senescence
Definition
Senescence is a state of permanent cell cycle arrest in which cells remain metabolically active but lose their ability to divide. This process can be triggered by various stressors including telomere shortening (replicative senescence), DNA damage, oxidative stress, or oncogene activation. Senescent cells develop a distinct phenotype characterized by the senescence-associated secretory phenotype (SASP), which involves secretion of pro-inflammatory cytokines, growth factors, and proteases. While senescence serves as a tumor suppression mechanism and plays roles in wound healing and development, accumulation of senescent cells contributes to aging, chronic inflammation, and age-related diseases. Understanding senescence mechanisms is crucial for developing senolytic therapies that selectively eliminate these cells to treat age-related pathologies.
Visualize senescence in Nodes Bio
Researchers can map senescence pathways by visualizing interactions between senescence triggers (DNA damage sensors, telomere dysfunction), cell cycle regulators (p53, p16INK4a, p21), and SASP factors. Network analysis reveals how senescence signals propagate through cellular pathways and identifies key regulatory nodes. Users can overlay gene expression data to compare senescent versus proliferating cells and discover potential senolytic drug targets.
Visualization Ideas:
- SASP factor secretion networks showing cytokine and chemokine interactions
- Cell cycle checkpoint pathway maps highlighting p53/p16INK4a regulatory cascades
- Senolytic drug-target networks connecting therapeutic compounds to anti-apoptotic proteins
Example Use Case
A pharmaceutical team investigating senolytic compounds for treating pulmonary fibrosis uses network analysis to map how candidate drugs affect senescence pathways in lung fibroblasts. They visualize connections between p53/p21 signaling, SASP cytokines (IL-6, IL-8), and extracellular matrix remodeling proteins. By overlaying RNA-seq data from treated versus untreated senescent cells, they identify that their lead compound disrupts BCL-2 family protein networks, revealing its mechanism as a senolytic agent that selectively induces apoptosis in senescent cells.