If we can get donations tax deductable in other countries that would be fantastic.
I just put $100 in.
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Big thanks for the support @AustraliaLongevity 
Could you check what rules there are in Australia around taxes and donations? Because I think it will differ between countries.
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I think you probably need a charity registered in a particular country to get a tax benefit (counting the EU as a single country from this perspective).
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Please help out in amplifying the social media posts so that we increase the chance of getting the project fully funded.
https://x.com/KristerKauppi/status/1945062001274708269
The social media post
This is the day I have been waiting for and it’s time to start to release preliminary data from the first phase of the lifespan screening of 301 of 601 compounds in roundworms. Below is the current top list of the 37 compounds. Out of the 301 compounds tested 5 have produced a higher median lifespan extension than than the best recorded lifespan of Rapamycin which is 27%.
My three key takeaways from this is
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When I started to look deeper at the compounds in the top list I was surprised that there were 3 compounds that indirectly activated mTOR instead of inhibiting it. This unexpected result turned out to be fortunate because the goal was to screen 601 mTOR inhibitors and not look at mTOR activators. It’s still early data but this challenges the assumption that mTOR activators would be connected to a decrease in lifespan. It’s very interesting data points that we have provided to the field and more research is of course needed here to understand why they seem to work and if it translates to other species as well. Due to all this a decision has been taken to change the project name from “Rapid lifespan analysis of 601 mTOR inhibitors” to “Rapid lifespan analysis of 601 mTOR modulators” to better reflect the scope. It is also good to point out that most of the compounds are mTOR inhibitors in the library according to the chemical company provider.
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It was discovered that the ATP-competitive mTOR kinase inhibitor PQR626 has lifespan extension properties that is better than Rapamycin. This is interesting because this compound targets both mTORC1 and mTORC2 unlike Rapamycin which targets directly mTORC1. This, and other data in the top list, challenges a bit the current view that mTORC1 inhibition is connected to lifespan and mTORC2 is connected to decrease in lifespan. Additional validation in other species such as mice will be key here. The goal is to send in proposals to both ITP and CITP next year for testing the PQR626 compound. Proposals for testing Omipalisib were submitted earlier this year.
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Every compound in this screen was tested at just one dose. That means potential for further lifespan extension if the dose is optimized. We will test different doses of both PQR626 and Omipalisib to see if we can optimize them even more. If someone is interested in testing any of the compounds that have been screened in other species or strains please reach out. Let’s collaborate!
PS 1. Ora Biomedical is validating the rest of the data and when this is done it will be published to their database and Rapamycin Longevity Lab LID database.
PS 2. Funding Need: We’re still seeking $28600 to finish screen of the remaining 300 compounds. If you’d like to support then please reach out to me!
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I’d love to hear any information people on this website have on these compounds, particularly the ones above the red line.
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It seems these are investigational new compounds that have limited human testing so far… so still very early in the process and not something I’d be looking at for personal consumption any time soon.
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Donated! Thanks for leading this!
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Rapamycin Longevity Lab has been utilizing the new Pump Science DeSci crypto platform to fund studies on molecules. It has been more effective that I could imagine. We’ve already funded worm, fly and mouse studies for Omipalisib ($OMIPAL), Doxycycline ($DOCS) and a combination of Omipalisib+Doxycycline ($OMIDOCS). Coming soon is a release for Rapamycin+Doxycycline ($RAPADOCS).
This is a huge amount of data which will be very useful. Lots of other interesting compounds and combinations are being done on the platform. Funding is obtained from trading fees of the tokens, which I think is the best use case of crypto outside of using it as a currency I have ever seen.
I’m excited to see the results from all of these studies.
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Thanks for sharing the details. How is the Rapamycin+Doxycycline regimen dosed?
SINGLE INTERVENTIONS
Experiment 1:
Doxycycline (HY-N0565).
Dose: 10uM
Experiment 2:
Doxycycline (HY-N0565).
Dose: 20uM
Experiment 3:
Doxycycline (HY-N0565).
Dose: 50uM
COMBINATIONS
Experiment 4:
Rapamycin (HY-10219)
Dose: 50uM
Doxycycline (HY-N0565).
Dose: 10uM
Experiment 5:
Rapamycin (HY-10219)
Dose: 50uM
Doxycycline (HY-N0565).
Dose: 20uM
Experiment 6:
Rapamycin (HY-10219)
Dose: 50uM
Doxycycline (HY-N0565).
Dose: 50uM
Experiment 7:
Omipalisib (HY-10297)
Dose: 10uM
Doxycycline (HY-N0565).
Dose: 10uM
Experiment 8:
Omipalisib (HY-10297)
Dose: 10uM
Doxycycline (HY-N0565).
Dose: 20uM
Experiment 9:
Omipalisib (HY-10297)
Dose: 10uM
Doxycycline (HY-N0565).
Dose: 50uM
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I have sponsored experiments with doxycycline and it is a know life extender in C elegance. My results with GSK 2126458 and Doxycyline was mindblowing. It is not on the leaderboard because to many worms were stil alive when the experiments was terminated. One thing to be aware of is that when c elegance recieve doxycycline (at least high does doxy) before they mature, then thay seem to be frail during maturing phase. But it makes them more resiliant when they are given doxy frpm the start of adulthood.
Ora Results.pdf (501.2 KB)
Doxy.pdf (253.6 KB)
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I have already learned quite a bit from my experiments with Doxycycline and GSK 2126458 and I hope the following experiments that now are undertaken will give us more useful information. Doxycycline is a tetracycline antibiotic and it is a known life-extender in C. elegans. Its mechanism is not primarily antibacterial but is thought to involve mitochondrial inhibition. By mildly stressing the mitochondria (a concept known as mitohormesis), the organism upregulates its defense and repair mechanisms, leading to increased longevity. Doxycycline is a compound that has an established baseline effect, which gives us a perfect starting point for combination therapy.
GSK 2126458 (Omipalisib) is a potent, dual PI3K/mTOR inhibitor. The PI3K and mTOR pathways are central hubs for sensing nutrients and regulating growth, metabolism, and aging. Inhibiting them is a well-known geroscience approach to extend lifespan.
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Doxycycline: Targets mitochondrial function (mitohormesis)
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GSK 2126458: Targets nutrient-sensing pathways (PI3K/mTOR).
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these pathways may work additively or even synergistically to improve healthspan. This is the dream and gold standard approach in additive and synergistic pharmacology: hitting multiple targets for an even greater effect than we get when we add two effects on top of each other.
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The “Problem” we face is Too Much Success, and this i s a classic and well-known issue in survival experiments. The experiment has a predefined endpoint (e.g., when 90% of the control group has died or after a maximum in amount of days). If a treatment is so effective that a large portion of the population is still alive at this point, you get “right-censored” data. and give us a Statistical Challenge. While it’s a “good problem to have,” it makes calculating a precise median lifespan difficult or impossible. The true effect is likely even larger than what can be measured. A proper analysis would require specialized statistical methods (e.g., Cox Proportional Hazards model) that can handle censored data to show the significant survival advantage.
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The combination doxycycline and GSK 2126458 isn’t just mildly effective; it’s so robust that it broke the standard measurement system for the assay.
Timing is everything in interventions. The C elegance developmental phase (larval stages L1-L4) is a period of intense growth, energy consumption, and mitochondrial activity. A high dose of a mitochondrial inhibitor (doxycycline) during this critical window likely disrupts essential energy production, leading to developmental delays, fragility, or even death. The worm is trying to build itself, and you’re limiting its primary energy source.
**C Elegance being more resiliant when they are given doxycycline from the start of adulthood indicates that we deal with The Concept of Hormesis. Where a low dose of a stressor is beneficial, but a high dose is harmful.
Possible explanation: In adulthood, the primary goal shifts from growth to maintenance. By applying the mitochondrial stressor after development is complete, you gently kick the maintenance and repair systems (e.g., autophagy, unfolded protein response) into high gear without the negative consequences of stunting growth. This enhances resilience and ultimately extends lifespan.
My key take aways are:
Powerful Synergy: The GSK 2126458 + Doxycycline combo appears to be highly effective, warranting replication and rigorous statistical analysis of the censored data.
Timing is Crucial: this identifies a critical treatment window for the GSK 2126458 + Doxycycline combo
The administration protocol must be carefully designed to avoid developmental toxicity and maximize the pro-longevity hormetic effect in adults.
it will be interesting to see what others have learned from similar experiments and with different spieces of animals.
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Alternatively, howeever, doxycycline kills the food.
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When I contacted Ora, they suggested repeating the experiment using both killed and live food as the next step. They also recommended testing the two substances individually with both live and killed food, resulting in six experiments running simultaneously. We also considered testing maximum lifespan and adding substances after the larva stage.
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What were the outcomes?
What kind of mouse studies are these?
We (I) did not go through with the follow up experiments. Sorry if I was unclear in my writing.
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Thanks. I think it is generally known that a limitation of C Elegans experiments where they are fed on E Coli arises from the fact that killing their food increases the lifespan of the worms. Hence the results on Doxycycline have that caution.
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The mouse studies are a rotarod performance test. I would prefer lifespan but it still provides some interesting data. The whole process also provides more publicity for particular molecules. Certain molecules will perform better in the rotarod performance test and this could be beneficial for finding healthspan promoting molecules.
I’m not sure how the human studies work but no molecule has gone to that level yet.
You can check it out at https://pump.science/
We just launched Rapamycin + Doxycycline ($RAPADOCS) last night and it already passed the bonding curve and funded multiple studies.
It’s very promising for me to see that Rapamycin Longevity Lab is capable of getting this done so rapidly. There are molecules launched on this platform from quite a while ago that haven’t been able to even finish the bonding curve.
RLL is using Pump Science as part of our overall strategy of validating molecules but we also are going to use other methods in combination.
A very exciting time for RLL and the longevity field in general imo.