Immune Aging in the Central Nervous System: Microglia, Neuroinflammation, and Cognitive Decline

Aging of the central nervous system is accompanied by a gradual decline in immune regulation, a process often described as immunosenescence, which leaves the brain more vulnerable to chronic low-grade inflammation. Microglia, the resident immune cells of the brain, sit at the center of this shift. With age, they can move from a protective, surveillance role toward a more reactive state, releasing inflammatory mediators, showing reduced clearance of debris and pathogens, and contributing to a self-sustaining cycle of neuroinflammation. This process is increasingly recognized as a driver, not just a byproduct, of cognitive decline and age-related neurodegenerative disease.This Research Topic examines how immune aging in the central nervous system shapes microglial function, cellular metabolism, neuroimmune interfaces, and cognitive outcomes. We invite contributions addressing, but not limited to, the following areas:• Mechanisms of microglial priming, activation, and senescence with age• Cellular metabolism and organelle dysfunction in CNS aging, including mitochondrial dysfunction, lysosomal impairment, autophagy/mitophagy, oxidative stress, and immunometabolic reprogramming• Neuroimmune interfaces and barrier systems in aging, including the blood-brain barrier, neurovascular unit, choroid plexus, meninges, border-associated macrophages, and infiltrating peripheral immune populations• The role of neuroinflammation in age-related cognitive decline and dementia, including Alzheimer’s disease and related disorders• Cross-talk between peripheral immune aging and central nervous system inflammation, including the gut-brain and infection-brain axes• Molecular and cellular pathways linking chronic inflammation to synaptic loss, neuronal dysfunction, and network-level changes in the aging brain• Non-coding RNAs, extracellular vesicles, and other emerging mediators of neuroinflammatory signaling• The impact of viral infection, substance use, or other environmental exposures on glial aging and neuroinflammation• Sex differences and individual variability in immune aging trajectories in the brain• Biomarkers of neuroinflammation and immune aging with translational or diagnostic potential• Therapeutic and lifestyle strategies aimed at modulating microglial activity or reducing neuroinflammatory burden in aging populations• Animal and cellular models used to study immune aging and neuroinflammation, including their strengths and limitationsArticles addressing related cell types, such as astrocytes, border-associated macrophages, or infiltrating peripheral immune cells, are also welcome where they inform our understanding of neuroinflammation in aging.The goal of this collection is to bring together current research on how immune and metabolic changes in the aging brain contribute to cognitive decline, while remaining open to the diverse mechanisms, interfaces, models, and methodologies through which this question is being addressed across the field. Topic editors: Ali Delbaz, Minglei Guo, Souptik Basu, Uma Maheswari Deshetty Source: https://www.frontiersin.org/research-topics/86648/immune-aging-in-the-central-nervous-system-microglia-neuroinflammation-and-cognitive-decline