Schisandra chinensis Modulates Cellular Senescence through Integrated Regulation of Redox, Mitochondrial, and...

Cellular senescence is a fundamental process that drives organismal aging and frailty through progressive oxidative stress, mitochondrial dysfunction, chronic inflammation, and impaired cellular quality-control systems. Accordingly, growing interest has focused on natural compounds capable of modulating the interconnected hallmarks of aging in a balanced and physiologically relevant manner. Schisandra chinensis (Turcz.) Baillon, a traditional medicinal fruit that is widely used in East Asian medicine, has recently emerged as a promising senostatic candidate. This review summarizes the current experimental evidence demonstrating that S. chinensis fruit (Schisandrae Fructus) extracts and their bioactive lignan constituents exert multilayered regulatory effects on cellular aging pathways. Accumulating evidence indicates that Schisandrae Fructus enhances redox homeostasis by suppressing excessive reactive oxygen species generation and activating endogenous antioxidant defense mechanisms. In parallel, Schisandrae Fructus constituents preserve mitochondrial function by maintaining the mitochondrial membrane potential, reducing mitochondrial oxidative stress, and promoting mitochondrial biogenesis. In addition to redox and mitochondrial regulation, Schisandrae Fructus suppresses senescence-associated secretory phenotype factors and inflammatory signaling cascades, thereby mitigating the chronic low-grade inflammation that reinforces senescence and tissue dysfunction. Emerging evidence further suggests that Schisandrae Fructus modulates autophagy- and mitophagy-related quality-control pathways, contributing to the removal of damaged cellular components and maintenance of cellular homeostasis. Importantly, the biological actions of Schisandrae Fructus favor adaptive and balanced regulation rather than excessive pathway activation, supporting its classification as a senostatic modulator rather than a cytotoxic agent. Overall, Schisandrae Fructus represents a compelling natural multitarget candidate for mitigating the core mechanisms of cellular aging and frailty. Further studies are needed to define its long-term efficacy and translational potential.