Molecular Mechanisms of Microglial Dysfunction and Epigenetic Regulation in Brain Aging

Aging of the central nervous system is characterized by a progressive decline in cognitive and neuropsychiatric resilience, a process intimately linked to chronic neuroinflammation and cellular senescence. At the center of this decline is the dysregulation of microglia, the resident immune cells of the brain. While healthy microglia maintain neural networks and support synaptic plasticity, aging triggers a phenotypic shift toward a dysfunctional, hyper-reactive state. Recent evidence indicates that this microglial transition is tightly regulated by specific epigenetic modifications, chromatin remodeling, and localized transcriptional shifts. Rather than static genomic changes, these dynamic molecular adjustments alter how microglial pathways respond to the aging brain environment, ultimately driving neurodegenerative and neuropsychiatric decline.This Research Topic aims to dissect the precise molecular pathways and regulatory mechanisms that control microglial behavior during brain aging. We seek to highlight research that moves beyond broad genomic profiling to uncover the direct molecular interactions, signal transduction cascades, and epigenetic regulatory networks governing microglial activation, senescence, and functional decline. By mapping these specific pathways, this collection aims to identify novel therapeutic targets capable of reversing microglial dysfunction and mitigating age-related neuropsychiatric deterioration.We welcome Original Research, Review, Mini Review, and Perspective articles that focus on the molecular, cellular, and pathway-level mechanisms of brain aging. Submissions should emphasize the functional and regulatory dynamics of microglia rather than purely descriptive genomic datasets.Suitable themes include, but are not limited to:- Regulatory Pathways of Neuroinflammation: Molecular signaling cascades (such as NF-κB, NLRP3 inflammasome, or TREM2 pathways) that drive age-associated microglial hyper-reactivity.- Epigenetic Regulation of Microglial States: The role of specific histone modifications, DNA methylation dynamics, and non-coding RNAs in shaping microglial phenotypes during brain aging.- Cellular and Synaptic Consequences: Molecular mechanisms through which dysfunctional microglia impair synaptic pruning, neural connectivity, and cognitive resilience.- Environmental and Metabolic Modulators: How localized metabolic shifts, mitochondrial dysfunction, and systemic aging factors molecularly reprogram microglial epigenetic landscapes.- Targeted Therapeutic Interventions: Novel molecular strategies, small molecules, or pathway-specific interventions aimed at restoring healthy microglial function and preventing neuropsychiatric decline. Topic editors: Li Mengdie, Yuyao Tian Source: https://www.frontiersin.org/research-topics/84699/molecular-mechanisms-of-microglial-dysfunction-and-epigenetic-regulation-in-brain-aging