Conclusions and future perspectives

Directions for future research

Current research on SIRT1 and stress-induced vascular senescence mainly depends on in vitro cell experiments, rodent animal models, and bioinformatic analysis of protein interaction networks, while several research gaps still need to be addressed in follow-up work.

First, most existing studies focus on the regulatory role of SIRT in vascular endothelial cells, whereas the differential regulatory effects of SIRT1 in vascular smooth muscle cells and vascular adventitial cells under persistent stress have not been systematically compared, and the intercellular crosstalk mediated by SIRT1 among multiple vascular cell types requires further clarification.

Second, this review summarizes multiple signaling pathways through which SIRT1 alleviates stress-induced vascular senescence, but the dynamic crosstalk among these pathways under the simultaneous stimulation of oxidative stress, inflammation, and autophagy dysfunction remains unclear. Moreover, the main molecules that coordinate these signaling networks still need to be further identified.

Third, most of the existing relevant evidence is derived from preclinical models, and there is a lack of systematic research on human vascular specimens and long-term population studies to verify whether the activity and expression level of SIRT1 can reflect the severity of stress-induced vascular senescence in clinical populations. Fourth, this study identifies multiple upstream microRNAs that regulate SIRT1, but few studies have examined tissue-targeted intervention strategies to modulate the expression of these non-coding RNAs and further activate SIRT1 to alleviate stress-induced vascular senescence. Fifth, combined interventions targeting multiple drivers of aging, such as RAAS activation, mitochondrial dysfunction, and telomere attrition through the SIRT1 pathway, still lack sufficient preclinical verification.

Thus, future research should focus on exploring compound intervention strategies centered on SIRT1 to simultaneously block multiple pathological processes involved in stress-induced vascular senescence.