Molecular and phenotypic analysis of rodent models reveals conserved and species-specific modulators of human sarcopenia.
Anastasiya BörschDaniel J HamNitish MittalLionel A TintignacEugenia MigliavaccaJérôme N FeigeMarkus A RüeggMihaela ZavolanPublished in: Communications biology (2021)
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.
Keyphrases
- skeletal muscle
- extracellular matrix
- endothelial cells
- transcription factor
- electronic health record
- insulin resistance
- big data
- oxidative stress
- single cell
- healthcare
- genome wide
- induced pluripotent stem cells
- public health
- small molecule
- pluripotent stem cells
- cell death
- signaling pathway
- gene expression
- data analysis
- high fat diet induced
- adipose tissue
- endoplasmic reticulum stress
- artificial intelligence
- risk assessment
- climate change
- machine learning