Impact of Circadian Disruption on Muscle Health in Shift Workers

A recent study reveals that the internal circadian clocks within muscle cells play a crucial role in maintaining muscle health and may accelerate aging processes for individuals engaged in shift work. Published in the Proceedings of the National Academy of Sciences, the research highlights the detrimental effects that shift work can impose on overall health.

The research team from King's College London has discovered that muscle cells possess their own intrinsic timekeeping mechanisms that regulate the turnover of proteins, affecting both muscle growth and functionality. During nighttime, these muscle clocks initiate the breakdown of defective proteins, thus aiding in muscle replenishment while the body is at rest.

Disruption of this intrinsic muscle clock has been linked to sarcopenia, the age-related decline in muscle mass and strength. This suggests that irregular circadian rhythms, particularly as experienced by shift workers, may expedite the aging process.

Utilizing zebrafish as a model organism, which share up to 70% of their genes with humans, researchers conducted an extensive study. Zebrafish are advantageous for laboratory studies due to their transparent bodies, allowing for easy observation of muscle fibers under a microscope.

In their investigation, the research team impaired muscle clock function in zebrafish by overexpressing a dysfunctional clock protein, observing the effects over a two-year period in comparison to healthy control fish. Initial observations at six months and one year showed no significant differences in muscle size. However, at the two-year mark, zebrafish lacking a functional muscle clock exhibited clear signs of premature aging, including reduced size, lower weight, decreased swimming frequency, and slower speeds. These characteristics are indicative of sarcopenia and decreased mobility, conditions often reported in shift workers.

To delve deeper into the underlying mechanisms, researchers focused on protein turnover, a fundamental process for sustaining muscle mass that often deteriorates with aging. Their findings indicated that during periods of rest at night, the muscle clock regulates the degradation of defective muscle proteins that accumulate throughout the day due to physical activity.

This nocturnal clearance is vital for preserving muscle function. The researchers concluded that the build-up of defective proteins could drive the accelerated muscle deterioration observed in aged zebrafish with dysfunctional muscle clocks, as well as in shift workers.

In the UK, approximately four million individuals participate in shift work, playing essential roles in maintaining business operations and emergency services around the clock. The study emphasizes that disruption of circadian rhythms in these workers adversely affects various aspects of health.

Understanding the role of circadian disruption in sarcopenia is critical for developing effective strategies to enhance the health and well-being of shift workers. The research team suggests that insights from circadian biology could inform the development of treatments aimed at mitigating muscle decline in this population. Current preclinical studies are exploring the potential of drugs that modulate specific clock proteins, paving the way for future therapeutic interventions that may improve aging outcomes in shift workers.

Professor Simon Hughes, a co-author of the study and an expert in developmental cell biology, remarked on the significance of using simpler biological systems, such as zebrafish larvae, to gain insights into complex processes like muscle growth. He noted that while further research is needed to confirm these findings in humans, the zebrafish model offers valuable guidance for future investigations.