As we age or face conditions such as type 2 diabetes or cancer, the tiny energy factories in our muscles – mitochondria – begin to falter, leading to weakness and reduced mobility. However, exercise has been shown to stimulate proteins that help to maintain mitochondrial function, offering a promising strategy for preserving muscle health. New research reveals that physical activity can boost the efficiency of mitochondria and repair damage at the cellular level, offering potential treatments for ageing-related muscle decline.
Muscles rely on tiny energy factories called mitochondria. As you age or develop such conditions as type 2 diabetes, these cellular power plants break down, leaving you weaker and less mobile. Simple tasks become more difficult. The key is preserving these mitochondria to maintain strength. Now researchers have figured out how exercise and certain proteins could safeguard mitochondria, offering new ways to help muscles stay strong and healthy as we grow older or become sick.
“By studying specially bred mice and even fruit flies, we explored how exercise affects proteins that keep mitochondria strong. We found that working out boosted these powerhouses, improved their protein-making machinery and cut harmful signals. This means that exercise can help muscles to bounce back, paving the way for treatments that mimic these effects and improve muscle health in ageing or disease,” explains co-author Lykke Sylow, Associate Professor, Molecular Metabolism in Cancer and Ageing group, Department of Biomedical Sciences, University of Copenhagen, Denmark.
The powerhouses behind muscle strength
Mitochondria, often called the powerhouses of cells, convert the food we eat into usable energy. In skeletal muscle, these tiny organelles play a key role in maintaining strength and endurance. However, as we age or develop conditions such as sarcopenia or type 2 diabetes, the efficiency of mitochondria declines, leading to weaker muscles and reduced mobility.
“Muscle health is tightly linked to mitochondrial function, and we know that when these energy-producing organelles are not working properly, the effects are felt throughout the body – especially as we get older or in the presence of metabolic diseases,” Lykke Sylow comments.
A critical factor in mitochondrial health is the stability of mitochondrial RNA, which acts as a set of instructions for producing the proteins that mitochondria need to function. This process is supported by such proteins as steroid receptor RNA activator protein (SLIRP), which ensures that these instructions are preserved and properly used within muscle cells.
“Our cells have two genomes. The nuclear genome is present in the cell nucleus and is inherited from both the mother and father. In contrast, the mitochondrial genome is present only in the mitochondria and is inherited solely from the mother,” explains co-author Tang Cam Phung Pham, a postdoctoral researcher in the Molecular Metabolism in Cancer and Ageing group.
The fact that mitochondria have their own genome makes them uniquely susceptible to genetic mutations that can affect their function. This understanding highlights the importance of discovering how such factors as exercise can influence both the nuclear and mitochondrial genomes to improve mitochondrial health.
“When we started examining the molecular impact of exercise on muscles, we realised that certain proteins, such as SLIRP, seem to play a much more important role in maintaining mitochondrial function than previously understood. This was an exciting discovery that opened new avenues for research,” Tang Cam Phung Pham states.
A key to vitality
One of the most promising findings in recent years is the profound effect that regular exercise has on mitochondria. Exercise not only strengthens muscles but also enhances the number and efficiency of mitochondria, helping to offset the natural decline that occurs with age or chronic conditions. This connection between physical activity and mitochondrial health has become a major focus of research into healthy ageing.
“We were fascinated by how exercise could essentially rejuvenate mitochondria in skeletal muscle. Physical activity was clearly not just improving muscle strength but also directly affecting the organelles that power our muscles,” says Tang Cam Phung Pham.
By understanding how exercise interacts with proteins such as SLIRP to stabilise mitochondrial RNA, researchers hope to uncover new ways to boost mitochondrial health. These insights could lead to innovative treatments for preserving muscle function and overall vitality as we age.
“To determine how exercise affects the proteins that keep our muscle energy factories working, we studied mice with higher or lower levels of two key proteins, SLIRP and leucine-rich pentatricopeptide repeat-containing protein,” Tang Cam Phung Pham adds.
SLIRP’s role in exercise
The study focused on endurance exercises such as running to observe how mitochondria adapted to different protein levels and how muscle recovery occurred after exercise ended.
“To understand the role of the proteins, the first step was to knock them out in certain models, including mice and fruit flies. This enabled us to observe what happens when the protein is entirely absent,” Lykke Sylow points out.
For ethical reasons, human genes cannot be knocked out. However, human muscle samples were analysed to validate the results in a real-world context. This approach ensured that the observations were not limited to a single species but reflected broader biological principles.
“The mitochondria’s structure became highly distorted in the absence of SLIRP, revealing its critical role in maintaining both function and integrity during physical activity,” Lykke Sylow notes.
Exercise reverses mitochondrial damage
Advanced imaging techniques provided detailed views of mitochondrial structure under different conditions. Specialised equipment was used to measure energy production, highlighting how exercise influenced mitochondrial efficiency and overall function when the levels of SLIRP and leucine-rich pentatricopeptide repeat-containing protein were altered.
“What stood out was the coordination between the mitochondrial and nuclear genomes. When one failed, the other was disrupted, showing how deeply interconnected they are,” explains Lykke Sylow.
Combining data from multiple species and various techniques provided comprehensive understanding of how these proteins support mitochondrial health, emphasising their importance in maintaining muscle function through physical activity.
“Exercise can do more than just make you stronger; it can actually help to fix your muscles at a cellular level,” Lykke Sylow notes.
The study revealed that SLIRP is vital for keeping mitochondria healthy. Regular exercise boosts SLIRP levels, helping the mitochondria to function better and supporting overall muscle performance.
“What we thought – and we were very wrong – was that if we trained these mice, they would not be able to boost their mitochondria, their health or their functions. But it turned out they could,” Lykke Sylow adds.
Boosting the factory
Surprisingly, even when SLIRP was at a low level or missing, exercise helped muscles to adapt and improve. Mitochondria increased in number and efficiency, and harmful signals within the muscle cells were reduced. This adaptation occurred even in genetically modified mice, suggesting that exercise can overcome some genetic barriers to muscle health.
“What happens with exercise is that you get more mitochondria, they work better and they send fewer harmful signals to the muscle cells,” Lykke Sylow says.
One standout discovery was how dramatically the production of mitoribosomes – the structures that help mitochondria produce proteins – increased with exercise. This finding shows that even when certain processes are impaired, physical activity can drive powerful compensatory mechanisms to restore muscle function.
“The number of mitoribosomes doubles – it increases massively. But we do not yet understand what specific signals cause this,” Lykke Sylow explains.
Not just a fitness tool
The implications of the results extend beyond fitness. Enhancing mitochondrial function through exercise could help to treat or manage people with conditions such as type 2 diabetes and age-related muscle loss. It also opens the door for therapies targeting proteins such as SLIRP to boost energy production and maintain muscle health.
“If you can boost the factory that produces proteins from the mitochondrial RNA, you can overcome some very severe genetic disorders,” Lykke Sylow notes.
The study shows that regular activity enhances the role of SLIRP, a key protein for maintaining healthy mitochondria. In other words, exercise is not only preventive but can also help to restore muscle health.
“It is fascinating that muscles can adapt this way, even when essential genes that normally control these processes are missing. The ultimate goal is to determine what boosts mitochondria, even when genetics fails. And if we can understand that, it would be pretty significant,” Lykke Sylow remarks.
Thus, the study opens an exciting frontier in which physical activity is not just a fitness tool but a cornerstone for biological repair and resilience.
“The challenge now lies in decoding the precise mechanisms and translating these findings into actionable therapies for the people who need them most,” concludes Lykke Sylow.