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mTOR-dependent translation amplifies microglia priming in aging mice
- Source :
- J Clin Invest, The journal of clinical investigation 131(1), e132727 (2021). doi:10.1172/JCI132727
- Publication Year :
- 2019
-
Abstract
- Microglia maintain homeostasis in the brain. However, with age, they become primed and respond more strongly to inflammatory stimuli. We show here that microglia from aged mice had upregulated mTOR complex 1 signaling controlling translation, as well as protein levels of inflammatory mediators. Genetic ablation of mTOR signaling showed a dual yet contrasting effect on microglia priming: it caused an NF-κB–dependent upregulation of priming genes at the mRNA level; however, mice displayed reduced cytokine protein levels, diminished microglia activation, and milder sickness behavior. The effect on translation was dependent on reduced phosphorylation of 4EBP1, resulting in decreased binding of eIF4E to eIF4G. Similar changes were present in aged human microglia and in damage-associated microglia, indicating that upregulation of mTOR-dependent translation is an essential aspect of microglia priming in aging and neurodegeneration.
- Subjects :
- 0301 basic medicine
genetics [Eukaryotic Initiation Factor-4E]
Aging
Priming (immunology)
chemistry.chemical_compound
Mice
0302 clinical medicine
Phosphorylation
Microglia
EIF4G
TOR Serine-Threonine Kinases
Neurodegeneration
EIF4E
NF-kappa B
General Medicine
genetics [TOR Serine-Threonine Kinases]
Cell biology
metabolism [Eukaryotic Initiation Factor-4G]
medicine.anatomical_structure
030220 oncology & carcinogenesis
genetics [Aging]
metabolism [NF-kappa B]
medicine.symptom
Corrigendum
enzymology [Microglia]
Research Article
Signal Transduction
genetics [Eukaryotic Initiation Factor-4G]
Inflammation
Mice, Transgenic
Biology
metabolism [TOR Serine-Threonine Kinases]
03 medical and health sciences
Downregulation and upregulation
medicine
Animals
Humans
ddc:610
metabolism [Aging]
genetics [Phosphorylation]
PI3K/AKT/mTOR pathway
medicine.disease
metabolism [Eukaryotic Initiation Factor-4E]
030104 developmental biology
Eukaryotic Initiation Factor-4E
nervous system
chemistry
Protein Biosynthesis
Eukaryotic Initiation Factor-4G
genetics [NF-kappa B]
Subjects
Details
- ISSN :
- 15588238
- Volume :
- 131
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- The Journal of clinical investigation
- Accession number :
- edsair.doi.dedup.....b05f392a7037319ea89ea4e19e111086