Proteomic and phosphoproteomic signatures of aging mouse liver

Abstract

The liver is a metabolic powerhouse, crucial for regulating carbohydrates, fats, and protein metabolism. In this study, we conducted a comparative proteomic and phosphoproteomic analysis of aging mouse livers from young adults (3–4 months) and old (19–21 months) mice to identify age-related changes in liver proteins and phosphosites, which were linked to various metabolic pathways. In old mice, proteins associated with the “complement and coagulation cascade,” “age-rage signaling in diabetic complications,” and “biosynthesis of unsaturated fatty acids” were increased, while those linked to “oxidative phosphorylation,” “steroid hormone biosynthesis,” and “tryptophan metabolism” were decreased. Interestingly, aging was marked by a significant decrease in liver protein phosphorylation, with nearly 90% of significant phosphosites being downregulated. Pathway analysis of the downregulated phosphosites highlighted connections to “non-small cell lung cancer,” “lysine degradation,” “cell differentiation,” and “glycerophospholipid metabolism.” Decreased phosphorylation of several kinases that are linked to cell proliferation, particularly those in the MAPK signaling pathway, including Erk1, EGFR, RAF1, and BRAF was also observed highlighting their important role in the liver. This study identified an important relationship between proteins, phosphosites, and their connections to known as well as new pathways, expanding upon our current knowledge and providing a basis for future studies focused on age-related metabolic traits.