Proteome profiling of aging in mouse models: Differential expression of proteins involved in metabolism, transport, and stress response in kidney

Abstract

Aging is a time-dependent complex biological phenomenon observed in various organs and organelles of all living organisms. To understand the molecular mechanism of age-associated functional loss in aging kidneys, we have analyzed the expression of proteins in the kidneys of young (19-22 wk) and old (24 months) C57/BL6 male mice using 2-DE followed by LC-MS/MS. We found that expression levels of 49 proteins were upregulated (p < or = 0.05), while that of only ten proteins were downregulated (p < or = 0.05) due to aging. The proteins identified belong to three broad functional categories: (i) metabolism (e.g., aldehyde dehydrogenase family, ATP synthase beta-subunit, malate dehydrogenase, NADH dehydrogenase (ubiquinone), hydroxy acid oxidase 2), (ii) transport (e.g., transferrin), and (iii) chaperone/stress response (e.g., Ig-binding protein, low density lipoprotein receptor-related protein associated protein 1, selenium-binding proteins (SBPs)). Some proteins with unknown functions were also identified as being differentially expressed. ATP synthase beta subunit, transferrin, fumarate hydratase, SBPs, and albumin are present in multiple forms, possibly arising due to proteolysis or PTMs. The above functional categories suggest specific mechanisms and pathways for age-related kidney degeneration.