Börsch Anastasiya, Ham Daniel J, Mittal Nitish, Tintignac Lionel A, Migliavacca Eugenia, Feige Jérôme N, Rüegg Markus A, Zavolan Mihaela
Biozentrum, University of Basel and Swiss Institute of Bioinformatics, Basel, Switzerland.
Biozentrum, University of Basel, Basel, Switzerland.
Commun Biol. 2021 Feb 12;4(1):194. doi: 10.1038/s42003-021-01723-z.
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.
肌肉减少症是与年龄相关的骨骼肌质量和功能丧失，影响着5%至13%的60岁以上人群。虽然啮齿动物是广泛使用的模式生物，但不同动物模型中模拟了肌肉减少症的哪些方面尚不清楚。在这里，我们生成了小鼠腓肠肌的一系列表型测量数据和RNA测序数据，并将其与来自大鼠和人类的类似数据一起进行分析。我们发现，啮齿动物再现了人类肌肉减少症中观察到的线粒体变化，而炎症反应在通路水平上是保守的，但在基因水平上并非如此。细胞外基质的扰动在大鼠中是共有的，而小鼠再现了RNA加工和自噬的变化。我们推断了早期和晚期转录组变化的转录调节因子，这些因子可以成为治疗靶点。我们的研究表明，诸如肌肉质量等表型测量比实际年龄更能反映肌肉健康状况，在分析与衰老相关的分子数据时应予以考虑。
