ИСТИНА

A balance between protein synthesis and degradation is crucial for organism survival and maintenance of physiological function. During aging, a gradual loss of general quality control leads to an accumulation of damaged proteins inside the cells. However, while protein synthesis represents a major metabolic activity, how it is affected by aging and how this impacts the cell remains largely unexplored. Here, we characterized age-related changes in the transcriptomes and translatomes of mouse liver and kidney over the entire lifespan. This analysis identified key age-related transcriptional markers and uncovered sustained down-regulation of protein synthesis and ribosome biogenesis machinery specifically at the translational level. Moreover, with age, ribosome coverage gradually decreased in the vicinity of start codons and increased near stop codons, consistent with a reduction of translation initiation and termination/ribosome recycling rates. Taken together, our results show a systematic dysfunction and decline in protein synthesis indicating deregulation of a major metabolic pathway with age.