The oxidative damages induced by a redox imbalance cause age-related changes in cells and tissues. Superoxide dismutase (SOD) enzymes play a pivotal role in the antioxidant system and they also catalyze superoxide radicals. Since the loss of cytoplasmic SOD (SOD1) resulted in aging-like phenotypes in several types of murine tissue, SOD1 is essential for the maintenance of tissue homeostasis. Melinjo (
Gnetum gnemonLinn) seed extract (MSE) contains trans-resveratrol (RSV) and resveratrol derivatives, including gnetin C, gnemonoside A, and gnemonoside D. MSE intake also exerts no adverse events in human study. In the present studies, we investigated protective effects of MSE on age-related skin pathologies in mice. Orally MSE and RSV treatment reversed the skin thinning associated with increased oxidative damage in the Sod1−/−mice. Furthermore, MSE and RSV normalized gene expression of Col1a1and p53and upregulated gene expression of Sirt1in skin tissues. In vitroexperiments revealed that RSV significantly promoted the viability of Sod1−/−fibroblasts. These finding demonstrated that RSV in MSE stably suppressed an intrinsic superoxide generation in vivoand in vitroleading to protecting skin damages. RSV derivative-rich MSE may be a powerful food of treatment for age-related skin diseases caused by oxidative damages.