#425

Thanks. I’m doing that in a very selfish way for myself :joy: If anyone has ideas or suggestions let me know, I’m willing to co-sponsor experiments.

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#426

May I ask how old was this batch you sponsored? Just so I know as a reference, I’ve got 1+ year old ones that haven’t been done yet

#427

I had some old ones in that batch (1+y), emailed them and complained and eventually got the results. Many were actually available but not sent by the system. Email them as well to know the state of your experiments. Please let us know how it goes.

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#428

I think the information is good quality, because the experiments are well-performed, well-controlled and have suitable statistical analyses. Plus, I believe that Ora are unbiased, which most researchers (let’s be honest) are not. The guys selling Urolithin A or NMN or whatever of course want to show you it’s amazing. The negative results and failures don’t get published. That’s the reality of it.

However, the utility of the data all depends on the question you’re asking. What Ora and the C.elegans studies are doing is looking for anything which taps into a fundamental aspect of aging. So your favourite molecule failing doesn’t really matter, if that thing isn’t relevant to worms. But if something comes out positive, and can’t be explained away by an artefact (like these antibiotics killing the worms’ food), then that’s something which should be investigated further. So I see this like a screening test. I think to say it’s not good quality is deeply unfair.

This would be incredible if that September 2025 repeat comes out positive. Guys like Eric Verdin (on recent Attia podcast) are already calling these molecules geroprotective.

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#429

fair point. Ora do a good job. The information is good quality about the effect on worms.

It is, however, not much use for predicting the outcome on mammals. (ie not good quality information for mammals)

I did contribute towards the IPAM study knowing of the mechanistic flaws.

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#430

Another lab already found a similar effect with various GLP-1RAs. I posted it somewhere but I’m on my phone now.

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#431

Here it is: Calcium channel blockers reduce aging rate (ARDD video) - #2 by adssx

This is typically an example of the value of Ora’s C. Elegans experiments: we have a class of drugs that seems beneficial in sick humans (T2D or obesity) and for $100 we see that they extend lifespan in worms. That’s already a good sign for off-label use in non-sick humans and it’s a signal that warrants further studies in larger models (flies? Zebrafish? Rodents?).

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#432

Can you ask ora if sema makes the works eat less of the bacteria? That seems maybe it’s similar to reducing food motility
Is it possible to try tirz even though no official pill there is a powder still

#433

I had a quote to test all GLP-1RAs, including tirzepatide: $18,000. I didn’t do it. Tirzepatide, administered in 3 doses, should cost $5,000. I’ll wait for the full results of the semaglutide study to decide.

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#434

Why so much more than sema? Cant just do initial powder?

#435

They quoted 50 mg of tirzepatide = $3k: https://www.adooq.com/tirzepatide-ly3298176.html

Semaglutide is way cheaper.

Also an additional cost per experiment as Mitchell said: “I’m a bit skeptical that the high doses will fully go into solution, but we will add drug into media at pouring to give ourselves the best chance of success (this will also double the number of replicates we currently test).” But the main problem is the sourcing.

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#436

Just ordered those, with 3 doses per compound. and also the Voxelotor + PT2399 combination. I added Oxaloacetate (one dose) to try to replicate this paper: Oxaloacetate supplementation increases lifespan in Caenorhabditis elegans through an AMPK/FOXO-dependent pathway - PMC I’ll add higher doses of melatonin.

Hopefully we’ll get results faster this time…

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#437

Answer: “Feel free to tell them that we’re developing a tool to monitor food intake and we’ll reanalyze the existing datasets to quantify if we see that behavior! I’m really excited to roll it out for exactly this reason:)”

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#438

Great to know! Something I’m concerned about in all animal trials of lifespan. Something that just makes you queasy so you don’t want to eat might appear to increase lifespan.

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#439

Important: Parental age effect on the longevity and healthspan in Drosophila and C Elegans (2023)

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#440

Has anyone asked Ora about this? I assume they are well aware.

#441

I did. WIP. Will update after.

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#442

Answer @CronosTempi:

We keep everything very highly standardized, and all experiments use the same age of parents across every test we do. We also pull freshly thawed strains every couple of months to account for in-lab evolution and genetic drift. We also have all generation times fully recorded and ready to do a meta-analysis on whenever it becomes needed!

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