Endothelial Sirt1 deficiency contributes to nephrosclerosis through the downregulation of matrix metalloproteinase-14 (MMP-14), which is primarily associated with vascular aging and fibrosis [125] while pharmacological activation of Sirt1 significantly decreased the pathologic changes of aging in the kidney via activation of AMPK and the PPARα signaling pathway [123]. This evidence concerns the gene MMP14 and nephrosclerosis.