Cellular Senescence and Vascular Disease: Novel Routes to Better Understanding and Therapy

Cellular senescence is a definable fate of cells within aging, diseased, and remodelling tissues. The traditional hallmark of cellular senescence is permanent cell cycle arrest but the senescent state is also accompanied by secretion of proteins that can reinforce the senescent phenotype and adversely affect the local tissue environment. Assessment for cellular markers of senescence has revealed the existence of senescent smooth muscle cells and senescent endothelial cells in vessels of patients with atherosclerosis and hypertension. This raises the possibility that cellular senescence might contribute to the initiation or progression of vascular disease. Potential disease-promoting pathways include blunted replicative reserve, reduced nitric oxide production, and increased cellular stiffness. Moreover, the secretory phenotype of senescent vascular cells might promote vascular degeneration through chronic inflammation and extracellular matrix degradation. Slowing of vascular cell aging and selective clearing of cells that have become senescent are emerging as exciting possibilities for controlling vascular disease.