2025-09-02 タフツ大学
<関連情報>
- https://now.tufts.edu/2025/09/02/immune-molecule-long-tied-inflammation-may-benefit-aging-brain
- https://www.cell.com/cell-reports/fulltext/S2211-1247(25)00520-0
ミクログリアのSTINGは、加齢に伴う神経機能低下の中心的な防御機構である Microglial STING is a central safeguard against neurological decline with age
Katherine B. Sulka ∙ Kimberly A. Carroll ∙ Machlan Sawden ∙ … ∙ Pilar Alcaide ∙ Philip Haydon ∙ Shruti Sharma
Cell Reports Published:May 31, 2025
DOI:https://doi.org/10.1016/j.celrep.2025.115749
Graphical abstract
Highlights
- STING signaling limits the accrual of damaged DNA and inflammation in the CNS with age
- STING is critical for maintaining BBB integrity and averting neuromotor deficits with age
- STING modulates microglial populations, transcriptomes, and cell-cell interactions
- Microglial STING is sufficient to protect against BBB decline and neuromotor deficits
Summary
Functional decline of the central nervous system (CNS) is driven by the breakdown of the blood-brain barrier (BBB) and attendant inflammation, all hallmarks of age-related neurodegeneration. Despite intense interest in how the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway impacts neurodegenerative processes in aging, its role in shaping these features of CNS fate during physiological aging remains unclear. Here, using physiologically aged mice, we uncovered an unexpected but vital role for STING in preserving CNS function. We find that STING deficiency exacerbates neurological decline through BBB breakdown, microhemorrhages, and neuromotor deficits. Furthermore, STING deficiency leads to an accrual of neuronal DNA damage and alters CNS proinflammatory, type I interferon, and senescence signatures. Cumulatively, these changes lead to a transformation in microglia phenotypes and transcriptomes. Finally, microglial-STING expression is sufficient to elicit protection against age-associated changes in the CNS and highlights the mechanistic basis for STING-dependent protective mechanisms within the aging brain.
