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Immunometabolic dysregulation in microglia drives brain ageing via neuroimmune cGAS-STING

ABSTRACT: Ageing and age-related brain disorders are typically concomitant with cellular mitochondrial dysfunction and metabolic dysregulation in immune cells. However, whether and how immunometabolic dysregulation in the brain affects neurological function are incompletely understood. Here we reveal the presence of metabolic dysregulation within microglia, the brain-resident immune cells, in aged mice. We discover that microglia with dysregulated immunometabolism, induced by dysfunctional mitochondria, initially act as triggers of brain ageing-related neurological dysfunctions in mice, which are mechanistically driven by microglial immunometabolic disturbance-induced inflammaging response depending on neuroimmune cGAS-STING pathway. We present evidence that a combined treatment targeting both metabolism and neuroinflammation partially rescues brain ageing in mice. These findings establish a causal link between immunometabolism, neuroimmunity, and brain ageing, underscoring the significance of tightly regulated immunometabolism in age-associated neurological diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE266053 | GEO | 2025/04/28

REPOSITORIES: GEO

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