A transcriptomic analysis reveals shared and inducer-specific expression patterns of cellular senescence

Area of Science:

• Cellular and Molecular Biology
• Aging Research
• Genomics

Background:

• Cellular senescence is a state of irreversible cell cycle arrest.
• Senescence can be triggered by various stressors like DNA damage and oxidative stress.
• Identifying universal biomarkers for senescence remains a challenge.

Purpose of the Study:

• To investigate whether different senescence-inducing stimuli converge on shared molecular processes or individual genes.
• To analyze transcriptomic changes in human fibroblasts under various senescence-inducing conditions.
• To understand the hierarchical organization of the senescent transcriptome.

Main Methods:

• Transcriptomic profiling of human lung fibroblasts (IMR-90).
• Induction of senescence via replicative exhaustion, bleomycin, hydrogen peroxide (H2O2), and ionizing radiation.
• Analysis of global transcriptomic variation, individual gene overlap, and pathway enrichment.

Main Results:

• Global transcriptomic variation aligned along a shared senescence progression axis across all inducers.
• Limited overlap was observed at the individual gene level; responses were largely inducer-specific.
• Pathway analysis revealed consistent enrichment of stress-related and pro-inflammatory pathways, with downregulation of proliferation pathways.

Conclusions:

• Cellular senescence exhibits a hierarchical transcriptomic organization.
• Diverse senescence inducers converge on shared pathway-level features, not just individual genes.
• These findings support the development of more robust transcriptome-based senescence markers for aging and disease.