Critical biological processes are under control of the circadian clock. Disruption of this clock, e.g. during aging, results in increased risk for development of chronic disease. Exercise is a protective intervention that elicits changes in both age and circadian pathologies, yet its role in regulating circadian gene expression in peripheral tissues is unknown. We hypothesized that voluntary wheel running would restore disrupted circadian rhythm in aged mice. We analyzed wheel running patterns and expression of circadian regulators in male and female C57Bl/6J mice in adult (~4 months) and old (~18 months) ages. As expected, young female mice ran further than male mice, and old mice ran significantly less than young mice. Older mice of both sexes had a delayed start time in activity which likely points to a disrupted diurnal running pattern and circadian disruption. Voluntary wheel running rescued some circadian dysfunction in older females. This effect was not present in older males, and whether this was due to low wheel running distance or circadian output is not clear and warrants a future study. Overall, we show that voluntary wheel running can rescue some circadian dysfunction in older female but not male mice; and these changes are tissue dependent. While voluntary running was not sufficient to fully rescue age-related changes in circadian rhythm, ongoing studies will determine if forced exercise (e.g. treadmill) and/or chrono-timed exercise can improve age-related cardiovascular, skeletal muscle, and circadian dysfunction.

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Background and Objective: Skeletal muscle is critical for overall health and predicts quality of life in several chronic diseases, thus quantification of muscle mass and composition is necessary to understand how interventions promote changes in muscle quality. The purpose of this investigation was to quantify changes in muscle mass and composition in two distinct pre-clinical models of changes in muscle quality using a clinical dual X-ray absorptiometry (DEXA), validated for use in mice. Materials and Methods: Adult C57Bl6 male mice were given running wheels (RUN; muscle hypertrophy) or placed in hypobaric hypoxia (HH; muscle atrophy) for four weeks. Animals received weekly DEXA and terminal collection of muscle hind limb complex (HLC) and quadriceps weights and signaling for molecular regulators of muscle mass and composition. Results: HH decreased total HLC muscle mass with no changes in muscle composition. RUN induced loss of fat mass in both the quadriceps and HLC. Molecular mediators of atrophy were upregulated in HH while stimulators of muscle growth were higher in RUN. These changes in muscle mass and composition were quantified by a clinical DEXA, which we described and validated for use in pre-clinical models. Conclusions: RUN improves muscle composition while HH promotes muscle atrophy, though changes in composition in hypoxia remain unclear. Use of the widely available clinical DEXA for use in mice enhances translational research capacity to understand the mechanisms by which atrophy and hypertrophy promote skeletal muscle and overall health.