In the current study, we utilized littermates of age‐matched wild‐type (WT) and TRPV4 endothelial specific knockout (TRPV4EC−/−) mice at both young (3–4 months; equivalent to humans aged 20–30 years) and aging (20–24 months; equivalent to humans aged 70–90 years) stages to investigate the specific involvement of TRPV4 in age‐related endothelial dysfunction. Here, TRPV4 is linked to endothelial dysfunction.