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Urolithin A improves physical performance and mitophagy in middle-aged adults

News
June 1, 2022
By
Olena Mokshyna, PhD.

The data showed significant improvement in muscle strength (especially leg muscle strength) at both doses.

Mitochondrial dysfunction is one of the hallmarks of aging, which manifests first and foremost in skeletal muscle deterioration. Studies associate this dysfunction with slow walking speed, loss of strength, muscle fatigue, and, ultimately, sarcopenia. Environmental factors, such as diet and exercise, have been shown to improve mitochondrial activity and prevent a gradual decline in muscle mass and strength. However, it becomes more complicated with age to adhere to an exercise regime strictly. One of the possible solutions is to activate the mitophagy via exercise mimetics – compounds that mimic the effects of exercise. Mitophagy is the recycling of faulty mitochondria aimed at improving mitochondrial function.

Urolithin A (UroA) is a compound produced by gut bacteria after metabolizing ellagitannins (a group of polyphenolic compounds present in foods such as pomegranate). UroA has shown promising results in multiple preclinical studies of aging in rodents and nematodes. Its administration has been associated with improved muscle function, delayed muscle disorders, and other benefits, including preventing cardiac, neurodegenerative, and kidney diseases. After 4-week oral administration, UroA has been shown to be safe and bioavailable in humans. A randomized clinical trial in older adults also demonstrated muscle strength improvement with long-term UroA intake.

Singh et al. designed a proof-of-concept study to investigate the efficacy of long-term UroA supplementation in middle-aged adults from the ATLAS study (randomized, double-blind, placebo-controlled, single-center intervention clinical trial). The study included untrained adults with an average age of around 50, overweight, and having low physical endurance. During the 4-month intervention period, UroA was administered at two different doses. Subjects were randomized to either placebo, 500 mg, or 1,000 mg daily doses groups.

UroA was found to be safe and well-tolerated during a 4-month period at both doses with few adverse effects. The data showed significant improvement in muscle strength (especially leg muscle strength) at both doses. Only the higher UroA dose led to the relevant improvement in measures of aerobic and physical performance (with not previous involvement in exercise routine). The authors also examined the compound effect on biological pathways related to muscle endurance and strength. UroA led to a significant increase in both mitophagy and mitochondrial biomarkers in previous preclinical studies. In this trial, the data analysis showed a specific increase in mitochondrial gene activation at a 500 mg dose. This increase was accompanied by the activation of genes related to muscle contraction. The biomarkers of inflammation and mitochondrial dysfunction were significantly lowered by UroA supplementation, suggesting improvement in both states. Last but not least, the proteins participating in mitophagy and mitochondrial metabolism were also increasingly expressed with UroA administration.

This study demonstrates the clinically meaningful impact of UroA and further establishes evidence for its use as a nutritional intervention for muscle strength, endurance, and healthy aging.

Source Cell Reports Medicine

Mitochondrial dysfunction is one of the hallmarks of aging, which manifests first and foremost in skeletal muscle deterioration. Studies associate this dysfunction with slow walking speed, loss of strength, muscle fatigue, and, ultimately, sarcopenia. Environmental factors, such as diet and exercise, have been shown to improve mitochondrial activity and prevent a gradual decline in muscle mass and strength. However, it becomes more complicated with age to adhere to an exercise regime strictly. One of the possible solutions is to activate the mitophagy via exercise mimetics – compounds that mimic the effects of exercise. Mitophagy is the recycling of faulty mitochondria aimed at improving mitochondrial function.

Urolithin A (UroA) is a compound produced by gut bacteria after metabolizing ellagitannins (a group of polyphenolic compounds present in foods such as pomegranate). UroA has shown promising results in multiple preclinical studies of aging in rodents and nematodes. Its administration has been associated with improved muscle function, delayed muscle disorders, and other benefits, including preventing cardiac, neurodegenerative, and kidney diseases. After 4-week oral administration, UroA has been shown to be safe and bioavailable in humans. A randomized clinical trial in older adults also demonstrated muscle strength improvement with long-term UroA intake.

Singh et al. designed a proof-of-concept study to investigate the efficacy of long-term UroA supplementation in middle-aged adults from the ATLAS study (randomized, double-blind, placebo-controlled, single-center intervention clinical trial). The study included untrained adults with an average age of around 50, overweight, and having low physical endurance. During the 4-month intervention period, UroA was administered at two different doses. Subjects were randomized to either placebo, 500 mg, or 1,000 mg daily doses groups.

UroA was found to be safe and well-tolerated during a 4-month period at both doses with few adverse effects. The data showed significant improvement in muscle strength (especially leg muscle strength) at both doses. Only the higher UroA dose led to the relevant improvement in measures of aerobic and physical performance (with not previous involvement in exercise routine). The authors also examined the compound effect on biological pathways related to muscle endurance and strength. UroA led to a significant increase in both mitophagy and mitochondrial biomarkers in previous preclinical studies. In this trial, the data analysis showed a specific increase in mitochondrial gene activation at a 500 mg dose. This increase was accompanied by the activation of genes related to muscle contraction. The biomarkers of inflammation and mitochondrial dysfunction were significantly lowered by UroA supplementation, suggesting improvement in both states. Last but not least, the proteins participating in mitophagy and mitochondrial metabolism were also increasingly expressed with UroA administration.

This study demonstrates the clinically meaningful impact of UroA and further establishes evidence for its use as a nutritional intervention for muscle strength, endurance, and healthy aging.

Source Cell Reports Medicine

Article reviewed by
Dr. Ana Baroni MD. Ph.D.
SCIENTIFIC & MEDICAL ADVISOR
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Dr. Ana Baroni MD. Ph.D.

Scientific & Medical Advisor
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Ana has over 20 years of consultancy experience in longevity, regenerative and precision medicine. She has a multifaceted understanding of genomics, molecular biology, clinical biochemistry, nutrition, aging markers, hormones and physical training. This background allows her to bridge the gap between longevity basic sciences and evidence-based real interventions, putting them into the clinic, to enhance the healthy aging of people. She is co-founder of Origen.life, and Longevityzone. Board member at Breath of Health, BioOx and American Board of Clinical Nutrition. She is Director of International Medical Education of the American College of Integrative Medicine, Professor in IL3 Master of Longevity at Barcelona University and Professor of Nutrigenomics in Nutrition Grade in UNIR University.

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