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Updated: Jun 27, 2026
Techniques to Induce and Quantify Cellular Senescence
Published on: May 1, 2017
Cellular Senescence Genes as Cutting-Edge Signatures for Abdominal Aortic Aneurysm Diagnosis: Potential for
Shuli Zhang1,2, Jiayin Li1,2, Ruichen Wang3
1College of Medical and Bioinformatics Engineering, Northeastern University, Shenyang, China.
Abstract:
Abdominal aortic aneurysm (AAA) is the most prevalent dilated arterial aneurysm that poses a significant threat to older adults, but the molecular mechanisms linking senescence to AAA progression remain poorly understood. This study aims to identify cellular senescence-related genes (SRGs) implicated in AAA development and assess their potential as therapeutic targets. Four hundred and twenty-nine differentially expressed genes (DEGs) were identified from the GSE57691 training set, and 867 SRGs were obtained. Through the intersection of DEGs with SRGs, 19 differentially expressed senescence-related genes (DESRGs) were uncovered. Functional enrichment analysis was performed to explore their biological roles in AAA. To identify hub genes, we applied machine learning algorithms, including LASSO, SVM-RFE and random forest. These hub genes were then validated in two independent datasets. In the initial validation cohort, significant differences in the expression levels of BTG2, ETS1, ID1 and ITPR3 were observed between the AAA and control groups. Receiver operating characteristic (ROC) analysis demonstrated a robust diagnostic performance. Further validation across different AAA stages (small, large and ruptured AAA) identified ETS1 and ITPR3 as potential diagnostic genes. Subsequently, the diagnostic relevance of ETS1 and ITPR3 was further validated in human serum samples and mouse models of AAA. In addition, single-cell RNA sequencing suggests that senescent endothelial cells play a pivotal role in AAA progression, we further confirmed the correlation between ETS1 and ITPR3 and senescent endothelial cells by WB, IF and RT-qPCR. In conclusion, our study reveals the pivotal role of cellular senescence in AAA progression and identifies ETS1 and ITPR3 as promising diagnostic biomarkers.
Insights
This study reveals that cellular senescence drives abdominal aortic aneurysm (AAA) progression. Researchers identified ETS1 and ITPR3 as key diagnostic biomarkers for AAA, offering new insights into this prevalent condition.
Area of Science:
- Vascular Biology
- Gerontology
- Genetics
Background:
- Abdominal aortic aneurysm (AAA) is a prevalent vascular disease in older adults.
- The molecular links between cellular senescence and AAA progression are not well understood.
- Identifying senescence-related genes is crucial for understanding AAA pathogenesis.
Purpose of the Study:
- To identify cellular senescence-related genes (SRGs) involved in AAA development.
- To explore the potential of these genes as therapeutic targets and diagnostic biomarkers.
- To elucidate the role of senescent cells in AAA progression.
Main Methods:
- Differential gene expression analysis and intersection with SRGs.
- Machine learning algorithms (LASSO, SVM-RFE, random forest) for hub gene identification.
- Validation in independent datasets, human serum samples, and mouse models.
- Single-cell RNA sequencing to investigate cellular roles.
Main Results:
- 19 differentially expressed senescence-related genes (DESRGs) were identified.
- ETS1 and ITPR3 emerged as significant diagnostic biomarkers for AAA.
- Senescent endothelial cells were found to play a pivotal role in AAA progression.
- ETS1 and ITPR3 expression correlated with senescent endothelial cells.
Conclusions:
- Cellular senescence is a key driver of abdominal aortic aneurysm progression.
- ETS1 and ITPR3 are promising diagnostic biomarkers for AAA.
- Further research into senescence-targeting therapies for AAA is warranted.
