Urolithin A (UA) is a gut metabolite derived from ellagic acid. This systematic review assesses the potential geroprotective effect of UA in humans. In five studies including 250 healthy individuals, UA (10-1000 mg/day) for a duration ranging from 28 days to 4 months, showed a dose-dependent anti-inflammatory effect and upregulated some mitochondrial genes, markers of autophagy, and fatty acid oxidation. It did not affect mitochondrial maximal adenosine triphosphate production, biogenesis, dynamics, or gut microbiota composition. UA increased muscle strength and endurance, however, had no effect on anthropometrics, cardiovascular outcomes, and physical function. Unrelated adverse events were mild or moderate. Further research across more physiological systems and longer intervention periods is required.

The aging of an organism is hallmarked by systemic loss of functional tissue, resulting in increased fragility and eventual development of age-related neurodegenerative, musculoskeletal, cardiovascular, and neoplastic diseases. Growing scientific evidence points to mitochondrial dysfunction as a key contributor in the aging process and subsequent development of age-related pathologies. Under normal physiologic conditions, the body removes dysfunctional mitochondria via an autophagic process known as mitophagy. Urolithin A (UA), a metabolite produced when gut microflora digests the polyphenol compounds ellagitannin and ellagic acid, is a known inducer of mitophagy via several identified mechanisms of action. The primary objective of this scoping review is to identify and summarize the clinical relevance of UA supplementation in the prevention of age-related pathology and diseases. A computer-assisted literature review was performed using PubMed and EMBASE for primary source research articles examining UA supplementation and aging-related pathologies. A total of 293 articles were initially identified from a database search, and 15 articles remained for inclusion in this review, based on predetermined criteria. Analysis of the 15 identified publications demonstrated that UA holds potential as a dietary intervention for slowing the progression of aging and preventing the development of age-related disease. This review also illustrates the potential role that mitochondrial health and inflammation play in the progression of age-related pathology. Identifying the clinical relevance of UA supplementation in the prevention of age-related pathology and diseases will help further the focus of research on treatments that may improve the longevity and quality of life in patients at risk for these comorbidities.

Foods rich in ellagic tannins are first hydrolyzed into ellagic acid in the stomach and small intestine, and then converted into urolithins with high bioavailability by the intestinal flora. Urolithin has beneficially biological effects, it can induce adipocyte browning, improve cholesterol metabolism, inhibit graft tumor growth, relieve inflammation, and downregulate neuronal amyloid protein formation via the β3-AR/PKA/p38MAPK, ERK/AMPKα/SREBP1, PI3K/AKT/mTOR signaling pathways, and TLR4, AHR receptors. But differences have been reported in urolithin production capacity among different individuals. Thus, it is of great significance to explore the biological functions of urolithin, screen the strains responsible for biotransformation of urolithin, and explore the corresponding functional genes. Tannin acyl hydrolase can hydrolyze tannins into ellagic acid, and the genera Gordonibacter and Ellagibacter can metabolize ellagic acid into urolithins. Therefore, application of \"single bacterium\", \"single bacterium + enzyme\", and \"microflora\" can achieve biotransformation of urolithin A. In this review, the source and metabolic pathway of ellagic tannins, and the mechanisms of the biological function of a metabolite, urolithin A, are discussed. The current strategies of biotransformation to obtain urolithin A are expounded to provide ideas for further studies on the relationship between urolithin and human health.