Ora Biomedical Million Molecule Challenge Results

[DeStrider]

I was thinking of a topical application trial.

[DeStrider]

It would be nice if they gave a leaderboard with all of the interventions that gave 20%+ life extension so we can see the playing field and be able to propose better combinations. It may be long, but it would be incredibly informative.

[Josh]

Its posted above only 9 found so far above 20%. The 10th was 19%

[Josh]

Sponsored an intervention (Ora Biomedical) — Trichostatin A (TSA). Hopefully we can replicate the 20% life extension even with a lower dose. It seems to have a similar CR function and effect to allantoin so it would probably also pair well with that GSK.

[John_Hemming]

Its quite a strong HDAC inhibitor. I think it probably would have a quite well defined sweet spot where if you go over that point any benefits drop off pretty quickly.

[adssx]

You tested doxycycline and it shortened the lifespan in the early period of the experiment but extended the lifespan in the later period. Carvedilol did the opposite. So I sponsored the combination, hoping to get the best of both worlds (we might also get the worst of both worlds ).

I’ve also just sponsored Sulforaphane + Nilvadipine.

[Lost]

@forceofnature

Isn’t Allantoin potentially fatal if ingested by humans?

You’d probably need a ton of it. Allantoin is naturally occurring in some foods, such as true yams. It’s the suspected antidiabetic agent in these, presumably acting similarly to metformin.

I took a few grams a day for a while, but then decided that was stupid.

[Curious]

Great, let’s see how it turns out. I now sponsor Doxycycline HCl + Lithium Citrate and Doxycycline HCl + GSK2126458.

Just a few thoughts:
I note that the first test with Nilvadipine as single agent had short-lived controls. The median was only 12,9 and the Nilvadipine group had a median of 17,9 days,

The results from Sulforaphane as single agent was good, but not as good as one would like. The controls were also in this experiment rather shortlived (14 days)

same goes for the controls in the experiment with GSK2126458 10µM / Allantoin 50µM, the median lifespan was only 14,5 days.

Compared to this the results could be considered better from the experiments with GSK2126458 10µM / Berberine 50µM and GSK2126458 10µM / Metformin HCl 50µM. In those expiriments we got a good result and the controls had a healthy lifespan.

[Karel1]

In the MMC research I do like all the well known patent free medicines and chemicals that are tested but I strongly dislike big pharma jumping on this bandwagon with patented analogs of cheap drugs like rapa. or a combi therewith be it in one molecule like GSK2126458 or in multiple molecules.
My hope is afordable increase in healthspan for the masses.

[Josh]

Big pharma isnt sponsoring any of these, its all just a few us members in the forum plus a few other regular people just picking stuff. You are free to pick whatever you want!

[adssx]

Also, whatever big pharma does, we can always count on Indian freedom fighters to make it affordable for us. So I hope big pharma will jump on this bandwagon! The more we screen the better.

[forceofnature]

Sponsored BEZ235 (Dactolisib)
and GDC-0980 (Apitolisib)

Single interventions

[Josh]

Double mtor inhibitors looks like or is there difference? I would think best to use just nest one of each pathway but maybe even 8 different pathways to hit most of the hallmarks of aging…
@adssx when you sponsor custom stuff is it still 100$ per chemical, assuming they have the supplies since those are extra? Hopefully they can get a quantity discount at a certain point…

[John_Hemming]

I have had discussions about C Elegans at BSRA and it is clear that it will not be a good model for senescence.

[adssx]

@Josh

@adssx when you sponsor custom stuff is it still 100$ per chemical, assuming they have the supplies since those are extra? Hopefully they can get a quantity discount at a certain point…

I don’t know because I said “I sponsored” above but actually they haven’t sent me the quote yet…

[forceofnature]

It’s two single interventions, not combined

[Krister_Kauppi]

Here is some of my thoughts around the topic which I posted on my channels.

Rapamycin Longevity Lab has made an interesting experiment with the Ora Biomedical’s WormBot-AI technology. The lab has pushed the median lifespan above the 50% line by combining the PI3K/mTOR inhibitor GSK2126458, a new longevity compound Rapamycin Longevity Lab discovered earlier this year, with the compound Allantoin. You have probably not heard of the compound Allantoin before but researcher such as Alex Zhavoronkov (pubmed: 29165314), João Pedro de Magalhães (pubmed: 26676933) and Jan Gruber (pubmed: 30269951) has done some interesting longevity research around this compound. It seems to have similarities with metformin which has glucose lowering effects.

I have previously shown research that combining a mTOR inhibitor with a glucose regulator may be an interesting combo. But I would like to see the above experiment replicated because the untreated worms were a bit short lived (14.5 days median lifespan). I also think a higher dose around 250µM instead of 50µM may result in a better longevity effect. That type of dose has also been tested in other papers successfully (pubmed: 26676933, 30269951). One other thing is that someone should write a publication on roundworm experiments and create a similar “900-day rule” as for untreated mice when it comes to median lifespan (doi: 10.1101/2023.10.08.561459). That way we get guidance if untreated worms are too short or long lived. Thereby we can interpret the lifespan results in a better way. So step by step we improve and push things forward.
Source: x.com

[forceofnature]

It’s a very interesting compound. Some information online makes it seems like oral consumption is possible:

This was interesting as well

Allantoin reduces cell death induced by cisplatin: possible implications for...

and here

https://journals.sagepub.com/doi/pdf/10.1177/1091581810362805

[adssx]

I’ll try to sponsor PF-06840003 ( https://www.caymanchem.com/product/25003/eos200271 ) which is supposed to be this miracle compound that can reverse Alzheimer’s: Predicting Alzheimers (and minimizing risk) - #186 by RapAdmin

[adssx]

Some great results!

Amlodipine lowered lifespan, but I think the dose was too high:

Felodipine, another DHP CCB, did way better at a low dose (even though controls lived longer than usual!):

And yet lacidipine failed:

So there are weird differences among DHP CCBs.

Ambroxol, studied for Parkinson’s disease, lowered lifespan a lot:

CoQ10: nothing

Gemfibrozil looks good:

Doxazosin as well:

Hydralazine:

And the best… the immunosuppressant azathioprine… +41%!:

So I’m now sponsoring low-dose amlodipine (to see if it can do better than other CCBs), alfuzosin and terazosin (to see if they’re better than doxazosin) and three azathioprine combinations:

• azathioprine + nilvadipine
• azathioprine + sulforaphane
• azathioprine + GSK2126458

I’m still waiting for the following results:

• Telmisartan + Amlodipine Besylate
• Lercanidipine
• Urolithin A
• Methyl-B12
• Methotrexate sodium
• UDCA (ursodiol)
• Lactoferrin
• Chlorogenic acid
• Nebivolol
• GlyNAC
• Ezetimibe 100 µM
• Fluoxetine 50 µM
• Fluoxetine 0.2 µM
• Caffeine 5 mM
• Sulforafane 100 µM
• Sitagliptin 2 µM
• Selegiline (L-deprenyl) 10 µM
• Selegiline (L-deprenyl) 100 µM
• Sildenafl citrate 50 µM
• GlyNAC (Glycine 8 mM + N-acetyl-L-cysteine 3.7 mM)
• Sertraline 10 μM
• Rilmenidine 200 μM
• Alfuzosin HCl
• Silodosin
• Carvedilol + Doxycycline HCl
• Sulforaphane + Nilvadipine
• EOS200271 / PF-06840003