Shift Work Impairs Muscle Clocks, Potentially Speeding Up Age-Related Decline

Muscle cells have their own circadian clocks, and research shows that disrupting these clocks, such as through shift work, can accelerate aspects of the aging process.

A study published in Proceedings of the National Academy of Sciences adds to growing evidence of the negative health effects of shift work. Researchers from King’s College London found that muscle cells contain an internal clock that regulates protein turnover, which is crucial for muscle growth and repair. This clock helps break down damaged proteins at night, allowing muscles to recover during rest.

Disrupting this muscle clock was linked to sarcopenia, the age-related loss of muscle mass, suggesting that circadian rhythm disruption, such as in shift work, may accelerate muscle aging.

The team used zebrafish in their research—an ideal model due to their genetic similarity to humans (up to 70 %) and transparent bodies that allow real-time observation of muscle activity.

To investigate the impact of circadian disruption on muscle cells, we impaired the muscle clock function in zebrafish by overexpressing a malfunctioning clock protein. We then monitored the fish for two years, comparing them to healthy controls.”

Jeffrey Kelu, Study Lead Author and Research Associate, King’s College London

Kelu said, “While no significant differences in muscle size were observed at younger ages – six months and one year–fish lacking a functional muscle clock showed clear signs of premature ageing at two years. They were shorter, weighed less, swam less frequently, and at slower speeds. These are hallmarks of sarcopenia and overall decline in mobility, which has been reported in shift workers.”

To better understand the mechanisms at play, the researchers examined protein turnover—a process essential for preserving muscle mass and often impaired with age. They discovered that during nighttime rest, the muscle’s internal clock helps break down damaged proteins that build up throughout the day due to physical activity.

This “nocturnal clearance” was found to be crucial for maintaining healthy muscle function. When the muscle clock was disrupted, as seen in aged fish and potentially in shift workers, defective proteins accumulated, contributing to faster muscle deterioration.

In the UK, approximately four million shift workers play a vital role in keeping businesses and emergency services operational around the clock. Our study provides further evidence that the disruption of circadian rhythms in shift workers compromises multiple aspects of health. Understanding how circadian disruption contributes to sarcopenia is essential for developing strategies to improve the health and well-being of shift workers.”

Jeffrey Kelu, Study Lead Author and Research Associate, King’s College London

Kelu remarked, “Our findings highlight the possibility of using circadian biology to develop treatments aimed at preventing muscle decline in shift workers. Preclinical studies using drugs to modulate specific clock proteins are currently underway. This paves the way for future therapies that could improve ageing in shift workers.”

“This work shows how studying something as complicated as muscle growth in a simple system, like little fish larva, can really teach us something. Of course, someone then has to check if it’s also true in people – but at least the fish show us where to look,” noted Co-author Professor Simon Hughes, an expert in developmental cell biology.