From Myelin Damage to Immune Dysfunction: Unraveling the Aging Brain

Aging is associated with progressive white matter degeneration, which impairs brain structure and function. Defects in myelinating glial cells, combined with chronic neuroinflammation, contribute to this decline. Recent studies reveal that dysfunctional and maladaptively activated microglia promote the recruitment and retention of harmful CD8+ T cells in aging white matter through chemokine signaling. Using single-cell and spatial transcriptomics, researchers in the Groh laboratory have uncovered the complex cellular and molecular interactions between glial cells and immune cells that drive these processes. These insights highlight the pivotal role of microglia–immune cell crosstalk in white matter pathology and open new avenues for therapeutic intervention in age-related neurodegenerative disease.

Learning Objectives:

• Learn how defects in myelinating glial cells and neuroinflammation contribute to structural and functional alterations in aging white matter

• Explore how single-cell and spatial transcriptomics reveal complex interactions between microglia, CD8+ T cells, and other immune cells in the aging brain

• Evaluate the role of microglia-driven chemokine signaling in facilitating immune cell recruitment and its implications for neurodegeneration