The body's internal clock, known as the circadian rhythm, not only regulates sleep patterns but also influences how quickly muscles heal. A study by Northwestern Medicine, published in Science Advances, reveals that muscle injuries in mice heal faster during their natural waking hours.
Clara Peek, senior author and assistant professor at Northwestern University Feinberg School of Medicine, suggests that these findings could have implications for shift workers and help understand the effects of aging and obesity. The research may also explain how disruptions like jetlag and daylight saving time affect muscle recovery.
Peek explained, "In each of our cells, we have genes that form the molecular circadian clock. These clock genes encode a set of transcription factors that regulate many processes throughout the body and align them with the appropriate time of day."
Previous research from Peek's laboratory showed that mice regenerate muscle tissues faster when damage occurs during their normal waking hours. In contrast, healing is slower when injuries happen during usual sleeping hours.
In this study, Peek and her team performed single-cell sequencing on injured and uninjured muscles in mice at different times. They discovered that the time of day affects inflammatory response levels in stem cells. This signaling to neutrophils—the innate immune cells involved in muscle regeneration—was stronger right after injury when it occurred during wake periods.
The study also found that the muscle stem cell clock influences post-injury production of NAD+, a coenzyme crucial for energy creation and metabolic processes. Using a genetically modified mouse model to boost NAD+ production specifically in muscle stem cells demonstrated its role in promoting inflammatory responses and neutrophil recruitment for muscle regeneration.
These findings are particularly relevant for understanding circadian rhythm disruptions linked to aging and obesity. Peek noted, "Circadian disruptions linked to aging and metabolic syndromes like obesity and diabetes are also associated with diminished muscle regeneration."
Looking ahead, Peek's team aims to identify how NAD+ induces immune responses and how these responses change in disease conditions. She emphasized the significance of exploring cell-cell interactions under stress conditions as an exciting new frontier.
The study received support from National Institutes of Health grants R01DK123358, P30DK020595, K08 AR081391, 5P01AG049665-09, T32 HL076139-11, along with additional funding from the U.S. Department of Veterans Affairs via grant IK6 RX003351.