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Yet the biological rationale and mechanism underlying this phenomenon remain largely unknown. Here we show that synthesis of the mitochondrial membrane lipid, cardiolipin, causally links mitochondrial dysfunction to fiber-type adaptations in aging mouse and human skeletal muscle. By mimicking the aging decline of skeletal muscle cardiolipin levels in young mice using inducible tissue-specific cardiolipin synthase 1 (\n                    <jats:italic>Crls1<\/jats:italic>\n                    ) deletion, we could reproduce key aging hallmarks, including the shift from glycolytic to oxidative fibers. This shift is mediated by mitochondria-to-nucleus signaling through the nuclear receptor, estrogen-related receptor \u03b3, which promotes reactive oxygen species-sensitive glucose uptake and enhanced glycolytic rerouting to sustain antioxidant defenses. Restoring\n                    <jats:italic>Crls1<\/jats:italic>\n                    expression in adult\n                    <jats:italic>Crls1<\/jats:italic>\n                    knockout mice reestablishes cardiolipin levels, initiates reversal of muscle atrophy and fully rescues premature mortality. These findings reveal how changes in a mitochondrial membrane lipid cell autonomously orchestrate fiber-type adaptations in aging and myopathies.\n                  <\/jats:p>","DOI":"10.1038\/s43587-026-01227-7","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:04:02Z","timestamp":1790672642000},"page":"2092-2109","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mitochondrial membrane lipid cardiolipin controls fiber-type adaptations in aging muscle via estrogen-related receptor 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