Rapamycin extends lifespan of worms in dose 100uM - 6.67 times higher dose than tested here
When it comes to taurine, I don’t know specific dose, but it requires much higher dose than Rapamycin - so probably 300 uM dose would be more accurate
Also combinations are not predictable - 2 things may extend lifespan separately but not work in combination - taurine is anti oxidant and may cancel autophagy benefits from Rapamycin
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The worms eat bacteria. How to get anything into the bacteria to be eaten is an interesting thought.
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The researcher Jan Gruber who has studied worms said to me in a mail conversation I had with him last week that they also give rapamycin to the bacteria which they then give to the worms. The result is like some kind of double dosing. You have rapamycin on the plate and also on the bacteria that the worms eat.
I’ve started investigating recently how the methodology may differ between different labs when they test rapamycin. This is the current status of that investigation. I’m not an expert in worm research but step by step I’m learning more. If there are any columns that I have missed or some data that is wrong just let me know. All help with this investigation is appreciated
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Josh
#105
The video said their skin is thick and they have to use high doses to penetrate. Ingestion should work at lower doses I’d think.
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One conclusion I’ve come to is that taking rapamycin pills probably requires a lower dose than what is used in animal trials, be it in mice or worms.
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Josh
#107
Why lower dose than mice that get it from their feed? I agree dosing from nematode to human is basically impossible, the video said as much have to use a mammal.
Krister, here is another nematode researcher that you may want to talk to. He has a company that is also doing nematode longevity research (perhaps a little competitive with Ora Biomedical)…
https://twitter.com/dweinkove
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There are updates in the Ora Million Molecule Challenge Data Hub!, mixtures and some more compounds have been included.
https://orabiomedical.com/mmcleaderboard/
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GIven all the stress about Omega 6 it is interesting to see Linoleic Acid in the leaderboard.
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Josh
#111
I was not surprised to see that. Ive seen lots of studies about how it doesnt cause inflammation
And it does promote longevity and heart health.
Omega 3 is still better and you want to take enough to keep omega 6 ratio not too bad to be safe.
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Josh
#112
I got excited by the new leaderboard and sponsored a bunch:
Berberine HCL
Epigallocatechin gallate (EGCG)
Sulforaphane
Tramiprosate
Glycine
Edit: Has anyone started trying to combine 2 of the top candidates? I think other amino acids like Serine would also be good to test. It seems taurine is not that good since with rapamycin it has no net effect, and rapamycin was tested individually to have no effect. Seeing if leucine or iso-leucine are negative would also be interesting
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Have you seen the result of the nilvadipine?
It appears in the intervention browser but not in the compiled data.
(I have not sponsored it)
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How were your concentrations/doses selected? 50 uM seems extraordinarily high for any drug. While SGLT may not be its mechanism of longevity enhancement, empagliflozin would provide 80% inhibition of SGLT-2 at about 12 nM. I would be concerned 50000 nM ( = 50 uM) would have nonspecific toxicities.
When people do in vitro testing, 10 uM is often used as a default real high concentration to see if anything happens. But unless you’re looking at the liver or a few other edge cases, biologically relevant concentrations of drugs are usually below 1 uM.
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adssx
#117
Can you please ask them? (on Twitter or by email) I don’t know enough about this issue but they said once that before testing something they look at a dose response with 3 different doses.
Sure. I’ll post if/when I get a response to my email.
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Josh
#119
I asked them and they said default they test at the maximum concentration that dissolves since worms have thick skin and they want to make sure it has an affect. Then they can try lower doses later. It doesnt seem they think too high doses is a big deal. For berberine or tumeric they cant get enough to dissolve to match other papers
Bicep
#120
Ok, this is funny to me. @AnUser accused me of believing in magic crystals and shungite:
https://www.amazon.com/Elite-Shungite-Stone-Purification-Mineral/dp/B071ZZ93FK/
Shungite is a magic crystal that is said to purify water or if you wear it around your neck it will keep away bad vibes. It is almost pure carbon and the form is mostly fullerines or buckyballs. So I wanted to have shungite tested in the Million molecule challenge. Emailed them and got this back:
Thank you for your interest in the Million Molecule Challenge and Ora Biomedical!
** We have not tested shungite. For safety and liability, we must source compounds from reputable research grade chemical suppliers.**
** That said, in my quick literature search, fullerene may be a suitable replacement. That is offered by chemical suppliers. To run that test, we would need to charge for compound purchase and shipping. An estimate for a single dose test would be around $400.**
** Let me know if you are interested and I can draft a custom contract.**
So the price is a little higher than I wanted, also not testing shungite (obviously magic for some reason) but fullerines. I have no idea how much to use or whether to mix it in the feed or just use it for some form of bedding to ward off bad vibes.
Does anybody have a good idea here?
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