Vanadyl Complexes (VOp-Dmada) Promote Healthy Aging by Regulating Electron Transport Mediated by Mitochondrial Complex II.
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| Main Authors: | , , , , , |
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| Format: | Artículo científico |
| Language: | en |
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ChemMedChem
2026
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| _version_ | 1868266069649522691 |
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| author | Wang, Jiayu Zhang, Bowen Liu, Liwen Li, Xin Xie, Zhengwei Yang, Xiaoda |
| author_facet | Wang, Jiayu Zhang, Bowen Liu, Liwen Li, Xin Xie, Zhengwei Yang, Xiaoda Wang, Jiayu Zhang, Bowen Liu, Liwen Li, Xin Xie, Zhengwei Yang, Xiaoda |
| collection | PubMed - marine biology |
| contents | Vanadyl Complexes (VOp-Dmada) Promote Healthy Aging by Regulating Electron Transport Mediated by Mitochondrial Complex II. Wang, Jiayu Zhang, Bowen Liu, Liwen Li, Xin Xie, Zhengwei Yang, Xiaoda Animals Mice Electron Transport Complex II Electron Transport Mitochondria Healthy Aging Coordination Complexes Caenorhabditis elegans Reactive Oxygen Species Molecular Structure Structure-Activity Relationship Dose-Response Relationship, Drug Vanadium Compounds Vanadium compounds are promising metallodrug candidates, with well-documented antidiabetic, antitumor, and anti-Alzheimer's activities. In search for the long-term beneficial or adverse effects of antidiabetic vanadyl complexes, we serendipitously discovered that the vanadyl complexes VOp-dmada exerted pro-healthy aging effects across a diverse panel of model organisms, i.e., yeast, C. elegans, and SAMP8 mice. Furthermore, VOp-dmada attenuated replicative senescence in mouse embryonic fibroblasts and alleviated thymic epithelial cell aging while preserving thymic architecture and function in a mouse model of dexamethasone-induced acute thymic atrophy. Mechanistic investigations revealed that VOp-dmada improved the structural integrity and functional capacity of mitochondrial complex II. This effect was mediated by activation of the c-Myc/S-phase kinase-associated protein 2 (SKP2)/sirtuin 3 (SIRT3) signaling axis, which in turn upregulated succinate dehydrogenase subunit A (SDHA) expression. Thus, vanadyl complexes suppressed reactive oxygen species (ROS) generation at the source, disrupted the deleterious ROS-thioredoxin-interacting protein (TXNIP) vicious cycle, and ultimately decelerated the aging process. Our findings highlight the potential application of antidiabetic vanadium complexes in the treatment of other aging-related disorders and corroborate the chronic safety profile. Moreover, these results support the targeting of mitochondrial complex II function and integrity as a novel strategy for the discovery of pro-healthy aging agents. |
| format | Artículo científico |
| id | pubmed_41885876 |
| institution | PubMed |
| language | en |
| publishDate | 2026 |
| publisher | ChemMedChem |
| record_format | pubmed |
| spellingShingle | Vanadyl Complexes (VOp-Dmada) Promote Healthy Aging by Regulating Electron Transport Mediated by Mitochondrial Complex II. Wang, Jiayu Zhang, Bowen Liu, Liwen Li, Xin Xie, Zhengwei Yang, Xiaoda Animals Mice Electron Transport Complex II Electron Transport Mitochondria Healthy Aging Coordination Complexes Caenorhabditis elegans Reactive Oxygen Species Molecular Structure Structure-Activity Relationship Dose-Response Relationship, Drug Vanadium Compounds Vanadyl Complexes (VOp-Dmada) Promote Healthy Aging by Regulating Electron Transport Mediated by Mitochondrial Complex II. Wang, Jiayu Zhang, Bowen Liu, Liwen Li, Xin Xie, Zhengwei Yang, Xiaoda Animals Mice Electron Transport Complex II Electron Transport Mitochondria Healthy Aging Coordination Complexes Caenorhabditis elegans Reactive Oxygen Species Molecular Structure Structure-Activity Relationship Dose-Response Relationship, Drug Vanadium Compounds Vanadium compounds are promising metallodrug candidates, with well-documented antidiabetic, antitumor, and anti-Alzheimer's activities. In search for the long-term beneficial or adverse effects of antidiabetic vanadyl complexes, we serendipitously discovered that the vanadyl complexes VOp-dmada exerted pro-healthy aging effects across a diverse panel of model organisms, i.e., yeast, C. elegans, and SAMP8 mice. Furthermore, VOp-dmada attenuated replicative senescence in mouse embryonic fibroblasts and alleviated thymic epithelial cell aging while preserving thymic architecture and function in a mouse model of dexamethasone-induced acute thymic atrophy. Mechanistic investigations revealed that VOp-dmada improved the structural integrity and functional capacity of mitochondrial complex II. This effect was mediated by activation of the c-Myc/S-phase kinase-associated protein 2 (SKP2)/sirtuin 3 (SIRT3) signaling axis, which in turn upregulated succinate dehydrogenase subunit A (SDHA) expression. Thus, vanadyl complexes suppressed reactive oxygen species (ROS) generation at the source, disrupted the deleterious ROS-thioredoxin-interacting protein (TXNIP) vicious cycle, and ultimately decelerated the aging process. Our findings highlight the potential application of antidiabetic vanadium complexes in the treatment of other aging-related disorders and corroborate the chronic safety profile. Moreover, these results support the targeting of mitochondrial complex II function and integrity as a novel strategy for the discovery of pro-healthy aging agents. |
| title | Vanadyl Complexes (VOp-Dmada) Promote Healthy Aging by Regulating Electron Transport Mediated by Mitochondrial Complex II. |
| topic | Animals Mice Electron Transport Complex II Electron Transport Mitochondria Healthy Aging Coordination Complexes Caenorhabditis elegans Reactive Oxygen Species Molecular Structure Structure-Activity Relationship Dose-Response Relationship, Drug Vanadium Compounds |
| url | https://pubmed.ncbi.nlm.nih.gov/41885876/ |