Antagonism of myostatin enhances muscle regeneration during sarcopenia.
A reduction in muscle mass and strength is often observed with aging, and this phenomenon is known as sarcopenia. This age-related atrophy frequently correlates with insufficient levels of muscle regeneration resulting from impairment of satellite cell involvement and myogenesis brought about by the aged environment. Using myostatin-null mice, we recently showed that negative regulators of muscle mass such as myostatin play an active role in the regulation of myogenesis during aging. The present study specifically tests the therapeutic value of a myostatin antagonist in sarcopenia. We report here that a short-term blockade of myostatin, through stage-specific administration of a myostatin antagonist, significantly enhanced muscle regeneration in aged mice after injury and during sarcopenia. Antagonism of myostatin led to satellite cell activation, increased Pax7 and MyoD protein levels, and greater myoblast and macrophage cell migration, resulting in enhanced muscle regeneration after notexin injury in aged mice. In addition, the antagonist demonstrated a high degree of efficacy, as only minimal doses during the critical period of regeneration after injury were sufficient to restore the myogenic and inflammatory responses in the aged environment. Thus, we propose that the antagonism of myostatin has significant therapeutic potential in the alleviation of sarcopenia.
Siriett
Victoria
V
Functional Muscle Genomics, AgResearch, Hamilton, New Zealand.
Salerno
Mônica Senna
MS
Berry
Carole
C
Nicholas
Gina
G
Bower
Rob
R
Kambadur
Ravi
R
Sharma
Mridula
M
D000375:Aging / Q000502:physiology*; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009132:Muscles / Q000293:injuries / Q000502:physiology*; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology / Q000378:metabolism; D055435:Myostatin; D051763:PAX7 Transcription Factor / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
C525912:Mstn protein, mouse; D017570:MyoD Protein; D055435:Myostatin; D051763:PAX7 Transcription Factor; D016212:Transforming Growth Factor beta