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Telomere length profiles in primary human peritoneal mesothelial cells are consistent with senescence
Melisa Lopez-Anton1, András Rudolf2, Duncan M Baird3
1Wales Kidney Research Unit, Division of Infection and Immunity, School of Medicine, College of Biomedical and Life Sciences, Cardiff University, Heath Park, Cardiff CF14 4XN, UK.
Abstract:
Mesothelial cell (MC) senescence contributes to malignancy and tissue fibrosis. The role of telomere erosion in MC senescence remains controversial, with evidence for both telomere-dependent and telomere-independent mechanisms reported. Single telomere length analysis revealed considerable telomere length heterogeneity in freshly isolated human peritoneal MCs, reflecting a heterogeneous proliferative history and providing high-resolution evidence for telomere-dependent senescence. By contrast the attenuated replicative lifespan, lack of telomere erosion and induction of p16 expression in in vitro-aged cells was consistent with stress-induced senescence. Given the potential pathophysiological impact of senescence in mesothelial tissues, high-resolution MC telomere length analysis may provide clinically useful information.
Insights
Mesothelial cell senescence, linked to cancer and fibrosis, may involve telomere changes. High-resolution analysis reveals telomere-dependent senescence in human cells, suggesting clinical relevance.
Area of Science:
- Cellular senescence
- Telomere biology
- Mesothelial cell function
Background:
- Mesothelial cell (MC) senescence is implicated in malignancy and tissue fibrosis.
- The precise mechanisms driving MC senescence, particularly the role of telomere erosion, remain debated.
- Existing research presents conflicting evidence for both telomere-dependent and independent senescence pathways.
Purpose of the Study:
- To investigate the role of telomere length dynamics in mesothelial cell senescence.
- To differentiate between telomere-dependent and stress-induced senescence mechanisms in MCs.
- To assess the potential clinical utility of high-resolution telomere length analysis in mesothelial tissues.
Main Methods:
- Single telomere length analysis was performed on freshly isolated human peritoneal mesothelial cells.
- In vitro aging models were used to study mesothelial cells under controlled conditions.
- Analysis included assessment of telomere length heterogeneity, replicative lifespan, and p16 expression.
Main Results:
- Freshly isolated human peritoneal MCs exhibited significant telomere length heterogeneity, supporting a telomere-dependent senescence mechanism.
- In vitro-aged MCs displayed an attenuated replicative lifespan without significant telomere erosion.
- In vitro-aged MCs showed increased p16 expression, characteristic of stress-induced senescence.
Conclusions:
- Mesothelial cell senescence can occur through both telomere-dependent and stress-induced pathways.
- High-resolution telomere length analysis provides evidence for telomere-dependent senescence in primary human MCs.
- Understanding MC senescence mechanisms, including telomere dynamics, may offer clinically relevant insights for mesothelial tissue pathologies.