Many processes in the body vary in a 24-hour rhythm called the circadian rhythm. These rhythms are controlled by molecular clocks, in organs such as the liver, in tissues such as skeletal muscle, and in the hypothalamus, a part of the brain. The clock in the hypothalamus is the central controller and keeps all the peripheral clocks in synch.
Exercise can reset circadian rhythms. Most scientists thought this process was mediated purely by inputs to the hypothalamus, which can alter the expression of genes in the central clock. Now researchers, from the Gladstone Institute of Cardiovascular Disease, the University of California, and Northwestern University, have found that exercise can also alter the expression of clock genes in the muscles themselves.
The research team, headed by Bruce Conklin, analysed the expression of a wide range of genes in human skeletal muscle biopsies. These biopsies were taken from both legs of four male volunteers, 6 and 18 hours after they had exercised only their right leg for half an hour.
To find out if the expression of different genes in skeletal muscle varied over time, the researchers assessed which genes were 'switched on or off' at different times of the day in the unexercised legs. They discovered hundreds of genes that increased or decreased their expression over time. By studying previously published results from similar experiments in mice, they found 44 genes that are regulated in a circadian rhythm in one or more mouse tissues and human skeletal muscle. These included some genes involved in the molecular clock, namely Per1, Per2 and Clock.
The team then went on to see if the timing of the expression of these genes could be altered by resistance exercise. They found that Per2 as well as two other clock genes, Cry1 and Bmal1, all increased their expression 6 hours after resistance exercise. In fact the expression levels of many of the genes that normally altered in a 24-hour cycle were affected by the exercise regime. Exercise increased the expression of genes that are normally 'switched off' in the morning, and reduced the expression of genes that are normally 'switched on' in the morning. In effect, exercise caused a phase shift in the expression of the genes, similar to winding on (resetting) the muscle clock.
"Our findings support the idea that peripheral clocks can regulate themselves independently of the clock in the hypothalamus" said Dr. Alex Zambon, Gladstone postdoctoral fellow and the lead author on the study. "If the central clock were responsible for the phase shifting, the same changes in gene expression would have occurred in both the control and exercised legs. While the central clock is still probably involved in the long-term effects of clock phase shifting in peripheral tissue, our evidence suggests that the skeletal muscle clock responds quickly to resistance exercise by regulating the transcription of specific clock genes."
This press release is based on the following article:
Time- and exercise-dependent gene regulation in human skeletal muscle
Alexander C Zambon, Erin L McDearmon, Nathan Salomonis, Karen M Vranizan, Kirsten L Johansen, Deborah Adey, Joseph S Takahashi, Morris Schambelan, Bruce R Conklin
Genome Biology 4(10):R61
To be published 25th September 2003
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