Zebrafish Study Finds Disrupted Muscle Clocks Accelerate Age-Related Decline

New research from King’s College London, published in the Proceedings of the National Academy of Sciences, demonstrates how disruption to the body’s internal clocks in muscle cells can accelerate age-related muscle loss, known as sarcopenia. The study highlights the negative health effects of shift work, which interferes with these natural rhythms.

Muscle cells possess their own circadian clocks that regulate the turnover of proteins, an essential process for maintaining muscle growth and function. During nighttime rest, this muscle clock triggers the breakdown of defective proteins, helping to restore muscle health. The research team found that when this intrinsic clock is disrupted, it leads to a buildup of damaged proteins and, over time, contributes to the muscle decline seen with ageing.

The scientists conducted their experiments using zebrafish, a model organism sharing substantial genetic similarity with humans. Zebrafish are transparent, allowing for easy observation of muscle tissues. To investigate the effects of circadian disruption, the scientists impaired the muscle clock by overexpressing a faulty clock protein in the fish. Over two years, they compared these fish to normal controls.

Initially, there were no noticeable differences in muscle size between the groups at six months and one year. However, by two years, fish with dysfunctional muscle clocks showed clear signs of premature ageing: they were shorter, weighed less, swam less often and at slower speeds-behaviors characteristic of sarcopenia and reduced mobility, similar to effects reported in human shift workers.

The study found that healthy muscle clocks ensure the removal of defective proteins during nighttime rest, a process termed “nocturnal clearance.” Without this clearance, damaged proteins accumulate, driving accelerated muscle decline. Lead author Jeffrey Kelu explained, “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,” Dr. Kelu added. The research suggests that targeting circadian biology could lead to new treatments to prevent muscle decline in shift workers, with preclinical studies exploring this possibility already underway.