More good news on Urolithin-A

#1

Long-term urolithin A had a beneficial effect on the secondary end points of muscle endurance and biomarkers of mitochondrial health.

Full Paper:

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#2

Reminds me of a similar article about stearic acid. However this is about mitochondria fusion rather than mitophagy. I wonder how those two processes are connected.

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#3

And zone-2 training is supposed to increase mitochondria density, size and functionality. I wonder what the best protocol that combines exercise and diet is for mitochondrial function!

On a similar note, metformin is also supposed to be a ā€œweak mitochondrial poisonā€. Does it benefit the mitochondria in any way due to hormesis? Or is its benefit essentially via keeping blood glucose levels low?

Sorry, Iā€™ve taken this post on many tangents now.

But itā€™s great to hear about urolithin-A. Iā€™ll keep my eye out for more on this supplement!

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#4

Another new study on Urolithin A

Full Paper Here:

https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(22)00158-6

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#5

And another recent paper on Urolithin A:

Urolithin A attenuates auditory cell senescence by activating mitophagy

https://www.nature.com/articles/s41598-022-11894-2

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#6

I hope Urolithin A gets formally tested by the ITP. Promising compoundā€¦

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#7

Urolithins will also be eventually produced after the intake of all ellagitannin-containing foods and medicinal plants as is the case of camu camu (Myrciaria dubia ), arctic bramble, rose hip, sea buckthorn, cranberry, Geranium , and oak-aged spirits (whisky, etc.).

Cheers. Make it single malt.

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#8

Is anyone taking Urolithin-A? Rather expensive.

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#9
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#10

A new paper:

Urolithin A Produced by Novel Microbial Fermentation Possesses Anti-aging Effects by Improving Mitophagy and Reducing Reactive Oxygen Species in Caenorhabditis elegans

Urolithin, intestinal microbiota metabolites of ellagitannin-rich foods, exhibit anti-aging activities. However, urolithin A is significantly superior to other types of urolithin with regard to this anti-aging function. This study aimed to screen edible urolithin A-producing strains of bacteria and explore the corresponding anti-aging efficacy of fermented products produced by these strains using Caenorhabditis elegans as a model. Our results showed that the Lactobacillus plantarum strains CCFM1286, CCFM1290, and CCFM1291 converted ellagitannin to produce urolithin A; the corresponding yields of urolithin A from these strains were 15.90 Ā± 1.46, 24.70 Ā± 0.82, and 32.01 Ā± 0.97 Ī¼M, respectively. Furthermore, it was found that the pomegranate juice extracts fermented by the CCFM1286, CCFM1290, and CCFM1291 strains of L. plantarum could extend lifespan by 26.04 Ā± 0.12, 32.05 Ā± 0.14, and 46.33 Ā± 0.12%, respectively, by improving mitochondrial function and/or reducing reactive oxygen species levels. These findings highlight the potential application of this fermentation in the subsequent development of anti-aging products.

Full paper (open access):

https://pubs.acs.org/doi/10.1021/acs.jafc.3c01062

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#11

I ordered a couple different varieties of yellow raspberries, so it looks like now I will need the CCFM1291 strains of L. plantarum in order to complete the plan.

Anybody know where to find this? I have only very time consuming methods.

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#12

More on Urolithin A, from the company/people that first researched it. (Iā€™ll wait for the third party validation, and a lower cost).

Urolithin A induces cardioprotection and enhanced mitochondrial quality during natural aging and heart failure

Cardiovascular diseases remain the primary cause of global mortality, necessitating effective strategies to alleviate their burden. Mitochondrial dysfunction is a driving force behind aging and chronic conditions, including heart disease. Here, we investigate the potential of Urolithin A (UA), a gut microbiome-derived postbiotic that enhances mitophagy, to ameliorate both age-related decline in cardiac function and cardiac failure. We highlight the significance of targeting mitochondria, by comparing gene expression changes in aging human hearts and cardiomyopathies. UA oral administration successfully counteracts mitochondrial and cardiac dysfunctions in preclinical models of aging and heart failure. UA improves both systolic and diastolic heart functions, distinguishing it from other mitochondrial interventions. In cardiomyocytes, UA recovers mitochondrial ultrastructural defects and decline in mitochondrial biomarkers occurring with aging and disease. These findings extend UA?s benefits to heart health, making UA a promising nutritional intervention to evaluate in the clinic to promote healthy cardiovascular function as we age.

Competing Interest Statement

J.F., C.T., D.D., are employees, P.A.A. was an employee of Amazentis SA, which holds patents on Urolithin A applications.

Sophia Liu, Julie Faitg, Charlotte Tissot, Dimitris Konstantopoulos, Ross Laws, Guillaume Bourdier, PĆ©nĆ©lope A Andreux, Tracey Davey, Anurag Singh, Chris Rinsch, David J Marcinek and Davide Dā€™Amico

bioRxiv. posted 24 August 2023, 10.1101/2023.08.22.554375

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#13

I bought Ultrapome developed by Harvard Medical School researchers.

Ultrapome (Amazon UK)

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#14

I went ahead and bought the Mitopure anyway. Going to try both the prebiotic and postbiotic options.

#15

Just started from Timeline. Yes, too pricey. Too early to say if beneficial but hoping will mitigate some negatives of my Metformin for longevity use. This is my IPad profile ( @Financial_Term_Struc ), but Iā€™m also @Walter_Brown

#16

Let us know how it goes.

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#17

A new paper (open access):

The aging of an organism is hallmarked by systemic loss of functional tissue, resulting in increased fragility and eventual development of age-related neurodegenerative, musculoskeletal, cardiovascular, and neoplastic diseases. Growing scientific evidence points to mitochondrial dysfunction as a key contributor in the aging process and subsequent development of age-related pathologies. Under normal physiologic conditions, the body removes dysfunctional mitochondria via an autophagic process known as mitophagy. Urolithin A (UA), a metabolite produced when gut microflora digests the polyphenol compounds ellagitannin and ellagic acid, is a known inducer of mitophagy via several identified mechanisms of action. The primary objective of this scoping review is to identify and summarize the clinical relevance of UA supplementation in the prevention of age-related pathology and diseases. A computer-assisted literature review was performed using PubMed and EMBASE for primary source research articles examining UA supplementation and aging-related pathologies. A total of 293 articles were initially identified from a database search, and 15 articles remained for inclusion in this review, based on predetermined criteria. Analysis of the 15 identified publications demonstrated that UA holds potential as a dietary intervention for slowing the progression of aging and preventing the development of age-related disease. This review also illustrates the potential role that mitochondrial health and inflammation play in the progression of age-related pathology. Identifying the clinical relevance of UA supplementation in the prevention of age-related pathology and diseases will help further the focus of research on treatments that may improve the longevity and quality of life in patients at risk for these comorbidities.

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#18

Inhibition of the NF-ĪŗB and mTOR targets by urolithin A attenuates D-galactose-induced aging in mice

Urolithin A (Uro-A), an intestinal microbiota metabolite of ellagitannin, has anti-aging properties. Through the direct intake of ellagitannin (or ellagic acid) and strains capable of producing Uro-A, the transformation of Uro-A in vivo is a potential method to develop anti-aging preparations. Therefore, this study aimed to investigate the dose-response relationship between the colonic infusion of Uro-A and its anti-aging effects. Results indicated that Uro-A exhibited a dose-dependent anti-aging effect in the colon, and the minimum effective dose might be 3.0 mg kg-1day-1. The main manifestations were that, compared with the model group, 3.0 mg kg-1 day-1 and 15.0 mg kg-1 day-1 of Uro-A can increase forelimb grip strength by 11.87% and 16.72%, respectively, and increase the discrimination index by 92.14% and 238.11%, respectively. Both doses effectively inhibited the D-galactose-induced increase in oxidative stress levels in the body, muscle atrophy, and neuronal apoptosis. Additionally, Uro-A released through the colon could alleviate D-galactose-induced aging in mice by inhibiting NF-ĪŗB and mTOR targets, providing significant protection for motor and cognitive functions. These findings provide a theoretical basis for future application and development of ellagitannin (or ellagic acid) in combination with strains capable of producing Uro-A.

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#19

Why did they use a colonic infusion? Does ellagitannin break down in the gut?

#20

Some thought on that here:

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