Stiffness of the surrounding material causes aging in blood vessel cells

Increased mechanical stress from extracellular matrix (ECM) stiffening induces an endothelial cell senescence phenotype characterized by elevated p16/p21 levels.

• Matrix stiffening leads to an endothelial cell senescence state even in the absence of inflammatory signals.
• This senescence phenotype is associated with an increase in a specific immune-modulating factor known as the senescence-associated secretory phenotype (SASP).
• A signaling pathway involving Notch, JNK, and FOS is engaged during stiffness-induced senescence.
• Inhibition of Notch signaling reduces the occurrence of senescence due to mechanical stress.
• Analysis of fibrotic tissue from patients with synthetic breast implants shows increased levels of senescent endothelial cells marked by p16 and Notch1.
• Single-cell RNA sequencing corroborates the enrichment of genes related to the Notch/JNK pathway and SASP in these senescent cell populations.

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