Stiffer gels prompt aging-related changes in human vessel cells
In a three-dimensional lab model, human blood-vessel-forming cells developed senescence signs after 48 hours in stiffened gels without added inflammatory signals.
Limit: Observation lasted only 48 hours after stiffening
Edited by Boris Djordjevic · AgingResearch.News
In lab experiments, researchers grew human endothelial colony-forming cells—blood-vessel-forming cells from umbilical cord blood—in soft gels for 48 hours. They stiffened some gels and observed the vessel networks for another 48 hours. Stiffening induced signs of senescence, a state in which cells stop dividing. Cells showed higher levels of proteins that halt cell division and changed the mix of immune-modulating substances they released, without added inflammatory signals.
Stiffening also activated Notch, a cell-to-cell communication pathway. Pretreatment with nirogacestat, a drug that inhibits Notch activation, reduced stiffness-induced senescence. Separately, tissue from patients with synthetic breast implants contained a higher proportion of blood-vessel cells bearing both senescence and Notch markers in fibrous capsules than in adjacent soft tissue.
Why it matters
Blood-vessel function declines with age and disease. The model offers a way to investigate how tissue stiffening may contribute to that decline and to explore potential drug targets.
Caveats
The main findings came from cells grown in the lab, not a treatment study in people. The patient-tissue comparisons were observational and could not establish that stiffness caused senescence.
