The Role of Skin Surface pH in Age Associated Pruritus: Mechanistic and Clinical Insights

Skin aging is characterized by progressive structural and biochemical changes that impair epidermal barrier function, alter the cutaneous microbiome, and predispose to chronic pruritus. Epidermal thinning, reduced lipid synthesis, and slowed barrier repair increase transepidermal water loss and vulnerability to irritation. Concurrently, age-related disruption of the acid mantle leads to elevation of skin surface pH, impairing acid-dependent lipid-processing enzymes while enhancing serine protease activity. These changes disrupt lamellar organization, weaken stratum corneum cohesion, and further compromise barrier integrity. Elevated pH and barrier dysfunction also reshape the skin microbiome. These changes favor alkalinity-tolerant and proinflammatory species while reducing protective commensals, thereby reinforcing inflammation and sensory irritation. Barrier impairment, dysbiosis, and pH-driven protease activation converge with neuroimmune dysregulation to sensitize peripheral nerves and promote chronic itch. Important contributors include kallikrein-protease-activated receptor-2 (PAR2) signaling and cytokines such as interleukin-31. This review highlights the pH-protease-itch axis as a unifying framework for pruritus in aging skin and discusses restoration of physiological acidity as a rational therapeutic strategy.