Low magnesium (Mg) affects endothelial function, thus playing a role in cardiovascular diseases, including atherosclerosis. We here show that Mg deficiency acts through the induction of the pro-inflammatory cytokine interleukin (IL)-lalpha in cultured human endothelial cells. Indeed, the inhibition of IL-lalpha prevents low Mg-induced adhesion of monocytoid cells to the endothelium as well as the upregulation of the cdk inhibitor p21. We also demonstrate that Mg deficiency induces several features typically associated with endothelial senescence. While low Mg can affect gene expression at the transcriptional level, it also modulates the activity of the proteasome. Since endothelial senescence contributes to atherogenesis, our findings indicating that low Mg promotes senescence may shed some light on the molecular mechanisms linking Mg deficiency to cardiovascular diseases.