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The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular ...

mitophagy urolithin a

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#1 Engadin

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Posted 15 June 2019 - 05:03 PM


S O U R C E :   Nature Metabolism   B E H I N D   P A Y W A L L !

 

 

 

The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans

 

 

 

Abstract

 

 

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 aging1. 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.

 

 

 


Edited by Engadin, 15 June 2019 - 05:07 PM.

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#2 Phoebus

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Posted 17 June 2019 - 01:30 PM

 

Published: 

14 June 2019 The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans

 

 
Abstract

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 aging1. 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.

https://www.nature.c...2255-019-0073-4

 

article on it here 

 

https://newatlas.com...l-trials/60153/


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#3 Phoebus

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Posted 17 June 2019 - 01:33 PM

 

 

Gut Microbiota Conversion of Dietary Ellagic Acid into Bioactive Phytoceutical Urolithin A Inhibits Heme Peroxidases                                                                                                                                 Abstract                                                                                                                                                                                                            Numerous studies signify that diets rich in phytochemicals offer many beneficial functions specifically during pathologic conditions, yet their effects are often not uniform due to inter-individual variation. The host indigenous gut microbiota and their modifications of dietary phytochemicals have emerged as factors that greatly influence the efficacy of phytoceutical-based intervention. Here, we investigated the biological activities of one such active microbial metabolite, Urolithin A (UA or 3,8-dihydroxybenzo[c]chromen-6-one), which is derived from the ellagic acid (EA). Our study demonstrates that UA potently inhibits heme peroxidases i.e. myeloperoxidase (MPO) and lactoperoxidase (LPO) when compared to the parent compound EA. In addition, chrome azurol S (CAS) assay suggests that EA, but not UA, is capable of binding to Fe3+, due to its catechol-like structure, although its modest heme peroxidase inhibitory activity is abrogated upon Fe3+-binding. Interestingly, UA-mediated MPO and LPO inhibition can be prevented by innate immune protein human NGAL or its murine ortholog lipocalin 2 (Lcn2), implying the complex nature of host innate immunity-microbiota interactions. Spectral analysis indicates that UA inhibits heme peroxidase-catalyzed reaction by reverting the peroxidase back to its inactive native state. In support of these in vitro results, UA significantly reduced phorbol myristate acetate (PMA)-induced superoxide generation in neutrophils, however, EA failed to block the superoxide generation. Treatment with UA significantly reduced PMA-induced mouse ear edema and MPO activity compared to EA treated mice. Collectively, our results demonstrate that microbiota-mediated conversion of EA to UA is advantageous to both host and microbiota i.e. UA-mediated inhibition of pro-oxidant enzymes reduce tissue inflammation, mitigate non-specific killing of gut bacteria, and abrogate iron-binding property of EA, thus providing a competitive edge to the microbiota in acquiring limiting nutrient iron and thrive in the gut

https://journals.plo...al.pone.0156811

 


Edited by Phoebus, 17 June 2019 - 01:34 PM.

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#4 Phoebus

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Posted 17 June 2019 - 02:16 PM

is UA available somewhere somehow? 

 

anyone know? 



#5 Engadin

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Posted 17 June 2019 - 06:35 PM

S O U R C E :   Business Wire

 

 

 

First human clinical trial results on the anti-aging compound Urolithin A, published by Amazentis and researchers from the EPFL and SIB. Nestlé Health Science to join.

 

Breakthrough translational science of dietary supplementation with Urolithin A, a pomegranate metabolite, on mitochondrial and cellular health in humans published in the journal Nature Metabolism

 

 

LAUSANNE, Switzerland--(BUSINESS WIRE)--Amazentis, an innovative life sciences company pioneering scientific breakthroughs in nutrition to manage health conditions linked to aging, announced today a collaborative publication in Nature Metabolism with scientists at the École Polytechnique Fédérale de Lausanne (EPFL) and the Swiss Institute of Bioinformatics (SIB) demonstrating the Company’s lead product, Urolithin A (UA), is safe, bioavailable and improves mitochondrial and cellular health in humans.

 

 

“Urolithin A induces mitophagy and prolongs lifespan in C. elegans and increases muscle function in rodents”

 

 

UA was orally administered in both single and multiple (4 weeks) daily dosing to 60 healthy elderly subjects in a double-blind, randomized, placebo-controlled study. The trial showed that regular UA dosing during 4 weeks is safe, bioavailable and effective in improving mitochondrial health through upregulation of mitochondrial gene expression localized to the skeletal muscle and by improving systemic plasma acylcarnitines associated with cellular and mitochondrial function.

 

Roger Fielding, PhD, Professor of Medicine and Nutrition and Associate Director of the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, commented, “There are currently no effective solutions to treat age-related decline in muscle function other than months of exercise. This is an important first clinical validation that shows Urolithin A could be a promising solution for the management of healthy muscle function during aging.”

 

“Mitochondrial and cellular health declines with age, making these results a pivotal milestone as we explore the full breadth of benefits Urolithin A offers for managing human health throughout the aging process,” stated Patrick Aebischer, MD, co-author on the article, EPFL President Emeritus, and Chairman and Co-founder of Amazentis.

 

“This positive clinical translation of Urolithin A shows its potential to play an important role in advanced nutritional approaches to improve mitochondrial health through mitophagy and biogenesis, and, as a result, cellular health in humans,” added Johan Auwerx, MD, PhD, co-author and Professor at the EPFL.

 

Nestlé Health Science recently announced a global partnership with Amazentis to develop products containing UA to pursue opportunities in consumer healthcare and medical nutrition.

 

Chris Rinsch, PhD, lead author, Co-founder and CEO of Amazentis, said, “The rigorous clinical science being published in Nature Metabolism is a critical step towards translating our breakthrough scientific discoveries in nutrition into clinically validated consumer health products that address today’s unmet needs for healthy aging.”

 

The results are being reported in the current issue of Nature Metabolism in an article titled, “The mitophagy activator Urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans” (doi: 10.1038/s42255-019-0073-4).

 

 

Background on Urolithin A

 

Amazentis’ proprietary lead product candidate is an oral formulation of Urolithin A. Urolithin A is a microflora-derived metabolite of ellagitannins, a class of compounds found in the pomegranate and other fruits and nuts. Administration of Urolithin A leads to improved mitochondrial function by stimulating mitophagy, a process by which aging and damaged mitochondria are cleared from the cell, leading to the growth of healthy mitochondria. Mitophagy declines in cells as we age, and the reduction in mitochondrial function in the muscles of the elderly is thought to be one of the main causes of age-related muscle impairment. Previously, Amazentis and the EPFL reported preclinical results in Nature Medicine in an article titled, “Urolithin A induces mitophagy and prolongs lifespan in C. elegansand increases muscle function in rodents” (doi:10.1038/nm.4132). For more information, please visit www.AboutUrolithinA.com.

 

 

About Amazentis

 

Amazentis is an innovative life science company that employs today’s leading research and clinical science to develop the next generation of products targeting mitochondrial health for advanced nutrition. The Company’s proprietary technology, Urolithin A, is currently being evaluated in two Phase 2 clinical trials. Amazentis has established an extensive intellectual property portfolio and know how around UA, enabling the manufacture and development of advanced nutrition products for human applications. For more information on Amazentis, please visit www.amazentis.com.


Edited by Engadin, 17 June 2019 - 07:21 PM.

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#6 Mind

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Posted 17 June 2019 - 07:01 PM

https://www.amazentis.com/

 

I wonder when they will have a product on the market. If it is just an extract of pomegranates, then it seems the marketplace could get rather crowded.


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#7 Engadin

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Posted 17 June 2019 - 07:31 PM

https://www.amazentis.com/

 

I wonder when they will have a product on the market. If it is just an extract of pomegranates, then it seems the marketplace could get rather crowded.

 

 

At least they are heating the market up already: About Urolithin A

 

Keep up to date at facebook, just in case you use it: Urolithin A in FB

 

IMHO, it looks like another promising compound to join the already growing potential anti-aging arsenal sooner than later.


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#8 ortcloud

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Posted 28 October 2019 - 03:56 PM

Has anyone tried Urolithin A yet?







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