Translational control in aging and neurodegeneration

Abstract Protein metabolism plays central roles in age‐related decline and neurodegeneration. While a large body of research has explored age‐related changes in protein degradation, alterations in the efficiency and fidelity of protein synthesis with aging are less well understood. Age‐associated changes occur in both the protein synthetic machinery (ribosomal proteins and rRNA) and within regulatory factors controlling translation. At the same time, many of the interventions that prolong lifespan do so in part by pre‐emptively decreasing protein synthesis rates to allow better harmonization to age‐related declines in protein catabolism. Here we review the roles of translation regulation in aging, with a specific focus on factors implicated in age‐related neurodegeneration. We discuss how emerging technologies such as ribosome profiling and superior mass spectrometric approaches are illuminating age‐dependent mRNA‐specific changes in translation rates across tissues to reveal a critical interplay between catabolic and anabolic pathways that likely contribute to functional decline. These new findings point to nodes in posttranscriptional gene regulation that both contribute to aging and offer targets for therapy. This article is categorized under: Translation > Translation Regulation Translation > Ribosome Biogenesis Translation > Translation Mechanisms