The most important fact justifying aging/longevity drug discovery is that *lifespan-extending drugs exist.* Lots of them. If you screen 1280 well-known drugs and natural products on nematode worms, 5% of them significantly extend lifespan. https://onlinelibrary.wiley.com/doi/pdf/10.1111/acel.12163 …
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There's unpublished data I've been told about from a very large mouse lifespan study finding again that 5% of drugs tested on mice significantly extended lifespan. (Small sample sizes in each drug group, and fairly small effect sizes, but still remarkable.)
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I think aging-modifying drugs are out there. It's just a matter of finding them. Which means industrializing drug discovery -- WITHOUT falling prey to Goodhart's Law. We need fast, cheap experiments at scale that have good predictive validity for the effects of drugs in mammals.
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IMO that means screening for lifespan, in *multiple* short-lived model organisms, with automation & machine learning to reduce the cost per experiment (e.g. monitoring with cameras instead of by eye).
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That's what we're doing at Daphnia Labs: big phenotypic screens on the small crustacean Daphnia magna. (Currently we're at the prototype stage.)
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In principle, gene therapies can be much more flexible and powerful tools than small molecules, and I'm impressed by some of the results so far (e.g. Oisin's DNA-targeting senolytics.) But small molecules can be tested faster, and some of them are already FDA-approved.
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Didn’t the “fasting mice live longer” thing get debunked? I am much more wary of mice results now Incidentally I’d be interested in reading a blog post breaking down what median longevity increases historically can be attributed to
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https://onlinelibrary.wiley.com/doi/full/10.1111/j.1474-9726.2006.00236.x … It doesn’t work in wild mice, or in thermoneutrally housed mice. For lab mice in standard conditions, dietary restriction does extend life.
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Turns out the may have similar circadian rhythm stuff tho? neat. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4232591/ …https://twitter.com/s_r_constantin/status/1164966775538122752 …
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