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Therefore, maintaining mitochondrial homeostasis is essential for healthspan. Mitochondrial respiratory chain complexes organize into higher-order assemblies known as supercomplexes (SCs), which enable to efficient energy or ATP production with repressed ROS generation. Notably, the assembly and stability of these SCs likely decline in aged mammals. In addition, factors such as COX7RP\/SCAF1 and mitochondrial lipid cardiolipin have emerged as key regulators of SC assembly. In this review, we summarize the molecular assembly, physiological roles, and longevity implications of SC in healthy mammals. We further discuss emerging evidence supporting SC modulation as a potential strategy for promoting healthy aging.<\/jats:p>","DOI":"10.3389\/fragi.2026.1876149","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T05:58:37Z","timestamp":1785304717000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mitochondrial respiratory supercomplexes associated with longevity in mammals"],"prefix":"10.3389","volume":"7","author":[{"given":"Shinichiro","family":"Suzuki","sequence":"first","affiliation":[{"name":"Division of Systems Medicine and Gene Therapy, Faculty of Medicine, Saitama Medical University","place":["Saitama, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Division of Systems Medicine and Gene Therapy, Faculty of Medicine, Saitama Medical University","place":["Saitama, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Takeiwa","sequence":"additional","affiliation":[{"name":"Department of Systems Aging Science and Medicine, Tokyo Metropolitan Institute for Geriatrics and Gerontology","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuniko","family":"Horie","sequence":"additional","affiliation":[{"name":"Division of Systems Medicine and Gene Therapy, Faculty of Medicine, Saitama Medical University","place":["Saitama, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Inoue","sequence":"additional","affiliation":[{"name":"Division of Systems Medicine and Gene Therapy, Faculty of Medicine, Saitama Medical University","place":["Saitama, Japan"]},{"name":"Department of Systems Aging Science and Medicine, Tokyo Metropolitan Institute for Geriatrics and Gerontology","place":["Tokyo, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"8031","DOI":"10.3390\/ijms21218031","article-title":"Cardiolipin, the mitochondrial signature lipid: implication in cancer","volume":"21","author":"Ahmadpour","year":"2020","journal-title":"Int. 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