Sirt1, a NAD+-dependent deacetylase, plays a crucial role in preventing vascular aging by modulating endothelial function and counteracting endothelial senescence. As aging progresses, Sirt1 expression declines, leading to endothelial dysfunction and increased cardiovascular disease risk. Sirt1 exerts its protective effects through deacetylation of various proteins, including histones, p53, FoxO, and PGC-1α, which regulate mitochondrial function, DNA repair, and inflammation. Sirt1 also influences vascular homeostasis by enhancing NO bioavailability and suppressing oxidative stress. Post-translational modifications such as phosphorylation, ubiquitination, and sumoylation regulate Sirt1 activity, affecting its deacetylase function and cellular responses. The biosynthesis of NAD+ is critical for Sirt1 activation, with pathways involving tryptophan, nicotinic acid, and nicotinamide riboside. Sirt1 deficiency is linked to endothelial dysfunction, vascular aging, and increased oxidative stress, while Sirt1 activation improves endothelial function and protects against vascular diseases. Sirt1 also plays a key role in preventing endothelial senescence by repressing NF-κB activity and modulating SASP. Sirt1 inhibition can induce premature senescence, while its activation delays senescence and promotes vascular health. Sirt1-based therapies, including senolytics and senomorphics, are being explored to combat vascular aging and endothelial dysfunction. Overall, Sirt1 is a promising therapeutic target for preventing vascular aging and related diseases.Sirt1, a NAD+-dependent deacetylase, plays a crucial role in preventing vascular aging by modulating endothelial function and counteracting endothelial senescence. As aging progresses, Sirt1 expression declines, leading to endothelial dysfunction and increased cardiovascular disease risk. Sirt1 exerts its protective effects through deacetylation of various proteins, including histones, p53, FoxO, and PGC-1α, which regulate mitochondrial function, DNA repair, and inflammation. Sirt1 also influences vascular homeostasis by enhancing NO bioavailability and suppressing oxidative stress. Post-translational modifications such as phosphorylation, ubiquitination, and sumoylation regulate Sirt1 activity, affecting its deacetylase function and cellular responses. The biosynthesis of NAD+ is critical for Sirt1 activation, with pathways involving tryptophan, nicotinic acid, and nicotinamide riboside. Sirt1 deficiency is linked to endothelial dysfunction, vascular aging, and increased oxidative stress, while Sirt1 activation improves endothelial function and protects against vascular diseases. Sirt1 also plays a key role in preventing endothelial senescence by repressing NF-κB activity and modulating SASP. Sirt1 inhibition can induce premature senescence, while its activation delays senescence and promotes vascular health. Sirt1-based therapies, including senolytics and senomorphics, are being explored to combat vascular aging and endothelial dysfunction. Overall, Sirt1 is a promising therapeutic target for preventing vascular aging and related diseases.