@Neo You could point Hevolution in Dr. Brad Stanfield’s direction. He is working on a Rapamycin trial in humans and needs about $400,000 USD.
Mohammed bin Salman may not embody the archetype of virtue, yet is the United States genuinely in a position to claim moral supremacy? It’s an unvarnished truth that great powers frequently partake in actions of questionable ethics.
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Oops I thought you were a bot since I didn’t understand who you were responding to Now I see you were responding to RapAdmin lol, ignore the flag.
I don’t think this is the number per compound. Sounds more like the yearly budget to me.
Calf intestinal alkaline phosphotase extends median and maximum lifespan in BL/6 mice (small sample size though)
Dosing is 100 U/ml per day for mouse. Mouse drinks 3-4 ml a day, so that’s about 300-400 U.
If anyone could help me find a supplier more cost effective than this one, it would be greatly appreciated.
Here is the information that Richard Miller conveyed to Peter Attia in their podcast discussion. The numbers don’t add up, but I’m assuming thats because the labs have indirect costs that may be covered by other budgets, and direct costs specific to each compound:
The ITP budget
The total program budget each year, in direct costs, is about a million dollars
That means that they can test about 6 new molecules per year at $500,000 each
Now, they have enough money—because the NIA has been extremely generous—to test
5 or 6 drugs each year for the first time, and then also go back and recheck one or two of
these a year
So, in the aspirin case, if they were to decide to try aspirin at a few more doses, they
would be eliminating from our program some other drugs that have never been tested,
but look really promising
I am probably missing something crucial here, but how can they have a million dollar yearly budget if they’re spending 6 * $500,000 on testing their compounds every year?
We can ask Richard in the online webinar that starts in 15 minutes…
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Not to get too heavily into politics, as that is not the purpose of this site. In this specific case being discussed you are comparing the ethical choices of one person (MBS) with the collective choices/mistakes and ethical lapses of thousands of people in a government. I think its a lot easier (and makes sense) for one person (e.g. a researcher) to directly question or criticize the choices another single person makes (eg. MBS), and not want to take money from that person because his or her personal values are at odds with that other person.
Nobody here (in this discussion thread) is making any claims about representing any collective moral superiority of any one country or group of people.
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I believe it would be most prudent to remove any remarks pertaining to the Saudis. We shouldn’t incite any tension as their financial support is crucial to us. Our survival hinges on this relationship.
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I would like the ITP to examine potential longevity effects from interventions in the arginase-Ornithine Pathway and also to investigate the longevity effects of normalizied nitric oxide. Citruline/Norvaline or sildenafil/tadalafil would be a good start.
[Frontiers | L-Citrulline Supplementation Increases Plasma Nitric Oxide Levels and Reduces Arginase Activity in Patients With Type 2 Diabetes (frontiersin.org)]
(https://www.frontiersin.org/articles/10.3389/fphar.2020.584669/full)
L-Norvaline, a new therapeutic agent against Alzheimer’s disease - PMC (nih.gov)
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What do you think of the report “Detrimental Effects of Chronic L-Arginine Rich Food on Aging Kidney”?
$500k per compound? How about asking the poster boy?
Quite concerning. Seems I have to pause the citrulline powder intake, until further evidence is published.
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Interesting, thank you for sharing. I did not know they had done this kind of study on mice. Yes, some research indicates that chronic supplementation with arginine could be detrimental. That is why I think Citrulline is a better option when it comes to improve conditions related to cardiovascular dysfunctions.
Inhibiting arginase is a potential target when it comes to managing cardiovascular dysfunctions. Since long term supplementation with arginine might increase arginase, arginine is not a preferred substance. Since there are some human data indicating that citrulline inhibit arginase and increasing NO, I prefer to test citrulline.
" …acute L-arginine treatment enhances endothelial NO production… chronic L-arginine supplementation causes endothelial senescence, up-regulation of the adhesion molecule expression, and eNOS-uncoupling (decreased NO and enhanced superoxide production), which are associated with S6K1 activation and up-regulation of arginase-II. Silencing either S6K1 or arginase-II inhibits up-regulation/activation of each other, prevents endothelial dysfunction, adhesion molecule expression, and senescence under the chronic L-arginine supplementation condition. These results demonstrate that S6K1 and arginase-II form a positive circuit mediating the detrimental effects of chronic L-arginine supplementation on endothelial cells."
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I’m hardly an expert. I thought that citrulline rapidly gets transformed to arginine once in circulation?
Citrulline and Arginine are not each others equals when it come to delivering NO to the the body. Arginine is rather ineffective in doing so.
*“Diminished bioavailability of nitric oxide (NO), the gaseous signaling molecule involved in the regulation of numerous vital biological functions, contributes to the development and progression of multiple age- and lifestyle-related diseases. While l-arginine is the precursor for the synthesis of NO by endothelial-nitric oxide synthase (eNOS), oral l-arginine supplementation is largely ineffective at increasing NO synthesis and/or bioavailability for a variety of reasons. l-citrulline, found in high concentrations in watermelon, is a neutral alpha-amino acid formed by enzymes in the mitochondria that also serves as a substrate for recycling l-arginine. Unlike l-arginine, l-citrulline is not quantitatively extracted from the gastrointestinal tract (i.e., enterocytes) or liver and its supplementation is therefore more effective at increasing l-arginine levels and NO synthesis.”
“Given the growing evidence that endothelial dysfunction has its origins in deficient l-arginine-NO metabolism and given the relative ineffectiveness of l-arginine supplementation on NO metabolism, researchers have begun to explore the potential therapeutic benefits of l-citrulline. l-citrulline is typically supplemented using pharmaceutical/nutraceutical grade l-citrulline, l-citrulline conjugated with malate”
Citrulline increase NO and inhibits arginase. That is how I read the data I have at hand. Arginine is rather ineffecient in doing so and long term use might be detrimental?
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What I get from skimming is that arginine is may be transported across the gut differently and gets chomped by the liver more than citrulline. Whereas citrulline effectively enters the bloodstream and gets converted to arginine in the kidneys. In both cases the target effects are primarily due to arginine levels in the blood. I am not an expert, as I said before.
yes, oral l-arginine supplementation is largely ineffective at the target, which is to increasing NO synthesis and it is not bioavailable. The target is to raise NO levels and/or decrease arginase. Citrulline do this. Arginine do not, or C is at least inferior when it comes to these targets. Tadalafil and sildenafil är other options.
Two more possible drugs to test, and a new interesting aging mechanism.
Article: https://scitechdaily.com/researchers-discover-new-way-to-fight-the-aging-process/
Paper: The DREAM complex functions as conserved master regulator of somatic DNA-repair capacities | Nature Structural & Molecular Biology
Working with Planaria, they used 2 drugs to inhibit the “Dream” complex, which appears to interfere with DNA repair in somatic cells, but not in germ line cells. This inhibition resulted in much improved resistance to DNA damage caused by UV light exposure. The two drugs are DYRK1A inhibitors:
harmine: see https://febs.onlinelibrary.wiley.com/doi/10.1111/j.1742-4658.2009.07346.x
INDY: see Development of a novel selective inhibitor of the Down syndrome-related kinase Dyrk1A | Nature Communications
It would be interesting to see these tested by the ITP.
Apparently both are quite specific, but the latter moreso. As a non-expert, I’m not sure from the paper whether any adverse effects were seen. You have to wonder why the DREAM complex is so well preserved in the genome, when it apparently has adverse effects on non-germline cells - but mainly when the organism is past reproductive age, so perhaps the species does better when older animals die off?
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