In this week’s newsletter

✅ Introduction to Episode 7 with Mark Hamalainen. ✅ Detailed show notes. ✅ The big bottleneck in longevity research: a lack of data. ✅ Progressive brain replacement. ✅ The very expensive and difficult bioengineering approach. ✅ The roadmap to solving aging. ✅ The mission of The Longevity Biotech Fellowship.

”Don't just optimize your diet and your exercise routine and hope for somebody else to solve the problem for you”

There are countless reasons to admire Mark Hamalainen, and one of them is his brutal honesty. While many longevity influencers confidently declare that longevity escape velocity and indefinite lifespans are just around the corner, you won’t get such easy assurances from Mark.

That’s because, and this might seem counterintuitive at first, he’s one of the most deeply committed advocates for solving aging that I’ve encountered. Mark, a former director of science at Synthego and a former researcher at SENS Research Foundation (Aubrey de Grey has called him his protégé), has dedicated over two decades to tackling humanity’s greatest challenge.

You see, Mark's honesty doesn't stem from pessimism, but from a deep commitment to reality-based thinking. His mission isn’t driven by hype but by a relentless pursuit of tangible progress in the fight against aging.

I first met Mark at the Longevity Biotech Fellowship (LBF) retreat in Sweden in January 2024, where I had the opportunity to witness his vision and dedication firsthand. It left a lasting impression, not only on me but likely on everyone who attended. Here was someone who wasn’t just dreaming about a future where aging is solved - he was meticulously planning it, working hard to remove the roadblocks that stand in the way.

His work with the LBF, the Longevity Acceleration Roadmap, and his broader efforts in the longevity community are all about taking concrete, actionable steps toward a future where the passing of time is not a death sentence - all the while knowing that this goal is one of the most complex challenges humanity has ever faced.

In this episode, Mark discusses several key strategies that he believes are essential to making real progress. These include advancing bioengineering to gain precise control over biological processes, developing comprehensive data sets to better understand aging at a molecular level, and exploring visionary ideas like the replacement strategy. He also highlights the potential of biostasis and cryopreservation as a last resort, potentially offering a way to preserve life until future technologies can fully reverse aging.

So, while Mark may not offer the easy assurances that some in the longevity space do, he offers something far more valuable: a realistic and deeply informed plan of action, a commitment to truth over convenience, and above all, a profound hope that by facing the realities of aging head-on, we can one day overcome them.

You can watch our episode with Mark below or listen to it on Spotify, Apple Podcasts or other places, like PocketCasts. Please follow, like and subscribe! 🙏🏼

A detailed overview of episode 7 with Mark Hamalainen

/

Introduction:

• Mark Hamalainen is introduced as a former director of science at Synthego and a former researcher at SENS Research Foundation.

• Aubrey de Grey has called Mark his protégé.

• Mark has dedicated over two decades to tackling aging, humanity's greatest challenge.

Background and Early Interest in Longevity:

• Mark grew up in Northern Ontario, Canada, with Finnish ancestry.

• His interest in longevity started at a very young age, as he recalls asking questions about death as a child.

• At age 13, Mark read Kim Stanley Robinson's Mars Trilogy, which inspired him to work on long-term projects and live to see their fruition.

• Quote: ”I decided pretty much right then that I would focus on aging first. And so I, as a high school student, got subscriptions to Science, Nature, and the aging journals at the time that existed and all the textbooks I could get my hands on and skipped my classes in order to read these”.

Early Work with Aubrey de Grey:

• Mark discovered Aubrey de Grey's work in the late 1990s, specifically his ”Engineer's approach to anti-aging medicine”.

• Quote: ”Finally, somebody saying something ambitious and not just talking about small tweaks to nutrient sensing genes and invertebrates, which was pretty obvious that that was not the way that we would extend human lifespan to me, even at the time.”

• Aubrey funded some of Mark's undergraduate research projects through the Methuselah Foundation.

Research Focus and Transition:

• Mark's first project focused on lysosomal aspects of aging, looking for enzymes to enhance the ability of lysosomes to break down accumulating substances.

• He later worked on mitochondrial aspects of aging during his PhD, which he ultimately dropped out of due to reproducibility issues in the field.

• Quote: ”I spent two years discovering that none of that work was reproducible. And so I got understandably frustrated and thought that I was manually moving petri dishes of cells from one incubator to another place and manually pipetting. And I just realized that that way of doing research was so slow and error prone that we wouldn't solve this problem in my lifetime if we did things that way. I call it artisanal science.”

Longevity Biotech Fellowship (LBF):

• Co-founded by Mark Hamalainen and Nathan Cheng.

• Merged from two pre-existing programs: Longevity Summer Camp and On Deck Longevity Biotech.

• Has had seven cohorts total, with close to 700 people participating.

• Quote: ”The Longevity Biotech Fellowship's mission is to increase the number of people working on those hard technology development problems, the things that we need, the capabilities that we need if we're going to actually make fast progress in our lifetimes.”

  

  The LBF3 retreat was held in Sweden in January 2024.

Bottlenecks in Longevity Research:

1. Funding

2. Talent

3. Data

   • Quote: ”The number one issue was access to data, actually. So people wanted more large databases, things like the protein databank, which allowed for the AlphaFold to come into existence”.

   • Researchers want aging data, including medical records, multiomics, longitudinal, and phenotypic data.

   • Need for large-scale projects similar to the Human Genome Project.

   • Here’s the full report.

Small Molecules in Longevity Research:

• Mark argues that small molecules have limited potential in solving aging.

• Quote: ”We actually don't include small molecules in our roadmap because we decided to only include technology pathways that in their mature form could plausibly solve aging altogether. And we already know that small molecules can't do that.”

Bioengineering Approach:

• Four major categories in bioengineering:

  1. Data collection

  2. Building models of biology

  3. Design tools for interventions

  4. Delivery methods (gene therapy, cell therapy, etc.)

• Challenges in delivery: biodistribution problem, getting molecular tools to all cells evenly.

• Quote: ”Getting those molecular tools to all of the cells in your body and doing so in an even manner is very important because if say one cell gets a million times the dose of another cell, the probability of the cell that got the million times extra dose having negative side effects is very, very high”.

AI and Computational Tools in Longevity Research:

• Mark emphasizes the importance of computational tools and automation in biology research.

• Quote: ”I think bringing computational tools and automation into biology research is essential in order to make progress at the speeds that matter to us so that will benefit in our lifetimes.”

• Discusses the potential of closed-loop, fully automated research cycles.

• Stresses the need for ongoing training programs for scientists to keep up with new tools and technologies.

The Replacement Strategy:

• Concept of replacing old parts of the body with young ones, similar to maintaining a car.

• Can potentially scale up to full body replacement, except for the brain.

• Quote: ”And by definition, it would be young. And so you wouldn't need any drugs, you wouldn't need any gene therapies, you would just do a body transplant and get a fresh, young body”.

• Challenges include nerve reconnection and cultural acceptance.

• Only about 10-30 people are currently working directly on this strategy for life extension purposes.

Progressive Brain Replacement:

• Based on the brain's plasticity and ability to migrate functions.

• Quote: ”There's proof of concept in mice where they actually have done grafts of cortical tissue and it's been incorporated and it's shown to function and be made use of.”

• Potential for gradual replacement of brain tissue over time.

• Mentions the possibility of cell therapies for replacing glial cells without surgery.

• Mark mentions Jean Hébert as a key figure in the development of the replacement strategy concept:

• Jean Hébert is the author of the book Replacing Aging.

• Mark credits Hébert with presenting a comprehensive case for the replacement strategy

• Quote: ”I think no idea is generated in a vacuum, right? And so I think a lot of the precursors to this idea have existed for a long time, but he was the first one to be very explicit and coherent and comprehensive and presenting the case for this. And his book Replacing Aging, I think does a good job of that."

• Mark mentions that Hébert appeared on the Longevity Acceleration Podcast to discuss these concepts further.

Biostasis and Cryopreservation:

• Mark discusses the potential of cryopreservation as a ”Plan B”.

• Mentions Tomorrow Bio expanding operations to the United States and Canada.

• Quote: ”I think once we've demonstrated full reversibility of cryostasis in an animal, I expect that there'll be quite a flood of interest in cryopreservation at that point”.

• Discusses other forms of biostasis, such as hibernation states, but notes their limitations.

Roadmap to Solving Aging:

• LBF is developing a comprehensive roadmap with three main categories: biostasis, transplant, and bioengineering (more on them above - and below).

• The roadmap aims to provide a coherent overview of different approaches to solving aging.

• Based on surveys and interviews with experts in the field.

• Quote: ”We wanted to create a document and actually like eventually a course, potentially something that could even be taught at universities that would give like a sort of a coherent overview rather than just getting like a random sample of different people's opinions”.

Current State of Longevity Research:

• Mark expresses cautious optimism about progress in the field.

• Quote: ”We've gone from having zero regulatory approved aging interventions to zero regulatory approved aging interventions. And while I think you have to maybe have a little bit of naive optimism in order to have hope on something as difficult as solving aging.”

• Emphasizes the need for faster progress to benefit more people currently alive.

Call to Action:

• Encourages people to actively engage in longevity research rather than just optimizing personal health.

• Quote: ”Don't just optimize your diet and your exercise routine and, and hope for somebody else to solve the problem for you, actually get into the field and get to work because that's what we need is actually people working on this.”

Mark’s request of what to include in the show notes:

• Regarding the Biostasis path of the Longevity Acceleration Roadmap:
  Quote: ”The cryo one is actually going to be available next weekend online [Note: it is available now].

• Regarding undirected screening for DNA-interacting enzymes:

  Quote: ”But more recently, there was a different paper that I could probably look up for you if you want to include in the show notes where people just did like a broad screen looking for any enzyme from bacteria that interacted with DNA.”

More Resources and How to Get Involved:

• Longevity Acceleration Podcast by Mark and Nathan.

• LBF is a volunteer-run 501(c)(3) nonprofit that accepts donations.

• Contact: [email protected]