Oligodendrocytes at the Crossroads: Central Players and Interactive Partners in White Matter Aging.

Xinxin Zhang, Peiyao Yu, Yicheng Chen, Yanzhi Xu, Ruofei Xu, Xinyu Yang, Shichao Lv, Hongcai Shang, Yue Hu

School of Integrative Medicine, Nanjing University of Chinese Medicine, No. 138, Xianlin Road, Qixia District, Nanjing City, Jiangsu 210023, People's Republic of China. Electronic address: [email protected] of Integrative Medicine, Nanjing University of Chinese Medicine, No. 138, Xianlin Road, Qixia District, Nanjing City, Jiangsu 210023, People's Republic of China. Electronic address: [email protected]. · pubmed

Paper

Abstract

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.

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Research summary

Oligodendrocytes play a central role in white matter integrity and their dysfunction contributes to cognitive decline in aging. The paper is relevant as it addresses the intrinsic aging mechanisms of oligodendrocytes and their interactions, which are crucial for understanding and potentially mitigating age-related cognitive decline.

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