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Comprehensive analysis of cellular senescence in the central nervous system revealed microglial senescence and its involvement in demyelinating diseases

ABSTRACT: Cellular senescence is a state of irreversible cell-cycle arrest caused by various cellular stressors. Accumulating evidence indicates that cellular senescence is one of the key factors causing age-related tissue dysfunction in various organs. However, the features of cells that undergo cellular senescence and their significance in neural impairment are still unclear in the central nervous system. We showed that microglia, particularly in the white matter, undergo cellular senescence in the brain and spinal cord during ageing and in disease models involving demyelination through comprehensive investigations utilizing single-cell transcriptome analysis and various mouse models. Microglial senescence is predominantly detected in disease-associated microglia (DAM), which emerge with ageing and in neurodegenerative diseases. Knockouts of the p16INK4a gene, a key inducer of cellular senescence, ameliorated the neuroinflammatory phenotype in damaged spinal cords in mice. Finally, we showed that commensal bacteria promote the accumulation of senescent microglia and DAM associated with ageing. These results advanced our understanding of cellular senescence’s role in the central nervous system and opened new strategies for treating age-related neural disorders.

ORGANISM(S): Mus musculus

PROVIDER: GSE204828 | GEO | 2023/05/25

REPOSITORIES: GEO

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