Jacob Kimmel: belief

Transcript context

…I love this idea of aging as a length regularizer. People might be familiar with the idea that when companies are training models, they'll have a regularizer for, “You can do chain of thought, but don't make the chain of thought too long.” You're saying how many calories you consume over the course of your life, is one such regularizer? That's interesting. The third point was... The third piece is basically optimization constraints. So this is where another ML analogy is helpful. Well, actually a two-layer neural network is technically a universal approximator, but we can never actually fit them in such a way. Why does that occur? People will wave their hands, but it basically comes down to the fact that we don't really know how to optimize them, even if you can prove out in a formal sense that they are universal approximators. I think we have similar optimization challenges with our genome as the parameters and evolution as the optimization algorithm. One of those is that your mutation rate basically bounds the step size you can take. So if you imagine that at each generation, you get some number of inputs, you can select for some number of alleles. The max number of variations in the genome is set by your mutation rate. If you dial your mutation rate up too high, you probably get a bunch of cancers, so you're selected against. If you have it too low, you can't really adapt to anything. You end up with this happy medium, but that limits your total step size. Then the number of variants you can screen in parallel is basically limited by your population size. So for most of evolution, there are lots of forces constraining population size as well. One of the dominant sources of selection on the genome is really prevention of infectious disease. It seems like when you study the history of early modern man, infectious disease is actually what shaped a lot of our population demographics. There's a lot of pressure pushing for those step sizes, those updates to the genome, really to be optimizing for protection against infectious disease rather than other things. Even if you imagine that maybe the arguments on the first and the second of these possible positive selection being absent for longevity and potentially some negative selection existing, you could construct a reasonable argument for why humans don't live forever and why the genome hasn't optimized for that, simply based on these optimization constraints. You have to imagine not only that the positive selection is there and the negative selection is absent, but that when you think about the weighted loss term of all the things the genome is optimizing for, that the weight on longevity is high enough to matter. Even if you imagine it's there, if you simply imagine that the lambdas are dialed toward infectious disease resilience more effectively, then you can construct an argument for yourself. ugh to matter. Even if you imagine it's there, if you simply imagine that the lambdas are dialed toward infectious disease resilience more effectively, then you can construct an argument for yourself. And so I think really when you start to ask “why don't we live forever, why didn't evolution solve this?” you actually have to think about an incredibly contingent scenario where both the positive selection is there, the negative selection is absent, and you have a lot of our evolutionary pressure going toward longevity to solve this incredibly hard problem in order to construct the counterfactual in which longevity is selected for and does arise in modern man and in which we are optimal. So I think that puts human aging and longevity and health really in this category of problems in which evolution has not optimized for it. Ergo, it should be, relatively speaking, relative to a problem evolution had worked on, easy to try and intervene and provide health. In many ways, the existence of modern medicines, which are incredibly simplistic—we are targeting a single gene in the genome and turning it off everywhere at the same time—the fact that these provide massive benefit to individuals is another sort of positive emission or piece of evidence.…

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