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In a small, recent human trial, a naturally occurring compound called urolithin A has yielded positive results and appears to slow down part of the aging process that is related to the production of energy in our cells.

What is urolithin A?

Urolithin A is the end product created when bacteria in the gut break down ellagitannins, which are polyphenols found in fruits such as pomegranates, strawberries, walnuts, and raspberries. The substance does not appear naturally in its end form, so we normally rely on the beneficial bacteria in the microbiome, our internal ecology of gut bacteria, to convert the polyphenols into urolithin A.

Because this compound needs a particular bacterium to create it, the bioavailability of urolithin A could vary considerably from person to person, having a greater or lesser effect depending on individual gut bacteria diversity.

Urolithin A has been a subject of interest to researchers for a while, as there have been promising early results in mice and flatworms, in which the compound increased lifespan. It appears to have geroprotective, meaning age-delaying, properties.

The geroprotective effect of urolithin A appears to be focused on improving the function of the mitochondria, the power plants of our cells, which are responsible for turning nutrient-derived molecules into a form of cellular energy called adenosine triphosphate (ATP).

The results of a human trial are positive

Recently, the details of a small human trial have been published, and they show some positive results. The purpose of this trial was to determine both the safety and efficacy of urolithin A.

For the study, the team synthesized urolithin A and gave it to a test group of 60 older people in various dosages. The participants had generally sedentary lifestyles but were healthy at the time of the study.

For the first part of the study, the research team gave some of the participants a single dose of between 250 and 2000 mg of urolithin A. There were no side effects reported from this test group compared to the control group, suggesting that the compound is well tolerated.

The following step saw the team move to a longer study of the safety and efficacy of urolithin A over a 28-day period. The 60 participants were divided into four groups and given either 250 mg, 500 mg, 1000 mg, or a placebo as a control group. After 28 days, the results showed that, once again, there were no serious side effects following sustained use. The 500 mg and 1000 mg dosage groups also had an increased level of mitochondrial gene expression, which is known to stimulate biogenesis in the same way that exercise does.

Urolithin A (UA) is a natural dietary, microflora-derived metabolite shown to stimulate mitophagy and improve muscle health in old animals and in preclinical models of aging. Here, we report the results of a first-in-human clinical trial in which we administered UA, either as a single dose or as multiple doses over a 4-week period, to healthy, sedentary elderly individuals. We show that UA has a favourable safety profile (primary outcome). UA was bioavailable in plasma at all doses tested, and 4 weeks of treatment with UA at doses of 500 mg and 1,000 mg modulated plasma acylcarnitines and skeletal muscle mitochondrial gene expression in elderly individuals (secondary outcomes). These observed effects on mitochondrial biomarkers show that UA induces a molecular signature of improved mitochondrial and cellular health following regular oral consumption in humans.

Conclusion

The researchers plan to develop urolithin A products for market as soon as possible, pending the results of additional research and human trials. Their hope is that urolithin A may be able to slow down the loss of skeletal muscle that happens with age and reduces mobility and independence.

Given that mitochondrial dysfunction is a hallmark of aging, the use of urolithin A may have merit as a geroprotector while more robust solutions to mitochondrial decline are developed, such as the MitoSENS mitochondrial repair approach from SRF.

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Literature

[1] Andreux, P. A., Blanco-Bose, W., Ryu, D., Burdet, F., Ibberson, M., Aebischer, P., … & Rinsch, C. (2019). The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nature Metabolism, 1(6), 595.

About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity created by the Aging Analytics Agency. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, and, Keep me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.
  1. July 29, 2019

    How can I be a part of trials? I’m dying, and I want to live. Just had my 4th heart attack in 10 years, total of 7 stents placed. Type 2 diabetic. My muscles have atrophied greatly as I used to be a amateur bodybuilder when I was younger in my 20’s. I’m now 57 but feel like i’m 77 and getting worse. Any advice on compounds available or trials I can apply for would be greatly appreciated. Thank you, Tim.

    • October 1, 2019

      Tim, you should definitely be on LCHF/Keto plus IF(Intermittent Fasting). These two combined, with a bit of exercise or just walking every day, WILL save your life. There are plenty of examples out there. Just check these two out, you will discover a new world! Best health!

  2. September 24, 2019

    Tim,
    check out sites such as fightaging.org, and longecity.org.

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