Inactivation of Myostatin Delays Senescence via TREX1-SASP in Bovine Skeletal Muscle Cells.

The myostatin () gene also regulates the developmental balance of skeletal muscle after birth, and has long been linked to age-related muscle wasting. Many rodent studies have shown a correlation between and age-related diseases. It is unclear how and age-associated muscle loss in other animals are related. In this study, we utilized gene-edited bovine skeletal muscle cells to investigate the mechanisms relating to and muscle cell senescence. The expression of was higher in older individuals than in younger individuals. We obtained consecutively passaged senescent cells and performed senescence index assays and transcriptome sequencing. We found that senescence hallmarks and the senescence-associated secretory phenotype (SASP) were decreased in long-term-cultured myostatin inactivated (MT-KO) bovine skeletal muscle cells (bSMCs). Using cell signaling profiling, was shown to regulate the SASP, predominantly through the cycle GMP-AMP synthase-stimulator of antiviral genes (cGAS-STING) pathway. An in-depth investigation by chromatin immunoprecipitation (ChIP) analysis revealed that influenced three prime repair exonuclease 1 () expression through the SMAD2/3 complex. The downregulation of contributed to the activation of the MSTN-SMAD2/3-TREX1 signaling axis, influencing the secretion of SASP, and consequently delaying the senescence of bSMCs. This study provided valuable new insight into the role of in cell senescence in large animals.