Mitochondrial-Mimicking Nanozyme-Catalyzed Cascade Reactions for Aging Attenuation

Population aging is an increasingly aggravated public issue worldwide. Nanomaterials with enzyme-like activities are recognized as potentially important nanomedicines, yet how to leverage their in vivo performance for ant-aging therapy is still challenging. Here inspired by vital roles of mitochondrial respiratory chain complex enzymes on bioenergy generation and longevity, we reported a Pd based single-atom nanozyme (Pd@PPy/GO) as cascade nanoreactors to improve mitochondrial activities for aging attenuation. By mimicking NADH oxidase (NOX) and Cytochrome c oxidase (CcO), the nanozyme can catalyze the cascade reactions on mitochondrial respiratory chain and produce NAD+ without any external stimuli. At both Caenorhabditis elegans (C. elegans) and cell levels, we verified that nanozyme treatment could boost the mitochondrial function and abundance. More importantly, Pd@PPy/GO nanozyme showed excellent anti-aging and neuroprotective effect. Mechanically, the activated mitochondrial unfolded protein response (UPRmt) pathway plays a vital role in its anti-aging effect. Together, this work paves a way for nanocatalytic anti-aging therapy by rationally designing a simple and powerful nanozymes with dual-enzymatic activities.