Transcriptional remodeling of human skeletal muscle following sleep restriction in postmenopausal women.

Sleep is a critical regulator of metabolic health, but its impact on skeletal muscle remains underexplored. Given the muscle's pivotal role in glucose metabolism, energy homeostasis, and immune signaling, understanding how insufficient sleep affects global transcriptomic responses in skeletal muscle is of significant interest. In a randomized crossover design, skeletal muscle biopsies were collected from healthy postmenopausal women following four nights of habitual or restricted sleep (40% reduction). RNA-seq was performed on seven paired samples and analyzed using differential expression (DE), gene correlation, pathway enrichment, and transcription factor motif analysis. Global DE analysis revealed modest transcriptomic shifts, with nine genes consistently altered across multiple DE methods. Gene set enrichment analysis showed upregulation of oxidative phosphorylation and myogenesis pathways and downregulation of immune and inflammatory signaling during sleep restriction. Differential correlation analysis identified substantial reorganization in gene coexpression networks, particularly within RNA degradation and ribosomal pathways. Transcription factor and motif analyses suggested Yin Yang (YY1) as a possible key mediator of transcriptional reprogramming during sleep restriction. Motif analysis confirmed enrichment of