Aging reprograms microglia toward an inflammasome-linked response to traumatic brain injury.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 42294901.
- Also identified by DOI 10.1172/JCI207022 and PMC identifier 13262710.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Traumatic brain injury (TBI) disproportionately kills and disables older adults, yet the biology driving this vulnerability remains unresolved. In this issue of the JCI, Lu et al. combined single-cell transcriptomics, metabolomics, and chromatin profiling in mice, validated in human TBI tissue, to define an age-dependent microglial dichotomy. They report that an NLRP3+/IL-1β-linked state dominates the aged brain, while a Lysozyme+/Lyz2+ state predominates in the young. Microglia-targeted perturbation of NLRP3 and ELF1 each shifted the balance and improved survival in mouse models of TBI, and the repurposed drug Imeglimin improved outcomes in these models, confirming that this pathway is druggable. By connecting NLRP3 inflammasome dominance, ELF1-driven transcription, and glycolytic reprogramming to the loss of a protective Lyz2+ response, this work converts age from a clinical risk factor to a set of druggable microglial targets.
Medical subject headings
- Microglia
- Inflammasomes
- Aging
- Brain Injuries, Traumatic