Aquaporin Channels in Skin Physiology and Aging Pathophysiology: Investigating Their Role in Skin Function and the Hallmarks of Aging

This study examines the critical role of aquaporins (AQPs) in skin physiology and aging pathophysiology. The skin plays a vital role in maintaining homeostasis by acting as a protective barrier against external pathogens and excessive water loss, while also contributing to the appearance and self-esteem of individuals. Key physiological features, such as elasticity and repair capability, are essential for its proper function. However, with aging, these characteristics deteriorate, reducing the skin's ability to tolerate environmental stressors which contribute to external aging as well as internal aging processes, which negatively affect barrier function, immune response, and overall well-being. AQPs, primarily known for facilitating water transport, are significant for normal skin functions, including hydration and the movement of molecules like glycerol and hydrogen peroxide, which influence various cellular processes and functions. In this context, we categorized aquaporin dysfunction into several hallmarks of aging, including mitochondrial dysfunction, cellular senescence, stem cell depletion, impaired macroautophagy, dysbiosis, and inflamm-aging. Eight aquaporins (AQP1, 3, 5, 7, 8, 9, 10, and 11) are expressed in various skin cells, regulating essential processes such as cell migration, proliferation, differentiation, and also immune response. Dysregulation or altered expression of these proteins can enhance skin aging and related pathologies by activating these hallmarks. This study provides valuable insights into the potential of targeting aquaporins to mitigate skin aging and improve skin physiologic functions.