Aging and Disease · 2026
The Role of Piezo Channel Proteins in Aging and Age-Related Diseases: From Molecular Mechanisms to Therapeutic Potential
The accelerating global aging trend has made age-related diseases a critical public health challenge. Piezo1 and Piezo2, as evolutionarily conserved mechanosensitive ion channels, convert mechanical signals such as membrane stretch, matrix stiffness, fluid shear stress, and osmotic pressure into electrochemical signals, mainly Ca²⁺ influx, thereby regulating cell proliferation, apoptosis, inflammation, matrix remodeling, and metabolic homeostasis. During aging, altered tissue mechanics and impaired mechanotransduction are associated with changes in Piezo channel levels, which may contribute to the development and progression of neurodegenerative diseases, musculoskeletal degeneration, cardiovascular and cerebrovascular diseases, organ fibrosis, diabetes, hypertension, and skin aging. Piezo channels may therefore represent potential therapeutic targets for these age-related disorders. However, most evidence supporting these approaches remains preclinical, with small molecules, natural compounds, dietary fatty acids, exercise, ultrasound stimulation, and nanotechnology-based targeted delivery systems showing beneficial effects in experimental models. Despite these advances, challenges including tissue-specific regulation, selective drug development, long-term safety, and clinical translation remain. Further investigation of Piezo channels will provide new insights and intervention targets for promoting healthy aging and treating age-related diseases.