Formation of skeletal muscle fibers (myogenesis) during development and after tissue injury in the adult constitutes an excellent paradigm to investigate the mechanisms whereby environmental cues control gene expression programs in muscle stem cells (satellite cells) by acting on transcriptional and epigenetic effectors. Here we will review the molecular mechanisms implicated in the transition of satellite cells throughout the distinct myogenic stages (i.e., activation from quiescence, proliferation, differentiation, and self-renewal). We will also discuss recent findings on the causes underlying satellite cell functional decline with aging. In particular, our review will focus on the epigenetic changes underlying fate decisions and on how the p38 MAPK signaling pathway integrates the environmental signals at the chromatin to build up satellite cell adaptive responses during the process of muscle regeneration, and how these responses are altered in aging. A better comprehension of the signaling pathways connecting external and intrinsic factors will illuminate the path for improving muscle regeneration in the aged.

Work in the authors' laboratory was supported by MINECO, Spain (SAF2015-67369-R, “María de Maeztu” Programme for Units of Excellence in R&D MDM-2014-0370), AFM, MDA, Convenio UPF-CNIC, E-RARE, Fundació Marató TV3. JS is recipient of a Juan de la Cierva postdoctoral fellowship.