Activation of brain immune cells by reactivated viral elements may cause inflammation and cell aging

Aging leads to downregulation of DAXX, a histone chaperone, which is associated with microglial activation and cellular senescence.

• Loss of DAXX in young-adult microglia triggers a reactive state characterized by chromatin decompaction at retrotransposable elements.
• This reactive phenotype results in the loss of homeostatic markers and promotes cell cycle re-entry.
• Microglial depletion occurs alongside DNA damage, followed by the emergence of DAXX-deficient microglia with features of senescence.
• The sustained activation of senescence is linked to promyelocytic leukemia protein, which interacts with DAXX and is an interferon target.
• Maintaining heterochromatin is essential for preserving adult microglial identity and function.

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