The Roles of Macrophage Lineage Cells (MLCs) in Brain Aging

Brain aging poses a major public health challenge and is the primary risk factor for neurodegenerative diseases. Macrophage lineage cells (MLCs) have emerged as pivotal mediators of brain aging. While fundamental to central nervous system (CNS) homeostasis through their scavenging, detoxification, and neurotrophic functions, their transition to a senescent state is a primary driver of pathology. This shift is marked by a loss of clearance capacity and the adoption of a pro-inflammatory senescence-associated secretory phenotype (SASP).

Here, we summarize the distinct and cooperative roles of MLC subsets in brain aging. We examine the key molecular drivers of MLCs senescence and detail how subset-specific dysfunction contributes to the propagation of cellular aging and related neuropathology. Finally, we evaluate current and emerging therapeutic strategies that target MLCs senescence.

We conclude by proposing a multidimensional management framework for brain aging. This framework positions MLCs as a central therapeutic hub, integrating advanced diagnostics and stratified interventions to preserve brain health and mitigate neurodegenerative pathology.