Urolithin A

Urolithin A is a natural compound produced by gut bacteria from ingested ellagitannins and ellagic acid, complex polyphenols abundant in foods such as pomegranate, berries, and nuts. ^[1] Urolithin A is better absorbed in the gastrointestinal tract than its parent substances, so the variable effects of ellagitannin-rich foods on health may be linked to differences in individual gut microbiota content. ^[2] Urolithins were discovered in humans almost 20 years ago, and the gut microbiota associated with their metabolism gives rise to distinct urolithin metabotypes (UM-A, UM-B, and UM-0) relevant in human health. ^[3]

Urolithin A enhances cellular health by increasing mitophagy and mitochondrial function and reducing detrimental inflammation. ^[1] It stimulates mitophagy through pathways such as PINK1/Parkin, leading to improved mitochondrial health and enhanced muscle function. ^[4] Urolithin A can cross the blood-brain barrier and exhibits anti-inflammatory, antioxidant, anti-senescence, and anti-apoptotic properties in addition to promoting mitophagy and mitochondrial homeostasis. ^[5]

A systematic review of targeting aging with urolithin A in humans included five studies with 250 healthy individuals given urolithin A at 10 to 1000 mg/day for durations from 28 days to 4 months. ^[6] In that human review, urolithin A showed a dose-dependent anti-inflammatory effect, upregulated some mitochondrial genes and markers of autophagy, and increased muscle strength and endurance, but had no effect on anthropometrics, cardiovascular outcomes, or physical function. ^[6] Several preclinical studies show that urolithin A protects against aging and age-related conditions affecting muscle, brain, and joints, and in humans benefits in muscle are supported by recent clinical trials in elderly people. ^[1] A scoping review identified 293 database articles and included 15, concluding that urolithin A holds potential as a dietary intervention for slowing the progression of aging and preventing age-related disease. ^[7]

Urolithin A was discovered about 40 years ago, but only recently has its impact on aging and disease been explored. ^[1] Because mitophagy levels decline during aging and negatively impact skeletal muscle performance, urolithin A has been shown to promote mitophagy and improve muscle function across species in experimental models and across multiple clinical studies. ^[8] Urolithin A exhibits a favorable safety profile, though translating urolithin A interventions into clinical practice for central nervous system disorders still faces challenges. ^[5]