As people get older, their muscles get weaker. A new study from the University of Copenhagen suggests that part of this decline may not be the muscle simply breaking down. It may be a trade: the muscle gives up some power to protect its cells from damage1.
The work centres on cardiolipin, a fat molecule found mainly in the inner membrane of mitochondria, the tiny structures that produce energy inside cells. The researchers found that cardiolipin levels fall in aging muscle, and that restoring part of it reversed signs of muscle wasting in mice1. The main experiments were done in mice and in muscle cells grown in a dish, so it is not known whether any of this applies to treating people1.
What the researchers found
Muscles contain different kinds of fibers. Fast-twitch fibers produce powerful, quick movements but tire fast. Slow-twitch fibers support steady, long-lasting activity and depend heavily on mitochondria1.
That creates a puzzle. With age, mitochondria work less efficiently and muscle strength drops. Yet aging muscles tend to end up with a higher share of slow-twitch fibers, the type that relies most on mitochondria. Similar shifts have been seen in diseases that cause muscle wasting1.
To make sense of this, the team looked at cardiolipin, which helps mitochondria keep their structure and carry out normal cell work. They report that cardiolipin levels dropped in the muscle mitochondria of aging or diseased mice and humans1.
Next, they lowered cardiolipin in young mice. The animals’ muscles shifted from fast-twitch to slow-twitch fibers, looking more like aging muscle. When the researchers brought cardiolipin back up to about two-thirds of its normal level, muscle wasting began to reverse and the mice were spared early deaths1.
How the muscle trades power for protection
Further experiments pointed to the fiber shift being a defence rather than just a sign of failure, according to the report1.
When cardiolipin falls, damaged mitochondria release more reactive oxygen species, often shortened to ROS. These are reactive molecules that can harm parts of the cell, but they also work as alarm signals that tell the cell it is under stress. The researchers found that ROS helped set off the change in fiber type. Lowering ROS with antioxidants made the shift weaker in muscle cells that lacked cardiolipin1.
The team also pointed to a protein called ERR-gamma, which helps coordinate changes in mitochondria and in muscle fibers. Blocking it in lab-grown muscle cells stopped the fiber shift1.
Finally, they looked at how the shift helps muscle cope. Mice short on cardiolipin took up more sugar (glucose) from their blood. Tests with specially labelled glucose showed that the muscle cells did not mainly burn it for energy. Instead they used it to make their own antioxidants, which helped shield them from the excess ROS1.
Fabian Finger, an assistant professor at the University of Copenhagen and the study’s first and co-corresponding author, described it this way:
“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,”1
What it does not show yet
The evidence has clear limits. The experiments on the protective mechanism and on restoring muscle function were done in mice. Human samples were used only to confirm that cardiolipin declines with age1. The researchers have not yet shown that the same approach can reverse muscle loss in people1.
Several other points are worth keeping in mind:
- The ERR-gamma finding comes from muscle cells grown in a dish, not from living animals or people1.
- The mice in the restoration experiments had their cardiolipin lowered on purpose. That is a model of aging-like changes, not natural old age itself1.
- The antioxidant results in mice suggest that simply mopping up ROS may not help, and could even make things worse, in this setting. That was a lab finding, not a test of any supplement in people1.
The coverage available to Biohack does not name the journal, give the number of mice or human samples, or describe who funded the work. Those details matter for judging the study and are not shown here.
Could it lead to treatments?
The researchers point to two possible routes: restoring cardiolipin, or working with the muscle’s protective response through ERR-gamma1.
Ways to act on cardiolipin already exist. The US Food and Drug Administration recently gave accelerated approval to elamipretide, a drug designed to help stabilise cardiolipin, for Barth syndrome, a rare inherited disorder. Whether it does anything for ordinary age-related muscle loss is unknown1.
ERR-gamma belongs to the nuclear receptor family of proteins, whose members are the targets of many existing medicines. Drugs that switch on ERR-gamma are being studied in early lab research for other uses1.
How it fits the field
Mitochondria have long been a focus in research on aging muscle. In a 2023 study in worms, researchers at Joslin Diabetes Center reported that a cycle of mitochondrial breakdown and repair after exercise weakened with age, alongside a fall in fitness. Daily swimming sessions improved the worms’ fitness in middle age and eased those mitochondrial changes2. That work was in microscopic worms, a very simple animal.
In people, a small 2020 study followed 16 untrained older adults, average age about 59, through 10 weeks of full-body strength training twice a week. Muscle samples showed higher levels of several mitochondrial proteins after training3. It measured proteins in muscle, not whether people became stronger or lived longer, and had no comparison group in the summary shown.
Other teams have looked beyond mitochondria. A 2018 Karolinska Institutet study reported that muscle stem cells in a healthy 70-year-old had built up more than 1,000 mutations each, and that the cells’ protection against such damage declined with age4. Biohack also recently covered research tying weaker muscles in old age to faulty signals between nerves and muscles (read that story).
The Copenhagen study adds a different angle. Rather than treating the slow-fiber shift as pure decline, it frames it as a costly defence, and suggests that blocking it without fixing the underlying damage could backfire1.
What to watch next
The open question, as the researchers put it, is whether cardiolipin can be raised in people and whether doing so would help aging muscle1. Signs to watch for include:
- publication details, including the journal, sample sizes and funding;
- any study testing cardiolipin-targeting drugs such as elamipretide in older adults with muscle loss;
- work on ERR-gamma in living animals, beyond lab-grown cells;
- independent groups checking whether cardiolipin falls in aging human muscle in larger samples.
For now, the finding offers a possible explanation for a long-standing puzzle in aging muscle, based mostly on mice. It is not a treatment, and it does not show that any product or drug slows muscle loss in people.
