Presentation: Modeling the aged brain through the microenvironment

Over the past six decades, life expectancy has increased significantly,highlighting the need to better understand and treat age-related diseases. The extracellular matrix (ECM), a dynamic network of biomolecules, plays a critical role not only in providing structural support but also in regulating cellular behavior. Aging induces distinct post-synthetic modifications in ECM components, which accumulate over time and are further exacerbated in neurodegenerative conditions. These changes lead to increased matrix stiffness and connectivity, ultimately altering the biomechanical and signaling landscape of brain tissue. Despite their relevance, such age-associated microenvironmental shifts are often neglected in current experimental models, limiting the translational success of CNS-targeting therapeutics. In this talk, we explore innovative approaches to recapitulate aging in human brain organoids by modulating the microenvironment, with a focus on inducing ECM aging through hyperglycation and simulating aging-related stress via free-fall exposure.