Unraveling skeletal muscle senescence in an in vitro cell culture model.

INTRODUCTION

Skeletal muscles are crucial for voluntary movement, posture, breathing, joint stability, and therefore are essential for maintaining overall health and quality of life. Aging, sarcopenia, cancer, immobilization, and several muscle pathologies can have an impact on muscle function, and muscle cell senescence is associated with these conditions.

METHODS

Here we aimed to develop a primary cell culture model to study skeletal muscle cell senescence. We induced cell cycle arrest in cultured embryonic chick muscle cells using a low concentration of cytosine arabinoside (Ara-C) for 9 days.

RESULTS

Our results show that Ara-C was able to induce several cellular senescence-associated bone fide characteristics, including reduced cell proliferation, increased β-galactosidase expression, increased reactive oxygen species production (ROS), increased p53 and p21 expression, increased muscle fibroblast cell size and nuclei numbers, increased lysosomal activity, decreased muscle differentiation (decreased muscle fiber size and decreased desmin expression), and increased secretion of IL-6, TNFα and TGFβ. Interestingly, inhibition of fibroblast growth factor receptor recovers the AraC-induced senescent phenotype in myogenic cells.

CONCLUSION

This new experimental model could be used to deepen our understanding of the molecules and signaling pathways associated with the initiation and establishment of skeletal muscle senescence. Furthermore, this model could be used to test new drugs and therapeutic interventions aiming the amelioration of senescence-associated conditions.