Could be interesting to connect
to what mechanism(s)
to what “hallmark(s)” of aging and
to what key aspects of healthy aging/longevity
— eg I feel quite ok re cardio vascular, metabolic and “frailty” areas of actions, protocols and risk mitigation,
— but feel a lack of things for anti cancer, long term neurodegeneration and overall true life extenders in a person who generally has optimized the basics.
I asked them about the super high dose used previously and suggested that they test a lot lower dose next time. I’m not sure if they took that suggestion of mine or why they decided on testing 800 ppm. While I’m glad they’re testing lower than last time, I think it’s still too high of a dose, for practical purposes. The dose they tested already, 4000 ppm, is equivalent to about 2 g daily for an adult human while 800 ppm is more equivalent to 400 mg daily. Much better but still a kind of impractically high dose. It will be interesting to see the results.
I’m glad to see they are testing DNP. I have been waiting for someone to replicate the old life span study that found that it extended life span in mice, IIRC.
Taurine Study:
Combination of Taurine and Black Pepper Extract as a Treatment for Cardiovascular and Coronary Artery Diseases
My first suggestion for ITP testing would be dietary nucleic acids: DNA + RNA. There’ve been six prior studies in mice and rats where they were either fed or injected. Previously discussed here. These hold the record for life extension. It was a mix of DNA and RNA that produced the largest increases rather than RNA alone. Perhaps a 50:50 mix should be tested.
These have largely been forgotten by researchers. If ITP can validate these older studies it may renew research interest.
the Kraig trial (phase 2, 2018) had no immunological response, I wonder what biomarkers they used.
Hmmmm… That’s a lot of Cana. Isn’t there anything better to test?
Feeling slightly disappointed.
I tend to agree. But - given the great results so far, I guess they’re trying to figure out if a low, persistent dose is at all effective. That would translate easily and quickly to humans I suspect with low risk.
Don’t know if it has been suggested before but I’d like to see Verteporfin tested. Probably needs to be injected though, which is a real bummer.
They won’t do injectables.
TPPU. Another one that seems to be involved in suppressing NF-κB signalling…
also seems involved in increasing the expression of tight junction proteins (that I think some people where discussing elsewhere on the forum).
Anyone know more about this compound?
TPPU restored the mechanical and thermal thresholds, decreased cell apoptosis, alleviated axonal injury and glial responses, and protected vascular permeability by increasing the expression of tight junction proteins. TPPU relieved PIPN by inhibiting the activation of the sEH and NF-κB signalling pathways by decreasing the levels of inflammatory cytokines and oxidative stress.
Any idea why they’re hitting H_2S so hard? They’ve tried pure sulfur (SG1002, a very specific preparation of 0-valent S) three times, with the summary reporting 2 failures and 1 in progress. (The first trial was apparently mis-dosed, IIRC). They already have a STS trial running. I think the main sulfur guy is a friend of Miller’s, but I’d have expected more positive results to be published for the amount they’re chasing this.
After looking more closely I don’t think this is a viable drug for the application – too toxic, hard to administer. I was briefly enthusiastic reading the Wikipedia page which said that it has been investigated for fibrotic disease, at least Peyronie’s if I recall. Turns out that was only in vitro stuff, not a serious suggestion.
The alleged action was through YAP, which to my limited knowledge is mostly involved in cell mechanics. Hence my continued (fruitless) agitation to test fasudil in more models.
I find luteolin being a very promising substance to test in the ITP. It shows potential to activate autophagy and apoptosis through a many pathways in many cell-lines. .
"Luteolin inhibits tumor growth by targeting cellular processes such as apoptosis, cell-cycle progression, angiogenesis and migration. Mechanistically, luteolin causes cell death by downregulating Akt, PLK-1, cyclin-B1, cyclin-A, CDC-2, CDK-2, Bcl-2, and Bcl-xL, while upregulating BAX, caspase-3, and p21. It has also been reported to inhibit STAT3 signaling by the suppression of STAT3 activation and enhanced STAT3 protein degradation in various cancer cells. "
" The autophagy process is classified into different types i.e., micro, macro and chaperone-mediated autophagy that transmits to the lysosome. Macroautophagy is a metabolic process that wraps protein cells to form autophagosomes with a bilayer membrane, the membrane fuses with the lysosomal membrane and degrades the wrapped protein by hydrolyzing [42]. Luteolin affects various pathways, i.e., it is involved in autophagy that includes nucleation and elongation that prevents the progression of cancer. Luteolin attenuates Wnt signaling (Wingless-related integration site) pathway for the upregulation of fizzled class receptor to downgrade cancer cells. Beclin1 plays an important role in autophagy, a process involved in cell survival that increases during cell stress and decreases over the cell cycle. The Beclin1 regulates autophagy during the initiation step that suppresses tumors and downregulates the Beclin1 expression in cells. Luteolin affects the ER chaperone binding and activates stress sensors and induces autophagy [43]. The Beclin1 promotes protein light chain formulation that effects elongation steps through the downregulation of light chains. Autophagy can also help in the survival of cells in cancer cells with Beclin1 downregulation [44]."
Impressive data from Luteolins role in autophagy.
What’s the list of things they’re considering for 2024?
I’ve just created this prediction market to identify the most successful interventions: ITP: Which drug(s) will increase median lifespan the most in males by 2030? | Manifold
Please add your prediction(s)! Hopefully, the “wisdom of the crowd” will converge towards what’s best… And then we can suggest that…
I saw Nathan Cheng suggest the market prediction idea yesterday… its a good idea, if you can get some critical mass of “voters”.
I found it very interesting to hear Richard Miller (on the recent Peter Attia podcast) mention they only had 28 submissions for the ITP program last year. It would be nice if there were a lot more ideas submitted… we have until Feb. 28th of 2024 to get our suggestions in… see here: Feb. 28th Cutoff For NIA ITP Aging Drug Submissions - Ideas for New Testing?
I must say that I didn’t even know Nathan Cheng, shame on me… His concept is amazing, we could have self-funding trials thanks to that:
https://twitter.com/realNathanCheng/status/1735762470575251481
I’ve been following prediction markets for the past few years, mostly on geopolitics and economics, and they tend to be more correct (or at least directionally correct, and more so than so-called “experts” in the media), even with a relatively small number of “voters”. I set my critical mass at about 25–50. Below 25, I don’t pay attention. Above 50, I somehow “trust”.
This paper puts the critical mass even lower, at n = 20! “We have shown that increasing the crowd size improves the quality of the data. This effect occurs especially with small n. From about n = 20, the improvements are only very small and rather not worthwhile in relation to the costs since the costs grow linearly with n. For n greater than 20, even a deterioration of the F1 score can be observed, which is mainly explained by the increase of FP.”
The most famous example is, of course, Francis Galton’s Vox Populi: 800 voters were accurate within 1% of the true result: Vox Populi | Nature
If we can get to these numbers, it would be amazing, but again, even small numbers may be informative. So please all vote 
=> ITP: Which drug(s) will increase median lifespan the most in males by 2030? | Manifold
Thank I’d never seen this
