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Lifelong dietary protein restriction induces denervation and skeletal muscle atrophy in mice

Ersoy, Ufuk
; 
Altinpinar, Atilla E.
; 
Kanakis, Ioannis
; 
Alameddine, Moussira
; 
Gioran, Anna
; 
Chondrogianni, Niki
; 
Ozanne, Susan E.
; 
Peffers, Mandy J.
; 
Jackson, Malcolm J.
; 
Goljanek-Whysall, Katarzyna
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Affiliation
University of Liverpool; University of Chester; National Hellenic Research Foundation, Athens; University of Cambridge; University of Galway
EPub Date
Publication Date
2024-09-06
Submitted Date
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Chester Medical School
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Abstract
As a widespread global issue, protein deficiency hinders development and optimal growth in offspring. Maternal low-protein diet influences the development of age-related diseases, including sarcopenia, by altering the epigenome and organ structure through potential increase in oxidative stress. However, the long-term effects of lactational protein restriction or postnatal lifelong protein restriction on the neuromuscular system have yet to be elucidated. Our results demonstrated that feeding a normal protein diet after lactational protein restriction did not have significant impacts on the neuromuscular system in later life. In contrast, a lifelong low-protein diet induced a denervation phenotype and led to demyelination in the sciatic nerve, along with an increase in the number of centralised nuclei and in the gene expression of atrogenes at 18 months of age, indicating an induced skeletal muscle atrophy. These changes were accompanied by an increase in proteasome activity in skeletal muscle, with no significant alterations in oxidative stress or mitochondrial dynamics markers in skeletal muscle later in life. Thus, lifelong protein restriction may induce skeletal muscle atrophy through changes in peripheral nerves and neuromuscular junctions, potentially contributing to the early onset or exaggeration of sarcopenia.
Citation
Ersoy, U., Altinpinar, A. E., Kanakis, I., Alameddine, M., Gioran, A., Chondrogianni, N., Ozanne, S. E., Peffers, M. J., Jackson, M. J., Goljanek-Whysall, K., & Vasilaki, A. (2024). Lifelong dietary protein restriction induces denervation and skeletal muscle atrophy in mice. Free Radical Biology and Medicine, 224, 457-469. https://doi.org/10.1016/j.freeradbiomed.2024.09.005
Publisher
Elsevier
Journal
Free Radical Biology and Medicine
Research Unit
URI
http://hdl.handle.net/10034/629004
DOI
10.1016/j.freeradbiomed.2024.09.005
PubMed ID
PubMed Central ID
Type
Article
Language
en
Description
© 2024 The Authors. Published by Elsevier Inc.
Series/Report no.
ISSN
0891-5849
EISSN
1873-4596
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Sponsors
Biotechnology and Biological Sciences Research Council (BB/P008429/1 & BB/W018276/1. U.E); Turkish Embassy in London; MRC-Versus Arthritis Centre for Integrated research into Musculoskeletal Ageing
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https://www.sciencedirect.com/science/article/pii/S0891584924006488?via%3Dihub