Abstract: Recent reports suggest that aging is not solely a physiological process in living beings; instead, it should be considered a pathological process or disease (Amorim et al., 2022). Consequently, this process involves a wide range of factors, spanning from genetic to environmental factors, and even includes the gut microbiome (GM) (Mayer et al., 2022). All these processes coincide at some point in the inflammatory process, oxidative stress, and apoptosis, at different degrees in various organs and systems that constitute a living organism (Mayer et al., 2022; AguilarHernández et al., 2023). However, one of the most studied organs in the aging process is the brain, due to the cognitive deficits observed in aging animals, including humans (Aguilar-Hernández et al., 2023). Moreover, with aging, a set of both metabolic and cardiovascular diseases manifests, among which are diabetes mellitus and high blood pressure. With the progression of both aging and these diseases, cognitive deficits have been demonstrated in both human and animal models (Flores-Gómez et al., 2019; Flores et al., 2020). These cognitive deficits can vary depending on the degree of affectation to interneuronal communication, specifically at the level of dendritic spines (Aguilar-Hernández et al., 2023). A recent study conducted by our research team has revealed that aging results in a decline in dendritic spine density and a reconfiguration of dendritic spine shapes in corticolimbic areas in rodents, such as the prefrontal cortex (PFC). The PFC plays a crucial role in cognitive functions like attention, decision-making, and control over reward and motivation (Reyes-Lizaola et al., 2024). While there is extensive data on the decrease in dendritic spine density due to aging in humans (AguilarHernández et al., 2023), the impact of aging on the structural neuroplasticity of dendritic spines remains unexplored, to the best of our knowledge.