In today’s newsletter

✅ Welcome to the longevity newsletter LEVITY - a (very long) manifesto of sorts. ✅ The largest longevity competition in history. ✅ A small step for big dogs - but maybe a giant leap for mankind. ✅ How to think about protein intake. ✅ Crappy mice and lemming scientists. ✅ The Swedish Bryan Johnson.

The ageless era is on the horizon. Let’s get there faster.

That is the elevator pitch for this newsletter.

The not so tl;dr version: last year my book was released in Sweden. Titled Evigt Ung - Min och Människans Dröm om Odödligheten (which translates to Forever Young - My and Humanity’s Dream of Immortality), it was the culmination of an interest that turned into an obsession.

It started when I realized that defeating aging was not only a truly worthy scientific goal, it was also within reach. Compared to the hundreds of thousands of years humans have been around we are just on the cusp of it. But from our vantage point we will either be one of the last generations to live such short lives as is the case now, or one of the first to reach the ageless era.

So what do I mean by ageless? Well, right off the bat I need to give credit to Andrew Steele, a British doctor in computational biology. I don’t know if he coined the term but he wrote an excellent book called Ageless: The New Science of Getting Older Without Getting Old. If you haven’t already you should buy it and then you should devour it.

”The new science of getting older without getting old”. It sounds like a paradox until you understand what ageless means.

We can’t really do much about the arrow of time (as far as we know). Each second that passes increases the gap between where you are now and the date of your birth. In that sense we are always getting older.

But it is not a given that we should also get sicker and more prone to disease just because time passes, it’s just that we take it for granted. Humans and indeed many other species in the animal kingdom are governed by the ruthless Gompertz law. Named after the British mathematician Benjamin Gompertz the law simply says there is an exponential increase in death rates with age.

Like this:

In fact, the risk of death for an adult human doubles about every eight years or so. For a ten-year-old in a rich country like Sweden, the risk of dying is one in 10,000. For those who have turned 30, the risk has increased to one in 1,500. From retirement age, it sharply rises: one in a hundred for 65-year-olds, one in 20 for those who have turned 80, and one in six for those who have passed 90. Eventually, one reaches the point where the probability of dying in a given year is like flipping a coin.

But this exponential and depressing trajectory towards frailty, disease and death is coming to an end.

Why?

Well, first of all we now have a fairly good understanding of what the biology of aging actually is. We might argue why we age (and I would bet good money on it being evolution not giving a damn once we’ve reproduced), but the scientific community are broadly in agreement of what happens when we age. Namely, an accumulation of different types of damage, mostly in our cells.

The hallmarks of aging

In medieval times (and by that I mean before the 1990’s) it was generally thought that aging was completely incomprehensible. Not to be studied, only to be accepted as a law of nature (which it’s not, by the way). Early in molecular biologist Cynthia Kenyon’s career she had a colleague that advised Kenyon not to pursue a career in that particular field of research. “Cynthia, I have friends who work on aging and it is as if they fall off the edge of the Earth”.

As is often the case in science a few renegade researchers - not least of all Kenyon herself - plowed through all that conventional so-called wisdom and broke new ground.

Just a few decades later, in 2013, some of the leading gerontologists in the world delivered the paper The Hallmarks of Aging in the journal Cell (in which, it has to be said, they simply reorganized ideas introduced by maverick biogerontologist Aubrey de Grey several years earlier).

This👆🏼is pretty much it. It’s not that complicated. Even I can understand most of it.

Okay, fine, it’s a bit more complicated than that to be fair. But in the spirit of fairness it’s worth pointing out that it is also not some big indecipherable riddle that could never be solved.

Just a quick note here before we move on. I am pretty much skipping over the entire history of gerontology for now. We’ll have ample time to revisit that later. But if you are dying (something this newsletter strongly advise against) to know, you’d be hard-pressed to find a more detailed encyclopedia than Ilia Stambler’s A History of Life-Extensionism In The Twentieth Century. Even better? You can read it all for free (but be prepared: it is dense):

Just a month or so after my book was released The Hallmarks of Aging was revised and a new paper was published. Somewhat frustratingly I knew this new version was under way as I wrote my book. One of the authors, Manuel Serrano, told me he was working on it when I visited him in his lab in Barcelona in the summer of 2022. He was also getting ready to move to Cambridge and join the hottest startup in all of geroscience: Altos Labs. And yeah, we will definitely get back to discuss Altos as well. But I digress.

In any case there are now twelve hallmarks instead of nine. Was there some fundamental new discovery behind this? Had we acquired some groundbreaking understanding that changed everything?

No, not at all.

The new categories mostly put some emphasis on processes that in the original article were baked in to the other hallmarks. Chronic inflammation, for example, is such a big part of aging that it deserves its own category. Dysbiosis is kinda new, in the sense that it was overlooked in the first paper. But there have been plenty of scientists pointing out that omission ever since.

Ok, so we know what causes us to age and it’s not too complicated. So what?

Well, let me tell you a story about a species that often have a hard time putting two and two together. Let’s call it homo sapiens.

It’s fairly uncontroversial to say that most, if not all, people would rather live in a world where we’d eradicated cancer. And dementia. And heart disease. And all other chronic diseases while we are at it.

It’s also fairly uncontroversial to say that most, if not all, people are in favor of science putting a lot of time, money and effort to find a cure for these diseases. In a time where we disagree on so much else, this is something that unites us. I certainly haven’t seen any activists blocking roads and marching the streets with protest signs decrying the latest immunotherapy (although taking anti-vaxxers into account I guess anything is possible).

We want these diseases about as much as we want a new pandemic.

Now say you want to defeat aging.

Silence. Confusion. Anger. Disbelief. Have you gone off the deep end? What do you mean, defeating aging?

It’s like people believe that those hallmarks af aging exists in one universe and the diseases I just mentioned lives in another.

But no, they are very much part of the same universe. Not only that, but they are in fact more or less the same thing. Nine out of ten people in much of the developed world will die from one of those chronic age-related diseases. These diseases arise from an accumulation of bodily damages. What kinds of damage? Would you care to venture a guess? Yup, the hallmarks of aging.

So if you want to get rid of chronic diseases it stands to reason that you want to defeat aging no matter how hard a time you have to wrap your head around that simple truth.

Let’s play chess with death

Can we do something about the hallmarks? Yes, indeed. This is the fun part.

It’s also the part that in the end defined the structure of my book.

You see, when I first pitched this idea of a longevity book to my publisher, Volante, it was a story about how science finally - and probably pretty soon - is about to...maybe not defeat death at chess, but at least make the game a lot more interesting.

Humanity has dreamt of this since long before science even existed. In fact, you could argue that the dream of eternal youth and immortality laid the foundation for modern science as we know it. The search for the elixir of life was one of the main goals for alchemists. And just as science today are in search for fundamental truths through experiment, so did alchemy (but practitioners of the latter had never heard of peer-review, systematic experimentation and they were very secretive, to put it mildly).

And now it’s within reach. The ageless era. A world where the risk of dying is always extremely low no matter how much time has passed since you were born. This I told my publisher. That more people - everyone, really - needed to know about this. That a growing number of prominent scientists were being increasingly bullish about the prospect of people living well into their 120’s. That there were stunning results in the lab. That the number of startup companies focusing on longevity were exploding. The signals were, to borrow a phrase from the renowned futurist Amy Webb, talking.

And my publisher was excited about the idea! But in a number of meetings kept asking me the same question: what can you do today to increase your chances of living a long time? Finally, they gave me an ultimatum. You can write your book if you yourself for one year change your habits and align with a longevity lifestyle.

The best book for my health, ever

As ultimatums go, this was one of the better ones. First of all my personal health really needed it: I was obese and borderline diabetic when I started. Second of all it gave my book structure, alternating between the small world (my health journey) and the big world (the cutting edge science). It was very inspired by the fantastic book How to Change Your Mind by Michael Pollan (he certainly changed my mind about psychedelics).

More importantly though, it’s all connected. Just like the symbiosis between the hallmarks of aging and the stuff that is going to get us all killed there is a bridge between my small world and the exciting big world.

Consider, for example, that some of the most important discoveries in aging biology has to do with metabolism. If you caloric restrict everything from yeast to mice they live longer. If you knock out genes to kind of emulate the effect of calorie restriction some organisms have longer lifespans. If you inhibit certain central regulators of energy and cell growth through a drug called rapamycin you can even prolong the lives of elderly mice (before this groundbreaking discovery in 2009 it was believed that it was impossible to intervene in the aging process late in life).*

* Also see the Landscape and Recommended sections in this newsletter.

What this means for humans is a little harder to discern but it seems very plausible that a healthy metabolism through nutrition and regular exercise could lead to a longer life. Metabolic syndrome on the other hand - characterized (very simplified, for now) by high blood pressure, high blood glucose and high cholesterol - is considered a fast track to all of our most deadly age-related diseases. In fact, metabolic syndrome probably accelerates all of the hallmarks of aging. And yeah, I ticked all those metsyn boxes.

Now and then

But more than that, the book is trying to bridge the gap between the now and then (to borrow the title of The Beatles’ rather excellent final song).

Peter Attia, the famous M.D. that focuses on the ”applied science of longevity”, has no intention of reaching 120 years of age. His aim is to maintain his health as long as possible and to be able to do most of the things he does today (he just turned 50) in what he calls his ”marginal decade” (a euphemistic way of saying the last decade of his life).

There is a debate raging whether scientists should focus on healthspan (the part of one’s life spent without chronic disease) or lifespan (where we also live much longer compared to today, while maintaining our health).

I don’t know if Peter Attia has taken sides here, but he clearly has opted to not get his hopes up. There is a last decade looming, and he wants to make it the best decade possible. For him, healthspan is the thing to focus on.

Now, the good thing about this is that he doesn’t shy away from thinking about debilitating sickness and death. As a doctor he’s seen plenty of it and he knows that best current methods to stay healthy involves hard work. Most people seem to repress all thoughts of chronic disease until they are so afflicted by it that it has become impossible to ignore. Not a good strategy. Chronic disease is best treated before it has even arrived.

Just like Peter Attia* I nowadays also spend a lot of time investing in my future. I also picture myself as and old person. There are these different scenarios I think of: the debilitated and increasingly forgetful Peter who needs the help of others just to wipe his ass. The independent Peter who can play with his grandkids and go shopping for groceries well into his 90’s, the mind still sharp.

* It should be noted that no one has taught me more about personal health, medicine and biology than Peter Attia. His podcast and the show notes for each episode is a treasure trove of information. And you should read his book too!

And sure, that second scenario is something that motivates me. But there is another one that is even more enticing. It’s the one where I arrive in a world where it is possible to repair most of the damages of aging. Where life expectancy is accelerating faster than the aging process. Where, for every year I live, the risk of dying actually decreases and Gompertz’ law no longer applies. The ageless era.

This idea, that life expectancy rises more than a year per calendar year is famously called longevity escape velocity, often abbreviated LEV. And that is why this newsletter is called LEVITY.

I am fairly certain we will reach this point. I am not at all certain how long it will take. I believe in the exponential, and I think developments in artificial intelligence will usher us into the ageless era sooner than many believe possible (Manifold, though, has longevity escape velocity by 2036 at 13 percent, which seems alright - even I don’t believe it will happen that fast). But I am hedging my bets here. Let’s lead a healthy lifestyle - I might need those extra years later.

Some think that the very concept of longevity escape velocity is absurd. All science fiction. All but impossible.

Three things comes to mind whenever I hear that.

1 All science starts out as fiction, as an idea in someone’s head. As early as 1783 the British scientist John Michell predicted the existence of black holes (he called them ”dark stars”). These ideas languished in obscurity for over a century and it wasn’t until 2019 humanity caught its first glimpse of them thanks to an instantly iconic image. And while the gravitational pull from a black hole means not even light can reach escape velocity, there are no such fundamental limits when it comes to solving aging biology.

Don’t pay too much attention to people who says a certain something is impossible even though this certain something doesn’t violate the laws of physics. Throughout history they have been proven wrong time and time again.

2 Arne Larsson. Born in 1915, technology like in the image below was out of reach for most people (maybe except for the spoon - thanks Dall-E!).

Arne died in 2001, at age 86. By that point we could already see the faint contours of a world that was about to be forever changed. Soon we would have the world’s information always accessible in the palm of our hands. Mere months before Arne passed away the precursor to the Iphone was released.

That Arne lived to see another century was all thanks to technological progress. Had he been born just a decade earlier it would have been all but impossible. At age 43 he was diagnosed with complete heart block with Stokes-Adams attacks. A death sentence were it not for a new Swedish invention: the pacemaker. Arne became the first person in the world to get a fully implantable pacemaker.

Ergo: make sure to be there when new technology arrives and never assume that it won’t arrive just in time.

3 Life expectancy increases by about three months per year. When I was born in 1977 it was estimated that I would live around 72 years. Today life expectancy for men is over 81 years.

In fact, for the past 200 years we have gained around three more months of life per year, almost like clockwork.

Evolution is of course remarkable but it advances at a glacial pace. The dramatic rise in life expectancy for humans since 1800 is something evolution never could muster in such a short time period (or maybe at all, for that matter). It’s all thanks to science and technology.

And if you don’t think that in the age of artificial intelligence, gene editing, dirt cheap genome sequencing, increasingly capable wearables, digital personal twins and all the tantalizing progress being made in geroscience - where scientists are addressing all those hallmarks of aging - will increase life expectancy I don’t know what to tell you. Except to say that you are wrong.

So LEVITY, this newsletter, will, just like my book, be about what I and you can do for our health today. But not because I argue that we should first and foremost focus on healthspan. It’s because, again, we need to make sure to be there when new technology arrives. I consider a great marginal decade a consolation prize.

In time this focus on what we must do to take care of our health will slowly fade away, thanks to new technology and progress in science. And LEVITY will stay on top of all the latest developments.

So if you’re interested in personal health, curious about the future and want to be better educated about were we’re heading I hope you’ll join me.

The ageless era is on the horizon. Let’s get there faster.

Landscape

Landscape is the section where I walk you through the latest news and developments in longevity and everything related to it.

A small step for big dogs, maybe a giant step for mankind

It is sometimes said that we need to change society’s views on aging and death in order to make progress on our way towards an ageless world. But it might be enough to just change the attitude of the FDA. The Food and Drug Administration wields enormous power of not just the U.S. but the entire world. Their counterparts in other states pays close attention to which drugs manages to make it through the eye of the FDA needle. And every major decision they make is scrutinized by media all over the world.

So what medicine company Loyal now has achieved could be very important. To quote CEO Celine Halioua: ”Loyal has earned what we believe is the FDA’s first-ever formal acceptance that a drug can be developed + approved for lifespan extension”.

Now, it must be noted that the FDA has not approved Loyal’s drug. And the efficacy of the drug is yet TBD. And oh, by the way, the drug is meant for dogs.

But what the FDA has done is essentially to give Loyal, as Business Insider put it, a vote of confidence. For a drug that targets lifespan extension. Not cancer or heart disease or cognitive decline. But rather the underlying, more fundamental, causes of those diseases. The hallmarks of aging.

Or, to be more precise, one of the hallmarks of aging: deregulated nutrient-sensing. You see, in dogs (as well as in humans) growth hormone IGF-1 is implicated in aging. And it could be that lower levels of IGF-1 may slow the aging process (it’s a somewhat controversial story, as many things in biology).

What Loyal is aiming for is a drug that lowers IGF-1 in big dogs as they tend to have much shorter lifespans than smaller canines (who, compared to big dogs, are genetically predisposed to lower levels of IGF-1).

Considering that most dog owners view their pet as part of the family the possibility of a lifespan extension drug is big in and of itself. But the biggest takeaway is of course the implications for us humans. The FDA are now signaling a willingness to approve drugs for lifespan extension in man’s best friend. Surely mankind should expect no less.

You can put a prize on health

Considering Peter Diamandis’ interest in longevity one wonders why it took so long. An Xprize that tackles aging has always felt inevitable. Maybe funding was an issue. Now, thanks to Saudi money via Hevolution Foundation, that’s no longer a problem. With $101 million this is the largest competition in Xprize history.

So here’s what you need to do in order to win: develop ”a proactive, accessible therapeutic that restores muscle, cognition, and immune function by a minimum of 10 years, with a goal of 20 years, in persons aged 65-80 years, in one year or less”. And you need to do it by 2030. No biggie.

There is a clear focus on healthspan and not lifespan here. The competition is even called Xprize Healthspan. It’s okay I guess (for better or for worse it’s still a lot more credible in the eyes of many to focus on healthspan). Especially since it looks like they are going about it the right way. From the announcement:

”Traditional medicine only treats one disease at a time and only once symptoms appear, without effectively extending human health. By developing therapeutics that target biological aging rather than disease, we can revolutionize the way we think about and treat aging,” said Jamie Justice, Ph.D., Executive Director of Xprize Healthspan. ”If these trials are successful, we will demonstrate that it is possible to improve health even as we age.”

Gene editing gets to the heart of it

The potential of gene editing is almost limitless. It’s still early days but of all the breakthroughs already happening the possibility of permanently lowering LDL-cholesterol is my favourite. Read about the latest from Verve Therapeutics in the link below.

An exciting rapamycin clinical trial

It’s only my first newsletter and there is rapamycin (see both above and below) all over it. You better get used to that. I was actually just about to hit publish when I learned of the upcoming RAPID clinical trial. It aims ”to evaluate the effectiveness of rapamycin in older adults with periodontal disease, a chronic oral inflammatory disease linked to other age-related conditions such as heart disease, diabetes, and Alzheimer’s Disease”.

Recommended

This section is pretty self explanatory no? In each newsletter I will write about something I read, heard or saw. It could be an old book or a new article hot of the press.

Of mice and men

It is beyond frustrating to learn that the most common mouse model - by far - used in aging studies is, at best, crap. So why are so-called B6 mice so common? Because scientists are familiar with them. Their peers and mentors uses them. And if everybody is using them they must be good, right?

Rich Miller compares this to the behavior of lemmings. Miller is a professor of pathology and the Director of the Center for Aging Research at the University of Michigan. He’s also the one of the architects of the Interventions Testing Program (ITP).

The ITP - which in 2009 found that rapamycin extended the lives of elderly mice - do their studies in a much more rigorous way and they stay well clear of B6 mice.

In a recent episode of the podcast The Drive with Peter Attia you can hear Rich Miller explain why. It’s well worth a listen, especially since there is something almost enchanting about the way Miller talks, and his voice. You automatically pay attention.

(Speaking of ITP they have a new paper out where they show two drugs demonstrating lifespan extension in (male) mice. That’s great news!)

Let’s accelerate rapamycin science!

I’ve signed up for the Rapamycin Longevity Lab. You should too!

Close-up

Close-up is the section where I take you through my own longevity journey. It could be everything from my training regimen, what supplements I take and what I learn about my latest blood work.

I’ve updated my view on protein intake

If you read my book you know that, as I was writing it, I was consuming a vegan diet + fish. I was (and remain) deeply inspired by the work of professor Valter Longo. In his book The Longevity Diet, and supported by his research, he is a proponent of a low protein intake, especially animal protein.

But in time I have become more convinced that strength training and hypertrophy is two of the most important things I can do for my health and so I’ve actually gone in the other direction. Rather than limit my protein intake, I try to consume more than the recommended intake - to support my exercise regimen. Still no meat for me, but today I follow a vegetarian + fish diet.

That’s not to say you can’t get enough protein on a plant-based diet (especially if you also consume fish). But I find my life a bit more simple when I can use eggs, milk and cheese in my cooking.

Anyway, Peter Attia recently wrote an excellent article about the many nuances to consider when it comes to protein intake.

Weird and Wonderful

Well, who isn’t?

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

Just a few things before I sign off:

✍🏼 My aim is for LEVITY to be a biweekly thing for now. We’ll se how it goes. And sometimes I’ll have much to say, sometimes the newsletter will be more of a snack.

🎁 I already have some new sections planned - and I am really excited about them. Keep an eye out for my upcoming newsletters!

🫵🏼 What do you want to know more about? Drop me an email at [email protected]! You can also find me on Linkedin and on X.

📢 Do you want to learn more about personal health, longevity and the ageless era? Sure you do! You can book me for a talk here.

🦾 Since you are interested in science and technology you should bookmark Ny Teknik (it helps if you understand Swedish though). As a reporter at Ny Teknik I cover such things as the telecom industry, AR&VR&MR, quantum computing and artificial intelligence. This year I have written lots and lots and LOTS about AI.

🙏🏼 And finally, hit the subscribe button below! Let’s do this together!