Reducing AP2A1 levels in aged human cells rejuvenates them by shrinking cell size, softening structural fibres, restoring mobility, and lowering senescence signals.
March 2025 – Cellular Signalling
Key takeaways
- AP2A1 drives cellular ageing: AP2A1 expression significantly increases in aged human fibroblasts, integrating along thickened actin stress fibres. This change reinforces enlarged cell architecture, suppresses mobility, and coincides with elevated senescence markers such as p53 and SA-β-gal. These structural and molecular alterations reflect core hallmarks of ageing, making AP2A1 a key player in the cellular ageing process
- Silencing AP2A1 triggers rejuvenation: Targeted knockdown of AP2A1 in senescent cells led to smaller cell size, thinner stress fibres, increased proliferation, and reduced expression of classic ageing markers. These rejuvenative effects suggest that lowering AP2A1 can partially reverse key aspects of cellular senescence, offering potential for therapeutic strategies aimed at improving cell function and restoring youthful characteristics
- Integrin recycling supports cell anchorage: Senescent cells reinforce their anchorage by transporting integrin β1 along actin fibres to focal adhesions, mature cell–matrix contact points, via AP2A1-mediated vesicle trafficking. This active recycling process supports the enlarged, flattened morphology typical of aged cells, highlighting how structural stability is maintained as cells lose mobility and dynamic response during ageing
- AP2A1 is a broad senescence marker: Across multiple ageing models, including natural replicative ageing, UV exposure, and drug-induced damage, AP2A1 consistently rises in both fibroblasts and epithelial cells. Its upregulation correlates with senescent morphology and stress fibre changes, positioning AP2A1 as a reliable biomarker for cellular ageing and a promising target for interventions that aim to delay age-related decline
Read the article at: Chantachotikul, Pirawan, et al. “AP2A1 modulates cell states between senescence and rejuvenation.” Cellular Signalling, vol. 127, 2025, https://doi.org/10.1016/j.cellsig.2025.111616.
