Abstract
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.
Highlights
Sarcopenia, the age-related loss of skeletal muscle mass and function, affects 5–13% of individuals aged over 60 years
Body mass progressively declined after 18 months, reaching 15.2 ± 3.1% at 28 months compared to 8–18 months (Fig. 1a)
As with many human diseases, aging is studied in model organisms, preeminently in rodents[43]
Summary
Sarcopenia, the age-related loss of skeletal muscle mass and function, affects 5–13% of individuals aged over 60 years. Major challenges in studying sarcopenia are the long time over which the disease develops and the lack of noninvasive methods to estimate molecular changes in skeletal muscles during aging. This is where model organisms such as mice and rats, which exhibit morphological changes consistent with human sarcopenia after just 22–24 months of age, are extremely important[12,13,14,15]. The value of these models for understanding human sarcopenia is still debated[19,20,21]
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