A 28-day high-salt diet (8% NaCl) induced endothelial dysfunction in mice through cellular senescence rather than direct vascular damage. The mechanism involves immune system activation that elevates interleukin-16 (IL-16), which then triggers senescence markers p21 and p16 in blood vessel walls. Treatment with navitoclax, a senolytic drug that clears senescent cells, restored normal vascular function and reduced inflammation markers. This finding reframes our understanding of salt-related cardiovascular damage. Rather than salt directly harming blood vessels, it appears to accelerate vascular aging through immune-mediated senescence. The discovery positions senolytics as potential therapies for salt-sensitive hypertension and cardiovascular disease. However, this mouse study used an extreme salt concentration far exceeding typical human intake, and the 28-day timeframe represents acute rather than chronic exposure. The IL-16 pathway offers a specific therapeutic target, but translating senolytic treatments to humans remains challenging given their broad cellular effects. This research adds to growing evidence that cellular senescence underlies multiple age-related diseases, suggesting that targeting aging processes themselves might address cardiovascular risk more effectively than traditional approaches.