#243

Rifampin affects metabolism of many many drugs, including ones popular here. It might be interesting to test to elucidate the mechanism, but it’s hard for me to imagine a scenario where one would want to take rifampin long term due to the complexity of the interactions with other drugs.

6 Likes
#244

Sorry it’s all from the same study.

You’re right, 900 days is just a neat eyeball estimate. You could absolutely justify using the control cohort record instead.

For the C.Elegans in MMC I would say the eyeball estimate is around 19 days.

1 Like
#245

Rapamycin appears to be synergistic with Rifamycin but Rifamycin was tested in the wormbot without much success. Initially I thought that could have to do with rapamycin crystallization issue they’ve talked about, but even when tested in combination with GSK2126458 it failed to produce results greater than GSK2126458 alone.

5 Likes
#246

So it doesn’t hold promise as a mono therapy but can boost other cocktails like nothing else? (Almost doubling of lifespan in a combination mentioned upthread, isn’t that a record?)

I also wonder how prevalent AGEs are in worms as a driver of aging. My intuition says, not as much as in humans. Also for Alzheimer’s prevention alone, nay, treatment in the early stages, my mind was blown. Simply look up rifampicin Alzheimer’s and Google’s new AI synthesis will point you in the right direction.

3 Likes
#247

Remember if something fails in C. Elegans it means nothing. If it works, then it may mean something, but still needs to be tested in mice. If it works in mice, then you should try monkeys or humans. Then if it still works, you’re golden.

2 Likes
#248

I would not say something failing in C Elegans means nothing. It is useful information, but not conclusive. Particularly anything relating to cell division and senescence is unlikely to have any effect in adult C Elegans.

3 Likes
#249

Here’s the published paper: The impact of short-lived controls on the interpretation of lifespan experiments and progress in geroscience – through the lens of the “900-day rule” 2024

In the absence of independent replication, a putative mouse longevity intervention should only be considered with high confidence when control median lifespans are close to 900 days or if the final lifespan of the treated group is considerably above 900 days. Using this “900-day rule” we identified several candidate interventions from the literature that merit follow-up studies.

If anyone has access to the paper, what are the “several candidate interventions from the literature that merit follow-up studies”?

2 Likes
#250

https://www.biorxiv.org/content/10.1101/2023.10.08.561459v1.full

Full paper

3 Likes
#251

@Yoo, here’s Ora Biomedical answer:

It looks like there is one experimental flight where the control is longer lived than we would expect and quite a few of the combinations were ran on that flight. The number of animals tested is a bit lower too, so I expect that might factor in. Ben will have a look at that data and see.
The “900-day rule” for these C. elegans experiments is 15 days.

Matt Kaeberlein is both the main author of the 900-day rule paper on mice and the cofounder and chair of Ora Biomedical. So I trust Ora Biomedical when they say that 15 days if the equivalent in worms.

Also, based on one image on their website I assumed they already found a compound with +250% life extension. It’s not the case (poke @Krister_Kauppi ):

The 250% extension in that study is with regards to suppression of a paralysis effect in an Alzheimer’s model we have. For survival effects in WT animals, 50-70% extension is best we have seen so far.

Hopefully we’ll find a combination that does 2x by the end of this year!

4 Likes
#252

Please check the median lifespan of controls in the single intervention leaderboard.

If you sort them in order you will see that 80% of experiments have a lifespan greater than 15 days.

Not sure how you can say this is the lifespan of C.Elegans under optimal conditions then (i.e 900 days rule). Respectfully agree to disagree.

Personally I prefer to look at the longest lived cohort and see whether it can further extend lifespan. If you took a cohort of Okinawans and gave them a given drug would it extend their lifespan?

1 Like
#253

How was the 900-day rule constructed? I don’t know but if the guys behind the 900-day rule say that the equivalent in worms is 15 days, I tend to trust them more. In any case these rules are just rules of thumb.

Okinawans live shorter than other Japanese people so probably yes.

2 Likes
#254

The problem arises when the people who suggested 900 days have a financial interest in the 15 days. 15 days is likely to be ok, but C Elegans is not a good model organism for testing interventions.

2 Likes
#255

They allow random people to sponsor out of patent generic compounds and supplements so I don’t think they have any strong financial incentives here.

3 Likes
#256

C. Elegans is a great starting point before moving on to mice. No one should be taking an intervention solely based on C. Elegans data. Their biology is too different from ours. Even mice aren’t all that great.

Now monkeys and dogs are much better.

2 Likes
#257

It is always worth noting conflicts of interest. However, I don’t personally think the 15 days figure is wrong.

#258

Ora has already changed temperature to have longer lasting controls so you cant just look at their median, you’d have to look at median of other labs. But worms arent as much work as mice so shouldn’t be as much variance.

1 Like
#259

Anyone gotten their results lately? I’ve been waiting for half a year already, it seems like they’ve slowed down with the studies.

1 Like
#260

Yah its been a while. Its due anytime now

#262

Lithocholic acid (LCA) is available on Ora if anyone wants to test
https://www.nature.com/articles/s41586-024-08329-5

#263

I ended up sponsoring testing Lithocholic acid (LCA) today. Hopefully we get some of those backlogged soon!

4 Likes