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 anti-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, the nanozyme showed excellent anti-aging and neuroprotective effect. Mechanically, the activated mitochondrial unfolded protein response (UPR^mt) 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.