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A robust neuromuscular system protects rat and human skeletal muscle from sarcopenia

Pann�rec, Alice; Springer, Margherita; Migliavacca, Eugenia; Ireland, Alex; Piasecki, Mathew; Karaz, Sonia; Jacot, Guillaume; M�tairon, Sylviane; Danenberg, Esther; Raymond, Fr�d�ric; Descombes, Patrick; McPhee, Jamie S.; Feige, Jerome N.

Authors

Alice Pann�rec

Margherita Springer

Eugenia Migliavacca

Alex Ireland

Sonia Karaz

Guillaume Jacot

Sylviane M�tairon

Esther Danenberg

Fr�d�ric Raymond

Patrick Descombes

Jamie S. McPhee

Jerome N. Feige



Abstract

Declining muscle mass and function is one of the main drivers of loss of independence in the elderly. Sarcopenia is associated with numerous cellular and endocrine perturbations, and it remains challenging to identify those changes that play a causal role and could serve as targets for therapeutic intervention. In this study, we uncovered a remarkable differential susceptibility of certain muscles to age-related decline. Aging rats specifically lose muscle mass and function in the hindlimbs, but not in the forelimbs. By performing a comprehensive comparative analysis of these muscles, we demonstrate that regional susceptibility to sarcopenia is dependent on neuromuscular junction fragmentation, loss of motoneuron innervation, and reduced excitability. Remarkably, muscle loss in elderly humans also differs in vastus lateralis and tibialis anterior muscles in direct relation to neuromuscular dysfunction. By comparing gene expression in susceptible and non-susceptible muscles, we identified a specific transcriptomic signature of neuromuscular impairment. Importantly, differential molecular profiling of the associated peripheral nerves revealed fundamental changes in cholesterol biosynthetic pathways. Altogether our results provide compelling evidence that susceptibility to sarcopenia is tightly linked to neuromuscular decline in rats and humans, and identify dysregulation of sterol metabolism in the peripheral nervous system as an early event in this process.

Citation

Pannérec, A., Springer, M., Migliavacca, E., Ireland, A., Piasecki, M., Karaz, S., …Feige, J. N. (2016). A robust neuromuscular system protects rat and human skeletal muscle from sarcopenia. Aging, 8(4), 712-728. https://doi.org/10.18632/aging.100926

Journal Article Type Article
Acceptance Date Mar 2, 2016
Online Publication Date Mar 24, 2016
Publication Date Apr 1, 2016
Deposit Date Nov 7, 2018
Publicly Available Date Nov 8, 2018
Journal Aging
Publisher Impact Journals
Peer Reviewed Peer Reviewed
Volume 8
Issue 4
Pages 712-728
DOI https://doi.org/10.18632/aging.100926
Keywords skeletal muscle, neuromuscular junction, sarcopenia, physical frailty
Public URL https://nottingham-repository.worktribe.com/output/1235143
Publisher URL https://www.aging-us.com/article/100926

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