Angiotensin-(1-7) counteracts Angiotensin II-induced senescence in telomerase-immortalized human mesenchymal stem cells

Objective: Angiotensin-(1-7) (Ang-(1-7)) exerts protective and anti-inflammatory effects, whereas angiotensin II (AngII) promotes pro-inflammatory and pro-oxidative processes. Cellular senescence is an irreversible cell cycle arrest that can be induced in vitro by a variety of cellular stresses, including AngII “stress-induced premature senescence (SIPS)”. This study aimed to evaluate the potential inhibitory role of Ang-(1-7) in AngII-induced senescence in telomerase-immortalized human mesenchymal stem cells (hMSCs-telo1). Materials and Methods: Senescence was induced using AngII at various time points and concentrations. Based on preliminary optimization experiments, cells were treated with AngII (10-⁶ M) for 48 hours, followed by Ang-(1-7) treatment (10-⁶ M) for an additional 24 hours. Following treatments, cellular senescence and functional responses were assessed using proliferation analysis based on population doubling levels (PDLs), senescence associated-beta-galactosidase (SA-β-gal) staining, and colony forming unit (CFU) assays. Results: No marked morphological differences were observed among the experimental groups. However, Ang-(1-7) treatment significantly reduced the proportion of SA-β-gal-positive cells in AngII-induced senescent hMSCs-telo1, showing a 1.65-fold decrease. In parallel, Ang-(1-7) partially restored cell proliferation capacity. Conclusion: Ang-(1-7) attenuates AngII-induced cellular senescence and improves proliferative potential in hMSCs-telo1 cells, suggesting a modulatory role in stress-induced senescence and potential relevance for stem cell-based therapies.