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Updated: Mar 16, 2026
Determining Genome-wide Transcript Decay Rates in Proliferating and Quiescent Human Fibroblasts
Published on: January 2, 2018
Identification of cellular senescence-specific genes by comparative transcriptomics
Taiki Nagano1,2, Masayuki Nakano1,2, Akio Nakashima1,3
1Biosignal Research Center, Kobe University, 1-1 Rokkodai-cho, Nada-ku, Kobe 657-8501, Japan.
Abstract:
Cellular senescence is defined as permanent cell cycle arrest induced by various stresses. Although the p53 transcriptional activity is essential for senescence induction, the downstream genes that are crucial for senescence remain unsolved. Here, by using a developed experimental system in which cellular senescence or apoptosis is induced preferentially by altering concentration of etoposide, a DNA-damaging drug, we compared gene expression profiles of senescent and apoptotic cells by microarray analysis. Subtraction of the expression profile of apoptotic cells identified 20 genes upregulated specifically in senescent cells. Furthermore, 6 out of 20 genes showed p53-dependent upregulation by comparing gene expression between p53-proficient and -deficient cells. These 6 genes were also upregulated during replicative senescence of normal human diploid fibroblasts, suggesting that upregulation of these genes is a general phenomenon in senescence. Among these genes, 2 genes (PRODH and DAO) were found to be directly regulated by p53, and ectopic expression of 4 genes (PRODH, DAO, EPN3, and GPR172B) affected senescence phenotypes induced by etoposide treatment. Collectively, our results identified several proteins as novel downstream effectors of p53-mediated senescence and provided new clues for further research on the complex signalling networks underlying the induction and maintenance of senescence.
Insights
Researchers identified key genes involved in cellular senescence, a permanent cell arrest state. Six genes, including PRODH and DAO, are upregulated by p53 and influence senescence, offering new insights into this crucial biological process.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- Cellular senescence is a state of permanent cell cycle arrest triggered by various cellular stresses.
- The tumor suppressor protein p53 plays a critical role in initiating senescence, but its downstream effectors remain largely unknown.
Purpose of the Study:
- To identify novel downstream genes regulated by p53 that are specifically involved in cellular senescence.
- To investigate the role of these identified genes in the induction and maintenance of senescence.
Main Methods:
- Utilized a developed experimental system to selectively induce cellular senescence or apoptosis using etoposide.
- Performed microarray analysis to compare gene expression profiles between senescent and apoptotic cells.
- Validated p53-dependent gene regulation by comparing gene expression in p53-proficient and -deficient cells.
Main Results:
- Identified 20 genes specifically upregulated in senescent cells compared to apoptotic cells.
- Discovered 6 of these genes exhibited p53-dependent upregulation and were also elevated in replicative senescence.
- Found PRODH and DAO directly regulated by p53, with PRODH, DAO, EPN3, and GPR172B affecting senescence phenotypes.
Conclusions:
- Identified novel downstream effectors of p53-mediated cellular senescence.
- Provided new insights into the complex signaling networks governing senescence induction and maintenance.
- Highlighted the potential roles of PRODH, DAO, EPN3, and GPR172B in senescence pathways.
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02:15Replicative Cell Senescence
02:15Replicative Cell Senescence