Role of damage and management in muscle hypertrophy: Different behaviors of muscle stem cells in regeneration and hypertrophy

So ichiro Fukada*, Takayuki Akimoto, Athanassia Sotiropoulos

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

36 Citations (Scopus)


Skeletal muscle is a dynamic tissue with two unique abilities; one is its excellent regenerative ability, due to the activity of skeletal muscle–resident stem cells named muscle satellite cells (MuSCs); and the other is the adaptation of myofiber size in response to external stimulation, intrinsic factors, or physical activity, which is known as plasticity. Low physical activity and some disease conditions lead to the reduction of myofiber size, called atrophy, whereas hypertrophy refers to the increase in myofiber size induced by high physical activity or anabolic hormones/drugs. MuSCs are essential for generating new myofibers during regeneration and the increase in new myonuclei during hypertrophy; however, there has been little investigation of the molecular mechanisms underlying MuSC activation, proliferation, and differentiation during hypertrophy compared to those of regeneration. One reason is that ‘degenerative damage’ to myofibers during muscle injury or upon hypertrophy (especially overloaded muscle) is believed to trigger similar activation/proliferation of MuSCs. However, evidence suggests that degenerative damage of myofibers is not necessary for MuSC activation/proliferation during hypertrophy. When considering MuSC-based therapy for atrophy, including sarcopenia, it will be indispensable to elucidate MuSC behaviors in muscles that exhibit non-degenerative damage, because degenerated myofibers are not present in the atrophied muscles. In this review, we summarize recent findings concerning the relationship between MuSCs and hypertrophy, and discuss what remains to be discovered to inform the development and application of relevant treatments for muscle atrophy.

Original languageEnglish
Article number118742
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Issue number9
Publication statusPublished - 2020 Sept


  • Damages
  • Hypertrophy
  • Muscle satellite cells
  • Regeneration
  • Skeletal muscle

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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