期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 117, 期 27, 页码 15581-15590出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2001788117
关键词
aging; proteostasis; ribosome profiling; transcriptome; 5 '-TOP
资金
- Russian Federation [14.W03.31.0012]
- NIH [DK117149, AG047745]
- Russian Science Foundation [18-14-00291]
- Russian Science Foundation [18-14-00291] Funding Source: Russian Science Foundation
Protein synthesis represents a major metabolic activity of the cell. However, how it is affected by aging and how this in turn impacts cell function remains largely unexplored. To address this question, herein we characterized age-related changes in both the transcrip- tome and translatome of mouse tissues over the entire life span. We showed that the transcriptome changes govern those in the translatome and are associated with altered expression of genes involved in inflammation, extracellular matrix, and lipid metabolism. We also identified genes that may serve as candidate biomarkers of aging. At the translational level, we uncovered sustained down- regulation of a set of 5 '-terminal oligopyrimidine (5 '-TOP) transcripts encoding protein synthesis and ribosome biogenesis machinery and regulated by the mTOR pathway. For many of them, ribosome occu- pancy dropped twofold or even more. Moreover, with age, ribosome coverage gradually decreased in the vicinity of start codons and in- creased near stop codons, revealing complex age-related changes in the translation process. Taken together, our results reveal systematic and multidimensional deregulation of protein synthesis, showing how this major cellular process declines with age.
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