Aging of the central nervous system is characterized by intricate changes in immune regulation, molecular signaling, and neuronal integrity. Among the key players in this process are microglia, the resident immune cells of the brain, whose fundamental role in maintaining tissue homeostasis becomes progressively impaired with advancing age. Evidence from preclinical and clinical studies indicates that microglial dysfunction contributes to chronic low-grade neuroinflammation, synaptic deterioration, and neuronal loss; hallmarks of neurodegenerative pathologies such as Alzheimer’s disease, Parkinson’s disease, and other forms of dementia. Despite major advances in understanding these associations, significant gaps persist regarding how microglial state transitions, metabolic reprogramming, and regional heterogeneity shape disease progression and resilience. The growing body of research emphasizes the need to clarify the molecular and cellular circuits linking age-related changes in microglia to neurodegeneration and cognitive decline.

This Research Topic aims to advance our understanding of the molecular mechanisms by which microglial aging contributes to neuroinflammation and neuronal vulnerability. It seeks to integrate studies that move beyond descriptive observations to delineate the causal pathways driving microglial activation, altered signaling, and loss of homeostatic function in the aging brain. The ultimate objective is to build a mechanistic framework capable of explaining how microglial plasticity interacts with other glial and neuronal cell types to influence brain function, degeneration, and repair. This includes identifying key regulatory nodes and cell states that could be targeted to alleviate age-related cognitive dysfunction and delay neurodegenerative disease onset.

To gather further insights into the interplay between microglial biology, inflammation, and neurodegenerative processes, we welcome submissions that explore experimental, computational, and translational perspectives. Contributions may address, but are not limited to, the following themes:

- Microglial state transitions from homeostatic to reactive phenotypes during aging

- Sex-specific differences in microglial function and neuroinflammatory outcomes

- Mechanistic modeling of microglial alterations in aging mice (e.g., DNA damage, telomere attrition, mitochondrial dysfunction)

- Microglia–synapse interactions shaping neuronal plasticity and degeneration

- Metabolic adaptations of microglia in neurodegenerative contexts

- Region- and cell-type–specific vulnerability to inflammatory damage

- Cross-talk between microglia, astrocytes, and neurons in degenerating brain circuits

- In-vitro and in-vivo modeling of microglial senescence and inflammatory signaling

- Development of biomarkers for monitoring microglial activity and neuroinflammation in humans

- Therapeutic strategies targeting microglial pathways to preserve brain health and slow cognitive decline

Article types welcomed include original research papers, reviews, and clinical perspectives.

Are you interested in contributing a manuscript to this Research Topic?

Microglia, Neuroinflammation, and Neurodegeneration in Brain Aging and Age-Associated Disease