In partnership with

In this week’s newsletter

✅ Why are we not talking about the ”other” amyloid? ✅ What a woolly mouse could mean for longevity. ✅ One of the most important companies in the world. ✅ Insilicos AI drug has anti-aging properties. ✅ Say hello to our next guest on the LEVITY podast.

🤙🏼 Want to connect? Add me on LinkedIn. 🙏🏼 Not subscribed to the LEVITY podcast on Youtube yet? Do it here. 🎧 More of a listener? The LEVITY podcast is also available on Spotify, Apple Podcasts and other places.

Looking for unbiased, fact-based news? Join 1440 today.

Join over 4 million Americans who start their day with 1440 – your daily digest for unbiased, fact-centric news. From politics to sports, we cover it all by analyzing over 100 sources. Our concise, 5-minute read lands in your inbox each morning at no cost. Experience news without the noise; let 1440 help you make up your own mind. Sign up now and invite your friends and family to be part of the informed.

Subscribe to 1440 today.

Sorry for the slight delay with the newsletter - I was out most of last week with the flu, which has been running rampant in Sweden.

That said, you’re getting two newsletters this week! After this one, I’ll be sending an introduction and show notes for our next guest on the LEVITY podcast (scroll down to find out who it is).

Now, let’s get to the good stuff!

Gene editing could spell the end for heart disease

Ever since I first learned about Verve Therapeutics - and researched and wrote about it in my book, Evigt Ung - I’ve believed it's one of the most important companies in the world today. Yet chances are, you've never heard of them.

Let me back up a bit.

PCSK9 (Proprotein convertase subtilisin/kexin type 9) is an enzyme encoded by the PCSK9 gene. Variations in this gene can dramatically affect heart health: some mutations increase the enzyme’s activity (gain-of-function), while others reduce it (loss-of-function). Which version you inherit can literally mean the difference between life and death.

Gain-of-function mutations increase the risk of an early heart attack, while loss-of-function mutations offer robust protection for our heart.

People with familial hypercholesterolemia carry the harmful type of PCSK9 mutation. In Sweden alone, around 50,000 people are estimated to have this hereditary condition, yet only about 2,000 have been diagnosed. Tragically, for many, the first indication of the disease can be a fatal heart attack.

When PCSK9 is in ”turbo mode”, the body's ability to remove LDL (low-density lipoprotein), often referred to as ”bad cholesterol”, from the bloodstream is severely impaired. As a result, cholesterol accumulates within the arterial walls, promoting atherosclerosis. On the other hand, when PCSK9's activity is reduced, LDL cholesterol can be more effectively cleared from the blood. In fact, the loss-of-function mutation acts almost like a superpower for heart protection.

In 2003, a team of French researchers discovered that people with familial hypercholesterolemia carry a gain-of-function mutation in the PCSK9 gene. Building on this finding, researchers Jonathan Cohen and Helen Hobbs at the University of Texas Southwestern Medical Center in Dallas set out to explore PCSK9 further. Analyzing data from multiple heart studies, they made a discovery: many African Americans carry a loss-of-function mutation in PCSK9, which results in LDL cholesterol levels that are, on average, 40% lower - and an astonishing 88% reduction in heart disease risk. This protection persisted even among individuals with high blood pressure, diabetes, or a history of smoking.

By 2015, the first PCSK9 inhibitors became available, offering a new treatment option for those who couldn't tolerate statins or needed additional cholesterol-lowering effects. While these drugs have undoubtedly saved lives, they come with drawbacks: they’re expensive and require ongoing injections. More critically, even with PCSK9 and other inhibitors, heart disease remains the world’s leading cause of death - because these treatments simply don’t lower LDL enough for some people.

Sekar Kathiresan believes there’s a better solution: permanently silencing PCSK9 using gene editing. For him, this mission is deeply personal. A cardiologist and geneticist formerly at Harvard Medical School, Kathiresan lost both his brother and uncle to heart attacks at a young age. He manages his own risk with medication and a healthy lifestyle, but if the company he founded - Verve Therapeutics - succeeds, soon we may not need to.

By altering just a single letter in the PCSK9 gene, Verve Therapeutics aims to eliminate its harmful effects and provide a permanent reduction in LDL cholesterol - a true ”one-and-done” procedure, as Sekar Kathiresan calls it.

In July 2022, Verve announced a historic milestone: the treatment of its first patient in New Zealand as part of an ongoing clinical trial. This patient, diagnosed with familial hypercholesterolemia, became the first person in the world to have their PCSK9 gene edited.

It's worth pausing to appreciate the magnitude of this breakthrough. When Verve tested this approach in monkeys, LDL cholesterol levels dropped by 60%, and - crucially - the effect has not faded over time. If these results translate to humans, we may be on the verge of curing heart disease with a single treatment.

And it could be affordable. Verve’s method delivers genetic instructions via lipid nanoparticles, a process similar to the mRNA vaccines used against Covid-19.

”At scale, mRNA packaged in a lipid nanoparticle can be made cost-effectively (100ug of this product can be made for about $5)”, Kathiresan wrote on X.

For now, Verve’s first target is the 34 million people worldwide with familial hypercholesterolemia, but the ultimate goal is far bigger: a treatment for everyone at risk of heart disease - which, realistically, means all of us.

2025 could be a transformational year for Verve, according to Kathiresan. In the second quarter, the company will reveal initial data from its Phase 1 trial. Depending on the results, the pharmaceutical giant Eli Lilly may opt to join Verve in co-funding the worldwide development of this groundbreaking treatment.

Speaking of Lilly, the company is already collaborating with Verve on another program aimed at inactivating the LPA gene to reduce Lp(a) levels. Lipoprotein(a) is a genetically determined variant of LDL and an independent risk factor for cardiovascular disease - meaning your standard cholesterol panel could look perfectly normal, yet you could still suffer a sudden heart attack. Current treatments for high Lp(a) are extremely limited.*

* We recently had longevity doctor David Luu on the LEVITY podcast, where he spoke about his own high Lp(a) levels.

By now, you can probably see why I consider Verve to be so important. And I’m not alone - renowned cardiologist Eric Topol has echoed this sentiment, saying, ”Of all the gene-editing projects, this is the one that can make the biggest impact given how many people would benefit from it.”

News from around the longevity and health space.

”We could already be on the way to 120-year lifespans”

Longevity investor Karl Pfleger wants you to spend less time obsessing over Bryan Johnson's regimen and more time focusing on ATTR (transthyretin amyloidosis). ATTR involves the harmful misfolding of the transthyretin protein, resulting in amyloid deposits primarily affecting the heart and nerves. Newly approved therapies effectively slow ATTR progression by stabilizing or reducing transthyretin production.

Pfleger points out that ATTR is intimately connected to loss of proteostasis - one of the core hallmarks of aging. He emphasizes the implications for aging science (I have edited it slightly for clarity):

”Proteostasis is an aging hallmark, SENS area, and pillar. [ATTR] controls mortality of the oldest humans. We have proven approved treatments and potential diagnostics. We could already be on the way to 120-year lifespans. Why is this not talked about more?”

Worth your time.

Expanding a DNA strand and blowing my mind

Next-generation sequencing with unprecedented speed, scalability, and efficiency? Yes, please. But what truly floored me was the technology behind it - developed by healthcare giant Roche. Just watch the video below - I promise, it’s worth it.

What I’ve been up to lately.

My article about Insilico was published - but the story continues

I’ve been wanting to write about AI drug development startup Insilico Medicine for some time, and late last year, I finally got the chance to interview CEO Alex Zhavoronkov. Now, the article has been published (in Swedish). Hopefully, we’ll also have Alex on the LEVITY podcast soon.

Alex, as you might know, is a dedicated longevity advocate, deeply involved in both AI-driven drug discovery and the broader effort to solve aging. He organizes the ARDD conference in Copenhagen each year and has recently launched a cryonics project.

Since I filed the story there’s been a new development: the TNIK inhibitor that Insilico has in clinical trials (targeting idiopathic pulmonary fibrosis) has also shown anti-aging potential. More specifically, it appears to act as a senomorphic* agent, helping to reduce the senescence-associated secretory phenotype (SASP) - a driver of cellular senescence, which is a key hallmark of aging.

* Senotherapeutics come in two classes: senolytics, which selectively kill senescent cells, and senomorphics, which attenuate the SASPs.

Here’s a sneak peak of our next episode

Our guest this time is the lovely, funny and scarily smart futurist Anders Sandberg. We talk about the risk of humanity going extinct soon, the rise and rise of artificial intelligence and why we should upgrade our bodies and minds. It will premiere on Youtube or where you listen to podcasts on Tuesday, March 11, 6 pm CET.

Beyond it’s cute exterior the woolly mouse could be a game-changer for longevity

The woolly mouse: indeed both weird & wonderful. On the path to de-extinct the woolly mammoth* biotech startup Colossal has designed a very cute proof-of-concept. The mice have striking phenotypes - curly, textured, golden-brown, and woolly coats. Naturally, people are already asking if they can keep them as pets (they cannot).

But this wasn’t just a cosmetic experiment. The goal was to engineer traits that helped mammoths thrive in cold environments. In addition to their woolly fur, the mice were also edited for changes in lipid metabolism - another key adaptation for surviving harsh climates.

For Colossal, this marks a, well, colossal step forward. However, not everyone is convinced. Many scientists remain skeptical, arguing that Colossal’s claims are more hype than substance, while some raise concerns about animal welfare.

I’ll leave that debate to others.

What intrigues me most is what this experiment reveals about the cutting edge (pun intended) of gene editing. The woolly mouse represents significant technical milestones.

Colossal successfully executed multiplex gene editing, making precise modifications to multiple genes simultaneously, while minimizing off-target effects and leveraging precision base editing.

This is the direction we’re heading. Aging-related diseases are complex, and if we hope to combat them through gene editing, single-gene interventions won’t cut it (pun again intended).

Even Colossal CEO Ben Lamm acknowledges the broader implications. In an interview with Longevity Technology, he stated:

”Colossal is currently focused on applying its technology to animal species (both extinct and endangered). However, we believe the advancements made through our research have the potential to impact human healthcare in the future, among those areas of application are healthspan and longevity research.”

* What Colossal hope to achieve is an Asian elephant with mammoth-like traits.

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