Molecular and phenotypic analysis of rodent models reveals conserved and species-specific modulators of human sarcopenia
Open accessAbstract
Sarcopenia, the age-related loss of skeletal muscle mass and function, affects 5-13% of individuals aged over 60 years. While rodents are widely-used model organisms, which aspects of sarcopenia are recapitulated in different animal models is unknown. Here we generated a time series of phenotypic measurements and RNA sequencing data in mouse gastrocnemius muscle and analyzed them alongside analogous data from rats and humans. We found that rodents recapitulate mitochondrial changes observed in human sarcopenia, while inflammatory responses are conserved at pathway but not gene level. Perturbations in the extracellular matrix are shared by rats, while mice recapitulate changes in RNA processing and autophagy. We inferred transcription regulators of early and late transcriptome changes, which could be targeted therapeutically. Our study demonstrates that phenotypic measurements, such as muscle mass, are better indicators of muscle health than chronological age and should be considered when analyzing aging-related molecular data.
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Time series RNA sequencing in skeletal muscle of mice and rats analyzed alongside human skeletal muscle from individuals aged 22-70 years evidenced that cellular senescence was one of the pathways with increasing gene expression during aging in all three species.
“time series RNA sequencing in the skeletal muscle of mice and rats analyzed alongside an RNA sequencing data set of human skeletal muscle from individuals aged 22–70 years evidenced that cellular senescence was one of the pathways with increasing gene expression during aging in all the three species”
From Skeletal muscle aging, cellular senescence, and senotherapeutics: current knowledge and future directions (2021) · cites this paper as Börsch et al., 2021
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- [27]Ham DJ The neuromuscular junction is a focal point of mTORC1 signaling in sarcopenia Nat. Commun. 2020 11 1 21 10.1038/s41467-020-18140-1 32908143 PMC7481251 · DOI
- [40]Mashinchian, O. et al. In-vivo transcriptomic profiling of systemic aging using cell encapsulation. 10.1101/2020.03.09.979054. PMC8926399 35245177 · DOI
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- Authors
- Börsch, A., Ham, D. J., Mittal, N., Tintignac, L. A., Migliavacca, E., Feige, J. N., Rüegg, M. A., & Zavolan, M.
- Affiliations
- SIB Swiss Institute of Bioinformatics (CH)
- University of Basel (CH)
- École Polytechnique Fédérale de Lausanne (CH)
- Corresponding author
- Zavolan, Mihaela
- ORCID
- Venue
- Communications Biology
- Published
- 2021-02-12
- Volume
- 4
- Issue
- 1
- Pages
- 194-194
- ISSN
- 2399-3642 (ISSN-L)
- PMC
- PMC7881157
- OpenAlex
- W3126225491
- Cited by
- 85
- References
- 93
- Citations by year
- 2026: 19 · 2025: 14 · 2024: 18 · 2023: 15 · 2022: 10 · 2021: 9
- FWCI
- 4.16
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Communications Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- edoc (University of Basel) (submittedVersion)
- Funders
- Novartis Stiftung für Medizinisch-Biologische Forschung (3BZ8003)
- 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, skeletal muscle aging, rodent models, gastrocnemius, mitochondrial dysfunction, inflammation, extracellular matrix, RNA processing, autophagy, transcriptome changes, muscle mass, species differences, aging biomarkers, transcription factors
- MeSH terms
- Age Factors, Aging, Animals, Body Composition, Disease Models, Animal, Gene Expression Regulation, Humans, Male, Mice, Inbred C57BL, Phenotype, Species Specificity, Signal Transduction, Disease Progression, Muscle, Skeletal, Mice, Rats, Sarcopenia, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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