1404 Melatonin improves mitochondrial function in human skin ex vivo and may unfold significant anti-aging properties

Since skin is constantly exposed to multiple extrinsic and intrinsic aging-promoting stressors, shows easily visible signs of aging, there a need for the development effective senolytics. The endogenous, well-tolerated indoleamine neurohormone, melatonin, which also synthesized in itself, very attractive candidate senolytic since it displays numerous anti-aging properties, including free radical scavenging as well oxidative, mitochondrial DNA damage repair. Therefore, we have asked this pilot study whether melatonin unfolds significant activities human skin. For this, used serum-free organ culture, shown greatly accelerate aging ex vivo examined how impacts on selected aging-related biomarkers. We upper eyelid (given that sun-exposed targeted by cosmetics; 3-4 donors; 49-70 years old) treated “systemically” adding culture medium 6 days every other day. Quantitative immunohistomorphometry revealed 100uM up-regulates activity, significantly increased epidermal expression MTCO1 TFAM protein. tendentially SIRT1. Instead, pS6 protein was slightly decreased, suggesting downregulation mTOR pathway. Interestingly, did not alter VEGF-A protein, had be both sufficient required rejuvenation vivo. This suggests observed effects are VEGF-A-independent. currently complementing above read-outs with additional These preliminary data already support concept applied (e.g., nutraceutical) an senolytic.