A robust neuromuscular system protects rat and human skeletal muscle from sarcopenia
Open accessAbstract
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.
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Denervation and neuromuscular dysfunction are important contributors to sarcopenia.
“Denervation and neuromuscular dysfunction are well-recognized as important contributors to sarcopenia.”
From Skeletal muscle aging, cellular senescence, and senotherapeutics: current knowledge and future directions (2021) · cites this paper as Pannérec et al., 2016
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- Authors
- Pannérec, A., Springer, M., Migliavacca, E., Ireland, A., Piasecki, M., Karaz, S., Jacot, G., Métairon, S., Danenberg, E., Raymond, F., Descombes, P., McPhee, J. S., & Feige, J. N.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Manchester Metropolitan University (GB)
- Nestlé Institute of Health Sciences, EPFL Innovation Park, 1015 Lausanne, Switzerland
- ORCID
- Venue
- Aging
- Publisher
- Impact Journals, LLC
- Published
- 2016-03-24
- Volume
- 8
- Issue
- 4
- Pages
- 712-728
- ISSN
- 1945-4589 (ISSN-L)
- PMC
- PMC4925824
- OpenAlex
- W2333271618
- Cited by
- 110
- References
- 60
- Citations by year
- 2026: 10 · 2025: 7 · 2024: 15 · 2023: 10 · 2022: 9 · 2021: 10 · 2020: 10 · 2019: 12 · 2018: 15 · 2017: 8 · 2016: 4
- FWCI
- 6.76
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Aging (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Repository@Nottingham (University of Nottingham) (publishedVersion, cc-by)
- e-space (Manchester Metropolitan University) (acceptedVersion)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
- Funders
- Neuromuscular Research Association Basel
- Medical Research Council (MR/K025252/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- sarcopenia, muscle excitability, vastus lateralis, tibialis anterior, cholesterol biosynthesis, sterol metabolism, skeletal muscle atrophy
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, Animals, Female, Humans, Male, Muscular Atrophy, Gene Expression, Muscle, Skeletal, Rats, Young Adult, Sarcopenia, Transcriptome
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