Presentation: 2025 ND EPSCoR Annual conference 

October 21, 2025, NDSU Memorial Union, Fargo, North Dakota

Decoding Muscle Stem Cells in Accelerated and Biologically Aged Mouse Models

Aging is associated with a progressive decline in the body’s capacity to maintain its physiological functions. One of the tissue systems that is severely affected during aging is skeletal muscle. Tissue resident skeletal muscle stem cells, also known as satellite cells (SCs) play a crucial role maintaining tissue homeostasis and facilitating tissue regeneration and repair following an injury. However, with advancing age, the number of SCs diminishes, and their regenerative potential becomes compromised. This project aims to elucidate molecular mechanisms disrupted in aging stem cells. We use an accelerated aging model of Hutchinson Gilford Progeria Syndrome (HGPS), caused by a point mutation in the LMNA gene, and compare their SCs with those of biologically aged mice. Our objective is to identify genomic and epigenetic alterations associated with aging and we hope to address them for potential therapeutic interventions. Our data indicate that genes involved in apoptosis, metabolic pathways, and cellular stress responses are differentially expressed with age. Notably, we observed a global reduction in histone acetylation levels at histone H3 lysine 14 (H3K14ac) in SCs from both accelerated and biologically aged mice. Treatment with the histone deacetylase inhibitor Trichostatin A (TSA) resulted in enhanced muscle regeneration following injury, highlighting a promising epigenetic target for restoring muscle function in aging.