A NADH Oxidase Nanozyme Restores Redox Homeostasis to Ameliorate Multi-Organ Aging and Ischemic Cardiomyopathy.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Redox imbalance resulting from NAD + [nicotinamide adenine dinucleotide (oxidized form)] depletion and NADH (reduced form of NAD + ) accumulation is a conserved hallmark of both aging and myocardial infarction (MI), promoting cellular senescence and limiting the efficacy of regenerative therapies. Despite several NADH oxidase (NOX)-mimetic nanozymes having been reported, their therapeutic utility in aging and cardiovascular repair remains largely unexplored. Here, we present a vanadium-based nanozyme (MXene-TA) that mimics bacterial NOX activity, catalytically oxidizing NADH to restore NAD + and directly fixing redox imbalance. In aged (24-month-old) mice, systemic MXene-TA administration restored NAD + /NADH homeostasis and reduced senescence markers (p16, p21, γH2AX, and SASP) in the heart, liver, and spleen, yet this effect was not observed in the lungs or kidneys, indicating organ-specific redox susceptibility. In a rat MI model, local injection of MXene-TA into the infarcted myocardium reprogrammed metabolism, activated NAD + -dependent pathways, attenuated oxidative damage in cardiomyocytes, decreased infarct area, and enhanced myocardial function. To further enhance stem cell retention and function, we embedded MXene-TA and adipose-derived stem cells (ADSCs) into a pH-responsive, conductive hydrogel that mimics cardiac mechanical and electrical properties. This platform

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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