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Propeptide-mediated inhibition of myostatin increases muscle mass through inhibiting proteolytic pathways in aged mice

Patel, K.; Macharia, R.; Sandri, M.; Dash, P. R.; Ray, S.; Flasskamp, H.; Foster, K.; Visanuvimol, K.; Collins-Hooper, H.; Sartori, R.; Collins-Hooper, Henry; Sartori, Roberta; Macharia, Raymond; Visanuvimol, Korntip; Foster, Keith; Matsakas, Antonios; Flasskamp, Hannah; Ray, Steve; Dash, Philip R.; Sandri, Marco; Patel, Ketan


K. Patel

R. Macharia

M. Sandri

P. R. Dash

S. Ray

H. Flasskamp

K. Foster

K. Visanuvimol

H. Collins-Hooper

R. Sartori

Henry Collins-Hooper

Roberta Sartori

Raymond Macharia

Korntip Visanuvimol

Keith Foster

Antonios Matsakas

Hannah Flasskamp

Steve Ray

Philip R. Dash

Marco Sandri

Ketan Patel


Mammalian aging is accompanied by a progressive loss of skeletal muscle, a process called sarcopenia. Myostatin, a secreted member of the transforming growth factor-β family of signaling molecules, has been shown to be a potent inhibitor of muscle growth. Here, we examined whether muscle growth could be promoted in aged animals by antagonizing the activity of myostatin through the neutralizing activity of the myostatin propeptide. We show that a single injection of an AAV8 virus expressing the myostatin propeptide induced an increase in whole body weights and all muscles examined within 7 weeks of treatment. Our cellular studies demonstrate that muscle enlargement was due to selective fiber type hypertrophy, which was accompanied by a shift toward a glycolytic phenotype. Our molecular investigations elucidate the mechanism underpinning muscle hypertrophy by showing a decrease in the expression of key genes that control ubiquitin-mediated protein breakdown. Most importantly, we show that the hypertrophic muscle that develops as a consequence of myostatin propeptide in aged mice has normal contractile properties. We suggest that attenuating myostatin signaling could be a very attractive strategy to halt and possibly reverse age-related muscle loss.


Collins-Hooper, H., Sartori, R., Macharia, R., Visanuvimol, K., Foster, K., Matsakas, A., …Patel, K. (2014). Propeptide-mediated inhibition of myostatin increases muscle mass through inhibiting proteolytic pathways in aged mice. The journals of gerontology. Series A, Biological sciences and medical sciences, 69(9), 1049-1059.

Journal Article Type Article
Acceptance Date Sep 16, 2013
Online Publication Date Jan 11, 2014
Publication Date Sep 1, 2014
Deposit Date May 21, 2015
Publicly Available Date May 21, 2015
Journal Journals of gerontology : series A
Print ISSN 1079-5006
Electronic ISSN 1758-535X
Publisher Oxford University Press
Peer Reviewed Peer Reviewed
Volume 69
Issue 9
Pages 1049-1059
Keywords Muscle, Myostatin, Aging, Mouse, Sarcopenia
Public URL
Publisher URL
Additional Information Copy of article first published in: Journals of gerontology : series A, 2014, v.69, issue 9.


Article.pdf (6.8 Mb)

Copyright Statement
© The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved.

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