biostudies-literatureHitpass Romero KMarsden FundAuckland Medical Research FoundationNCATS NIH HHSRoyal Society Te ApārangiHugh Green FoundationNCI NIH HHSNeurological Foundation of New ZealandNIGMS NIH HHS109https://www.ebi.ac.uk/biostudies/studies/S-EPMC12007191biostudies-literatureUnknown22(1)Efficient clearance of central nervous system (CNS) waste proteins and appropriate immune surveillance is essential for brain health. These processes are facilitated by lymphatic networks present in the meninges that drain cerebrospinal fluid (CSF). Age-related impairments to meningeal lymphatic drainage contribute to CNS waste accumulation and immune dysfunction, yet the underlying mechanisms remain poorly understood. Here, we identify extracellular matrix (ECM) remodeling in the aged dura as a key driver of CSF clearance deficits, demonstrating that peri-lymphatic collagen accumulation disrupts lymphatic function. Exploring immune-derived factors contributing to this ECM remodeling, we identify transforming growth factor beta 1 (TGFβ1) as a major regulator using primary human dural fibroJournal of neuroinflammationAge-related meningeal extracellular matrix remodeling compromises CNS lymphatic function.PMC12007191P30 CA091842P41 GM103422UL1 TR000448Stevenson TJSmith AMWatkin BVinnell LKipnis JCorreia JARustenhoven JDragunow MSchweder PMcCullough SJCSmyth LCDHitpass Romero KfalseAge-related meningeal extracellular matrix remodeling compromises CNS lymphatic function.Efficient clearance of central nervous system (CNS) waste proteins and appropriate immune surveillance is essential for brain health. These processes are facilitated by lymphatic networks present in the meninges that drain cerebrospinal fluid (CSF). Age-related impairments to meningeal lymphatic drainage contribute to CNS waste accumulation and immune dysfunction, yet the underlying mechanisms remain poorly understood. Here, we identify extracellular matrix (ECM) remodeling in the aged dura as a key driver of CSF clearance deficits, demonstrating that peri-lymphatic collagen accumulation disrupts lymphatic function. Exploring immune-derived factors contributing to this ECM remodeling, we identify transforming growth factor beta 1 (TGFβ1) as a major regulator using primary human dural fibro2025-01-01T00:00:00Z2025 Apr2025-07-12T03:04:39.514Z2025-07-12T03:04:39.514ZS-EPMC120071914024725710.1186/s12974-025-03436-0