Muscle cells have their own internal clock, and according to new research, disrupting this clock through shift work can have profound effects on the aging process. A study published in the Proceedings of the National Academy of Sciences (PNAS) provides further evidence of the harmful effects of shift work on health.

Disrupted Muscle Clock in People Who Work Shifts

The team at King’s College London has discovered that muscle cells have their own time-measuring mechanism that regulates protein turnover and thus controls muscle growth and function. At night, the muscle clock activates the breakdown of defective proteins, thereby regenerating the muscles while the body rests. A change in this internal muscle clock has been linked to age-related muscle loss, known as sarcopenia. This means that a disruption of the circadian rhythm, as occurs in shift work, accelerates the aging process.

The scientists used zebrafish, which are often used in biological studies, for their research. Zebrafish share up to 70% of their genes with humans, are easy to modify in the laboratory, and are transparent, allowing their muscles to be easily observed under a microscope. Lead author Jeffrey Kelu, a research fellow at King’s College London, said: “To investigate the effects of circadian rhythm disruption on muscle cells, we disrupted the function of the muscle clock in zebrafish by overexpressing a defective clock protein. We then observed the fish for two years and compared them with healthy control animals.

While no significant differences in muscle size were observed at younger ages (six months and one year), fish without a functioning muscle clock showed clear signs of premature aging at two years of age. They were shorter, weighed less, swam less frequently, and swam more slowly. These are typical characteristics of sarcopenia and a general decline in mobility, which has also been observed in shift workers.” To understand the underlying mechanism, the researchers examined protein turnover, a process essential for maintaining muscle mass that is often impaired with age. They showed that during nighttime rest, the muscle clock regulates the breakdown of defective muscle proteins that accumulate due to use during the day.

Circadian Biology for the Development of Treatments to Prevent Muscle Loss in Shift Workers

The study showed that this “nighttime clearance” is essential for maintaining muscle function. The accumulation of defective proteins could therefore cause accelerated muscle breakdown in old fish with a disrupted muscle clock and in shift workers. Dr. Kelu said: “In the UK, around four million shift workers play a vital role in keeping businesses and emergency services running around the clock. Our study provides further evidence that disruption of the circadian rhythm in shift workers affects multiple aspects of health. According to the researchers, understanding how circadian disruption contributes to sarcopenia is critical for developing strategies to improve the health and well-being of shift workers.

The findings highlight the potential of using circadian biology to develop treatments to prevent muscle loss in shift workers. Preclinical studies are currently underway with drugs that modulate specific clock proteins. This paves the way for future therapies that could improve the aging process in shift workers. Co-author Professor Simon Hughes, an expert in developmental cell biology, added: “This work shows how studying something as complex as muscle growth in a simple system such as small fish larvae can really teach us something. Of course, we still need to verify whether this also applies to humans – but at least the fish are showing us where to look.”