This editorial refers to ‘SIRT6 protects human endothelial cells from DNA damage, telomere dysfunction, and senescence’ by A. Cardus et al ., pp. 571–579, this issue. Vascular endothelial homeostasis is critical to health and is a significant factor in many human diseases. It is established that endothelial cell (EC) dysfunction is one of the earliest pathological steps in the initiation and progression of vascular diseases such as atherosclerosis and vascular remodelling.1–3 How to maintain a healthy or repair an injured endothelial lining of the vasculature has been a scientific mystery and a clinical challenge. In general, two theories have been proposed. On the one hand, it is thought that during their turnover, injured ECs, due to senescence, ageing, or other pathological challenges, might be replaced by circulating EC progenitors that can repopulate the damaged endothelium. Although this hypothesis has undergone rigorous investigation and achieved some promising initial results,4,5 recent studies demonstrated that circulating EC progenitors do not contribute to the regeneration of a damaged endothelium, thus significantly reducing this theory's promise in the field.6 On the other hand, healing damaged EC areas with adjacent mature ECs through their migration and proliferation is still a viable theory.7 In order to achieve this ‘ in situ healing’, however, the pre-existing mature ECs in the vasculature may have to maintain a ‘threshold’ of healthy …