University of Copenhagen study links cardiolipin decline to protective shifts in ageing muscles

Researchers at the University of Copenhagen have identified a biological mechanism in ageing muscles that trades physical strength for cellular protection. The study sheds light on why muscles undergo structural changes during the natural ageing process and points to potential new targets for treating muscle wasting.

As people age, muscle strength naturally declines and cellular structures known as mitochondria become less efficient. At the same time, ageing muscles develop a greater proportion of slow-twitch fibres, which support sustained activity, even though these fibres depend on mitochondria that are losing function. Similar shifts are observed in various conditions that cause muscle wasting.

To understand this shift, researchers examined cardiolipin, a specialised fat molecule located almost exclusively within the inner membrane of mitochondria. Cardiolipin is essential for maintaining the membrane architecture required for proper mitochondrial activity. The study found that cardiolipin levels decrease in muscle mitochondria from both mice and humans as they age or experience disease, accompanied by structural abnormalities.

When researchers experimentally lowered cardiolipin levels in young mice, the results mirrored natural ageing, shifting muscle fibres away from the fast-twitch type. Conversely, restoring cardiolipin to approximately two-thirds of its normal concentration began reversing muscle wasting and prevented premature deaths in the affected animals.

The transformation appears to be a protective response. When cardiolipin concentrations fall, damaged mitochondria produce larger quantities of reactive oxygen species (ROS). These molecules signal that something is wrong and help initiate the transition from fast-twitch to slow-twitch fibres. A protein called ERRγ plays a central role in coordinating this response by directing cells to reorganise their mitochondria.

Instead of using additional glucose for energy, the remodelled fibres redirected sugar toward manufacturing their own antioxidants to protect against excess ROS. Assistant Professor Fabian Finger noted that the fibre switch represents the muscle trading power for protection rather than failing.

While the experiments demonstrating the protective mechanism and reversal of muscle wasting were conducted in mice, human muscle samples confirmed that cardiolipin levels decrease with age in people. Researchers noted that targeting cardiolipin or ERRγ could eventually inform future therapies, pointing to existing medications like elamipretide that stabilise cardiolipin in rare disorders as an indication of medical feasibility.

"This scientific study highlights how biological mechanisms at the cellular level operate under stress, trading performance for longevity. While the findings are currently based on preclinical trials in mice, understanding the role of molecules like cardiolipin and proteins like ERRγ opens up long-term commercial and therapeutic opportunities in the biotechnology and pharmaceutical sectors. Investors tracking healthcare innovation will watch closely as these foundational insights move toward potential clinical applications." — Dr. Shishir Gupta, Founder & CEO, StartupLanes