VSMCs from human atherosclerotic plaques undergo senescence and VSMC senescence promotes atherosclerosis and plaque instability,15 while removal of senescent cells can reduce atherosclerosis.32 However, while plaque VSMCs, human VSMCs undergoing replicative senescence or palmitate-induced senescence all showed reduced SIRT6 protein expression, whether downregulation of SIRT6 is a cause or merely a consequence of VSMC senescence was unclear. This evidence concerns the gene SIRT6 and atherosclerosis.