N-Acetylcysteine Worsened Muscle Wasting in Cardiolipin-Deficient Mice

N-Acetylcysteine Worsened Muscle Wasting in Mice with Cardiolipin Deficiency

N-acetylcysteine worsened muscle loss in mice whose cardiolipin synthesis had been genetically switched off. Cardiolipin is a lipid in the inner mitochondrial membrane. Fabian Finger, Zachary Gerhart-Hines and their team at the University of Copenhagen published the findings in the journal Nature Aging on September 29, 2026.

N-Acetylcysteine acts as an antioxidant, reducing reactive oxygen species. These molecules can damage cells, but in this experiment they also contributed to the muscle's protective response.

The researchers switched off Crls1, a gene needed for cardiolipin synthesis, selectively in the muscles of young mice. With cardiolipin depleted, mitochondria lost the internal folded structure needed for energy production. Fast, powerful muscle fibers converted to slow, endurance-type fibers. The same shift in fiber types occurs in human aging.

Damaged mitochondria produced more reactive oxygen species. The remodeled fibers absorbed several-fold more glucose from the blood and redirected it from energy production toward antioxidant synthesis. In the authors' explanation, the muscle sacrificed power to protect its cells. By reducing reactive oxygen species, N-acetylcysteine interfered with this protective response, and muscle wasting worsened.

The reverse experiment showed that these changes could be reversed. When the researchers switched Crls1 back on in adult mice, cardiolipin reached roughly two-thirds of its normal level. That was enough to reverse atrophy and prevent premature death. Without restoration, more than half the animals died.

These results came from mice with an artificially disabled gene. The authors' next planned step is to raise cardiolipin levels in naturally aged mice and test whether this helps during ordinary aging.

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Sources
[1] nature.com
[2] medicalxpress.com
[3] t.me