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Alterations in mitochondria within senescent cells primarily encompass two interrelated aspects: intrinsic mitochondrial dysfunction and compromised mitochondrial quality control systems, including mitophagy, dynamics, and biogenesis. However, a comprehensive synthesis that bridges mechanistic insights into mitochondrial dysfunction with an analysis of therapeutic obstacles remains lacking. Here, we systematically summarized the pathways leading to mitochondrial dysfunction in aging and deeply analyzed how this dysregulation, including mitochondrial DNA instability and mitochondria driving inflammation through the cGAS\u2013STING pathway, contributed to the etiology of aging\u2010related diseases, including muscle, bone, neurodegeneration, cardiovascular, and metabolic diseases. Additionally, we analyzed a series of mitochondrial targeted treatment strategies, from metabolism and kinetic regulation to disease\u2010specific intervention and emerging technologies, such as mitochondrial transplantation and mitochondrial DNA base editing. Finally, we emphasized the key obstacles that must be overcome for clinical transformation, including tissue\u2010specific mitochondrial heterogeneity. By combining the basic mechanism with the development of treatment and its potential challenges, this review provides a key perspective for promoting the emerging field of mitochondrial medicine to intervene in aging\u2010related pathology more accurately and effectively.<\/jats:p>","DOI":"10.1002\/mco2.70790","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T06:13:02Z","timestamp":1780639982000},"source":"Crossref","is-referenced-by-count":2,"title":["Targeting Mitochondria in Aging\u2010Related Diseases: Therapeutic Potential and Obstacles"],"prefix":"10.1002","volume":"7","author":[{"given":"Zijie","family":"Xiang","sequence":"first","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of 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