Astrocytes in the Aging Brain: Molecular Mechanisms of Neurodegeneration and Neuroprotection

Ageing is the single largest risk factor for neurodegenerative disease, yet decades of neuron-centric research have yielded only modest therapeutic progress. Increasing attention has turned to astrocytes, the star-shaped glial cells that outnumber neurons in many brain regions and are essential for synaptic function, ion and neurotransmitter homeostasis, metabolic support, blood-brain barrier integrity and the clearance of waste from the brain. In Alzheimer’s disease, where astrocyte involvement is best characterised, these cells undergo profound morphological, transcriptional and functional changes. Similar shifts begin in the ageing brain long before overt pathology appears, along a continuum of reactive states that can be either neuroprotective or neurotoxic. Disrupted calcium signalling, altered handling of misfolded proteins including amyloid-beta, tau and alpha-synuclein, and changes in the astrocytic secretome have all been implicated in the transition from healthy ageing to disease.What determines where an astrocyte sits on that continuum remains unresolved. Cell-intrinsic stress pathways, including endoplasmic reticulum stress and the unfolded protein response, are emerging as candidate switches that couple astrocyte state to synaptic and circuit outcomes. Ageing shifts the starting point, and acute insults such as systemic inflammation, illness, injury or surgery can push an already vulnerable astrocyte population across the threshold. Astrocytes also govern glymphatic and perivascular clearance, so their dysfunction may drive protein accumulation as much as it responds to it. Advances in in vivo imaging, human iPSC-derived astrocyte models and single-cell transcriptomics now make these questions tractable in ways they were not a decade ago.This Research Topic invites contributions that move from correlation to mechanism, and that connect astrocyte biology to measurable outcomes in synapses, circuits and cognition. Work on Alzheimer’s disease is central to the collection, and we equally welcome studies in other age-related conditions and in normal brain ageing. We welcome original research, reviews and methodological papers addressing, but not limited to:• Calcium signalling and astrocyte-neuron crosstalk across the lifespan• Cell-intrinsic stress pathways, proteostasis and the unfolded protein response as determinants of reactive state• Astrocytic handling of amyloid-beta and tau in Alzheimer’s disease, and of other misfolded proteins in related age-associated proteinopathies• Glymphatic, perivascular and blood-brain barrier clearance under astrocytic control• The astrocytic secretome and its effect on synapse maintenance and loss• Acute stressors as modifiers of astrocyte function in the ageing brain, including systemic inflammation, injury and perioperative insults• Astrocyte heterogeneity across brain regions and ages, resolved by in vivo imaging, human iPSC models or single-cell approaches• What distinguishes protective from harmful astrocyte states, and whether that switch is therapeutically reversibleWe encourage a wide range of submissions, including original research, methods papers, brief research reports, data reports, systematic reviews, mini reviews and perspectives. Topic editors: Kai Chen, Santosh Jadhav, Yuhua Huang, Ning Shen Source: https://www.frontiersin.org/research-topics/85455/astrocytes-in-the-aging-brain-molecular-mechanisms-of-neurodegeneration-and-neuroprotection