Researchers from the University of Copenhagen have resolved the paradox of why aging muscles weaken despite an increased proportion of durable, slow-twitch fibers. The study reveals that this fiber-type transition is a protective response to age-related mitochondrial damage, specifically driven by a decline in cardiolipin, a crucial mitochondrial lipid. This depletion triggers increased reactive oxygen species (ROS) production, which signals the protein ERRγ to reprogram fast-twitch muscle fibers into slow-twitch ones, effectively sacrificing muscle power for cellular protection. Notably, preclinical experiments demonstrated that partially restoring cardiolipin levels reverses this age-related muscle tissue loss, highlighting a promising therapeutic target for mitigating sarcopenia and age-related muscle decline.

Scientists in the Gerhart-Hines Group pinpoint a molecular cause of muscle aging, and a possible fix. By investigating how muscles adapt to age and disease-related decline, the scientists discovered the involvement of a druggable nuclear receptor, ERRγ, that could be targeted to preserve muscle function. The findings were published in Nature Aging.