Prolonged absence of myostatin reduces sarcopenia.
Sarcopenia is a progressive age-related loss of skeletal muscle mass and strength. Parabiotic experiments show that circulating factors positively influence the proliferation and regenerative capacity of satellite cells in aged mice. In addition, we believe that negative regulators of muscle mass also serve to balance the signals that influence satellite cell activation and regeneration capacity with ageing. Myostatin, a negative regulator of pre- and postnatal myogenesis, inhibits satellite cell activation and muscle regeneration postnatally. To investigate the role of myostatin during age-related sarcopenia, we examined muscle mass and regeneration in young and old myostatin-null mice. Young myostatin-null muscle fibers were characterized by massive hypertrophy and hyperplasia and an increase in type IIB fibers, resulting in a more glycolytic muscle. With ageing, wild-type muscle became increasingly oxidative and fiber atrophy was prominent. In contrast no fiber type switching was observed and atrophy was minimal in aged myostatin-null muscle. The effect of ageing on satellite cell numbers appeared minimal, however, satellite cell activation declined significantly in both wild-type and myostatin-null muscles. In young mice, lack of myostatin resulted in increased satellite cell number and activation compared to wild-type, suggesting a greater propensity to undergo myogenesis, a difference maintained in the aged mice. In addition, muscle regeneration of myostatin-null muscle following notexin injury was accelerated and fiber hypertrophy and type were recovered with regeneration, unlike in wild-type muscle. In conclusion, a lack of myostatin appears to reduce age-related sarcopenia and loss of muscle regenerative capacity.
Siriett
Victoria
V
Functional Muscle Genomics, AgResearch, East Street, Hamilton, New Zealand.
Platt
Leanne
L
Salerno
Mônica Senna
MS
Ling
Nicholas
N
Kambadur
Ravi
R
Sharma
Mridula
M
D000375:Aging / Q000502:physiology*; D000818:Animals; D048430:Cell Shape; D004546:Elapid Venoms / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024510:Muscle Development / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000473:pathology* / Q000502:physiology*; D009133:Muscular Atrophy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D055435:Myostatin; D012038:Regeneration / Q000187:drug effects / Q000502:physiology; D032496:Satellite Cells, Skeletal Muscle / Q000166:cytology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D004546:Elapid Venoms; C525911:MSTN protein, human; C525912:Mstn protein, mouse; D055435:Myostatin; D016212:Transforming Growth Factor beta; C005082:notexin