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Propeptide-Mediated Inhibition of Myostatin Increases Muscle Mass Through Inhibiting Proteolytic Pathways in Aged Mice

Collins-Hooper, H; Sartori, R; Macharia, R; Visanuvimol, K; Foster, K; Matsakas, A; Flasskamp, H; Ray, S; Dash, P R; Sandri, M; Patel, K

Authors

H Collins-Hooper

R Sartori

R Macharia

K Visanuvimol

K Foster

A Matsakas

H Flasskamp

S Ray

P R Dash

M Sandri

K Patel



Abstract

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.

Citation

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. https://doi.org/10.1093/gerona/glt170

Journal Article Type Article
Acceptance Date Sep 16, 2013
Publication Date Jan 11, 2014
Deposit Date Nov 12, 2014
Journal JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
Peer Reviewed Peer Reviewed
Volume 69
Issue 9
Pages 1049-1059
DOI https://doi.org/10.1093/gerona/glt170
Public URL https://rvc-repository.worktribe.com/output/1406141
Additional Information Corporate Creators : Hull, Padova, Reading