ИСТИНА

Proper balance between protein synthesis and degradation, or proteostasis, is crucial for an organism to survive and maintain physiological function. A gradual loss of protein quality control during aging leads to an accumulation of damaged proteins inside the cell, potentially with devastating consequences. Some of these alterations have been studied broadly, such as decline in the activity of chaperone and proteolytic systems. However, little is known about changes in protein synthesis machinery and translational control mechanisms in the context of aging. Here, we took advantage of ribosome profiling and transcriptome analysis to track mRNA expression during aging in mouse liver and kidney. Ribosome profiling is a powerful method revealing changes in ribosome abundance at start and stop codons, selection of translation initiation sites, stop codon readthrough and ribosome stalling events at a single nucleotide resolution. In combination with RNA-Seq, ribosome profiling helps exploring gene expression and distinguishing the role of transcription and translation. We observed an age-related decrease in the expression levels of many translation-associated genes, including those involved in ribosome biogenesis and mRNA recruitment. Strikingly, ribosome occupancy tended to decrease at start codons and increase at stop codons systematically, consistent with systematic proteostasis deregulation during aging. The work was supported by the Russian Federation grant №14.W03.31.0012.