Clock Gene Expression Modulation by Low- and High-Intensity Exercise Regimens in Aging Mice

The circadian rhythm controls the sleep/wake cycle and a wide variety of metabolic and physiological functions. Clock genes regulate it in response to both external and endogenous stimuli, and their expression may change because of aging, leading to an increased risk of health problems. Despite the well-described benefits of physical exercise as a circadian synchronizer, there is a lack of literature regarding the role of chronic exercise intensity in clock gene expression during aging. This article aims to analyze the differential expression of genes that regulate the biological clock under the effects of variable-intensity aerobic swimming training in aging mice, determining whether these exercise regimens interfere with the genomic regulation of the circadian rhythm. For this purpose, the mice were exposed to low- and high-intensity exercise and had their heart and gastrocnemius tissues molecularly analyzed by cDNA synthesis and qPCR to determine the expression levels of the selected genes: <i>Clock</i>, <i>Arntl</i>, <i>Per1</i>, <i>Per2</i>, <i>Cry1</i>, <i>Cry2</i>, and <i>Nr1d1</i>. The results showed that low-intensity exercise, performed at workloads below the anaerobic threshold, significantly changed their expression in the gastrocnemius muscle (<i>p</i> < 0.05), while high-intensity exercise had no statistically significant effects (<i>p</i> > 0.05), with the heart being immune to exercise influence except when it comes to the <i>Per1</i> gene, for which expression was increased (<i>p</i> = 0.031) by low-intensity exercise. Additionally, both body weight and lactate thresholds had no change during the experiment (<i>p</i> > 0.05), while the maximum supported workload was maintained for high-intensity exercise (<i>p</i> > 0.05) and increased for low-intensity exercise (<i>p</i> < 0.01), with the control group experiencing a decay instead (<i>p</i> < 0.05). Thus, the present study highlights the importance of chronic exercise in modulating clock genes and opens exciting possibilities for circadian medicine, such as improvements in exercise capacity, heart condition, and lipid metabolism for subjects of low-intensity regimens.