Usually when real life VOI come up, I find that it is useful to also think about ROI timescales in a complimentary analysis. Do you have any sense of roughly how many years it would take to EITHER find a master switch OR basically rule one out?
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Replying to @almostlikethat
I think it would take <10 years to: a.) get reliable, replicable results on which small molecules, out of diverse libraries, delay aging in multiple short-lived invertebrate species; b.) find out if any of them delay aging in rodents.
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Replying to @s_r_constantin @almostlikethat
If this approach doesn't work, anti-aging treatment is still possible but we'll have to work harder and more "meta", as in, developing better tools and doing more basic research.
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Replying to @s_r_constantin @almostlikethat
"test existing drugs and see what works" is *so* much easier than actually developing novel technology and understanding of aging biology, and it might not be enough, but it's silly not to do it first in case the problem is actually that easy.
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Replying to @s_r_constantin
1/4 (Twitter's algo changed (again). Tweet sequences often drop some for some readers. I see 5 tweets from you ~linearly responding to my question.) It sounds like there's actually kind of a lot of pragmatically different "master switch hypotheses" to group into families.
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Replying to @almostlikethat @s_r_constantin
2/4 One family is that there is a {highly, moderately, non} conserved master switch up-regulated by {some dose} of an {existing, not-yet-existing} {druggable,biologic} drug. (Maybe call this the "pillable" family and define the master switch to be touchable by a "pillable"?)
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Replying to @almostlikethat @s_r_constantin
3/4 Defined this way, I see ~12 "pillable" meta hypotheses, each with a continuous dose variable. The 6 "existing" versions could be falsified at biolab speeds! :-) 3 have "new druggable chemical synthesis" delays. 3 have "Jurassic Park manufacturing" setup challenges.
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Replying to @almostlikethat @s_r_constantin
4/4 "How conserved" seems like a BIG locus of optimization no matter what. Do you have hunches here? If forced to bet, I'd guess that IF humans have a master switch, it would "somehow touch" the V(D)J immune system we share with sharks, but not with lampreys or arthropods.
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Replying to @almostlikethat
1/2 My rough hunch, which I got from the (few existing) comprehensive screens of drugs or genetic knockdowns on lifespan, is that ~10% of things that "work" to delay aging in yeast/cell culture also "work" in multicellular invertebrates,
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Replying to @s_r_constantin @almostlikethat
and a further ~10% of things that "work" to delay aging in multicellular invertebrates also "work" in mammals.
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What caveats are the quotation marks around “work” pointing to here? (Are there 1% clear wins?)
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Replying to @Meaningness @almostlikethat
Lifespan in single-celled organisms isn't well defined. In yeast we use replicative lifespan, which is how long cells keep dividing; in human cell culture senescence (=nonproliferation) is a similar metric; that's not quite the same thing as the lifespan of an organism.
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