29 October 2026 (Navroze Bureau) Scientists have discovered that ageing muscles may sacrifice some of their strength to protect themselves from cellular damage, revealing a surprising mechanism behind age-related muscle decline. A study led by researchers at the University of Copenhagen has found that changes in a molecule called cardiolipin can trigger muscles to switch from powerful, fast-twitch fibres to more endurance-oriented, slow-twitch fibres.
The findings, published in the journal Nature Aging on September 29, 2026, offer a new explanation for why muscles change as they grow older. Researchers also found that restoring cardiolipin levels reversed signs of muscle wasting and prevented premature deaths in experimental mice, raising the possibility of future treatments for age-related muscle loss.
However, the researchers cautioned that the therapeutic findings have not yet been established in humans.
Why Muscles Become Weaker With Age
Muscles contain different types of fibres that perform different functions. Fast-twitch fibres generate powerful movements and allow people to produce force quickly, but they fatigue relatively rapidly. Slow-twitch fibres are better suited to sustained activity and rely heavily on mitochondria, the structures inside cells that produce energy.
As people age, muscle strength tends to decline and mitochondrial function becomes less efficient. Yet ageing muscles often develop a greater proportion of slow-twitch fibres, which depend heavily on these energy-producing structures.
Researchers have observed this apparent contradiction in ageing and in certain conditions associated with muscle wasting. The new study investigated why muscles make this shift and whether it serves a protective purpose.
The findings suggest that the change is not simply a sign of muscle failure. Instead, it may represent an adaptation that helps muscle cells survive when their energy-producing systems become damaged.
Cardiolipin Plays a Key Role
The researchers focused on cardiolipin, a specialised fat molecule found mainly in the inner membrane of mitochondria. It helps maintain mitochondrial structure and supports the processes that allow cells to generate energy efficiently.
The study found that cardiolipin levels declined in the skeletal muscles of ageing mice and in human muscle samples from older participants. The researchers then reduced cardiolipin production in young mice to investigate whether the decline could directly cause age-related changes.
The results were striking. The mice developed changes resembling those seen in ageing muscles, including a shift away from fast-twitch fibres towards slow-twitch fibres. Their muscle function also deteriorated, indicating that reduced cardiolipin could contribute directly to muscle wasting.
These experiments helped the team establish a connection between mitochondrial changes and the transformation in muscle-fibre composition.
How Muscles Trade Power for Protection
Further experiments revealed why the fibre switch might occur. When cardiolipin levels fall, damaged mitochondria produce increased amounts of reactive oxygen species, commonly known as ROS.
These molecules can damage cellular structures when present in excessive amounts. However, ROS also act as signalling molecules that help cells respond to stress.
The researchers found that these signals activate a protein called estrogen-related receptor gamma, or ERRγ, which helps coordinate changes in muscle-fibre characteristics and cellular metabolism.
As part of this response, the muscles increased their uptake of glucose. Rather than using all the additional sugar to produce energy, the cells redirected some of it towards making compounds that support their antioxidant defences.
This process appeared to help the muscle cells manage the stress associated with impaired mitochondria. The shift towards slow-twitch fibres may therefore be part of a wider protective response, even though it comes with a loss of some power-generating capacity.
The findings suggest that a biological change associated with ageing can have both harmful and protective effects at the same time.
Restoring Cardiolipin Reversed Muscle Wasting in Mice
One of the study’s most encouraging findings came when researchers restored cardiolipin production in affected adult mice.
Increasing cardiolipin to approximately two-thirds of normal levels began reversing signs of muscle wasting and prevented the premature deaths observed in the experimental animals.
The result suggests that some of the changes linked to impaired mitochondrial function may be reversible, at least under the conditions studied.
Researchers also found that interfering with the protective response using an antioxidant made certain muscle outcomes worse in their experimental models. This highlights the complexity of cellular stress responses: a process that appears damaging can also trigger mechanisms that help cells defend themselves.
The results do not mean that antioxidants are generally harmful to people. The experiments involved specific mouse models with experimentally reduced cardiolipin, and their findings cannot be directly applied to ordinary supplement use in humans.
Could the Discovery Lead to New Treatments?
The study identifies cardiolipin and ERRγ as possible targets for future research into age-related muscle decline. Scientists hope that therapies designed to restore cardiolipin levels or influence the relevant cellular pathways could eventually help preserve muscle function.
A medicine called elamipretide, designed to interact with mitochondrial membranes and help stabilise cardiolipin, has received accelerated approval in the United States for Barth syndrome, a rare inherited disorder. However, its effectiveness against ordinary age-related muscle loss has not been established.
Researchers will need to conduct further studies to determine whether similar approaches can safely improve muscle health in older people.
The distinction between animal and human evidence is particularly important. Although the researchers found declining cardiolipin levels in human muscle samples, the experiments demonstrating reversal of muscle wasting were conducted in mice.
What the Findings Mean for Healthy Ageing
The research offers a new perspective on muscle ageing by showing that the body may make biological trade-offs to protect cells under stress. The shift towards slow-twitch fibres may reduce some aspects of strength while supporting mechanisms that help muscle cells cope with mitochondrial damage.
The next challenge is to determine whether scientists can preserve the protective benefits while preventing the loss of muscle power.
Until further evidence is available, the findings should be viewed as an important step in understanding the biology of muscle ageing rather than a proven treatment for age-related weakness.