Conclusions

In summary, SIRT1 functions as a key NAD + -dependent deacetylase that regulates stress-induced vascular senescence through multiple interconnected signaling pathways, primarily by counteracting oxidative stress and inflammation. Based on our network analysis and evidence-weighted synthesis, SIRT1/Nrf2, SIRT1/FoxOs, SIRT1/NF-κB, and SIRT1/eNOS/NO appear to be the most robust and relevant pathways underlying stress-induced vascular senescence. Future studies should focus on validating these main network-central nodes in standardized stress-induced endothelial senescence models, comparing SIRT1 signaling across diverse vascular beds and cell types, and linking SIRT1 modulation to clinically recognized indicators of stress-induced vascular senescence such as endothelial function and arterial stiffness. Further investigation is also required to clarify the context-dependent and dose-dependent effects of SIRT1 activation and to validate key pathways in human ex vivo vascular tissue, thus enhancing translational relevance. Overall, this review identifies SIRT1 as a promising target for the prevention and treatment of stress-induced vascular senescence and its associated CVDs.