Scientists at the University of Copenhagen have discovered that age-related muscle weakness is partly driven by a hidden defence mechanism, where muscles trade strength for cellular protection. The study identifies a molecule called cardiolipin whose decline triggers this trade-off, and shows that partially restoring it in mice reverses muscle wasting and prevents premature death.
Muscles naturally become weaker with age. New research suggests that some of this decline represents a deliberate shift in strategy rather than simple cellular decay. Scientists have long observed that aging muscles develop a greater proportion of slow-twitch fibres, which depend heavily on mitochondria, even as those mitochondria become less efficient. The new study, led by the University of Copenhagen and published on October 28, explains this paradox: the transformation is a defence mechanism.
The researchers focused on cardiolipin, a specialized fat molecule located within the inner membrane of mitochondria that is essential for proper energy production. Levels of cardiolipin decrease in muscle mitochondria as both mice and humans age. The team discovered that this decline triggers the production of reactive oxygen species, which act as signals to initiate the muscle fiber transition.
“The fiber switch is not the muscle failing, but the muscle trading power for protection,” said Assistant Professor Fabian Finger, first author of the study. “That's also why interfering with it can backfire: when we gave the mice antioxidants to mop up the ROS, their muscles fared worse, not better.”
The protective shift is coordinated by a protein called ERRγ. In lab experiments, inhibiting ERRγ stopped the transition entirely. The remodeled fibres also redirected glucose intake to produce their own antioxidants, further shielding cells from damage.
Crucially, when the researchers restored cardiolipin to roughly two-thirds of its normal concentration in mice, the signs of muscle wasting were reversed and premature deaths were completely prevented. Senior author Zachary Gerhart-Hines, Associate Professor at the NNF Center for Basic Metabolic Research, said the finding highlights the therapeutic potential of the pathway.
“What encourages me most is that even a partial recovery of cardiolipin was enough to bring the muscle back,” Gerhart-Hines said. “The question now is whether we can increase cardiolipin in aging muscle or target ERRγ to promote healthy adaptations. This is where the therapeutic potential lies.”
The study involved scientists from more than 20 institutions and was supported by the Novo Nordisk Foundation and the European Research Council, among others. Although the experiments demonstrating the reversal of muscle wasting were conducted in mice, the findings point toward possible new treatments. Elamipretide, a drug designed to stabilize cardiolipin, recently received accelerated FDA approval for Barth syndrome, and drugs targeting ERRγ are already in preclinical development for other applications.
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12 claims in this story checked against 1 source: 8 supported.
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- Partly supportedThe summary says partial restoration of cardiolipin reverses muscle wasting in mice.Latest Science News -- ScienceDaily: “restoring cardiolipin to approximately two-thirds of its normal concentration began reversing muscle wasting”
- Partly supportedThe story says aging muscles make a deliberate strategic shift, rather than simply undergoing cellular decay.Latest Science News -- ScienceDaily: “the shift toward slow-twitch fibers appears to be a protective response”
- Not in the sourcesThe study was published on October 28.Latest Science News -- ScienceDaily: “Date: October 28, 2026”
- SupportedThe headline says aging muscles sacrifice strength for protection.Latest Science News -- ScienceDaily: “Scientists discover why aging muscles sacrifice strength for survival”
- SupportedThe story says partially restoring cardiolipin in mice prevented premature death.Latest Science News -- ScienceDaily: “restoring cardiolipin to approximately two-thirds of its normal concentration began reversing muscle wasting and completely prevented the premature deaths seen in the affected animals.”
- SupportedThe story says cardiolipin levels decline in muscle mitochondria as mice and humans age.Latest Science News -- ScienceDaily: “The researchers discovered that cardiolipin levels decrease in muscle mitochondria from both mice and humans as they age or experience disease.”
- SupportedThe story attributes the quote about trading power for protection and the mice faring worse after antioxidants to Assistant Professor Fabian Finger, identified as the study’s first author.Latest Science News -- ScienceDaily: ““The fiber switch is not the muscle failing, but the muscle trading power for protection. That's also why interfering with it can backfire: when we gave the mice antioxidants to mop up the ROS, their muscles fared worse, not better,” says Assistant Professor Fabian Finger, first and co-corresponding author”
- SupportedThe story says cardiolipin decline triggers reactive oxygen species that initiate the muscle-fiber transition.Latest Science News -- ScienceDaily: “When cardiolipin concentrations fall, damaged mitochondria produce much larger quantities of reactive oxygen species (ROS).”
- SupportedThe story says inhibiting ERRγ stopped the muscle-fiber transition entirely in lab experiments.Latest Science News -- ScienceDaily: “When scientists inhibited ERRγ in muscle cells grown in the laboratory, the transition between fiber types stopped entirely.”
- SupportedThe story says remodeled muscle fibers redirected glucose to produce their own antioxidants.Latest Science News -- ScienceDaily: “muscle cells redirected the sugar toward manufacturing their own antioxidants.”
- Partly supportedThe story says drugs targeting ERRγ are already in preclinical development for other applications.Latest Science News -- ScienceDaily: “Drugs that activate ERRγ are also being investigated in preclinical research for other medical applications.”
- SupportedThe story quotes senior author Zachary Gerhart-Hines saying that partial cardiolipin recovery was enough to bring the muscle back and describing the pathway’s therapeutic potential.Latest Science News -- ScienceDaily: ““What encourages me most is that even a partial recovery of cardiolipin was enough to bring the muscle back. The question now is whether we can increase cardiolipin in aging muscle or target ERRγ to promote healthy adaptations. This is where the therapeutic potential lies,” says senior author Zachary Gerhart-Hines”