Global quantitative proteomics of mouse hippocampus during ageing

Understanding the molecular changes associated with the aged brain forms the basis for developing potential strategies for slowing cognitive decline associated with normal aging. Focusing on the hippocampus, a critical brain region involved in learning and memory, we employed tandem mass tag methodology to investigate proteomic changes that occur in advanced aged (20-month) relative to young (3-month) C57BL/6 mice. Our analysis revealed a total of 324 proteins that were significantly altered in the old mice relative to the young mice. Upregulated proteins (236 total proteins) were enriched within several age-related processes, such as the adaptive immune response and molecular metabolic pathways, whereas downregulated proteins (88 total proteins) were mainly involved in axonogenesis and growth cone-related processes. By categorising proteins according to their cell-type enrichment in the brain, a general upregulation was observed in the level of proteins preferentially expressed in microglia, astrocytes, and oligodendrocytes. In contrast, proteins with neuron-specific expression display an overall age-related downregulation. By integrating our proteomic and transcriptomic data, we discovered a mild but significant positive correlation between mRNA and protein expression changes in the aged hippocampus. Therefore, this proteomic data is a valuable resource for age-related molecular studies.