Dissecting Muscle Stem Cell Aging Through Integrative Genomic Analysis

During aging, there is a progressive loss of volume and function in skeletal muscle that impacts mobility and quality of life. The repair of skeletal muscle is regulated by tissue resident stem cells called satellite cells (MuSCs), but in aging, MuSCs decrease in numbers and regenerative capacity. The transcriptional networks and epigenetic changes that confer diminished regenerative function in MuSCs as a result of natural aging are partially understood. Herein, an integrative genomics approach was utilized to profile MuSCs from young and aged animals before and after injury. Integration of these datasets revealed aging impacts multiple regulatory changes through significant differences in gene expression, metabolic flux, chromatin accessibility and patterns of transcription factor (TF) binding activities. Collectively, these datasets facilitate a deeper understanding of the regulation tissue resident stem cells utilize during aging and healing.