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Ultra-small polydopamine nanomedicine-enabled antioxidation againstsenescene

Senescence is a cellular response characterized by cells that irreversibly stop dividing and enter a permanent growth arrest state. One of the underlying pathophysiological causes of aging is due to oxidative stress damage, suggesting that the elimination of reactive oxygen and nitrogen species (RONS) may be beneficial for the prevention and / or mitigation of aging. Here, we developed small polydopamine nanoparticles (UPDA NPs) with superoxide dismutase (SOD) / catalase (CAT) enzyme mimetic activity with broad-spectrum RONS scavenging ability to induce cytoprotection against RONS-mediated damage. Engineered UPDA NPs can restore aging-related renal function, tissue homeostasis, coat density, and motility in mice, which may be related to the regulation of multiple genes involved in lipid metabolism, mitochondrial function, energy homeostasis, telomerase activity, neuroprotection, and inflammatory responses. Importantly, dietary UPDA NPs can enhance antioxidant capacity, improve climbing ability, and extend lifespan in Drosophila. Notably, UPDA NPs has excellent biocompatibility due to its extremely small size, ensuring rapid in vitro clearance. These findings suggest that UPDA NPs can delay aging by reducing oxidative stress and provide a paradigm and practical strategy for treating aging and aging-related diseases, such as Alzheimer's disease.