Negative regulation of stress-induced matrix metalloproteinase-9 by Sirt1 in skin tissue

Solar ultra-violet (UV) radiation and the ensuing photo-damage are adverse factors affecting human skin directly exposed to the sun. Stress responses induced by UV radiation (UVR) elicit premature skin ageing (photoageing), resulting in extensive damage to dermal connective tissue. Disruption of the normal dermal structure of skin connective tissue, primarily collagen, impairs a variety of skin functions and is considered to be the main cause of wrinkle formation. Matrix metalloproteases (MMPs) may be responsible for the degradation of collagen and other extracellular matrix proteins, which are major targets for relieving skin photoageing. Herein, we demonstrated that Sirt1, a putative anti-ageing enzyme, reduced MMP-9 transcriptional expression in skin. The known agonists of Sirt1, resveratrol and metformin, also significantly inhibited MMP-9 expression and appeared to protect collagen from degradation after UVR. These studies suggest that the Sirt1 activator could be used as a novel therapeutic agent to delay skin photoageing.