Aging and inflammation-induced cellular senescence may contribute to oligodendrocyte dysfunction in multiple sclerosis (MS). The study used directly converted oligodendrocytes (dehiOL) from young, adult, and old human donors to investigate age-associated changes. DehiOL from all age groups differentiated similarly into O4+ immature oligodendrocytes, but the proportion of MBP+ mature dehiOL decreased with increasing donor age. This was associated with increased ROS production and upregulation of cellular senescence markers such as *CDKN1A* and *CDKN2A*. Transcriptomic analysis revealed 1324 differentially regulated genes in old dehiOL compared to adults, with limited overlap with fibroblast or neuron transcriptomic profiles. Methylation analyses showed that chronological and epigenetic age correlate in CNS white matter and dehiOL, and an age-specific epigenetic signature was identified. Accelerated epigenetic aging was observed in the normal appearing non-demyelinated white matter (NAWM) of MS patients compared to healthy individuals. Young dehiOL exposed to pro-inflammatory microglial supernatants exhibited impaired differentiation and upregulation of cellular senescence markers, suggesting that chronic inflammation contributes to oligodendrocyte pathology in MS. These findings highlight the role of physiological aging and inflammation-induced cellular senescence in oligodendrocyte dysfunction in inflammatory demyelinating diseases like MS.Aging and inflammation-induced cellular senescence may contribute to oligodendrocyte dysfunction in multiple sclerosis (MS). The study used directly converted oligodendrocytes (dehiOL) from young, adult, and old human donors to investigate age-associated changes. DehiOL from all age groups differentiated similarly into O4+ immature oligodendrocytes, but the proportion of MBP+ mature dehiOL decreased with increasing donor age. This was associated with increased ROS production and upregulation of cellular senescence markers such as *CDKN1A* and *CDKN2A*. Transcriptomic analysis revealed 1324 differentially regulated genes in old dehiOL compared to adults, with limited overlap with fibroblast or neuron transcriptomic profiles. Methylation analyses showed that chronological and epigenetic age correlate in CNS white matter and dehiOL, and an age-specific epigenetic signature was identified. Accelerated epigenetic aging was observed in the normal appearing non-demyelinated white matter (NAWM) of MS patients compared to healthy individuals. Young dehiOL exposed to pro-inflammatory microglial supernatants exhibited impaired differentiation and upregulation of cellular senescence markers, suggesting that chronic inflammation contributes to oligodendrocyte pathology in MS. These findings highlight the role of physiological aging and inflammation-induced cellular senescence in oligodendrocyte dysfunction in inflammatory demyelinating diseases like MS.