AGE-RELATED BIOMECHANICAL AND STRUCTURAL REMODELING OF HUMAN MIDDLE CEREBRAL ARTERIES

Proper cerebral artery function is essential for maintaining the brain's microenvironment. The multilayered organization of cellular and extracellular matrix (ECM) constituents enables large cerebral arteries to accommodate pulse pressure and ensure both effective blood distribution and protection of the microcirculation. However, aging and disease induce compositional and structural remodeling in cerebral arteries, such as the middle cerebral artery (MCA), which can alter biomechanical properties and increase susceptibility to cerebrovascular conditions including atherosclerosis and aneurysms, both major contributors to stroke. Understanding how age-related changes in arterial structure and composition influence biomechanical behavior is critical for improving prediction of cerebrovascular risk. In this study, we characterized the age-dependent elastic and viscoelastic properties of human MCAs and related these changes to ECM structure and composition using imaging and biochemical assays. Our results demonstrate that aging is associated with increased stiffness and stress relaxation in MCAs. Biochemical analyses revealed age-related increases in collagen and glycosaminoglycan (GAG) content, both of which correlated with altered mechanical properties. Histological staining further showed denser collagen organization within the adventitia and elevated GAG presence, consistent with mechanical and biochemical findings. Additionally, multiphoton imaging under mechanical loading provided insight into layer-specific collagen reorganization in the adventitia. Collectively, these findings elucidate key age-dependent alterations in the structure-function relationship of human cerebral arteries and provide a mechanistic basis for increased cerebrovascular risk with aging. STATEMENT OF SIGNIFICANCE: Age-related remodeling of the extracellular matrix is a fundamental driver of tissue dysfunction, yet its effects on human cerebral artery mechanics remain poorly understood. In this study, we combine biomechanical testing, biochemical assays, histology, and multiphoton microscopy to characterize structural and functional remodeling of human middle cerebral arteries across a broad age range. We demonstrate that aging is associated with increased arterial stiffness and viscoelastic relaxation, accompanied by elevated collagen and glycosaminoglycan content. By directly linking extracellular matrix composition and organization to biomechanical function, this work provides new insights into the mechanisms governing cerebrovascular aging. These findings establish an important structure function framework for understanding vascular tissue remodeling and have broader implications for age related vascular dysfunction, mechanobiology, and biomaterials research.