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.

Exercise and healthy diet consumption support healthy aging. Schisandra chinensis (Turcz.) also known as “Baill.” has anti‐inflammatory and antioxidant properties. However, the role of S. chinensis as an antiaging compound has yet to be demonstrated. This study elucidated the antiaging effect of S. chinensis ethanol–hexane extract (C1) and the effect of C1 treatment on muscle and bone following physical exercise in ovariectomized (OVX) rats. RAW 264.7, human diploid fibroblasts (HDFs), C2C12 myoblasts, bone marrow macrophages, and MC3T3‐E1 cells were used for in vitro, and muscle and bone of OVX rats were used for in vivo study to demonstrate the effect of C1. The C1 significantly inhibited the expression of inflammatory molecules, β‐galactosidase activity, and improved antioxidant activity via down‐regulation of reactive oxygen species in RAW 264.7 and aged HDF cells. The C1 with exercise improved muscle regeneration in skeletal muscle of OVX rats by promoting mitochondrial biogenesis and autophagy. C1 induced osteoblast differentiation, and C1 + exercise modulated the bone formation and bone resorption in OVX rats. C1 exhibited anti‐inflammatory, antioxidant, myogenic, and osteogenic effects. C1 with exercise improved age‐related muscle wasting and bone loss. Therefore, S. chinensis may be a potential prevent agent for age‐related diseases such as sarcopenia and osteoporosis.