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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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    1. Sarah Constantin‏ @s_r_constantin May 14
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      Ok so here’s the aging paper everyone’s so excited about. Horvath et al found a way to reverse biomarkers of aging in rats. https://www.biorxiv.org/content/10.1101/2020.05.07.082917v1.full.pdf …

      10 replies 58 retweets 278 likes
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    2. Sarah Constantin‏ @s_r_constantin May 14
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      The rats were treated with what’s described as a “plasma fraction treatment” from young rats. The authors aren’t specifying what it is.

      2 replies 1 retweet 14 likes
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    3. Sarah Constantin‏ @s_r_constantin May 14
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      The primary outcome was the score on methylation clocks, trained on the different patterns of DNA methylation between old and young tissue samples. Elsewhere, methylation clocks of this sort have been found to be predictive of mortality.

      1 reply 0 retweets 10 likes
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    4. Sarah Constantin‏ @s_r_constantin May 14
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      (In humans, few of these blood-based biomarkers are as predictive as functional tests of frailty or locomotor fitness, so I tend to be suspicious of them as endpoints.)

      2 replies 0 retweets 12 likes
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    5. Sarah Constantin‏ @s_r_constantin May 14
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      So, did this treatment work? Pretty dramatically, on the epigenetic clocks (except for hypothalamus)pic.twitter.com/46VMbTYFlD

      1 reply 0 retweets 13 likes
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    6. Sarah Constantin‏ @s_r_constantin May 14
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      It does reassuring things to blood work (glucose & cholesterol & triglycerides down, HDL up).pic.twitter.com/rTcqDwgRTs

      2 replies 0 retweets 13 likes
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      Sarah Constantin‏ @s_r_constantin May 14
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      The treated old rats did perform better on a cognitive task, learning a maze:pic.twitter.com/XoaErcwGcB

      8:06 AM - 14 May 2020
      • 1 Retweet
      • 13 Likes
      • Julio Protzek 🇧🇷 JamesonLaw Manas Joglekar Kurt Barry Divia Eden Sarah Brodsky @micahstubbs Jaime Sevilla hikikomorphism🏳️‍🌈🏝🛰️
      1 reply 1 retweet 13 likes
        1. New conversation
        2. Sarah Constantin‏ @s_r_constantin May 14
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          And they have way higher levels of antioxidants like superoxide dismutase. The relevance of this to diseases of aging is mixed as I recall, but more oxidative stress correlates to more chronic disease *sometimes*.pic.twitter.com/OiXcYGLWIl

          1 reply 0 retweets 9 likes
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        3. Sarah Constantin‏ @s_r_constantin May 14
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          Lower chronic inflammation— this is also a good sign. IL-6 correlates with pretty much every chronic disease of aging and long-lived mouse strain.pic.twitter.com/9hYhk3qIX0

          2 replies 0 retweets 14 likes
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        4. Sarah Constantin‏ @s_r_constantin May 14
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          Reduced senescence — I’m not crazy about using pictures here, they’re so easy to cherry-pick, but ok sure.pic.twitter.com/TruTh72DoP

          2 replies 2 retweets 10 likes
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        5. Sarah Constantin‏ @s_r_constantin May 14
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          I can criticize the methylation clocks all day. They’re trained on chronological age not remaining time to mortality, so not what we care about.

          1 reply 0 retweets 13 likes
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        6. Sarah Constantin‏ @s_r_constantin May 14
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          They’re also novel — why? Lots of old, validated methylation clocks out there. Too easy to game by testing your treatment on your own invented metric.

          1 reply 1 retweet 11 likes
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        7. Sarah Constantin‏ @s_r_constantin May 14
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          Improving performance on learning mazes in aged rats is also not unique.

          1 reply 0 retweets 8 likes
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        8. Sarah Constantin‏ @s_r_constantin May 14
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          You can do it with substance P: https://cyber.sci-hub.tw/MTAuMTAwNy9iZjAyMjUzNzEy/10.1007@BF02253712.pdf …

          1 reply 0 retweets 7 likes
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        9. Sarah Constantin‏ @s_r_constantin May 14
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          Or with etazolate: https://www.ndineuroscience.com/userfiles/Etazolate%20EU%20J%20PHARM%202010-4.pdf …

          1 reply 0 retweets 4 likes
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        10. Sarah Constantin‏ @s_r_constantin May 14
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          Or with a MAPK inhibitor:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923728/ …

          1 reply 0 retweets 4 likes
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        11. Sarah Constantin‏ @s_r_constantin May 14
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          Or montelukast:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4639806/ …

          3 replies 0 retweets 4 likes
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        12. Sarah Constantin‏ @s_r_constantin May 14
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          Basically, improving cognition in aged rodents, even all the way down to young levels, is not that unusual. And doesn’t always translate to humans. (Neuroprotective drugs have a really bad translation track record.)

          1 reply 2 retweets 14 likes
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        13. Sarah Constantin‏ @s_r_constantin May 14
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          I still think it’s a good sign! But keep in mind that lab rats are kept in the rat equivalent of prison. You can improve cognitive performance just by giving them an exercise wheel or toys or other rats to interact with.

          2 replies 4 retweets 24 likes
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        14. Sarah Constantin‏ @s_r_constantin May 14
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          Also of course there are lots of interventions that reduce inflammation, oxidative stress, and blood glucose and lipids. Dietary restriction being the most famous.

          1 reply 1 retweet 9 likes
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        15. Sarah Constantin‏ @s_r_constantin May 14
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          The “wow factor” on this paper seems to be from the fact that it claims reversal on epigenetic clocks. And epigenetic clocks are (IMHO) bad.

          2 replies 3 retweets 15 likes
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        16. Sarah Constantin‏ @s_r_constantin May 14
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          Even if you disagree, epigenetic clocks are *new*. The reason a bajillion other interventions haven’t been found to improve them isn’t because few things work but because few things have been tested on these new metrics.

          1 reply 1 retweet 12 likes
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        17. Sarah Constantin‏ @s_r_constantin May 14
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          My reaction is “ok, add this mystery intervention to the list of ~100 things that seem like they might do something to aging symptoms in mammals”. I’m not sure where Josh Mitteldorf’s extreme endorsement is coming from here.

          2 replies 5 retweets 23 likes
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        18. End of conversation

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