The article reviews the multifaceted role of NAD+-dependent deacetylase sirtuin-1 (Sirt1) in vascular aging, particularly focusing on its impact on endothelial function and senescence. Sirt1, a longevity regulator, plays a crucial role in preventing vascular aging by maintaining endothelial health and function. As aging progresses, Sirt1 expression declines, leading to endothelial dysfunction and increased risk of cardiovascular diseases. The review highlights the importance of Sirt1 in counteracting endothelial senescence, a key process in vascular aging, and discusses recent therapeutic strategies aimed at boosting Sirt1 activity to prevent or treat vascular aging. Key mechanisms include Sirt1's ability to modulate mitochondrial biogenesis, reduce oxidative stress, and improve nitric oxide (NO) bioavailability. The article also explores the intricate cross-talk between Sirt1 and other molecules, such as p53, FoxO, and NF-κB, and the role of post-translational modifications in regulating Sirt1 activity. Additionally, it covers the biosynthesis of NAD+ and its impact on Sirt1 regulation, as well as the therapeutic potential of targeting Sirt1 to improve endothelial function and vascular health.The article reviews the multifaceted role of NAD+-dependent deacetylase sirtuin-1 (Sirt1) in vascular aging, particularly focusing on its impact on endothelial function and senescence. Sirt1, a longevity regulator, plays a crucial role in preventing vascular aging by maintaining endothelial health and function. As aging progresses, Sirt1 expression declines, leading to endothelial dysfunction and increased risk of cardiovascular diseases. The review highlights the importance of Sirt1 in counteracting endothelial senescence, a key process in vascular aging, and discusses recent therapeutic strategies aimed at boosting Sirt1 activity to prevent or treat vascular aging. Key mechanisms include Sirt1's ability to modulate mitochondrial biogenesis, reduce oxidative stress, and improve nitric oxide (NO) bioavailability. The article also explores the intricate cross-talk between Sirt1 and other molecules, such as p53, FoxO, and NF-κB, and the role of post-translational modifications in regulating Sirt1 activity. Additionally, it covers the biosynthesis of NAD+ and its impact on Sirt1 regulation, as well as the therapeutic potential of targeting Sirt1 to improve endothelial function and vascular health.