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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\n                    <jats:sup>+<\/jats:sup>\n                    and directly fixing redox imbalance. In aged (24-month-old) mice, systemic MXene-TA administration restored NAD\n                    <jats:sup>+<\/jats:sup>\n                    \/NADH homeostasis and reduced senescence markers (p16, p21, \u03b3H2AX, 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\n                    <jats:sup>+<\/jats:sup>\n                    -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 extended ADSC survival beyond 4 weeks (versus 1 week in controls) and further improved cardiac repair. Together, these findings uncover the therapeutic potential of NOX-mimetic nanozymes in aging and ischemic heart disease and introduce a redox-regulating hydrogel system that addresses both oxidative stress and stem cell integration for effective myocardial repair.\n                  <\/jats:p>","DOI":"10.34133\/research.0973","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T10:08:51Z","timestamp":1760350131000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":11,"title":["A NADH Oxidase Nanozyme Restores Redox Homeostasis to Ameliorate Multi-Organ Aging and Ischemic Cardiomyopathy"],"prefix":"10.34133","volume":"8","author":[{"given":"Yu","family":"Chen","sequence":"first","affiliation":[{"name":"The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, 510900, People\u2019s Republic of China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunsong","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, People\u2019s Republic of China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Shen","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, People\u2019s Republic of China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueyan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, People\u2019s Republic of China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoni","family":"Qiu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, People\u2019s Republic of China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7133-9760","authenticated-orcid":true,"given":"Honghao","family":"Hou","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, People\u2019s Republic of China."},{"name":"Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering","place":["People\u2019s Republic of China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5944-9812","authenticated-orcid":true,"given":"Xiaozhong","family":"Qiu","sequence":"additional","affiliation":[{"name":"The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, 510900, People\u2019s Republic of China."},{"name":"School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, People\u2019s Republic of China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"issue":"8","key":"e_1_3_4_2_2","first-page":"e93","article-title":"Heart disease and stroke statistics\u20142023 update: A report from the American Heart Association","volume":"147","author":"Tsao CW","year":"2023","unstructured":"Tsao CW, Aday AW, Almarzooq ZI, Anderson CAM, Arora P, Avery CL, Baker-Smith CM, Beaton AZ, Boehme AK, Buxton AE, et al. 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