Disrupted muscle clocks linked to accelerated aging in shift workers

Muscle cells contain their own circadian clocks and disrupting them with shift work can have a profound impact on aging, according to new research.

A study published today in Proceedings of the National Academy of Sciences (PNAS) contributes to the growing evidence of the damage shift work has on health.

The King's College London team revealed how muscle cells have an intrinsic timekeeping mechanism that regulates protein turnover, modulating muscle growth and function. At night, the muscle clock activates the breakdown of defective proteins, replenishing muscles while the body rests.

Altering this intrinsic muscle clock was associated with muscle decline seen with age, known as sarcopenia. This implies that disrupting circadian rhythms, as with shift work, accelerates the aging process.

The scientists used zebrafish in the research – which are often used in biological studies. Zebrafish share up to 70% of genes with humans, which are easy to modify in the laboratory, and are transparent, so their muscles are easily observed under a microscope.

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.

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 aging 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."

Jeffrey Kelu, Lead Author, Research Associate, King's College London

To understand the underlying mechanism, the researchers investigated protein turnover, a process essential for maintaining muscle mass, often impaired with aging. They showed that during rest at night, the muscle clock regulates the degradation of defective muscle proteins, which accumulate throughout the day due to usage.

The study showed that this 'nocturnal clearance' is essential for preserving muscle function. So, the accumulation of defective proteins may drive the accelerated muscle decline observed in aged fish with a dysfunctional muscle clock and in shift workers.

Dr. Kelu said: "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 wellbeing of shift workers.

"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 aging in shift workers."

Co-author Professor Simon Hughes, expert in developmental cell biology, added: "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."