Transcriptional drift in aging cells: A global decontroller

• 成果类型: Article
• 署名作者: Matsuzaki, Tyler; Weistuch, Corey; de Graff, Adam; Dill, Ken A.; Balazsi, Gabor
• 署名单位: State University of New York (SUNY) System; Stony Brook University; Memorial Sloan Kettering Cancer Center; State University of New York (SUNY) System; Stony Brook University; State University of New York (SUNY) System; Stony Brook University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13028
• DOI: 10.1073/pnas.2401830121
• 发表日期: 2024-07-23
• 关键词: turnover

摘要

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.