Sara Hägg, PhD is an associate professor at Karolinska Institutet, where she leads the Molecular Epidemiology of Aging Group. Her work focuses on human biomarkers of aging - especially biological age “clocks” built from epigenetic, proteomic, and metabolomic data - and on turning Nordic registry resources into clinically useful aging measures.

In this episode:

* What biological/epigenetic age clocks actually measure (and what they don’t)

* Accuracy, error bars, and why clocks aren’t clinic-ready yet

* Epigenetic vs. proteomic vs. metabolomic clocks - strengths and trade-offs

* Organ-specific clocks (liver, ovary, kidney) and what they reveal

* Why uncertainty spikes at life transitions; menopause as a natural “stress test”

* PC (principal-component) clocks and noise reduction

* Nordic registry & Swedish Twin Registry advantages; UK Biobank use

* Direct-to-consumer tests: interpreting results and common pitfalls

* AI’s role in building/validating clocks and handling uncertainty

* What would move the field fastest (data, standards, trials) and where Sweden stands

Show notes for this episode will be available after this airs. Sign up for the LEVITY newsletter to get them straight to your inbox: reachlevity.com

LEVITY is co-hosted by Patrick Linden, philosopher and author, and Peter Ottsjö, journalist and author.

CHAPTERS

00:00 Introduction

03:27 Why Sweden lags behind in longevity science

08:04 Nordic registry & Swedish twin registry advantages; UK Biobank use

10:05 What is biological age?

16:33 The rise of epigenetic clocks

24:22 The importance of aging clocks

32:04 Beyond methylation: proteomic and metabolomic clocks

35:12 Organ clocks

39:37 Do aging clocks generalize?

54:37 The cost of aging clocks

01:03:18 Uncertainty and AI

01:17:10 Solving aging - where do we stand?

01:28:10 Book recommendations

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We are always excited about the next technological solution. But what if it does not come? Or what if it comes only for the few, or with terrible side-effects? And while we are waiting for the easy tech fix, are we neglecting what we can do now to better our lives?

Many of our previous guests have been excited about the prospect of radically extending our lives, and some have been optimistic about the prospect of achieving this in our life time, perhaps even within a few decades. We are Levity, the real longevity podcast after all.

Todays guest thinks that we should be less excited about radical longevity, and radical enhancements in general. And he does not think radical life extension is on the horizon.

Nicholas Agar is a New Zealand philosopher specializing in ethics. He holds a BA from the University of Auckland, an MA from Victoria University of Wellington, and a PhD from the Australian National University. As of 2022, he is a Professor of Ethics at the University of Waikato. He is a prolific writer and the author of How to think about Progress, and Truly Human Progress, to mention two recent books.

CHAPTERS

00:00 Introduction

03:38 The hype and the reality

06:02 Too much enthusiasm for radical life extension -- or too little?

17:15 Distribution worries -- more life only for the rich?

23:06 Pessimism about distribution and feasability

29:00 Structural reasons for bad science and big promises

33:30 Is it wise to spend money on radical life extension?

37:13 Should we die if we have had good life?

48:48 Deat as tool for solving housing crisis

58:27 Liberal eugenics

01:06:45 How to attract funding -- hype + conservative grant proposals

01:09:40 What is enhancement?

01:25:30 A mechanical Roger Federer with robot arms

01:38:12 Is it bad to cease to exist?

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One idea I’ve had lately is to put together a list of people to trust in geroscience and the longevity field more broadly. (And I might do it - keep an eye on reachlevity.com

- and subscribe while you’re at it!)

Matt Kaeberlein would not only make that list - he’d likely be right at the top. He’s rigorous, precise in his wording, and always puts integrity ahead of hype. But, and this is important, I wouldn’t characterize him as a skeptic. He’s a realist who insists on evidence, yet at the same time he’s visionary and deeply optimistic about what aging science can deliver.

Matt is probably best known for his pioneering work on rapamycin and for co-founding the Dog Aging Project. In this episode, though, we also talk about Optispan - his proactive healthcare company - and Ora Biomedical, where the WormBot platform is screening thousands of interventions for effects on lifespan. We get into therapeutic plasma exchange (TPE), how artificial intelligence might accelerate discovery, and even his favorite science fiction books.

And true to form, Matt doesn’t hold back. He calls out irresponsible use of biological age tests - going so far as to label it “medical malpractice” - and criticizes hype-driven actors, sloppy science communication, and the inertia of institutions like the NIH. At the same time, he shows how rigorous, honest work could move the entire field forward.

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Show notes for this episode will be available soon after this airs. Sign up for the LEVITY newsletter to get them straight to your inbox: reachlevity.com

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CHAPTERS

00:00 Teaser

01:38 Introduction to Dr. Matt Kaeberlein

11:50 mTOR and rapamycin

21:37 The Dog Aging Project

51:08 Personal experiences with rapamycin

01:05:33 The inertia of the NIH

01:08:54 The right to try law and access to experimental therapies

01:13:21 Ora Biomedical and The WormBot Platform

01:21:41 The role of AI in longevity research

01:28:29 Optispan: A new approach to proactive healthcare

01:33:56 Biological age tests

01:39:39 Therapeutic plasma exchange: A personal experience

01:46:39 Book recommendations

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When you give a child a pet, you also expose them to death—since most pets pass away long before their owners. But what if we could cryopreserve Buddy or Tiger, and bring them back from suspended animation once we have a cure for what ended their lives?

Kai Micah Mills is a pioneering figure in radical life extension and biostasis. As the founder of Cryopets, he is leading efforts to make cryopreservation accessible for pets, with aspirations to extend these technologies to humans. He left high school early to pursue entrepreneurship, becoming a tech entrepreneur in his teens. A Thiel Fellow and co-founder of CryoDAO and HydraDAO, Kai is deeply involved in decentralized science initiatives aimed at advancing longevity research.

00:00 Introduction

04:44 Timeship in Texas

05:36 Vitalism

11:54 Bryan Johnson, Mormonism and Vitalism

18:25 Dropping out of highschool to play video games

24:25 Becoming a Thiel Fellow

40:37 Why Cryonics?

49:53 We want Immortality

53:19 Cosmism

01:01:36 AI

01:05:47 Building Cryopets

01:27:42 Cryonics science

01:37:24 Cryo rat

01:46:01 CryoDAO HydraDAO and replacement

01:59:30 Talent shortage in cryogenics

02:05:08 Book recommendations

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As you may have heard, AI-designed medicines have crossed a historic line. In this episode, Alex Zhavoronkov - CEO of Insilico Medicine and founder of ARDD walks us through how Insilico’s rentosertib became the first AI-generated small molecule with peer-reviewed clinical efficacy, while arguing against AI hype and reminding us that biology still moves at “the speed of traffic.” That duality runs through the whole conversation. On one side: a pragmatic operator obsessed with credible science, biomarkers, and clinical benchmarks; on the other: an AI visionary investing in cryonics, sketching “pharmaceutical superintelligence,” and thinking in decades, not quarters.

We start in Basel, home to Roche and Novartis, where ARDD was born, then trace how the conference morphed into a ”high-signal filter for longevity” - packed with startups (who also fund it), hard data, and mainstream pharma.

Alex looks back at his 2014 Nvidia talk (”Can Nvidia solve aging?”) and explains why Insilico trains its AI to learn age first - so it actually grasps biology. Years of problem-solving with pharma turned into their Pharma.AI toolkit (Biology42, Chemistry42, Medicine42, Science42).

Insilico now runs 40+ programs and in an early Phase 2 study for idiopathic pulmonary fibrosis (IPF), their drug rentosertib showed a dose-dependent boost in lung capacity.

Compared with the old path - often $150–200M and ~5 years just to pick a lead molecule - Insilico says it can often reach that point for under $3M or even less. Still, Alex is cautious: no matter how smart the AI gets, real-world testing and regulation won’t speed up overnight.

Also in this episode:

What made Alex cry.

Why he wouldn’t give his own drug to patients - yet.

How a mirror on a conference poster led to a proposal.

How ARDD became the “WEF of longevity”.

Why internal “kill teams” try to stop their own drug candidates.

Why labeling aging a disease helps - but won’t shortcut approvals.

Why he writes to “feed AI”.

How Nvidia threads through the story - from free GPUs to Jensen’s video.

🚀 Special offer for our LEVITY audience: Join Vitalism today and receive a 30% discount on your membership using the code LEVITY at checkout. https://www.vitalism.io/membership

Show notes for this episode will be available soon after this airs. Sign up for the LEVITY newsletter to get them straight to your inbox: reachlevity.com

LEVITY is co-hosted by Patrick Linden, philosopher and author, and Peter Ottsjö, journalist and author.

CHAPTERS

00:00 – Teaser

03:08 – Introduction to Alex Zhavoronkov

06:11 – Alex talks ARDD

15:15 – Big-pharma starting to embrace ARDD

17:31 – The proposal story

24:52 – Why Alex decided to fight aging

27:44 – Neuralink, humanoids and the brain-aging bottleneck

30:52 – Keeping ARDD pharma-credible

32:02 – The path to Insilico

48:03 – The Zhavoronkov crystal ball

57:29 – The Insilico platform

1:07:16 – The rentosertib story

1:16:42 – What made Alex cry

1:17:44 – Aging-as-disease: rhetoric vs. regulation (GLP-1 analogy)

1:26:53 – Culture check: Middle East momentum, China’s stance

1:34:28 – Costs & timelines: what AI compresses - and what it can’t

1:41:30 – Insilico’s fully automated lab

1:47:21 – “I respect Demis, but…”

1:51:10 – Why even superintelligence won’t skip clinical validation

1:52:15 – Cryonics as plan B: organ preservation, TimeShift, use-cases

2:00:56 – Writing Forever AI & the roadmap to “pharma superintelligence”

2:06:42 – Book recommendations

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Anyone who is interesed in emerging science and futurism will come across the name Natasha Vita-More; a suggestive name for a charismatic and important philosopher and artist envisioning human possibilities. She wrote the Transhuman Manifesto in 1983. But did you know that she has also made a scientific discovery with big implications for cryopreservation?

Natasha Vita-More is a trailblazing futurist, acclaimed author, and pioneering designer whose work stands at the thrilling intersection of science, technology, and art. Renowned for her visionary contributions to transhumanism and human enhancement, she has spent decades exploring how we can transcend biological limitations and reimagine what it means to be human. From her iconic “Primo Posthuman” prototype to her influential writings on life extension and ethical AI, Vita-More has inspired global audiences to think boldly about the future.

🔍 In this conversation

✅ Experiment show that memory can survive cryopreservation

✅ The origin of transhumanism

✅ What is stoic extropianism?

✅ Pragmatic optimism and the concept of progress

✅ How to feel and look great past 70

✅ AI and the way to superlongevity

✅ The bottlenecks for nanotechnology as a tool for health and longevity

✅ Books that we need to read

CHAPTERS

00.00 Introduction

04:27 Scottsdale Arizona

05:21 Making a scientific discovery: memory survives cryonics

16:13 The making of Natasha Vita-More

33:00 Humanity+ and its critics

41:04 Writing the Transhumanist Manifesto & origin of futurist movements

50:58 Transhumanism today

57:13 The soul of transhumanism - troubles with the concept of progressive

01:04:05 Stoicism and extropy

01:06:12 Knowing what you can change

01:17:04 Solving aging with AI?

01:24:29 Pragmatic optimism

01:27:38 Hope and science

01:34:50 Staying healthy and alive

01:45:15 Bottlenecks for nanotechnology

01:50:50 3 books we have to read

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Even though it’s undeniably...aesthetic-challenged, the naked mole-rat is the envy of the longevity world. Its risk of death barely changes with time; it shrugs off cancer, stays fertile for decades and seems to skip every hallmark of aging that hobbles the rest of us.

But why? What evolutionary forces gave a mouse-sized, subterranean rodent near-immunity to aging - and what can its biology teach us about extending healthy human life?

Comparative biologist Prof. Rochelle Buffenstein (University of Illinois Chicago) - who has maintained the world’s largest captive colonies and authored 200+ papers - joins LEVITY to dissect the evidence.

In this episode

✅ Rochelle’s journey: from Zimbabwe farm kid to the pre-eminent naked mole-rat researcher.

✅ Eusocial society: queens, worker castes and lethal succession battles.

✅ No Gompertz slope: hard numbers that show mortality risk stays essentially flat for 40 years.

✅ Cancer resistance → high-molecular-weight hyaluronan, unusual immune cell profiles.

✅ Telomere maintenance and DNA-methylation reversal.

✅ Proteostasis on easy-mode: slow translation, durable proteins, super-charged autophagy.

✅ What actually kills a mole-rat?

✅ Translational angles: small-molecule screens, CRISPR edits, and why funding is still an uphill battle.

✅ Other long-lived species worth studying - and how young scientists can break into comparative gerontology.

🚀 Special offer for our LEVITY audience: Join Vitalism today and receive a 30% discount on your membership using the code LEVITY at checkout. https://www.vitalism.io/membership

Show notes for this episode will be available soon after this airs. Sign up for the LEVITY newsletter to get them straight to your inbox: reachlevity.com

LEVITY is co-hosted by Patrick Linden, philosopher and author, and Peter Ottsjö, journalist and author.

00:00 Teaser

02:37 Meet Prof. Rochelle Buffenstein

07:04 Naked mole-rats crash course

10:23 Eusocial life: Queens, workers, death matches

11:46 Extreme underground lifestyle (Low O₂, High CO₂)

18:12 Problems with inbreeding?

26:07 Don’t call them cold-blooded!

29:15 Keeping the world’s largest colony of naked mole-rats

31:45 Eating naked mole-rats

36:01 Lifespan of the naked mole-rat

38:20 Two remarkable papers

50:53 How long can they live?

52:45 Resistance to cancer

57:03 The Hallmarks of aging are no match for this rodent

59:48 Surprising immune defense

01:04:18 What’s the evolutionary rationale?

01:10:08 Translating the research

01:18:51 Other longevity champions

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🎁 Our giveaway is live!

10 winners will receive FMD kits from Prolon. It’s free to enter – just follow the link below 👇

https://gleam.io/NaVa0/prolon-fasting-mimicking-diet-giveaway

🔬 Can food rejuvenate you from within?

In this special episode of LEVITY, Peter talks with Andrea Ghirardi, CEO of L-Nutra Europe — the company behind Prolon, the fasting-mimicking diet (FMD) developed from Dr. Valter Longo’s research.

🧠 We cover:

– How Prolon mimics fasting without starvation.

– Real-world results: 2.5 years bio-age reversal.

– Why FMD may beat GLP-1 drugs for long-term health.

– What’s inside the new NextGen kit.

– Prolon’s potential as a medical treatment.

📘 Dive deeper with our companion article:

https://reachlevity.com/p/the-fasting-mimicking-diet-explained-5ce17b65d00c14c1

💌 Our newsletter: Weekly biotech + aging breakthroughs:

https://reachlevity.com/subscribe

LEVITY is co-hosted by Patrick Linden, philosopher and author, and Peter Ottsjö, journalist and author.

Note: Nothing in this post or episode is medical advice. We're not doctors. Before trying this, you should consult your physician. Prolon is not intended to diagnose, treat, cure or prevent any diseases.

CHAPTERS

00:00 Teaser

00:41 A message from Peter

02:35 Introduction to L-Nutra and Andrea Ghirardi, CEO

05:02 What is the fasting-mimicking diet?

07:23 The clinically validated formulation

08:32 The formation of L-Nutra

13:22 How does FMD compare to other fasting methods?

18:07 Are weight-loss drugs a tough competitor to Prolon?

20:05 What's inside the 5-day Prolon kit?

22:54 The next-gen formula

25:41 Peter's and Andrea's experience of trying the FMD

28:23 FMD studies

35:15 The future of FMD and L-Nutra

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When is someone really dead? What does it mean to survive? Is mind-uploading really a possible future way of surviving? These are some of the questions we are discussing with Dr Ariel Zeleznikow-Johnston.

Dr Ariel Zeleznikow‑Johnston is a neuroscientist and Research Fellow at Monash University in Melbourne, Australia, whose work delves into the neural basis of consciousness - from understanding how genetics and environment shape cognition to exploring the subtle qualities of perceptual experience such as color qualia. A 2019 PhD graduate from The University of Melbourne, he has published extensively on how cognitive function changes across the lifespan.

He is the author of The Future Loves You: How and Why We Should Abolish Death, which advocates for brain preservation technology as a means to suspend death and revive individuals in the future.

Check out Peter's review of the book here: https://reachlevity.com/p/a-clear-case-for-cryonics-a-review-of-the-future-loves-you

His multidisciplinary approach combines rigorous neuroscience with philosophy and ethics, positioning him at the forefront of contemporary debates about identity, mortality, and the future of human life.

🔍 In this conversation:

✅ When do we consider someone to be dead?

✅ What is vitrifixation?

✅ Cryonics.

✅ Palliative philosophy.

✅ Personal identity and the connectome.

✅ Are neurons the same over time?

✅ Teleportation as a test of the information view of personhood.

✅ How do we make the future love us?

✅ Survival and medical priorities.

🚀 Special offer for our LEVITY audience: Join Vitalism today and receive a 30% discount on your membership using the code LEVITY at checkout. https://www.vitalism.io/membership

🚀 Show notes for this episode will be available soon after this airs. Sign up for the LEVITY newsletter to get them straight to your inbox: reachlevity.com

🚀 LEVITY is co-hosted by Patrick Linden, philosopher and author, and Peter Ottsjö, journalist and author.

CHAPTER

00:00 Intro

03:45 Jonathan is 190-years-old

07:00 Learned helplessness

10:00 Incoherent medical strategies

11:30 Aging is unhealthy

14:22 Palliative philosophy

20:44 The book in brief - how to cheat death

23:30 Different ways of biostasis - vitrifixation

35:01 Digital snap-shot emulation of our essense

37:59 What is a person? Connectome preservation

43:30 Do neurons stay the same over a life?

47:00 Is mind-uploading preserving personal identity?

01:03:52 We are not our brain - is the connectome model a dualist view?

01:07:50 Teleportation and survival I

01:14:19 Duplicate myself to increase utility

01:15:31 Teleportation and survival II

01:24:30 "Dead people" may not be dead

01:33:30 Saving lives by biostasis brainpreservation

01:36:04 Priority of medicine

01:38:05 Saving everyone that can be saved

01:40:07 Justice and survival - an unusual angle

01:43:36 What kind of world will we wake up to?

01:44:48 How to make the future love us

01:44:59 What are the odds of today's cryonics working?

01:49:10 What year is resurrection?

01:56:33 Ariel's book recommendations

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Just about the hottest thing in longevity science right now is partial reprogramming - using Yamanaka factors to rewind the biological clock in our cells. Billion-dollar giants like Altos, Retro and New Limit are betting on it.

But in this episode a far smaller player, Shift Bioscience, argues that the field may be looking in the wrong place. CEO Daniel Ives explains how his team used AI-powered virtual cells to uncover a single gene that seems to match OSK-level rejuvenation without the tumor risk that haunts classical reprogramming - and why their just-released data could change the game for aging research.

🔍 In this conversation

✅ Daniel’s journey from mitochondrial PhD work to founding Shift Bioscience.

✅ Why Yamanaka-factor–based partial reprogramming excites the field and why it’s inherently risky.

✅ Epigenetic clocks 101 — Horvath, single-cell versions, and what they really measure.

✅ Building AI “virtual cells” (transformers / GNNs) to run millions of in-silico experiments.

✅ Discovery of new rejuvenation factor sets - including SB000, a lone gene that rejuvenates without inducing pluripotency.

✅ Early wet-lab validation across fibroblasts & keratinocytes; next-step mouse studies already under way.

✅ How inhibition targets (not just over-expression) could slash timelines from 15 years to ~5 years.

✅ Mapping a “risk landscape” of age-linked diseases and why fibrosis may be the fastest clinical entry point.

✅ Funding Shift: from personal redundancy money to a $16 M seed and the next raise.

✅ Timelines, escape-velocity hopes, and where cryonics still fits.

✅ What Daniel would ask Jeff Bezos, and why the pharma ecosystem needs to “plug in” now.

🚀 Special offer for our LEVITY audience: Join Vitalism today and receive a 30% discount on your membership using the code LEVITY at checkout. https://www.vitalism.io/membership

🚀 Show notes for this episode will be available soon after this airs. Sign up for the LEVITY newsletter to get them straight to your inbox: reachlevity.com

🚀 LEVITY is co-hosted by Patrick Linden, philosopher and author, and Peter Ottsjö, journalist and author.

CHAPTERS

00:00 Introduction to Daniel Ives

05:34 The Evolution of Shift's Focus

13:25 Understanding Aging Clocks

19:28 Commercial Clocks is ”Mostly Entertainment”

21:03 A Pivotal Meeting with Steve Horvath

24:35 A Brief Crash Course in Yamanaka Factors

28:16 Finding Something Better Than Yamanaka Factors

33:20 The Origin Story For This Approach

36:50 What Does Shift’s New Results Show?

37:33 Defining the Virtual Cell in This Context

44:22 The Gene is Called SB000

46:45 “This Could be Hugely Important”

01:01:44 Speeding up Drug Development with AI

01:11:12 What do Investors Say?

01:17:15 What Daniel Hope Will Happen Next

01:19:34 What Would Daniel Ask of Jeff Bezos?

01:27:00 Why is the company called Shift?

01:32:55 The Pride Day for Closeted Aging Biologists

01:42:28 How Should We Think About Cryonics?

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