnology raised $116m from investors, including Thiel and Amazon’s Jeff Bezos, to create therapies that flush out senescent cells.

Amazon CEO Jeff Bezos 

 

Unity’s co-founder, Ned David, believes the drugs could “vaporise a third of human diseases in the developed world”. 

The evidence so far is encouraging. 

In 2018, James Kirkland, a researcher at the Mayo Clinic in Minnesota, showed that “senolytic” drugs that destroy senescent cells not only improved the physical capabilities of aged mice, but also extended their lifespans.

More than a dozen clinical trials are under way in humans, targeting osteoarthritis, Alzheimer’s, and frailty.

In case death turns out to be a hard nut to crack, Thiel and others have hedged their bets and signed up with the Alcor Life Extension Foundation, which has been freezing bodies and brains of the dead since 1976. 

For about $200,000 and annual dues, the Arizona-based firm (motto: “A fulfilling life doesn’t have to end”) will keep your corpse on ice until science can reanimate you. 

For those of more modest means, Alcor will freeze your dead head for $80,000. 

Altos emerged from stealth mode last month, with the Russian-Israeli tech billionaire Yuri Milner a confirmed backer. Bezos is rumoured to be involved, too. Clearly, they mean business. 

The chief scientist and co-founder, Rick Klausner, is the former head of the US National Cancer Institute, while the chief executive, Hal Barron, left a role at GlaxoSmithKline that paid more than £8m a year.

But what is it with middle-aged male billionaires and anti-ageing research? Has the penny dropped that they, too, will one day fade away? Is rejuvenation science poised to swell their fortunes further? Or — and humour me for a moment here — could this be about the greater good?

Asked about the trend after Calico launched, Bill Gates was scathing: “It seems pretty egocentric, while we still have malaria and TB, for rich people to fund things so they can live longer,” he told an 'ask me anything' forum on Reddit.

Bill Gates.

Perhaps the motivation doesn’t matter. 

Altos’s Cambridge Institute of Science is under construction at Granta Park, a landscaped 120 acres south of the city that is home to AstraZeneca, Pfizer, and Illumina, a gene-sequencing firm. 

The first researchers are due to arrive in May. Two more institutes are being set up in San Diego and the San Francisco Bay Area, with further support coming from Prof Shinya Yamanaka, a Nobel prizewinning stem-cell scientist at Kyoto University in Japan.

One area Altos will explore is called the integrated stress response (ISR). 

When cells in the body become stressed by, say, a viral infection, a lack of oxygen, or the buildup of malformed proteins, the ISR can reboot the cell’s protein-making machinery. 

It is the biological equivalent of the IT department’s “turn it off and on again”. 

If this doesn’t work, the ISR tells the cell to self-destruct: The biological equivalent of chucking your laptop in the bin.

In the past decade, scientists have discovered that the ISR is involved in a host of age-related diseases, including Alzheimer’s. 

In December 2020, Peter Walter, who will run Altos’s Bay Area institute, showed that drugs can retune the ISR and rapidly restore youthful cognitive powers to aged mice. If nothing else, Altos is good news for over-the-hill rodents.

Another area in which Altos hopes to make headway is rejuvenating the immune system. 

As we age, our immune system weakens, leaving us more prone to cancer and infections. Part of this is driven by changes in the thymus, a gland the size of an oyster that sits between the lungs. The thymus is where the immune system’s protective T cells go to mature, but from puberty onwards it shrinks and is steadily replaced by fat.

Central to Altos’s vision is a procedure called cellular reprogramming. 

With every human birth, biology demonstrates its powers of rejuvenation by turning the old cells from parents into the youthful tissues of a newborn. 

In 2006, Yamanaka created a similar effect in the lab. He found that activating four genes in skin cells transformed them into an embryonic state, from which they could grow into the body’s numerous tissues. 

The work fuelled a wave of interest in growing spare parts for patients, but the procedure has its risks: activate the “Yamanaka factors” inside living animals and they can develop teratomas — tumours made due to a grim confusion of different cell types.

Scientists are refining the procedure, winding back the clock just enough to make cells youthful, but not cancerous. 

In one landmark study, Juan Carlos Izpisua Belmonte, a developmental biologist who will lead the Altos institute in San Diego, showed that switching on Yamanaka factors for a six-week burst rejuvenated old mice and extended their lifespan by nearly one-third. 

“With careful modulation, ageing might be reversed,” he says.

The same trick would be hard to pull off in humans. Instead, the hope is to find new biological pathways that, when targeted with drugs, rejuvenate old or senescent cells without causing cancer. 

There are no guarantees of success, of course, but that is the nature of medical research.

“What excites me about Altos is that it’s a new way to do science,” Reik says. “It appeals to me because you can achieve so much more in a bigger team. We want to knuckle down.”

Guardian