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Dwarkesh Podcast

Evolution designed us to die fast; we can change that — Jacob Kimmel

21 Aug 2025

Transcription

Full Episode

0.149 - 11.631 Dwarkesh Patel

Today, I have the pleasure of chatting with Jacob Kimmel, who is president and co-founder of New Limit, where they epigenetically reprogram cells to their younger states. Jacob, thanks so much for coming on the podcast. Thanks so much for having me. Looking forward to the conversation. All right.

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11.972 - 26.979 Dwarkesh Patel

First question, what's the first principles argument for why evolution just like discards that so easily? Look, I know evolution cares about our kids, but if we have longer, healthier lifespans, we can have more kids, right? Or we can care for them longer. We can care for our grandkids.

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27.66 - 37.075 Dwarkesh Patel

So is there some pleiotropic effect that anti-aging medicine would have, which actually selects against you staying young for longer? Mm-hmm.

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37.055 - 52.921 Jacob Kimmel

Yeah, so I think there are a couple different ways one can tackle this. One is you have to think about what's the selective pressure that would make one live longer and encode for higher health over longer durations. Do you have that selective pressure present? There's another, which is are there any anti-selective pressures that are actually pushing against that?

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53.302 - 68.385 Jacob Kimmel

And there's a third piece of this, which is something like the constraints of your optimizer. If we think about the genome as a set of parameters and the optimizer as natural selection, then you've got some constraints on how that actually works. You can only do so many mutations at a time. You have to kind of spend your steps that update your genome in certain ways.

68.986 - 83.447 Jacob Kimmel

So tackling those from a few different directions, like what would the positive possible selection be? As you highlighted, it might be something like, well, if I'm able to extend the lifespan of an individual, they can have more children, they can care for those children more effectively, that genome should propagate more readily into the population.

83.427 - 98.986 Jacob Kimmel

And so one of the challenges then, if you're trying to think back in sort of a thought experiment style of evolutionary simulation here, would be what were the conditions under which a person would actually live long enough for that phenotype to be selected for and how often would that occur?

99.527 - 112.729 Jacob Kimmel

And so this brings us back to some very hypothetical questions, things like what was the baseline hazard rate during the majority of human and private evolution? The hazard rate is simply, what is the likelihood you're going to die on any given day? And that integrates everything.

112.769 - 125.078 Jacob Kimmel

That's like diseases from aging, that's getting eaten by a tiger, that's falling off a cliff, that's like scraping your foot on a rock and getting an infection and dying from that. And so from the best evidence we have, the baseline hazard rate was very, very high.

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