Daylight and darkness influence the function of this internal “clock,” and disruption to our sleep-wake cycles can have health consequences, as studies have shown. These circadian rhythms influence functions ranging from sleep patterns to metabolizing food. They are controlled by several “clock” genes, the functioning of which can become dysregulated by altering sleep-wake cycles, as often happens in older people. A new study in mice has found that rather than being controlled entirely by a clock located in the brain, circadian rhythms are more complex and rely on cooperation between molecular clocks in the brain and muscle tissue to keep muscles healthy and functioning daily.
The study, which appears in Science, also suggests that manipulating these clocks by altering eating times could help protect muscle function in older people. The researchers used a mouse model Bmal1 knockout (KO), in which the expression of one clock gene, Bmal1, in the suprachiasmatic nucleus (SCN) the area of the brain that regulates circadian rhythms was prevented. However, in their model, they could reconstitute Bmal1 in tissues, including skeletal muscle.
At 26 weeks, the KO mice had reduced weight and muscle mass from 10 weeks and showed signs of damage to mitochondria in the muscles. However, when the researchers restored the expression of the gene in the muscle and brain in some mice, muscle mass and force were preserved. The researchers suggest that communication between the brain and muscle clocks is required to prevent premature muscle ageing.
Two-way communication between central and peripheral tissues has been reported previously, but this study shows how peripheral clocks in the skeletal muscle and the central clock signal to each other. As people age, the sleep cycles change, and people lose muscle mass.
For some older people, particularly those with neurodegenerative disorders such as Alzheimer’s disease, sleep patterns can become extremely irregular and disrupted. Animal studies have found that expression of many of the clock genes is reduced in the SCN as animals age, leading to disruption of circadian rhythms. Although there has been little research in this area, and these results are derived from animals, similar mechanisms may be in play in humans. However, this study has found that there may be a way to reinstate the functioning of the circadian clocks in the brain and muscles.
By implementing time-restricted feeding in old adult mice (66-74 weeks old), the researchers restored rhythmic gene expression in the muscles, which prevented the deterioration of muscle function. These findings help to explain some of the physiological changes that might be occurring as people age and time restricted eating may help correct this. Time-restricted eating, or intermittent fasting, has been shown to have some metabolic benefits, including weight loss and positive effects in nonalcoholic fatty liver disease, cancer, and cardiovascular disease.
