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The Circadian Clocks That Control Exercise Response

How Time Determines Muscle Efficiency and Response

This article was originally published in the Northwestern University Feinberg School of Medicine News Center

Northwestern Medicine scientists have discovered circadian clocks in muscle tissue that control the muscle’s metabolic response and energy efficiency depending on the time of day. The finding sheds light on the time-of-day differences in muscle’s ability to adapt to exercise and use oxygen for energy.

All cells in the body, including those in muscle, contain a clock that regulates how cells adapt to changes in the environment and activity across the 24-hour day. Muscle cells are more efficient during normal waking hours, the study found.

“Oxygen and the internal clock are doing a dance together inside muscle cells to produce energy, and the time of day determines how well that dance is synchronized,” said Joseph Bass, MD, PhD, chief and Charles F. Kettering Professor of Endocrinology in the Department of Medicine. “The capacity for a cell to perform its most important functions, to contract, will vary according to the time of day.”

More research is needed before the finding can be translated into workout advice.

“We’re not saying we can tell athletes when they should work out,” said Bass, who is also a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “But in the future, perhaps, you may be able to take advantage of these insights to optimize muscle function.”

Clara Bien Peek, PhD, the first author and a research assistant professor of Medicine in the Division of Endocrinology, spearheaded the work on muscle and timing.

New Ways to Control Oxygen Response

“In the future, we may discover new ways to manipulate the oxygen response of the cell by resetting the clock,” Bass said. He noted drugs are available that can manipulate the internal clock in cells.

“If we can optimize muscle function,” he said, “It’s also a critical step in understanding how to impact glucose metabolism in diabetes.”

Diabetes is characterized by a failure of muscle to consume glucose, which in turn controls blood sugar levels.  Strengthening the muscle clock may provide a new way to eliminate excess glucose and treat diabetes.

The scientists tested their theories about the internal clock in muscle cells because those cells are particularly dependent on oxygen for contraction and metabolism.

“We wanted to determine the rules that interconnect clocks with the physiological use of oxygen,” Bass said. “We believe that studying muscle can provide us with the rules of how clocks govern response to oxygen, and we would like to test these principles in a variety of conditions.”

The research has implications beyond muscle cells because oxygen response is important in all cells. In particular, the deprivation of oxygen is a key factor in heart attacks and in cancer, in which the depletion of oxygen curiously enables cancer cells to grow.