Rodríguez-Callejas and colleagues revealed that astrocyte ageing is not uniform but highly region-specific within the hippocampus. They found that a ubiquitous increase in GFAP levels across hippocampal subregions, accompanied by elevated oxidative stress, reflected by increased 8OHG+ oxidative RNA level. While the total number of GFAP positive astrocytes remained constant, their morphology changed dramatically in different ways depending on the subregion. Astrocytes in the DG and CA2-CA1 areas became hypertrophic with longer, more complex GFAP+ processes, whereas those in the CA3 region showed a clear atrophic phenotype with shorter, simplified processes. These findings challenge the perception of a single "ageing astrocyte" state and emphasise that the local brain microenvironment critically determines cellular fate during ageing. In addition, it is important to note that GFAP staining alone cannot accurately reflect astrocytic morphological changes. Examining changes in the astrocytic fine processes with other markers, such as Aldh1L1 or with fluorescent protein labelling, would be more informative. Nonetheless, such regional diversity of astrocytic response could partially explain the lack of consensus about how astrocyte morphology changes during ageing.
Su et al. (Wed,) studied this question.