Senescence-induced impairment of muscle regeneration during aging or in progeria models has been explained by persistent P38 MAPK activity, downregulation of Slug, a member of the Slug/Snail superfamily of zinc-finger transcriptional factor, downregulation of the cell surface protein CDON [52], reduced mitophagy, TGF-β–induced SMAD3 activation, and over-activation of Notch [53,54], all promoting stem cell exhaustion by increased senescence [22,23,55]. The gene discussed is SMAD3; the disease is progeroid syndrome.