ABSTRACT: Ageing is a key risk factor for disease and mortality in humans and other animals, with most insights derived from genomic, epigenomic, and transcriptomic studies. However, large-scale datasets on age-related changes at the protein level remain scarce. To fill this gap, we performed a comprehensive quantitative proteomic analysis across eight major organs—brain, heart, lungs, liver, kidneys, spleen, skeletal muscle, and testis—in male C57BL/6J mice, sampled at key life stages: young adult (3–5 months), adult (8 months), mid-life (14 months), and late life (20–26 months). Our results revealed diverse rates of protein expression changes, ranging from rapid (kidneys, spleen) to moderate (liver, lungs) to minimal (skeletal muscle, testis) and subtle (heart, brain). Aging onset appeared earlier in the spleen and kidneys compared to the liver and lungs. By isolating the non-blood proteome, we identified enriched organ-specific processes like oxidative phosphorylation (kidneys) and lipid metabolism (liver), along with shared processes across organs. These findings provide valuable insights into organ-specific and shared protein dynamics underlying age-related diseases.
