Topical Melatonin Unfolds Differential Anti-Aging Effects in Human Skin by Inhibiting mTORC1 Activity via TSC2 Stimulation

This study investigates the anti-aging effects of topical melatonin (MT) on aged scalp skin from 3 healthy male donors. When applied at concentrations of 100μM and 1mM for 6 days, MT significantly increased SIRT1 and collagen I expression while reducing matrix metalloprotease 1 in the skin. At 100μM, MT also increased PGC1α expression and reduced mTORC1 pathway activity, similar to rapamycin. Notably, MT prevented the up-regulation of p-S6 and rescued TSC2 downregulation when TSC2 was silenced. These findings highlight MT's potential as a topical anti-aging agent and its novel role in stimulating TSC2, a key inhibitor of mTORC1, offering insights into its diverse functions.