Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults

Singh, Anurag; D’Amico, Davide; Andreux, Pénélope; Fouassier, Andréane M; Blanco-Bose, William; Evans, Malkanthi; Aebischer, Patrick; Auwerx, Johan; Rinsch, Chris

doi:10.1016/j.xcrm.2022.100633

Cited by 90 publications

(111 citation statements)

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“…UA's health benefits were reported also in other diseases (D'Amico et al, 2021), including inflammatory bowel disease (IBD) (Singh et al, 2019), heart failure (Savi et al, 2017), and neurodegenerative disorders (Fang et al, 2019). Clinical studies showed that UA is safe, bioavailable, improves biomarkers associated with better mitochondrial function (Andreux et al, 2019; Liu et al, 2022; Singh et al, 2022) and significantly increases muscle strength (Singh et al, 2022) and resistance to fatigue (Liu et al, 2022) in humans.…”

Section: Introductionmentioning

confidence: 99%

Urolithin A improves mitochondrial health, reduces cartilage degeneration, and alleviates pain in osteoarthritis

et al. 2022

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Osteoarthritis (OA) is the most common age‐related joint disorder with no effective therapy. According to the World Health Organization, OA affects over 500 million people and is characterized by degradation of cartilage and other joint tissues, severe pain, and impaired mobility. Mitochondrial dysfunction contributes to OA pathology. However, interventions to rescue mitochondrial defects in human OA are not available. Urolithin A (Mitopure) is a natural postbiotic compound that promotes mitophagy and mitochondrial function and beneficially impacts muscle health in preclinical models of aging and in elderly and middle‐aged humans. Here, we showed that Urolithin A improved mitophagy and mitochondrial respiration in primary chondrocytes from joints of both healthy donors and OA patients. Furthermore, Urolithin A reduced disease progression in a mouse model of OA, decreasing cartilage degeneration, synovial inflammation, and pain. These improvements were associated with increased mitophagy and mitochondrial content, in joints of OA mice. These findings indicate that UA promotes joint mitochondrial health, alleviates OA pathology, and supports Urolithin A's potential to improve mobility with beneficial effects on structural damage in joints.

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Section: Introductionmentioning

confidence: 99%

Urolithin A improves mitochondrial health, reduces cartilage degeneration, and alleviates pain in osteoarthritis

et al. 2022

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“…For example, the benefits of Uro A supplementation in muscles have been supported by recent clinical trials in older adults [2,3]. Additionally, Uro A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in middle-aged adults [4].…”

Section: Introductionmentioning

confidence: 99%

Ameliorative Effects of Gut Microbial Metabolite Urolithin A on Pancreatic Diseases

Xiao

Bian

et al. 2022

Nutrients

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Urolithin A (Uro A) is a dietary metabolite of the intestinal microbiota following the ingestion of plant-based food ingredients ellagitannins and ellagic acid in mammals. Accumulating studies have reported its multiple potential health benefits in a broad range of diseases, including cardiovascular disease, cancer, cognitive impairment, and diabetes. In particular, Uro A is safe via direct oral administration and is non-genotoxic. The pancreas plays a central role in regulating energy consumption and metabolism by secreting digestive enzymes and hormones. Numerous pathophysiological factors, such as inflammation, deficits of mitophagy, and endoplasmic reticulum stress, can negatively affect the pancreas, leading to pancreatic diseases, including pancreatitis, pancreatic cancer, and diabetes mellitus. Recent studies showed that Uro A activates autophagy and inhibits endoplasmic reticulum stress in the pancreas, thus decreasing oxidative stress, inflammation, and apoptosis. In this review, we summarize the knowledge of Uro A metabolism and biological activity in the gut, as well as the pathological features and mechanisms of common pancreatic diseases. Importantly, we focus on the potential activities of Uro A and the underlying mechanisms in ameliorating various pancreatic diseases via inhibiting inflammatory signaling pathways, activating autophagy, maintaining the mitochondrial function, and improving the immune microenvironment. It might present a novel nutritional strategy for the intervention and prevention of pancreatic diseases.

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“…Building from these promising results, the first‐in‐human clinical trial showed that urolithin A supplementation is safe and increases the expression of multiple genes regulating mitochondrial health in the skeletal muscle of healthy sedentary elderly individuals (Andreux et al., 2019). Very recently, the same group showed that urolithin A supplementation in middle‐aged adults led to clinically meaningful improvements in muscle strength, aerobic endurance as assessed by an increase peak oxygen consumption (

{\dot V_{{{\rm{O}}_{\rm{2}}}}}

Section: Introductionmentioning

confidence: 99%

“…Very recently, the same group showed that urolithin A supplementation in middle‐aged adults led to clinically meaningful improvements in muscle strength, aerobic endurance as assessed by an increase peak oxygen consumption (

{\dot V_{{{\rm{O}}_{\rm{2}}}}}

) and physical performance assessed using the 6 min walk test (Singh et al., 2022). Importantly, proteomic analysis of muscle biopsy samples revealed that the most significantly enriched pathway induced by a daily supplementation of 500 mg of urolithin A was ‘Parkin‐mediated ubiquitin and proteasomal systems’ (Singh et al., 2022). This change was also associated with an increase in the phosphorylation level of Parkin on serine 65, a marker of Parkin activation (Singh et al., 2022).…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, proteomic analysis of muscle biopsy samples revealed that the most significantly enriched pathway induced by a daily supplementation of 500 mg of urolithin A was ‘Parkin‐mediated ubiquitin and proteasomal systems’ (Singh et al., 2022). This change was also associated with an increase in the phosphorylation level of Parkin on serine 65, a marker of Parkin activation (Singh et al., 2022). Taken altogether, these data place urolithin A as a potential activator of Parkin in humans with the potential to promote healthy ageing.…”

Section: Introductionmentioning

confidence: 99%

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Parkin: a potential target to promote healthy ageing

Leduc‐Gaudet

Hussain

Gouspillou

2022

The Journal of Physiology

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support-information-section). Jean-Philippe Leduc-Gaudet (left) obtained a PhD from McGill University (Montréal, Canada). During his PhD, he studied the roles played by mitochondrial quality control processes in muscle health, ageing and diseases. He is currently a postdoctoral Fellow at the University of Padova (Padova, Italy) under the supervision of Dr Marco Sandri and investigates novel regulators of autophagy and muscle health. Sabah Hussain (centre) is a Distinguished James McGill Professor working in the Department of Medicine at McGill University (Montréal, Canada). His research investigates the signalling pathways regulating angiogenesis, muscle regeneration and skeletal muscle health. Gilles Gouspillou (right) is an associate professor at the Université du Québec à Montréal (Montréal, Canada) and investigates the mechanisms underlying the ageing-related loss of muscle mass and function in both animal models and humans as well as the role played by mitochondrial quality control processes in mammalian ageing.

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Urolithin A improves muscle strength, exercise performance, and biomarkers of mitochondrial health in a randomized trial in middle-aged adults

Cited by 90 publications

References 69 publications

Urolithin A improves mitochondrial health, reduces cartilage degeneration, and alleviates pain in osteoarthritis

Urolithin A improves mitochondrial health, reduces cartilage degeneration, and alleviates pain in osteoarthritis

Ameliorative Effects of Gut Microbial Metabolite Urolithin A on Pancreatic Diseases

Parkin: a potential target to promote healthy ageing

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