Loss of muscle strength or weakness is associated with poor outcomes for aging and patients with a number of chronic diseases. In this session, I will present data to support the concept that one mechanism for weakness emerges from disruption of the circadian, or molecular clock mechanism in skeletal muscle. The molecular clock is comprised of a core set of genes that function as a self-sustaining 24hr feedback loop. Beyond timekeeping, the molecular clock has a critical function in regulating a daily cell-specific transcriptional program. Studies from our lab, and others, have shown that targeted disruption of the molecular clock only in skeletal muscle is sufficient to induce muscle weakness defined by reduced force normalized for cross-sectional area . Our current work is focused on two areas: 1) We are working to define the skeletal muscle specific transcriptional landscape directed by the core clock factors, BMAL1:CLOCK. 2) We are using the transcriptomic analyses to guide our analysis of muscle structure and sarcomeric protein expression. To date, we have identified the muscle specific transcription factor, MYOD1 as key transcription factor linking the ubiquitous molecular clock to a daily muscle specific transcriptional program. We have also found that loss of clock function leads to altered expression of important sarcomeric genes that contribute to muscle structure. These results define a link between molecular clock disruption and muscle weakness and suggest a potential to target the muscle clock in conditions of weakness with aging and chronic diseases.