Both iron homeostasis and erythropoiesis are known to be affected by aging. Iron needs in mammals are met primarily by iron recycling from senescent red blood cells (RBCs), a task chiefly accomplished by red pulp macrophages (RPMs) in the spleen. Given that RPMs continuously process iron, their cellular functions might be susceptible to age-dependent decline, a possibility that has been unexplored to date. In our project, we identified a formation of undegradable iron- and heme-rich extracellular aggregates in the spleens of 10-11-month-old female mice. We further found that feeding mice an iron-reduced diet alleviates the deposition of iron in the spleen in the form of these insoluble aggregates. Here, we performed: i) label-free proteomic analysis of the aggregates that were magnetically isolated from the aged mice (maintained on a standard diet), using samples from young mice as a background control; and ii) TMT-based quantification of the differences in the aggregate protein composition between mice that aged on a standard versus iron-reduced diet. In each experiment, three biological replicates per group were analyzed.