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They explain how working shifts accelerates aging

They explain how working shifts accelerates aging

Muscle cells contain their own clocks, and disrupting them with shift work can have a profound impact on aging, according to new research published in the Proceedings of the National Academy of Sciences (PNAS), adding to growing evidence of the health risks of shift work.

The study reveals how muscle cells possess an intrinsic timing mechanism that regulates protein turnover, modulating muscle growth and function. At night, the muscle clock triggers the breakdown of defective proteins, restoring muscles while the body rests.

Disruption of this intrinsic muscle clock has been associated with the muscle decline observed with age, known as sarcopenia. This suggests that disruption of circadian rhythms, such as occurs with shift work, accelerates the aging process.

The scientists used zebrafish in the research, which are commonly used in biological studies. Zebrafish share up to 70% of their genes with humans , making them easy to modify in the lab, and their transparent nature makes their muscles easy to observe under a microscope.

Lead author Jeffrey Kelu, a research associate at King's College London , explains: "To investigate the impact of circadian disruption on muscle cells, we disrupted muscle clock function in zebrafish by overexpressing a faulty clock protein. We then monitored the fish for two years, comparing them with healthy controls."

While no significant differences in muscle size were observed at younger ages (six months and one year), the fish without a functional muscle clock showed clear signs of premature aging at two years of age. They were shorter, weighed less, swam less frequently, and swam at slower speeds. These are hallmarks of sarcopenia and the general impairment of mobility that has been reported in shift workers.

To understand the mechanism, the researchers studied protein turnover, an essential process for maintaining muscle mass that is often impaired with aging.

They demonstrated that, during nighttime rest, the muscle clock regulates the breakdown of defective muscle proteins, which accumulate throughout the day due to use.

The study demonstrated that this " nightly cleanup " is essential for preserving muscle function. Therefore, the accumulation of defective proteins could drive the accelerated muscle decline observed in aged fish with a dysfunctional muscle clock and in shift workers.

"Our study provides further evidence that disrupted circadian rhythms in shift workers compromise multiple aspects of health," Kelu said.

The findings highlight the potential for using circadian biology to develop targeted treatments to prevent muscle deterioration 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 aging in shift workers.

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