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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Has anyone asked Ora about this? I assume they are well aware.
I did. WIP. Will update after.
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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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I think that is this:
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Saw it claimed that Cyrene provides 75% lifespan increase (preprint)… though also suggests caffeine should work well from older experiments Cyrene: A Novel Geroprotective Compound that Extends Lifespan and Healthspan in C. elegans and Drosophila - PMC . Some of the data from previous studies they show further down doesn’t seem consistent with ora results.
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orforglipron.
Oral glp1
Also myo Inositol trispyrophosphate
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@Krister_Kauppi: @Curious: @adssx:
What is the current longest living lifespan of C Elegans from Wormbot or other testing platform?
– From what I’ve found:
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Placebo: 22.9 days
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Carvedilol 50uM + Doxycycline HCl 50uM: 27 days (adssx)
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Sulforaphane 50uM + Nilvadipine 10uM: 27 days (adssx)
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GSK2126458 : 27.8 days (Krister_Kauppi)
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Doxycycline HCl + GSK2126458: 33 - 34 days? (Curious)
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Doxycycline HCl + lithium : 34 days (Curious)
Do we have any better results?
(from what I’ve found Ora database is not updated regularly - it doesn’t has these combinations yet on leaderboard)
https://orabiomedical.com/mmcleaderboard/
I wonder what would be the result if we would test this combination: Doxycycline HCl + lithium + GSK2126458
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They told me a few days ago that they will update it…
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Also Epiterna did experiments similar to Wormbot:
- GSK2126458 + Doxycyline: 40 days
- GSK2126458 + LY-294002 41.5 days
It seems like PI3k inhibitors work best in C Elegans - in 2008 some study found 900% lifespan extension with PI3k mutation (160 days median lifespan):
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I like that you look att total days but its important to also take inconsideration that the lifespan on the control group can differ between the treatments. If I remember it right then Ora has observed that the worm lives a bit longer then now compared to what they did. So if we only look at total days lived then the comparison between compounds can be misleading. Just something to keep in mind but I like your list!
@adssx Thanks for the update!
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I have added the epiterna data to the LID database. My plan is to add also the Ora data there as well this year.
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UDCA vs TUDCA:
UDCA medium dose increases by +15% (p=0.001), whereas TUDCA massively decreases at all doses (p<0.01):
Lercanidipine dose-response failed despite previous promising results:
Methylene blue:
Pantethine: neutral?
Hypoxia-in-a-pill (to reproduce this paper: Therapeutic hypoxia for mitochondrial disease via enhancement of hemoglobin affinity and inhibition of HIF-2α - PMC ):
Compound A:
Compound B:
Combination A+B:
Oxaloacetate (“intermediate of the citric acid cycle, where it reacts with acetyl-CoA to form citrate, catalyzed by citrate synthase”) => Massive negative impact on lifespan (p<0.001):
Citrate @John_Hemming: massive negative impact, p<0.01 (trying to replicate the flies study: Dietary citrate supplementation enhances longevity, metabolic health, and memory performance through promoting ketogenesis - PMC )
Melatonin (trying to replicate https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1016/j.jalz.2013.05.249 ): neutral
Menaquinone: Neutral
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The Krebs cycle is a massive dead end. Should’ve been obvious ever since the 20,000 ppm AKG ITP study failed to extend lifespan.
Unsurprisingly I disagree with the thesis that the Krebs cycle does not matter. Different parts of Krebs have different effects.
C Elegans is really different to other species. I have not really tried to get into the mechanistic differences as I don’t personally care about C Elegans.
I did contribute to one of the tests in C Elegans, (IPAM) but generally I don’t think it produces useful information.
When all animal models fail, no actual human clinical data exist and you’re left with mechanistic speculation maybe it is time to reconsider your approach.
I have my own n=1 data. In the end that has to be my own personal priority. Obviously my family are important as well. However, if I find something works for me and my family I don’t care about any quantity of worm experiments.
BTW, did anybody test Thioflavin T?
It was the winner in CITP (Caenorhabditis Intervention Testing Program)
ThT was the most robust of the chemicals we tested, as it significantly and reproducibly extended lifespan in five of the six strains tested, with only JU1348 failing to respond to treatment with significant lifespan extension (Fig. 4a, Supplementary Fig. 5 and Supplementary Table 4). In addition to being the most robust of the treatments, ThT also showed the most potent effect. We found that in some trials, for certain strains, ThT-treated populations exhibited a doubling of the median lifespan relative to control-treated populations (Fig. 4a and Supplementary Fig. 5). The average median lifespan (across all the trials for a given strain) ranged from a small but reproducible effect on HK104, the long-lived C. briggsae strain, to a significantly large effect (70% extension of median lifespan) on C. elegans strain MY16
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