Note: Extremely grateful for Geltor (http://geltor.com/) for sponsoring this podcast, and for the founder of it (https://www.linkedin.com/in/alexanderlorestani) for reaching out to make to start with! Geltor produces designer proteins for beauty and wellness.

The current in-vogue thing to do for most longevity companies is to go for cellular reprogramming. As in, fill a cell with the right transcription factors needed to reduce epigenetic noise, restore mitochondrial dysfunction, and so on. I’ve written about the promise there before, it’s definitely an exciting field.

So, when I first met Alan— who told me that he was a longevity researcher — last October, I naively assumed he was also on the reprogramming train. But he told me that he was investigating something a bit different. His pitch was that, instead of reprogramming the cell to fix age-related damage, what if you just protected it from (genetic) insult first? It’s an obvious idea, but one that I’d never really deeply considered. He sold me on the concept, and I was very curious to hear what he’d do next to push it forwards.

A few months after our chat, he spun up a company to pursue this line of thinking: Permanence Bio, which develops molecules that stabilize/protect the genome. They are just about eight months old, but there are already some exciting results coming out. I’m a sucker for people doing ‘contrarian research in consensus fields’, and I immediately knew I wanted to have Alan on the podcast. He graciously agreed and, during my trip to SF last month, we sat down and talked for a few hours.

In this episode, we talk about why DNA protection is so important, what indications is it useful for, how to mentally conceptualize the idea of a molecule ‘stabilizing’ a genome, what it was like to raise money for a company pursuing such an out-of-distribution thesis, and lots more.

Finally, Alan has a really great blog (something I mention in the video), and I wanted to attach a much longer article he’s written about the topic here.

[00:00:00 ] Teaser clip

[00:01:39 ] Introduction

[00:07:32 ] What is Permanence working on?

[00:11:48 ] What does DNA protection actually look like?

[00:27:12 ] Why is DNA protection not focused on as much?

[00:41:03 ] The utility of epigenetic clocks

[00:46:47 ] Do you need multimechanism approaches for longevity?

[00:51:58 ] Longevity outside of DNA protection

[00:55:57 ] What's going on inside of Permanence?

[01:05:54 ] How could Permanence fail?

[01:09:03 ] How do you stay optimistic?

[01:10:26 ] Why work on aging?

[01:15:26 ] What are you bearish on?

[01:19:12 ] Weirder types of aging beyond 110

[01:21:37 ] How did you decide on DNA protection and what else would you have done?

[01:25:27 ] What was it like raising money?

[01:31:48 ] What do you think of past cancer prevention trials?

[01:34:12 ] What does good wet-lab talent look like?

[01:37:02 ] What does your information diet look like?

[01:40:06 ] What's it like going from research to being a CEO?

[01:42:20 ] What happens after cancer prevention for Permanence?

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