One twist to exercise could help reset a misaligned body clock — study

If you’re interested in completely reworking the body’s internal clock, you might be intrigued by medicinal fungi with transformative effects. If you’re just looking to tweak it, you may not need to go to such extremes. Research published on Monday suggests that exercise may give the body what it needs to fine-tune an internal clock that’s out of sync — as long as it happens at certain times.

The phrase “body clock” refers to one's circadian rhythm, a cycle of hormone release that responds to cycles of light and dark. That cycle influences when we naturally wake up, go to sleep, or feel hungry or burn calories.

The “master clock” that helps govern that rhythm is located in the brain, but there are thousands of peripheral clocks that linger in tissues throughout the body. This includes muscle cells, where certain genes are expressed at certain times in sync with the master clock.

A new study conducted in extremely athletic mice and electrically stimulated cells suggests that exercise (or muscle contractions) can help advance, or delay the circadian rhythms of peripheral clocks located in the muscle tissue. Timing, however, appears to be key.

When mice exercised five hours into their resting phase (which would be the middle of the night for humans), they “advanced” the phase of those muscular clocks by 100 minutes on average. When they exercised one hour before that resting phase ended (which would be an hour before wakeup time for humans) they delayed the phase of those muscular clocks by 62 minutes.

The authors write that exercise may serve as “a time cue for the muscle clock.” This suggests that using our muscles could be one way to help the body keep time, and reset those clocks if their typical rhythms become altered — something that' sometimes happens when we live out of sync with our natural rhythms (as night-shift workers often do).

The study was published in The Journal of Physiology

How exercise changes the muscle's clock – In the study, the team had 30 female mice (they run more than male mice do) run at moderate intensity for an hour during three periods of time: in the middle of their resting phase, at the end of their resting phase, and in the middle of their active phase.

The active phase is akin to the middle of the day for humans, but since mice are nocturnal, the active phase was the “dark period” in the study. Correspondingly, the lights were on during the resting phase.

Exercising in the middle of the resting phase caused that significant 100-minute phase advancement. Exercising towards the end of the resting period resulted in a phase delay. Importantly, exercising in the middle of the active period was not linked to any significant changes.

To test whether it was truly muscle contractions that cause these phase shifts, the team did a followup experiment in cells, which were electrically stimulated to mimic a real workout. To see how muscle contractions affect the overall clock's cycle, they chose to stimulate those cells when one transcription factor (Bmal1) was at it's the highest level and lowest level. Bmal1 is the core driver of the mammalian clock.

They found that the muscle contractions applied when Bmal1 was at the peak and trough levels caused a phase delay of 27.2 minutes and 64.6 minutes respectively. But when those contractions happened during a transition from a peak to a trough, it actually caused a phase advance of about 49.8 minutes.

Taken together, the researches demonstrated that muscle contractions can directly simulate changes in these muscular clocks, allowing extremely specific fine-tuning. Crucially, it's the muscle movements themselves that are making these changes happen, the study suggests.

Fixing a misaligned clock – There lots of ways these clocks might become misaligned.

On a macro-level, you might have a work schedule that’s not compatible with your preferred sleep and wake times. This type of circadian misalignment called “social jetlag.”

On a micro-level, your peripheral tissue clocks can become misaligned with the central one. In a 2015 mouse study, the misalignment of peripheral and central clocks (caused by eating during the “rest” phase) produced a metabolic-like syndrome. This is similar to what is seen in night shift workers who are forced to work against their circadian rhythms.

This study suggests that exercise might be one way of combating the latter type of circadian misalignment, especially when done at the right time.

"If this is replicated in humans it means that night-shift workers can use exercise to help shift their body clocks."

In a statement, a co-lead author of the study Christopher Wolf, a post-doctoral researcher at the University of Florida, noted that using exercise to tinker with the body clock could be particularly useful for night shift workers.

“If this is replicated in humans it means that night-shift workers can use exercise to help shift their body clocks,” Wolff said. “We may also be able to use exercise as a treatment for a 'body clock disorders' that can occur in many chronic diseases such as heart disease."

For now, that's a hypothesis — future research conducted on humans is needed to say for sure. Fom these findings alone, it’s hard to tell if resetting these peripheral clocks may actually influence the activity of the all-powerful master clock as well.

That said, there have been studies showing that our human circadian rhythms can be tinkered with using a combination of behaviors — especially exercise.

A study on 101 people conducted in 2019 found that when people exercised at 7 a.m., or some time between 1 p.m. and 4 p.m., advanced some participant's internal clock. These made those people feel alert earlier in the day. Meanwhile, exercising between 7 p.m. and 10 p.m. delayed the internal clock, making people feel more alert later in the day.

This study goes a bit deeper and shows the microscopic ways that exercise can reset the thousands of peripheral clocks within our muscles. To do so, we might just need to do one simple thing: use them.

Abstract: Exercise has been proposed to be a zeitgeber for the muscle circadian clock mechanism. However, this is not well defined and it is unknown if exercise timing induces directional shifts of the muscle clock. Our purpose herein was to assess the effect of one bout of treadmill exercise on skeletal muscle clock phase changes. We subjected PERIOD2::LUCIFERASE mice (n = 30F) to one 60‐minute treadmill exercise bout at three times of day. Exercise at ZT5, 5 h after lights on, induced a phase advance (100.2 ± 25.8 min; p = 0.0002), whereas exercise at ZT11, 1 h before lights off, induced a phase delay (62.1 ± 21.1 min; p = 0.0003). Exercise at ZT17, middle of the dark phase, did not alter muscle clock phase. Exercise induces diverse systemic changes so we developed an in‐vitro model system to examine effects of contractile activity on muscle clock phase. Contractions applied at peak or trough Bmal1 expression induced significant phase delays (applied at peak: 27.2 ± 10.2 min; p = 0.0017; applied at trough: 64.6 ± 6.5 min, p < 0.0001). Contractions applied during the transition from peak to trough Bmal1 expression induced a phase advance (49.8 ± 23.1 min; p = 0.0051). Lastly, contractions at different times of day resulted in differential changes of core‐clock gene expression demonstrating an exercise and clock interaction, providing insight into potential mechanisms exercise‐induced phase shifts. These data demonstrate that muscle contractions, as part of exercise, are sufficient to shift muscle circadian clock phase, likely through changes in core‐clock gene expression. Additionally, our findings that exercise induces directional muscle clock phase changes confirms exercise is a bone fide environmental time cue for skeletal muscle.