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s_r_constantin's profile
Sarah Constantin
Sarah Constantin
Sarah Constantin
@s_r_constantin

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Sarah Constantin

@s_r_constantin

Math/ML/data-science person now working on solving aging...and helping with COVID19?! Founder, LRI and Daphnia Labs. Married to @oscredwin

Be
srconstantin.posthaven.com
Joined February 2019

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    Sarah Constantin‏ @s_r_constantin 20 May 2019
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    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 …

    7:09 AM - 20 May 2019
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    5 replies 1 retweet 30 likes
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      2. Sarah Constantin‏ @s_r_constantin 20 May 2019
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        Worms are very different from people, of course. But 7% of the drugs in the DrugAge database that were reported to extend life in worms were also tested in mice and found to extend life in mice.

        3 replies 1 retweet 12 likes
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      3. Sarah Constantin‏ @s_r_constantin 20 May 2019
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        There's unpublished data I've been told about from a very large mouse lifespan study finding again that 5% of drugs tested on mice significantly extended lifespan.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.)

        2 replies 0 retweets 7 likes
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      4. Sarah Constantin‏ @s_r_constantin 20 May 2019
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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.

        1 reply 0 retweets 11 likes
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      5. Sarah Constantin‏ @s_r_constantin 20 May 2019
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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).

        2 replies 0 retweets 8 likes
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      6. Sarah Constantin‏ @s_r_constantin 20 May 2019
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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.)

        1 reply 0 retweets 10 likes
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      7. Sarah Constantin‏ @s_r_constantin 20 May 2019
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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.

        1 reply 1 retweet 4 likes
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      8. End of conversation
      1. New conversation
      2. Vinayak‏ @OneBigOh 20 May 2019
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        Replying to @s_r_constantin

        Just curious: how much have we progressed in simulating organisms for testing drugs? Is it possible to perhaps to filter out the least promising drugs by means of a simulation? Is any work even being done in this direction

        1 reply 0 retweets 0 likes
      3. Sarah Constantin‏ @s_r_constantin 20 May 2019
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        Replying to @OneBigOh

        we're really not there yet. protein binding simulations are ok but not yet a substitute for experiment; organism simulations are totally not ready.

        0 replies 0 retweets 1 like
      4. End of conversation
      1. Toviah Moldwin‏ @TMoldwin 20 May 2019
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        Replying to @s_r_constantin

        Isn't 5% exactly the number that you'd expect to be significant with a null hypothesis rejection criteria of p < 0.05?

        0 replies 0 retweets 2 likes
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      1. Daniel Lawhon‏ @DTLawhon 20 May 2019
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        Replying to @s_r_constantin

        Curious if you've seen interesting research on BCAAs as they relate to longevity? Seeing some tell-tale signs of improving insulin sensitivity, inflammation, apoptosis, etc from reducing their intake or blood serum levels after the fact.

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