Polydopamine nanomedicine-enabled antioxidation against senescence

Abstract Senescence is a cellular response characterized by cells irreversibly stopping dividing and entering a state of permanent growth arrest. One of the underlying causes of senescence is the oxidative stress-induced damage, indicating that eliminating the reactive oxygen and nitrogen species (RONS) may be beneficial to prevent and/or alleviate senescence. Herein, we develop biocompatible ultra-small polydopamine nanoparticles (UPDA NPs) featuring broad-spectrum RONS-scavenging capacities. The UPDA NPs can restore senescence-related renal function, tissue homeostasis, fur density and motor ability in mice, potentially associated with the regulation of multiple genes involved in lipid metabolism, mitochondrial function, energy homeostasis, telomerase activity, neuroprotection, and inflammatory responses. We also demonstrate that the dietary UPDA NPs can reduce the RONS level, enhance the climbing ability and prolong the lifespan of Drosophila. Our findings reveal that the developed UPDA NPs can delay aging through RONS elimination and provide a paradigm and practical strategy for clinically treating senescence and senescence-related diseases.