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Overview

1. The paradox of ageing muscles
2. Fast and slow muscle fibres
3. How cardiolipin supports mitochondria
4. How the researchers approached the question
5. The study's key findings
6. ERRγ: signalling between mitochondria and the nucleus
7. What the study means for people
8. What we can already do to support our muscles
9. Conclusion

As we grow older, our muscles often lose strength and mass. The characteristics of our muscle fibres and their energy supply also change. Understanding why this happens has long been a focus of scientific research. Much of this is basic research: work that helps us understand the processes behind staying mobile, physically capable and independent for as long as possible.

A newly published study in Nature Aging offers a possible explanation for why muscle composition changes with age. At its centre is cardiolipin, a little-known lipid in the inner membrane of our mitochondria. Mitochondria provide much of the energy our muscles need to work, and cardiolipin helps maintain their structure and function.

To understand these findings, we will take a closer look at the underlying biology. Step by step, we explain what the researchers discovered, why their results address an important question about muscle ageing, and what we can reasonably take from them. Basic research investigates fundamental cellular mechanisms. It does not immediately produce a treatment, but it can lay the foundations for future therapeutic approaches — which makes it worth understanding.

The paradox of ageing muscles

Our muscles perform different tasks throughout the day. During a walk, they work steadily over a longer period. When we lift a heavy box or catch ourselves after a stumble, they need to generate substantial force quickly. To meet these demands, muscles contain different fibre types that work together during most movements.

Slow type I fibres specialise in sustained activity. They contain many mitochondria and produce energy mainly through processes that use oxygen. Often called red muscle fibres, they tend to be particularly well developed in endurance athletes such as marathon runners. Fast type II fibres can deliver more power over a short period. Depending on the subtype, they make greater use of pathways that supply energy quickly without directly requiring oxygen. These fibres are important for sprinting and other rapid, forceful movements, although they generally fatigue more quickly.

Researchers have long known that fast fibres are often particularly affected by age-related loss. Slower, endurance-oriented fibres may therefore become relatively more prominent. At the same time, mitochondrial performance can decline. This creates a paradox: muscle composition shifts towards fibres that rely heavily on mitochondria, even as those mitochondria may be working less effectively.

Imagine a factory relying more heavily on a production line whose machinery is losing capacity. A higher proportion of endurance-oriented fibres does not automatically mean the whole muscle becomes better at sustained activity or performs more effectively.

This is where the new study comes in. It investigated how an age-related decline in the membrane lipid cardiolipin affects energy production and muscle fibre composition. The findings suggest that this remodelling could be a response to problems with energy supply. Muscle cells alter their metabolism and activate protective mechanisms to cope with stress in their mitochondria. However, a response that protects an individual cell does not necessarily preserve the strength of the whole muscle. This connection between cellular protection and altered muscle function is a central idea in the study.

Cardiolipin: a distinctive lipid in mitochondria

When we think of fats, food and the body's energy stores often come to mind. But some lipids primarily serve a different purpose: they form the membranes surrounding our cells and the structures inside them. Many of these are phospholipids, a group that includes cardiolipin.

Cardiolipin is found mainly in the inner mitochondrial membrane. This membrane is highly folded. The folds, called cristae, create a large surface area in a small space. The membrane houses the proteins of the respiratory chain. They work together through a series of steps to create the conditions needed to produce ATP — the molecule that makes energy immediately available to our cells.

The inner membrane is therefore a central site of energy production, and cardiolipin helps keep this working surface functional. It supports the membrane's shape and organisation and interacts with important energy-producing proteins. In the energy-factory analogy, cardiolipin is part of the infrastructure in which the machinery operates, rather than the fuel.

Changes in the amount or composition of cardiolipin can affect both membrane structure and energy production. This is particularly relevant to muscle cells, which need ATP for every movement.

How the researchers approached the question

The researchers wanted to answer a central question: does cardiolipin loss contribute to changes in muscle, or does it arise as a consequence of other changes?

First, the team examined muscle tissue from mice and people. They found evidence that cardiolipin levels or its production were altered or reduced in association with ageing and certain muscle diseases. This observation alone does not establish cause and effect. A plant with wilting leaves offers a useful comparison: we can see that something is wrong, but further investigation is needed to determine whether it lacks water, has damaged roots or faces another problem.

The researchers therefore intervened directly in cardiolipin production. In young mice, they switched off the Crls1 gene specifically in skeletal muscle. This gene contains the instructions for cardiolipin synthase 1, an enzyme that produces cardiolipin. Without these instructions, muscle cells cannot make enough of it. This allowed the team to induce cardiolipin deficiency and observe the resulting changes without waiting for the mice to age naturally. Additional experiments in laboratory-grown muscle cells helped them investigate the processes involved.

They then tested the reverse approach. In adult experimental mice, they restored Crls1 expression, allowing the enzyme to be produced again. If the muscle changes began to reverse, this would support the idea that cardiolipin deficiency had contributed to them. It also allowed the researchers to test whether the effects of the artificially induced deficiency were reversible in this model.

The study's key findings

Although the mice were still young, the induced cardiolipin deficiency triggered several changes also seen in ageing muscle. Both mitochondrial function and muscle characteristics were affected:

• Mitochondria worked less effectively. Their internal structure was disrupted and their capacity to produce energy declined.
• More reactive oxygen species were produced. These highly reactive molecules can damage cellular components when present in excess. They can also act as signals that trigger adaptation.
• Muscle fibres changed their characteristics. The pattern shifted from fibres that rely more heavily on rapid energy supply through glucose breakdown towards more oxidative, endurance-oriented fibres. This did not automatically improve endurance, because mitochondrial function was impaired at the same time.
• The animals developed muscle wasting and higher mortality. The artificially induced deficiency therefore had serious consequences that went beyond ordinary age-related changes.

The next step was particularly informative. When the researchers restored cardiolipin production in adult experimental mice, cardiolipin levels partially recovered. Muscle wasting began to reverse, and premature mortality was fully prevented in the model studied.

Why does this matter scientifically? If switching off a process causes problems and restoring it reduces those problems, this supports a causal contribution. In this mouse model, cardiolipin loss was more than a feature accompanying muscle changes: it contributed substantially to them.

ERRγ: signalling between mitochondria and the nucleus

How can a problem in mitochondria change the characteristics of a muscle cell? The researchers identified an important mediator: ERRγ, pronounced “ERR gamma”. Its full scientific name is estrogen-related receptor gamma. Despite its name, it is not a conventional oestrogen receptor.

ERRγ is a protein that influences which genes are expressed in the cell nucleus. Proteins with this role are called transcription factors. Think of genes as a collection of construction and operating instructions: ERRγ helps the cell make greater use of particular instructions, especially those governing metabolism.

When cardiolipin was deficient, impaired mitochondria produced more reactive oxygen species. These molecules can cause damage, but they also serve as chemical signals. In the model studied, this stress signal was translated through ERRγ into altered gene activity. Muscle cells took up more glucose and redirected its processing towards metabolic pathways that support their own antioxidant defences.

In simple terms, the response resembles a business reorganising its operations after technical problems and allocating more resources to protection and maintenance. Cells do this without making conscious decisions: chemical signals change which genes are active and how nutrients are processed.

The shift towards more oxidative muscle fibres could be part of this adaptation programme. Muscle remodelling would then be an active response to stress as well as a consequence of deterioration. Such a response may help cells cope with strain, but it does not automatically improve the performance of the whole muscle. It could also accompany the loss of characteristics needed for rapid, forceful movements.

What does the study mean for people?

The study reveals a connection that has previously been poorly understood: a component of the mitochondrial membrane can influence how muscle cells produce energy, respond to stress and change their characteristics. This raises new research questions, including whether the mechanism could eventually be targeted to preserve muscle function. For now, it does not establish a new treatment or supplementation recommendation. Four distinctions are particularly important.

1. The decisive evidence of causality comes from mouse models

The human muscle samples suggest that the mechanism could also be relevant to people. However, the decisive interventions took place in mice: cardiolipin production was deliberately interrupted and subsequently restored. This demonstrated that cardiolipin deficiency contributes to muscle changes in that model. Whether a corresponding intervention would be effective and safe in people was not tested.

2. Natural ageing is more complex than a single gene defect

Our muscles do not age for one reason alone. Physical activity, nutrition, hormonal changes, disease and nerve supply all interact. The capacity to repair muscle tissue may also change. Switching off Crls1 helps researchers study a particular mechanism. It is rather like removing one component from a machine to understand its function: useful, but insufficient to explain every change that occurs when the whole machine is used for decades.

3. The study does not establish a cardiolipin-based treatment for age-related muscle loss

The researchers enabled the experimental animals to produce the enzyme needed for cardiolipin synthesis again. They did not show that a food or food supplement achieves the same effect. The study therefore does not establish a product that restores cardiolipin in human muscle or reverses age-related muscle wasting. Those effects would need to be investigated separately in people.

4. More antioxidants do not automatically mean more protection

Reactive oxygen species have a dual role. In excess, they can damage cellular components. They also carry signals that help cells respond to challenges and initiate adaptations. The findings therefore challenge the simple idea that all these molecules should be suppressed as completely as possible. A stronger protective response within a cell is also different from taking additional antioxidants. This study provides no basis for recommending high-dose antioxidants to preserve muscle strength.

What we can already do to support our muscles

Although the new study does not yet translate into a treatment, established approaches can support muscle strength and physical function as we age. These recommendations come from the wider evidence base, rather than the cardiolipin experiment itself.

Regular resistance training

Progressive resistance training is one of the most effective established approaches to countering loss of muscle strength and mass. It provides mechanical and metabolic stimuli, activates adaptation processes and helps maintain the ability to perform everyday movements safely. A starting programme should suit your current ability and take any medical conditions into account.

Enough energy and protein

Muscles need energy and amino acids for remodelling as well as a training stimulus. Particularly in older age, unnoticed nutritional shortfalls, reduced appetite or a limited diet can contribute to muscle loss. If you have kidney disease or another relevant medical condition, discuss a higher protein intake with your doctor or a registered dietitian.

Endurance activity, everyday movement and recovery

Endurance activity and regular movement complement resistance training, support metabolic health and provide repeated signals for mitochondrial adaptation. Your body also needs sufficient sleep and recovery time for exertion to translate into adaptation.

Conclusion: muscle ageing involves more than wear and tear

Muscles may change with age partly because their cells are trying to cope with an impaired energy supply. The new study shows, in a mouse model, how cardiolipin loss places mitochondria under stress and triggers an adaptation programme through ERRγ. Both metabolism and muscle fibre characteristics change as a result.

A response that protects individual cells does not automatically preserve the strength of the whole muscle. This could help explain why ageing muscles develop more endurance-oriented characteristics while still losing performance.

The mechanism opens new avenues for research. Whether it can lead to a safe and effective treatment for people remains unresolved. For everyday life, the established foundations remain essential: regular resistance training, varied physical activity, enough energy and protein, and time to recover. These support the abilities you use every day, from climbing stairs to catching yourself after a stumble.

References

Finger F, Frost M, Watanabe S, et al. Mitochondrial membrane lipid cardiolipin controls fiber-type adaptations in aging muscle via estrogen-related receptor γ. Nature Aging. Published online 29 September 2026. doi: 10.1038/s43587-026-01227-7.

Fragala MS, Cadore EL, Dorgo S, et al. Resistance Training for Older Adults: Position Statement From the National Strength and Conditioning Association. J Strength Cond Res. 2019;33(8):2019–2052. doi: 10.1519/JSC.0000000000003230.

Dent E, Morley JE, Cruz-Jentoft AJ, et al. International Clinical Practice Guidelines for Sarcopenia (ICFSR): Screening, Diagnosis and Management. J Nutr Health Aging. 2018;22(10):1148–1161. PubMed.