Aging, which is associated with protein homeostasis defects, is one of the most prominent risk factors for neurodegenerative disorders and the regulation of protein homeostasis is essential for brain health. While several studies have addressed changes in protein abundance due to aging, little is known about differences in protein stability in the mammalian brain proteome. In particular, pre-symptomatic alterations of protein stability might be instrumental for understanding the pathological alterations that occur during neurodegeneration. To explore these alterations, we measured proteome turnover with a pulse-SILAC approach in aged mice from total cortex and cerebellum homogenates and from the respective synaptic-enriched fraction. We compared the stability of young and aged proteomes. Our analyses revealed several differences and the large dataset that we created will serve as a resource for the community to develop approaches that explore these alterations with diagnostic and therapeutic purposes.