Cellular Senescence as a Systems-Level Driver of Cardiovascular Ageing - PubMed
3 hours ago
- #Cardiovascular Ageing
- #Cellular Senescence
- #Systems Biology
- Cellular senescence is a key driver of cardiovascular ageing, characterized by molecular heterogeneity and varying effects across cell types.
- Senescence arises from interactions among endothelial, vascular smooth muscle, immune, and stromal cells, influenced by metabolic stress, immune dysregulation, and epigenetic changes.
- Major hallmarks include DNA damage responses, telomere attrition, mitochondrial dysfunction, SASP, and epigenetic remodeling, with regulators integrating oxidative stress, inflammation, and metabolism.
- A systems-level inflammation-coagulation-senescence axis links chronic inflammation, immunothrombosis, arterial stiffening, and heart failure.
- Metabolic checkpoints in vascular smooth muscle cells modulate senescence initiation and progression, highlighting their role in ageing.
- Current anti-senescence strategies are limited by heterogeneity and context; precision interventions are needed based on temporal, cell-specific, and metabolic factors.
- Integrating single-cell and spatial multi-omics with biological age metrics and machine learning is crucial for identifying therapeutic windows and targeted strategies.