Lipids at the meningeal-tumor interface: aging, anatomical niches, and meningioma biology

Meningiomas exhibit substantial molecular, anatomical, and microenvironmental heterogeneity, yet the spatial organization of their lipid biology remains poorly understood. Emerging lipidomic studies demonstrate extensive remodeling of membrane, signaling, and mitochondrial lipid classes, with profiles varying according to molecular genotype, histopathological grade, and potentially patient characteristics. In parallel, developmental, single-cell, and spatial studies have revealed the meninges and meningiomas as regionally organized systems comprising distinct stromal, vascular, immune, and neoplastic populations. Here, we integrate these lines of evidence and propose the aging meningeal lipid niche as an anatomically grounded framework for understanding lipid biology across the meningioma–meningeal interface. We examine the dural attachment and tumor–bone interface, perivascular niche, immune-enriched regions, tumor core, and tumor–brain boundary as candidate metabolic compartments in which cellular composition, vascular access, extracellular architecture, and inflammatory signaling may shape local lipid states. We further consider how aging may modify these environments through remodeling of the meningeal extracellular matrix, lymphatic function, immune composition, and lipid homeostasis, while distinguishing direct evidence in meningioma from mechanistic inference. A central limitation of current studies is their reliance on bulk tissue, which precludes confident attribution of lipid signals to specific anatomical and cellular sources. We therefore outline a spatially resolved strategy integrating anatomically registered sampling with mass spectrometry imaging, histopathology, molecular classification, and single-cell or spatial transcriptomic approaches. This framework provides testable hypotheses to determine whether meningioma lipid states reflect tumor-intrinsic programs, anatomically defined microenvironments, aging-associated remodeling, or interactions among these determinants, and how these states relate to invasion, recurrence, edema, and treatment resistance.