#12

More on Urolithin A, from the company/people that first researched it. (I’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, Pénélope A Andreux, Tracey Davey, Anurag Singh, Chris Rinsch, David J Marcinek and Davide D’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 I’m also @Walter_Brown

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#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-κB 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-κB 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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#21

Evidence of Urolithin A as geroprotector in humans.

source: x.com

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#22

Thank you for bringing the good news about Urolithin A. I’m ready to start taking it, and also, would a daily dose of 1000mg offer greater benefits?

#23

I’m not sure that’s good news. Most trials are outside the inner circle so they are no significant changes.
In particular that shows again that there are mostly no significant clinical outcomes and only in-vitro ones.

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#24

However, there is no double-blind study on whether weekly administration of rapamycin, coupled with the uncertainty of weekly administration, prolongs human lifespan or improves certain inflammatory markers.

#25

Didn’t the Mannick study at least show an improvement in immune function?

#26

Yes, one phase 2 study did, for ResTORbio, but then the FDA changed the endpoints for the phase 3 trial and that trial the drug failed.

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#27

Chris Masterjohn gives a convincing reason why we shouldn’t waste our money on Urolithin A. You have to have a twitter profile to see the entire thread.

Chris Masterjohn on X: “THE CLAIM: Four months of Mitopure Urolithin A will boost your VO2max by 14.3%, your strength by 12%, and in just 8 weeks will boost your endurance by 17%, without doing any exercise! :thinking: Since four months of Mitopure costs $500, it’s worth taking a closer look at this claim. https://t.co/qX94D5emBl” / X

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The latest worm lifespan experiment：Urolithin A extended the lifespan of worms by 45%, surpassing other compounds such as rapamycin
#28

There are several brands of urolithin A in addition to Timeline. Any experience with the less expensive brands?

#29

I’m taking the capsules from get healthspan. It’s still expensive but definitely better than timeline, and I feel I can trust their quality.

Having said that, I’d love to find an even less expensive trustworthy option.

It was just last week someone here said they are sourcing it from Aeternum Urolithin A (UA) Powder – The Aeternum Company
They do 3rd party testing, so maybe this is a good source, too?
My only worry, for me, is that it’s a powder and I tend to be a baby about the taste of things.

#30

I have seen urolithin A brands that are liposomal. What do you think about that?

#31

I am curious about liposomal supplements as well, but I don’t know enough about the topic. My number one would be if it’s a trustworthy brand and if the ingredient inside is actually UA. It’s the only reason I’m paying more at the moment, because I don’t know who to trust.

I did just buy two different supplements from Renue By Science in thinking that my gut is potentially not very good, so perhaps getting something that supposedly absorbs better was worth a shot. I hope others who are better informed chime in!

Edit: @Bruce4654 btw, I got 3 months worth at 20%, which makes them 54.66 per month. Also, I just noticed the brand that sells the powders also sells capsules with no fillers. I see each pill contains 500mg, so if this is a quality brand (I don’t know), their capsules become very affordable.

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