Aging in the brain is a multifaceted process marked by gradual alterations across diverse cellular populations, including neurons, glia, and vascular cells. Recent advances in single-cell multiomics, and imaging have revealed increasing heterogeneity and region-specific vulnerabilities with age. Glial cells, particularly microglia and astrocytes, exhibit shifts toward pro-inflammatory and reactive states, contributing to neuroinflammation and impaired homeostasis. Age-related changes in neuronal function, such as synaptic and mitochondrial dysfunction, underlie cognitive decline and increased susceptibility to neurodegenerative diseases. Vascular aging, including blood–brain barrier breakdown and reduced cerebral perfusion, further exacerbates neural dysfunction. Emerging models like in vivo tracing, iPSC-derived organoids, and comparative lifespan studies, are shedding light on the divergent aging trajectories across species. Together, these efforts are helping us elucidating the picture of brain aging, revealing intricate mechanisms that span decades and influence brain health.

Brain aging is a complex, gradual process driving increased risk for cognitive decline and neurodegenerative diseases, yet the precise cellular and molecular mechanisms remain poorly defined. Key challenges include disentangling age-related changes from disease-specific processes and capturing the heterogeneity of aging across brain regions and cell types. Recent advances in single-cell technologies, longitudinal imaging, and human stem cell models have enabled unprecedented resolution in tracking cellular aging trajectories. To tackle this problem, integrative approaches combining omics, functional assays, and in vivo models are needed to map dynamic changes, identify early biomarkers, and uncover potential interventions that promote healthy brain aging.

This Research Topic aims to explore the cellular and molecular foundations of brain aging and their connection to neurological disorders. We welcome studies that address:

• Age-associated changes in neurons, glia, and vascular cells

• Cellular senescence, proteostasis, mitochondrial dysfunction, and DNA damage responses

• Neuroinflammation and immune system dynamics in the aging brain

• Epigenetic and transcriptomic remodeling across the aging lifespan

• Brain region-specific vulnerabilities and cellular heterogeneity

• Longitudinal studies tracking aging trajectories at single-cell resolution

• Comparative aging across species and models

• iPSC-derived and organoid models of neural aging

• Early molecular signatures linking aging to neurodegeneration

We accept Original Research, Reviews, Mini Reviews, and Perspectives. Methodological and Data Reports that provide novel tools or datasets relevant to brain aging are also encouraged. Contributions should aim to deepen mechanistic insight or offer integrative perspectives that advance the understanding of brain aging across time and context.

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

Tracing the Cellular Symphony: Unraveling Brain Aging