This study investigated the influence of the circadian rhythm on muscle repair. Using single - cell sequencing in mice, the researchers found that the time of muscle injury affects the inflammatory response in muscle stem cells. The circadian clock in muscle stem cells regulates muscle repair by controlling NAD+ production. An increase in NAD+ can induce an inflammatory response and neutrophil recruitment, promoting muscle regeneration. The research also reveals the significance of circadian rhythm in muscle repair, providing insights into the negative impacts of circadian rhythm disruptions on muscle repair ability, especially in relation to aging, obesity, and diabetes. This study offers a theoretical basis for developing new therapeutic strategies to improve muscle repair and addresses the health challenges associated with circadian rhythm disorders.
In the hustle and bustle of modern life, many of us have experienced the lingering muscle soreness after a late - night workout or a strenuous activity followed by a sleepless night. Ever wondered why that is? Or why athletes seem to bounce back more quickly from early - morning training sessions compared to those grueling late - night workouts? The answers might lie deep within our bodies, in an internal timekeeper known as the circadian rhythm.
Recently, a research report titled "Immunomodulatory role of the stem cell circadian clock in muscle repair" was published in the international journal Science Advances. Scientists from institutions such as the Feinberg School of Medicine at Northwestern University in the United States have made a fascinating discovery: the repair rate of our body's muscles is significantly influenced by the circadian rhythm. This research not only serves as a wake - up call for night owls but also holds the potential to open new doors in addressing the challenges of aging and obesity.
DOI: 10.1126/sciadv.adq8538
The circadian rhythm is a natural, periodic physiological regulation mechanism within living organisms. It governs various aspects of our lives, including sleep, eating patterns, body temperature, and even our mood. In recent years, the scientific community has gradually uncovered that the circadian rhythm is also intricately linked to tissue repair and regeneration. Previous studies have shown that in mice, when muscle tissue is injured during their normal waking hours, the regeneration process is more rapid. Conversely, when the injury occurs during their sleep time, the healing process slows down considerably. The underlying reasons for this phenomenon have long remained a mystery, until a series of elaborate experiments recently shed light on the mechanisms by which the circadian rhythm affects muscle repair.
Uncovering the Mechanism: How Circadian Rhythm Regulates Muscle Stem Cells
In this study, the research team utilized single - cell sequencing technology to analyze the changes in gene expression of muscle stem cells in mice at different times after injury. The results revealed that the time of injury has a profound impact on the level of the inflammatory response in muscle stem cells. These inflammatory response signals, in turn, can regulate the behavior of neutrophils, which are the "first responders" in the muscle repair process. Neutrophils play a crucial role in clearing debris from damaged tissue and secreting cytokines that promote healing.
A pivotal turning point in the research came with the in - depth exploration of the "biological clock" within muscle stem cells. The researchers discovered that the circadian clock in muscle stem cells not only influences their own metabolic processes but also impacts muscle repair by regulating the production of nicotinamide adenine dinucleotide (NAD+). NAD+ is a coenzyme present in all cells and plays a vital role in energy metabolism and hundreds of other metabolic processes. Through the use of genetically modified mouse models, the researchers found that an increase in NAD+ levels can induce an inflammatory response and recruit neutrophils, thereby promoting muscle regeneration.
Fig. 1. Elevated expression of glycolysis and inflammation-related genes in SCs following CTX injury.
Specifically, after CTX injury, the expression levels of genes related to glycolysis and inflammation in stem cells increase. This finding not only explains why muscles injured during waking hours repair more quickly but also reveals how the circadian rhythm affects the healing process by regulating the metabolism and immune response of muscle stem cells. Professor Clara Peek, one of the researchers, pointed out that when injury occurs during the waking period of mice, the signal transmission between cells is more intense. This further validates that the regulatory effect of the circadian rhythm on muscle regeneration is achieved through the interaction between muscle stem cells and immune cells.
The Far - Reaching Impact: From Daily Life to Disease Treatment
The significance of this research goes far beyond explaining a simple physiological phenomenon. With the accelerating pace of modern life, more and more people are facing circadian rhythm disruptions. In Europe and the United States, frequent late-night work, shift work, jet lag, and daylight saving time adjustments are particularly common. These lifestyles and work arrangements often prioritize efficiency while neglecting the body's natural circadian rhythms. These factors can negatively impact muscle repair capacity. Furthermore, circadian rhythm disruptions are closely linked to metabolic diseases such as aging, obesity, and diabetes. People with these conditions often experience decreased muscle repair capacity, and this study offers a possible explanation: disrupted circadian rhythms may impair the metabolic function and immune regulation of muscle stem cells, thereby impacting muscle regeneration.
Fig. 2. Interactions between SCs and neutrophils during early muscle regeneration.
Now, researchers are exploring whether disrupted circadian rhythms contribute to impaired muscle repair in patients with these conditions and how this disruption interacts with the immune system. This discovery provides a theoretical foundation for developing novel therapeutic approaches targeting circadian rhythms and metabolic pathways to improve muscle repair and address the health challenges of aging and obesity, two of the most pressing issues facing European and American populations, particularly with their aging populations and high obesity rates.
Despite the remarkable achievements of this research, the work of the research team is far from over. In the next step, the researchers hope to further explore how NAD+ induces an immune response and how these responses change in disease states. The researchers stated that previous circadian rhythm studies have mostly focused on the molecular clocks of single cell types, often under non - stressful conditions. Now, they have the technological means to study the interactions between different circadian clocks under stress and regeneration conditions, which is undoubtedly an exciting new field.
This research not only deepens our understanding of the circadian rhythm but also serves as a gentle reminder to respect our body's natural rhythms. In Europe countries, where late - night work, long work hours, and irregular exercise schedules are common, this reminder is particularly relevant. The next time you're tempted to pull an all - nighter for work or an intense workout, spare a thought for your hard - working muscle stem cells that might be struggling to cope with this "unconventional" challenge. Perhaps adjusting our daily routines to align with the natural circadian rhythm is the best way to maintain good health and speed up the recovery process.