Distinct and diverse chromatin proteomes of ageing mouse organs reveal protein signatures that correlate with physiological functions

Abstract

Temporal molecular changes in ageing mammalian organs are of relevance to disease aetiology because many age-related diseases are linked to changes in the transcriptional and epigenetic machinery that regulate gene expression. We performed quantitative proteome analysis of chromatin-enriched protein extracts to investigate the dynamics of the chromatin proteomes of the mouse brain, heart, lung, kidney, liver, and spleen at 3, 5, 10, and 15 months of age. Each organ exhibited a distinct chromatin proteome and sets of unique proteins. The brain and spleen chromatin proteomes were the most extensive, diverse, and heterogenous among the six organs. The spleen chromatin proteome appeared static during the lifespan, presenting a young phenotype that reflects the permanent alertness state and important role of this organ in physiological defence and immunity. We identified a total of 5928 proteins, including 2472 nuclear or chromatin-associated proteins across the six mouse organs. Up to 3125 proteins were quantified in each organ, demonstrating distinct and organ-specific temporal protein expression timelines and regulation at the post-translational level. Bioinformatics meta-analysis of these chromatin proteomes revealed distinct physiological and ageing-related features for each organ. Our results demonstrate the efficiency of organelle-specific proteomics for in vivo studies of a model organism and consolidate the hypothesis that chromatin-associated proteins are involved in distinct and specific physiological functions in ageing organs.