Growing older often means losing some of the muscle strength that once made everyday movements feel effortless. But scientists at the University of Copenhagen have found that certain changes in aging muscles may protect their cells from damage.
In mouse experiments, researchers found that restoring a crucial molecule to about two-thirds of its normal level helped reverse muscle wasting.
Published in Nature Aging on September 29, 2026, the findings offer a different explanation for some of the physical changes associated with aging.
Rather than representing deterioration alone, certain changes in muscle fibers may reflect a biological defense mechanism that helps cells withstand stress.
The discovery provides scientists with a new direction for investigating age-related muscle weakness, although its potential applications in humans remain uncertain.
A Small Molecule With an Important Role in Muscle Aging
The researchers traced some of the changes in aging muscles to declining levels of cardiolipin, a molecule that helps mitochondria function properly. As cardiolipin levels fall, muscles may change how they produce energy and respond to cellular stress.
Cardiolipin is a specialized fat molecule concentrated in the inner membrane of mitochondria, the structures responsible for producing energy inside cells. It accounts for approximately 10% to 15% of mitochondrial phospholipids and helps maintain the machinery that supports energy production.
The researchers compared muscle samples from younger adults aged 22 to 35 with those from older adults aged 53 to 69. Cardiolipin levels were lower in the older group, although the human comparison involved only a small number of participants.
To investigate the molecule’s role more directly, the scientists conducted experiments involving mice.
They disrupted a gene called Crls1, which is necessary for cardiolipin production. The affected animals developed mitochondrial abnormalities, muscle wasting, and changes in their muscle fiber composition.
These observations helped establish that cardiolipin deficiency could reproduce several features associated with muscle aging.
But the resulting changes revealed something more complicated than simple deterioration.
Related: Why exercise alone is not enough to keep muscles strong
Why Weaker Muscles May Be Protecting Their Cells
The study found that muscles affected by cardiolipin loss began shifting toward fibers better suited for sustained activity rather than quick, powerful movements. This change also seemed to help muscle cells defend themselves against stress, even as they lost some ability to generate force.
Muscles contain different fiber types suited to different demands. Some support quick, powerful movements, while others are better adapted to prolonged activity.
As cardiolipin production declined, the affected muscles developed more characteristics of slower, oxidative fibers. This transition strengthened cellular defenses against oxidative stress, suggesting the muscles responded to internal damage rather than simply losing function.
Fabian Finger, an assistant professor at the University of Copenhagen and one of the study’s leading researchers, described the finding: “The fiber switch is not the muscle failing, but the muscle trading power for protection.”
The researchers also identified a protein called ERRγ as an important regulator of this process. In laboratory experiments, inhibiting its activity prevented the observed muscle fiber transition.
The precise mechanism connecting cardiolipin loss to ERRγ activity remains unresolved.
The Surprising Connection Between Stress and Muscle Survival
The researchers found that certain molecules normally associated with cellular damage also helped muscles protect themselves. Rather than simply causing harm, these molecules signaled the muscles’ natural defenses against stress.
These molecules, known as reactive oxygen species, can damage cellular components when present in excessive amounts. However, they also signal and influence how cells respond to stress.
In the experimental model, reducing these signals with antioxidants interfered with protective adaptation. Antioxidant administration was also associated with worse muscle outcomes in the affected mice.
This does not establish that antioxidants are generally harmful to older adults or that people should change their supplement use.
Another finding concerned glucose, which cells use in several metabolic processes. The researchers observed that affected muscles increased glucose uptake and redirected some of it toward producing antioxidant defenses.
Together, the findings revealed how muscle cells can reorganize their metabolism when mitochondrial function becomes impaired.
What Happened When Scientists Restored Cardiolipin
The researchers found that restoring some of the lost cardiolipin helped damaged muscles in genetically modified mice begin to recover. Even without restoring the molecule to normal levels, the intervention reversed some of the muscle wasting caused by its deficiency.
After disrupting cardiolipin synthesis, the team restored Crls1 activity.
As cardiolipin levels increased, muscle wasting began to reverse. The intervention also prevented the premature deaths observed in the affected mouse model.
Zachary Gerhart-Hines, an associate professor at the University of Copenhagen and the study’s senior author, highlighted the significance of the recovery. “What encourages me most is that even a partial recovery of cardiolipin was enough to bring the muscle back.”
The results suggest that targeting cardiolipin production could become a subject of future treatment research.
However, the recovery experiments were conducted in mice with experimentally disrupted cardiolipin production. They did not demonstrate that the same intervention could reverse natural muscle aging in humans.
What the Discovery Could Mean for Future Treatments
The findings have given researchers new biological targets to investigate as they search for ways to address muscle weakness associated with aging. However, the discovery is still early, and scientists have yet to establish whether these findings can lead to an effective treatment for older adults.
One potential research direction involves cardiolipin production, while another concerns ERRγ and its role in coordinating cellular responses. An FDA-approved medication already targets cardiolipin-related mitochondrial biology.
On September 19, 2025, the U.S. Food and Drug Administration granted accelerated approval to elamipretide, marketed as Forzinity, for eligible patients with Barth syndrome, a rare inherited mitochondrial disorder.
That approval does not extend to ordinary muscle aging, and the Copenhagen researchers did not establish the medication’s effectiveness for that purpose.
Future investigations will need to determine whether the biological mechanisms observed in the experimental mice can be safely targeted in naturally aging human muscle.
The findings also challenge a familiar assumption about aging: that every physical decline reflects a system simply wearing out. Sometimes, what looks like deterioration may involve a more complicated biological response to damage.
That raises an intriguing question: Could some changes that weaken our muscles also reveal how the body keeps its cells alive?
