Gomisin A modulates aging progress via mitochondrial biogenesis in human diploid fibroblast cells

Summary Gomisin A from the fruit of Schisandra chinensis has many pharmacological properties, including hepato‐protective, anti‐diabetic, and anti‐oxidative stress. However, the potential benefit of gomisin A is still not well understood, especially in aging progression. Therefore, the aim of this study was to clarify whether the promotion of mitochondrial biogenesis and autophagy of gomisin A affects anti‐aging progression, and its mechanism. Intermediate (PD32) human diploid fibroblast (HDF) cells were brought to stress‐induced premature senescence (SIPS) using hydrogen peroxide. Gomisin A inhibited reactive oxygen species production even in the SIPS‐HDF cells. Gomisin A was also able to attenuate the activity of senescence‐associated β‐galactosidase and the production of pro‐inflammatory molecules in the SIPS as well as aged HDF cells. The antioxidant activity of gomisin A was determined by recovering the Cu/Zn, Mn‐SOD, and HO‐1 expression in the SIPS‐HDF cells. In mechanistic aspect, gomisin A inhibited the mitogen‐activated protein kinase pathway and the translocation of nuclear factor kappa B to the nucleus. In addition, gomisin A promoted the autophagy and mitochondrial biogenesis factors through the translocation of nuclear factor erythroid 2‐related factor‐2, and inhibited aging progression in the SIPS‐HDF cells. In summary, the enhanced properties of mitochondrial biogenesis and autophagy of gomisin A has a benefit to control age‐related molecules against SIPS‐induced chronic oxidative stress, and gomisin A may be a potential therapeutic compound for the enhancement of intracellular homeostasis to aging progression.