Brain Macro-Structural Alterations in Aging Rats: A Longitudinal Lifetime Approach.

Aging is accompanied by macro-structural alterations in the brain that may relate to age-associated cognitive decline. Animal studies could allow us to study this relationship, but so far it remains unclear whether their structural aging patterns correspond to those in humans. Therefore, by applying magnetic resonance imaging (MRI) and deformation-based morphometry (DBM), we longitudinally screened the brains of male RccHan:WIST rats for structural changes across their average lifespan. By combining dedicated region of interest (ROI) and voxel-wise approaches, we observed an increase in their global brain volume that was superimposed by divergent local morphologic alterations, with the largest aging effects in early and middle life. We detected a modality-dependent vulnerability to shrinkage across the visual, auditory, and somato-sensory cortical areas, whereas the piriform cortex showed partial resistance. Furthermore, shrinkage emerged in the amygdala, subiculum, and flocculus as well as in frontal, parietal, and motor cortical areas. Strikingly, we noticed the preservation of ectorhinal, entorhinal, retrosplenial, and cingulate cortical regions, which all represent higher-order brain areas and extraordinarily grew with increasing age. We think that the findings of this study will further advance aging research and may contribute to the establishment of interventional approaches to preserve cognitive health in advanced age.