Morphological and Metabolic Features of Brain Aging in Rodents, Ruminants, Carnivores, and Non-Human Primates

Brain aging in mammals is characterized by morphological and functional changes in neural cells. Macroscopically, this process, leading to progressive cerebral volume loss and functional decline, includes memory and motor neuron deficits, as well as behavioral disorders. Morphologically, brain aging is associated with aged neurons and astrocytes, appearing enlarged and flattened, and expressing enhanced pH-dependent β-galactosidase activity. Multiple mechanisms are considered hallmarks of cellular senescence in vitro, including cell cycle arrest, increased lysosomal activity, telomere shortening, oxidative stress, and DNA damage. The most common markers for senescence identification were identified in (i) proteins implicated in cell cycle arrest, such as p16, p21, and p53, (ii) increased lysosomal mass, and (iii) increased reactive oxygen species (ROS) and senescenceassociated secretory phenotype (SASP) expression. Finally, dysfunctional autophagy, a process occurring during aging, contributes to altering brain homeostasis. The brains of mammals can be studied at cellular and subcellular levels to elucidate the mechanisms on the basis of age-related and degenerative disorders. The aim of this review is to summarize and update the most recent knowledge about brain aging through a comparative approach, where similarities and differences in some mammalian species are considered.