Impact of the Natural Compound Urolithin A on Health, Disease, and Aging

Urolithin A (UA) is a gut microbiome-derived natural compound that only 40% of people can naturally convert from dietary precursors at meaningful levels.Positive effects of direct UA administration in health, aging, and age-related conditions have been identified in several recent studies.Experimental models consistently show that UA increases mitophagy and mitochondrial function and blunts excessive inflammatory responses.UA increased biomarkers of mitochondrial function in preclinical models of aging and in healthy elderly people.UA is a promising strategy to target health and disease conditions of aging, especially those linked to mitochondrial and muscle dysfunction. Urolithin A (UA) is a natural compound produced by gut bacteria from ingested ellagitannins (ETs) and ellagic acid (EA), complex polyphenols abundant in foods such as pomegranate, berries, and nuts. UA was discovered 40 years ago, but only recently has its impact on aging and disease been explored. UA enhances cellular health by increasing mitophagy and mitochondrial function and reducing detrimental inflammation. Several preclinical studies show how UA protects against aging and age-related conditions affecting muscle, brain, joints, and other organs. In humans, benefits of UA supplementation in the muscle are supported by recent clinical trials in elderly people. Here, we review the state of the art of UA’s biology and its translational potential as a nutritional intervention in humans. Urolithin A (UA) is a natural compound produced by gut bacteria from ingested ellagitannins (ETs) and ellagic acid (EA), complex polyphenols abundant in foods such as pomegranate, berries, and nuts. UA was discovered 40 years ago, but only recently has its impact on aging and disease been explored. UA enhances cellular health by increasing mitophagy and mitochondrial function and reducing detrimental inflammation. Several preclinical studies show how UA protects against aging and age-related conditions affecting muscle, brain, joints, and other organs. In humans, benefits of UA supplementation in the muscle are supported by recent clinical trials in elderly people. Here, we review the state of the art of UA’s biology and its translational potential as a nutritional intervention in humans. UA belongs to the family of urolithins, characterized by a chemical structure containing an α-benzo-coumarin scaffold (Figure 1). Urolithins are produced in the colon following the microbiome-mediated transformation of the natural polyphenols ETs and EA, which are contained in dietary products, such as pomegranates, strawberries, raspberries, and walnuts [1.Espín J.C. et al.Biological significance of urolithins, the gut microbial ellagic acid-derived metabolites: the evidence so far.Evid. Based Complement. Alternat. 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