Molecular and phenotypic analysis of rodent models reveals conserved and species-specific modulators of human sarcopenia

Loss of skeletal muscle mass and function (sarcopenia), affects 5-13% of individuals aged 60-70 years. Mice and rats are widely used as model organisms to identify predisposing factors, yet what aspects of the disease are recapitulated in different animal models is not known. Here we generated a time series of phenotypic measurements and RNA sequencing data from the gastrocnemius muscle of mice, and analyzed them along analogous data from rats and humans. We found that rodents recapitulate especially the mitochondrial function changes observed in human sarcopenia, while inflammatory responses are more conserved at the pathway and not the gene level. Rats recapitulate human sarcopenia-associated perturbations in extracellular matrix, while mice those in RNA processing and autophagy. We further inferred transcription regulators of early and late molecular changes, which could be targeted by therapeutic interventions. Finally, our study demonstrates that phenotypic measurements should be considered in analyzing aging-related molecular data.