Transcriptional drift in aging cells: A global decontroller Journal Article
| Authors: | Matsuzaki, T.; Weistuch, C.; de Graff, A.; Dill, K. A.; Balázsi, G. |
| Article Title: | Transcriptional drift in aging cells: A global decontroller |
| Abstract: | As cells age, they undergo a remarkable global change: In transcriptional drift, hundreds of genes become overexpressed while hundreds of others become underexpressed. Using archetype modeling and Gene Ontology analysis on data from aging Caenorhabditis elegans worms, we find that the up-regulated genes code for sensory proteins upstream of stress responses and down-regulated genes are growth- and metabolism-related. We observe similar trends within human fibroblasts, suggesting that this process is conserved in higher organisms. We propose a simple mechanistic model for how such global coordination of multiprotein expression levels may be achieved by the binding of a single factor that concentrates with age in C. elegans. A key implication is that a cell’s own responses are part of its aging process, so unlike wear-and-tear processes, intervention might be able to modulate these effects. © 2024 the Author(s). Published by PNAS. |
| Keywords: | controlled study; genetics; nonhuman; animal; metabolism; animals; gene expression; genetic transcription; transcription, genetic; gene expression regulation; fibroblast; fibroblasts; aging; caenorhabditis elegans; cell aging; caenorhabditis elegans protein; caenorhabditis elegans proteins; global change; gene ontology; cellular senescence; physiological stress; humans; human; article; archetype analysis; transcriptional drift |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 121 |
| Issue: | 30 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 2024-07-23 |
| Start Page: | e2401830121 |
| Language: | English |
| DOI: | 10.1073/pnas.2401830121 |
| PUBMED: | 39012826 |
| PROVIDER: | scopus |
| PMCID: | PMC11287169 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
