Oligodendrocytes at the crossroads: Central players and interactive partners in white matter aging

White matter degeneration in aging drives cognitive and motor decline. Oligodendrocytes (OLs) and their precursors are central to this process. Their intrinsic aging, marked by differentiation failure, metabolic and mitochondrial deficits, and transcriptional epigenetic dysregulation, causes myelin thinning and axonal support loss. Degeneration is amplified by dysfunctional crosstalk: microglia clear debris poorly and turn inflammatory; astrocytes disrupt lipid balance and secrete inflammatory signals; vascular defects impair metabolic supply; and T cell infiltration injures OLs. We review therapies targeting OL lineage, glial networks, vascular health, and lifestyle. Positioning OLs as integrative hubs of white matter integrity offers new strategies to maintain brain function during aging.