Here is the list of all the compounds tested:
3 Likes
yes, Lifespan-extending effects of royal jelly and its related substances on the nematode Caenorhabditis elegans
https://pubmed.ncbi.nlm.nih.gov/21858156/
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0023527
2 Likes
Interesting theory. Would love to see some literature of royal jelly being tested in more organisms (might be an ant specific pathway that makes it so effective). Otherwise it might be a difficult pitch for a proposal.
2 Likes
Thanks for the input! Great questions. Will get back to you on these.
1 Like
Three papers about Taurine. Taurine is a supplement that I wish the ITP program could test. Taurine has many interesting effects. It has distinct effects on mitochondrial health and on cardiovascular health.
The Role of Taurine in Mitochondria Health: More Than Just an Antioxidant - PMC (nih.gov)
“Taurine is a naturally occurring sulfur-containing amino acid that is found abundantly in excitatory tissues, such as the heart, brain, retina and skeletal muscles. Taurine was first isolated in the 1800s, but not much was known about this molecule until the 1990s. In 1985, taurine was first approved as the treatment among heart failure patients in Japan. Accumulating studies have shown that taurine supplementation also protects against pathologies associated with mitochondrial defects, such as aging, mitochondrial diseases, metabolic syndrome, cancer, cardiovascular diseases and neurological disorders. In this review, we will provide a general overview on the mitochondria biology and the consequence of mitochondrial defects in pathologies. Then, we will discuss the antioxidant action of taurine, particularly in relation to the maintenance of mitochondria function. We will also describe several reported studies on the current use of taurine supplementation in several mitochondria-associated pathologies in humans.”
“Taurine is a sulfur-containing amino acid and known as semi-essential in mammals and is produced chiefly by the liver and kidney. It presents in different organs, including retina, brain, heart and placenta and demonstrates extensive physiological activities within the body. In the several disease models, it attenuates inflammation- and oxidative stress-mediated injuries. Taurine also modulates ER stress, Ca2+ homeostasis and neuronal activity at the molecular level as part of its broader roles. Different cellular processes such as energy metabolism, gene expression, osmosis and quality control of protein are regulated by taurine. In addition, taurine displays potential ameliorating effects against different neurological disorders such as neurodegenerative diseases, stroke, epilepsy and diabetic neuropathy and protects against injuries and toxicities of the nervous system.”
https://www.biomolther.org/journal/view.html?volume=26&number=3&spage=225&year=2018
“Taurine is an abundant, β-amino acid with diverse cytoprotective activity. In some species, taurine is an essential nutrient but in man it is considered a semi-essential nutrient, although cells lacking taurine show major pathology. These findings have spurred interest in the potential use of taurine as a therapeutic agent. The discovery that taurine is an effective therapy against congestive heart failure led to the study of taurine as a therapeutic agent against other disease conditions. Today, taurine has been approved for the treatment of congestive heart failure in Japan and shows promise in the treatment of several other diseases. The present review summarizes studies supporting a role of taurine in the treatment of diseases of muscle, the central nervous system, and the cardiovascular system. In addition, taurine is extremely effective in the treatment of the mitochondrial disease, mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), and offers a new approach for the treatment of metabolic diseases, such as diabetes, and inflammatory diseases, such as arthritis.”
The intracellular concentration of taurine is commonly 5–50 mM and the plasma concentration of taurine is approximately 100 μM. When taurine is supplemented, the plasma taurine content usually reaches its peak within 1 h to 2.5 h of taurine intake. In an analysis on the pharmacokinetics of oral taurine supplementation (4 g) in healthy adults. These individuals, who had fasted overnight, showed a baseline taurine content in a range of 30 μmol to 60 μmol. Then, 1.5 h after taurine intake, the plasma taurine content increased to approximately 500 μmol. Plasma taurine content subsequently decreased to baseline level 6.5 h after taurine intake.
4 Likes
i guess one issues with having a large combination is that we won’t know what’s contributing to any benefit that is observed. And perhaps some of the elements counteract each other? But I guess each combination of the molecules at different doses could potentially be tested on simple models like worms, etc. (e.g. with the technology at Ora Biomedicals)
3 Likes
I’d be interested in Rapamycin + Acarbose + Luteolin + ezetimibe
Acarbose for inhibiting alpha-glucosidase and alpha-amylase
Luteolin for inhibiting fructokinase
Ezetimibe for inhibiting the absorption of cholesterol
I believe these 3 have minimal side effects so one need not worry too much about the ideal dose
3 Likes
I understand that issue, but I think ITP should think outside the box once in a while. If you combine several compounds you could find surprising synergy effects that is unexpected. They won’t know before they try it.
One of 5 trials they do, should be a moon shot if you ask me.
6 Likes
I agree in spirit. 5 may be a bit excessive at this point, but I’d be curious how some of the supported interventions work with new interventions. E.g. acarbose with white kidney bean extract, rapamycin with rifampicin, etc. The only 3 drug intervention I see being viable right now is 17-alpha estradiol, rapa, and acarbose.
2 Likes
How about rilmenidine? It’s been approved as a blood pressure reducer, but it appears to also inhibit MTORC1. See https://onlinelibrary.wiley.com/doi/10.1111/acel.13774
5 Likes
Thanks, added it to the list.
-Added a fibrate drug called fenofibrate, which is a PPAR-alpha agonist, and removed PPAR-gamma drugs from the list.
-Fair enough, not really. According to this study though losartan enhanced Klotho levels by 23% in diabetic patients, so there may be something there. Added to the list.
-Noted. I couldn’t find any evidence that deprenyl is a sigma_1 agonist, only that it binds to the receptor (if you could send me some literature suggesting the contrary, I’d be happy to see it). I’m considering adding something like Cutamesine, which is a known sigma_1 agonist.
-Caffeic acid has been tried by the ITP– no observed lifespan benefit from it.
4 Likes
The ITP needs desperately to consider other types of interventions, foremost among them gene therapy. Liz Parrish’s telomerase and follistatin therapy has already been tested in mice with a 41% life extension.
4 Likes
Yes, fibrates are possibly interesting. There is a report of some of them being senolytic, too.
Losartan hasn’t been tested in the ITP, though candesartan has been and telmisartan is in progress (both in combination with other agents).
You might be right, I can’t find the primary source for the claim that deprenyl activates \sigma_1. (I didn’t make it up – Wikipedia says the same, citing books I don’t have access to)
Caffeic acid is interesting, but I don’t think it has pharmacologic overlap with caffeine. You might consider cocoa extract, actually.
1 Like
My mistake about caffeic acid and caffine! Seems like they’re false cognates. I am hesitant about adding caffeine to the list– it’s been used so universally for so long in people that we probably can conclude it doesn’t have any significant lifespan effects in people.
1 Like
ITP Drugs of Interest - Single drug.pdf (58.8 KB)
ITP Drugs of Interest - Multi drug.pdf (56.5 KB)
Here is the updated list! Let me know what you all think.
2 Likes
Perhaps another drug / compound…
Increased hyaluronan by naked mole-rat HAS2 extends lifespan in mice
Abundant high molecular weight hyaluronic acid (HMW-HA) contributes to cancer resistance and possibly longevity of the longest-lived rodent, the naked mole-rat1,2. To study whether the benefits of HMW-HA could be transferred to other animal species, we generated a transgenic mouse overexpressing naked mole-rat hyaluronic acid synthase 2 gene (nmrHAS2). nmrHAS2 mice showed increase in hyaluronan levels in several tissues, and lower incidence of spontaneous and induced cancer, extended lifespan and improved healthspan. The transcriptome signature of nmrHAS2 mice shifted towards that of longer-lived species. The most striking change observed in nmrHAS2 mice was attenuated inflammation across multiple tissues. HMW-HA reduced inflammation via several pathways including direct immunoregulatory effect on immune cells, protection from oxidative stress, and improved gut barrier function during aging. These findings demonstrate that the longevity mechanism that evolved in the naked mole-rat can be exported to other species, and open new avenues for using HMW-HA to improve lifespan and healthspan.
5 Likes
Do we know where normal hyaluronic acid
supplements are on the molecular weight scale compared to this?
I noticed that Blueprint includes 300mg hyaluronic acid at the second meal each day and Bryan Johnson uses the brand below.
Does anyone have experience with HA supplements, I was thinking of starting them for my joints (and understand that it may have skin benefits as a “side effect”) if it also has any longevity benefit that would be a good bonus 
https://www.amazon.com/Hyaluronic-tablets-Strength-stronger-tablet/dp/B00GYZ7S2S
1 Like
Do you think there is correlation between increased lifespan and increased health span, specifically are there supplements that we should take for health span that will fail ITP. Senolytics for example.