Has anyone gone the rabbit hole of figuring out the optimal way to boost these specific strains?
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Urolithin A Derivatives Targeting Mitophagy in Clinical Trials
While there seems to be no firmly established mechanism by which urolithin A acts to modestly improve mitochondrial function, it seems presumed that this (and a number of other compounds, such as mitoQ) largely function via improving the operation of mitophagy. Mitophagy, mitochondrially targeted autophagy, is a maintenance process that removes damaged and worn mitochondria. Too little of that and the mitochondrial population in a cell become incrementally more dysfunctional. Impaired mitophagy and mitochondrial dysfunction are features of aging, while improved autophagy is a feature of cell stress responses and many interventions known to modestly slow aging in animal studies.
Vandria is one of a number of companies attempting to make therapies for age-related conditions based on novel modifications of established autophagy or mitophagy promoting compounds. Here, Vandria is noted to have started an initial clinical trial for a urolithin A derivative. So far, efforts in this direction have failed to improve on calorie restriction, and only the rapalogs have done better in some aspects than exercise. It remains to be seen as to how this line of work will fare. Certainly, the original urolithin A compound isn’t all that impressive in animal studies.
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Vandria SA, a company at the vanguard of mitochondrial therapeutics developing first-in-class small molecule mitophagy inducers, today announces that the first subjects have been dosed in its first-in-human clinical trial of its lead Central Nervous System (CNS) compound VNA-318. Readout of this combined single and multiple ascending dose trial is expected in the summer of 2025.
VNA-318 is an orally available first-in-class small molecule against a novel target to rejuvenate cells and treat age-related diseases through the induction of mitophagy. The target has strong genetic links to several human diseases including Alzheimer’s disease. It has a dual mode of action with an immediate improvement of memory, learning, and cognitive function, paired with long-term disease-modifying effects such as reduced neuroinflammation, less toxic protein aggregation, and improved mitochondrial function, as shown in pre-clinical models of Alzheimer’s and Parkinson’s disease. Toxicity studies have demonstrated VNA-318 has a wide safety window. A composition of matter patent covering VNA-318 and other compounds has been issued by the US Patent Office.
This Phase 1 randomized, double-blind trial is a combined single and multiple ascending dose trial of VNA-318, designed to assess safety, tolerability, pharmacokinetic, and pharmacodynamic parameters in healthy male subjects.
Company Website:
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adssx
#283
Interesting. I cannot find explicit sources saying that VNA-318 is a urolithin derivative. But Vandria was spun out of Amazentis SA (developers of Mitopure) and they filed this patent: WO2024023585A2 - Urolithin derivatives and therapeutic uses - Google Patents
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Karel1
#284
If I am correct this patent application is extremely broad and could cover thousands of substances and could therefore potentially prohibit competition to do any research on them.
This way vulture capitalist could dominate the marketplace in a way not beneficial to mankind…
Most patent applications start out as broadly as possible, but then get narrowed over time through the patent approval process, challenges by competitors, etc. so I wouldn’t worry about this right now.
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adssx
#286
Also, unfortunately, without that kind of patent there’s 0 financial incentive to do research on compounds such as urolithin A. So I’m glad they found a way to make money with this compound. Otherwise we just have small low-quality trials funded by academia (often in Iran, India or China) as we see with other supplements…
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Maxi
#287
I took Urolithin for 9 months to beat ME/CFS based on the autophagy expectations. One of the many trials which had no effect whatsoever. Now I started Rapa.
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Jay
#288
francesss7ca, In what ways do you want to see if it will help your eyes? Do you have any research to suggest it may have some eye health benefits, especially at only 1 mg per week?
adssx
#289
Urolithin A Provides Cardioprotection and Mitochondrial Quality Enhancement in Rodents and Improves Human Cardiovascular Biomarkers 2025
Paper by the Amazentis/Mitopure team:
Urolithin A enhances heart mitochondrial quality in aging and heart failure models
Cardiac function decline in these models is reduced by Urolithin A
In humans, Urolithin A lowers plasma ceramides associated with heart disease risk
Urolithin A is a promising nutritional approach to support heart health as we age
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For the record, the reduction in ceramides is not new data: they are referring back to their 2022 trial in JAMA Network Open.
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adssx
#291
Urolithin A alleviates NLRP3 inflammasome activation and pyroptosis by promoting microglial mitophagy following spinal cord injury 2025
UrolithinA attenuates NLRP3 inflammasome activation and pyroptosis in microglia.
UrolithinA alleviates NLRP3 Inflammasome Activation and Pyroptosis by Promoting Microglial Mitophagy.
UrolithinA alleviates NLRP3 inflammasome activation and pyroptosis by promoting the activation of autophagy in spinal cord injuried mice.
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Every now and then I look at the bottle of Double Wood Urolithin A I bought, but haven’t yet used, and wonder about it. If you’ve been taking it, do you think it’s the real thing?
Doublewood is a good manufacturer. The supplement is probably the real deal. I just wonder if it moves the needle for longevity.
On my long list of things to test I want to see if a high dose of UA moves the needle on glucose/WBC etc. If it inhibits mTOR then it should have the same effects as Rapamycin.
My assumption at the moment is that it does the same as Rapamycin, but at a much lower intensity.
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Please let us know the results of your experience with it!
I will do, but I have a long list of things to try. It has a half life of under a day which in some ways makes it better than rapamycin as the period of vulnerability to infection is shorter.
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adssx
#297
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adssx
#298
Urolithin A alleviates schizophrenic-like behaviors and cognitive impairment in rats through modulation of neuroinflammation, neurogenesis, and synaptic plasticity 2025
The findings suggest that changes in cognitive function linked to schizophrenia are driven by the interaction among neuroinflammation, neurogenesis, and synaptic plasticity and that UA has the potential to reverse these processes. These observations provide evidence for future clinical trials of UA as a dietary supplement for preventing schizophrenia.
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Great read, I hope there will some human studies some time soon
