Microglia activation by derepression of endogenous retroviruses drives inflammation and cellular senescence.

Loss of DAXX during aging causes microglia to activate via derepressed endogenous retroviruses, leading to inflammation and cellular senescence in the brain.

• Why it matters: Understanding how chromatin changes contribute to microglia activation is crucial because microglial dysfunction is linked to age-related neurodegenerative diseases and brain aging.
• What they did: The study examined DAXX downregulation in mouse microglia, using genetic models to show that its loss induces chromatin decompaction at retrotransposable elements, triggering reactive and senescent states.
• The result: Findings reveal that maintaining heterochromatin via DAXX preserves microglial identity and function, offering insights into mechanisms of brain aging and potential targets for intervention.