How can shift work impact muscle health and aging?
The impact of circadian disruption on muscle health and aging has been uncovered.
A research team at King’s College London (UK) has uncovered the intrinsic and extrinsic effects that circadian disruption can have on muscle health and aging. This disruption, seen with shift work, can affect protein turnover and contribute to muscle wasting. A better understanding of these impacts enables strategies for improving health in shift workers to be developed.
There is growing evidence of the damage shift work can have on health and aging, due to the disruption of the circadian rhythm – the body’s internal clock. This disruption can lead to muscle wasting and age-related muscle loss, known as sarcopenia.
Muscle cells have their own circadian clocks that can be disrupted. However, the intrinsic and extrinsic effects of circadian disruptions on muscle cells, as well as the mechanistic basis of sarcopenia, are not well understood.
With this in mind, the team turned to zebrafish, which share up to 70% of genes with humans. “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,” commented lead author Jeffrey Kelu.
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The transparent bodies of the zebrafish allowed their muscles to be easily observed under the microscope, with the team finding that younger zebrafish, less than 1 year old, had no significant difference in muscle size. However, at 2 years old, zebrafish with impaired muscle clock function showed signs of early-onset sarcopenia. These zebrafish were found to be shorter, weigh less, and swim less frequently and at lower speeds. This decline in mobility has also been reported in shift workers.
To further investigate the intrinsic effects, the team investigated protein turnover, an essential process for maintaining muscle mass. This revealed that during rest at night, the muscle clock regulates degradation of defective muscle proteins through the upregulation of ubiquitin-proteasome systems and autophagy.
This nocturnal proteolysis is essential for clearing defective muscle proteins that accumulate throughout the day and preserving muscle function. Additionally, this observation suggests that defective proteins may drive sarcopenia in zebrafish with impaired muscle clock function and 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,” concluded Kelu.
