ИСТИНА

Aging animals are characterized by dysregulation in proteostasis. However, little is known about changes in protein synthesis and translational control with age. We performed ribosome profiling and transcriptome analysis to track gene expression in liver and kidney of mice aged from 1 to 32 months. Both qualitative and quantitative changes in translatome were observed, including a decrease in the expression levels of many genes involved in translation itself. The translational down-regulation of mRNAs encoding ribosomal proteins and other components of protein synthesis machinery with age was likely caused by a decrease in mTOR kinase activity. Analysis of metagene profiles revealed a general ribosome occupancy decreased gradually at start codons and increased at stop codons of mRNA transcripts. Our results showed a systematic decline in protein synthesis and deregulation of translation machinery components consistent with proteostasis deregulation during aging. The work was supported by the RF government grant №14.W03.31.0012 and RSF grant 18-14-00291.