In this week’s newsletter

✅ Death acceptance propaganda. ✅ A silly longevity feud. ✅ Elevating AI to Nobel heights. ✅ Senescent cells - more than just zombies. ✅ Insights from Episode 9 of the LEVITY podcast.

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A new study in Nature Aging is provocative for all the wrong reasons

I've never met Jay Olshansky, so it's hard to say what he's like in person - he might very well be the crowd-pleaser, the fun-maker and the soooooul-shaker. The life of the party, for all I know.

However, my only encounters with him have been through his publications and various quotes in books and news articles, where he often appears more like Gloomy Gus and the Buzzkillers.

Consider some of his statements over the years:

”Lifespan extension has never really been a goal of aging science nor should it.”

”There are biological forces that limit how long we can live.”

”Absence of a genetic program determining how long we live doesn’t mean there are no limits. Let me give you an example: The world record for running a mile currently stands at three minutes and 43 seconds. Some 150 years ago, it was five minutes. The record has thus been cut by one minute and 17 seconds. Now, if I were to ask you whether it’s possible for someone to run a mile in one minute, what would your answer be?”

Yeah, about that last one: Comparing improvements in mile-running times to the possibility of human indefinite life extension is of course a non sequitur.

Or, as Aubrey de Grey once put it: ”Jay Olshansky is a smart guy, and a friend of mine. But he says some incredibly stupid things. I mean, it’s almost embarrasing”.

So why am I telling you all of this?

Well, Olshansky has just published a new study in Nature Aging - a study that, despite its provocative title, offers little substance. The study, entitled ”Implausibility of radical life extension in humans in the twenty-first century”, lacks any evidence to support such a claim. Olshansky, who has often criticized proponents of ambitious life extension for what he sees as exaggerated claims, appears to be guilty of the same offense here.

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What the study should have been titled is ”Time to settle the score with James Vaupel and his disciples”.

If you’re not versed in various beefs between aging biologists you might need a helping hand.

James Vaupel, who passed away two years ago, was the founding director of the Max Planck Institute for Demographic Research in Rostock, Germany. He had this idea of ”plasticity of longevity”.

In 2002, Vaupel noted that since 1840, life expectancy has consistently risen by approximately three months per year. This remarkable trend was largely due to reductions in child mortality, advancements in combating infectious diseases, improvements in sanitation and nutrition, higher levels of education and so on.

Moreover, Vaupel contended that the increase in life expectancy would persist without a foreseeable plateau. He highlighted data showing that since the 1950s, and particularly from the 1970s onward, mortality rates among those over 80 have continued to decline, with some countries even experiencing an accelerating pace in this decrease.

From these observations, Vaupel concluded that the continuous linear rise in record life expectancy over more than 165 years did not indicate an imminent limit to human lifespan.

This perspective was in stark contrast to the views of Jay Olshansky, who, in a 1990 study published in Science titled ”In Search of Methuselah: Estimating the Upper Limits to Human Longevity”, argued that it seemed highly unlikely life expectancy at birth would surpass 85 years.

This disagreement escalated into a significant feud, with tensions running so high that they both took pains to avoid each other at scientific conferences.

Which, to an outsider, seems rather silly.

It’s not that their research is not important. Decision-makers in fields such as healthcare, social welfare, and insurance are particularly interested in these findings, as they need accurate predictions of life expectancy to plan and allocate resources effectively.

Anyway, this context sets the stage for the aforementioned study by Olshansky and colleagues, in Nature Aging. The study indicates that while life expectancy from 1990 to 2019 continued to rise, the rate of increase has decelerated, no longer adhering to the three-month-per-year increase* previously projected by James Vaupel - a finding they might consider a victory.

* By the way, the study refers to Vaupel’s predictions of a linear rise in life expectancy as ”radical life extension”. That’s odd and probably not in line with most people’s definition of the concept.

In truth, neither Vaupel's nor Olshansky's research offers definitive insights about the future. Both have analyzed historical data to make projections, each drawing different conclusions based on the evidence at hand.

If I were to wager on whose predictions might hold, I'd lean towards Vaupel's view. His anticipated rate of longevity increase accounts for ongoing technological advancements. The period between 1990 and 2019 might just represent a temporary deviation in a broader trend, suggesting that we've reached the limits of what current methods can achieve and are now facing a gap until new innovations emerge.

And ironically, despite its title, the Nature Aging study takes great care to cover its bases. The discussion section at the end of the paper highlights this caution, with the authors noting that ”given rapid advances now occurring in geroscience, there is reason to be optimistic that a second longevity revolution is approaching in the form of modern efforts to slow biological aging, offering humanity a second chance at altering the course of human survival”.

A second longevity revolution is approaching? How do you square that with ”Implausibility of radical life extension in humans in the twenty-first century”?

Look, there is no reason to dispute Olshansky’s findings here. There is every reason to dispute his extrapolations from those findings. This is echoed by Steven Austad* in The Guardian.

”For life expectancy to again accelerate, we need a new approach focused on disease prevention. Geroscience focuses on improving health by treating the underlying biological processes of ageing, which underlie virtually all of the maladies that degrade our quality of life or kill us.”

Austad continues:

“These advances are beginning to make their way to the clinic. So as much as I buy this analysis of slowed life expectancy increase, the authors’ projection for a continued gradual slowing for the rest of this century strikes me as premature.”

* It's worth noting that Steven Austad and Jay Olshansky, who are friends, made a bet back in 2001 about whether anyone born before that year would live to be 150 years old. You can probably guess which of them bet against that possibility.

Others made more damaging interpretations. Eric Verdin, CEO of the Buck Institute for Research on Aging, told Stat News:

”What this paper will hopefully do is impose a reality check on the field. Talking about things that are unattainable sells books, and it generates clicks, and it generates enthusiasm … but it also detracts from the serious work that can be done now.”

I don’t even know where to begin with this quote.

There are (way too few) people dedicating their lives to solve aging because they’ve rightly concluded that it’s the greatest threat to each and every person. Part of addressing this challenge involves communicating effectively with the public. Dismissing these dedicated efforts as mere profit-seeking undermines the importance of their work.

But Verdin wasn’t done. On X, he wrote:

”Happy to contribute to story in @statnews on study that shows we are nearing the limit of human longevity. We need to focus on extending healthspan, not lifespan.”

Why, exactly? What we need to focus on is making sure that the risk of dying does not increase as time passes. Make no mistake: people who say that we should focus on healthspan are of the opinion that we all should die from a chronic disease albeit with less time spent having that chronic disease. This is unacceptable.

It’s the wise view (see the first episode of the LEVITY podcast) all over again. Some might even call it ”death acceptance propaganda”.

To be fair, Andrew Steele, author of Ageless, and Morgan Levine, VP of Computation at Altos Labs, view the Nature Aging study as a ”call to arms”. That’s very generous of them, but when the “second longevity revolution” arrives, we may look back on this paper as yet another instance of skepticism that was eventually proven wrong. After all, history is replete with such skeptics.

I'll conclude this discussion with a prediction of my own. To anticipate future life expectancy, keep an eye on the declining costs and expanding capabilities of graphics processing units (GPUs). I bet that those trends will offer more insights into our future longevity than any demographic study could.

News from around the longevity and health space.

More than zombies

”Want to live for ever? Flush out your zombie cells.” That’s a headline for an article in The Guardian from six years ago.

Let’s examine it.

First of all: it suggests that aging has only one cause and therefore only one remedy is needed. This is in all likelihood very far from the truth.

Second of all: it falls into the ”longevity zeitgeist trap”. Around that time, there were considerable hype around the removal of senescent cells thanks to some interesting results in mice and some considerable investments being made in a few biotech startups.

Third, is it fair to call senescent cells ”zombies” that wreak havoc on surrounding tissues? Not really, at least not as a catch-all term. While some senescent cells under certain conditions do secrete a toxic cocktail known as SASP (Senescence-Associated Secretory Phenotype), this is not always the case.

In fact, two recent studies add to the growing literature on just how diverse senescent cells can be. One study demonstrates that senescent cells in the liver, such as macrophages and endothelial cells, can have opposing effects - some harmful, others beneficial. Another study highlights the varied stress responses of senescent cells, depending on the type of cell and the nature of the stressor.

Now, cellular senescence is indeed one of the hallmarks of aging. But the challenge for scientists is to selectively target the damaging cells while preserving those that play a positive role. Simply flushing them all out isn’t a viable solution.

What I’ve been up to lately.

Hinton and Hassabis: Elevating AI to Nobel heights

This year, I’ve had the privilege of covering not just one, but two Nobel Prizes for Ny Teknik. Geoffrey Hinton was awarded the Nobel Prize in Physics, while Demis Hassabis, co-founder of DeepMind, received the Nobel in Chemistry. You can find my analyses linked below, though they are, of course, in Swedish.

Hinton and Hassabis have significantly influenced recent advancements in artificial intelligence, yet their visions for the future diverge sharply. Hinton have reservations about his contributions, fearing that we are on the brink of creating something beyond our control. Hassabis, on the other hand, foresees a promising future, particularly in healthcare, highlighted by his Nobel-winning work on AlphaFold, a groundbreaking tool in biological research.

To underline the last paragraph in my earlier discussion about Jay Olshansky: it’s clear that any future projections must consider the impact of AI.

Insights from Episode 9 with Maria Rankka.

Want show notes? Find them here.

”We truly believe that, you know, we're at the threshold of the paradigm shift in medicine.”

Insight: Maria Rankka foresees a fundamental transformation in medical treatment, where cellular therapies could become as commonplace as pharmaceuticals are today, potentially reshaping the entire healthcare landscape.

”They're anti-inflammatory. So you can use them for inflammatory conditions. They are immunomodulatory. So you can also use them for autoimmune conditions - and they work in a regenerative way.”

Insight: Mesenchymal stromal cells (MSCs) offer a unique triple-threat in therapeutic potential, addressing inflammation, autoimmune disorders, and tissue regeneration simultaneously.

”As far as we know, our production of bone marrow derived MSCs [mesenchymal stromal cells] in Stockholm today, it's probably […] the world's largest production facility for these kinds of cells.”

Insight: Cellcolabs' achievement in large-scale production suggests a breakthrough in making cell therapies more accessible and affordable, potentially accelerating their adoption in mainstream medicine.

”We are aiming at […] 10 years ahead, that the price will be 10% of what it is today. And that should be possible to achieve.”

Insight: This ambitious goal reflects Cellcolabs’ commitment to democratizing access to treatments, potentially transforming MSC therapy from a luxury to a widely available preventative health measure.

”One thing that is good about Sweden when it comes to this kind of production is that we are not allowed to pay donors anything here. So we have people who actually volunteer to donate bone marrow. We think that is good.”

Insight: This approach to donation highlights the importance of ethical considerations in biotechnology. It suggests that advanced medical treatments can be developed without compromising ethical standards, potentially setting a global precedent for responsible innovation in regenerative medicine.

Hey, you’ve made it all the way here! Thank you so much for reading! 🫶🏼