Aging is a physiological process occurring in all living organisms. It is characterized by a pro-gressive deterioration of the physiological and cognitive functions of the organism, accompanied by a gradual impairment of mechanisms involved in the regulation of tissue and organ homeo-stasis, thus exacerbating the risk of developing pathologies, including cancer and neurodegener-ative disorders. In the present work, we sought to investigate the influence of aging upon the expression protein profile in the brain cortex of grazing cattle, through LC-MS/MS-based differ-ential proteomics and bioinformatic analysis approach. We found a significant downregulation of proteins involved in synaptic plasticity, myelination, dendritic process, and oxidative stress in the cortex of aged bovine when compared to the adult samples. In conclusion, our data pave the way for a better understanding of molecular mechanisms underlying brain aging in cattle.