A taxifolin-zinc nanozyme with SOD-like activity attenuates oxidative-stress-induced senescence and extends lifespan in C. elegans.

Oxidative stress is a key driver of cellular senescence and functional decline. However, many natural polyphenols have limited bioavailability because they are difficult to formulate into stable systems. Here, we report a polyphenol-metal coordination nanozyme prepared by coordinating zinc with taxifolin and using L-arginine to regulate assembly. The resulting Tax-Zn nanozyme formed a well-dispersed nanoscale system with an average hydrodynamic diameter of 57.53 nm. Functionally, the nanozyme exhibited broad antioxidant capacity in several assays and showed slightly stronger activity than Tax in selected assays. In MEFs, Tax-Zn nanozyme showed low cytotoxicity and markedly suppressed intracellular ROS under H2O2 challenge, accompanied by improved mitochondrial function and attenuation of senescence-associated phenotypes. In C. elegans, Tax-Zn nanozyme extended lifespan and improved healthspan-related indicators. Collectively, these results support the nanozyme as a natural-product-derived coordination platform that mitigates oxidative-stress-related senescence phenotypes and supports the development of antioxidant nano-formulations.