#359

The eminent researcher of mitochondria, Dr. Mark Tarnopolsky, MD, PhD, gave an interesting interview about mitochondria in general and ways to boost them and preserve their health. In passing, he expressed extreme scepticism toward the utility of Urolithin A, and debunks some of the prominent studies of Urolithin A (approx. minute 25). He’s also pretty unenthusiastic about NAD.

Dr Mark Tarnopolsky, MD, PhD | Mitochondrial Mastery: Supplements, Exercise & Longevity Insights (degrees of health)

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#360

Urolithin a modulates inter-organellar communication via calcium-dependent mitophagy to promote healthy ageing 2025

Our multi-omic analyses reveal that UA reorganizes ER, mitochondrial and lysosomal networks, linking inter-organellar dynamics to mitochondrial quality control.
In C. elegans, UA induces calcium release from the ER, enhances lysosomal activity, and drives DRP-1/DNM1L/DRP1-mediated mitochondrial fission, culminating in efficient mitophagy.
Similarly, in mammalian cells, UA increases intracellular calcium, enhances mitophagy and mitochondrial metabolism, and mitigates stress-induced senescence in a calcium-dependent manner.

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#361

For anyone interested in Timeline Urolithin A, it is on sale now, 40% off. I just bought 3 on Amazon…

Neurogan price for their Urolithin A product looks tempting but they were unable to provide me a 3rd party COA showing how much Urolthin A was actually in the product. I doubt there is any.

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#362

Thanks Stan!

I was never willing to spend on those, but I’ve been curious about the gummies, so I pulled the trigger and chose the subscription for 46% off!

FYI, I checked and saw they are offering 40% off on their website, but they link Amazon as an option, and that way I could lower the price a touch by choosing subscribe and save. If they didn’t offer that link, I would not have known I could trust the amazon source.

Still most likely overpaying for no reason, but if I can have a yummy gummy, it was worth a gamble. FWIW, I’ve been taking Aeternum brand.

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#363

Can you provide the link to the Timeline product? Thanks.

#364

Either Amazon or Timeline. Try these:

https://www.amazon.com/ Search for Timeline Urolithin A

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#365

ConsumerLab reports that tests done by SuppCo showed that Neurogan, CodeAge, Pure Encapsulations and Timeline contained the claimed amount.
Neurogan being the cheapest.

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#366

I tracked down that report and yes, Neurogan did pass their testing as having the claimed amount of Urolithin A.

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#368

I have been taking 1,000 mg/day of Urolithin-A for over two months, which is one of three periods of time required to produce different types of benefits. Two months is the target period for beginning to see measurable functional gains in muscle endurance. As someone over 70 who has experienced increasing challenges in fatigue and recovery time related to exercise over the past few years, I can report a significant improvement in both. A few years back, I did strenuous 45–60-minute mountain hikes 4-6 days a week. Gradually, these hikes became more challenging in terms of muscle soreness and especially recovery time. This past year, I have had to allow at least four and sometimes six days to elapse before I could hike again. The most interesting change I attribute to Urolithin-A is how the improvement, especially in recovery time, manifested itself. The change was almost binary. For most of the two months, I felt no effect at all. I had committed to giving the experiment a four-month run but was beginning to think I was wasting my time and money. Then, recently, I want for a hike that immediately felt like it did several years ago. The soreness was typical for the level of effort at any age but the recovery period was ~24 hours and the soreness was gone. I was eager for another hike! I do not have exact records but I estimate that it has been 15 years, maybe 20, since I felt that way. According to the research I have reviewed, this effect begins to manifest itself at around two months and plateaus at four months. I will report again at that time. I’m not going to take the time to detail the reasons I attribute these gains to Urolithin-A and not to other environmental, biochemical, or psychological effects but I am careful to rule such possibilities out to the extent possible in these contexts.

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#369

Thanks for sharing your experience. What brand did you use?

#370

For most of that time, I have used aeternum. I’m switching to Neorogan because they had a discount offer on Amazon and they seem to be one of the most used brands.

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#371

Given that the improvements seem to be to a younger period and nothing beyond that, I wonder if younger people would experience meaningful benefits from Urolithin-A.

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#372

I’m wondering the same. I think at the very least, it wont do any harm and at best, prevent any age related decline in whatever the Urolithin A is supposed to improve. The same can probably be said about a lot of interventions like GlyNAC for instance (which works in different ways).

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#373

New Nature Aging paper of a Randomized Clinical trial of Urolithin A on aging immune systems.
Published Nov 5th 2025 but I didnt see it in this thread or w/ search.

Randomized Controlled Trial
Nat Aging 2025 Nov;5(11):2309-2322.

doi: 10.1038/s43587-025-00996-x. Epub 2025 Oct 31.

Effect of the mitophagy inducer urolithin A on age-related immune decline: a randomized, placebo-controlled trial

https://www.nature.com/articles/s43587-025-00996-x

#374

Discussed here: More good news on Urolithin-A - #54 by RapAdmin

It’s annoying to have two UA threads.

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#375

Thanks! I agree, two threads is annoying. I tried to post it in the “main” thread for Urolithin-A.

#376

This randomized, double-blind, placebo-controlled trial investigated the effects of urolithin A (UA), a mitophagy inducer, on age-related immune decline in 50 healthy middle-aged adults over a 4-week period. Participants received either 1,000 mg/day of UA or placebo, with assessments at baseline and day 28 13.

UA supplementation led to a significant expansion of peripheral naive-like, less terminally exhausted CD8+ T cells. This was accompanied by an increase in CD8+ T cell fatty acid oxidation capacity, indicating metabolic remodeling towards improved mitochondrial function 15.

Beyond CD8+ T cells, UA also increased the frequency of peripheral CD56dimCD16bright natural killer (NK) cells and nonclassical CD14loCD16hi monocytes. These immune cell populations are important for immune surveillance and inflammation regulation 7.

Mitochondrial biogenesis was augmented in CD8+ T cells of UA-treated participants, demonstrated by elevated expression of PGC-1α, the master regulator of mitochondrial biogenesis. Despite no change in mitochondrial mass or membrane potential at the 28-day timepoint, ex vivo experiments confirmed rapid mitophagy induction by UA, supporting mitochondrial quality control 7852.

UA improved immune cell function as evidenced by enhanced TNF secretion upon T cell activation and increased phagocytosis of Escherichia coli by monocytes. These functional improvements suggest a more robust immune response capability 89.

Single-cell RNA sequencing revealed that UA induced transcriptional changes across immune populations, particularly CD8+ T cells. These changes included upregulation of Wnt-associated stemness factors (TCF7, LEF1), increased IL7R expression, and downregulation of genes linked to T cell exhaustion and immune suppression. Pathways related to T cell receptor signaling, cytoskeletal remodeling, and adhesion were activated, while inhibitory GPCR–Gαs–PKA signaling was suppressed 9105253.

In NK cells and monocytes, UA induced gene expression profiles indicative of a less inflammatory, more mature state. Monocytes showed upregulation of mitochondrial genes and markers associated with anti-inflammatory M2-like polarization, along with downregulation of interferon response genes. B cells also exhibited a reduction in inflammatory gene signatures 1011.

The study concludes that short-term UA supplementation leads to phenotypical, metabolic, functional, and transcriptomic alterations that counteract features of immune aging and inflammaging.

These findings support the potential of UA as a safe and effective intervention to improve immune health during

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#377

Thanks desertshores…I appreciate all those studies. As a long time biomedical researcher, I do put a lot more weight on in vivo studies, eg, in animals or, even, better, human clinical trials.

In vitro (eg, in glass) studies are great for helping elucidate specific mechanisms and pathways but don’t always translate to whole animal effects. I sometimes feel like you can almost show any effect in vitro with the right setup/cell system/perturbation, etc.

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#378

I’ve been saying that for years on this site, and I’m surprised even RapAdmin cites them still. I don’t even bother reading them. The conclusion I’ve made is that it has little to no effect of telling someone this, they deeply want to still believe it.

It’s maybe because they can find anything they want that way. I prefer things that work, and I like the fact that some things do and others don’t.

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#379

I will probably need to adjust the dose in my Max 5 Super mix as I only have 500mg per daily dose

1 Like