One Born Every Minute

Longevity Part II: More centibillions than sense

We now know a little^⌘ about the often flawed science of longevity. Let’s explore those who fund this ‘science’, either by buying the products, or as research sponsors.

Looking into this, I’ve come up against a few problems. Some rich donors are rather coy about what they’re funding and how much they’re putting in. Similarly, the outputs of the research can be sketchy, dodgy or both.¹ Finally, not a few greedy people latch on to the wealthy, embedding their products among regurgitated factoids about billionaires. We’ll encounter examples of all of these.

⚠ Warning. Some of the images may distress viewers who (a) are of a sensitive disposition; and (b) aren’t billionaires. This gets a lot worse than the rat king image above.²

Rodent quilting!

“If we could enable people to live forever, we should do that. I think this is absolute.” Peter Thiel

People who believe in absolutes can end up doing very nasty things. Peter invites our attention for many reasons. First, he’s embraced anti-ageing tech more vigorously than most; second, his pet show-pony is a man called Vance, so if Trump has yet another, bigger stroke, Peter is even more firmly in the pound seats; third, his intrusive data-mining company Palantir Technologies likely knows more about your family than you do. Whoever you are.³

Superficially, Peter Andreas Thiel is far from an idiot. He founded PayPal (with Max Levchin and Luke Nosek) in 1998 and sold it for $1.5 billion in 2002. He’s built successful hedge funds, and of course, Palantir. He was the first outside investor in Facebook, taking 10%.

But I struggle to completely avoid the label “miserable fascist libertarian nutjob” here. After effectively buying New Zealand citizenship in 2011 he’s now pulling back because we said ‘No’ to the sprawling bunker he tried to build overlooking Lake Wānaka (image above). He doesn’t seem to understand how taxation works,^⌘ or indeed the role of community in human success and worth. He has a smattering of other little defects like disparaging the extension of voting rights to women. He’s chumming up to Israel’s military, slightly at odds with his support for the rights of journalists to report freely and not be killed. He’s gay and a self-professed ‘Christian’, but still supports the gay-disparaging American Right. The less said about male model Jeff Thomas, the better.

And yes, he’s into anti-ageing. Bigly.⁴ He’s backed Aubrey de Grey, whom we’ll meet in my next post, and based on a widely reported article in Inc Magazine, he seems keen on parabiosis. What? I did warn you.

Heterochronic parabiosis

This is where it gets weird. Weirder. Over the past two decades a Stanford brain researcher called Tony Wyss-Coray has done a huge array of frankenexperiments where he sutures young and aged mice together. That’s ‘heterochronic’ (different ages) joining up (parabiosis).

The old mice may sometimes frisk up slightly—but it knocks the stuffing out of the young ‘uns. It’s actually quite difficult to obtain pictures of the procedure (like those above), which are normally replaced by sanitised drawings of happy conjoined mice.⁵ Can you think why?

Simplistically, the old mouse gains “youthful blood” from the young one. A disturbing feature is that even the ‘serious research’ on the subject refers to ‘young blood’. It’s obvious that they’re joining up the immune and metabolic functions of the mice too, but this is almost never mentioned. The mice need to be highly inbred, to prevent catastrophic immune rejection. A tiny side effect is that a fair number of the parabiotic mice die quickly. It’s the survivors that are studied. Often, briefly.⁶

Needless to say, these limitations haven’t stopped rich old people from getting FDA-disapproved infusions of ‘young donor plasma’. Between 2016 and 2019, an unlicensed doctor used a company called Ambrosia to sell “young blood transfusions” for $8000 a pop.⁷ They closed, and then opened in a different guise; similar clinics are still in operation. A venture capitalist called Bryan Johnson even took regular blood plasma from his son.⁸ He is also said to gulp down 100 pills a day at a cost of $2 million per year, but we’ll leave this for Part III!

Paleo and HGH

Back to Thiel. As with many of the ultra-rich, some of his practices may be anecdotal. According to Business Insider, his anti-ageing regimen includes eating ‘paleo’, taking human growth hormone (HGH) and metformin, and a customised exercise regimen. Let’s look at these.

The enticing idea is that a ‘stone age’ diet is better suited to our metabolism. Sadly, the ‘palaeolithic’ diet is dodgy as.⁹ First, we’re far from knowledgeable about what palaeolithic people ate. Their multiple ‘Venus’ figurines like the above Woman from Willendorf don’t provide a compelling picture of slim metabolic health.

The truth is that forbidding foods like, well, all grains and dairy products is pretty much unsupported.¹⁰ Effects of paleo on glucose and insulin balance are no different from those of several other diets. Sure, cut back on energy-dense processed food and eat your veg; but this is close to fanaticism.

Human growth hormone (HGH) is harmful. It is useful in a tiny set of young people who are deficient in it and thus destined to be short, but given to healthy adults it predisposes to a long litany of complications.¹¹

What about metformin? It’s a great drug. A great drug, that is, for controlling type 2 diabetes if you have it. It has been promoted as a near-magical anti-ageing potion too, and that’s where there is more doubt than substance. In those with diabetes, it seems to lower cardiovascular disease and cancer. Unfortunately, there is increasing skepticism about these alleged effects.¹² They’re likely statistical artefacts!

Exercise is OK, provided you don’t overdo it. Well, one out of four ain’t bad, I guess.

Scorbutic Sam

What is it with the software world? About five years ago, a rather unwell computer programmer was admitted to my ward with bleeding into his muscles. He had the worst teeth and gums I’ve ever seen. Looking more carefully, I clinched the diagnosis by spotting the changes you can see above. He just didn’t like vegetables, and developed scurvy! A few years before, an even sicker scorbutic programmer ended up in our intensive care unit. He lived solely off pot noodles. And today I learnt that when Sam Altman was working on his first startup Loopt, he too ended up with scurvy.

Currently though, the on-off chairman of the increasingly unopen OpenAI is assiduously into life prolongation. Like Thiel, he’s a metformin gulper.¹³ According to MIT Technology Review, he too has been captivated by ‘young blood’, and sponsored the setting up of Retro Biosciences to the tune of $180M. Retro is now looking for a billion in funding to “add ten years to the healthy human lifespan”. The irony here, though, is that the one large metformin trial, TAME, is still trying to find a billionaire backer after 8 years!

Calico

Uber-wealthy Google founders Sergey Brin and Larry Page are also into not ageing. They set up Calico Life Sciences LLC as a subsidiary of Alphabet in 2013. Calico works closely with the pharmaceutical company AbbVie, an Abbott spinoff rich from its monoclonal Humira, and a bunch of other drugs. Over a decade later, what’s to show for this? Their flagship drug is ABBV-CLS-628, but they are very coy about how it works, or even what it is.¹⁴

And so many more

“Death has never made any sense to me. How can a person be there and then just vanish, just not be there?” Larry Ellison.

The Oracle boss is a surprisingly youthful-looking 80. His mind appears sharp, and his appearance is, well, youthful. I perhaps shouldn’t comment on his gait, though. Previously heavily into anti-ageing, he’d pulled the funding by 2020. Do you recall how at the start, I mentioned coat-tails? There are not a few websites out there that segue from his youthful looks to their pesky products, despite his ‘anti-ageing regimen’ apparently being nothing more than exercise, and eating fish and veg.

Jeff Bezos, the Amazon boss, is the third richest man in the world. He’s 61 but looks older to me. He also had that embarrassing little fall the other day, when he welcomed back the Space Barbies.^⌘

In 2021 Bezos and Russian-Israeli tech businessman Yuri Milner co-funded Altos Labs, venturing into ‘cellular reprogramming’.¹⁵ I find this interesting quite because the usual hype is absent. They’re doing basic research. Although I may not like how Jeff treats his staff, here he seems to be being more sensible than most.

Buuut … in 2009, together with Peter Thiel, he also backed Unity Biotechnology to develop drugs targeting senescent cells. They shut up shop on 27 June, 2025. It seems they ran out of money, just as their flagship drug foselutoclax (UBX1325) was starting to show real promise.¹⁶ It all comes down to …

The bottom line

Although there’s a lot of money sloshing around here, I’d suggest that there are two main categories of—what shall I call them—victims? Suckers? The first group is people who latch onto and pay good money for poorly tested nostrums.¹⁷ The second group is ultra-wealthy people who can see the hype, and may even have some hopes here for themselves, but who are fundamentally just behaving as venture capitalists do. This explains the conspicuous lack of funding for TAME, and why an apparently successful new-in-class drug (UBX1325) had the rug pulled from under it.

Okay, some might be in it for the longer haul. And yes, something spectacular may result. But I’m not sanguine. It appears to me that a lot of the investment is based on a rosy interpretation of dodgy data. This will become even more apparent as we move to Part III, where we put some nostrums under the microscope, and look at the people who are purveying them.

These peddlers sometimes make the mouse-mutilators seem quite benign—until we realise they’re often one and the same. There’s nothing quite like bad basic research for prompting subsequent bad behaviour. Especially if you can find someone willing to hand over a pile of cash.

On, on to Part III.

My 2c, Dr Jo.

1. In contrast, those who are manic self-publicists are almost certainly trying to sell you something.

2. Rat kings are brilliantly explained in Terry Pratchett’s The Amazing Maurice and his Educated Rodents. I won’t spoil it for you.

3. He doubtless understands that Tolkein’s indestructible crystal ball ‘palantirs’ were ambivalent and unreliable, and that Sauron had control over one and could use it to bias and bend people to the will of Evil. I just don’t think he realises his true role here.

4. Thiel has however hedged his bets by signing up to be cryonically preserved.

5. This goes back quite a bit, to 1860, when the French physiologist Paul Bert did basically the same thing. In the literature, you tend to encounter interesting comments like:

This is also why it is necessary to ensure that the mice can stand independently, freely, and steadily on the ground on all eight limbs, as it prevents the subordinate partner from dying due to excessive passive movements.

6. Often just long enough to chop out a giblet and say “Look! It’s improved!!” (manic grin)

7. Almost-doctor Dr Karmazin who ran the show started off his venture as xVitality, but this flopped so he scrubbed all traces of it and reincarnated it as Ambrosia.

8. All the while, it appears, monitoring his son’s erections. You can’t make this up.

9. Apologies for the New Zealand turn of phrase. If you don’t like it, you can amend this to “as dodgy as, well, a dodgy thing”. Or anything you consider particularly dodgy.

10. Quite apart from the ecological devastation that would ensure if the whole world tried to go paleo, compared to vegan, Mediterranean and climatarian diets. There’s also a clear, historical survival benefit from consuming dairy, shown by the persistence of lactase in some populations.

11. As seen with tumours that produce it, causing acromegaly. But proponents will, of course, argue that they’ve got the dose ‘just right’. Ironically, GH supplementation seems to induce DNA damage, and despite ‘normalising’ body composition, may promote ageing! Also, cancer.

12. This is a remarkably thorough and insightful analysis, focusing on analytic flaws in the literature, especially time-related biases. Metformin really doesn’t seem to work for cancer, especially in prospective trials. Similarly, the alleged cardioprotective effects seem spurious.

13. He may wish to check his B12 level.

14. It may inhibit pappalysin-1. They also have fosigotifator, and some oncology drugs. They had a bit of a dust-up with BioArctic.

15. They’ve raised a serious $3 billion in investor funding, sucking in prominent scientists like Juan Belmonte, Steve Horvath and Shinya Yamanaka, who respectively work on cellular reprogramming, epigenetic ageing clocks, and turning somatic cells into stem cells using Nobel-prizewinning work.

16. The drug worked in a Phase 2 trial, eliminating senescent cells with good improvements in vision. It seems it just couldn’t compete with established therapy!

17. ‘Nostrum’ is such a fun word, encompassing a solution that’s not all that good, a patent medicine made by the person who pushes it, and something with no demonstrable value that is sold under false pretences.