Muscle cells possess internal circadian clocks, finely tuned biological systems that regulate various cellular processes. According to recent research, disrupting these clocks, as often occurs with shift work, can significantly accelerate the ageing process. This study, published in the Proceedings of the National Academy of Sciences (PNAS), adds to a growing body of evidence linking irregular work schedules with long-term health impacts. The findings reveal that muscle clocks are crucial in maintaining muscle health by regulating protein turnover, a process critical for muscle growth, repair, and function. When this internal timing is disturbed, it can lead to premature muscle decline, echoing the effects of natural ageing.
The research, conducted by a team at King’s College London, highlights the critical function of these muscle clocks in coordinating the nightly breakdown and replenishment of defective proteins. During rest periods, muscle cells activate specific pathways to clear out damaged proteins that accumulate throughout the day due to physical stress and everyday wear. This nightly ‘housekeeping’ is essential for maintaining muscle strength and mass, as it clears cellular debris and ensures the continued function of muscle fibres. Disruption of this nocturnal process, as seen in shift workers, compromises this essential repair cycle, potentially accelerating the onset of sarcopenia – the age-related loss of muscle mass and strength.
To investigate this connection, the researchers turned to zebrafish, a popular model organism in biological studies. Zebrafish share about 70% of their genetic material with humans, making them an excellent choice for exploring fundamental biological processes. Their transparency as larvae allows for direct observation of muscle fibres under a microscope, providing a unique window into the cellular changes driving muscle health and decline. By impairing the muscle clocks in these fish through the overexpression of a malfunctioning clock protein, the researchers could simulate the long-term effects of circadian disruption.
Lead author Jeffrey Kelu, a King’s College London research associate, described the experimental approach: “We monitored these genetically altered zebrafish over two years, comparing them to healthy controls. No significant differences in muscle size or function were observed in the early stages of life – at six months and one year. However, by the two-year mark, the fish with disrupted muscle clocks displayed clear signs of premature ageing. They were smaller, weighed less, swam less frequently, and moved more slowly, all hallmarks of sarcopenia and overall physical decline – a pattern also seen in human shift workers.”
The study also uncovered the underlying mechanisms contributing to this accelerated ageing. The muscle clock is critical for managing protein turnover, a process essential for muscle maintenance. It activates the breakdown of defective muscle proteins during rest, preventing the accumulation of cellular damage. When this clock is disrupted, the faulty proteins remain, gradually undermining muscle function and accelerating physical decline. This insight explains why muscle deterioration occurs more rapidly in those with irregular work schedules.
Dr Kelu emphasised the broader implications of this work: “In the UK, approximately four million shift workers are essential to keeping businesses, healthcare, and emergency services running around the clock. Our study adds to the growing understanding that the disruption of circadian rhythms can have widespread health impacts, particularly on muscle health. This knowledge is crucial for developing strategies to support the long-term well-being of shift workers.” Looking ahead, the researchers are exploring potential treatments aimed at countering these effects. Preclinical studies are underway, investigating drugs that could modulate specific clock proteins, potentially slowing or reversing muscle decline in those whose work patterns disrupt their natural biological rhythms.
More information: Jeffrey Kelu et al, Muscle peripheral circadian clock drives nocturnal protein degradation via raised Ror/Rev-erb balance and prevents premature sarcopenia, Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.2422446122
Journal information: Proceedings of the National Academy of Sciences Provided by King’s College London
