Age-related changes in meningeal lymphatic function are closely associated with vascular endothelial growth factor-C expression

Middle-aged mice showed enhanced meningeal lymphatic function with MLVs expansion. Age-related changes in the function of MLVs are closely associated to the expression of VEGF-C in the cerebral cortex. Moreover, the cognitive function was enhanced in middle-aged mice compared to young and aged mice. These results indicate that the cerebral cortex may serve as a target for VEGF-C supplementation to ameliorate meningeal lymphatic dysfunction. MLVs, meningeal lymphatic vessels; VEGF-C, vascular endothelial growth factor-C. [Display omitted] •Middle-aged mice show improved meningeal lymphatic function and MLV expansion.•The middle-aged mice performed better in the Y maze test.•Age-related changes in meningeal lymphatic function are associated with VEGF-C expression. Meningeal lymphatic vessels (MLVs) have crucial roles in removing metabolic waste and toxic proteins from the brain and transporting them to the periphery. Aged mice show impaired meningeal lymphatic function. Nevertheless, as the disease progresses, and significant pathological changes manifest in the brain, treating the condition becomes increasingly challenging. Therefore, investigating the alterations in the structure and function of MLVs in the early stages of aging is critical for preventing age-related central nervous system degenerative diseases. We detected the structure and function of MLVs in young, middle-aged, and aged mice. Middle-aged mice, compared with young and aged mice, showed enhanced meningeal lymphatic function along with MLV expansion and performed better in the Y maze test. Moreover, age-related changes in meningeal lymphatic function were closely associated with vascular endothelial growth factor-C (VEGF-C) expression in the brain cortex. Our data suggested that the cerebral cortex may serve as a target for VEGF-C supplementation to ameliorate meningeal lymphatic dysfunction, thus providing a new strategy for preventing age-related central nervous system diseases.