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

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. Anastasiya Borsch, Daniel Ham, and colleagues generated a time series of phenotypic measurements and RNA-Seq data from mouse skeletal muscle and comparatively analyzed these along comparable rat and human data, to assess the relevance of rodent models for human muscle aging. This study draws attention to the utility of phenotypic measurements in analyzing aging-related molecular data, as several measurements such as muscle mass, were better indicators of muscle health than chronological age.