In conclusion, the multilevel activation of SIRT1 deacetylase by 1,25(OH)2D3 broadens the range of known 1,25(OH)2D3 targets and positions SIRT1 as an important mediator of the protective action of VD against CRC and potentially other neoplasias and non-tumoral diseases. Here, SIRT1 is linked to colorectal carcinoma.