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Jan 21, 2021Liked by Nathan S. Cheng

I have an idea of a strategy that might work to cure aging that involves 'iterated embryo selection' and transcriptome analysis. Let me expound upon my idea a bit.

Imagine we intentionally induce a mutation that causes 1 particular aging damage category to accumulate faster in a short lived mammal (transthyretin amyloid, for example), then, we breed many generations of those species so they adapt a way to fix that 1 damage type. However, the problem is that #1, because it takes too many generations, this will be completely impractical. Additionally, #2, because any such adaptation will generally involve subtle changes to the regulation of a large number of genes, it will be completely pointless and untranslatable to humans.

However, we can get around these two problems if instead of breeding these animals and reproducing them sexually, we use iterated embryo selection to simulate evolution on a much short time scale. (https://www.lesswrong.com/tag/iterated-embryo-selection)

Then, after we have the thousandth iteration of the zygote derived dna-recombined zygotes (theoretically a species that would result from 1000 generations of natural evolution), we could actually let those zygotes develop into full fledged species, induce the damage accumulation of transthyretin at a faster rate, and see which individuals accumulated a greater ability to remove taht damage. However, we still have to deal with problem #2. To deal with this, when selecting zygotes in the iterated embryo selection process, we select ones that don't have subtle changes to the entire network of genes. Instead we choose zygotes that have only small clusters of gene changes. Then we test which clusters are beneficial. Additionally, when we induce the damage accumulation to quicker for transthyretin, we should make it go ALOT quicker by inserting the mutation very suddenly late into the organisms life, so that we are testing for their ability to remove damage instead of simply slowing it down over an extended period of time. Then we choose the species who are best at removing the damage, analyze the transcriptome of those small gene clusters, and try to develop affective damage removal therapies based on the enzymes / proteins produced by those clusters. Then we insert mRNA into humans so that there is a temporary damage removal that doesn't permanently affect the humans metabolism, potentially causing 'unwanted tinkering'. Does what I said make any sense?

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Hey Nathan,

Have you ever looked into Eidos Therapeutics? Seems to me like a good candidate to be added to your list of longevity stocks.

Cheers

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