Muscle recovery depends on time of day

The human body operates on an internal schedule, known as the circadian rhythm. This biological clock influences sleep, metabolism, and even muscle recovery. While most people associate circadian rhythms with sleep cycles, new research shows that these rhythms also affect how quickly injuries heal.

A study from Northwestern Medicine, conducted on mice, reveals that muscle injuries heal faster when they occur during the body’s natural waking hours.

These findings could have significant implications for shift workers, aging individuals, and those with metabolic disorders.

The study also raises important questions about how disruptions like jetlag and daylight saving time changes impact muscle recovery.

Faster recovery during active hours

The study, conducted on mice, shows that muscle injuries recover more quickly when they occur during active hours. Injuries during usual sleeping periods heal at a slower rate.

Clara Peek, assistant professor of biochemistry and molecular genetics at Northwestern University Feinberg School of Medicine, believes these findings could help shift workers and those experiencing aging-related muscle issues.

The study also highlights how disruptions such as jetlag and daylight saving time changes affect circadian rhythms. “In each of our cells, we have genes that form the molecular circadian clock,” Peek said.

“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. Things like sleep/wake behavior, metabolism, body temperature and hormones – all these are circadian.”

How time affects muscle recovery

Peek’s lab previously found that muscle tissues regenerate faster when damaged during natural waking hours.

To understand why, the researchers examined muscle stem cells at different times of the day. They used single-cell sequencing to analyze injured and uninjured muscle tissue.

The findings revealed that the inflammatory response in stem cells varies by time of day. These stem cells signal neutrophils, immune cells crucial to muscle recovery.

“We discovered that the cells’ signaling to each other was much stronger right after injury when mice were injured during their wake period,” Peek said.

“That was an exciting finding and is further evidence that the circadian regulation of muscle regeneration is dictated by this stem cell-immune cell crosstalk.”

Aging may slow muscle recovery

The research also uncovered the role of NAD+, a coenzyme essential for energy production and metabolism. The muscle stem cell clock influences NAD+ production after injury, which in turn affects immune responses.

To test this, the scientists used genetically modified mice with increased NAD+ production in muscle stem cells. They found that boosting NAD+ levels led to stronger inflammatory responses and improved muscle healing.

These findings may be crucial in understanding muscle recovery issues linked to aging and metabolic disorders. Peek believes circadian rhythm disruptions could explain slower healing in older individuals and those with obesity or diabetes.

“Circadian disruptions linked to aging and metabolic syndromes like obesity and diabetes are also associated with diminished muscle regeneration,” Peek said.

“Now, we are able to ask: do these circadian disruptions contribute to poorer muscle regeneration capacity in these conditions? How does that interact with the immune system?”

Future research directions

Peek and her team plan to explore the exact mechanisms by which NAD+ influences immune responses. They hope to uncover whether this process can be manipulated to improve muscle recovery in those affected by aging or metabolic disorders.

“A lot of circadian biology focuses on molecular clocks in individual cell types and in the absence of stress,” Peek said.

“We haven’t had the technology to sufficiently look at cell-cell interactions until recently. Trying to understand how different circadian clocks interact in conditions of stress and regeneration, is really an exciting new frontier.”

This research opens new possibilities for enhancing muscle repair by aligning treatment approaches with the body’s natural rhythms.

Optimizing recovery schedules and boosting NAD+ production could improve muscle healing. This study reveals how the body’s internal clock affects regeneration, offering new possibilities for better treatments.

Understanding these processes may help aging individuals, shift workers, and those with metabolic disorders recover faster and maintain stronger muscles.

The study is published in the journal Science Advances.

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