Topical application of urolithin A activates mitophagy and enhances mitochondrial function to promote skin longevity

Urolithin A (UA, Mitopure), a postbiotic that promotes mitophagy and mitochondrial function following oral administration, was evaluated for its effects on skin health in human skin models and when applied topically to healthy subjects in randomized clinical studies. UA tested in 2D and 3D reconstructed human skin and ex vivo human skin explants showed enhanced mitochondrial respiration, activated mitophagy markers, reduced inflammatory mediators and senescence-associated markers, and increased proteins involved in extracellular matrix structure and epidermal differentiation. Safety was confirmed in a human repeat-insult patch test. In randomized, placebo-controlled clinical studies, UA reduced periorbital wrinkle depth after 8 weeks and attenuated UVB-induced erythema. Skin transcriptomics supported increased extracellular matrix and epidermal development programs together with decreased inflammatory and senescence-associated signaling. These findings indicate that topical UA engages cellular pathways associated with skin resilience to promote skin health and longevity.