Mechanobiology · Jul 2026
Mechanobiological changes in the aging brain
By 서은우, Kim HN
Aging and Alzheimer’s disease (AD) are traditionally viewed through a biochemical lens, yet they involve profound mechanobiological transformations. During aging and disease progression, the central nervous system (CNS) undergoes a complex biomechanical shift characterized by a profound spatial dichotomy: widespread macroscopic tissue softening juxtaposed against localized microscopic stiffening. This review explores the mechanobiological changes of the aging brain. We first outline the macroscopic structural remodeling of the extracellular matrix (ECM) and the consequent failure of microenvironmental fluid dynamics, including glymphatic clearance failure and neurotoxic protein accumulation. We then detail the specific molecular mechanotransduction pathways—mediated by sensors such as Piezo1, YAP/TAZ, and integrins—triggered by these physical changes. Ultimately, we synthesize how these mechanical-to-biochemical conversions drive maladaptive cellular responses, chronic neuroinflammation, and neurodegeneration across different CNS cell types. Finally, we highlight the translational potential of this mechanobiological paradigm.