Age-induced gene expression in Thoroughbred horse skeletal muscle highlights genes that enhance muscle architecture and function.

Abstract: Early skeletal muscle development is critical for young racehorses, yet research on the transcriptional changes during this period is limited. Additionally, the impact of age on the transcriptional response to exercise training in equine athletes is not well understood. A transcriptome-wide analysis of differential gene expression in skeletal muscle was performed for five untrained Thoroughbred horses sampled at rest at two years old (UR2) and three years old (UR3). A total of 136 differentially expressed genes (DEGs) were identified, with 95 increased and 41 decreased in expression. GO enrichment analysis revealed that the DEGs were primarily associated with terms related to muscle assembly and system development, including Developmental process (GO:0032502), Anatomical structure development (GO:0048856), Actin cytoskeleton (GO:0015629), and Growth factor binding (GO:0019838). KEGG pathway analysis indicated that ECM-receptor interaction, Protein digestion and absorption, Focal adhesion, and PI3K-Akt signalling pathway were the significant functional pathways. Protein-protein interaction network and hub gene analyses identified seven key regulatory genes: COL1A1, COL1A2, COL3A1, S100A4, NOTCH1, THY1 and MT-ND2. In addition, the MSTN, COL4A1, COL4A2, SPEN, S100A4, NOTCH1, NOTCH3, and THY1 genes were found to play key roles in the functional development of skeletal muscle. This study provides insight into the transcriptional landscape of skeletal muscle development in young Thoroughbred horses. The period between two and three years of age represents a crucial stage in skeletal muscle adaptation in the juvenile horse, with a particular emphasis on muscle structural and functional integrity.