The cellular choreography of brain aging: a neuroimmune network perspective

Brain aging is increasingly recognized as a heterogeneous and systems-level process involving dynamic interactions among neuronal, glial, vascular, and immune-associated cell populations. Recent advances in single-cell and spatial omics technologies have revealed diverse cellular aging trajectories, region-specific vulnerabilities, and extensive remodeling of intercellular communication networks across the aging brain. These findings challenge reductionist views of aging and emphasize the importance of understanding how cellular interactions collectively shape neural function and resilience. In this mini-review, we examine brain aging from a neuroimmune and network-based perspective, focusing on how coordinated interactions among neurons, glial cells, and vascular elements regulate tissue homeostasis during aging. We propose the concept of a cellular choreography as a system-level framework for understanding how dynamic interactions among neurons, glial cells, vascular elements, and neuroimmune signaling pathways shape brain aging. Rather than acting independently, these cellular systems continuously coordinate metabolic support, inflammatory responses, synaptic activity, and vascular regulation across the neurovascular unit. Aging progressively alters these interactions, contributing to synaptic dysfunction, glial reactivity, blood-brain barrier impairment, and chronic low-grade inflammation. We further discuss shared molecular programs-including mitochondrial dysfunction, impaired proteostasis, cellular senescence, DNA damage responses, and epigenetic remodeling-that influence multiple cell populations and propagate dysfunction across interconnected cellular networks. Finally, we highlight emerging longitudinal, multiomic, and stem cell-based approaches that are beginning to map cellular aging trajectories across multiple biological scales. Integrating these approaches within systems-level frameworks may improve the identification of early biomarkers and therapeutic targets aimed at promoting resilient and healthy brain aging.