#284

Natural vanilla is a lot more expensive

#285

It looks like leaderboard updated and sulforaphane has been dethroned by Doxycycline Hcl!?
D-Mannitol and Xylose sweeteners seem to also be pretty good.

2 Likes
#286

Rapamycin + Berberine-Hcl also extremely effective! Moreso than GSK2126458 + Berberine or metformin!
(Neither rapa nor berberine by themselves did anything, and the GSK chemical is strong by itself or with just about anything it seems)

3 Likes
#287

Waiting for someone to double worm lifespan or something, at this relatively marginal difference it doesn’t look so enticing to even consider without mouse data. If you made a worm immortal that would be different.

An off-shoot project might be a LEV worm project. Feed worms one substance for awhile then switch to another one. If that even have any biological plausibility.

3 Likes
#288

They told me they haven’t finished updating the full leaderboard yet.

#289

Why don’t you sponsor compounds yourself or suggest some here instead of waiting for someone to do the job?

2 Likes
#290

Waiting for use in humans.
To be clear, I was remarking on when to consider even investigating a substance for use in humans without mouse data. The results can be interesting or even impressive but still not ready for human use. I don’t know when it is.

#291

Ah yes, of course. The next step for Ora Biomedical is to test in human cells. Then mice. Worms are just here to identify some candidates on the cheap.

5 Likes
#292

What does testing on human cells look like? They measure lots of stats for cell health like divisions or mostly just look at some sort of avg lifespan of individual cell? Is there any evidence that it scales to mouse or human lifespan? I know I have seen in vitro models to show a drug is absorbed and effects a certain organ, maybe even helps a dementia model like reducing Aβ plaques, but not for lifespan effects.

#293

You’re right the cell models are more for specific diseases (Ora Biomedical is also working on that). I don’t know for lifespan.

#294

Look at the CAS number and if that is the “same” then it’s the same compound with a different description. If it’s different, try to find what is used in trials, with a CAS number.

#295

Not sure why human cells aren’t used in the first place. We might be biasing the results of the the “first pass” experiments by even doing worms at all. There could be idiosyncrasies in worms that can give false positives or false negatives. A couple of human cell lines should do the trick, no? But then I wonder if it’s possible to get contradictory results based on what type of human cell lines are tested….

1 Like
#296

I wonder if there is a way we can help them update the leaderboard more often? It seems they are doing a ton of manual work. I have seen some typos and things copied wrong before. It should be just a script they can run automatically to email out PDFs to donors and update the leaderboard from just entering in the results when experiment is complete…
I want to sponsor more but can’t do it on way out of date data, might even duplicate…

I think we are seeing this important issue since antibiotics are doing well in our leaderboards? This paper is worth reading with lots tested
https://x.com/kgiperez/status/1807763436308246536
We confirmed that a UV-killed OP50 diet extends C. elegans lifespan, and revealed that only six compounds (resveratrol, metformin, GSK2126458, LY-294002, doxycycline, and caffeine) retained their lifespan-extending effects with this diet.
The reduced efficacy of rifampicin, captopril, CCCP, and minocycline with this diet suggests that their effect with live OP50 may be due their antibiotic activity rather than a direct effect on C. elegans. This was further confirmed by assessing their impact on OP50 viability, where these compounds significantly reduced bacterial growth.

It looks like Matt K is aware of this antibiotic effect
https://x.com/mkaeberlein/status/1363186941420728321

3 Likes
#297

Sponsored one of the winners from 200 samples tested in above paper:
Combinatorial Intervention (Ora Biomedical) — GSK2126458 - SPONSORED - LY 294002
Sponsor an intervention (Ora Biomedical) — Ellagic acid (in pomegranate extract, related to Punicalagin which tested well)

3 Likes
#298

I agree 100%. I complained about that. I had a call with them. They told me they hired new people and they’re working automating everything (including creating a dashboard with all ongoing experiments and at which step they are). They seem to have other priorities than the MMC (which is understandable). I think you could/should email them as well to say what you said here “I want to sponsor more but can’t do it on way out of date data, might even duplicate…”

Please ask them as well about the antibiotics, it’s an excellent question. (Or I can ask them if you prefer).

4 Likes
#299

It’s very interesting that doxycycline retained lifespan extending effects but minocycline did not. It’d be great if the ITP could test doxycycline at sub-antibiotic doses.

1 Like
#300

I sent most of the above plus the following:

“I’m worried much of the positive results are somewhat due to antibacterial effects. Maybe all of the E.coli should be killed with UV or antibacterial before feeding the worms to separate this issue? Or at least have it be an option when sponsoring?”

Does anyone know if there is any evidence for mice or humans living longer with antibiotics? I doubt any human population studies would be informative, (with a sicker population taking antibiotics). Even if a mouse lived longer with antibiotics I would suspect saving disease rather than enhancing longevity.

#301

I think this is a big problem with essentially all animal studies in the geoscience field.

Basically the control lifespan is not optimised via environmental factors, so you end up with control mice in the ITP with diabetic level glucose.

So the question you end up answering is does X intervention extend lifespan in fat, diabetic mice.

This optimisation needs to occur if we are ever to hope to find interventions to extend life in humans.

4 Likes
#302

I don’t think that is a similar example, since most civilized people aren’t constantly in need of antibiotics, but they actually are in need of help to not become fat or diabetic in modern overabundance of food. Even if you eliminate the bottom 50% least healthy people it is still a big issue!

1 Like
#303

It’s similar in the sense that basic environmental optimisation can increase the control lifespan of the animals (whether by avoiding obesity/metabolic dysfunction or microbial load).

Against this we can identify real life extension interventions (not yet another diet/exercise mimetic).

1 Like