ArticleJournal of neuroinflammation2024
Microglia undergo sex-dimorphic transcriptional and metabolic rewiring during aging.
Article in Journal of neuroinflammation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Shared and niche-specific transcriptional signatures of macrophage aging revealed by a cross-tissue meta-analysis.BMC biology · 2026Pooled it
- Nicotinamide riboside supplementation restores microglial health and improves cognition in aged male mice.GeroScience · 2026Article
- Microglia-derived extracellular vesicle content as a biomarker for early detection of Alzheimer's disease.Translational neurodegeneration · 2026Review
- Article
- Article
- Metabolic Reprogramming of Brain Microglia: Implications for Aging and Aging-Associated Neurodegenerative Diseases.Aging cell · 2026Review
- XYomics: detecting sex-dependent molecular mechanisms in omics data.Nucleic acids research · 2026Article
- STAT6 Targets the Autophagy Pathway to Regulate Microglial Senescence in Cognitive Impairment Caused by Cerebral Small-Vessel Disease.Neuromolecular medicine · 2026Article
- The ageing immune system as a driver of systemic ageing.Nature reviews. Immunology · 2026Review
- Review
- Expression of GPR34 in microglia remains stable in human Alzheimer's disease.Acta neuropathologica · 2026Article
- C1q-CD44 interactions regulate microglial phagocytosis, proliferation, and migration.Journal of neuroinflammation · 2026Article
- Microglia Rank signaling regulates GnRH neuronal function and the hypothalamic-pituitary-gonadal axis.Science (New York, N.Y.) · 2026Article
- Alzheimer's Disease Risk Factor APOE4 Exerts Dimorphic Effects on Female Bone.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- A multi-omic atlas in the African turquoise killifish reveals increased glucocorticoid signaling as a hallmark of brain aging.bioRxiv : the preprint server for biology · 2026Article
- Dual Role of Microglial TREM2 in Neuronal Degeneration and Regeneration After Axotomy.bioRxiv : the preprint server for biology · 2026Article
- Sex Differences in Metabolite-Immune Circuits of Neuroinflammation.Immunological reviews · 2026Review
- Reframing brain aging: neuroinflammation as an interconnected network process.Frontiers in aging · 2026Review
- From metabolism to neurodegeneration: how microglial functional reprogramming drives neurodegenerative diseases.Frontiers in molecular neuroscience · 2026Review
- Atypical antipsychotics alter microglial functions via astrocyte-derived extracellular vesicles.Brain, behavior, and immunity · 2026Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Microglia, the brain's resident macrophages, maintain brain homeostasis and respond to injury and infection. During aging they undergo functional changes, but the underlying mechanisms and their contributions to neuroprotection versus neurodegeneration are unclear. Previous studies suggested that microglia are sex dimorphic, so we compared microglial aging in mice of both sexes. RNA-sequencing of hippocampal microglia revealed more aging-associated changes in female microglia than male microglia, and more sex differences in old microglia than young microglia. Pathway analyses and subsequent validation assays revealed a stronger AKT-mTOR-HIF1α-driven shift to glycolysis among old female microglia and indicated that C3a production and detection was elevated in old microglia, especially in females. Recombinant C3a induced AKT-mTOR-HIF1α signaling and increased the glycolytic and phagocytic activity of young microglia. Single cell analyses attributed the aging-associated sex dimorphism to more abundant disease-associated microglia (DAM) in old female mice than old male mice, and evaluation of an Alzheimer's Disease mouse model revealed that the metabolic and complement changes are also apparent in the context of neurodegenerative disease and are strongest in the neuroprotective DAM2 subset. Collectively, our data implicate autocrine C3a-C3aR signaling in metabolic reprogramming of microglia to neuroprotective DAM during aging, especially in females, and also in Alzheimer's Disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.